1. science
2. medicine
3. veterinary medicine

DERMATOLOGY
Allergic skin diseases in dogs
and cats: an introduction
R.E.W. Halliwell(1)
for the development of the Coombs’ test, and who died in
2005. He and his colleague proposed four types based upon the
then current understanding of the underlying immunological
mechanisms.
• Type 1, with an onset from minutes to hours after allergen
exposure, and involving IgE antibody and mast cells.
• Type 2, involving antibody-dependant cytotoxicity.
• Type 3, involving antigen/antibody immune complexes.
• Type 4, or delayed hypersensitivity in which the onset occurs
24-48 hours after application of the antigen, and which is
mediated by lymphocytes rather than antibody.
This paper was commissioned by FECAVA for
publication in EJCAP.
Allergy in man – a brief history
The study of allergy, and of the allergic diseases has fascinated
scientists in the medical and veterinary field for many years. The
immune responses are supposed to be protective. How and why
does the damaging immune response – which we term allergy,
develop?
Allergy in the dog and cat
The earliest documented report of the existence of a condition
resembling atopic dermatitis (AD) in man concerned the
Emperor Octavian Augustus who was born in 63BC. In the
1920s, Coca and Cooke had introduced the term “atopy”,
literally meaning “strange disease” to include the conditions
of allergic asthma and hay fever, both of which had familial
tendencies [1]. Immunotherapy was used extensively at that
time, with the first report of its successful use appearing in 1911
[2]. The classical work of Prausnitz and Küstner showed in a
series of elegant experiments that the antibody associated with
these conditions (termed “reagin”) was an unusual one, in that
it (i) was heat labile, and (ii) could be transferred to the skin
of normal individuals as shown by a resultant wheal and flare
reaction upon subsequent injection of allergen [3]. The study of
AD really commenced in the 1930s, when it was termed Prurigo
Besnier. It was included under the heading of “atopy” in that it
shared the same familial tendencies, and children who suffered
from AD often went on to develop asthma or hay fever Also,
similarly to the former two conditions, affected patients usually
had positive skin tests to environmental allergens.
The importance of allergy in skin diseases of dogs and cats
became apparent to veterinarians in the USA in the 1930s.
Schnelle, working at the Angel Memorial Hospital in Boston
documented that 15% of all cases seen were accorded a
diagnosis of “eczema”, and further that 56.9% of all dogs
with skin disease, and 26.6% of all cats similarly affected were
deemed to be suffering from this condition [6]. Similar figures
were reported from the clinics at Cornell University in Ithaca,
New York [7].
Although it was generally believed that “eczema” was a
manifestation of allergy, the exact nature of the inciting cause
was controversial, with most emphasis being placed upon foods.
The seasonal nature of many cases puzzled the early workers,
and it was Kisileff who in 1938 proposed that an allergic reaction
to the bites of fleas was the cause of ”summer eczema” [8].
In 1941, Whittich, who was a human allergist, reported on a
dog with perennial pruritus due to a food allergy that suffered
seasonal exacerbations from a concomitant pollen allergy [9].
This was, in fact, the first well-documented case of canine
AD. The dog was treated with an appropriate hypoallergenic
diet and effectively hyposensitized with injections of allergenic
extracts of the pollens to which sensitivity was shown.
Little progress was made in further unravelling the pathogenesis
until the 1960s. At that time it was believed that the reagin was
IgA. But the painstaking work of the Ishizakas showed that it
was a previously undescribed immunoglobulin class that they
termed IgE [4].
In the 1960s and 1970s, the condition was known as canine
“atopy” or “atopic disease”, and was studied extensively by
Schwartzman and colleagues at the University of Pennsylvania
[e.g. 10]. These terms were at that time preferred to that of
atopic dermatitis in that it was unclear whether the canine
disease represented the true analogue of the well-characterised
At that time, the nomenclature used to describe the allergic
diseases was in some disarray, and it was Gell and Coombs who
proposed the modern day classification [5]. Robin Coombs was
a Cambridge veterinary graduate, who of course is best known
1) Richard E.W. Halliwell Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin Midlothian EH25 9RG, UK
209
EJCAP - Vol. 19 - Issue 3 December 2009
pruritic dogs [23]. Reliable information on the incidence of
atopic dermatitis and of AFRs in the cat, and on the relative
incidence of the two is not available.
atopic dermatitis of children. It was also termed “allergic inhalant
dermatitis” from the mistaken belief that the route of access of
allergen was primarily, if not exclusively via the respiratory tract.
Indeed it was not until 2006 that the major route was shown to
be percutaneous [11], with research over the past two decades
highlighting the similarities between the canine disease and
human AD [e.g. 12, 13].
Fewer studies have been conducted on allergic contact dermatitis
in animals, but it is clear that the incidence in dogs is far less
than that of either AD or AFRs. True allergic contact dermatitis
is exceedingly rare in the cat, although the susceptibility of this
species to contact sensitisation has been demonstrated [24].
In the 1970s, canine IgE was identified, purified and characterized.
It was shown to share common antigenic determinants with its
human counterpart, and to be associated with mast cells in
canine skin [14]. Indeed the dog was the first species in which
this was directly demonstrated. At that time also techniques
for the serological quantitation of allergen-specific IgE were
developed for both man and dogs.
Genetic susceptibility to allergic
skin diseases
Atopic dermatitis
Under the original definition of an atopic disease, a genetic trait
is a prerequisite, and familial tendencies in both man and in the
dog have long been known. Hence breed predispositions are
inevitable, and are well-known. These will vary from one part
of the world to another. In a study conducted at the University
of California, where the incidence was compared to the base
clinic population, the Labrador retriever, golden retriever, West
Highland white terrier, Chinese shar-pei, bull terrier, bichon frisé,
Tibetan terrier and English springer spaniel were all significantly
over-represented, whereas mixed breeds were protected [25].
The populations of teaching hospitals can be biased, however,
and more reliable data is obtained when comparisons are made
with the national population. The requirement in Switzerland for
a national canine register has enabled such a study, in which the
West Highland white terrier, boxer, French bulldog, bull terrier,
Dalmatian, Vizsla and Basset hound were significantly over
represented [26]. In a study conducted in the United Kingdom,
the heritability of AD amongst Labrador and golden retrievers
was found to be high, at 0.47, implying a strong genetic trait
[27]. Few studies have been conducted in cats, apart from a
report of three littermates all of whom were affected with AD
[28].
Research on the mechanisms of the allergic diseases in cats
lagged behind the canine studies by several decades. Although
the existence of feline IgE could have been readily anticipated,
and evidence of cross-reactivity between canine and putative
feline IgE was provided in 1993 [15], it was not until 1998 that
the production of antisera specific for that isotype was reported
[16].
Incidence of allergic skin diseases
It is widely held that skin disease is very common, and in a
recent survey in the UK such cases comprised 24% of all nonroutine presentations to veterinarians for treatment [17] and this
was the single most common system affected. In temperate
climates there is no doubt that flea infestation and/or allergy
has contributed the highest proportion of such cases, but the
availability of the newer ectoparasiticides, some as over-thecounter products, has helped to reduce these numbers. The
reported incidence of canine AD has ranged from a high of 15%
of the general population [18] to 8% of referrals to a teaching
hospital – which obviously is a selected and biased population
[19]. In a recent survey of >30,000 cases presented to 52 private
practices in the USA, a diagnosis of atopic/allergic dermatitis,
allergy or atopy was made in 8.7%, which accounted for 21.6%
of dogs and cats presented with skin or ear disease [20].
Given the clear heritability of AD, an attempt was made to
develop a beagle model by selective inbreeding for IgE levels
[29]. This high IgE-producing beagle strain also has the abnormal
barrier function that is a feature of AD in both man and dogs
[30], and develops a disease indistinguishable from AD upon
epicutaneous exposure with house dust mite antigen.
The incidence of adverse food reactions (AFRs) in dogs will depend
upon the rigor with which the diagnosis is made. Commonly,
one hypoallergenic diet trial, using either a commercial or
home-prepared diet, is cited in publications as justification for
excluding a diagnosis in a perennially pruritic dog. Lamb and
rice was a popular choice, in that lamb is uncommonly fed. But
the demonstration that cross-reacting antigens between beef
and lamb are frequently recognized [21] implies that AFRs have
probably been underdiagnosed in the past. It is generally agreed
that AFRs, as a cause of perennial pruritus in dogs, are much less
frequent than is AD. In a recent study of 181 perennially pruritic
dogs, the diagnosis was made (often with concomitant AD) in
29% and 32% of cases respectively using a home prepared or
commercial hydrolysate diet [22], with AD presumably being
responsible for the greater proportion. However the incidence
relative to AD was apparently higher in another study of 113
dogs in which AFRs were implicated in 41% of perennially
Human AD is not caused by a single gene defect, but is a
polygenic disorder with complex inheritance. Recently, results
of a canine study using microarray and quantitative PCR analysis
of candidate genes, demonstrated striking similarities with the
gene abnormalities reported in man [31].
Other allergic skin disease
It has been shown that atopic dogs are predisposed to the
development of flea allergy dermatitis [32,33,34], but no
further studies on the heritability have been undertaken. No
predisposition to allergic contact dermatitis has been noted in
man, and a heritable trait would not be expected in animals.
But interesting recent information has emerged regarding AFRs.
In the Swiss study referred to above, a breed predisposition
has been shown for West Highland white terriers, German
210
Allergic skin diseases in dogs and cats: an introduction - R.E.W. Halliwell
shepherds, pugs, boxers and the Rhodesian ridgeback [26]. Also
clearly indicating a genetic trait was the chance discovery of an
inbred colony of beagle Maltese crosses showing spontaneous
IgE-mediated food allergy with both gastrointestinal and
dermatological signs [35].
conditions in small animals in general practice. Vet Rec. 2006;
158:533-539.
[18] Chamberlain KW. Atopic (allergic) dermatitis. Vet Clin N Am.
1974; 4: 29-39.
[19] Scott DW, Paradis M. A survey of canine and feline skin disorders
seen in a university practice: small animal clinic, University of
Montreal, Saint-Hyacinthe, Quebec, (1987-1988). Can Vet J.
1990; 31: 830-835.
[20] Lund EM, Armstrong PJ, Kirk CA, Kolar LM, Klausner JS. Health
status and population characteristics of dogs and cats examined
at private veterinary practices in the United States. J Am Vet Med
Assoc. 1999; 214: 1336-1441.
[21] Martin A, Sierra M-P, Gonzales JL, Arevalo M-A. Identification
of allergens responsible for cutaneous adverse food reactions to
lamb, beef and cow’s milk. Vet Dermatol. 2004; 15: 349-356.
[22]. Loeffler A, Soares-Magalhaes R, Bond R, Lloyd DH. A retrospective
analysis of case series using home-prepared and chicken
hydrolysate diets in the diagnosis of adverse food reactions in 181
pruritic dogs. Vet Dermatol. 2006; 17: 273-279.
[23] Jackson HA, Murphy KM, Tater KC, Olivry T, Hummel JB,
Itensen J et al. The pattern of allergen hypersensitivity (dietary
or environmental) of dogs with non-seasonal atopic dermatitis
cannot be differentiated of the basis of historical or clinical
information: a prospective evaluation 2003-2004. Vet Dermatol.
2005; 16: 200.
[24] Schultz KT, Maguire HC. Chemically induced delayed
hypersensitivity in the cat. Vet Immunol Immunopathol. 1982; 3:
585-590.
[25] Zur G, Ihrke PJ, White SD, Kass PH. Canine atopic dermatitis: A
retrospective study of 266 cases examined at the University of
California, Davis, 1992-1998. Part 1. Clinical features and allergy
testing results. Vet Dermatol. 2002; 13: 89-102.
[26] Picco F, Zini E, Nett C, Naegeli B, Bigler B, Rufenacht S et al. A
prospective study on canine atopic dermatitis and food-induced
allergic dermatitis in Switzerland. Vet Dermatol. 2008; 19: 150155.
[27] Shaw SC, Wood JLN, Freeman J, Littlewood JD, Hannant D.
Estimation of the heritability of atopic dermatitis in Labrador and
Golden Retrievers. Am J Vet Res. 2004; 65: 1014-1020.
[28] Moriello, K. Feline atopy in three littermates. Vet Dermatol. 2001;
12: 177-181.
[29] Olivry T, Deangelo KB, Dunston SM, Clarke KB, McCall CA. Patch
testing of experimentally sensitized beagle dogs: development of
a model for skin lesions of atopic dermatitis. Vet Dermatol. 2006;
17: 95-102.
[30] Marsella R, Girolomoni G. Canine models of atopic dermatitis: A
useful tool with untapped potential. J Invest Dermatol 2009; 19:
2351-2357.
[31] Wood SH, Clements DN, Ollier WE, Nuttall T, McEwan NA, Carter
SD. Gene expression in canine atopic dermatitis and correlation
with clinical severity scores. J Dermatol Sci. 2009; 55: 27-33.
[32] Halliwell REW, Preston JF, Nesbitt J. Aspects of the
immunopathogenesis of flea allergy in dogs. Vet Immunol
Immunopathol. 1987; 17: 483-494.
[33] Schick RO, Fadok VA. Responses of dogs to regional allergens:
268 cases 1981-1984. J Am Vet Med Assoc. 1986; 189: 14931496.
[34] Carlotti DN, Costargent F. Analysis of positive skin tests in 449
dogs with allergic dermatitis. Eur J Comp Anim Pract. 1994; 4:
42-59.
[35] Jackson HA, Hammerberg B. Evaluation of a spontaneous canine
model of immunoglobulin E-mediated food hypersensitivity:
dynamic changes in serum and fecal allergen-specific
immunoglobulin E values relative to dietary change. Comp Med.
2002; 52: 316-321.
Conclusions
Allergic skin diseases continue to pose challenges for clinicians
and researchers alike. Close interaction between these two, and
between those investigating the human disease counterparts
with veterinary colleagues will surely enable speedier progress.
Nonetheless, the past three decades has seen remarkable
advances both in our understanding of the disease processes,
and the delivery of better therapeutic approaches, many of
which are detailed in this issue.
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
Noon L. Prophylactic inoculation against hay-fever. Lancet 1911;
1: 1572-1573.
Prausnitz C, Küstner H. Studien über die Uberimfindlichkeit.
Zentralb Bact. 1921; 86: 160-169.
Coca AF, Cooke RA. On the classification of the phenomenon of
hypersensitiveness. J Immunol. 8: 163-166, 1923.
Ishizaka K, Ishizaka T. Identification of γ-E antibodies as carriers of
reaginic antibody. J Immunol. 1967; 99: 1187-1198.
Coombs RRA, Gell PGH. Classification of allergic reactions
responsible for clinical hypersensitivity and disease. In: Gell PGH,
Coombs RRA (Eds). Clinical Aspects of Immunology. Blackwell
Scientific, Oxford, 1975; 761-770.
Schnelle GB. Eczema in dogs – an allergy. North Am Vet. 1933;
14: 37-40.
Milks HJ. The role of allergy in skin diseases of dogs. Cornell Vet.
1938; 28: 142-147.
Kissilef A. The dog flea as a causative agent in summer eczema. J
Am Vet Med Assoc. 1938; 93: 21-25.
Wittich FW. Spontaneous allergy (atopy) in the lower animal. J
Allergy. 1941; 12: 247-251.
Halliwell REW, Schwartzman RM. Atopic disease in the dog. Vet
Rec. 1971; 89: 209-214.
Marsella R, Nicklin C, Lopez J. Studies on the routes of allergen
exposure in high IgE-producing beagle dogs sensitized to house
dust mites. Vet Dermatol. 2006; 17: 306-312.
Olivry T, Moore PF, Affolter VK, Nayadan DK. Langerhans cell
hyperplasia and IgE expression in canine atopic dermatitis. Arch
Dermatol Res. 1996; 288: 579-585.
Olivry T, Naydan DK, Moore PF. Characterization of the cutaneous
inflammatory infiltrate in canine atopic dermatitis. Am J
Dermatopathol. 1997; 19: 477-486.
Halliwell REW. The localization of IgE in canine skin – an
immunofluorescent study. J Immunol. 1973; 110: 422-430.
De Boer DJ, Saban R, Schultz KT, Bjorling DE. Feline immunoglobulin E: preliminary evidence of its existence and cross-reactivity
with canine IgE. Ihrke PJ, Mason IS, White SD (eds). Advances in
Veterinary Dermatology 11. Pergamon, Oxford, 1993; 51-62.
Gilbert S, Halliwell REW. Production and characterisation of
polyclonal antisera against feline IgE. Vet Immunol Immunopathol
1998; 63: 223-233.
Hill PB, Eden CA, Huntley S, Morey V, Ramsey S, Richardson C
et al. Survey of the prevalence and treatment of dermatological
211
EJCAP - Vol. 19 - Issue 3 December 2009
UB Cam 2.0TM Videoscope
A useful tool for various applications in veterinary clinics
•
•
•
•
•
Small and handy
Excellent image quality
Live recordings as well as still images
Easy way to show images (before/after) to client
Easy way to file image documentation
UB Cam enables the vet to record high resolution images, eg as image
documentation in terms of patient journalisation.
The videoscope is also an excellent tool for visual client information from
narrow spaces such as the ear ducts and the oral cavity.
These options make the videoscope highly useful for eg otoscopy,
dermatoscopy and as an oral camera during dental procedures.
Includes:
5 different speculae (funnels): 3 mm, 4 mm, 5 mm short, 5 mm long and 7 mm
1 speculum, 7 mm, with working channel
1 ear speculum, 9 mm
1 speculum for dermatoscopy and ophthalmoscopy, 35 mm
5 m extension cable
Used here as a
dermatoscope
to depict skin changes
Cat. No 270175
EXPERIENCE · QUALITY · SERVICE
For more information please contact JØRGEN KRUUSE AS · tel +45 72 14 15 16 · e-mail: [email protected]
212
DERMATOLOGY
The immunopathogenesis of allergic
skin diseases in dogs and cats
R.E.W. Halliwell(1)
SUMMARY
Hypersensitivity in veterinary medicine has been recently redefined as “Objectively reproducible clinical signs
initiated by exposure to a defined stimulus at a dose tolerated by normal dogs” [1]. A number of different types exist,
broadly mediated by antibody or immunocompetent lymphoid cells. However this represents an oversimplification,
and, as exemplified especially by atopic dermatitis (AD), a complex interplay between various arms of the innate and
acquired immune systems is involved.
that accompany AD, are attributable to defects in the innate
immune system, which has been extensively studied in man, and
which has several components. There have been few studies in
veterinary medicine, but the similarities in the disease between
man and dog are such that similar abnormalities are likely. The
description that follows draws heavily on studies undertaken in
man [2], with veterinary studies specifically referred to when
available.
This paper was commissioned by FECAVA for
publication in EJCAP.
Atopic dermatitis
The currently accepted definition of canine atopic dermatitis
(AD) is: “A genetically predisposed inflammatory and pruritic
skin disease with characteristic clinical features associated with
IgE antibodies most commonly directed against environmental
allergens” [1]. There exists also a subset of canine AD in which
IgE antibodies are not detectable. This is termed “atopic-like”
dermatitis, and appears to be the equivalent of intrinsic AD in
man.
(a). Pattern recognition receptors: These receptors recognize
pathogens in the context of broad molecular patterns termed
“pathogen-associated molecular patterns” (or PAMPS). Best
characterised are the Toll-like receptors (TLRs). They are
expressed by antigen-presenting cells, mast cells, neutrophils
and keratinocytes. One of these, TLR2, has been shown to be
deficient in some patients with AD thus rendering the skin more
susceptible to infection.
The definition of classical canine AD implies a pivotal role for
IgE in the pathogenesis which may well be the case. However
in fact the pathogenesis of AD is exceedingly complex, and can
be categorised under three headings, viz (i) defects in innate
immunity, (ii) defects in barrier function, and (iii) defects in
acquired immunity.
(b). Neutrophils: Histopathology of both human and canine AD
patients – even in the face of significant infection – are notable
for the paucity of neutrophils. A number of studies in man have
shown that upregulation of the leucocyte adhesion molecule
CD11b is markedly decreased in human patients with AD as
compared to normal individuals.
(i) Defects in innate immunity
The innate immune system is phylogenetically the oldest,
and provides the first line of defence against invading microorganisms. In man, 80-100% of nonlesional skin of AD
patients is colonised with Staph aureus as compared with
5-30% of normals. This, and many of the other abnormalities
(c). Antimicrobial peptides (AMPs): These come from a number
of sources, including keratinocytes, neutrophils, sebocytes and
the cells of sweat gland ducts. They are generally present at low
or undetectable levels, and at markedly increased levels in the
1) Richard E.W. Halliwell Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin Midlothian EH25 9RG, UK
213
EJCAP - Vol. 19 - Issue 3 December 2009
face of injury. They have broad antimicrobial activity. A number
have been shown to be deficient in human patients with AD,
including LL-37. Vitamin D enhances LL-37 activity, and thus
vitamin D, and particularly D3, may offer potential in treating
infections. Canine studies on AMPs, however, have so far shown
equivocal results [3].
high IgE-producing beagle model, have suggested that a Th2
response is associated with the acute phase of AD, whereas a Th1
response is associated with the chronic phase, were secondary
infection is superimposed [15, 16, 17, 18, 19, 20]. The cytokines
derived respectively from a Th2 and Th1 response promote that
response via a positive feedback mechanism. Conversely, they
are mutually inhibitory – i.e. γIFN inhibits the Th2 response,
which has led to the use of γ-INF as a treatment for CAD [21].
Similarly, successful immunotherapy in CAD is accompanied by
a shift from Th2 to Th1 [22].
Defects in barrier function
That barrier function is abnormal in both human and canine AD
is well known. Barrier function is at two levels: (i) at the level
of the Stratum corneum, composed of terminally differentiated
corneocytes surrounded by a matrix of specialised lipids, and (ii)
the tight junctions of the Stratum granulosa. In man, a mutation
of filaggrin has been shown to be highly associated with AD,
but is not present in all cases, and so other abnormalities
must contribute [4]. In the dog, studies regarding filaggrin
are ongoing, but it has been shown that the skin of dogs with
AD contain lipids in globules, rather than dispersed to fill in
all the intercellular spaces [5,6]. In man, abnormalities of the
tight junctions have also been shown and are associated with
reduction of claudin-1 in patients with AD [7].
Mediators involved
The preformed, mast cell derived mediators are clearly of
importance in canine and feline AD. They include histamine,
proteases and serotonin, although there is little evidence that
the latter is contributory. The limited efficacy of antihistamines
as a sole treatment implies that other mediators are likely to
have more pronounced pruritogenic and inflammatory effects.
The membrane-derived mediators, especially the leukotrienes,
and particularly LTB4 are implicated in a range of inflammatory
dermatoses including AD and are promising targets for
pharmacologic intervention [23]. In addition, the inflammatory
cell milieu that characterizes AD offers the potential for the
involvement of many other inflammatory mediators that are
derived from keratinocytes and other epidermal and dermal
sources. The spectrum of inflammatory mediators is thus
multiple, which explains why drugs that target single mediators
are generally only marginally effective.
Abnormalities in acquired immunity
Histopathology of the lesions
A study of the histopathology and immunohistochemistry of
infiltrating cells gives valuable insights into disease pathogenesis.
This has been studied in clinical cases, and also in atopy patch
tests, were an antigen (usually house dust mite) is applied to
the skin under occlusion. Biopsies of cases of canine AD, show
evidence of epidermal Langerhans’ cell hyperplasia, and these
often appear in clusters [8]. Armed with IgE antibody, these
play a pivotal role in allergen capture and processing. Also
noted are increased numbers of dermal dendritic cells that have
similar functions [8,9]. Mast cell hyperplasia is frequently noted
on histopathology reports, but careful studies have failed to
demonstrate significant differences in the mast cell density in
the dermis of atopic and normal dogs, [10]. Lymphocytes are
frequent in the cellular infiltrate, with the vast majority being
T cells, with only few B cells [9]. Both CD4+ and CD8+ cells
are found in increased numbers, with a major increase in CD8+
cells in the epidermis. Finally, neutrophils and eosinophils are
certainly seen in biopsies of affected skin, but in neither case are
they a dominant feature.
Secondary features in the pathogenesis
Both bacterial overgrowth and overt pyoderma are common
features of canine AD, although much less so in feline AD. A major
reason for this is the enhanced ability of canine staphylococcal
species to adhere to corneocytes of atopic dogs. This has been
demonstrated by both in vitro and in vivo studies [24, 25]. The
fact that IgE antibodies to antigens of the organism can develop
makes this an important factor in the disease process [26].
Similarly, malassezia overgrowth is well documented [27],
although precise quantitative studies comparing colonisation
densities in atopic and normal dogs are lacking. As is the case
with staphylococcal infection, an IgE response can compound
the disease process [28]. Malassezia overgrowth has also been
documented in allergic cats [29].
Histopathological features of feline AD are highly variable from
case to case, although to an extent this may be reflective of a
lack of defined criteria for the diagnosis [11]. There is generally
an increase in the numbers of mast cells and eosinophils, with
the latter being more prominent than in the dog [12]. Increases
in CD4+ and CD8+ cells are noted as is an increase in dermal
dendritic cells [13, 14].
The likely sequence of events
The complexity of the immunopathogenesis of AD is such that
any schematic representation of the chain of events involved
must of necessity be speculative. Nonetheless, it is helpful to
document the current views of the process – albeit in simplified
form (see Fig 1).
1. Impaired barrier function facilitates the percutaneous
absorption of allergen.
2. Allergen is captured by Langerhans’ cells armed with IgE
antibody.
3. In the resultant immune response to the allergen, the genetic
features of the atopic trait favour the development of an
IgE response (Th2) – which is largely elaborated in the local
lymph node.
Th1 vs Th2
It is well established that T cell responses in man and animals
fall into one of two patterns – a Th1 response associated with
IL-2, IL-12, γ-IFN and IL-18, which is expressed as cell-mediated
immunity, and a Th2 response associated with IL-4, IL-5, IL-6
and IL-13 and facilitating antibody production, including IgE.
Multiple studies undertaken in dogs and cats, including the
214
The immunopathogenesis of allergic skin diseases in dogs and cats - R.E.W. Halliwell
Fig. 1 A simplified scheme depicting the acquisition of sensitivity and the development of inflammation in canine atopic dermatitis.
4. Exposure of mast cells armed with IgE antibody initiates
release of preformed and newly generated mediators, which
aids the influx of inflammatory cells.
5. In turn, these release other pro-inflammatory mediators.
6. Particularly in the chronic phase, a concomitant Th1 response
occurs with γIFN prominent.
7. Secondary infection compounds the problem, leading to
further Th1 responses.
8. A failure of immune regulation allows the continuation of
the immune responses and resultant inflammation.
organ that is affected (e.g. skin vs gastrointestinal tract).
That IgE-mediated food hypersensitivity exists in the dog is
clear from (i) studies on experimental induction [30], (ii) on
thorough immunological investigations of spontaneous cases
[31], and (iii) on the characterization of an in-bred colony of
beagle/Maltese crosses [32]. However it should be emphasized
that although in the latter case IgE to incriminated allergens
is readily demonstrable, dynamic changes in allergen-specific
levels do not reliably follow withdrawal of the incriminated
food and challenge – for which there are a number of possible
explanations.
The pathogenesis of food
hypersensitivity
However IgE-mediated food hypersensitivity is likely to be
involved only in cases that relapse within 24-48 hrs of challenge
– which accounts for only a small proportion of the confirmed
cases [33].
Conventionally, adverse reactions to foods are divided into food
hypersensitivity, where immune mechanisms are involved, and
food intolerance where pharmacological factors are responsible
(e.g. histamine and histamine-releasing factors). There is no
data on the relative incidence of the two types. This discussion
will dwell solely on the former.
If one extrapolates from the situation in man, the majority
of cases are likely to result from a combination of IgEmediated reactions, with cell-mediated hypersensitivity and/
or IgG antibody. In people with atopic dermatitis where food
hypersensitivity is involved, the best diagnostic results are
achieved when IgE is measured and patch testing with food
antigens is also undertaken, and this is probably reflective of the
dual nature of the immunopathogenesis [34].
Compared to the situation in man, there is a paucity of
data on the pathogenesis of food hypersensitivity, and the
veterinary literature contains a plethora of dogma based upon
unreliable information. The first point to emphasize is that food
hypersensitivity is not one disease – rather it is a spectrum of
diseases that vary in their immunological mechanisms and in the
215
EJCAP - Vol. 19 - Issue 3 December 2009
A
B
C
D
Fig. 2 Histopathology depicting the immunopathogenesis of canine flea allergy dermatitis. (a) Acute oedema 15 minutes after a flea bite. (b)
Histpathology of the immediate (15 minute) reaction showing egress of eosinophils from a blood vessel into the dermis. (c) Predominantly
mononuclear infiltrate at 48 hrs after a flea bite depicting the delayed (cell-mediated) hypersensitivity component. (d) Biopsy 12 hrs after a
flea bite showing influx of basophils (arrows) as compared to mast cells (pink arrow).
The pathogenesis of flea allergy
dermatitis
The relevance of IgG antibody measurements, and hence of the
involvement of this isotype in the pathogenesis is controversial.
In a study which measured food-specific IgE and IgG in 22
cases of confirmed adverse food reactions, the difference in
antibody levels between normal dogs and those with confirmed
adverse food reactions was actually greater in the case of IgG
than it was for IgE [35]. However, association is not causation.
Similarly, in a recent study of irritable bowel syndrome in man,
a placebo-controlled diet trial was undertaken based upon the
measurement of food antigen-specific IgG. Those patients who
were fed a diet that excluded antigens to which an IgG response
was shown exhibited significantly superior outcomes than did
those fed a diet including such antigens [36]. Again, this does
not, of course, necessarily indicate that the IgG was implicated
in the disease process – it could well be an epiphenomenon.
The immunopathogenesis of flea allergy dermatitis (FAD) has
been the subject of much study over the past 3 decades. Initially,
it was assumed that the work done on guinea pigs in the 1960s
was directly applicable to the dog and cat, but it was established
that this was not the case.
The flea allergen
It is generally held that salivary allergens injected when the flea
sucks blood are responsible for the immune response. Early
work suggested that the allergen was a hapten which became
a complete allergen on union with dermal collagen [37], but
more recent studies have shown that there are a number of
protein allergens involved [38], and the major allergen which is
recognised by some 90% of flea allergic dogs has been cloned
and produced in recombinant form [39].
In summary, there is good data on the role of IgE in a small
proportion of cases. Whether cell-mediated hypersensitivity or
IgG antibody is responsible for the majority of cases, perhaps in
conjunction with IgE, must await results of further studies.
216
The immunopathogenesis of allergic skin diseases in dogs and cats - R.E.W. Halliwell
dogs often maintain this state indefinitely, although with time
the incidence of hypersensitivity tends to decline [38, 43]. It
does not appear, however, that the same features are applicable
to feline FAD [45].
The pathogenesis of allergic contact
dermatitis
It is generally believed that uncommon condition results from
a delayed, cell-mediated hypersensitivity [46, 47]. However
the characteristic epidermal spongiosis that is seen in man is
infrequently observed in clinical cases and in biopsies of positive
patch test sites, and whilst the dermal infiltrate does contain
mononuclear cells, a significant neutrophilic influx suggests that
the immunopathogenesis, and hence the cytokine milieu may
differ from that in man (Fig 3) [48]. The infrequency with which
this condition is observed in veterinary medicine makes in depth
investigations difficult.
Conclusions
The current state of knowledge of the pathogenesis of allergic
skin diseases in the dog and cat has been reviewed. Although
much progress has been made over the past three decades,
much remains to be done. The realization that canine AD in
particular is a good model for the study of human AD, will likely
facilitate further studies in this area.
Fig. 3 Biopsy of a positive patch test in a case of allergic contact
dermatitis. Epidermal spongiosis with a mixed cell inflammatory
infiltrate is seen.
References
Immunological mechanisms involved
Observation of the sites of flea feeding in allergic dogs show that
in the majority of dogs, an immediate reaction occurs which is
papular or urticarial. This may wane to be replaced by a papular
eruption which is maintained for up to 4-5 days. Histopathology
of these reaction sites at varying times has revealed features
of both immediate (IgE-mediated) hypersensitivity evidenced
by oedema between the collagen bundles, and an egress of
eosinophils from dermal blood vessels and of delayed (cellmediated) hypersensitivity with a perivascular predominantly
mononuclear cell infiltrate (Fig 2 a, b, c) [40]. In some 10-20%
of patients, delayed reactions only are noted, and assays for
flea allergen-specific IgE will be negative. If biopsies are taken
between 4 and 18hrs after a flea bite, special processing and
staining will reveal an influx of basophils which may account
for up to 20% of the cellular infiltrate (Fig 2 d) [41]. The
pathogenesis is thus quite complex, and it is also possible that
IgG antibodies may be involved, as they are readily detectable
in the sera of patients with FAD [42]. Interestingly, animals who
are continually exposed and who suffer no obvious clinical signs
are totally or partially immunologically tolerant, and their sera
have an absence of IgE antibodies, and low or undetectable
levels of IgG [42, 43].
[1]
Halliwell R. Revised nomenclature for veterinary allergy. Vet
Immunol Immunopathol. 2006; 114: 207-208.
[2] De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA.
Atopic dermatitis: a disease caused by innate immune defects? J
Invest Dermatol. 2009; 129: 14-30.
[3] Van Damme CMM, Willemse T, van Dijk A, Haagsman HP,
Veldhuizen EJA. Altered cutaneous expression of β-defensins in
dogs with atopic dermatitis. Molecular Immunol. 2009; 46: 22492455.
[4] Barker JN, Palmer CN, Zhao Y, Liao H, Hull PR, Lee SP et al.
Null mutations in the filaggrin gene (FLG) determine major
susceptibility to early-onset atopic dermatitis that persists into
adulthood. J Invest Dermatol. 2007; 127: 564-567.
[5] Inman AO, Olivry T, Dunston SM, Montiero-Rivierre NA, Gatto H.
Electron microscopic observations of stratum corneum intercellular
lipids in normal and atopic dogs. Vet Pathol. 2001; 38: 720-723.
[6] Marsella R, Girolomoni G. Canine models of atopic dermatitis: A
useful tool with untapped potential. J Invest Dermatol 2009; 19:
2351-2357.
[7] De Benedetto A, Latchney L, McGirt L, Vidyasagar S, Cheadle C,
Barnes KC et al. The tight junction protein claudin-1 is dysregulated
in atopic dermatitis. J Allergy Clin Immunol. 2008; 119: s280
(abstr).
[8] Olivry T, Moore PF, Affolter VK, Nayadan DK. Langerhans cell
hyperplasia and IgE expression in canine atopic dermatitis. Arch
Dermatol Res. 1996; 288: 579-585.
[9] Olivry T, Naydan DK, Moore PF. Characterization of the cutaneous
inflammatory infiltrate in canine atopic dermatitis. Am J
Dermatopathol. 1997; 19: 477-486.
[10] Welle MM, Olivry T, Grimm S, Suter M. Mast cell density and
subtypes in the skin of dogs with atopic dermatitis. J Comp Pathol.
1999; 120: 187-197.
The development of hypersensitivity
Studies on the experimental induction of FAD have shown
that all dogs can become sensitized, although atopic dogs
are predisposed [44]. Early antigenic exposure and continual
exposure tend to be protective, whereas intermittent exposure
favours the development of hypersensitivity. Once hypersensitive,
217
EJCAP - Vol. 19 - Issue 3 December 2009
dog: A model for food allergy. Lab Anim Sci. 1997; 47: 40-49.
[31] Martin A, Sierra M-P, Gonzales JL, Arevalo M-A. Identifications
of allergens responsible for cutaneous adverse food reactions to
lamb, beef and cow’s milk. Vet Dermatol. 2004; 15: 349-356.
[32] Jackson HA, Hammerberg B. Evaluation of a spontaneous model
of IgE-mediated food hypersensitivity; dynamic changes in serum
and fecal allergen-specific immunoglobulin E values relative to
dietary change. Comp Med. 2002; 52: 316-321.
[33] Rosser EJ. Diagnosis of food allergy in dogs. J Am Vet Med Assoc.
1993; 203: 259-262.
[34] Roehr CC, Reibel S, Zeigert M, Sommerfield C, Wahn U,
Niggemann B. Atopy patch test, together with determination of
specific IgE levels, reduces the need for oral food challenges in
children with atopic dermatitis. J Allergy Clin Immunol. 2001; 107:
548-553.
[35] Halliwell REW, Gordon CM, Horvath C, Wagner R. IgE and IgG
antibodies to food antigens in sera from normal dogs, dogs
with atopic dermatitis and dogs with adverse food reactions. In:
Hillier A, Foster AP, Kwochka KW (eds). Advances in Veterinary
Dermatology Vol 5, Blackwell, Oxford, 2005, 28-35.
[36] Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination
tests based upon IgG antibodies in irritable bowel syndrome: a
randomised controlled trial. Gut. 2004; 53: 1459-1464.
[37] Michaeli D, Benjamini E, Deburen FP, Larivee DH, Feingold BF. The
role of collagen in the induction of flea bite hypersensitivity. J
Immunol. 1965; 95: 162-170.
[38] Halliwell REW, Preston JF, Nesbitt J. Aspects of the
immunopathogenesis of flea allergy in dogs. Vet Immunol
Immunopathol. 1987; 17: 483-494.
[39] McDermott MJ, Weber E, Hunter S, Stedman KE, Best E, Frank
GR et al. Idenification, cloning and characterization of a major cat
salivary flea allergy (Cte f 1). Molecular Immunol. 2000;37:361375.
[40] Gross TL, Halliwell REW. The histopathology of experimental flea
allergy dermatitis in dogs. Vet Pathol. 1985; 22: 78-81.
[41] Halliwell REW, Schemmer KR. The role of basophils in the
immunopathogenesis of hypersensitivity to fleas (Ctenocephalides
felis) in dogs. Vet Immunol Immunopathol. 1987; 15: 283-289.
[42] Halliwell REW, Longino, SL. IgE and IgG antibodies to flea allergen
in differring dog populations. Vet Immunol Immunopathol. 1985;
8: 215-223.
[43] Halliwell REW. Clinical and immunological aspects of allergic skin
diseases in domestic animals. In: von Tscharner C, Halliwell REW
(eds). Advances in Veterinary Dermatology Vol 1, Balliere Tindall,
London, 1990, 91-116.
[44] Carlotti DN, Costargent F. Analysis of positive skin tests in 449
dogs with allergic dermatitis. Eur J Comp Anim Pract. 1994; 4:
42-59.
[45] Kunkle GA, McCall CA, Stedman KE, Pilny C, Nicklin C, Logas
DB. Pilot study to assess the effects of early flea exposure on the
development of flea hypersensitivity in cats. J Fel Med Surg. 2003;
5: 287-294.
[46] Kunkle GA. Contact dermatitis. Vet Clin N Am Small Anim Pract.
1988; 18: 1061-1068.
[47] Kunkle GA, Gross TL. Allergic contact dermatitis to Tradescantia
fluminensis (wandering Jew) in a dog. Comp Cont Ed Pract Vet.
1984; 5: 925-929.
[48] Thomsen MK, Thomsen HK. Histopathological changes in canine
allergic contact dermatitis patch test reactions. A study on
spontaneously hypersensitive dogs. Acta Vet Scand. 1989; 30:
379-384.
[11] Taglinger K, Day MJ, Foster AP. Characterization of inflammatory
cell infiltration in feline allergic skin disease. J Comp Pathol. 2007;
137: 211-223.
[12] Roosje PJ, Koeman JP, Thepen T, Willemse T. Mast cells and
eosinophils in feline allergic dermatitis: A qualitative and
quantitative analysis. J Comp Pathol. 2004; 131: 61-69.
[13] Roosje PJ, van Kooten PJS, Thepen T, Bihari IC, Rutten VPMG,
Koeman JP et al. Increased numbers of CD4+ and CD8+ T cells in
lesional skin of cats with allergic dermatitis. Vet Pathol. 1998; 35:
268-273.
[14] Roosje PJ, Thepen T, Rutten VPMG, van den Brom WE, BruijnzeelKoomen CAFM, Willemse T. Immunophenotyping of the
cutaneous cellular infiltrate after atopy patch testing in cats with
atopic dermatitis. Vet Immunol Immunopathol. 2004; 101: 143151.
[15] Olivry T, Dean GA, Tomkins MB, Dow JL, Moore PF. Toward a
canine model of atopic dermatitis: Amplification of cytokine-gene
transcripts in the skin of atopic dogs. Exp Dermatol. 1999;8:204211.
[16] Nuttall TJ, Knight PA, McAleese SM, Lamb JR, Hill PB. T-helper
1, T-helper 2 and immunosuppressive cytokines in canine atopic
dermatitis. Vet Immunol Immunopathol. 2002; 87: 379-384.
[17] Nuttall TJ, Knight PA, McAleese SM, Lamb JR, Hill PB. Expression
of Th1, Th2 and immunosuppressive cytokine gene transcripts in
canine atopic dermatitis. Clin Exp Allergy. 2002; 32: 789-795.
[18] Marsella R, Olivry T, Maeda S. Cellular and cytokine kinetics after
epicutaneous allergen challenge (atopy patch testing) with house
dust mites in high-IgE beagles. Vet Dermatol. 2006; 17: 111-120.
[19] Roosje PJ, Dean GA, Willemse T, Rutten VPMG, Thepen T.
Interleukin 4-producing CD4+ T cells in the skin of cats with
allergic dermatitis. Vet Pathol. 2002; 39: 228-233.
[20] Taglinger K, Van Nguyen N, Helps CR, Day MJ, Foster AP.
Quantitative real-time RT-PCR measurement of cytokine mRNA
expression in the skin of normal cats and cats with allergic skin
disease. Vet Immunol Immunopathol. 2008; 122: 216-230.
[21] Iwasaki T, Hasegawa A. A randomized comparative clinical trial of
recombinant canine interferon-gamma (KT-100) in atopic dogs
using antihistamine as control. Vet Dermatol. 2006; 17: 195-200.
[22] Shida M, Kadoya M, Park S-J, Nishifuji, K, Momoi Y, Iwasaki T.
Allergen-specific immunotherapy induces Th1 shift in dogs with
atopic dermatitis. Vet Immunol Immunopathol. 2004;102:19-31.
[23] Kietzmann M. Eicosanoid levels in canine inflammatory skin
disease. In: Von Tscharner C, Halliwell REW (Eds). Advances in
Veterinary Dermatology, Vol 1, Balliere Tindall, London, 211-220.
[24] McEwan NA, Kalna G, Mellor D. A comparison of adherence
by four strains of Staphylococcus intermedius and Staphyloccus
hominus to canine corneocytes collected from normal dogs and
dogs suffering from atopic dermatitis. Res Vet Sci. 2005; 78: 193198.
[25] Simou C, Thoday KL, Forsythe PJ, Hill PB. Adherence of
Staphylococcus intermedius to corneocytes of healthy and atopic
dogs: Effect of pyoderma, pruritus score, treatment and gender.
Vet Dermatol. 2005; 16: 385-391.
[26] Morales CA, Schultz KT, DeBoer DJ. Antistaphylococcal antibodies
in dogs with recurrent staphylococcal pyoderma. Vet Immunol
Immunopathol. 1994;42:137-147.
[27] Nardoni S, Dini M, Taccini F, Mancianti F. Occurrence, distrtibution
and population size of Malassezia pachydermatis on skin and
mucosae of atopic dogs. Vet Microbiol. 2007; 122: 172-177.
[28] Nuttall TJ, Halliwell RE. Serum antibodies to Malassezia yeasts in
canine atopic dermatitis. Vet Dermatol 2001; 12: 327-332.
[29] Ordeix L, Galeotti F, Scarampella F, Dedola C, Bardagi M, Romano
E et al. Malassezia spp overgrowth in allergic cats. Vet Dermatol.
2007; 18: 316-323.
[30] Ermel RW, Kock M, Griffey SM, Reinhart GA, Frick OL. The atopic
218
DERMATOLOGY
Clinical signs and diagnosis of
canine atopic dermatitis
C. Favrot1)
SUMMARY
Canine Atopic Dermatitis (CAD) is the most frequent canine dermatosis. It has been defined by the International
Task Force on Canine Atopic Dermatitis ( ITFCAD) as a “genetically predisposed inflammatory and pruritic allergic
skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against
environmental allergens”[1]. A ITFCAD-revised nomenclature for veterinary allergy also takes into account dogs
with clinical signs of atopic dermatitis but no demonstrable allergen-specific IgE (Intradermal tests and/or serology):
the term atopic-like dermatitis (ALD) was coined to described this group of dogs[1].
breeds while some others have been based on a comparison
between atopic dogs and the hospital or insurance population
[5-13]. The former do not present any statistical analysis and the
latter may be biased by the absence or the underrepresentation
of healthy dogs. One single study is based on a large population
of insured dogs but contains another potential bias: the authors
did not make the diagnosis of CAD themselves but referred to
the diagnosis of general practitioners, who may have
This paper was commissioned by FECAVA for
publication in EJCAP.
Introduction
In veterinary dermatology, cutaneous adverse food reaction
(CAFR) and CAD have been historically considered as two
different conditions[2]. In fact, CAFR includes both immunemediated and non immune-mediated food intolerances and
may be associated with a wide range of clinical signs such as
gastro-intestinal disturbances, urticaria, angioedema, and signs
mimicking those of atopic dermatitis. This latter point has led
the ITFCAD International Task Force on Canine Atopic Dermatitis
to suggest that some cases of CAFR may trigger flares of atopic
dermatitis[3]. The clinical signs of CAD may thus be associated
with sensitization to environmental (CAD sensu stricto), food
allergens (CAFR with clinical signs of CAD: Food-Induced
Atopic Dermatitis: FIAD) or with ALD. The present article will
consequently describe the clinical features and diagnostic
methods of dogs affected by CAD from whatever cause. The
clinical signs and diagnostic methods of food allergy are however
beyond the scope of this article.
used variable inclusion criteria [6]. To further complicate the
analysis, predisposed breeds may vary by geographical areas
[14, 15]. One single study is based on the comparison of a
population of atopic dog and a validated population of healthy
dogs [16]. This study was however limited to Switzerland. Some
breeds such as West Highland white terriers, boxers, Bulldogs
are, however, mentioned in virtually all these studies. Some
others such as German shepherd dogs, golden retrievers or
Labrador retrievers seem to be predisposed for CAD only in
some geographical regions.
Signalement of CAD dogs
Reports of sex predisposition in CAD dogs are inconsistent.
Some studies reported predisposition for male, female or for
neither sex [14]. We have recently studied a large population of
843 CAD dogs and no sex predilection was detected when the
whole population was taken into account [17]. However, some
sex predispositions were detected in some breed such as golden
or Labrador retrievers (more female) or Boxer (more male).
The definition of CAD suggests strong breed and/or familial
predispositions. Reliable evaluation of breed predispositions for
veterinary diseases is complicated by the fact that the population
at risk is often unknown. Several studies have, however,
addressed the question of breed predisposition for CAD [4].
Some studies only mentioned the most frequently represented
The typical age at onset of CAD is reported to be between 6
months and 3 years [14]. We have however recently shown that
about 78% of CAD present with clinical signs before three years
of age [17]. It does mean that every fifth CAD dog develops the
first clinical signs later in life.
1) Claude Favrot, Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of. Zurich
219
Clinical signs and diagnosis of canine atopic dermatitis -
History of CAD dogs
Information regarding the history of the affected dog should be
recorded carefully. Some important questions have already been
mentioned (age at onset, breed, familial predisposition) but some
others such as seasonality, presence of “pruritus sine material”
(pruritus with no skin changes) at onset, efficacy of previous
treatment, should be asked before any clinical examination.
Clinical signs of CAD may be seasonal or not but seasonality is
often present at onset (42-75%) [14]. Approximately 80% of
dogs with seasonal signs are symptomatic in spring or summer
while the others exhibit signs in winter or autumn [18]. It should
be mentioned that some dogs with non seasonal disease do
exhibit worsening of clinical signs during one specific season.
Fig. 2 Secondary infections develop in the vast majority of atopic
dogs ( in this case, malassezia dermatitis)
Pruritus must be present and its absence rules out the diagnosis
CAD. In fact, some CAD dogs do exhibit initially pruritus sine
material. This feature was recorded in 61% of affected dogs
in our recent study [17]. As well, 43% of CAD dogs presented
first with an episode of otitis externa. In comparison, associated
conjunctivitis /blepharitis are much rarer. CAD dogs are often
treated with glucocorticoids and responses to such therapy
should be evaluated carefully. In the same study, we have
shown that 78% of CAD dogs responded adequately to such
treatment. In the first stages of the disease, the pruritus responds
well and readily to the administration of reduced amount of
glucocorticoid (i.e. 0.3-0.5mg/kg Prednisolone daily). In chronic
cases however, the development of secondary bacterial or yeast
infections usually corresponds with a poorer response to such
treatment.
to the lack of pathognomonic signs and the protean clinical
picture. Erythema and pruritus are however virtually always
present and often represent the first clinical signs (Fig. 1).
However, mild pruritus may remain unrecognized by the owner
and the veterinarian may sometimes rely on indirect proofs of
pruritus such as the presence of excoriations or saliva-coloured
hairs.
Most of the signs are actually due to self-trauma and/or
secondary infections. In fact, small erythematous papules,
which are considered the primary lesion of CAD, are rarely
observed in CAD dogs [14]. The practitioner will usually observe
the consequences of the inflammation and pruritus, namely
excoriations and self-induced alopecia and/or the signs of the
secondary bacterial infection (papules, pustules, crusts, erosions)
and/or the symptoms of secondary yeast dermatitis (epidermal
hyperplasia, hyperpigmentation, lichenification). Recurrent or
chronic skin or ear infections are very frequently observed in
CAD (Fig. 2): In our study, bacterial infections were observed
in 66% of the patients while malassezia dermatitis and otitis
externa were present in 33% and 50% of all affected dogs,
respectively.
Last but not least, we have also showed that 82% of atopic dogs
spend most of their time indoor. This suggests that prolonged
exposure to house dust mites may trigger or worsen CAD clinical
signs.
Clinical signs of CAD
Although very frequent, CAD may be difficult to diagnose owing
Fig. 1 Pruritus and erytham are virtually always present in atopic
dogs.
Fig. 3 Feet are very often affected in atopic dogs.
220
EJCAP - Vol. 19 - Issue 3 December 2009
Tab. 1 Criteria for the diagnosis of canine atopic dermatitis
and associated sensitivity and specificity.
1.
Age at onset < 3years
2.
Mostly indoor
3.
Corticosteroid-responsive pruritus
4.
Chronic or recurrent yeast infections
5.
Affected front feet
6.
Affected ear pinnae
7.
Non –affected ear margins
8.
Non-affected dorso-lumbar area
Sensitivity when 5 criteria are fulfilled: 85%
Specificity when 5 criteria are fulfilled: 79%
Sensitivity when 6 criteria are fulfilled: 58%
Specificity when 6 criteria are fulfilled: 88%
Fig. 4 Axillae are affected in about 62% of atopic dogs.
Most of these signs are however not specific at all and the
distribution of these lesions is consequently more helpful. The
most often affected areas are the pinnae (58%), the axillae
(62%), the abdomen (66%), the front (79%) and hind feet
(75%), the lips (42%) and the perineal area (43%) (Figures 3
and 4). Unfortunately, all these areas are rarely simultaneously
affected in the same individual, except in chronic cases.
ruled out. Depending on the clinical presentation and the age
of the affected dog, some other differentials, i.e.demodicosis,
dermatophytosis, cheyletiellosis, cutaneous lymphoma should
be properly ruled out. It should also be mentioned that the
histological aspect of allergic skin is usually not specific and that
this test is consequently not adequate to make the diagnosis.
It may be indicated, however, to perform skin biopsies in some
instances, to rule out some differentials such as cutaneous
lymphoma, for example. As well, allergy testing (serological
evaluation of allergen-specific IgE and intradermal skin testing)
are not regarded as criteria for the diagnosis of CAD. This is
because numerous healthy dogs are sensitized to environmental
allergens and are consequently positive (poor specificity of this
criterion) and ALD and some FIAD dogs are deemed negative.
These tests should consequently be only carried out to identify
the offending allergens (i.e. to choose the allergens for allergenspecific immune therapy: desensitization). In the same way,
inorder to identify FIAD dogs, a 6-to 8-week elimination diet
and a subsequent challenge with the previous food should be
carried out in all dogs with clinical signs of CAD.
Dermatological (pyotraumatic dermatitis, interdigital fistulae)
and non dermatological signs are sometimes associated
with CAD and their presence should reinforce the suspicion.
Spring/summer conjunctivitis, for example, is presented in
approximatively 20% of CAD dogs while gastro-intestinal signs
(soft stools, diarrhea, vomiting) are recognized in 26% of FIAD
dogs.
Clinical signs of FIAD dogs differ very slightly from those
of classical, environment-induced AD. In fact, in our study,
statistically significant differences were only uncovered for
gastro-intestinal signs, seasonality, cortico-sensible pruritus and
pruritus sine material (less frequent in FIAD dogs). As well, more
FIAD dogs show the first clinical signs early in life (less than one
year) or, on the contrary, rather late (more than 6 years of age).
Several sets of criteria have been proposed for the diagnosis of
CAD. These criteria are however mainly used for clinical trial to
increase homogeneity of the recruited dogs [12, 14, 19, 20]. We
have recently performed a study, in which 1800 pruritic dogs
were included by experienced dermatologists throughout the
world [17]. One of the goals of the study was to identify criteria
for the diagnosis of CAD. The best identified set of criteria (see
table) has been associated with a sensitivity and specificity of
about 80%, when 5 out of 8 criteria are fulfilled (Tab. 1). It does
mean that using these sole criteria would lead the practionner
to make a wrong diagnosis in every fifth dog. These data
confirm that ruling out resembling diseases should always be a
compulsory prerequisite for the diagnosis of CAD.
Diagnosis of CAD
The diagnosis of CAD is based on the history (age at onset,
seasonality, pruritus sine material at onset, familial or breed
predisposition, previous response to glucocorticoids), the
development of the disease (seasonality, “wax and wane”
character, development of secondary skin infections) and the
lesional pattern. A diagnosis of CAD should however never been
made, as long as resembling diseases such as fleas, ectoparasites
(sarcoptic mange) and primary skin infections have not been
221
Clinical signs and diagnosis of canine atopic dermatitis -
References
[1]
Halliwell R. Revised nomenclature for veterinary allergy. Vet
Immunol Immunopathol. 2006; 114(3-4): p. 207-8.
[2] Hillier A, Griffin CE. The ACVD task force on canine atopic
dermatitis (X): is there a relationship between canine atopic
dermatitis and cutaneous adverse food reactions? Vet Immunol
Immunopathol. 2001; 81: p. 219-226.
[3] Olivry T, et al. Food for thought: pondering the relationship
between canine atopic dermatitis and cutaneous adverse food
reactions. Vet Dermatol. 2007; 18(6): p. 390-1.
[4] Sousa CA, Marsella R. The ACVD task force on canine atopic
dermatitis (II): genetic factors. Vet Immunol Immunopathol. 2001;
81: p. 153-158.
[5] Koch HJ, Peters S. 207 intrakutantests bei hunden mit verdacht
auf atopische dermatitis. Kleintierprax. 1994; 39: p. 25-36.
[6] Nodtvedt A. et al. Canine atopic dermatitis: validation of recorded
diagnosis against practice records in 335 insured Swedish dogs.
Acta Vet Scand. 2006; 48(1): p. 8.
[7] Nodtvedt A. et al. Incidence of and risk factors for atopic dermatitis
in a Swedish population of insured dogs. Vet Rec. 2006; 159(8):
p. 241-6.
[8] Saridomichelakis MN. et al. Canine atopic dermatitis in Greece:
clinical observations and the prevalence of positive intradermal test
reactions in 91 spontaneous cases. Vet Immunol Immunopathol.
1999; 69(1): p. 61-73.
[9] Sture GH. et al. Canine atopic disease: the prevalence of positive
intradermal skin tests at two sites in the north and south of Great
Britain. Vet Immunol Immunopathol. 1995; 44(3-4): p. 293-308.
[10] Tarpataki N. et al. Prevalence and features of canine atopic
dermatitis in Hungary. Acta Vet Hung. 2006; 54(3): p. 353-66.
[11] Willemse A, Brom WE vand den. Investigations of the
symptomatology and the significance of immediate skin test
reactivity in canine atopic dermatitis. Research in Veterinary
Sciences. 1983; 34: p. 261-265.
[12] Willemse TA. Atopic dermatitis: a review and reconsideration of
diagnostic criteria. Journal of Small Animal Practice. 1986; 27: p.
771-778.
[13] Carlotti D, Costargent F. Analysis of positive skin tests in 449 dogs
with allergic dermatitis. European Journal of Companion Animal
Practice. 1994; 4: p. 42-59.
[14] Griffin CE, De boer DJ. The ACVD task force on canine atopic
dermatitis (XIV): clinical manifestations of canine atopic dermatitis.
Vet Immunol Immunopathol. 2001; 81: p. 255-269.
[15] Nodtvedt A. et al. The spatial distribution of atopic dermatitis
cases in a population of insured Swedish dogs. Prev Vet Med.
2007; 78(3-4): p. 210-22.
[16] Picco F. et al. A prospective study on canine atopic dermatitis and
food-induced allergic dermatitis in Switzerland. Vet Dermatol.
2008; 19(3): p. 150-5.
[17] Favrot C. et al. A prospective study on the clinical features of
chronic canine atopic dermatitis and its diagnosis. Veterinary
Dermatology. 2009; 20: p. In Press.
[18] Scott DW. Obersvations on canine atopic dermatitis. Journal of
the American Animal Hospital Association. 1981; 17: p. 89-102.
[19] Prélaud P. et al. [Reevaluation of diagnostic criteria of canine
atopic dermatitis]. Rev Med Vet. 1998; 149: p. 1057-1064.
[20] Williams HC. Diagnostic criteria for atopic dermatitis. Lancet.
1996; 348(9038): p. 1391-2.
The big relief!
For
cats
and
dogs!
The effective approach to allergy in dogs and cats starts with the Artuvetrin® Serum Test;
the reliable allergy test that makes the allergen-specific IgE in the serum visible via the Fc region.
Based on the outcome of this test, we can provide you with an allergen-specific vaccine:
a big relief for allergy patients!
The authority on animal allergies
T E L . : + 3 1( 0 ) 3 2 0 - 2 6 7 9 0 0 - W W W. A R T U V E T R I N . C O M
DERMATOLOGY
Feline atopic dermatitis:
Clinical signs and diagnosis
C. Prost (1)
SUMMARY
Although feline atopy was first decribed more than 25 years ago, the immunopathogenesis of this disease is still not
entirely understood. It is thought to be similar to that of canine atopy .Cats can develop a variety of pruritic skin
conditions including self-induced alopecia, cervico-facial pruritus and eosinophilic dermatosis (miliary dermatitis,
eosinophilic plaques, eosinophilic granuloma and indolent ulcer). Feline atopy can also present as a respiratory
disease similar to human atopic asthma. Establishing a diagnosis of atopy is difficult and requires exclusion of other
cutaneous diseases such as flea bite allergy, food hypersensitivity, parasitic diseases and dermatophytosis. Evaluating
the allergic status in cats with intradermal allergy testing or in vitro methods remains a challenge. Here is a diagnostic
approach for identifying cats with atopic dermatitis.
Atopy is a genetic predisposition to develop IgE-mediated
allergy to environmental allergens. In cats, atopy usually results
in pruritic skin diseases, but there may also be a relationship
between atopy and asthma. Feline atopy remains poorly
understood, but its immunopathogenesis is thought to be
similar to that of canine atopy. Characterization of inflammatory
cell infiltration in feline allergic skin diseases showing one or
more features (alopecia, eosinophilic plaques or granulomas,
papulocrusting lesions) confirm infiltration of activated antigenpresenting cells and T lymphocytes in addition to increased
numbers of dermal mast cells. This pattern mimics the dermal
inflammation that occurs in the chronic phase of both canine
and human atopic dermatitis [1]. In cats with recurrent “miliary”
papulo-crusting dermatitis a significant total increase in dermal
T-cells numbers was reported. Significantly more IL-4 positive
cells were found in lesional and non lesional skin from allergic
cats than from healthy controls [2]. Nevertheless, atopic cats do
not have significantly higher concentrations of allergen-specific
IgE than normal cats [3].
Clinical signs
Estimates of the incidence of Feline Atopic Dermatitis (FAD) vary
widely. Genetic predilection has not been proved. The strongest
evidence to date in support of heritability is the presence of a
disease closely resembling atopic dermatitis in three littermates
[4].
FAD is associated with several cutaneous reaction patterns.
Lesions include self-induced alopecia, cervico-facial dermatoses,
miliary dermatitis and feline eosinophilic skin diseases such as
feline eosinophilic plaques, feline eosinophilic granuloma and
feline indolent ulcer.
The age of onset is usually under 3 years of age. A unifying
description of expected clinical features is not available for cats.
The most consistent clinical feature is chronic recurrent pruritus
manifested by scratching, biting and licking. Some cats hide to
lick and tend to be secret groomers. Owners are often unable
to distinguish pruritus from normal grooming behavior and may
deny that the cat traumatizes itself. Pruritus may then need to
be deduced clinically via indirect evidence such as trichograms
revealing barbered hairs, tufts of hair in the cat’s hiding places,
vomiting of hair balls and excess hair in the feces.
Self-traumatized areas may be localized or generalized. The
face, neck, pinnae, forelegs and ventrum may, as in dogs, be
more severely affected. Nevertheless chronic skin changes such
as lichenification and hyperpigmentation and secondary skin
and ear infections due to bacteria or Malassezia yeasts are less
common in atopic cats than in atopic dogs.
1) Christine Post, DVM, DECVD, TUFTS VETS 525 South Street Walpole, MA 02081, USA
Email: [email protected]
223
EJCAP - Vol. 19 - Issue 3 December 2009
Eosinophilic plaques in atopic cat with intradermal positive reactions to pollens.
Eosinophilic plaques, eosinophilic granuloma, and eosinophilic
ulcers are often grouped into what is called the ‘eosinophilic
granuloma complex”. This term is not completely accurate, since
the only condition histologically consistent with a granulomatous
lesion is the eosinophilic granuloma and the etiology of these
conditions is not always the same.
Eosinophilic dermatoses occur when there is an underlying
pruritic condition irrespective of whether the cause is parasitic,
allergic (atopy included), or fungal in nature. However, the ulcer
and eosinophilic granuloma can be asymptomatic.
Miliary dermatitis of the cat is the eosinophilic dermatosis
most specific to cats. It is characterized by small crusty papules,
more or less erosive or ulcerated. They can be localized (along the
back, face and neck) or generalized. Histologically, intercellular
edema of the keratinocytes (spongiosis) is observed, with or
without epidermal vesiculation ,and eosinophilic exocytosis.
Dermal inflammation consists mostly of eosinophils and mast
cells. In the most severe cases, marked spongiosis and secondary
focal erosions or ulcerations make it difficult to distinguish the
lesions of miliary dermatitis from those of eosinophilic plaques
[6]. In fact, miliary dermatitis lesions are thought to be precursors
of eosinophilic plaques, and both types of lesion can be found
concurrently on the same animal. Miliary dermatitis is caused
most frequently by allergic reactions, most notably associated
Eosinophilic granuloma presenting as nodules and plaques on the
head.
Severely inflammed eosinophilic plaques in a cat allergic to house
dust mites.
with flea bite hypersensitivity but also allergy to environmental
allergens.
Eosinophilic plaques accompanied by severe pruritus are
typically localized on the ventral abdomen, medial aspect of
thighs, and peri-anal region. They are firm, raised, often ulcerated,
and markedly inflamed. Chronic trauma due to constant licking
contributes to the development of these plaques. Histologically,
severe epidermal and follicular acanthosis, eosinophilic
exocytosis , spongiosis , and epidermal and follicular mucinosis
are frequently noted. The dermis is densely infiltrated with
eosinophils associated with mast cells and a small degree of
lympho- plasmacytic inflammation. An allergic reaction (e,g. to
224
Feline atopic dermatitis: Clinical signs and diagnosis- C. Prost
Eosinophilic granuloma presenting as painful edema of the paws.
Severe facial pruritus with secondary crusts and ulcerations.
ectoparasites, food allergens or airborne allergens) is mostly to
blame for this type of lesion.
• As pododermatitis with ulcerations of the toe pads,
interdigital erythema, or edema of the toe pads.
• Edema of the lower lip or chin
• \Very firm nodules affecting the tongue and/or palate,
sometimes ulcerated. Buccal lesions are sometimes
accompanied by other signs including malodorous breath,
anorexia, dysphagia, or hypersalivation.
The eosinophilic granuloma is a clinical entity that occurs
very frequently in the cat. The histological appearance of this
lesion is pathognomonic for the condition. In the cat, lesions
tend to have a cutaneous, muco-cutaneous, or oral location.
They typically present in one of the following ways:
• As plaques or very firm papules, erythematous and
occasionally yellowish, well circumscribed and with a linear
distribution. They are located on the caudal thighs, or more
rarely on the neck, thorax, or front legs.
• As plaques or nodules on the ears
These lesions do not initially seem pruritic. Eosinophilic
degranulation may lead to the development of small, pinpoint,
white or pink spots which cause pruritus and secondary erosion
or ulceration due to chronic licking.
Face and neck pruritus in an atopic cat.
Linear eosinophilic granuloma.
225
EJCAP - Vol. 19 - Issue 3 December 2009
Seasonal bilateral indolent ulcer in a atopic cat.
The diverse clinical appearances of the eosinophilic granuloma
make it difficult to diagnose, and cutaneous biopsies are often
necessary to distinguish the nodular form of eosinophilic
granuloma from neoplasia, mycosis, or abscess.
Histological H&E staining reveals irregular and granular collagen
fibers that suggest a degenerative process. However, studies using
special stains such as Gallego’trichrome and Masson’trichrome
and electron microscopy have shown that the collagen fibers
in eosinophilic granulomas are not degenerate, but covered by
granules and products released during eosinophil degranulation
that agglutinate around them (= flame figures). It is the poorly
soluble proteins released by the eosinophilic granules that cause
granulomatous reactions visible in their chronic form as zones
surrounded by macrophages and giant cells, often is palisading
array. [9].
Seasonal keratitis concomitant with the lip ulcer.
of the upper lip apposing the lower canine tooth, just lateral
to the philtrum. Lesions are usually solitary and unilateral,
sometimes bilateral. They can create a somewhat monstrous
appearance to the face. The lesion is bothersome to the affected
cat especially as it makes eating difficult, but is not painful. An
accompanying lymphadenopathy is sometimes described. The
co-existence of an indolent ulcer with plaques or an eosinophilic
granuloma suggests that an underlying allergy plays a role in
its pathogenesis especially as the lesion often resolves with
anti-parasitic therapy, an elimination diet, or immunotherapy.
In one study, flea allergy dermatitis was induced in 10 cats both
with intermittent and continual flea exposure. Five of the ten
cats developed lip ulcers during this study period and all were
exposed to fleas at the time of onset [10]. The POWER study
identified hereditary transmission of the syndrome in a family of
cats that developed lesions spontaneously without associated
pathology. A genetic predisposition is therefore likely [11].
The main causes of eosinophilic granulomas are allergic or
parasitic, sometimes complicated by secondary bacterial
infection.
The indolent ulcer is a very common condition, although its
pathogenesis is unknown. Lesions are well defined ulcers, with
raised firm edges, varying from 2mm-5cm in size. The most
common site is the junction of the skin and mucous membrane
Extensive alopecia in an atopic cat.
226
Feline atopic dermatitis: Clinical signs and diagnosis- C. Prost
Differential diagnosis should include ulcers of infectious origin
(bacterial, fungal, or secondary to FeLV), traumatic ulcers, and
neoplasia (e.g.carcinoma, mast cell tumors and lymphoma).
The chronic indolent ulcer is characterized by a cellular infiltrate
consisting of mononuclear cells and neutrophils, dermal
fibrosis, and focal necrosis in the deepest areas of the dermis.
If the lesion is biopsied in its acute phase, the cellular infiltrate
consists mostly of eosinophils and mast cells, macrophages, and
neutrophils. However, granulomatous changes are occasionally
noted. In some cases, the interstitial and perivascular infiltrate
consists of neutrophils and the ulcer is colonized by bacteriae.
This is a dermatosis for which therapeutic failures are common
and remission is often short lived.
All four forms of eosinophilic dermatoses may occur
simultaneously or at different times in the same cat.
Intradermal skin testing in a cat. the cat is sedated, hair is clipped
and skin is marked to visualize the injections dots.
believed to involve a type I hypersensitivity to inhaled allergens. In
a recent study, 20 cats presented with respiratory signs (recurrent
bouts of coughing, wheezing, dyspnea) , radiographic images
and bronchial cytology compatible with asthma showed positive
reactions on intradermal allergy testing. Avoidance of dried
food in 3 cats positive for storage mites or cockroach led a good
and lasting remission of clinical signs. Specific immunotherapy
was effective in controlling signs in12 cats [13]. ) It is likely than
airborne allergens act as starting factors in feline asthma. Feline
asthma is another clinical presentation of atopy in cats.
Feline self-induced alopecia (= feline symmetrical alopecia)
presents as hair loss due to constant excessive licking with
no inflammatory lesions. The ventral abdomen is commonly
affected but medial and lateral limbs, flanks and lumbosacral
region may also be involved. Notable histopathological findings
are superficial eosinophilic and mild lymphohistiocytic infiltrate.
Differential diagnosis includes psychogenic alopecia. A recent
study suggests that psychogenic alopecia is overdiagnosed in
cats and that a medical cause (e.g. adverse food reaction or
atopy) of pruritus is present in 76 % of feline patients with a
presumptive diagnosis of behavior problem [12].
Diagnosis
Considering so many diseases with similar signs, it is often
difficult to make an accurate clinical diagnosis of atopic dermatitis
in cats. The same cutaneous reaction patterns may accompany
flea hypersensitivity, adverse food reaction and feline atopy. It is
essential to perform a thorough physical examination and obtain
a detailed history before proceeding to diagnostic tests and
therapeutic trials to rule out differentials and confirm feline atopic
dermatitis. The following diagnostic approach is proposed:
Cervicofacial pruritus leads to severe inflammatory selfinduced lesions including erosions, ulcers and crusts. The
location of the head may be due to the snooping behavior of
cats and their tendency for hunting that expose the head to
transmissible organisms or offending allergens, the sparseness
of hair on the preauricular , dorsal muzzle and pinnae areas or
anatomical particularities such as voluminous sebaceous glands
on the chin . The lesions appear sometimes very impressive
to owners. Atopy may be a cause of face and neck pruritus.
Secondary bacterial infections occur more commonly than they
are reported ( probably underdiagnosed).
1. First and foremost it is critical to identify the type of
lesion present. A biopsy may be necessary for atypical
eosinophilic granuloma presentations and for nodular
lesions. Cytological evaluation can also be very useful, and
may reveal the presence of many eosinophils (confirming
the diagnosis of eosinophilic dermatoses) or the presence
of bacteria and granulocytes (suggesting pyoderma or even
Malassezia dermatitis).
Feline asthma is very similar to human asthma. Feline asthma is
Miliary dermatitis in an allergic Positive skin tests in an atopic
cat.
cat, distinct papules.
2. Basic diagnostic tests and therapeutic trials must
always be carried out before specific allergy testing for
environmental allergens.
a. skin scrapings, direct examination of the cerumen
and ear cytology are indicated particularly with facial
lesions,
b. use of Wood’s lamp, direct examination of hair and
scale, fungal cultures are systematically performed
c. a flea control trial with topical flea products for 1-2
months in affected cats and in other pets living in the
same environment should be conducted first. The best
choice is an adulticide with effects on egg production
and/or larva emergence or an adulticide associated with
227
EJCAP - Vol. 19 - Issue 3 December 2009
Positive skin tests with erythematous papules.
Positive skin tests in a white atopic cat, see the erythematous
wheals.
Stress induces a rise in serum cortisol, corticotropin, and α MSH
(melanocyte stimulating hormone), which interferes with the
reactivity of the test. As a result, cats should be anesthetized
for intra-dermal skin testing in order to limit the stress response.
The author recommends that the animal should not be
hospitalized beforehand, and that the test should be performed
as soon as the cat arrives at the clinic. Cats can be sedated with
medetomidine, tiletamine/zolazepam, xylazine hydrochloride or
ketamine hydrochloride.
an insect growth regulator. The goal is to minimize the
number of fleas or at least maintain it below the threshold
which triggers an allergic reaction, and to provide long
term control of parasitic infestation. Regular application
of all products is critical to prevent recurrence. Bimonthly
treatment is recommended for diagnostic purposes, and
should be continued during the season in which fleas are
most abundant. For the remainder of the year even in
winter, monthly treatment can be administered. Products
containing fipronil, imidacloprid, or selamectin can be
used. In the cat, anti-parasitic therapy alone often leads
to resolution of signs. However, lesions with a significant
inflammatory component such as eosinophilic plaques
may require a short course of corticosteroids. In these
cases, absence of recurrence following cessation of
corticosteroid therapy confirms the importance of anti
parasitic therapy.
d. elimination diet of 8 weeks duration then. It can be
a hydrolyzed protein diet or a home-cooked diet with
a novel protein meat source (e.g. horse, lamb, rabbit,
pork).A vegetable source is not required in the cat,
although many cats seem to enjoy pumpkin. Beef, dairy,
fish, eggs, and chicken have been implicated as the most
commonly offending food allergens. Preservatives and
other additives are also occasionally involved.
e. Search for hypersensitivity to environmental
allergens
Cat skin is finer and tougher than dog skin. Interpretation
of intra-dermal testing requires some experience; there is
currently a lack of consensus as how to interpret these tests in
the cat. Interpretation should take place 15 minutes following
injection, with the following signs to be evaluated: presence of
erythema, swelling of the injection site, firmness of the swelling,
diameter of the swelling, and to some degree the presence of
pseudopods. Interpretation occurs ‘with the eye and with the
hands’. Subjective comparisons are inevitably made with positive
and negative controls. Examination of the reaction sites is made
in dim light with an oblique light source to examine the margins
of the reaction sites, their size and volume. Erythema in cats
with light colored skin is best visualized under normal lighting.
When in doubt, reactions should be considered negative.
One study suggested the use of liquid fluorescein in 10% saline
injected intravenously (5-10 mg/kg) after the last intra-dermal
injection to facilitate interpretation of the cutaneous reactions.
A Wood’s lamp would then be used after 15-30 minutes to
compare the diameter of each reaction to positive and negative
controls, with a positive result being a diameter equal to or
larger than the average of the positive and negative controls.
The intensity of the fluorescence is not a necessary criterion for
interpretation of the test. [14].
Allergy testing is reserved for those patients where environmental
allergies are strongly suspected. The goal is to identify offending
allergens for inclusion in specific immunotherapy.
Intra-dermal allergy testing was for a long time the only
test available for cats. Skin testing is still considered the “gold
standard” in feline allergy medicine. Selection of seasonal
allergens to be included in the test is based on geographical
location of the cat’s home. Testing with allergen mixtures is not
recommended unless strong cross-reactions have been proved
(grasses). Intra-dermal skin testing is considered difficult to
perform and to interpret in the cat.
Diagnostic blood testing in the cat with hypersensitivity has
not proved to be very useful. This is because of poor correlation
with the results of skin testing, and because feline anti-IgE
has questionable specificity in cats. All studies even the most
recent ones have failed to demonstrate significant differences
in allergen-specific IgE levels in sera from supposed atopic cats
and that of normal cats. These studies have concluded that IgE
Steroids should be stopped 2 months before skin testing is
performed; anti-histamines should be stopped 2 weeks before.
228
Feline atopic dermatitis: Clinical signs and diagnosis- C. Prost
References
serology should not be used to diagnose feline atopy [15,16].
Direct cat basophil activation test or passive sensitization of
human basophils by cat sera can be applied to allergy diagnosis in
cats. Tests are based on the measurement of basophil activation
or on the release of mediators such as histamine and LTC4 by
flow cytometry. In a preliminary study, good clinico-biological
correlation was obtained using a basophil activation model
in a population of 40 allergic cats [17]. A more recent study
adapted this method as a tool for the diagnosis of feline flea bite
hypersensitivity on cats experimentally sensitized to fleas [18].
[1]
[2]
[3]
House dust mites are the most commonly incriminated allergens.
In a study of 90 cats, Dermatophagoides farinae was positive in
80 % of cases and Dermatophagoides pteronyssinus in 46%
of cases. 40 % of cats had one or more positive reactions to
pollens [19]. In another study, house dust mites were reported
to be common causes of positive intradermal test reactions [8].
[4]
[5]
[6]
In a study on 20 atopic cats with feline asthma, intradermal
allergic tests were performed in 18 cats [13]. Three of these were
negative even after when tested for a second time. 15 cats had
positive reactions to Dermatophagoides farinae (8/15), Acarus
siro (6/15), Glyciphagus domesticus (4/15), Dermatophagoides
pteronyssinus (4/15), Tyrophagus putrescentiae (4/15),
Cockroach (2/15), Ox-eye daisy, ragweed, false acacia (2/15),
Hazel-tree, plane-tree (1/15), flea (3/15)
Specific immunotherapy was prescribed in 12 cats.
[7]
[8]
[9]
[10]
[11]
In conclusion, it is difficult to make an accurate clinical diagnosis
of atopic dermatitis in cats as we lack the major and minor
clinical criteria that we have in dogs. The diagnosis of feline
atopic dermatitis is based on dermatological clinical signs
specific to cats, exclusion of other skin diseases such as flea
bite allergy, food hypersensitivity, ectoparasitic infestation and
dermatophytosis, and skin test results. Evaluating the allergic
status in cats with intradermal allergy testing or in vitro methods
remains a challenge. Offending environmental allergens should
be identified in order to initiate specific immunotherapy.
Working on experimental models of allergic feline asthma might
help to improve our understanding of the immunopathogenesis
of feline atopy.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
229
Taglinger K, Day MJ, Foster AP. Characterization of Inflammatory
Cell Infiltration in Feline Allergic Skin Disease. J.Comp. Path. 2007;
vol.137: 211-223
Roosje PJ, Thepen T, Rutten VPMG, Van den Brom WE, BruijnzeelKoomen CAFM, Willemse T. Immunophenotyping of the cutaneous
cellular infiltrate after atopy patch testing in cats with atopic
dermatitis. Vet Immunol Immunopathol 101. 2004; 143-151
Taglinger K, Helps CR, Day MJ, Foster AP. Measurement of serum
immunoglobulin E (IgE) specific for house dust mite antigens
in normal cats and cats with allergic skin disease. Vet Immunol
Immunopathol 105. 2005; 85-93
Moriello KA. Feline Atopy in three littermates. Vet Dermatol.
2001; 12 (3): 177-181
Prost C. Atlas d’allergologie cutanee chez les carnivores
domestiques. Editions Med’Com, Paris 2000
Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Feline Eosinophilic Plaque
in Skin Diseases of the dog and cat, Clinical and Histopathologic
Diagnosis, II Edition, Blackwell. 2005; 109-111
Foster A. Clinical approach to feline eosinophilic granuloma
complex. In Practice Jan. 2003; p. 2-9
Foster A. Diagnosing and treating feline atopy. Vet Med March.
2002; pp 226-240
Fondati A, Fondevila D, Ferrer L. Histopathological study of feline
eosinophilic dermatoses. Vet Dermatol. 2001; 12: 333-338
Colombine S, et al. Induction of feline flea allergy dermatitis and
the incidence and histopathological characteristics of concurrent
indolent lip ulcers. Vet Dermatol. 2001; 12: 155-161
Power HT, Irhke PJ. .Selected eosinophilic skin diseases. Vet Clinics
of North America. 1995; 25: 833-850
Waisglass SE, Landsberg GM, Yager JA, Hall JA. Underlying
medical conditions in cats with presumptive psychogenic alopecia.
JAVMA, Vol 228, No.11, June 1, 2006
Prost C. L’asthme felin : apport des tests allergiques et de
l’immunotherapie specifique. A propos de 20 cas. Revue Francaise
d’Allergologie et d’Immunologie Clinique 48. 2008; 409-413
Schleifer SG, Willemse T. Evaluation of skin test reactivity to
environmental allergens in healthy cats and cats with atopic
dermatitis. American journal of veterinary Research, 2003; vol 64:
773-778
Bexley J, et al. Levels of house dust mite-specific serum
immunoglobulin E (IgE) in different cat populations using a
monoclonal based anti-IgE enzyme-linked immunosorbent assay
(ELISA). Vet Dermatol, vol 19 supp 1, november 2008; p20
Diesel A., DeBoer D.J – Allergen specific IgE in atopic and healthy
cats – comparison of rapid screening immunoassay and completepanel analysis. Proceedings of the 24th North American Veterinary
Dermatology Forum, Savannah, April 15-18, 2009; p 208
Prost C. Allergy diagnosis in companion animals: clinical experience
with the basophil activation model. Vet Dermatol. 1998; 9: 213215
Stuke K,
Monitoring of basophil sensitization to antigens
of the cat flea (Ctenocephalides felis felis): a new tool for the
diagnosis of feline flea bite hypersensitivity? Parasitol Res. 2008;
103: 807-820
Prost C. Diagnosis of feline allergic disease, a study of 90 cats.in
Advances in Veterinary Dermatology, vol 3, C. von Tscharner et al
eds, Butterworth Heinemann, Oxford. 1998; 516-517
DERMATOLOGY
Food allergy in dogs- clinical signs
and diagnosis
H. A. Jackson(1)
SUMMARY
Clinicians have long recognized a dermatitis which appears to be triggered by dietary components. The first
descriptions of food induced canine dermatitis date back to 1933 [1,2]. However, although we make a clinical diagnosis
of canine “food allergy” it is not clear at this time whether these cases are truly immunologically mediated or due
to a “food intolerance” (Tab. 1). Furthermore, although there is evidence of a role for IgE in the pathogenesis of food
allergy in colony dogs with spontaneous food allergy [3] it is not clear whether this is representative of the disease in
the general population. Thus for the purpose of this discussion, although the term food allergy is used throughout, it
should be recognized that this term is a presumptive clinical diagnosis and adverse food reaction is a more accurate
term for these canine cases.
This paper was commissioned by FECAVA for
Other presentations of food allergy are recognized such as
a recurrent superficial pyoderma [7,8] and pruritic papular
eruptions over the trunk and head (Fig. 4). Recurrent otitis
externa is a common complaint and may be present in 56% to
80% of cases [7-11]. Dogs may present with only otitis externa
and occasionally this affects a single ear. There is debate over
the frequency of concurrent gastrointestinal signs in patients
with dermatologic signs of food allergy [5-7,10,11]. In this
author’s experience, intermittent vomiting, diarrhoea, colitis,
or borborygmus may be present. It has been reported that
canine food allergy may respond poorly to antipruritic doses of
glucocorticoids, but most clinicians now agree this distinction
is not a useful diagnostic feature. Two studies report that the
majority of dogs with food allergy present before three years of
age (Fig. 5) [5,6]. However, this disorder can occur at any age
and should be considered in the older dog with no previous
history of pruritus (Figures 6 and 7). Labrador retrievers, West
Highland White terriers, boxers, Rhodesian ridgebacks and
pugs are reportedly at increased risk for developing food allergy
[5,6,10].
publication in EJCAP.
Clinical presentation
Food allergy in dogs often assumes the clinical presentation
that we traditionally associate with canine atopic dermatitis
(CAD) triggered by environmental allergens [5,6]. Thus, they
present with pruritus and the ventral abdomen, axillae, groin,
muzzle, periocular, perianal, and palmar or plantar and dorsal
interdigital skin are usually involved (Figures 1-3). Not all body
regions are necessarily affected in individual dogs. A primary
papular eruption may also be present. Secondary infections
with Staphylococci or Malassezia often occur. A history of
non-seasonal pruritus is present in the older dog, but a pattern
cannot be determined in puppies and young adults with only
a few weeks to months of discomfort. Food allergy often coexists with environmental allergies in the same individual, the
reported incidence varying from 33-49% of allergic dogs [5-7].
Atopy
a genetic predisposition to develop allergic disease
Atopic disease
any manifestation of atopy i.e. dermatitis, conjunctivitis etc.
Atopic dermatitis
a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features.
Adverse food reaction
any clinically abnormal response attributable to the ingestion of food or food additive
Food intolerance
abnormal physiological response to food with no immunological basis
Food allergy
Immunologically mediated adverse food reaction.
Tab. 1.
1) Hilary A Jackson BVM&S DVD DipACVD MRCVS, Dermatology Referral Service, 528 Paisley Road West, Glasgow G51 1RN, Scotland
230
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 1 Chronic facial dermatitis and otitis in a dog with food allergy.
Fig. 3 Ventral interdigital erythema and pruritic pododermatitis.
Fig. 4 Multifocal alopecia and papules on the trunk of a young dog
with food allergy.
Fig. 2 Lichenification and erythema of the axilla, limb and sternum
of the same dog (Fig. 1).
of questions which might be asked to determine what the
dog is currently being fed. The optimal duration of a diet trial
has not been determined but most veterinary dermatologists
recommend a period of six to eight weeks which allows for
evaluation of sustained improvement. Additionally, it is often the
case that other treatments are instituted along with the initiation
of the diet trial such as antibiotic or antifungal therapy for
concurrent microbial infections. The diet needs to be continued
once this treatment has finished in order to determine whether
clinical improvement is sustained or merely attributable to the
antimicrobal treatment itself. It is usually easiest to perform the
challenge with a small amount of previously fed dog food. Clinical
signs generally manifest within 2 weeks of challenge although,
in my experience often within 2-48 hours. If the dog does not
relapse with “dog food” then other previously fed treats should
be introduced one by one. Serological or intradermal testing for
Prior to embarking on a diagnostic work up for food allergy the
possibility of the presence of other pruritic skin diseases should
be entertained. Ectoparasitic infestations in particular should be
ruled out. If skin scrapings and coat brushings are negative then
a therapeutic trial with a parasiticide is warranted.
Diagnosis of food allergy
A diagnosis is achieved by documenting a clinical improvement
during the course of feeding a novel diet (see below) with
recrudescence of clinical signs when previously fed foods are
re-introduced. This diet should be fed exclusively and any
additional food elements avoided. Table 2 provides an example
231
Food allergy in dogs- clinical signs and diagnosis - H. A. Jackson
1. What is your dog’s current and past dog food?
2. What dog treats does your dog receive?
3. Do you feed your dog table scraps?
4. Does your dog get raw hide chews, pigs ears or anything
similar?
5. If you need to give your dog pills do you hide them in
food?
6. What does your dog drink?
7. Does your dog have access to the cat food?
8. If there is another dog in the house what does it eat and do
the dogs share bowls?
9. Will your dog eat food it finds on the street or in the
park?
10.Does anyone else feed your dog ie the neighbour or dog
walker?
Tab. 2 Diet history.
food allergy is not diagnostically reliable at this time and is not
to be recommended.
Fig. 5 A six month old Labrador with facial pruritus due to
food allergy. Pruritus was so intense the dog had been put in an
Elizabethan collar.
Performing an effective food trial is challenging. It takes time
to determine the dog’s current food intake and educate the
client about performing a diet trial correctly. It is often the case
that the interview is conducted with one family member who
embraces the concept and plan but the diet fails because other
family members continue to feed treats. It is a good idea to make
contact with the owners one or two weeks after initiating the
trial to ensure the diet is going to plan and offer moral support.
Clients generally find the first week the hardest, particularly of
the dog is habituated to a lot of extra treats and table scraps.
Fig. 6 A ten year old dog with a 6 month history of ventral
pruritus. Food allergy was diagnosed.
Before and during the diet trial the dog’s weight should be
monitored carefully. Diets designed for the diagnosis and
management of food allergy are nutritionally complete but
occasionally a rapid gain or loss of weight can be seen.
Diet selection
Fig. 7 A close up view of the same dog (Fig. 6). Malassezia was
demonstrated on cytology from the ventral abdomen.
Limited antigen diets in common use fall into three categories:
commercially available novel protein diets, hydrolysed protein
diets and novel protein home cooked diets. Commercially
available diets are generally designed for the management of
true food allergy, although as discussed, the true incidence
of immunologically mediated disease in the dog is currently
unknown.
Food allergens have been characterized at the molecular level
in man and are generally glycoproteins with a molecular weight
greater than 10 000 kD and they are stable to digestive processes
[12]. The nature of food allergens in the dog is largely unknown.
Home cooked diets are often advocated when performing a
diet trial, thus avoiding pet food additives which might have
the potential to cause adverse reactions. However, although
additives are often incriminated as causing adverse reactions
in pets there are no well documented reports to support this
232
EJCAP - Vol. 19 - Issue 3 December 2009
References
idea. Furthermore, the use of home cooked diets often lead to
poor client compliance due to the added effort required for diet
preparation. Home cooked diets are contra-indicated in growing
animals and should be nutritionally balanced if used for long
term feeding.
[1] Burns PW. Allergic reactions in dogs. Journal of the American
Veterinary Medical Association. 1933; 83: 627-34.
[2] Schnelle GB. Eczema in dogs-an allergy. North American Vet.
1933; 14: 37-44.
[3] Jackson HA, Hammerberg B. Evaluation of a spontaneous canine
model of immunoglobulin E-mediated food hypersensitivity:
dynamic changes in serum and fecal allergen specific IgE values
relative to diet change. Comparative medicine. 2002; 52: 316-21.
[4] Loeffler A, Lloyd DH, Bond R, Kim JY, Pfeiffer DU. Dietary trials
with a commercial chicken hydrolysate diet in sixty three pruritic
dogs. Veterinary Record. 2004; 154: 519-22.
[5] Jackson HA, Murphy KM, Tater KC, et al. The pattern of allergen
hypersensitivity (dietary or environmental) of dogs with nonseasonal atopic dermatitis cannot be differentiated on the basis
of historical or clinical information: A prospective evaluation 20032004 (abstract). Vet Dermatol. 2004; 16: 200.
[6] Picco F, Zini E, Nett C, Naegeli C, Bigler B, Rufenacht S et al. A
prospective study on canine atopic dermatitis and food-induced
allergic dermatitis in Switzerland. Vet Dermatol. 2008; 19: 150-155
[7] Chesney CJ. Food sensitivity in the dog: A quantitative study.
Journal of Small Animal Practice. 2002; 43: 203-207.
[8] Harvey R. Food allergy and dietary intolerance in dogs: a report of
25 cases. J Small Anim Pract. 1993; 34:175-179.
[9] Olson M, Hardin JA, Buret A, et al. Hypersensitivity reactions to
dietary antigens in atopic dogs. In: Rheinhart GA, Carey DP, eds.
Recent advances in canine and feline nutrition, Vol. 3. Wilmington,
Ohio: Orange Frazer Press, 2000;69-77.
[10] Rosser EJ Jr. Diagnosis of food allergy in dogs. J Am Vet Med
Assoc. 1993; 203: 259-262.
[11] Carlotti D, Remy I, Prost C. Food allergy in dogs and cats. A review
and report of 43 cases. Vet Dermatol. 1990; 1: 55-62.
[12] Taylor SL, Lehrer SB. Principles and characteristics of food allergens.
Critical Reviews in Food Science and Nutrition. 1996; 36(S):
S91-S118.
[13] Biourge VC, Fontaine J, Vroom MW. Diagnosis of adverse reactions
to food in dogs: efficacy of a soy-isolate hydrolysate based diet.
Journal of Nutrition. 2004; 134: 2062S-64S.
[14] Rosser ER. Evaluation of a novel carbohydrate and hydrolyzed
protein containing diet in previously confirmed food allergic dogs
(abstract). Vet Dermatol. 2001; 12: 230.
[15] Olivry T, Kurata K, Paps JS et al. A blinded randomized controlled
trial evaluation the usefulness of a novel diet (Aminoprotect Care)
in dogs with spontaneous food allergy. Journal of Veterinary
Medical Science. 2007a; 69: 1025-31.
[16] Jackson HA, Jackson MW, Coblentz L et al. Evaluation of the
clinical and allergen specific serum immunoglobulin E responses
to oral challenge with cornstarch, corn, soy and a soy hydrolysate
diet in dogs with spontaneous food allergy. Vet Dermatol. 2003;
14: 181-7.
[17] Ricci R., Jackson H.A., Paps J.S., Hammerberg B. The magnitude
of the clinical response to oral proteins in dogs with spontaneous
chicken allergy is significantly reduced when the protein is
hydrolyzed (abstract). Vet Dermatol. 2006; 17: 210.
[18] Beale KM and Laflamme DP. Comparison of a hydrolyzed soy
protein diet containing corn starch with a positive and negative
control diet in corn- or soy-sensitive dogs (abstract). Veterinary
Dermatology. 2001; 12: 237.
[19] Glos K, Linek M, Loewenstein C, Mayer U, Mueller RS. The efficacy
of commercially available veterinary diets recommended for dogs
with atopic dermatitis. Vet Dermatol. 2008; 20: 280-7
[20] Bensignor E, Morgan DM, Nuttall T Efficacy of an essential
fatty acid-enriched diet in managing canine atopic dermatitis: a
randomized, single-blinded, cross-over study. Vet Dermatol. 2008;
19; 156-62
Commercial novel protein diets contain whole proteins which
are not commonly found in dog foods. Although a truly “novel”
protein is becoming more difficult to find as the diets available
for general consumption increasingly contain more varied and
exotic ingredients. The diet should be selected on the basis of
the protein content which should be one which has not routinely
been fed to the pet in the past, and ideally not at all.
Hydrolysed diets theoretically negate the need to find a “novel”
protein. The Parent protein in these diets is usually from a readily
available source such as chicken or soy in which the peptide bonds
of the parent protein have been broken to create small peptide
fragments. These peptides are too small to bridge adjacent
allergen specific IgE molecules on the surface of mast cells thus
degranulation does not occur. The rationale behind the use of
these diets assumes that canine food allergy is mediated by IgE,
which as previously discussed has not been determined. Various
studies have examined the performance of hydrolysed diets in
a clinical setting and found them to be well tolerated [5,13-15].
There is less critical evaluation however on the performance of
these diets in dogs known to be hypersensitive to the parent
protein. A small number of studies suggest that 20-50% of
individuals will react adversely to the hydrolysed diet if they are
sensitive to the parent protein [16-18]. Furthermore these diets
tend to be more costly and less palatable.
For optimal compliance the selected diet should be of similar
consistency to the diet currently being fed. Thus, if the dog is
on a mixture of dry and moist food this should be adhered to if
at all possible.
Long term management of the food
allergic dog
For long term management the dog with food allergy may be
maintained on the limited antigen diet which was used in the
diet trial. Alternatively, and if the offending allergens have been
identified, an alternative diet which is “allergen” free for that
dog can be utilized. In the author’s experience some dogs with
food allergy can develop a hypersensitivity to the new diet after
months to years on this diet and under such circumstances a
new diet needs to be found. Young dogs may also progress
to develop concurrent hypersensitivities to environmental
allergens.
Dietary responsive disease
Various studies have demonstrated an apparent beneficial effect
of feeding limited antigen diets to dogs with AD in the absence
of demonstrable food allergy [19,20]. This precise reason is
undetermined but may be attributable to the enhanced essential
fatty acid content of these diets.
233
DERMATOLOGY
Food hypersensitivity in the cat
E. Guaguère1, P. Prélaud2
SUMMARY
The term food hypersensitivity refers to all the clinical manifestations of allergy to ingested allergens (immunological
mechanisms), and intolerance (non-immunological mechanisms). Few studies of the immunopathogenesis of feline
food allergy have been conducted so most immunological data are extrapolated from the human field. The list of
incriminated foods varies according to local feeding habits in countries where the animals live. In cats, the most
common food allergens are beef, lamb, milk, fish, tinned food and dried food. Food hypersensitivity often manifests
in cats as a pruritic dermatosis of the face and neck, miliary dermatitis, self-induced alopecia and generalised scaling
or symmetrical alopecia. In addition to the other clinical presentations, all the entities of the eosinophilic granuloma
complex should be considered. The incidence of gastrointestinal involvement is underestimated. Most cases of
recurrent lymphoplasmacytic colitis seem to be related to food hypersensitivity. In practice, establishing a definitive
diagnosis can be difficult and requires a rigorous approach. An elimination diet of one or more foodstuffs, never
previously eaten by the cat, should be fedover six to ten weeks, period considered optimal by most dermatologists.
Introduction
was not routinely undertaken. Food hypersensitivity represents
the third most important cause of feline hypersensitivity [5, 11,
12, 26, 35].
The term food hypersensitivity refers to all the clinical
manifestations of allergy to ingested allergens (immunological
mechanisms),
and
intolerance
(non-immunological
mechanisms). However, in the vast majority of cases, neither
identification of the actual allergen responsible nor elucidation
of the exact immunological mechanisms involved is possible
so it may be wiser to use the term food intolerance [11, 12,
14, 27, 31, 35, 39]. Moreover, certain kinds of clinical problem
may be associated with the ingestion of foodstuffs but without
any evidence of any causal immunological reaction : food can
contain pharmacologically active substances (e.g. histamine
which induces vasodilatation) [19]; metabolic reactions due to
some kind of enzyme deficiency (e.g. lactase) are common ; and
both fungal toxins (in dried, poorly prepared or inadequately
preserved food) and plant toxins (e.g. tannins and alkaloids) can
elicit non-immunological reactions [11].
Aetiopathogenesis
Few studies of the immunopathogenesis of feline food
allergy have been conducted so most immunological data are
extrapolated from the human field.
Food allergens
Any foodstuff is potentially allergenic but, in practice, a finite
number of ingredients are involved [2, 5, 10, 17, 27, 36, 38,
39]. The actual list varies according to local feeding habits in
countries where the animals live. In cats, the most common
food allergens are beef, lamb, milk, fish, tinned food and dried
food. Less commonly, chicken, gluten and additives can also
induce reactions.
The incidence of food intolerance in cats is difficult to establish
with any precision because it depends on both the definition
of food intolerance and to what extent the possibility of
food intolerance is considered in the diagnosis. The reported
prevalence of food hypersensitivity varies from 1% to 11% of
all feline dermatoses [31,36]. In a recent study [5], 6% of all
dermatoses in cats were attributed to food intolerance but this
figure cannot be taken as definitive because challenge testing
The foodstuffs most likely to be allergenic are those which
contain the most protein and those which are most commonly
fed. The cat will often have been eating the foodstuff in question
for a long time [2, 5, 10, 17, 27, 36, 38, 39] and the more a
particular protein has been consumed, the more likely it is to
induce hypersensitivity [12, 35]. The exact nature of allergenic
proteins in cats has never been studied.
(1) Eric Guaguère, Doct Vét, Dip ECVD, DESV D, Clinique Vétérinaire Saint Bernard, 598 avenue de Dunkerque, F 59160 Lomme, France
(2) Pascal Prélaud, Doct Vét, Dip ECVD, DESV D, Clinique Vétérinaire Advetia, 5 rue Dubrunfaut. F 75012 Paris, France
234
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 1 Facial pruritus and erythema on the lateral pinnae of a cat
with food allergy.
Fig. 2 Same cat as in Figure 1, erythema on the lateral pinnae.
It is likely that many foodstuffs are also responsible for nonimmunologically based intolerance. Certain fish contain high
levels of histamine, e.g. tuna and any dried or inadequately
preserved fish. Shellfish – common allergens in humans – have
not often been identified as allergens in cats even though they
are a common ingredient in “cat treats”. Nevertheless, prawns
may induce non-specific histamine release [11, 19].
allergy is probably a Type I immediate hypersensitivity although
Type III (Arthus) reactions and Type IV (delayed) hypersensitivity
may also occur [5, 12, 14, 27, 31, 35, 36]. Immediate responses
appear within minutes or hours of ingestion of the allergen
whereas delayed responses take several hours or days. Defence
mechanisms to prevent development of food allergy include
the protective gastrointestinal mucosa and immune tolerance
maintained by cellular immunity associated with the digestive
tract [6, 17, 30]. The mucosal barrier excludes most ingested
allergens although it is permeable to peptides and small proteins,
especially if there is any kind of inflammation, e.g. due to viral
or parasitic infection [8]. Although no exact mechanisms have
been demonstrated in cats, it is assumed that local and systemic
IgA eliminates potential allergens and that any defect in this
defence would predispose an animal to potentially damaging
hypersensitivity reactions. Food allergy can develop along
with other kinds of allergy, e.g. flea allergy dermatitis, atopic
dermatitis, etc. [8,19,20].
Most of the commonly suspected additives are haptens (small
molecules which are allergenic only when conjugated with a
carrier protein), and hypersensitivity to this type of antigen has
never been demonstrated in cats. Many of the additives used
in the human food industry, like benzoates and tartrazine, are
never used in cat food. However, the use of others is widespread,
including sodium bisulphite, monosodium glutamate, azodyes, sodium nitrite, spices, sodium alginate, vegetable gums,
propylene glycol and ethoxyquin [28].
Storage (forage) mites in commercial, dried cat food could be a
major source of oral sensitisation for carnivorous animals [13].
In dogs, allergy to storage mites is common although in cats
it has never been possible to demonstrate that the sensitivity
is specific to forage mites and not due to cross-reaction with
house dust mites or mites present in food.
Clinical features
Food allergy is a non-seasonal dermatosis with no age, breed
or sex predilection. Age of onset varies between 3 months and
11 years with most studies showing a mean age of 4 to 5 years
[2, 10, 26, 33, 38]. There is no breed predilection although two
different studies have shown a higher incidence in Siamese and
Immune response
The most common immunological response involved in food
Fig. 4 Facial pruritus, erythema, scaling and crusting in a Persian
cat with food allergy.
Fig. 3 Same cat as in Figures 1-2, lesions of miliary dermatitis.
235
Food hypersensitivity in the cat - E. Guaguère
Fig. 5 Erosions around the skin behind the ears in a cat with food
allergy.
Fig. 6 Same cat as in Figure 5, blepharoconjunctivitis.
Burmese cats [12, 32, 35]. It is usually believed that food allergy
is more common in cats than in dogs although it is impossible
to carry out meaningful epidemiological studies because allergic
dermatitis is poorly defined and the means of investigating
feline allergies are limited [12]. As it is easier to carry out an
elimination diet and control flea allergy dermatitis in the cat
than it is to perform intradermal allergy testing, food allergy
is usually considered the most likely differential in this species
(unlike in the dog) after flea allergy dermatitis [12].
otitis, pododermatitis and perianal inflammation are sometimes
observed (Figs 10, 11). Food hypersensitivity can also present as
miliary dermatitis (Fig. 12), self-induced alopecia and generalised
scaling or symmetrical alopecia (Figs 13,14), each of which carries
a detailed differential diagnosis. In addition to the other clinical
presentations, all the entities of the eosinophilic granuloma
complex should be considered, e.g. indolent lip ulcers (Fig. 15)
and eosinophilic plaques, wherever they occur [24]. Urticaria
and secondary bacterial or fungal infections (e.g. Malassezia
dermatitis) seem to be relatively rare in cats [10, 31, 32].
Dermatological signs
Clinical signs are not specific although varying degrees of nonseasonal pruritus (either generalised or localised) have been
reported in over 90% of cases [2,10,16,18, 26,38]. Response to
glucocorticosteroid therapy was good in almost 50% of cases
[10]. In some studies, glucocorticosteroids have been found to
be less effective although these were either retrospective studies
of chronic cases or studies that involved doses similar to those
used in dogs [2, 26, 32, 33, 38, 39].
Gastrointestinal signs
The incidence of gastrointestinal involvement, which may or may
not be associated with dermatological signs, is underestimated.
In a series of 17 cases [10], gastrointestinal involvement (e.g.
vomiting and intermittent diarrhoea) was observed in 30% of
the animals. Most cases of recurrent lymphoplasmacytic colitis,
common in cats, seem to be related to food hypersensitivity
in this species [6, 17, 22]. In one case, food hypersensitivity
mimicked alimentary lymphoma [37].
Food hypersensitivity is characterised by a clinical polymorphism
[2, 4, 5, 10-12, 14, 18, 26, 27, 31-33, 35, 38, 39]. It often
manifests in cats as a pruritic dermatosis of the face (cheilitis
and bilateral blepharitis) and neck with erythema, papules,
erosions and crusts (Figs 1-9). Bilateral erythemato-ceruminous
Diagnosis
In practice, establishing a definitive diagnosis can be difficult
and requires a rigorous approach. The animal’s history must
Fig. 7 Severe facial pruritus and very crusty lesions in a Persian
cat with food allergy (sardines).
Fig. 8 Same cat as in Figure 7 seen after clipping, showing severe
erosive and ulcerative lesions on the face.
236
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 9 Erosions, excoriations and facial pruritus in a domestic
short-haired cat with food allergy (beef).
Fig. 10 Same cat as in Figure 9, erythematous pododermatitis.
be thoroughly reviewed, including the cat’s living and eating
habits, and the diet itself, especially with respect to protein
and carbohydrate sources. The physical examination should be
methodical. Food hypersensitivity should always be considered
in an animal with a non-parasitic pruritic dermatosis [12, 31,
32].
Certain preliminary guidelines are important: the food must be
offered on a plate (avoid plastic or metal), toys should be taken
away and, in theory, no treats, vitamins, mineral supplements or
drugs should be given during the time of the diet [10,12, 25, 27,
31-33, 35, 39].
Prescribing glucocorticosteroids, antihistamines or cyclosporine
A cannot always be avoided. In cases, the special diet can be
started immediately but, for proper assessment of its effect, it
should be prolonged for at least two weeks following the end of
the drug course [12, 31, 32]. If pills must be given with food, all
protein sources, including butter, cheese, ice cream, meat and
animal treats must be avoided. Honey is preferable [25].
Differential diagnosis
The differential diagnosis is that of all pruritic dermatoses,
including initially the ectoparasitic infestations (e.g. cheyletiellosis,
notoedric mange, trombiculiasis and pediculosis), other causes
of allergic dermatitis and dermatophytosis [5,12, 27, 31, 32, 33,
35, 39]. Facial involvement requires a more detailed diagnostic
approach to rule out auto-immune dermatoses, mural
lymphocytic folliculitis and certain viral infections [5,12, 27, 31,
32, 33, 35, 39].
Selecting an elimination diet
Protein
ln an elimination diet, protein must be restricted to sources never
previously eaten by the animal. Duck, horse, lamb and white fish
are often appropriate [12, 14, 27, 29-33, 35, 38, 39]. Hydrolysed
proteins are low in molecular weight and allergenicity, highly
digestible and can be used whatever their origin. Most hydrolysed
diets are poultry- or soya-based [3]. None of the industrial foods
on the market has a sufficient amount of hydrolysed proteins
to guarantee a complete absence of allergens (on average,
molecular weight of 12 kd). In fact, in order to guarantee the
absence of allergens, it would be necessary for hydrolysed
proteins to contain peptides at a maximum level of 1 to 3 kd.
This would lead to the cost of hydrolysis and ultrafiltration
becoming excessive. It is reasonable to choose an industrial diet
that does not contain any protein sources to which the cat may
be sensitive. In general, diets containing hydrolysed proteins are
effective and well-tolerated [3, 25].
Diagnostic tests
Haematological profiles (differential count, etc.) are worthless;
at best they might reveal non-diagnostic eosinophilia.
Histopathological examination of skin biopsies does not
provide any specific information, but usually reveals perivascular
inflammation with varying numbers of eosinophils and mast
cells, indicating allergic dermatitis in general [9, 10, 12, 31,
32]. In rare cases, histopathological features include a mural
lymphocytic folliculitis [4, 9].
Dietary history
Elimination diets
The next stage is to instigate an elimination diet of one or more
foodstuffs which the cat has never previously eaten. Although
this sounds simple, in practice it can be fraught with problems.
This is partly because commercial cat foods nowadays contain
a wide variety of different proteins and partly because owners
often find it difficult to make their cat follow a strict diet; prior
to settling on a diet, it is crucial to assess the owner’s motivation
[12].
Home-prepared diets
Home-prepared diets should include just one source of protein
and one source of carbohydrate. The choice of foodstuffs should
take into account the cat’s normal eating habits. The choice of
diet needs to be a joint decision, taken with the owner, and
the cat’s eating habits should not be changed too rapidly [12].
The new diet should therefore be introduced gradually, over
the course of 4 to 5 days. It should also be given at the same
times and correspond to about the same total amount of food
Before the effects of an elimination diet can be properly
evaluated, all secondary and concomitant skin conditions
must be controlled, e.g. flea allergy dermatitis and secondary
infections (although these are rare in cats).
237
Food hypersensitivity in the cat - E. Guaguère
Fig. 11 Same cat as in Figures 9-10, perianal erythema.
Fig. 12 Severe miliary dermatitis in a domestic short-haired cat
with food allergy (beef).
as given previously. It must include a relatively lean protein
source (lamb, chicken, turkey, horse, duck, rabbit or game),
offered either cooked or raw, together with boiled vegetables
(potatoes, tomatoes, lentils, banana, pumpkin, etc.). The
advantage of these diets lies with the owner having control over
all basic ingredients. For cats used to home-prepared diets, they
are often more palatable than commercial dry diets (Tab. 1) [12,
25, 31-32, 39].
The advantage of commercial diets is their ease of use (Tab. 2).
However, this should not lead the owner to underestimate the
difficulties of sticking to such a diet. A commercial diet should
be fed as strictly as a home-prepared diet in relation to amount
and timing of feeding, preventing other foods being eaten,
checking for gastrointestinal side-effects and monitoring the
animal’s weight [25].
Tab. 1 Examples of protein and carbohydrate sources in a
home-prepared diet [25].
Tab. 2 Advantages and disadvantages of home-prepared and
commercial diets [25].
Protein
Carbohydrate
-
Advantages:
Rice
White fish
Maize
Advantages:
Duck
Tapioca (cassava)
Owner becomes involved
Practical
Chicken
Potato
No additives
Turkey
Lentils
Well-balanced, highly
digestible
Game
Sweet potato
Control over protein sources
Low allergenicity / hydrolysed
Lamb
Banana
Diversity of protein sources
Palatability
Rabbit
Pumpkin
Efficacy
Palatability
Commercial diets
There are a multitude of commercial diets marketed as
hypoallergenic or for skin allergies [14, 16, 28-33, 35, 39]. These
diets fit into three categories:
-
Commercial
Horse
Ostrich
-
Home-prepared
protein coming mostly from specific sources. These diets
cannot be considered suitable as elimination diets as the
protein source is too varied.
protein coming entirely from specific sources (e.g. ostrich,
kangaroo, catfish, rabbit and duck). These diets are suitable
but may contain hidden traces of food allergens.
hydrolysed protein. These diets are theoretically less likely to
be allergenic than non-hydrolysed diets. Hydrolysis reduces
protein into small, low molecular weight peptides. Hydrolysed
diets are therefore the most practical commercial preparations
[3, 25, 35]. Hydrolysis effectively reduces the molecular
weight and intrinsic antigenicity of the food and also makes
it more digestible. These two factors combine to provide low
stimulation to the gastrointestinal immune system [3, 25, 35].
Disadvantages:
Disadvantages:
Preparation time consuming
No control over protein
sources
Often too rich in protein
Additives
Need to balance the diet for
growing cats
Large range of foods
Side-effects
Cost
Palatability
Palatability
Monitoring
The patient must be monitored to ensure good compliance.
Potential side-effects such as weight loss / gain and
gastrointestinal problems, or practical difficulties such as refusing
to eat or behavioural changes can also be spotted. To reduce
the likelihood of gastrointestinal problems, the elimination diet
should be introduced gradually, over at least 4 days, alongside
the familiar diet. If the cat loses weight, the diet must be adjusted
(for example, protein intake increased) [12].
238
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 14 Self-induced alopecia on the abdomen of a domestic shorthaired cat with food allergy.
Fig. 13 Generalised scaling dermatitis (mural lymphocytic
folliculitis) associated with eosinophilic plaques in a domestic
short-haired cat with food allergy (beef).
Challenge tests
The principle of the challenge test is to reintroduce, at regular
intervals, each of the foodstuffs for a period of one week and
monitor for reappearance of signs. This is a demanding process
which is often rejected by the owner, does not absolutely
prove that any particular foodstuff is responsible, and gives no
information on mechanisms. However, this approach can be
useful because few allergens tend to be involved; just one or
two account for over 90% of cases [2, 10, 27, 38, 39]. The vast
majority of cats do not relapse when an incriminated foodstuff
is reintroduced. This may be due to a change in the immune
response with time or, more likely, because eating very digestible
food for a while gives the intestine time to re-establish normal
permeability.
Length of diet
Six to eight weeks is considered optimal by most dermatologists.
A response can be observed by the end of the third week (Figs
16, 17) but it may take up to 10 weeks for the diet to have any
effect [2, 10, 12, 26, 27, 35, 38, 39].
If no response is observed with a hypoallergenic commercial
diet, it does not necessarily mean that the cat does not have any
kind of food allergy. In this case, a traditional elimination diet
should be instigated [30]. If only a partial response is observed,
there may be other, concomitant skin problems (and it should be
checked with the owner that the diet was rigorously followed).
If no response is seen within 10 weeks, the diagnosis should be
reviewed. Feeding a cat commercial food ensures a balanced
diet – a recent study on hypoallergenic diets prescribed by
American vets revealed that 90% failed to provide the officially
recommended daily intakes for adult animals [28].
Allergy tests
Allergenic extracts derived from food allergens
Commercially available extracts of animal-derived food allergens
(e.g. beef, milk, fish and eggs) are of very variable allergenicity
but give satisfactory results in humans. In contrast, studies
in humans have shown that extracts of plant-derived food
allergens need to be native and prepared immediately before
use; laboratory preparations are inactive [30]. However, it has
never been possible to extrapolate these findings to cats. There
are no published data on what concentrations of these extracts
should be used in cats.
One study investigated the use of two different brands of
hypoallergenic product with non-hydrolysed proteins, sold in cans
(chicken/rice) and in containers (lamb/rice) for cats with food allergy
[16]. Of 20 cats included in the study, 8 experienced relapses with
the lamb/rice diet (40%) and 13 cats had relapses with the chicken/
rice diet (65%). On the other hand, only 3 of the cats experienced
relapses while exposed to the two diets at the same time (15%).
Home-prepared diets seem superior to commercial wet food diets,
deemed hypoallergenic through diagnostic tests [16].
Fig. 16 Same cat as in Figure 15, erosions and ulcerations on
upper and lower lips.
Fig. 15 Indolent ulcer on the upper lip of a domestic short-haired
cat with food allergy (milk).
239
Food hypersensitivity in the cat - E. Guaguère
mg/kg dexamethasone BID) are effective especially in the early
stages [12, 31, 32]. Antihistamines are ineffective. Some reports
have recommended chlorpheniramine (4-8 mg/animal BID,
orally) [12, 32]. Cyclosporine A (5 mg/kg SID) can be also used
for controlling pruritus and cutaneous lesions associated with
food allergy [23, 34].
Treating secondary infections
Secondary skin infections are rare but, in cats with gastrointestinal
signs, it is important to control bacteria in the small intestine by
prescribing a suitable antibiotic (e.g. metronidazole). The aim of
this is to break the vicious cycle of sensitisation followed by the
aggravation of gastrointestinal lesions leading to exacerbated
dermatological signs [11].
Fig. 17 Same cat as in Figures 15-16, 3 weeks after starting an
elimination diet.
References
Diagnostic value of intradermal testing and in vitro IgE testing
Intradermal skin testing [1, 15], in vitro IgE testing [21] and
cellular testing have no value in the diagnosis of food allergy in
cats. A particular foodstuff cannot be excluded on the basis of a
negative result and asymptomatic sensitisation is common [11].
These tests are theoretically useful in human medicine because
they are helpful in establishing a more acceptable elimination
diet, i.e. a more varied diet can be prescribed once certain
important potential food allergens have been eliminated. Even
so, opinions are divided on this approach which could get it
seriously wrong [7]. It has been stated that “an elimination diet
should always be well-constructed and never put together on
the basis of a few misleading positive in vitro test results”.
[1]
[2]
[3]
[4]
[5]
[6]
[7]
In veterinary medicine, such an approach is definitely worthless
because we can impose as strict a diet as necessary for a period
of weeks without any serious problem. Nevertheless, this has
not stopped certain companies from promoting food allergenspecific IgE assays to diagnose food allergy. This commerciallyappealing approach often goes down well with owners.
Whatever the outcome, the change in diet is often associated
with clinical improvement, if only because the new diet is more
balanced or more digestible than the former one. In this way,
food intolerance can be misdiagnosed as food allergy [12].
[8]
[9]
[10]
Treatment
[11]
Hypoallergenic diets
The only acceptable, effective way of treating food intolerance is
by eliminating the foodstuff(s) responsible. However, this must
not adversely affect the nutritional balance of the diet.
[12]
[13]
Hypoallergenic diets cannot be prolonged for more than 3
weeks without risking skeletal damage [29], unless vitamin and
mineral supplements are included. Therefore, owners can either
feed their animals a balanced home-prepared diet based on the
hypoallergenic diet used in the diagnosis, or give very digestible
commercial products [16,25].
[14]
[15]
[16]
Symptomatic therapy
Corticosteroids (1-2 mg/kg prednisolone SID, orally, 0.2 to 0. 5
[17]
240
AUGUST JR. The reactions of canine skin to the intra-dermal
injection of allergic extracts. J Am Anim Hosp Ass. 1982; 18: 157163.
CARLOTTI DN, REMY I, PROST C. Food allergy in dogs and cats: a
review and report of 43 cases. Vet Dermatol. 1990; 1: 55-62.
CAVE NJ. Hydrolyzed protein diets for dogs and cats. Vet Clin
Small Anim Pract. 2006; 36: 1251-1268.
DECLERCQ J. A case of diet-related lymphocytic mural folliculitis
in a cat. Vet Dermatol. 2000; 11: 75–80.
DENIS S, PARADIS M. L’allergie alimentaire chez le chien et le chat.
II : étude rétrospective. Le Médecin Vétérinaire du Québec. 1994;
24: 15-20.
DENNIS JS. Lymphocytic/plasmacytic colitis in cats; 14 cases
(1985-1990). J Am Vet Med Ass. 1993; 202: 313-318.
DUTAU G, FRANCE F, JUCHET A, FEJJI S, NOUIIHAN P, BREMONT
F. De l’eczéma atopique à l’asthme et à l’allergie. Rev Fr Allergol.
1985; 35: 429-439.
GILBERT S, HALLIWELL REW. The effects of endoparasitism and
of the administration of viral vaccines on the immune reponse to
orally administered antigen in cats: possible implications for the
pathogenesis of food hypersensitivity. Proc. AAVD-ACVD, San
Antonio. 1998: 105-106.
GROSS TL, IHRKE PJ, WALDER EJ, AFFOLTER VK. Skin Diseases of
the dog and cat: clinical and histopathologic diagnosis. second
edition, Editions Blackwell Publishing Company. 2005; pp 932.
GUAGUERE E. Intolérance alimentaire à manifestations cutanées:
à propos de 17 cas chez le chat. Prat Méd Chir Anim Comp. 1993;
28: 451-460.
GUAGUERE E, PRELAUD P. Les intolérances alimentaires. Prat Méd
Chir Anim Comp. 1998; 33: 389-407.
GUAGUERE E, PRELAUD P Food Intolerance In Practical Guide of
Feline Dermatology (Eds Guaguère E, Prélaud P) Editions Merial.
1999; 11.1-11.17.
KAMPHUES J. Mites infestation of feedstuffs for small companion
animals. J Nutr. 1991; 121: S165.
KENNIS RA. Food Allergies: Update of pathogenesis, diagnoses,
and management. Vet Clin Small Anim Pract. 2006; 36: 175184.
KUNKLE GA, HORNER S. Validity of testing for diagnosis of food
allergy in dogs. J Am Vet Med Ass. 1992; 200: 677-680.
LEISTRA M, WILLEMSE T. Double-blind evaluation of two
commercial hypoallergenic diets in cats with adverse food
reactions. J Feline Med Surg. 2002; 4: 185-188.
MARKWELL PJ, GUILFORD WG, JONES BR, HARTE JG, WILLS
EJCAP - Vol. 19 - Issue 3 December 2009
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29] ROUDEBUSH P, MCKEEVER P. Evaluation of a commercial canned
lamb and rice diet for the management of cutaneous adverse
reactions to foods in cats. Vet Dermatol. 1993; 4: 1-4.
[30] ROUDEBUSH P, GROSS KL, LOWRY SR. Protein characteristics of
commercial canine and feline hypoallergenic diets. Vet Dermatol.
1994; 5: 69-74.
[31] SCOTT DW. Feline dermatology (1983-1985): the secret sits. J Am
Anim Hosp Ass. 1987; 23: 255-274.
[32] SCOTT DW, MILLER WH, GRIFFIN CE. Muller & Kirk’s Small Animal
Dermatology, 6th edition, Saunders, W.B., Philadelphia. 2000; pp
1528.
[33] STOGDALE L, BOMZOM L, VAN DEN BERG P. Food allergy in cats.
J Am Anim Hosp Ass. 1982; 18: 188-194.
[34] VERCELLI A, RAVIRI B, CORNEGLIANI L. The use of oral cyclosporin
to treat feline dermatoses: a retrospective analysis of 23 cases.
Vet Dermatol. 2006; 17: 201-206.
[35] VERLINDEN A, HESTA M, MILLET S. Food allergy in dogs and cats:
A review. Critical Reviews in Food Science and Nutrition. 2006;
46: 259-273.
[36] WALTON GS. Skin responses in the dog and cat to ingested
allergens. Vet Rec. 1967; 81: 709-713.
[37] WASMER ML. Food intolerance mimicking alimentary
lymphosarcoma. J Am Anim Hosp Ass. 1995; 31: 463-466.
[38] WHITE SD, SEQUOIA D. Food hypersensitivity in cats: 14 cases
(1982-1987). J Am Vet Med Ass. 1989; 194: 692-695.
[39] WILLIS JM. Diagnosis and managing food sensitivity in cats. Vet
Med. 1992; 87: 884-892.
J. Prevalence of food sensitivity in cats with chronic pruritus,
vomiting, or diarrhea in Advances in Veterinary Dermatology
vol. 3 (eds Kwochka, K.W., Willemse, - T. & von Tscharner, C.),
Butterworth & Heinemann Oxford. 1998; 493.
MEDLEAU L, LATIMER KS, DUNCAN JR. Food hypersensitivity in a
cat. J Am Vet Med Ass. 1986; 189: 692-693.
MONERET-VAUTRIN DA. Allergies alimentaires et fausses allergies
alimentaires in Allergologie. vol. 3 (eds Charpin, J. & Vervloet, D.),
Flammarion Médecine Sciences, Paris. 1992; 349-365.
MONERET-VAUTRIN DA, KANNY G, RANCE F, DUTAU G.
Dermatite atopique et allergie alimentaire. Rev Fr Allergol. 1996;
36: 239-244.
MUELLER RS, TSOHALIS J. Evaluation of serum allergen specific
IgE for the diagnosis of food adverse reaction in the dog. Vet
Dermatol. 1998; 9: 167-171.
NELSON RW, DIMPERIO ME, LONG GG. Lymphocytic-plasmacytic
colitis in the cat. J Am Vet Med Ass. 1984; 184: 1133-1135.
NOLI C, SCARAMPELLA F. Prospective open pilot study on the use
of ciclosporin for feline allergic skin disease. J Small Anim Pract.
2006; 47: 434-438.
POWER HT, IHRKE PJ. Selected feline eosinophilic skin diseases
(eosinophilic granuloma complex). Vet Clin Small Anim Pract.
1995; 25: 833-850.
PRELAUD P, POWER HT. Atopic dermatitis syndrome. In Practical
Guide of Canine Dermatology (Eds Guaguère E, Prélaud P ; Craig
M), Editions Merial. 2008; 229-252.
ROSSER EJ. Food allergy in the cat: A prospective study of 13
cats. in Advances in Veterinary Dermatology. vol. 2 (eds Ihrke, P.J.,
Mason, I. & White, S.D.), Pergamon, Oxford. 1993; 33-39.
ROSSER EJ. Food allergy In dogs and cats: A review. Vet Allergy
Clin Immunol. 1998; 6: 21-24.
ROUDEBUSH P, COWELL CS. Results of a hypoallergenic diet survey
of veterinarians in North America with a nutritional evaluation of
homemade diet prescriptions. Vet Dermatol. 1992; 3: 23-28.
241
DERMATOLOGY
Flea allergy in dogs: Clinical signs
and diagnosis
C. Laffort-Dassot(1)
SUMMARY
Flea allergy is a very common pruritic dermatological condition in the dog. This dermatitis occurs in young adult dogs
of any sex. Certain breeds may be predisposed. Clinical signs are usually more severe during the warm season. They
are characterised by a pruritic erythematous papular eruption affecting the caudal aspect of the dog. Dorsolumbar
pruritus and lesions are characteristic diagnostic criteria. With time, lichenification, hyperpigmentation, scaling and
crusts appear gradually. Recurrent pyotraumatic dermatitis in the dorsolumbar area, and fibropruritic nodules and
crusted papules in the umbilical area may be particularly suggestive of flea allergy dermatitis. Secondary infections
are common. Demonstration of fleas or their feces can be difficult because flea allergic dogs remove them from their
hair coat during excessive grooming. A flea comb can greatly improve this examination but a negative search should
not rule out this hypothesis. Whatever the test used (live flea challenge, intradermal skin testing with flea extracts, in
vitro serological or cellular test) allergy testing is controversial in the diagnosis of flea allergy dermatitis because of
its poor reliability. Although not perfect, a clinical approach combining thorough history and physical examination,
elimination of other differentials and response to strict anti-flea treatment is adopted by most authors.
sensitisation introduced many veterinary practitioners and
dermatologists to dermato-allergology [2] and for decades, a
positive reaction with this test was required to make a definitive
diagnosis of flea allergy dermatitis [3].
This paper was commissioned by FECAVA for
publication in EJCAP.
Introduction
Historical findings
Flea allergy dermatitis (FAD) is one of the most common small
animal dermatological conditions and probably the most
common pruritic dermatosis in these species. This is particularly
true in areas of the world where fleas are endemic, i.e. where
fleas find the optimal environment in which to proliferate: lowaltitude geographical location, a temperature of approximately
23°C and a relative humidity of 78% [1]. Frequently, clinical signs
associated with flea infestation are mild with low to moderate
pruritus, the intensity of which is directly correlated to flea
burden. Simple infestation is not associated with hypersensitivity
reactions. On the other hand, in flea allergy dermatitis, clinical
signs and pruritus are not related to the parasitic load and
may be extremely severe. Suggestive historical and clinical
data sustain the diagnosis of flea allergy dermatitis. In the
1980’s, intradermal skin testing with flea extracts documenting
Suggestive historical data include the presence and/or recurrence
of a pruritic dorsolumbar dermatitis in young adult dogs. FAD can
occur in animals of any age although clinical signs rarely develop
in animals under 6 months of age [4]. The most common age
of onset is 3 to 5 years [3]. There is no sex or breed predilection
although one study showed a breed predisposition in ChowChows, Labrit, Pyrenean Shepherd dogs, Setters, Fox-terriers,
Pekinese and Spaniels [5].
Pruritus may or may not be seasonal, depending on the
geographical location and climate. Even when pruritus is yearround, clinical signs are usually more severe during the warm
season. Owners may report onset or increase in pruritus
following the introduction of a new pet, or visit to a boarding or
grooming facility [6].
1) Catherine Laffort-Dassot, Clinique Vétérinaire Alliance – 8 Boulevard Godard – F-33000 Bordeaux. Tel: +33(0)556391548, fax: +33(0)556699089
Email: [email protected]
242
EJCAP - Vol. 19 - Issue 3 December 2009
Initially, corticosteroids produce a marked
but temporary remission [7].
The presence of fleas reported by the
owner reflects only infestation. In-contact
animals, particularly cats, can also be
infested and are sometimes the source of
infestation.
Clinical signs
Canine flea allergy dermatitis is
characterised in its early stages by a
pruritic, erythematous and papular
dermatitis affecting the caudal aspect
of the dog. Lesions are confined to the
dorsolumbar area, inner and posterior
thighs, ventral abdomen and flanks (Fig.
1) [3]. FAD is the only known canine
pruritic dermatitis that consistently affects
this region [8, 9] even though one study
showed dorsolumbar involvement in only
Fig. 3 Brownish stain of the hairs in the
76% of flea-allergic dogs. Furthermore, Fig. 1 Alopecia and scaling in the
dorsolombar area of a flea allergic West
the dorsolumbar region was involved dorsolombar area in a flea allergic dog.
Highland White terrier.
in 39% of atopic dogs. In this study,
34% of dogs with FAD exhibited facial
pruritus and lesions but the feet were involved in only 1.2%
Pruritus is associated with self-induced alopecia, excoriations,
[10]. Whether these signs were related to an adverse food
pyotraumatic dermatitis, and a dull and coarse hair coat [6].
reaction and/or atopic dermatitis or to FAD could have been
Flea allergy dermatitis could be the underlying cause of a
evaluated for example, by using appropriate flea control. It must
majority of recurrent pyotraumatic dermatitis cases arising in the
be emphasised that atopic status may predispose to flea allergy
dorsolumbar region in dogs with a dense hair coat (Fig. 2) [3,
dermatitis [1, 4]. Another study evaluated the diagnostic value
9]. In dogs with a light coat colour, hair is stained brown from
of some clinical clues in the diagnosis of flea allergy dermatitis: it
licking and saliva (Fig. 3) [9].
was found that dorsolumbar involvement (lesions and pruritus)
was a discriminating diagnostic criterion. Its sole presence in
With time, lichenification and hyperpigmentation, crusts and
a pruritic dermatitis has a sensitivity of 92% and a specificity
scaling appear gradually. Fibropruritic nodules may also occur
of 84% when compared to response to strict flea control [9].
in some chronic cases, usually in the dorsolumbar area. They
Sometimes, particularly in severely hypersensitive dogs, lesions
represent a highly characteristic clinical marker of flea allergy
become generalised and may mimic scabies [3].
dermatitis in susceptible dogs [8, 9]. Possibly more frequent in
old (over 8 years old) German Shepherd dogs with chronic flea
Lesions consist of erythema and papules that may become
allergy dermatitis, they consist of multiple, firm, alopecic and
crusted. Crusted papules in the umbilical area may be particularly
sometimes pedunculated nodules (diameter from 0,5 to 2 cm)
suggestive of flea bite allergy, especially in male dogs [3, 8].
(Fig. 4) [9].
Fig. 2 Pyotraumatic dermatitis in a flea allergic dog: alopecia,
erosions, erythema and oozing in the flank region
Fig. 4 Pruritic and fibrotic nodule in a flea allergic boxer.
243
Flea allergy in dogs: Clinical signs and diagnosis - C. Laffort-Dassot
Fig. 5 Bacterial folliculitis in a flea allergic dog: erythema, papules,
pustules, crusts and eipdermal collarettes.
Fig. 6 Flea feces dissolving to form brown stain on a wet piece of
blotting paper.
Secondary infections such as superficial bacterial folliculitis
or Malassezia dermatitis are common [3]. They increase
inflammation and pruritus. Malassezia dermatitis seems to be
less frequent in dogs with flea allergy dermatitis than in dogs
with atopic dermatitis but secondary superficial bacterial
folliculitis is commonly noted (Fig. 5) [9].If corticosteroids are
used for long-term pruritus management, superficial bacterial
infection can lead to deep pyoderma with furunculosis in the
dorsolumbar area [3, 9].
study, fleas were observed in only 65% of flea-allergic dogs. In
15% of these cases, neither fleas nor flea faeces were found
[12].
Differential diagnosis
The differential diagnosis includes all pruritic dermatoses. The
most common differentials are bacterial folliculitis, Malassezia
dermatitis, scabies, trombiculosis, cheyletiellosis, pediculosis,
demodicosis, adverse food reaction and atopic dermatitis.
Sometimes diagnosis is made difficult by the association of flea
allergy dermatitis with one of these other dermatoses, especially
bacterial folliculitis and/or Malassezia dermatitis [3].
Histopathological examination of skin biopsies reveals superficial
perivascular inflammation with variable eosinophilia. This pattern
can be seen in other hypersensitivity reactions [13] and is nonspecific.
In severely infested dogs, clinical anaemia may be present [3].
Due to the fastidious grooming induced by pruritus, some
dogs can ingest adult fleas carrying the tapeworm Dipylidium
caninum and may have segments of it in their faeces or around
the anus [3].
Demonstration of fleas
Close examination of the skin and hair coat may reveal the
presence of adult fleas or flea faeces. This can be difficult,
sometimes impossible because flea-allergic dogs scratch and
lick themselves more than other dogs, removing fleas from
their skin and hair coat. The reliability of this examination can
be considerably improved by using a flea comb. Combing for
a few minutes, especially in lesional areas, after applying an
insecticidal spray can help reveal adult fleas. Even if adult fleas
are not found, it is sometimes possible to demonstrate flea
faeces. These small, reddish-brown comma-shaped fragments,
[11] made from haemoglobin crystals, will readily dissolve to
form reddish-brown stains if placed on a wet piece of blotting
paper (Fig. 6). They can also be examined under the microscope
to reveal their characteristic colour and shape.
Blood eosinophilia and anaemia are sometimes reported [3].
Allergy testing
Provocative tests are considered to be the gold standard in
allergy testing, particularly for food or contact hypersensitivity.
They have also been used in flea allergy dermatitis diagnosis (live
flea challenge tests), especially to compare the diagnostic value
of different assays [14].
A few, newly-emerged, unfed fleas are placed in a universal
container the open end of which is covered by a gauze lid,
through which the fleas can feed. This container is held for 15
to 20 minutes against the clipped skin of the dog to be tested,
usually the skin of the lateral thorax. The container is then
removed. The fleas are killed and then crushed to ensure that
they contain ingested blood, confirming feeding and exposure
of the dog to flea saliva allergens. The challenge site is inspected
at 15/20 minutes for evidence of immediate reactivity, then at
24h and/or 48h. Possible lesions include erythema, papules, skin
thickening, oedema, wheals, crusts or a combination thereof
[14, 15].
Human infestation with young adults, recently emerged from
their cocoons, may be an indirect sign of a severely infested
environment.
In many instances, neither fleas nor flea faeces will be
demonstrated but this should not be used to rule out a diagnosis
of flea allergy dermatitis if clinical suspicion is high. In a French
244
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 7 Intradermal skin testing with flea extracts (lecture at 20
min): from top left to bottom right, negative control, positive
control, biophady extract, Greer extract, pure flea saliva, Cte f1(2
dilutions).
Fig. 8 Intradermal skin testing with flea extract (lecture at 48h):
erythematous papule.
Intradermal skin testing
Intradermal skin testing with flea extracts is used to demonstrate
in vivo immediate (at 20 minutes) and/or delayed (at 48h)
hypersensitivity reactions. Non-standardised whole-body
extracts of Ctenocephalides felis felis at a concentration of
1:1000 (W/v) are currently the only flea allergens commercially
available for intradermal skin testing.
These provocative exposure tests are practical on a research basis,
but not for most veterinary practitioners and dermatologists.
Moreover, their reliability is not excellent: in a study where they
took into account only immediate reactions after provocative
exposure, Stolper et al. showed that sensitivity of this reference
test was only around 50% although specificity was excellent
(94%). [15]
The intradermal skin testing protocol for flea extracts is the
same as that for aeroallergens. It requires experience and
practice to avoid the most frequent causes of false positive
and false negative reactions. For example, all drugs that could
interfere with testing must be withdrawn for a suitable length
of time prior to the intradermal test (3 weeks for oral and topical
glucocorticoids, 8 weeks for injectable glucocorticoids, 10 days
for antihistamines, and 10 days for products and diets containing
w3/w6 fatty acids)[3]. It seems that even a short administration
of glucocorticoids could strongly decrease delayed reactions at
48h [1]. Secondary infections should be cleared and stressed
dogs can be anaesthetised.
Allergenic extracts of Ctenocephalides felis felis
Whole-body flea extracts
Allergenic extracts used for immunotherapy and in vivo and
in vitro diagnosis are whole-body flea extracts. They are
produced after crushing of the flea bodies, protein extractions
and purification. They are not biologically standardised; their
composition and allergenicity may vary, altering diagnostic
reproducibility and therapeutic efficacy. Furthermore, crossreactivity to other insect antigens has been demonstrated [16].
A few studies have tried to identify the allergens included in
these extracts: several proteins with molecular weights between
14 and 150kδ have been isolated [14, 16]. Purified fractions of
these could be less active [15].
Dogs are placed in lateral recumbency and clipped carefully
over the thorax. After the area has been cleaned with ether,
injection sites are marked with a felt-tip pen. Each solution
(0.05 mL) is injected strictly intradermally in a standard order,
equidistant to the others. Two controls are used: a positive
control (histamine phosphate 0.01%) and a negative control
(phenolated physiological diluent).
Flea Salivary extracts
An artificial flea feeding system on membranes has allowed the
in vitro collection and purification of flea saliva. Several antigenic
fractions have been isolated but results from different studies
are controversial. Lee et al. isolated 2 proteins with molecular
masses of 8-12 kδ and 40 kδ [18]. Franck et al. isolated 15
fractions, some of which could elicit a positive immediate
intradermal test reaction in sensitised dogs [19]. One of these
proteins with a molecular mass of 18 kδ was then cloned and
expressed to produce a recombinant allergen; rCte f1 could
be a major allergen of flea saliva as IgE directed against this
protein has been detected in 95% of experimentally-induced
flea-allergic dogs. In naturally occurring flea-allergic dogs, IgE
directed against Cte f 1 were detected in only 80% of dogs
[20].
Reactions are first read after 15/20 minutes in the dark with the
aid of an oblique light source. A raised erythematous wheal is
considered a positive reaction. If erythema is absent, the result is
considered negative, even if a small wheal is visible. The greatest
diameter of each reaction is measured precisely using a ruler
provided by the allergen suppliers. To be considered positive,
the diameter of the wheal at the suspected allergen injection
site has to be greater than or equal to the mean of the wheal
diameters at the histamine and diluent control sites (Fig. 7).
245
Flea allergy in dogs: Clinical signs and diagnosis - C. Laffort-Dassot
When the reaction read at 15/20 minutes is negative, a second
measurement is made at 48h. This interval is considered optimal
because the immediate reaction can sometimes persist for up
to 24h. Moreover, in a delayed reaction, maximal development
of a cutaneous lesion provoked by intradermal injection of an
antigen in a sensitive dog occurs between 12 and 72 h [11].
The delayed reaction to flea extract appears as a skin thickening
(detected by palpation of a skin fold) or as a papule, both of
which can be encrusted (Fig. 8) [4].
allergy dermatitis based on history, clinical signs and response
to strict flea control [7]. This result is in accordance with another
study which showed that flea allergens involved in flea allergy
dermatitis are mostly found in flea saliva [24]. The fact that flea
saliva only represents 0.5% of the proteins in whole-body flea
extracts might somehow explain why intradermal skin testing
with whole-body flea extracts has been associated with variable
results [24]. In the same study, rCte f1 was also used as a reagent
for intradermal skin testing and the results were not as accurate
as for pure flea saliva: sensitivity was 40% and specificity 90%
[7]. Pure flea saliva and rCte f1 are not commercially available
for skin testing.
The majority of dogs show an immediate reaction followed by a
delayed reaction. Halliwell and Gorman demonstrated that 60%
of dogs show an immediate and a delayed reaction, 25% only
an immediate reaction and 14% only a delayed reaction [4]. For
others, the percentage of delayed reactions can be as high as
33% [2].
In vitro tests
Serological tests
The use of serological tests for the diagnosis of flea allergy
dermatitis has also been a great source of debate. Sensitivity,
specificity and reproducibility vary greatly, as does the quality
of flea allergens used. Whatever the technique used, delayed
reactions are missed.
Whatever the immediate and/or delayed reaction, a positive
reaction only means that the dog is sensitised to flea extracts
and does not prove that the dermatological problem the clinician
is dealing with is flea allergy dermatitis. Results of intradermal
skin testing have always to be interpreted in the light of history
and clinical signs [3].
These tests are based on the detection by enzyme-linked
immunosorbent assays (ELISA) of specific immunoglobulin IgE
or IgG. IgE or IgG specific to Ctenocephalides felis felis in the
serum of a dog suspected of FAD is detected by addition of an
antiglobulin linked to an enzyme; the complex immunoglobulin/
antiglobulin/enzyme is then detected and measured by addition
of the enzyme substrate [26]. In the case of IgE, this system has
to be very sensitive because of the small concentration of IgE in
serum [20]. Results of different studies using these serological
tests vary considerably: some authors have found high levels
of IgE or IgG in flea-allergic dogs when compared with normal
dogs [27] whereas others have found the opposite [24, 28].
Reports of reliability of intradermal skin testing using wholebody flea allergens for the diagnosis of canine flea allergy
dermatitis vary greatly. Although some authors report that they
give reliable results [2, 3], most of them report poor reliability
with sensitivity varying between 70 and 80% and specificity
around 60% [21]. This controversy is in part linked to the fact
that results vary considerably between studies, one reason for
this being whether or not delayed reactions were taken into
account.
One of the most recent assays uses the high affinity Fc epsilon
receptor (FcεRIα) to detect anti-flea saliva IgE in canine sera.
This test has an excellent specificity whereas sensitivity is
improved by the use of highly purified flea salivary antigens and
rCte f1. In one study, when results of this test were compared to
those of intradermal skin testing with pure flea saliva in clinical
cases of flea allergy artificially sensitised dogs, and dogs never
exposed to fleas, the test was found to be reliable for FAD
diagnosis (sensitivity 78%; specificity 91% and accuracy 88%)
[29]. In another independent study, results of this in vitro test
were compared to a clinical approach to FAD diagnosis based
on history, clinical signs and response to strict flea control.
Sensitivity of the test was 87%, specificity 53% and accuracy
64% [7].
It must be emphasised that positive reactions may be observed
in clinically normal dogs. In Florida, a flea-rich environment,
immediate positive reactions have been detected in 24% of
clinically normal dogs [22]. Furthermore, this was not predictive
of the future development of flea allergy dermatitis as two years
later, only 2.5% of these dogs had developed clinical signs
of flea allergy dermatitis. However, in Norway, a flea-scarce
environment, only 2% of clinically diagnosed “atopic dermatitis”
dogs and no clinically normal dogs or dogs with dermatoses
other than atopic dermatitis had positive reactions to flea [23].
Positive reactions against flea allergens in atopic and clinically
normal dogs in a flea-rich environment might represent truly
false positive reactions, subclinical hypersensitivity [22] or crossreactivity to other insect antigens [16]. This poor specificity has
led some authors to abandon intradermal skin testing with flea
extracts as a diagnostic tool for flea allergy dermatitis.
Cellular tests
Only direct activation of canine basophils has been used with
flea extracts. In this test, basophil degranulation is provoked by
contact with the offending allergen, in this case coming from
a flea extract. When results of this assay are compared with
those of intradermal skin testing with flea extracts, sensitivity
and specificity were 80%. However, the diagnostic value of
these tests for the diagnosis of FAD has not yet been established
[21].
Furthermore it seems that not all commercially available flea
extracts have the same diagnostic value. One study showed
that sensitivity varied between 27 and 67% and specificity
varied between 83 and 90% when whole-body flea extracts
were used as reagents for intradermal skin testing. When pure
flea saliva was used, sensitivity raised to 93% and specificity
90%. The results of intradermal tests comprising immediate and
delayed reactions were compared to clinical diagnosis of flea
246
EJCAP - Vol. 19 - Issue 3 December 2009
Response to flea control
Referenses
In the face of poor reliability of allergy testing with commercially
available flea assays, response to strict flea control can be
used to confirm flea allergy dermatitis. Trial flea control should
involve the flea-allergic dog, all in-contact animals and their
environment. The aim is to kill adult fleas on affected animals, to
eliminate fleas acquired from infested premises and to prevent
re-infestation. Effective residual insecticides are nowadays
available to kill adult fleas, and insect growth regulators should
be used to disrupt the flea life cycle. A permethrin-pyriproxyfen
spray has been found to be a useful product for performing a
therapeutic trial to confirm a diagnosis of flea allergy dermatitis
in dogs [30].
[1]
[2]
[3]
[4]
[5]
Mechanical control procedures (vacuuming, cleaning, possibly
removing all furniture or materials the pets are in contact with)
and preventing other animals that can carry fleas from entering
resting areas of pets are also important. Cats that wander in and
out are a frequent cause of treatment failure [8].
[6]
[7]
Trial flea control is not always reliable in FAD diagnosis because
it must take into account the level of flea challenge and the level
of “allergenic threshold” for that individual dog. It is essential for
the clinician to be aware of efficacy, frequency of administration,
dosage and mode of action of flea control products. In the study
with the permethrin-pyriproxyfen spray, flea control was applied
weekly on the flea allergic dogs only (no flea control on the
in-contact animals or in the environment was performed) for
3 times. This extra-label use led to a reduction in lesional and
pruritus scores of more than 75% in all of these dogs. No sideeffects were observed [30]. Strict owner compliance is necessary
both at the outset of flea control measures and also throughout
their duration. [14]. Even with adequate flea control, clinical
improvement can take a long time (4 to 8 weeks) [31, 32].
[8]
[9]
[10]
[11]
[12]
[13]
No anti-pruritic drug should be used during the trial. This can
be a problem in dogs that show slow clinical improvement.
When secondary infections are present, they must be cleared
but treatment required in these cases makes interpretation of
the trial difficult.
[14]
[15]
Conclusion
[16]
Diagnosis of canine flea allergy dermatitis relies on a thorough
history and physical examination, eliminating other differential
dermatoses, providing appropriate flea control for the fleaallergic dog, all in-contact animals and their environment.
Clinical signs and lesion distribution are strongly suggestive
of the diagnosis. Dorsolumbar lesions and pruritus have been
found, in many cases, to be discriminating criteria . However,
this is not sufficient for a definitive diagnosis. Demonstration of
fleas is not always possible in flea allergic dogs and appropriate
flea control is often difficult both to initiate and maintain. Some
in-vivo and in-vitro allergy tests can be used to document
sensitisation to flea allergens in flea-allergic dogs but their use is
controversial. A definitive diagnosis of flea allergy in the dog is
made by pooling evidence from different sources.
[17]
[18]
[19]
[20]
247
Reedy LH, Miller WH, Willemse T. Arthropod hypersensivity
disorders. In: Allergic skin disease of dogs and cats, 2nd edn.
Philadelphia. W.B.Saunders. 1999: 202-33.
Carlotti DN. Diagnostic de la dermatite par allergie aux piqûres
de puces (DAPP) chez le chien. Intérêt des intradermoreactions.
Pratique Médicale et Chirurgicale de l’Animal de Compagnie.
1985; 20: 41-7.
Scott DW, Miller WH, Griffin CE. Muller and Kirk’s Small Animal
Dermatology 6th edn. Philadelphia: WB Saunders. 2001: 543666.
Halliwell REW, Gorman NT. In: Veterinary Clinical Immunology.
Philadelphia: W.B.Saunders. 1989: 261-7.
Carlotti DN, Costargent F. Analysis of positive skin tests in 449
dogs with allergic dermatitis. The European Journal of Companion
Animal Practice. 1994; 4: 42-59.
Yu A, Lam A. Overview of Flea Allergy Dermatitis. Compendium:
continuing Education for Veterinarians. 2009, 220-5.
Laffort-Dassot C, Carlotti DN, Pin D, Jasmin P. Diagnosis of flea
allergy dermatitis: comparison of intradermal testing with flea
antigens and a fceRIa-based assay in response to flea control.
Veterinary Dermatology. 2004, 15: 321-30.
Ihrke PJ. Flea Allergy Dermatitis (how I treat). Proceedings of the
31st annual meeting of the WSAVA, Prague. 2006, p 32-5.
Prélaud P. Diagnostic clinique des dermatites allergiques. Revue
de Médecine vétérinaire. 2004, 155 : 12-19.
Bourdeau P. Relationship between the distribution of lesions and
positive intradermal reactions in 307 dogs suspected of atopy and/
or flea bite hypersensitivity. Proceedings of the Annual Member
Meeting of the ESVD/ECVD, Maastricht, 1998, p 157-8.
Vroom M. Flea allergy dermatitis. In: Guaguère E., Prélaud P. eds,
A practical guide to feline dermatology, Lyon: Mérial, 1999: 916.
Carlotti DN, Héripret D. La dermatite par allergie aux piqûres de
puces chez le chien Pratique Médicale et Chirurgicale de l’Animal
de Compagnie. 1986; 21 (suppl): 1-64.
Gross TL, Ihrke PJ, Walder, EJ, coll. Skin diseases of the dog and
cat. Clinical and histopathological diagnosis 2nd Ed. London:
Blackwell Publishing, 2005: 932p.
Bond R, Hutchinson MJ, Loeffler A. Serological, intradermal and
live flea challenge tests in the assessment of hypersensitivity to
flea antigens in cats (Felis domesticus). Parasitology Research.
2006, 4: 392-7.
Stolper R, Opdebeeck JP. Flea allergy dermatitis in dogs diagnosed
by intradermal skin tests. Research Veterinary Science. 1994; 57:
21-7.
Pucheu-Haston CM, Grier TJ, Esch RE. et al. Allergenic crossreactivities in flea-reactive canine serum samples. American
Journal of Veterinary Research. 1996; 57: 1000-5.
Greene WK, Carnegie RL, Shaw SE. et al. Characterization of
allergens of the cat flea, Ctenocephalides felis: detection and
frequency of IgE antibodies in canine sera. Parasite Immunology.
1993 ; 15 : 69-74.
Lee SE, Johnstone IP, Lee RP. et al. Putative salivary allergens of the
cat flea, Ctenocephalides felis felis. Veterinary Immunology and
Immunopathology. 1999; 69: 229-37.
Frank GR, Hunter SW, Stiegler GL. et al. Salivary allergens of
Ctenocephalides felis: collection, purification and evaluation by
intradermal skin testing in dogs. In: Kwochka K.W. et al, eds.
Advances in veterinary Dermatology III. Boston: Butterworth
Heinemann, 1998: 201-12.
McDermott MJ, Weber E, Hunter S. et al. Identification, cloning
and characterization of a major cat flea salivary allergen (Cte f 1).
Molecular Immunology. 2000; 37: 361-75.
Flea allergy in dogs: Clinical signs and diagnosis - C. Laffort-Dassot
[21] Prélaud P. Allergies aux parasites et aux insectes piqueurs. In:
Masson, ed. Allergologie canine, Paris. 1999: 85-106.
[22] Kunkle GA, Jones L, Petty P. Immediate intradermal flea antigen
reactivity in clinically normal adult dogs from South Florida, USA.
Veterinary Dermatology. 2000; 11: 9-11.
[23] Saevik BK, Ulstein TL. Immediate intradermal flea antigen reactivity
in dogs in a flea scarce environnement. Proceedings of the Annual
Member Meeting of the AAVD/ACVD, New Orleans, 2002, 18.
[24] Lee SE, Jackson LA, Opdebeeck JP. Salivary antigens of the cat
flea, Ctenocephalides felis felis. Parasite Immunology. 1997; 19:
13-9.
[25] Cook CA, Stedman KE, Frank GR et al. the in vitro diagnosis of
flea bite hypersensitivity : flea saliva vs whole flea extracts. In:
Kwochka K.W. et al, ed. Advances in veterinary Dermatology III.
Boston: Butterworth Heinemann, 1998: 494-5.
[26] Tizard IR. Veterinary Immunology: an introduction. 6th ed.
Philadelphia: WB Saunders Co, 2000: 191-209.
[27] Halliwell REW, Longino SJ. IgE and IgG antibodies to flea antigen
in differing dog populations. Veterinary Immunology and
Immunopathology. 1985; 8 : 215-23.
[28] McKeon SE, Opdebeeck JP. IgE and IgG antibodies against antigens
of the cat flea, Ctenocephalides felis felis, in sera of allergic and
non allergic dogs. International Journal of Parasitology. 1994; 24:
259-63.
[29] McCall CA, Stedman KE, Penner SJ. et al. FceRIa- based
measurement of antiflea Saliva IgE in Dogs. Compendium on
Continuing Education: Small Animal Practice. 1997; 19 (suppl):
24-8.
[30] Jasmin P, Briggs M, Schroeder H, Sanquer A. Comparison of a
permethrin-pyriproxyfen spray and fipronil spot-on used alone in
a therapeutic trail for diagnosis of canine flea allergy dermatitis.
Veterinary Dermatology. 2004, 15 (suppl 1): 47.
[31] Prélaud P. Diagnostic de la dermatite par allergie aux piqûres de
puces. Proceedings of the Annual Meeting of the CNVSPA AFVAC
2001, Lille, 144.
[32] Medleau L, Clekis T, McArthur TR, Alva R, Barrick RA, Jeannin
P, Irwin J. Evaluation of fipronil spot-on in the treatment of flea
allergy dermatitis in dogs. Journal of Small Animal Practice. 2003,
44: 71-5.
248
DERMATOLOGY
Flea allergy in cats – clinical signs
and diagnosis
C. Noli(1)
SUMMARY
Fleas are the most common ectoparasites and flea bite allergy is often seen in cats. The clinical signs are represented
by pruritus, excoriations, self-inflicted alopecia, manifestations of the eosinophilic granuloma complex and miliary
dermatitis, which often, but not exclusively, involve the posterior dorsal and ventral part of the body. The diagnosis is
obtained with the clinical presentation and response to flea control, and is supported by finding fleas, their feces or
taenia infestation, and by a positive intradermal and/or in vitro allergy test.
immediate wheal, when injected intradermally with a commercial
flea allergen [21]. Also allergen-specific IgE can be found in the
serum of flea allergic dogs by means of ELISA or RAST [4, 16,
23]. In some dogs a type-4 (delayed) cell-mediated reaction
may also be present, as an indurated wheal may appear 2448 hours after the intradermal injection of the allergen [10,23].
Other types of immunologic response, in addition to the classic
type-1 and type-4 reaction have been suggested in dogs [11],
i.e. a late phase IgE-mediated cellular response, which occurs 3
to 6 hours after the antigen exposure and a cutaneous basophil
hypersensitivity, with infiltration of basophils in the dermis.
This paper was commissioned by FECAVA for
publication in EJCAP.
Introduction
More than 2000 species of fleas have been identified, which
infest mammals and birds. The species identified in cats is
Ctenocephalides felis felis, by far the most prevalent flea in cats,
dogs and ferrets. Many diseases have been associated with fleas,
such as anemia, tape worm infestations, Lyme disease, the pest,
viruses, hemoparasites, cat scratch disease and flea allergy [22].
Flea allergy is the most frequent dermatological disease
associated with fleas [21], and its prevalence depends on the
geographical region.
Less is known about the pathogenesis of flea allergy in cats.
Most flea allergic cats have immediate positive intradermal skin
test reactions to flea allergens, and delayed type-4 reactions
have been also described [14]. As in dogs, allergen-specific IgE
can be found in the serum of flea allergic cats by means of ELISA
[17]. Late phase IgE-mediated cellular response and cutaneous
basophil hypersensitivity have not yet been identified in cats.
Pathogenesis of flea allergy
Fleas of both sexes bite the host several times a day [6]. It is
thought that non-allergic animals suffer little or no discomfort
while being bitten, and that only flea-allergic subjects develop
pruritus and skin disease.
Dogs continuously exposed to fleas become tolerant and
fail to become allergic. On the contrary, dogs intermittently
exposed to fleas develop immediate positive and/or delayed
skin reactions within 12 weeks, and have allergen-specific IgG
and IgE antibodies in their serum [11]. In a study specifically
designed to clarify the role of intermittent exposure to flea bites
in the development of flea bite allergy in cats it was concluded
that it had neither a protective nor a predisposing effect on the
development of clinical signs [3].
Several studies have dealt with the pathogenesis of flea bite
allergy in dogs. These investigations have suggested that
the allergic reaction in this species is most probably a type-1
(immediate) IgE-mediated response, with development of an
1) Chiara Noli, DVM, Dip ECVD, Ospedale Veterinario Cuneese, Via Vocaturo 13, 12016 Peveragno (CN), Italy
249
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 1 Small, round crusts typical of miliary dermatitis on the back
of a cat with flea bite allergy.
Fig. 2 Large areas of self inflicted alopecia on the abdomen.
It has been reported that dogs exposed to fleas early in their
life are less likely to develop flea allergy than dogs exposed
at a later age [10]. Results of a study of early sensitization of
12 weeks-old kittens, which developed only mild clinical signs
in 10/18 subject, suggest that this may be true in the cat also
[13]. The authors suggested that early ingestion of fleas could
induce tolerance, as cats experimentally exposed to fleas orally
tended to have limited symptoms and lower in vivo and in vitro
test scores, although this was not statistically different from the
controls [13].
dorsolumbar region, has been associated with flea allergy,
less frequently it can be due to other causes including bacterial
infection, dermatophytosis, drug reactions, pemphigus foliaceus,
and ectoparasites.
Self-inflicted alopecia
Self-induced alopecia in the cat is caused by licking either as a
result of pruritus due to flea or other allergies, parasitism or a
psychological disturbance. The sites of the licking in case of flea
bite allergy most commonly are the ventral abdomen, dorsum,
medial and lateral thighs (Fig. 2). Less commonly the lick induced
alopecia extends to the entire trunk. The affected areas may be
completely bald or have clumps of hair which the cat’s tongue
has not damaged as much. With a magnifying lens or by stroking
the skin against the line of the fur, broken hairs can be detected
emerging from the follicular openings. The faeces or vomit of
the cat may contain excessive quantities of hair.
The incidence of positive skin tests to flea antigen in atopic
dogs is significantly greater than in the general population. This
indicates that the atopic state may predispose the animals to the
development and maintenance of flea allergy [2]. It is not know
if the same is true for the cat.
Clinical appearance
The eosinophilic plaque
The eosinophilic plaque is a very pruritic, well circumscribed,
round to oval, erythematous, oozing, ulcerated plaque, mostly
located on the abdomen and medial thighs (Fig. 3). Less
frequently it may develop on other skin sites. It is found in cats
of all ages and breeds, and is often seen associated with flea
There is no breed or sex predilection, and animals may develop
flea bite hypersensitivity at any age [21]. In most cases flea
control of these animals is absent or incomplete or wrong. Flea
bite hypersensitivity may be observed the whole year round in
warm climates, although signs are usually worse in the warmer
months, particularly at the end of the summer, when the flea
population is at its highest point.
Fig. 3 Lesions of eosinophilic plaque on the medial aspect of a thigh.
Clinical signs of flea allergy in cats are miliary dermatitis,
self-inflicted alopecia, eosinophilic plaque and eosinophilic
granuloma, indolent ulcus and pruritus [15, 21]. All of these signs
could be reproduced in experimental sensitization studies [3].
Miliary dermatitis
The macroscopic lesions of miliary dermatitis are represented
by discrete light-brown crusts, diffusely distributed on the trunk
(Fig. 1). The animals are often only mildly pruritic. Histologically
the lesions appear similar to eosinophilic plaque (see herunder),
but less severe. These lesions have been considered the initial
stage of the eosinophilic plaque, because they share a common
histologic picture and because they may be seen on the same
animal. Miliary dermatitis, particularly if observed on the
250
Flea allergy in cats – clinical signs and diagnosis - C. Noli
allergy, as well as with atopic dermatitis and food allergy. The
eosinophilic plaque probably develops due to chronic trauma
caused by the cat’s tongue, when licking pruritic areas. A
secondary bacterial infection is frequent. Histologically this
lesion appears as a hyperplastic superficial to deep perivascular
to diffuse eosinophilic dermatitis with high amounts of mastcells
and an ulcerated epidermis [7] (Fig. 4). This pattern is similar to
that of miliary dermatitis, suggesting a common pathogenesis.
The eosinophilic granuloma
The eosinophilic granuloma is a well circumscribed, raised, firm,
yellow-pink, linear lesion usually located on the caudal thigh
(Fig. 5). It may also be located on the chin, paws or oral cavity.
It is generally asymptomatic but can occasionally ulcerate and
show pinpoint white foci of collagen degeneration and become
pruritic. The eosinophilic granuloma has been associated to fleabite allergy, as well as to food hypersensitivity, atopic dermatitis,
mosquito bites, insect hypersensitivity, genetic predisposition,
bacterial and viral infections (calicivirus) [20]. Histologically
it appears as a nodular to diffuse granulomatous dermatitis
with multifocal areas of “eosinophilic mush” (formerly called
“collagen degeneration”, now it appears that collagen is not
degenerated at all) [7] (Fig. 6). The eosinophilic material seen is
probably formed by granules of degranulated eosinophils and
these, along with multinucleated giant cell, form a palisading
granuloma around the foci of eosinophilic mush. The epidermis
is initially unaffected, and may ulcerate as the eosinophilic
material is expelled as a foreign body through the skin surface
and the hair follicles.
Fig. 5 Linear lesions of eosinophilic granuloma on the caudal
aspect of a thigh.
Fig. 4 Histological appearance of eosinphilic plaque: a thick
eosinophilic crust overlies an area of epidermal ulceration,
interstitial eosinophilic infiltrate in the underlying dermis
(Hematoxilin-Eosin 100x).
The indolent ulcer
The indolent ulcer is a well circumscribed, necrotic ulcer with
raised borders located mono- or bilaterally on the upper lip (Fig.
7). It is usually not painful. The indolent ulcer has also been
associated with flea allergy in experimental flea sensitization
studies [3]. The histological picture is usually non diagnostic:
a hyperplastic, ulcerated superficial perivascular dermatitis with
variable amounts of neutrophils, mononuclear cells and fibrous
tissue. A eosinophilic infiltrate or eosinophilic mush may be
observed.
Differential diagnoses
The main differential diagnoses of flea allergy in all its clinical
manifestations are other allergies, such as adverse reactions to
food and atopic dermatitis. In case of pruritus one should also
consider otodectic and notoedric mange and dermatophytosis.
Differentials of allergic self-inflicted alopecia are psychogenic
alopecia and Cheyletiella infestation. Common differential
diagnosis for eosinophilic granuloma is xanthomatosis, and, if the
lesion is a solitary nodule, mast cell tumour. Extended erosions/
ulcerations on the abdomen similar to eosinophilic plaque may
be seen in autoimmune diseases (pemphigus foliaceus, other
autoimmune disases), metastases of mammary tumours, or
bacterial/deep fungal ulcerative diseases. Indolent ulcer can
appear similar to labial squamous cell carcinoma. Miliary
dermatitis has as differentials cheyletiellosis, dermatophytosis,
mild pemphigus foliaceus and incipient paraneoplastic
desquamative diseases.
251
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 6 Histological appearance of eosinphilic granulma: large
aggregates of eosinophilic “mush” are visible in the dermis
(Hematoxilin-Eosin 40x).
Fig. 7 Monolateral lesions of indolent lip ulcer in a cat.
Diagnostic approach
hours), but it can be a good alternative in animals with a very
sensitive skin, which do not stand any topical application.
There are several problems in the approach to flea allergy in
cats. The first is that it is difficult per se to make an inequivocal
diagnosis of allergy in this species, the reason being, that
allergies have not yet been well defined in cats.
A more practical flea control measure involves a spot-on adulticide
(imidacloprid, fipronil, selamectin, metaflumizone) given every
three to four weeks, associated with an insect growth regulator
(IGR). The latter can be sprayed in the environment or be
contained in the spot-on product (methoprene, piryproxiphene)
or administered systemically to the cat as an injectable or oral
formulation (lufenuron). Some adulticides, such as imidacloprid
[12] or selamectin [18], also provide an IGR effect, as treated hairs
shed in the environment are able to inhibit eggs’ hatching. The
use of an IGR is fundamental to reduce the environmental flea
population, thus the flea burden on the cat and the consequent
clinical symptomatology. A product with a rapid knock down
effect would allow flea death before these parasites bite and
inject their antigens into the cat’s body, and would particularly
indicated in allergic animals. Unfortunately molecules with
the best knock down effect (pyrethroids) are toxic in cats and
cannot be used.
Clinical manifestations of allergy in cats are not as site-specific
as in dogs, e.g. a cat scratching on the neck may have a flea
allergy as well as food allergy, or a cat licking on its belly may
have a flea allergy, food allergy or atopic dermatitis. To make
things even more complicated, in cats there are some clinical
manifestations of flea allergy which may be due to other causes.
For example a “bold belly” may be due to allergy, as well as to
psychogenic causes, and a linear granuloma may be associated
to flea hypersensitivity or may be hereditary or idiopathic.
Finding fleas or flea dirt is not always possible, because even
one or a few fleas can elicit severe pruritus. Allergic cats in
particular are excellent groomers and can eliminate all of the
fleas put on them in less than 48 hours. Furthermore recent
bathing may also have removed all fleas and feces. Infestation
with Dipylidium caninum is a useful sign of flea presence.
The diagnosis of flea allergy may be confirmed by performing
an intradermal skin test. The flea allergen is injected (0.05 ml)
intradermally together with a negative (saline) and a positive
(histamine) control, and reactions are read at 15 minutes, 24
and 48 hours. Current or recent administration of steroids or
antihistamines may cause false-negative results. False-positive
reactions in normal cats have been described : in one study 36%
of clinically normal cats that had been exposed to fleas had a
positive immediate skin test reaction to flea antigens (19).
The best way to identify a flea allergy is to first treat all
secondary infections (rare in cats and mainly bacterial, seen on
eosinophilic plaques and/or excoriations) and all other possible
parasitic diseases (with spot on selamectin or moxidectin), then
perform a correct flea control for at least two months and then
recheck the animal.
A flea infestation can be best and quickly eliminated with oral
nitempyran. Its effect is seen as soon as 15-30 minutes after
administration [5]. Nitenpyran is thus an excellent means of
diagnosing the presence of fleas, if given as soon as the cat
enters the clinic, as fleas can be seen falling on the table during
the consultation. However, being it’s duration of effect so short
(>90% eliminated in 48h in cats), it is not very practical as a flea
prevention means (the drug should be administered every 48-72
A positive predictive value of 85-100% has been reported in
earlier studies (3, 8), while a more recent study performed with
three different extracts obtained a sensitivity of 0.33 and a
specificity of 0.78 to 1 [1]. In a study on laboratory induction
of flea hypersensitivity the presence of a positive immediate
intradermal test reactions did not correlate with the development
of symptoms [13].
252
Flea allergy in cats – clinical signs and diagnosis - C. Noli
Allergens used initially for this test were whole body flea extracts
(1:1000 w/v), now flea saliva or purified salivary antigens have
been developed for a more sensitive in vivo test [9]. However,
in experimentally induced feline flea bite allergy, results of
intradermal tests with purified allergens were not superior than
crude extracts in the correlation with clinical signs [3, 13].
[7]
[8]
[9]
In vitro serologic tests (ELISA) with whole flea extracts or flea
saliva are available for determination of allergen-specific IgE
in the feline serum. It is questioned if these tests only identify
animals with IgE mediated disease and fail to diagnose those
individuals who only show a delayed reaction. Furthermore,
there are normal cats who may have allergen-specific IgE in the
absence of clinical disease [1, 3, 13]. Sensitivity and specificity of
serological tests were reported to be 0.88 and 0.77 respectively
in one study [1] and 0.77 and 0.72 in another study [8], with a
low positive predictive value of 0.58 in the latter one.
[10]
[11]
[12]
[13]
Flea saliva represents only 0.5% of whole flea extracts, and
in vitro tests performed with flea salivary antigens gave much
better results in dogs than those performed with whole flea
extracts [4]. Furthermore, a new ELISA technology based on
FcεR1α has been developed for the in vitro diagnosis of feline
flea bite hypersensitivity [17]. In vitro test with salivary antigens
and the use of high-affinity receptors gave an overall accuracy
of 82% and may represent a more reliable tool for the diagnosis
of flea allergy in cats [17].
[14]
[15]
[16]
Conclusion
[17]
Flea bite hypersensitivity is one of the most important allergic
skin conditions in cats, which can manifest with different clinical
signs, and which has many possible differential diagnoses.
Intradermal and in vitro allergy tests are not always reliable
diagnostic tools, and a rigorous flea control, by means of
adulticides and insect growth regulators, represents the best
means of diagnosing and treating this condition.
[18]
References
[19]
[1]
[20]
[2]
[3]
[4]
[5]
[6]
Bond R, Hutchinson MJ, Loeffler A. Serological, intradermal and
live flea challenge tests in the assessment of hypersensitivity to
flea antigens in cats (Felis domesticus). Parasitol Res. 2006; 99(4):
392-7.
Carlotti DN, Costargent F. Analysis of positive skin tests in 449
dogs with allergic dermatitis. Eur J Comp Anim Pract. 1994; 4:
42-59.
Colombini S, Hodgin EC, Foil CS, Hosgood G, Foil LD. Induction of
feline flea allergy dermatitis and the incidence and histopahological
characteristics of concurrent indolent lip ulcers. Vet Dermatol.
2001; 12(3): 155-61.
Cook CA, Stedman KE, Frank GR, Wassom DL. The in vitro
diagnosis of flea bite hypersensitivity: Flea saliva vs. whole flea
extracts. Proceedings of the 3rd Veterinary Dermatology World
Congress, 1996 Spet 11-14; Edinburgh, Scotland; 1996. p. 170.
Dobson P, Tinembart O, Fisch RD, Junquera P. Efficacy of
nitenpyram as a systemic flea adulticide in dogs and cats. Vet Rec.
2000 Dec 16; 147(25): 709-13.
Dryden MW, Rust MK. The cat flea: biology, ecology and control.
Vet Parasitol. 1994; 52: 1-19.
[21]
[22]
[23]
253
Fondati A, Fondevila D, Ferrer L. Histopathological study of feline
eosinophilic dermatoses. Vet Dermatol. 2001; 12(6): 333-8.
Foster AP, O’Dair H. Allergy skin testing for skin disease in the cat
in vivo vs in vitro tests. Vet Dermatol. 1993; 4(3): 111-115.
Frank GR, Hunter SW, Wallenfels Lj, Kwochka KW. Salivary
allergens of Ctenocephalides felis: Collection, purification and
evaluation by intradermal skin testing in dogs. Proceedings of the
3rd Veterinary Dermatology World Congress; 1996 Spet 11-14;
Edinburgh, Scotland; 1996. p. 26 .
Halliwell REW, Preston JF, Nesbitt JG Aspects of the
immunopathogenesis of flea bite dermatitis in dogs. Vet Immunol
Immunopathol. 1987; 17: 483-94.
Halliwell REW, Gormann T : Nonatopic allergic skin diseases. In:
Halliwell REW, Goman NT, editors. Veterinary Clinical Immunology.
Philadelphia: WB Saunders; 1989. p. 262-7.
Jacobs DE, Hutchinson MJ, Stanneck D, Mencke N. Accumulation
and persistence of flea larvicidal activity in the immediate
environment of cats treated with imidacloprid. Med Vet Entomol.
2001; 15(3): 342-5.
Kunkle GA, McCall CA, Stedman KE, Pilny A, Nicklin C, Logas
DB. Pilot study to assess the effects of early flea exposure on the
development of flea hypersensitivity in cats. J Fel Med Surg. 2003;
5: 287-294.
Lewis DT, Ginn PE, Kunkle GA. Clinical and histological evaluation
of immediate and delayed flea antigen intradermal skin test and
flea bite sites in normal and flea allergic cats. Vet Dermatol 1999;
10, 29-38.
MacDonald JM. Flea allergy dermatitis and flea control. In: Griffin,
CE, Kwochka K, MacDonald JM editors. Current Veterinary
Dermatology. St. Louis: Mosby; 1993. p. 57-71.
McCall CA, Stedmann KE, Penne SJ et al. Fcε RIα-based
measurment of anti-flea saliva IgE in dogs. Comp Cont Educ Pract
Vet. 1997; 19(Suppl. 1): 24-8.
McCall CA, Stedman KE, Bevier DE, Kunkle GA, Foil CS, Foil LD.
Correlation of feline IgE, determined by Fcε RIα-based ELISA
technology, and IDST to Ctenocephalides felis salivary antigens
in a feline model of flea bite allergic dermatitis. Comp Cont Educ
Pract Vet. 1997; 19(Suppl. 1): 29-32
McTier TL, Shanks DJ, Jernigan AD, Rowan TG, Jones RL, Murphy
MG, et al. Evaluation of the effects of selamectin against adult
and immature stages of fleas (Ctenocephalides felis felis) on dogs
and cats.Vet Parasitol. 2000 (Aug 23); 91(3-4): 201-12.
MorielloKA, McMurdy MA. The prevalence of positive intradermal
skin test reactions to lea extracts in clinically normal cats. Comp
Anim Pract. 1989; 19: 28-30.
Rosenktantz WS. Feline Eosinophilic Granuloma Complex. In
Griffin CE, Kwochka KW, MacDonald JM (editors). Current
Veterinary Dermatology. St. Louis: Mosby Year Book; 1993. p.
319-24.
Scott DW, Miller WH, Griffin CE. Skin immune system and allergic
skin disease. In Scott DW, Miller WH, Griffin CE (editors) Small
Animal Dermatology, Philadelphia: WB Saunders; 2001. p. 6325.
Shaw SE, Birtles RJ, Day MJ. Arthropod-transmitted infectious
diseases of cats. J Feline Med Surg. 2001; 3(4):193-209.
Wilkerson MJ, Bagladi-Swanson M, Wheeler DW, Floyd-Hawkins
K, Craig C, Lee KW, Dryden M. The immunopathogenesis of flea
allergy dermatitis in dogs, an experimental study, Vet Immunol
Immunopathol. 2004, 99: 179-192.
DERMATOLOGY
Microbial diseases secondary to
allergic skin disease – clinical
significance and control
D. H. Lloyd(1)
SUMMARY
Allergic skin diseases predispose dogs and cats to cutaneous infections including microbial overgrowth and surface,
superficial and deep pyoderma, most commonly involving pathogenic staphylococci and Malassezia pachydermatis.
These can be treated successfully with systemic and topical antimicrobial agents but tend to recur unless the
allergy is well controlled. In the face of emerging multiresistance in Europe, particularly in Staphylococcus aureus
and S. pseudintermedius, antibacterial treatment should be based on culture and sensitivity tests, and adoption of
treatment regimens ensuring good compliance and antimicrobial administration for appropriate periods. Recurrence
of infection can be controlled with topical antimicrobials and especially shampoos containing chlorhexidine and
benzoyl peroxide but long term low dose or pulse therapy should be avoided. Staphylococcal vaccines can be effective
in some cases of superficial pyoderma.
amongst the commonest diagnoses. Systemic antibiotics were
prescribed in 25% of cases [3]. Thus dealing effectively with
infection secondary to allergy has a high priority in small animal
practice.
This paper was commissioned by FECAVA for
publication in EJCAP.
Introduction
Allergy and microbial infection
The skin is a very effective defensive organ. Despite exposure
to dirt, trauma and changing environments, under normal
conditions it remains healthy or recovers quickly with minimal
attention. This is because intact skin has an efficient epidermal
barrier with its own self-cleaning process, represented by
continual desquamation of the stratum corneum and a variety
of immune mechanisms which resist proliferation and invasion
by pathogens [1,2]. Cutaneous infection occurs only when
these processes fail. One important factor which impairs these
processes is allergic skin disease.
Both animals and humans with allergic skin disease are
predisposed to secondary microbial infection of the skin.
Allergy induces changes in skin, which lead to colonisation and
infection with pathogenic staphylococci in both dogs and in
humans. Colonisation and infection with other organisms and
particularly species of the genus Malassezia are also promoted.
These changes have been best studied in staphylococcal disease
associated with atopy. In man more than 90% of patients with
atopic dermatitis have massive skin colonisation with S. aureus
and in lesional skin up to 107 colony-forming units per cm2
of skin may be present [4]. Up to 68% of dogs with canine
atopy have been reported to have pyoderma and populations
of S. intermedius that are significantly elevated in both lesional
and non-lesional skin and, also in the mucosae [5]. Cutaneous
hypersensitivity reactions have also been shown to be associated
with increased skin permeability to substances including bacterial
virulence factors such as staphylococcal protein A [6,7].
Allergy and recurrent bacterial infection are amongst the
commonest reasons for consultation and treatment of dogs
and cats in small animal practice. In a survey of the prevalence,
diagnosis and treatment of dermatological conditions in general
practice in the UK, involving 3707 small animal consultations,
pruritus was the most common presenting sign (30-40% of
dermatological consultations) and bacterial infections were
1) David H. Lloyd, Department of Veterinary Clinical Sciences, Royal Veterinary College Hawkshead Campus, North Mymms, Hertfordshire AL10 0EJ,
United Kingdom. Tel: +44 1707 666234, Fax: +44 1707 666298. E-mail: [email protected]
254
EJCAP - Vol. 19 - Issue 3 December 2009
Dry skin commonly occurs in humans with atopy and evidence
has been produced indicating that they have ceramide and
sphingosine deficiencies in the lipid barrier of the epidermis.
However, such deficiency does not appear to be a feature
of atopy itself as comparison of uninvolved skin of atopic
dermatitis patients with healthy skin has shown no difference
in ceramide profiles [8]. Furthermore, in dogs, studies of water
absorption-desorption in normal and atopic dogs have not
shown differences suggesting that the water barrier is not
affected [9]. However, electron microscopy has demonstrated
abnormal intercellular lipid lamellae and reduced thickness and
continuity of lipid lamellae in the stratum corneum of canine
atopic skin, supporting the concept of defective barrier lipid
function [10]. If sphingosine deficiency is a feature of atopic
skin, this may favour colonisation by pathogenic staphylococci
since sphingosine has potent antimicrobial activity against S.
aureus [11]. Staphylococcal activity could also cause or enhance
damage to the epidermal barrier in various ways. For instance,
ceramidase from S. aureus can cause hydrolysis of ceramides
in atopic skin whilst IL-4 from T helper type 2 (TH2) cells in
atopic skin has been shown to suppress ceramide production in
human epidermal sheets and induce synthesis of fibronectin, an
adherence target of staphylococci [12]. Once established at the
skin surface a staphylococcal biofilm may become established,
as in bacterial overgrowth, promoting adherence and toxin
production. Thus bacterial action may be able to further reduce
barrier function and promote changes in the epidermis favouring
colonisation and infection in atopic skin.
Thus confirmation of the presence and type of infection is an
important part of the diagnostic process.
The great majority of bacterial skin infections involve grampositive organisms and particularly the coagulase positive
staphylococci. The commonest of these is Staphylococcus
pseudintermedius which represents over 90% of infections. This
new species was first described in 2005 and was formed by the
division of isolates previously known as S. intermedius into 2
species [13]. The name S. intermedius is now applied to isolates
that are principally found in pigeons. Infections with S. aureus are
relatively uncommon (around 5% or less). S. schleiferi coagulans
and S. schleiferi schleiferi (coagulase negative) are less often
recognised as causes of infection, but are found particularly
in otitis and in certain regions [14]. S. hyicus is occasionally
implicated. Other coagulase-negative staphylococci are rarely
involved and normally only if immunity is greatly reduced or
when implants are used.
Gram-negative bacteria are sometimes found in pyoderma,
particularly when lesions are moist. Organisms such as Proteus
and coliforms may be secondary invaders that fail to persist
when more significant pathogens are removed. Pseudomonas
aeruginosa is more serious and requires specific therapy
[15]. Deep infections are much less common but are more
serious and can involve a wide variety of organisms including
staphylococci, Nocardia and Actinobacillus and mycobacteria.
Anaerobic infections are particularly associated with faecal
contamination and may involve Actinomyces spp., Clostridium
spp., Peptostreptococcus spp., Bacteroides spp., Fusobacterium
spp., and Prevotella spp. [16].
A further cause of damage to the skin leading to microbial
infections in allergic dogs and cats is self-inflicted trauma caused
by pruritus. Pruritus is one of the primary signs in allergy and is
also a consequence of surface and superficial microbial infections.
Thus a vicious circle can readily occur in allergic animals causing
an itch-scratch cycle and exacerbating the disease.
The Diagnostic Approach
Cytology of exudate or aspirates of lesions will commonly confirm
the presence of bacteria and a neutrophilic exudate. Cocci will
normally be staphylococci but occasionally streptococci. Rods
are normally gram-negative. Evidence of phagocytosis is good
evidence of infection but is not always present. Cytology may be
supported by culture to confirm bacterial identity and provide
sensitivity data. Cultures are essential in severe, recurrent or nonresponsive cases, and where there is a recognised problem with
highly resistant organisms in the area where the affected animal
resides. In deep pyoderma, samples of exudate or tissue obtained
from deep lesions by biopsy or aspiration may be required. Other
diagnostic procedures are necessary to investigate concurrent
underlying problems which could reduce immunity and promote
infection, in addition to allergic skin disease
Allergic skin diseases are common but may be difficult to
diagnose. Even when an accurate diagnosis has been established
they may be difficult to control and require continual therapy.
The consequences of inadequate control in many dogs and
cats are recurrent microbial overgrowth, pyoderma and otitis.
These diseases require repeated or long-term therapy with
topical and systemic antimicrobial agents, incurring cost and
the risk of acquiring resistant organisms. This review focuses
on the diagnosis and management of pyoderma and microbial
overgrowth with an emphasis on monitoring and prompt
therapy that will minimise infection and reduce the use of
antimicrobials.
Pyoderma in Dogs
Canine pyoderma can be conveniently considered according to
the depth of infection within the skin (Tab. 1). Not all forms of
pyoderma are predisposed by allergic skin disease.
Pyoderma
Pyoderma in its various manifestations is one of the commonest
problems in small animal practice. Particularly in dogs, cases are
often chronic or recurrent and cause considerable suffering.
Although “pyoderma” literally means “pus in skin” the term is
generally used to denote bacterial infections where pus may not
always be visible macroscopically. However, many conditions
in addition to bacterial infection can result in accumulation of
pus, including some fungal infections and autoimmune disease.
Surface pyoderma
This involves damage and bacterial proliferation only in the
outermost layers of the skin and can normally be resolved with
minimal antibacterial therapy provided that underlying problems
are identified and resolved. Skin immunity is not compromised.
255
Microbial diseases secondary to allergic skin disease – clinical significance and control - D. H. Lloyd
Skin fold pyoderma is associated with irritation and lack of
ventilation between skin folds. Bacteria other than the pathogenic
staphylococci may also be involved and Malassezia populations
may be raised as in microbial overgrowth which is described
below; demodicosis is an important differential diagnosis. The
occluded skin is moist, erythematous and may be malodorous,
especially in the lip folds. Exudate may sometimes be seen
flowing from affected folds (Fig. 2). The clinical appearance is
diagnostic in almost every case and can be confirmed by tape
strip cytology. If in doubt, histopathology should be carried
out.
Surface pyoderma
• Acute moist dermatitis (pyotraumatic dermatitis, “hot
spots”)
• Skin fold pyoderma (intertrigo)
Superficial pyoderma
•
•
•
•
•
Impetigo (“puppy pyoderma”)*
Superficial spreading pyoderma
Superficial folliculitis
Mucocutaneous pyoderma*
Dermatophilosis*
Treatment of surface pyoderma is based on normalising
the surface microbial populations. In acute moist dermatitis,
prevention of further trauma is essential and will sometimes
allow healing without further therapy. It is important to ensure
that there is no underlying folliculitis or furunculosis. Recovery
is normally rapid. However, lesions are often painful and topical
therapy, requiring direct contact with skin, can be hazardous.
Topical antibiotic and steroid gels or creams are effective but
spraying with a soothing, antimicrobial, astringent preparation
[17] has been shown to be as effective and is likely to be less
dangerous. Lesions should be substantially healed in 7-10 days.
Where there is marked pruritus, glucocorticoids may be required
and can be given conveniently systemically, or topically using
hydrocortisone aceponate spray. Treatment of fold pyoderma
can be carried out as described below for microbial overgrowth.
Surgery to remove the folds is effective where this is feasible.
Deep pyoderma
• Muzzle folliculitis and furunculosis “canine acne”)*
• Pyotraumatic folliculitis and furunculosis
• Localised deep pyoderma (nasal, pedal, pressure point
and acral lick pyoderma,)*
• Generalised deep pyoderma*
• Bacterial granuloma*
Tab. 1 Classification of Canine Pyoderma
*Not normally associated with allergic skin disease.
Acute moist dermatitis commonly occurs when self-inflicted
damage disrupts the epidermis and allows proliferation of grampositive and gram-negative bacteria. It commonly occurs in flea
allergy. Moist, painful, focal area(s) of erythema and hair loss,
often on the gluteal region, arise within hours (Fig. 1). Diagnosis
is based on the characteristic history and clinical signs. Some
cases may also involve deeper infection (pyotraumatic folliculitis
and furunculosis). After cleansing, look for satellite papules and
pustules which are indicative of this syndrome. If in doubt or
the lesion does not resolve quickly, histopathology should be
carried out.
Superficial Pyoderma
This involves infection of the epidermis, often affecting the hair
follicle epithelium.
Superficial folliculitis is very common. It is characterised by
focal erythema, papules and pustules centred on hair follicles
and is usually very pruritic. Pustules give rise to thin scabs
Fig. 2 Exudate can be seen flowing from the facial folds of this
bulldog with fold pyoderma and atopy.
Fig. 1 Acute moist dermatitis affecting the thigh of a dog with
fleabite hypersensitivity.
256
EJCAP - Vol. 19 - Issue 3 December 2009
can be reduced to once or twice a week; in winter weekly to
monthly shampooing may be sufficient to maintain remission.
Glucocorticoids should be avoided as they can mask clinical signs
which enable the clinician to judge when to stop antimicrobial
therapy; they may also impair the immune response.
Where there is recurrent infection and underlying causes
cannot be controlled, long-term treatment options need to
be considered. Regular use of antibacterial shampoo may give
control. Otherwise, the main options are pulse therapy with
antibiotics and staphylococcal vaccination. Vaccination is a
better choice. Well-prepared autogenous vaccines (bacterins)
are effective in up to 50% of cases; responding dogs may not
need other therapy [18]. An American bacterial lysate prepared
from S. aureus, has also been shown to reduce the frequency of
folliculitis and decrease the need for repeated antibiotic therapy
[19]. Pulse or continual low dose therapy [20] should be a last
resort as it may promote development of antimicrobial resistance
and acquisition of more resistant bacteria.
Fig. 3 Papules and pustules affecting the ventral abdomen of a dog
with recurrent superficial pyoderma.
and may spread centrifugally. Loss of the scab may leave a
circular epidermal collarette. Lesions often occur on the ventral
areas, axillae, medial surfaces of the thighs and groin (Fig. 3).
Lesions of the trunk are associated with focal areas of hair loss
and in shorthaired dogs these are apparent as focal areas of
alopecia, so-called ‘shorthaired dog pyoderma’. Clinical signs
are characteristic but other causes of pustular disease (e.g.
demodicosis, dermatophytosis, impetigo, pemphigus foliaceous,
sterile eosinophilic pustulosis, subcorneal pustular dermatosis)
need to be considered. Cytology demonstrating a neutrophilic
exudate and bacteria and or biopsy may be used to confirm the
diagnosis.
The increasing recognition of meticillin-resistant strains
of S. aureus (MRSA) and recently of meticillin-resistant S.
pseudintermedius (MRSP) in dogs and cats is a problem that
requires vigilance when treating pyoderma [21, 22]. These
organisms can be resistant to a wide range of antimicrobials
and may be acquired from infected or carrier individuals when
animals are being treated with agents to which they are resistant.
Owners and veterinary staff may become carriers. S. schleiferi
schleiferi and S. schleiferi coagulans that are meticillin-resistant
are also sometimes isolated in canine pyoderma, particularly in
certain countries, but are generally less resistant than MRSA or
MRSP [23]. Thus antimicrobial sensitivity tests should be carried
out whenever the identity and sensitivity of infecting organisms
cannot be predicted or when treatment does not yield the
expected response.
Superficial spreading pyoderma is a syndrome seen in association
with superficial folliculitis and with similar underlying causes. The
pathogenesis is not understood but may relate to production of
exfoliative toxin by S. pseudintermedius. Erythematous macules
give rise to expanding erythematous rings with borders formed
by thin, peeling crusts. Lesions generally occur in relatively
hairless, intertriginous zones. Diagnosis and treatment is as for
superficial folliculitis.
Deep Pyoderma
This is rarer and generally involves much more threatening
infections. Occurrence of such diseases often indicates presence
of more severe localised or generalised predisposing causes
compared with superficial pyoderma. Only those conditions
likely to be associated with allergic skin disease are described
here.
Treatment of superficial folliculitis. Normally systemic
antimicrobial therapy is used and the registered doses based
on accurate weights of the affected animals will be effective in
uncomplicated cases. Bacteriostatic antibiotics can be used but
bactericides are likely to be more effective. Treatment for at least
one week beyond clinical cure is advisable and drug regimens
facilitating compliance, e.g. with palatable tablets, should be
chosen if possible. In cases of adverse food reaction/dietary
hypersensitivity care should be taken to avoid flavourings or
capsules that contain substances to which the affected animal
may be sensitive.
Deep folliculitis and furunculosis involves infection of both
hair follicles and the dermis with rupture of hair follicles and
consequent exposure of hair fragments to dermal inflammatory
mechanisms leading to foreign body reactions (foreign body
granuloma). Furunculosis is indicated by the presence of large
papules or nodules and thicker crusts, dark lesions suggesting
haemorrhage and or necrosis, and by presence of pus, which may
be haemorrhagic, draining from fistulae (Fig. 4). In longhaired
dogs, extent and severity of lesions may be disguised by the
coat.
Recovery may be promoted by use of antibacterial shampoos
containing chlorhexidine or benzoyl peroxide, which aid removal
of crusts and reduce surface bacterial populations. Mild superficial
pyoderma can be treated with such shampoos without systemic
antibiotic but this is labour-intensive; shampooing every 2-3
days is required. Once lesion resolution occurs, shampooing
Bacteria other than the pathogenic staphylococci are more
often present, particularly gram-negatives including coliforms,
Pseudomonas and Proteus spp. A variety of underlying
factors may be involved and must be thoroughly investigated;
257
Microbial diseases secondary to allergic skin disease – clinical significance and control - D. H. Lloyd
Fig. 4 Nodular lesions with haemorrhagic crusts on the limb of a
dog with deep pyoderma.
Fig. 5 Microbial overgrowth affecting the foot of a boxer; all four
feet were affected. The dog alo suffered from recurrent superficial
pyoderma.
hypothyroidism and demodicosis are common but in some
instances no cause may be found. Cytology, culture and
sensitivity, blood screens and biopsy will be required in most
cases. Deep fungal infection may be involved and thus both
fungal and bacteriological cultures should be requested.
Pyoderma in Cats
Cats occasionally develop superficial and deep pyoderma in dogs
but seem much more resistant to these diseases. Essentially the
same processes of diagnosis are used. Skin infections in cats are
most commonly abscesses, which occur following bite wounds.
Pyotraumatic folliculitis and furunculosis presents as
acute moist dermatitis but concealing deeper infection. Lesions
commonly occur on the cheeks and neck and in young dogs,
particularly in retrievers, St. Bernards and Newfoundlands.
Histopathology is advisable to confirm the nature of infection;
underlying causes including allergy should be investigated.
Microbial overgrowth
Bacterial overgrowth is a newly described skin condition
of dogs characterised by the presence of substantially
increased populations of bacteria, particularly Staphylococcus
pseudintermedius [24]. Commonly, the yeast Malassezia
pachydermatis is also present and in such cases the term “microbial
overgrowth” is appropriate. When only M. pachydermatis is
present the condition is equivalent to Malassezia dermatitis
[25]. However, bacterial overgrowth and microbial overgrowth
occur much more commonly and in a wider range of clinical
situations than has been classically described for Malassezia
dermatitis. These conditions are often an unrecognised cause of
pruritus, particularly in occluded areas such as the pedal webs.
They commonly occur in atopy or other allergic dermatoses and
successful treatment will often greatly reduce the measures
needed to bring pruritus under control. Failure to recognise
the microbial cause may lead to inappropriate and excessive
prescription of anti-inflammatory drugs.
Treatment of deep pyoderma. It is essential to correctly
identify the causative bacteria and use appropriate systemic
antimicrobial therapy, selecting bactericidal drugs if possible
and ensuring compliance. Registered doses are effective
but commonly higher doses are used in more severe cases.
Systemic antimicrobial treatment is given for a period at least
two weeks beyond clinical resolution of the lesions. Recovery
may be promoted by the use of topical antimicrobial shampoos
containing chlorhexidine or benzoyl peroxide every two to three
days. This is aided by clipping the coat which allows easier access
to the affected skin and can promote compliance as the owners
are able to see the extent and severity of the disease. Continuing
use of antibacterial shampoos may help to prevent recurrence
and vaccines may be helpful in recurrent cases but seem less
effective than in superficial pyoderma.
Aetiology and pathogenesis
Bacteria. Bacteria generally maintain low populations on
healthy skin as a consequence of the unfavourable surface
microenvironment and defensive measures maintained by the
skin [2]. When the skin is damaged or its defences are impaired
bacterial adherence to the keratinocytes is promoted and the
bacteria are able to proliferate. The pathogenic staphylococci
and, in dogs, particularly S. pseudintermedius (formerly S.
intermedius) seem especially able to take advantage of such
changes. When high local cell densities (biofilm formation) of
staphylococci are established, quorum sensing can take place.
If the pyoderma fails to respond to antimicrobial therapy despite
evidence of compliance with an appropriate treatment regimen,
cytology and cultures should be repeated and biopsy specimens
submitted for histopathology, ensuring that infected tissue deep
within the lesions is sampled. In all cases of deep pyoderma
it is very important to identify and resolve underlying causes.
Treatment with glucocorticoids is contraindicated.
258
EJCAP - Vol. 19 - Issue 3 December 2009
This is a mechanism in which cell density signals are exchanged
amongst the staphylococci when population sizes reach a certain
threshold allowing them to initiate the production of toxins that
can irritate and damage the skin [26]. Once toxin production
has been initiated, more cutaneous damage is induced and
immunity may be further impaired leading to a vicious circle of
damage and bacterial proliferation.
treatment of microbial overgrowth will often permit other
underlying pruritic or inflammatory diseases to be identified.
Unless such underlying problems are identified and controlled,
overgrowth is likely to recur.
Treatment and Control
The condition normally responds to topical therapy with
antimicrobial shampoos containing chlorhexidine, or
chlorhexidine and miconazole that are active against
staphylococci and Malassezia. Benzoyl peroxide shampoo can
also be used. Shampooing every 2-3 days for 2 weeks will
normally bring the condition under control. Then treatment once
or twice a week is usually sufficient. An astringent, soothing
antimicrobial spray has also been shown to be a convenient and
effective treatment for microbial overgrowth [24], especially
in areas that are localised or difficult to reach. It can also be
used for prophylaxis in recurrent cases. In severe or extensive
cases of microbial overgrowth or when washing/spraying of the
affected areas is not practicable, systemic therapy with cefalexin
at 15 mg/kg twice daily [29] and or imidazoles (if Malassezia is
present) can be very helpful, depending on the nature of the
microbes involved. Ketoconazole (5-10 mg/kg twice daily with
food) or itraconazole (5 mg/kg twice daily or 10 mg/kg once
daily) are effective when used for 2-4 weeks.
Malassezia. M. pachydermatis is present as a commensal
of the skin and mucosae of most dogs. In healthy animals it
exists at higher population densities at the lips and interdigital
skin than at the ears [27]. The anus seems to be the most
frequently colonised mucosal site. M. pachydermatis acts as an
opportunistic pathogen and factors promoting its pathogenicity
may include increased temperature and humidity, excessive lipid
secretion, intercurrent diseases, and therapy with antibiotics and
glucocorticoids; however, this remains controversial [28].
Breed-related factors are important in Malassezia dermatitis;
basset hounds and West Highland white terriers are particularly
predisposed. Since S. pseudintermedius and M. pachydermatis
are inhabitants of the mucosae, including the oral cavity, they
will continually be transferred to the skin, particularly in areas
which require cleaning or grooming, and which are pruritic. Thus
there is potential for the establishment of microbial overgrowth
whenever the skin is damaged or there is underlying disease
impairing cutaneous function.
Whatever treatment is used, it is important to monitor response
and adjust the nature and frequency of treatment as necessary.
This can be quickly and easily be achieved using tape strip
specimens stained with DiffQuik.
Clinical Features
Microbial overgrowth is characterised by the presence of
erythema, greasiness or exudation, pruritus and saliva staining
in the absence of papules and pustules. Pruritus may be quite
marked. Owners may be unaware of the lesions and careful clinical
examination with good illumination is necessary. In chronic or
severe lesions there may be excoriation and lichenification. There
is commonly malodour, especially when Malassezia is involved.
Overgrowth is normally seen in areas of skin that are moist or
occluded such as the lips, between the pads and digits, in the
groin, perivulvar and perianal areas, on the ventral abdomen,
in the axillae, on the pinnae of the ears, and in skin folds. It is
frequently present in dogs with allergic skin disease. It can be
very localised or may affect several sites on a dog.
Microbial Overgrowth in Cats
Overgrowth of bacteria and Malassezia in cats is relatively rare
but increasingly recognised [30]. It is suggested that Malassezia
spp. overgrowth may represent a secondary cutaneous problem
in allergic cats with greasy adherent brownish scales. Favourable
response to treatment with imidazole antifungal treatments
alone suggests that, as in dogs, Malassezia spp. may be partly
responsible for both pruritus and cutaneous lesions in such
cats [31]. Devon rex cats appear to be particularly prone to
Malassezia dermatitis.
Conclusions
Diagnosis
Microbial overgrowth should be suspected when pruritus
occurs and compatible lesions are present, even if they are mild.
Diagnosis is confirmed by cytology using tape strip samples, glass
slide impressions or swab smears stained with DiffQuik showing
elevated populations of bacteria or Malassezia. Tape strips are
preferred because they organisms are sometimes not located at
the surface of the lesions and repeated application of the tape
to the same site will reveal deeper populations. The technique
is quick and easy to perform and, with experience, tapes can
be examined in the microscope and diagnosis made within
2-3 minutes. The presence of numbers of bacteria above 5 or
Malassezia above 2 per high power x1000 oil immersion field is
suggestive of microbial overgrowth. Commonly populations are
very much higher but the organisms may be found in clusters
so at least 20 high power fields should be examined. Successful
The microbial infections associated with allergic skin disease can
be effectively treated with antimicrobial drugs and, if the allergy
is brought under good control, may cease to be a problem.
Where only partial control is achieved, vaccines, and topical
antimicrobial therapy with shampoos and sprays, may enable
recurrence to be minimised.
Emerging problems with multi-resistant bacteria emphasise the
need to reduce the duration of use antimicrobials. This can be
done by selecting the most effective appropriate antimicrobial
with the aid of culture and sensitivity tests and ensuring good
compliance in the treatment regimen, so that exposure of the
animal to systemic antimicrobial agents ceases as soon as the
lesions have resolved and the one or two-week extra treatment
periods specified for superficial and deep pyoderma have been
observed.
259
Microbial diseases secondary to allergic skin disease – clinical significance and control - D. H. Lloyd
In cases of recurrent pyoderma, pulse therapy or continual low
dose therapy should be avoided if at all possible and further
efforts made to identify and correct underlying problems.
the American Veterinary Medical Association. 2003; 222: 451-4.
[15] Hillier A, Alcorn JR, Cole LK, Kowalski JJ. Pyoderma caused by
Pseudomonas aeruginosa infection in dogs: 20 cases. Veterinary
Dermatology. 2006; 17: 432-9.
[16] Scott DW, Miller WH, Griffin CE. (2001) Bacterial skin disease. In:
Muller and Kirk’s Small Animal Dermatology 6th ed. Philadelphia,
WB Saunders Company. 2001, pp. 274-335.
[17] Ascher, Madin, Guaguere et al. Intérêt d’une solution topique
non antibiocorticoide dans le traitement de la dermatite
pyotraumatique du chien. Pratique Médicale et Chirurgicale de
l’Animal de Compagnie. 1995; 30: 345-54.
[18. Curtis CF, Lamport AI, Lloyd DH. Masked, controlled study
to investigate the efficacy of a Staphylococcus intermedius
autogenous bacterin for the control of canine idiopathic recurrent
superficial pyoderma. Veterinary Dermatology. 2006; 17: 163-8.
[19] DeBoer DJ, Moriello KA, Thomas CB, Schultz KT (1990) Evaluation
of a commercial staphylococcal bacterin for management of
idiopathic recurrent pyoderma in dogs. American Journal of
Veterinary Research. 1990; 51: 636-9.
[20] Carlotti D-N, Jasmin P, Gardey L, Sanquer A. Evaluation of
cephalexin intermittent therapy (weekend therapy) in the control
of recurrent idiopathic pyoderma in dogs: a randomized, doubleblinded, placebo-controlled study. Veterinary Dermatology. 2004;
15 (s1): 8-9.
[21] Loeffler A, Linek M, Moodley A, Guardabassi L, Sung JML, Winkler,
M, Weiss R, Lloyd DH. First report of multi-resistant, mecA-positive
Staphylococcus intermedius in Europe: 12 cases from a veterinary
dermatology referral clinic in Germany. Veterinary Dermatology.
2007: 18; 412-21.
[22] Leonard FC, Markey BK. Meticillin-resistant Staphylococcus aureus
in animals: a review. Veterinary Journal. 2008; 175: 27-36.
[23] Jones RD, Kania SA, Rohrbach BW, Frank LA, Bemis DA. Prevalence
of oxacillin- and multidrug-resistant staphylococci in clinical
samples from dogs: 1,772 samples (2001-2005). Journal of the
American Veterinary Medical Association. 2007; 230: 221-7.
[24] Pin D, Carlotti D-N, Jasmin P, DeBoer DJ, Prelaud P. Prospective
study of bacterial overgrowth syndrome in eight dogs. Veterinary
Record. 2006; 158: 436-41.
[25] Bond R, Ferguson EA, Curtis CF, Craig JM, Lloyd DH. Factors
associated with elevated cutaneous Malassezia pachydermatis
populations in dogs with pruritic skin disease. Journal of Small
Animal Practice. 1996; 37: 103-7.
[26] Sung JML, Chantler PD, Lloyd DH. The accessory gene regulator
locus of Staphylococcus intermedius. Infection and Immunity.
2006; 74: 2947-56.
[27] Bond R, Saijonmaa-Koulumies L, Lloyd DH. Population sizes and
frequency of Malassezia pachydermatis at skin and mucosal sites
in healthy dogs. Journal of Small Animal Practice. 1995; 36: 14750.
[28] Guillot J, Bond R. Malassezia pachydermatis: a review. Medical
Mycology. 1999; 37: 295-306.
[29] Jasmin P, Pin D, Carlotti DN. Efficacy and interest of a systemic
antibiotic treatment with cephalexin in dogs affected with
bacterial overgrowth (BOG). Proceedings of the 7th FECAVA and
47th Annual Congress of the FK-DVG, Berlin, October 2001, p.
51.
[30] Ordeix L, Galeotti F, Scarampella F, Dedola C, Bardagí M, Romano
E, Fondati A. Malassezia spp. overgrowth in allergic cats.
Veterinary Dermatology. 2007; 18: 316-23.
[31] Ahman S, Perrins N, Bond R. Treatment of Malassezia
pachydermatis-associated seborrhoeic dermatitis in Devon Rex
cats with itraconazole - a pilot study. Veterinary Dermatology.
2007; 18: 171-4.
Acknowledgements
The author is most grateful to colleagues of the Royal Veterinary
College, London, Dermatology Unit for providing illustrations
used in this review.
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Elias PM. The skin barrier as an innate immune element. Seminars
in Immunopathology. 2007; 29: 3-14.
Lloyd DH. The canine skin microbiota: habitats, acquisition,
interactions and exchange. European Journal of Companion
Animal Practice. 2008; 18: 61-8.
Hill PB, Lo A, Eden CA, Huntley S, Morey V, Ramsey S, Richardson
C, Smith DJ, Sutton C, Taylor MD, Thorpe E, Tidmarsh R,
Williams V. Survey of the prevalence, diagnosis and treatment of
dermatological conditions in small animals in general practice.
Veterinary Record. 2006; 158: 533-9.
Matsui K, Nishikawa A, Suto H, Tsuboi R, Ogawa H. Comparative
study of Staphylococcus aureus isolated from lesional and nonlesional skin of atopic dermatitis patients. Microbiology and
Immunology. 2000; 44: 945-7.
Saijonmaa-Koulumies, L.E., Lloyd, D. H. Colonisation of the canine
skin with bacteria. Veterinary Dermatology. 1996; 7: 153-63.
Mason IS, Lloyd, DH. The role of allergy in the development of
canine pyoderma. Journal of Small Animal Practice. 1989; 30:
216-8.
Mason IS, Mason KV, Lloyd DH. A review of the biology of canine
skin with respect to the commensals Staphylococcus intermedius,
Demodex canis and Malassezia pachydermatis. Veterinary
Dermatology. 1996; 7: 119-32.
Farwanah H, Raith K, Neubert RH, Wohlrab J. Ceramide profiles
of the uninvolved skin in atopic dermatitis and psoriasis are
comparable to those of healthy skin. Archives for Dermatological
Research. 2005; 296: 514-21.
Chesney CJ. The microclimate of the canine coat: The effect
of heating on coat and skin temperature and relative humidity.
Veterinary Dermatology. 1997; 8: 183.
Inman AO, Olivry T, Dunston SM, Monteiro-Riviere NA, Gatto H.
Electron microscopic observations of stratum corneum intercellular
lipids in normal and atopic dogs. Veterinary Pathology. 2001; 38:
720-723.
Arikawa J, Ishibashi M, Kawashima M, Takagi Y, Ichikawa
Y, Imokawa G. Decreased levels of sphingosine, a natural
antimicrobial agent, may be associated with vulnerability of
the stratum corneum from patients with atopic dermatitis to
colonization by Staphylococcus aureus. Journal of Investigative
Dermatology. 2002; 119: 433-9.
Hatano Y, Terashi H, Arakawa S, Katagiri K. Interleukin-4
suppresses the enhancement of ceramide synthesis and cutaneous
permeability barrier functions induced by tumor necrosis factoralpha and interferon-gamma in human epidermis. Journal of
Investigative Dermatology. 2005; 124: 786-92.
Devriese LA, Vancanneyt M, Baele M, Vaneechoutte M, De Graef
E, Snauwaert C, Cleenwerck I, Dawyndt P, Swings J, Decostere
A, Haesebrouck F. Staphylococcus pseudintermedius sp. nov., a
coagulase-positive species from animals. International Journal of
Systematic and Evolutionary Microbiology. 2005; 55: 1569-73.
Frank LA, Kania SA, Hnilica KA, Wilkes RP, Bemis DA. Isolation of
Staphylococcus schleiferi from dogs with pyoderma. Journal of
260
DERMATOLOGY
Flea control in flea allergic
dogs and cats
Marie-Christine Cadiergues(1)
SUMMARY
Flea allergy dermatitis (FAD) remains the most common allergic skin disease of dogs and cats, although its frequency
varies according to geographical location. Despite the availability of safe, effective products, treating FAD remains a
challenge. This challenge should be more readily overcome once both practitioner and owner(s) are entirely convinced
of the diagnosis. The main difficulties and pitfalls facing the practitioner are described. Treatment requires appropriate
knowledge of the flea life cycle and flea-related biology, and understanding of the mode of action of the relevant flea
control products. An integrated approach to treatment should be adopted, involving all the players in the flea life cycle
- the FAD patient, all in-contact pets, and the environment. Each case must be customised, with effective flea control
products used in combination with cleaning measures such as steaming, vacuuming and regular grooming.
The vet should ensure that the client understands these relevant
basic principles of flea biology.
This paper was commissioned by FECAVA for
publication in EJCAP.
Host phase
The adult stage of both Ctenocephalides felis felis and
Ctenocephalides canis (also called cat flea and dog flea
respectively), lives permanently in the hair coat of its host.
Exchanges between animals are possible but limited, and should
not be considered the main source of infestation. Fleas have
a tendency to leave their host when the host’s temperature
decreases (e.g. death, anaesthesia), when the species is not well
adapted to the host (e.g. C. canis in cats) or when the on host
population is extremely high [2].
Introduction
Flea allergy dermatitis (FAD) remains the most common allergic
skin disease of dogs and cats, although its frequency varies
according to geographical location. The past twenty years have
brought important advances in flea biology as well as better
insecticides [1]. Nevertheless, flea control in general, and more
specifically in dogs and cats with FAD, remains a real challenge
for vets.
Early onset of blood feeding
Once the adult (imago) has colonised a new host, it will take
its first blood meal very rapidly. About 25% of cat fleas start
to feed within 5 minutes of being free in the coat and about
97% have taken a blood meal within 1 hour [3]. Although C.
canis takes its meal more slowly, 72.5% of fleas begin blood
feeding within one hour [4]. The mean duration of the first
blood meal, evaluated on individual fleas confined on animals,
has been found to be 25± 18 minutes in females C. felis and 11±
8 minutes in males C. Felis [3]. It was significantly shorter (5 and
6 minutes, respectively for C. canis) [4]. These data demonstrate
the difficulty if not the impossibility of preventing newly emerged
fleas from taking a blood meal and hence injecting their saliva.
This paper will be divided into four sections. The first will focus
on flea biology on which flea control programmes are based. In
the second, the main difficulties and pitfalls facing practitioners
will be described. The third section will outline the various active
ingredients and formulations currently available.The last chapter
will consider specific flea control recommendations.
Flea biology and flea control
Various aspects of flea biology may be useful in improving flea
control and/or understanding failure or inadequacy of flea
control programmes.
1) Marie-Christine Cadiergues, DrMedVet, DipECVD, PhD, MRCVS, Groupe de Recherches Animaux de Compagnie- Ecole Nationale, Vétérinaire de
Toulouse, 23 chemin des Capelles 31076 Toulouse cedex France. E-mail: [email protected]
261
EJCAP - Vol. 19 - Issue 3 December 2009
Blood feeding and lifespan
Although it is clearly established that blood-feeding is necessary
for mating and laying viable eggs [2], the number of blood
meals and their frequency remain unknown. It is thought that
fleas will continue to bite and have blood meals until they die.
The lifespan of C. felis felis is usually considered to be between
2 and 3 weeks. Under experimental conditions, mean survival
of C. canis in the canine coat was 8.6 days [5]. Clearly, flea
lifespan depends highly on the level of grooming (by the animal
itself or the owner). Survival of 250 unfed fleas of both species
was evaluated in the environment at 19°C and 27°C (RH 70%).
Mean survival of 50% of C. canis was 15.9 days (19°C) and 9.0
days (27°C). Under similar conditions, mean survival of C. felis
was 11.7 days (19°C) and 9.6 days (27°C). After 48 hours on a
dog, mean survival of females was 7.9 days (19°C) and 4.8 days
(27°C) for C. canis and 4.9 days (19°C) and 3 days (27°C) for C.
felis. Survival of males was shorter [5].
formed out of various bits of environmental debris stuck
together. Pupae are often found in well-protected areas such
as the back of carpets, skirting boards and cushion seams.
Inside, the future imagos remain dormant for several months
(the so-called “pupal window”) until stimulated to hatch by
triggers such as vibrations, increased carbon dioxide levels
and/or temperature changes. Pupae are resistant to freezing,
desiccation, insecticides and IDIs.
First eggs
Female fleas lay their first eggs between 24 and 36 hours after
colonising a host. Eggs are laid in the coat and subsequently fall
to the ground. They are then susceptible to insect development
inhibitors (IDIs) applied on the coat or on the ground, as well as
insecticidal products. Egg production reaches a peak (around
15-20 eggs per day) during the second and third weeks and
then decreases, but a female will lay eggs until it dies. Cat flea
egg production usually peaks during the night, coinciding with
normal sleep periods for indoor pet dogs and cats [6], hence
a higher density of immature stages in animal resting places,
including bedrooms. Around areas such as sofas and beds,
where pets jump and play, eggs and flea faeces will be more
easily dislodged from the haircoat [6].
Preventing a new life cycle would require killing all the adults in
the first 24-36 hours of infestation and/or applying an IDI either
to the adult or to the immature stages before pupa formation.
Vacuuming is not very effective due to the mobility and positive
geotaxis of the larvae. Although immature stages concentrate
in rooms or areas where animals spend most of their time, it is
crucial to take into account places visited infrequently or visited
by other animals including wildlife.
Imago
Once stimulated, the imago tears open the cocoon, probably as
a consequence of its agitated movements, and jumps onto the
first mobile, warm “object”, usually an animal. The young, unfed
adult is susceptible to adulticides and IDIs. As stated earlier, the
unfed flea survives longer in the environment than fed fleas. The
entire life cycle can be completed in 13 to 14 days under optimal
conditions but can take up to 7-9 months.
Main difficulties and pitfalls
Convincing the owner and customising flea control
measures
Surprisingly, one major difficulty in FAD control is convincing
the owner (and sometimes the referring practitioner) that FAD
is the correct diagnosis. It is rather common to be faced with
owner disbelief or scepticism. Because fleas are not seen by the
owner, and their presence is difficult to prove on animals with
FAD, the owner is sometimes absolutely convinced that fleas
cannot be the cause of his/her pet’s dermatitis. Some people
associate fleas with a lack of hygiene and cannot accept that
their pet(s) might have fleas. Other people, who recognise fleas
in dogs to be common, doubt that their pet would present with a
flea-related skin disease when other pets with fleas do not have
a skin problem? Furthermore, why should pruritus be so severe
if only a few fleas are present? Owners may be sceptical because
they think, or have been told, that they are doing everything they
can to kill fleas and/or that they have used the wonder product.
Environmental phase and factors affecting egg
production
Once on the ground, eggs require favourable environmental
conditions (humidity and temperature) to develop further. Ideal
conditions for the life cycle of the cat flea (relative humidity of
70% and a temperature of between 20 and 30°C) are provided
by a modern home environment. The environmental phase has
major implications in control because larval and pupal stages
develop there and because pupae remain dormant in the
environment for an extended period of time.
Larval instars
The first-instar larvae hatch from eggs in the pet’s immediate
environment. They then tend to move to the base of the carpet,
not travelling far from where they hatched. They search for
suitable food, particularly dried blood faeces [6] but also other
debris including non-viable flea eggs [7]. The second-instar
larvae tend to search more widely for food and darker areas
where they are less likely to be disturbed. They tend to move
away from carpets, making vacuuming, which only removes
15-27% of the larvae, a rather ineffective procedure. However,
regular vacuuming of pet resting places can remove 90% or
more of flea eggs as well as flea faeces [6].
Clinical features, at least in dogs, may help to convince a sceptical
owner. These include a typical dorso-lumbar distribution pattern
extending to the tail base, perineum and medial/caudal thighs,
and crusted papules in the umbilical fold (especially in male dogs).
The presence of fipropruritic nodules is also highly suggestive.
The client might accept the diagnosis more readily if given clear
and simple explanations about both allergy in general and flea
allergy in particular. Emphasising the difference between flea
infestation and flea allergy, and outlining the role of flea saliva
and therefore that of flea bites is important. Describing the life
cycle in relation to the pet’s individual circumstances may help
the owner to understand why fleas are still present. Additional
Pupal stage
The third-instar larva becomes a pupa encased within a cocoon
262
Flea control in flea allergic dogs and cats - Marie-Christine Cadiergues
testing and strict trial flea control for 6 weeks might finally
convince the owner.
Swimming, bathing and excessive grooming
Dogs that swim or bathe regularly should receive systemic
treatment (e.g. nitenpyram once daily or every other day,
selamectin once monthly) as swimming or bathing degrades the
efficacy of topical products. Spinosad, a new oral, beef-flavoured
tablet for dogs, not yet available in Europe, would also be a
product of choice as it kills fleas rapidly and remains effective
for one month after application. Cutaneous inflammation,
hyperhydrosis, cornification disorders (primary and secondary)
and excessive grooming should be considered when applying
a topical flea product. Not only may the product irritate the
skin but its diffusion may also be impaired by the skin changes.
Excessive grooming might reduce the amount of insecticide
present on the skin thereby reducing or delaying its efficacy.
Once convinced, the owner needs guidance and motivation.
Again, a clear explanation of the flea life cycle combined
with information on the way products work is usually helpful.
Demonstrating how to apply the product(s) correctly is
recommended; a small area on the skin of the back of the neck
could be shaved to ensure that a spot-on formulation is applied
onto the skin and not in the fur.
The therapeutic regimen should always be customised,
necessitating a thorough patient history and details of the
owner’s circumstances.
In-contact animals and premises
All the in-contact animals should be treated, albeit less strictly
perhaps that the patient with FAD. Cats, especially, are easily
forgotten either because they live outdoors or because they may
not be around when it is time to treat the dog(s). Cats can also
be difficult to medicate and are sometimes not considered by
owners to be part of the problem. All areas regularly visited by
the pet with FAD (including cars and sheds) should be treated
with a suitable product at an appropriate frequency. Visiting
pets inadequately treated for fleas, represent a risk as they can
re-introduce fleas (mainly immature stages which can develop
and lead to delayed re-infestations but possibly also adults) in a
well-controlled household. Similarly, visiting infested places can
trigger a flare. When such possibilities cannot be avoided, strict
preventive treatment, similar to a trial therapy regimen, should
be recommended.
Over-the-counter products
Extensive and long-term flea control measures require
considerable effort and expense. This can produce a progressive
reduction in compliance, and may also explain why over-thecounter (OTC) products are sometimes preferred by owners.
Most OTC products do not have the efficacy, residual activity or
safety profile of the veterinary products. With time, substitution
of OTC products could lead to poor control of FAD, owner’
frustration or even suspicion of resistance.
Active ingredients and formulations
Neonicotinoids
This class of insecticides was developed for crop protection
and subsequently found to be highly effective for flea control
in dogs and cats, with an excellent tolerance. Imidacloprid
(Advantage®, Advantix®, Advocate® - Bayer Health Care),
nitenpyram (Capstar® - Novartis SAS) and dinotefuran (Vectra
3D - Summit VetPharm, unavailable to date in Europe) are the
active ingredients available for pets.
Maintaining consistency of flea control
After a while, particularly when there is clinical improvement,
attention given to flea control tends to flag. However, this must
not be allowed to happen. The practitioner and/or well-trained
nurses from the practice must regularly emphasise the importance
of consistent flea control. Reminders can be sent, using modern
communication forms (text messages, Multimedia Messaging
Services on mobile phones, emails). These are sometimes offered
free of charge by pharmaceutical companies.
Imidacloprid has a high affinity for the nicotinergic acetylcholine
receptors in the post-synaptic region of the central nervous
system (CNS) in insects. The ensuing inhibition of cholinergic
transmission in insects results in paralysis and death of the
parasite. It is only available as a spot-on with surface action.
It is effective against adult fleas, requiring 8 hours of contact
[9-11]. It also has, in common with most insecticidal products,
a larvicidal effect [12, 13]. Combination with permethrin is likely
to enhance its speed of action [14, 15].
Efficacy of ectoparasiticides [8]
Controlled studies are advocated to assess the efficacy of flea
control products. Classically, efficacy is determined by comparing
parasite numbers on groups of treated and control animals after
experimental infestations. Fleas are deposited 48 to 72 hours
before the application of a product to be assessed. Immediate
therapeutic efficacy is evaluated 24 or 48 hours post-treatment
by combing off and counting the surviving fleas. Parasite counts
24 or 48 hours following subsequent infestation(s) at 7-day
intervals are used for residual efficacy calculations. Residual
efficacy is evaluated by re-infesting the animals in each study.
A threshold of 90 or 95% efficacy is required. Most products
with a European licence have a 95% efficacy threshold 48 hours
after infestation. TEven if a product is applied according to the
manufacturer’s recommendations, 100% efficacy should not,
therefore, be expected. Furthermore, efficacy tends to decrease
with time.
Nitenpyram is a fast-acting, orally administrated flea treatment.
Like imidacloprid, it acts on the nicotinic acetylcholine receptor
channel. It is readily absorbed, with peak plasma levels reached
within 30 minutes and a half-life of about 8 hours [16, 17]. First
signs of efficacy are seen 15 minutes or more after infestation.
Fleas are dislodged after 30 minutes, and within 6 hours, over
95% are killed. The effect is prolonged for 24-48 hours [17,
18].
Dinotefuran is a third generation neonicotinoid; dinotefuran was
synthesised with acetylcholine as the lead compound whereas
imidacloprid was based on nicotine. It is also a fast-killing
insecticide, effective for 30 days following application [19]. It is
263
EJCAP - Vol. 19 - Issue 3 December 2009
available in the US as a spot-on. For dogs, it is combined with
pyriproxyfen and permethrin, and for cats with pyriproxyfen
only.
Pyrethrins and Pyrethroids
These products cause spontaneous depolarisation, augmented
neurotransmitter secretion, and neuromuscular blockade
by sodium and potassium ion transport disruptions in nerve
membranes. Action is extremely rapid, but paralysed insects
can also recover rapidly. Natural pyrethrum is extracted from
chrysanthemum flowers and notable for its rapid but brief
action and relatively good tolerance in dogs and cats. Synthetic
pyrethroids are pyrethrum-like compounds with greater potency
and residual effects. They are, however, toxic in cats. This is
especially true for permethrin, a second-generation pyrethroid.
Permethrin is available in several formulations and is particularly
prominent in over-the-counter products, for which efficacy
data are difficult to find. Among the formulations which have
been extensively evaluated, spot-on formulations include a
65%-permethrin spot-on [35-37] (Defend Exspot® treatment
for dogs – Schering-Plough Animal Health), combination
products e.g. imidacloprid10%/permethrin 50% [14, 15] (K9
Advantix® – Bayer) and pyriproxyfen 0.3%/permethrin 40%
(Duowin® Contact – Virbac). Sprays containing 2% permethrin
(Defendog® – Virbac) or combination products such as
pyriproxyfen 0.02%/permethrin 1.9% (Duowin® – Virbac) are
also available. Efficacy against fleas was assessed in several trials.
After one application, under controlled conditions, adulticidal
efficacy of the imidacloprid 10%/permethrin 50% product was
99.4% (day 1), 95.7% (day 29) and 90.4% (day 36) [15]. The
same formulation was assessed in a field trial at 23 centres in
Germany, France and Italy on 229 dogs treated once. 134 other
dogs were treated once with a topical 10% fipronil formulation.
The immediate (day 2) efficacy against fleas of the imidacloprid
permethrin combination vs. the control product was 98.3%
vs. 97.0%. Residual efficacy (day 28) of the two products was
92.5% vs. 93.5% [14].
Phenylpyrazoles
Introduced in Europe in 1994, fipronil has been a market
leader ever since. First available as a spray (Frontline® spray –
Merial), fipronil later became available in a spot-on formulation
(Frontline® spot-on, Frontline® Top spot – Merial) eventually
being combined with methoprene, still as a spot-on (Frontline®
Combo, Frontline® Plus – Merial). More recently, pyriprole from
the same chemical group has become available as a spot-on
(Practic® - Novartis). Now that fipronil’s patent has expired,
generic products have appeared on the market (e.g. Effipro®
- Virbac). Phenypyrazoles block the gamma-aminobutyric acid
(GABA)-gated chloride channels of neurons in the central
nervous system, sharing a common binding site with cyclodienes.
Fipronil also binds to two different glutamate-gated chloride
channels [20, 21]. Efficacy of fipronil was evaluated in dogs
[22] and cats [23] with FAD. The 10%-fipronil solution, applied
monthly three times, reduced flea counts on day 90 by 98%.
Pruritus was reduced or eliminated in 84% of dogs [22]. The
same formulation, applied monthly to cats with FAD, reduced
flea counts by 94% on day 90 with pruritus reduced or absent
in 78% of cats [23]. In a study comparing efficacy of selamectin,
imidacloprid and fipronil in dogs experimentally infested with
both Ctenocephalides felis and C. canis, the efficacy of fipronil,
48 hours after each infestation, was 100%. This persisted for
35 days after one application [24]. In studies investigating the
efficacy of a single application of a 12.5% pyriprole spot-on
formulation, persistence of the active ingredient was assessed
after repeated washing and shampooing. Neither shampooing
24 hours post-treatment nor weekly washes altered the efficacy
which was 99.8-100% and 100%, respectively, for 30 days
[25].
Metaflumizone
Metaflumizone (Promeris®, Promeris®Duo – Fort Dodge) is
derived from pyrazoline and acts by binding the voltagedependent sodium channels in insects. Studies in controlled
environment (experimental infestations, comb-counts 48h after
treatment and re-infestations) showed over 90%-efficacy for 6
weeks in dogs [38] and 7 weeks in cats [39]. Speed of kill was
evaluated in adult cats and compared with a product containing
a combination of fipronil-(S) and methoprene. It was found to
be slower [40]. A European multicentric study was performed
on 170 dogs with flea infestation, randomly allocated to one of
two treatments, metaflumizone plus amitraz (minimum dosage
of 20 plus 20mg/kg) or fipronil (at the recommended label
rate). Both treatments resulted in consistent (>89%) reductions
in flea numbers relative to baseline counts, throughout the
study (8 weeks), although fipronil resulted in numerically higher
reductions on each count day [41].
Avermectins
Selamectin (Stronghold®, Revolution® – Pfizer) is believed to
bind to glutamate-gated chloride channels in the parasite’s
nervous system, increasing permeability and allowing the rapid
and continued influx of chloride ions into the nerve cell. This
inhibits nerve activity thereby causing paralysis [26]. Selamectin
is applied topically, is rapidly absorbed through the skin, and is
distributed via the blood [27]. It has activity against both internal
and external parasites. Several studies have been published
supporting its efficacy against fleas [10, 12, 24, 28-32]. Topical
application was over 98% effective after 36 hours in dogs and
24 hours in cats [31, 32]. In dogs, mean efficacy, 3 and 8 hours
after treatment, was 39.7 and 74.4%, respectively [11]. A study
performed in dogs and cats with FAD housed in flea-infested,
simulated home environments [33] and a multicentre field trial
performed in dogs [34] both showed a significant reduction in
clinical signs of FAD in dogs and cats after two applications, one
month apart. The multicentre study did not show any difference
between the group treated with fipronil and the group treated
with selamectin. Improvement was observed after two weeks
and clinical signs had almost resolved after two months [34].
Spinosad
Spinosad is an aerobic fermentation product of the soil
bacterium, Saccharopolyspora spinosa. Spinosad kills insects
through activation of the acetylcholine nervous system
through nicotinic receptors. The mode of action is unique and
incompletely understood. It is available in the United States as
an chewable tablet (Comfortis® – Lilly). Its efficacy against fleas
264
Flea control in flea allergic dogs and cats - Marie-Christine Cadiergues
appears excellent (98-100%) [42, 43]. A recent controlled study
showed that when administered to infested dogs, efficacy was
81%, four hours post-treatment. When treated animals were
re-infested, efficacy was over 96% for 14 days, four hours after
infestation [44].
A female flea starts laying eggs within 24-36 hours and then
continues to do so for the rest of its life. Consequently, to prevent
additional environmental contamination, a product which
becomes effective in under 24 hours should be recommended.
Adulticidal products on the animal with FAD
Given what has already been said about the testing and
evaluation of antiparasitic substances, and also the effects of
over-grooming, excessive bathing, and skin inflammation on
reducing product efficacy, it might be wise either to apply a
product more frequently (for example, every 2-3 weeks) than
recommended by the manufacturer or, better still, alternate
every fortnight, between two different products each with a
different mode of action.
Juvenile hormone analogues (JHAs)
The pharmacological properties of juvenile hormone analogues
are characterised by mimicking the juvenile hormones of insects
resulting in interference with metamorphosis and reproduction.
Prevention of larval development breaks the flea life cycle. Due
to specificity of juvenile hormone for insects, pyriproxyfen has
virtually no effects on mammals. Two products, methoprene and
pyriproxyfen, are used for flea control, either administered to the
animal or applied in the environment. They are usually combined
with an adulticide: fipronil (Frontline® Combo/Frontline® Plus –
Merial) [45] or permethrin (Duowin®, Duowin®Contact – Virbac).
A spot-on containing 1% pyriproxyfen only (Fleegard® - Bayer)
[46] and a commercial diet (Virbac Vet Complex® dermatology
– Virbac) containing 50 mg/kg are also available in several
countries.
The efficacy of insecticidal products is dose-dependent. The
dose itself is time-dependent, varying according to whether the
product is applied all over the body surface or to a more restricted
area. Systemic products have the advantage of not being altered
by any skin change/action. Similarly, applying a product all over
the body (e.g. spraying in dogs), should, assuming the correct
dose is given, ensure rapid and homogenous covering of the
body surface with adequate amount of product.
Insect developmental inhibitors (IDIs)
Lufenuron (Program® - Novartis) is a systemic IDI which interferes
with chitin synthesis, polymerisation and deposition [47].
Lufenuron has no effect on adult fleas. Excreted in flea faeces, it
prevents normal pupation of larvae feeding on those flea faeces.
Numerous studies have shown its efficacy either administered
orally to dogs or cats or injected to cats [18, 28, 48-50]
Treatment of in-contact-animals
All must be treated, including cats. Their treatment regimen
does not have to be as strict as that of the pet with FAD. A single
adulticidal product (instead of possibly two on the animal with
FAD), applied according to the manufacturer’s recommendations
(instead of every fortnight) should be suggested. Should the
animal with FAD be treated with a systemic (or possibly topical)
IGR such as lufenuron (or methoprene/pyriproxyfen), all incontact animals should also be treated.
Recommendations
As yet, the ideal product does not exist
Flea avoidance is certainly the goal for a dog or cat with
FAD. This is difficult and takes time. Symptomatic, antipruritic
therapy (beyond the scope of this article) is often necessary.
Furthermore, there are so many opportunities for a dog to
pick up fleas (e.g. environment, neighbourhood and occasional
visiting animal) that even if flea control is considered optimal, it
may still fail. Allergen-specific immunotherapy has, to date, not
been helpful.
Targeting the different steps of the life cycle: integrated
control
An insect growth regulator (IGR) - JHA or an IDI - should be
combined with an adulticide(s), either on the animal or in the
environment. Prior to application of flea control products in
the environment, hygienic measures should be recommended,
bearing in mind the relative lack of efficacy of vacuuming against
larvae. Prior steam cleaning should be suggested.
The ideal product to protect an animal with FAD against fleas
would be one with repellent action, i.e. a product which ideally,
would prevent fleas (mainly newly-emerged adults but also
fleas coming from infested animals) from jumping on, or at least
disturbing any fleas that did arrive in the coat so that they would
leave immediately without biting (flushing effect). Unfortunately,
although such products are effective against some insects (e.g.
mosquitoes), they are not very helpful in flea control.
When premises are too large, or when young children are at
high risk of coming in contact with the products (particularly
pyrethroids) whilst playing on carpets, the IGR should be
administered directly to the animal, preferably systemically.
Customising flea control
Factors which may influence failure in a flea control programme
may be product-related or animal/owner-related. Client
compliance, short-term and long-term, is essential in FAD cases.
Therefore, any control plan has to be practical for the owner and
must be adapted to individual circumstances. Compliance, ability,
health, financial resources, presence of young children, degree
of pet and owner contact must all be taken into consideration.
One should remember that a newly-emerged flea will start
feeding within a few minutes of its arrival on the host. The first
blood meal lasts from 10 minutes (males) to 25 minutes (females)
[3]. It is therefore, not surprising that none of the aforementioned
products is able to kill fleas before the fleas start to bite. However,
some of them (particularly pyrethroids, but also nitempyram and
spinosad) can certainly shorten the blood meal duration thereby
reducing the amount of saliva injected.
265
EJCAP - Vol. 19 - Issue 3 December 2009
13. Fourie LJ, Kok DJ, Peter RJ. Control of immature stages of the flea
Ctenocephalides felis (Bouche) in carpets exposed to cats treated
with imidacloprid. J S Afr Vet Assoc. 2000; 71(4): 219-21.
14. Hellmann K, Knoppe T, Krieger K, Stanneck D. European
multicenter field trial on the efficacy and safety of a topical
formulation of imidacloprid and permethrin (Advantix) in dogs
naturally infested with ticks and/or fleas. Parasitol Res. 2003; 90
Suppl 3: S125-6.
15. Epe C, Coati N, Stanneck D. Efficacy of the compound preparation
imidacloprid 10%/permethrin 50% spot-on against ticks (I.
ricinus, R. sanguineus) and fleas (Ct. felis) on dogs. Parasitol Res.
2003; 90 Suppl 3: S122-4.
16. Dobson P, Tinembart O, Fisch RD, Junquera P. Efficacy of
nitenpyram as a systemic flea adulticide in dogs and cats. Vet Rec.
2000; 147(25): 709-13.
17. Rust MK, Waggoner MM, Hinkle NC, Stansfield D, Barnett S.
Efficacy and longevity of nitenpyram against adult cat fleas
(Siphonaptera: Pulicidae). J Med Entomol. 2003; 40(5): 678-81.
18. Cadiergues MC, Steffan J, Tinembart O, Franc M. Efficacy of an
adulticide used alone or in combination with an insect growth
regulator for flea infestations of dogs housed in simulated home
environments. Am J Vet Res. 1999; 60(9): 1122-5.
19. Correia TR, Cruz VP, Ribeiro Fde A, Melo RM, Fernandes JI, Verocai
GG, et al. [Residual activity in vitro of treated dog’s hair coat with
dinotefuran on larvae and adults of Ctenocephalides felis felis
(Bouche, 1835) (Siphonaptera: Pulicidae)]. Rev Bras Parasitol Vet.
2008; 17(4): 195-9.
20. Zhao X, Yeh JZ, Salgado VL, Narahashi T. Fipronil is a potent
open channel blocker of glutamate-activated chloride channels
in cockroach neurons. J Pharmacol Exp Ther. 2004; 310(1): 192201.
21. Zhao X, Salgado VL, Yeh JZ, Narahashi T. Differential actions of
fipronil and dieldrin insecticides on GABA-gated chloride channels
in cockroach neurons. J Pharmacol Exp Ther. 2003; 306(3): 91424.
22. Medleau L, Clekis T, McArthur TR, Alva R, Barrick RA, Jeannin P,
et al. Evaluation of fipronil spot-on in the treatment of flea allergic
dermatitis in dogs. J Small Anim Pract. 2003; 44(2): 71-5.
23. Medleau L, Hnilica KA, Lower K, Alva R, Clekis T, Case J, et al.
Effect of topical application of fipronil in cats with flea allergic
dermatitis. J Am Vet Med Assoc. 2002; 221(2): 254-7.
24. Cadiergues MC, Caubet C, Franc M. Comparison of the activity
of selamectin, imidacloprid and fipronil for the treatment of
dogs infested experimentally with Ctenocephalides canis and
Ctenocephalides felis felis. Vet Rec. 2001; 149(23): 704-6.
25. Schuele G, Barnett S, Bapst B, Cavaliero T, Luempert L, Strehlau
G, et al. The effect of water and shampooing on the efficacy
of a pyriprole 12.5% topical solution against brown dog tick
(Rhipicephalus sanguineus) and cat flea (Ctenocephalides felis)
infestations on dogs. Vet Parasitol. 2008; 151(2-4): 300-11.
26. Zakson-Aiken M, Gregory LM, Meinke PT, Shoop WL. Systemic
activity of the avermectins against the cat flea (Siphonaptera:
Pulicidae). J Med Entomol. 2001; 38(4): 576-80.
27. Dupuy J, Derlon AL, Sutra JF, Cadiergues MC, Franc M, Alvinerie M.
Pharmacokinetics of selamectin in dogs after topical application.
Vet Res Commun. 2004; 28(5): 407-13.
28. Ritzhaupt LK, Rowan TG, Jones RL, Cracknell VC, Murphy MG,
Shanks DJ. Evaluation of the comparative efficacy of selamectin
against flea (Ctenocephalides felis felis) infestations on dogs and
cats in simulated home environments. Vet Parasitol. 2002; 106(2):
165-75.
29. Shanks DJ, Rowan TG, Jones RL, Watson P, Murphy MG, Smith
DG, et al. Efficacy of selamectin in the treatment and prevention
of flea (Ctenocephalides felis felis) infestations on dogs and cats
housed in simulated home environments. Vet Parasitol. 2000;
91(3-4): 213-22.
Conclusion
Despite the availability of safe, effective products, treating FAD
remains a challenge. This challenge should be more readily
overcome once both practitioner and owner(s) are entirely
convinced of the diagnosis. Appropriate knowledge of the
flea life cycle and flea-related biology, an understanding of
the mode of action of flea control products, and motivation
are all required. An integrated approach to treatment should
be adopted, involving all the players in the flea life cycle - the
FAD patient, all in-contact pets, and the environment. Each
case must be customised, with effective flea control products
used in combination with cleaning measures such as steaming,
vacuuming and regular grooming.
References
1.
Rust MK. Advances in the control of Ctenocephalides felis (cat
flea) on cats and dogs. Trends Parasitol. 2005; 21(5): 232-6.
2. Hsu MH, Wu WJ. Off-host observations of mating and postmating
behaviors in the cat flea (Siphonaptera: Pulicidae). J Med Entomol.
2001; 38(3): 352-60.
3. Cadiergues MC, Hourcq P, Cantaloube B, Franc M. First bloodmeal
of Ctenocephalides felis felis (Siphonaptera: Pulicidae) on cats:
time to initiation and duration of feeding. J Med Entomol. 2000;
37(4): 634-6.
4. Cadiergues MC, Santamarta D, Mallet X, Franc M. First blood
meal of Ctenocephalides canis (Siphonaptera: Pulicidae) on dogs:
time to initiation of feeding and duration. J Parasitol. 2001; 87(1):
214-5.
5. Cadiergues MC, Roques M, Franc M. Survival performances of the
dog flea, Ctenocephalides canis and the cat flea, Ctenocephalides
felis felis : a comparative study. In: ESVD-ECVD-GEDAC, editor.
18th ESVD-ECVD Annual Congress; 2002 September 26-28,
2002; Nice (France); 2002. p. 216.
6. Robinson WH. Distribution of cat flea larvae in the carpeted
household environment. Vet dermatol. 1995; 6(3): 145-150.
7. Hsu MH, Hsu YC, Wu WJ. Consumption of flea faeces and eggs
by larvae of the cat flea, Ctenocephalides felis. Med Vet Entomol.
2002; 16(4): 445-7.
8. Marchiondo AA, Holdsworth PA, Green P, Blagburn BL, Jacobs
DE. World Association for the Advancement of Veterinary
Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of
parasiticides for the treatment, prevention and control of flea and
tick infestation on dogs and cats. Vet Parasitol. 2007; 145(3-4):
332-44.
9. Dryden MW, Denenberg TM, Bunch S. Control of fleas on naturally
infested dogs and cats and in private residences with topical spot
applications of fipronil or imidacloprid. Vet Parasitol. 2000; 93(1):
69-75.
10. Ritzhaupt LK, Rowan TG, Jones RL. Evaluation of efficacy of
selamectin, fipronil, and imidacloprid against Ctenocephalides
felis in dogs. J Am Vet Med Assoc. 2000; 217(11): 1669-71.
11. Schenker R, Tinembart O, Humbert-Droz E, Cavaliero T,
Yerly B. Comparative speed of kill between nitenpyram,
fipronil, imidacloprid, selamectin and cythioate against adult
Ctenocephalides felis (Bouche) on cats and dogs. Vet Parasitol.
2003; 112(3): 249-54.
12. Mehlhorn H, Hansen O, Mencke N. Comparative study on the
effects of three insecticides (fipronil, imidacloprid, selamectin)
on developmental stages of the cat flea (Ctenocephalides felis
Bouche 1835): a light and electron microscopic analysis of in vivo
and in vitro experiments. Parasitol Res. 2001; 87(3): 198-207.
266
Flea control in flea allergic dogs and cats - Marie-Christine Cadiergues
30. Benchaoui HA, Clemence RG, Clements PJ, Jones RL, Watson P,
Shanks DJ, et al. Efficacy and safety of selamectin against fleas
on dogs and cats presented as veterinary patients in Europe. Vet
Parasitol. 2000; 91(3-4): 223-32.
31. McTier TL, Jones RL, Holbert MS, Murphy MG, Watson P, Sun
F, et al. Efficacy of selamectin against adult flea infestations
(Ctenocephalides felis felis and Ctenocephalides canis) on dogs
and cats. Vet Parasitol. 2000; 91(3-4): 187-99.
32. McTier TL, Shanks DJ, Jernigan AD, Rowan TG, Jones RL, Murphy
MG, et al. Evaluation of the effects of selamectin against adult
and immature stages of fleas (Ctenocephalides felis felis) on dogs
and cats. Vet Parasitol. 2000; 91(3-4): 201-12.
33. Dickin SK, McTier TL, Murphy MG, Bond R, Mason IS, PayneJohnson M, et al. Efficacy of selamectin in the treatment and
control of clinical signs of flea allergy dermatitis in dogs and cats
experimentally infested with fleas. J Am Vet Med Assoc. 2003;
223(5): 639-44.
34. Prelaud P, Calmon J, Delmas H, Deveze M, Guillaume P,
MLaumonier M. Double blind comparative study of the efficacy
of selamectin and fipronil in the treatment of canine flea allergy
dermatitis: a multiple field trial. Rev. Med. Vet. 2003; 154(11):
689-694.
35. Endris RG, Hair JA, Katz TL, Zobre E, Pennington RG, Meyer JA.
Efficacy of three dose volumes of topically applied 65% permethrin
against Ctenocephalides felis and Rhipicephalus sanguineus on
dogs weighing 30 kg or more. Vet Ther. 2002; 3(4): 435-40.
36. Endris RG, Hair JA, Anderson G, Rose WB, Disch D, Meyer
JA. Efficacy of two 65% permethrin spot-on formulations
against induced infestations of Ctenocephalides felis (Insecta:
Siphonaptera) and Amblyomma americanum (Acari: Ixodidae) on
beagles. Vet Ther. 2003; 4(1): 47-55.
37. Endris RG, Everett R, Cunningham J, Katz TL, Thompson K.
Efficacy of two 65 % permethrin spot-on formulations against
canine infestations of Ctenocephalides felis and Rhipicephalus
sanguineus. Vet Ther. 2002; 3(3): 326-33.
38. Rugg D, Hair JA, Everett RE, Cunningham JR, Carter L. Confirmation
of the efficacy of a novel formulation of metaflumizone plus
amitraz for the treatment and control of fleas and ticks on dogs.
Vet Parasitol. 2007; 150(3): 209-18.
39. Holzmer S, Hair JA, Dryden MW, Young DR, Carter L. Efficacy
of a novel formulation of metaflumizone for the control of fleas
(Ctenocephalides felis) on cats. Vet Parasitol. 2007; 150(3): 21924.
40. Franc M, Beugnet F. A comparative evaluation of the speed of kill
and duration of efficacy against weekly infestations with fleas on
cats treated with fipronil-(S)-methoprene or metaflumizone. Vet
Ther. 2008; 9(2): 102-10.
41. Hellmann K, Adler K, Parker L, Pfister K, Delay RL, Rugg D.
Evaluation of the efficacy and safety of a novel formulation of
metaflumizone plus amitraz in dogs naturally infested with fleas
and ticks in Europe. Vet Parasitol. 2007; 150(3): 239-45.
42. Robertson-Plouch C, Baker KA, Hozak RR, Zimmermann AG, Parks
SC, Herr C, et al. Clinical field study of the safety and efficacy of
spinosad chewable tablets for controlling fleas on dogs. Vet Ther.
2008; 9(1): 26-36.
43. Snyder DE, Cruthers LR, Slone RL. Preliminary study on the
acaricidal efficacy of spinosad administered orally to dogs infested
with the brown dog tick, Rhipicephalus sanguineus (Latreille,
1806) (Acari: Ixodidae). Vet Parasitol. 2009.
44. Franc M, Bouhsira E. Evaluation of speed and duration of efficacy
of spinosad tablets for treatment and control of Ctenocephalides
canis (Siphonaptera: Pulicidae) infestations in dogs. Parasite.
2009; 16(2): 125-8.
45. Young DR, Jeannin PC, Boeckh A. Efficacy of fipronil/(S)methoprene combination spot-on for dogs against shed eggs,
emerging and existing adult cat fleas (Ctenocephalides felis,
Bouche). Vet Parasitol. 2004; 125(3-4): 397-407.
46. Stanneck D, Larsen KS, Mencke N. Pyriproxyfen concentration in
the coat of cats and dogs after topical treatment with a 1.0% w/v
spot-on formulation. J Vet Pharmacol Ther. 2003; 26(3): 233-5.
47. Dean SR, Meola RW, Meola SM, Sittertz-Bhatkar H, Schenker
R. Mode of action of lufenuron in adult Ctenocephalides felis
(Siphonaptera: Pulicidae). J Med Entomol. 1999; 36(4): 486-92.
48. Dryden MW, Perez HR, Ulitchny DM. Control of fleas on pets
and in homes by use of imidacloprid or lufenuron and a pyrethrin
spray. J Am Vet Med Assoc. 1999; 215(1): 36-9.
49. Jacobs DE, Hutchinson MJ, Fox MT, Krieger KJ. Comparison of
flea control strategies using imidacloprid or lufenuron on cats in
a controlled simulated home environment. Am J Vet Res. 1997;
58(11): 1260-2.
50. Franc M, Cadiergues MC. Use of injectable lufenuron for
treatment of infestations of Ctenocephalides felis in cats. Am J
Vet Res. 1997; 58(2): 140-2.
267
DERMATOLOGY
How to treat atopic dermatitis
in dogs
D. N. Carlotti(1)
SUMMARY
This paper summarizes all the aspects of the therapy of canine atopic dermatitis, particularly on a long-term basis.
The principles of threshold phenomenon and summation of effects are underlined. Treatment of the disease includes
first the treatment of dermatoses which are related or secondary to atopic dermatitis: microbial infection (bacteria
and Malassezia), flea allergy dermatitis, food reactions, keratoseborrhoeic skin disease, otitis externa and pyotraumatic
dermatitis. Specific therapy is then envisaged: it includes allergen eviction and allergen-specific immunotherapy
which is a major approach for the long-term management of the disease. Finally, symptomatic therapy with various
drugs, including glucocorticoids, various topicals and ciclosporin, is detailed. A “combination therapy” is needed and
should be tailored for each case.
infestation or a mild pyoderma may produce marked discomfort
while either condition on its own might be asymptomatic (PJ
Ihrke – dermatology course – School of veterinary medicine, UC
Davis, 1982).
This paper was commissioned by FECAVA for
publication in EJCAP.
Introduction
Treatment of dermatoses which are
related or secondary to atopic dermatitis
Canine Atopic Dermatitis is a very common disease. Management
of this disease, both on a long term basis and during acute flares
has led to multiple studies published in the veterinary literature.
This review encompasses all the therapeutic aspects of the
management of CAD.
1 - Treatment of microbial infections: An adequate
antibacterial treatment regimen of secondary pyoderma,
based upon systemic antibiotics and appropriate antibacterial
topicals, may return the animal to a quasi-normal state. Such a
case of CAD will only be treated specifically in case of regular
reoccurrence of pyoderma and/or if the clinical signs of CAD
itself become a concern. Also, some atopic dogs will respond to
a well carried out antibiotic treatment, even without visible signs
of secondary pyoderma [1]. A true bacterial overgrowth (BOG)
syndrome is plausible in such cases and the author treats with
antibiotics patients showing an abundant coccoid surface flora
after cytological tests, as an empiric therapeutic test [2].
Threshold phenomenon and
summation of effects
Two important principles must be remembered in the frame of
CAD therapy.
1 - Threshold phenomenon: A certain allergic load may be
tolerated by an individual without any disease manifestations,
but a small increase in that load may push the individual over
the threshold and initiate clinical signs (PJ Ihrke – dermatology
course – School of veterinary medicine, UC Davis, 1982).
The same reasoning is undoubtedly applicable as well to cases
of Malassezia dermatitis. Systemic (ketoconazole) and topical
therapy are required with a careful follow-up (Figures 1 and 2)
[3].
2 – Summation of effects: Concomitant diseases fostering
pruritus may raise an animal above its pruritic threshold.
Therefore, all factors contributing to pruritus must be
investigated: i.e., a subclinical allergy in combination with a flea
2 - Treatment of Flea Allergy dermatitis (FAD): A well
conducted flea control regimen can eliminate the FAD and
therefore, in certain cases can enable the animal to fall under
1) Didier Noel Carlotti, Dip ECVD, Ospedale Veterinario Cuneese, Via Vocaturo 13, 12016 Peveragno (CN), Italy
268
EJCAP - Vol. 19 - Issue 3 December 2009
Fig. 1 Malassezia dermatitis on the face of an atopic Labrador
retriever.
Fig. 2 Same dog as illustrated in figure 1, twenty days after
initiation of antifungal therapy.
its pruritic threshold (Figures 3 and 4) [4]. In such a case, atopic
dermatitis treatment is not necessary if the clinical signs are not
obvious. If this not the case, the atopic dermatitis should be
treated while maintaining absolute antiparasitic treatment.
5 - Treatment of otitis externa: Otitis externa is a major
feature of canine atopic dermatitis which causes inflammation
of the external ear canal and ear pinnae. Secondary infections
occur (bacterial and fungal) and perpetuating factors such as
hyperplasia of epidermis and both sebaceous and apocrine glands
lead to chronicity. It is typically erythemato-ceruminous at the
beginning of the disease and it becomes eventually suppurative.
The associated lesions of the ear pinnae (lichenification,
alopecia, crusting) require therapy. Ear cleansing must be
repeated regularly (eg twice or three times a week). Numerous
commercial otic preparations are available which are usually
easy to use and effective. They contain active substances such as
antibiotic, antifungal and corticosteroid agents. Selection must
be made after performing a smear and bacterial culture and
sensitivity testing if the smear shows rods and/or if the otitis is
suppurative. Corticosteroids included in otic preparations reduce
pruritus, pain and proliferative reactions. They also decrease
cerumen secretion. Systemic antibiotic therapy can be useful
in otitis externa due to CAD, particularly if it is suppurative,
because of associated otitis media which has to be diagnosed by
imaging. Surgical therapy can be avoided in many circumstances
with appropriate medical therapy. Surgical failure is often due to
failure to recognise and control CAD [8].
3 - Management of food reactions: Food intolerance may
resemble CAD or may trigger flares of atopic dermatitis [5],
which leads to the concept of food-induced atopic dermatitis,
in comparison to CAD sensu stricto. An elimination diet should
be performed in all cases of CAD and followed by sequential
reintroductions in case of good response. If an offending food
is identified, this should be definitely withdrawn from the
patient’s diet, which is easy to perform. A concomitant CAD
sensu stricto should be treated specifically only if clinical signs
can be attributed to it [6].
4 - Treatment of keratoseborrhoeic skin disease: A
keratoseborrhoeic disorder can occur in CAD particularly in
ancient cases. Treatment is mainly topical although systemic
Essential Fatty Acids, used in the treatment of CAD may have an
effect on seborrhoea. Shampoos and moisturizing agents are
valuable supporting therapy in keratoseborrhoeic skin disorders
[7].
Fig. 3 Flea allergy dermatitis in an atopic German shepherd.
Fig. 4 Same dog as illustrated in figure 3, three months after
initiation of flea-control.
269
How to treat atopic dermatitis in dogs - D. N. Carlotti
6 – Treatment of pyotraumatic dermatitis: Lesions of
pyotraumatic dermatitis are common in CAD. They are poorly
understood. They should be differentiated from pyotraumatic
folliculitis. Although there may be a spontaneous healing in a
few days, treatment is beneficial. Clipping and cleansing with
antiseptic shampoos can be followed by the application of
creams containing antibiotics and corticosteroids. If pruritus or
above all pain are important, a short systemic glucocorticoid
treatment is useful [9].
and grasses) or not (particularly house dust mites and above all
Dermatophagoides farinae, but also storage mites, moulds and
danders).
Test results are to be interpreted in an anamnesis and clinical
light in each of the cases. A (good) test means ONLY that the
animal has developped specific IgE towards allergens. It does
not mean that the clinical signs are linked to this sensitization.
Indeed the clinical signs must be compatible with Flea Allergy
Dermatitis and/or Atopic Dermatitis to take in account positive
tests. In addition, in case of positive reactions, allergens should
be included in an immunotherapy protocol only if they are
present in the environment (however cat dander can in fact be
transported through the air or by people [17]).
Specific treatment
1 – Allergenic eviction: Allergenic eviction is “theoretically”
the ideal treatment for all cases of allergic dermatitis in enabling
the animal to fall beneath its pruritic/allergic threshold. Pollens
cannot be avoided but it is possible to eliminate environmental
feathers and fabrics, and moulds can be destroyed by antiseptic
or antifungal sprays or even anti-mould paint. However, the role
of these allergens in dogs’ atopic dermatitis is minimal in Europe
[10] and moreover feathers and fabrics are mostly sources of
house dust mite allergen [11].
No standardisation exists for the ASIT methods used. Only
aqueous extracts are used in North America, whereas in Europe,
mainly alum precipitated extracts are available [13]. It seems
that the combination of moulds and pollen extracts alters their
quality (due to the presence of protease in the mould extracts)
and that different types of vials are necessary [18].
Various methods exist to destroy house dust mites and these
may be tried around atopic dogs such as the use of acaricide
sprays and foggers (some of which contain an Insect Growth
Regulator [IGR] and a denaturing agent such as tannic acid
which is very efficient for both mites’ faeces and fungal spores).
The elimination of house dust mites has been shown to be
effective in human atopic dermatitis but only one study has
been published in canine dermatology, showing good efficacy
[12].
Fig. 5 Erythema,
excoriations
and crusts in
an atopic Fox
Terrier.
2 – Allergen Specific Immunotherapy (ASIT): ASIT
(hyposensitisation, desensitisation) has been used in humans for
a century, to treat asthma, allergic rhinitis and hypersensitivity
to hymenoptera bites but not treat allergic skin disease. It
started in dogs in the 1940s, and become commonly used in
North America in the 1960s and in Europe in the 1980s. The
first explanation for desensitisation efficacy in man was in
the production of blocking antibodies (lgG), which combine
with allergens before they combine with the IgE. Today, many
mechanisms are proposed [13,14]. In particular, acting on Th2Th1 substitution will lead to a reduction in the IL4 production
and an increase in the INF-gamma production [15]. The IL4
offers potential for the IgE synthesis, increases the number of
weak affinity IgE receptors or their CD23 soluble form. The INFgamma inhibits IgE synthesis. Late phase reaction inhibition
in desensitized subjects is accompanied by the apparition of
T-lymphocytes with a Th1 profile. Finally, desensitization may be
accompanied by a cellular and tissue hyposensitisation. These
mechanisms can sequentially intervene and differ between the
induction and maintenance phases. Recently, the role of blocking
antibodies has been emphasized again in the dog [16].
Fig. 6 Close-up of the face of the dog illustrated in figure 5.
The choice of allergens mainly depends on the in vivo (skin-tests)
or in vitro (ELISA = Enzyme-Linked Immuno-Sorbent Assay)
test results. Allergy testing, including selection of allergens
for testing, is discussed in many dermatology manuals. The
allergens that are used are seasonal (pollens of trees, weeds
270
EJCAP - Vol. 19 - Issue 3 December 2009
The results of ASIT are more or less difficult to evaluate in
dogs. In fact, they depend on the animals (age and especially
diagnostic criteria), evaluation criteria (telephone follow-up,
clinical score), follow-up duration, and recognition or not of
“loss of follow-up” as setbacks. Presently, it is considered that
50 to 100 % of animals respond to immunotherapy in open
studies (Figures 5,6,7,8,9,10) [13,14]. T. Willemse demonstrated
in 1984 the method’s efficacy through a double blind placebo
controlled study [19]. The 9-month evaluation seems important:
it is usual that improvement at this stage is followed by success.
The result variation factors include (apart from the diagnostic
method and the clinical criteria of each one), allergens nature
(controversial), number of allergens (controversial), breed and
sex (controversial), age (probably no influence) and appropriate
patients’ follow-up (indispensable) [13,14]. Also, specifity of
ASIT has been confirmed, including recently [20]. As far as
the allergen identification method is concerned, it is of course
impossible to confirm for all in vitro tests the same success rates
in immunotherapy as the one obtained after skin-tests (i.e. 60 to
100 % of improvement) but it is likely that the best in vitro tests
will give a high percentage of good results, comparable to skin
testing. In addition, it is also felt that some dogs with negative
skin tests or poor results to immunotherapy based on skin tests
may respond well to immunotherapy based on in vitro testing. It
is also possible that the combination of in vivo and in vitro tests
increase success rates.
Fig. 7 Close-up of an ear pinna of the dog illustrated in figure 5.
The use of highly purified allergens (Der f 15 and Der f 18?)
could improve results. No study has yet proven that the use of
corticosteroids or ciclosporin during desensitisation would have
a very harmful effect on its efficacy.
Fig. 8 Same dog as illustrated in figure 5, six months after
initiation of allergen-specific immunotherapy.
Rare cases of secondary effects have been mentioned in
an anecdotal manner (urticaria, angioedema, anaphylaxis).
An exacerbation of clinical signs’ is often noticed in the
hours following injections. Limited local reactions which are
spontaneously reversible often appear with alum precipitated
extracts. A majority of veterinary dermatologists believe that
the efficacy and absence of secondary effects justifies ad vitam
eternam hyposensitization. They empirically remarked that the
clinical signs reappear in a period of months to years after the
treatment has been stopped.
Fig. 9 Close-up of the face of the dog illustrated in figure 6, six
months after initiation of allergen-specific immunotherapy.
Fig. 10 Close-up of the ear pinna of the dog illustrated in figure 7,
six months after initiation of allergen-specific immunotherapy.
271
How to treat atopic dermatitis in dogs - D. N. Carlotti
Rush immunotherapy could be effective but secondary effects
occur in a fourth of the cases [21]. The use of immunostimulatory
liposome-nucleic acid complexes could be interesting [22].
Recently a monodose ASIT technique has been proposed in a
preliminary study, in association with a long-term therapy with
cetirizine [23].
hepatomegaly, inhibition of the hypothalamo-hypophysoadrenal axis, dryness of the skin and the haircoat and even
iatrogenic Cushing’s syndrome with alopecia. Secondary
infections (pyoderma, demodicosis, dermatophytosis) can occur.
The following rules must be respected regarding their long term
side effects: glucocorticoids should be used as little as possible,
at the lowest possible dose, preferably every other day and only
if alternative anti-pruritic medications are not effective enough.
Symptomatic treatment
This is useful at the beginning of immunotherapy (within the
first year in successful cases) or on a long-term basis in failed
cases (total or partial), or even in cases where immunotherapy is
not required (aged animal, owner’s hesitation or even, clinically
slightly worrying cases apart from a few signs). Symptomatic
therapy is also indicated for canine atopic-like dermatitis. Major
reviews on evidence-based pharmacotherapy of CAD, including
a recent “Cochrane” systematic review of randomized controlled
trials, have been made and include most of the following data
[24,25].
2 - Non steroidal topicals
Various non steroidal topicals can be used. Non steroidal
antipruritic sprays or rinses, e.g. containing colloidal oatmeal
or aloe vera can be useful. A spray containing Hamamelis
extract and menthol has become popular to treat localized
lesions and has been shown to kill Malassezia [27]. Two microemulsion lotions/sprays have been developed to complement
shampoos specifically designed for canine atopic dermatitis (see
below). One contains mono and oligosaccharides (free and in
Spherulites®), vitamin E and linoleic acid, the other (available
also in concentrate) contains phytosphingosine (see below),
hinokitiol (= β-thujaplicin, antimicrobial and anti-inflammatory)
and essential fatty acids from raspberry seed oil. Tacrolimus, a
calcineurin inhibitor with immunomodulatory properties has
been shown to be effective in the treatment of localized lesions
of canine atopic dermatitis.
1 - Glucocorticoids
Glucocorticoids are the most effective medications to treat
allergic dermatitis. They have anti-inflammatory and antipruritic
properties as well as antiproliferative and immunosuppressive
effects. They act at almost all inflammation and immunologic
response stages. Their activity, however, varies tremendously.
There is no consistency in the individual response not only
in relation to the glucorticoid used but also for the same
glucocorticoid. The effect is reduced over time, and the doses
required are increased. They are used topically or systemically.
Topical glucocorticoid ointments, creams and gels are useful
for localised lesions (e. g. cheilitis, blepharitis, pododermatitis,
nasal lesions, excoriations and pyotraumatic dermatitis). Many
molecules are available in human dermatology, classified from
class I (the least potent) to class IV (the most potent). Some
potent human formulations can be used in the dog (e.g.
clobetasol propionate). Most of the traditional veterinary
formulations are in fact combined with antimicrobials and
contain less potent agents. However, their overuse can lead to
tachyphylaxis, atrophy and microbial infections.
All shampoos are likely to remove allergens from the skin, and
this is probably helpful in CAD. They also help to rehydrate
dry skin (xerosis) particularly when associated to humectant
sprays. Shampoos containing fatty acids can help in allergic
skin disorders. Shampoos with an antipruritic effect (colloidal
oatmeal) can be good adjunctive treatments. A micro-emulsion
shampoo specifically designed for canine atopic dermatitis
contains linoleic acid and gamma linolenic acid, mono and
oligosaccharides, vitamin E, and piroctone olamine and has
been shown to be effective on pruritus [28]. In fact, exogenous
monosaccharides downregulate the inflammatory response to
allergen challenge. This is why they are used in topical products
for atopic/reactive skin patients in humans and are beneficial in
animal with allergic skin disease. Another shampoo containing
phytosphingosine, hinokitiol and raspberry seed oil in an
hydrating formulation has also been shown to be beneficial in
atopic dermatitis, in association with the corresponding spray
(see above), in a comparative study with the previous one [29].
Glucocorticoids are also available in lotions, rinses, sprays and
even shampoos in the USA. Small spray containers are used
to treat localized lesions, as creams and ointments. Several
glucocorticoids are available, usually not the most potent. A
new class of glucocorticoids, the diesters, is used in human
dermatology. Diesters are lipophilic compounds that quickly
penetrate the stratum corneum and are stored and metabolised
within the skin after topical application (with reduced systemic
secondary effects). They have consequently a high therapeutic
index. One of them, hydrocortisone aceponate, is now available
as a medium-sized spray as a veterinary product for dogs and has
been shown to be effective in the management of CAD [26].
3 - Antihistamines
AntiH1 antihistamines, which block H1 receptors, may be useful
(whereas antiH2 are inefficient). They are not effective in human
atopic dermatitis. Many studies have been performed in dogs
but there is insufficient evidence to conclude for or against the
efficacy of antihistamines for treatment of CAD (15 to 25 %
good results, close to a placebo effect) [30].
In an evidence-based review [31], the following agents were
considered as having:
– no or low efficacy: chlorpheniramine, pheniramine,
diphenhydramine, hydroxyzine, promethazine, trimeprazine
(first generation), astemizole and loratadine (second
generation)
Systemic glucocorticoid therapy should be limited to the
administration of prednisolone or methyl-prednisolone by
oral route (0.5 to 1 mg/kg/day during 5 to 7 days followed
by 1 mg/kg every other day, as shortly as possible). They have
significant side effects including polyuria-polydipsia, polyphagia,
272
EJCAP - Vol. 19 - Issue 3 December 2009
– conflicting evidence of efficacy: terfenadine (second
generation)
– medium efficacy: clemastine, chlorpheniramine-hydroxyzine
combination (first generation), oxatomide (second
generation).
and there is no supplement or diet that is appropriate to all.
Several tests can be made as for antihistamines. A dietary
approach, based on a high quantity of omega-3 and the ratio
omega-3/omega-6 may also be helpful. A sub-population of
non-responsive atopic dogs is likely.
Perhaps the dosage of clemastine should be increased in the
dog. More recently, cetirizine has been shown to be ineffective
and topical diphenhydramine has been shown to be relatively
effective. Moreover, some frequently used products such as
ketotifene or rupatidine have not been evaluated at all.
There are still doubts, so, on the real efficacy of EFA in CAD
especially since several elements have not yet been made clear:
the dosage (varying from 2 to 10 times the recommended
doses), minimal duration of the therapeutic test to predict
efficacy (1 to 12 weeks), optimal ratio between omega-3 and
omega-6 (between 5 and 10), the function of co-factors, criteria
to select responder dogs, responder breeds, synergy with other
anti-inflammatory agents. They are to be principally used with
other anti-pruritic treatments. They have few side effects.
The relatively low success rates of these antiH1 justify successive
tests during at least one week at a time, until a satisfactory
result is obtained.
Trimeprazine, which alone is inefficient, has proven to be able to
clearly reduce the need for prednisone. There is a synergic effect
between the essential fatty acids and antihistamines.
5 - Ciclosporin
Ciclosporin, an orally administered calcineurin inhibitor, is an
effective drug for the treatment of CAD, as shown in four
controlled studies including two placebo controlled doubleblind studies and two showing a similar effect as prednisolone
and methylprednisolone [32].
4 - Essential Fatty Acids
Many clinical studies have been done in dogs on the use of
Essential fatty acids (EFA) for the treatment of CAD, although
there are not used in human atopic dermatitis. They are
polyunsaturated, administered by oral route, particularly
omega-3 series eicosapentanoic acid (EPA) and omega-6 series
gamma linolenic acid (GLA). These fatty acids compete with
the arachidonic acid in the cascade of eicosanoids synthesis
where leukotrienes and prostaglandins are formed having an
anti-inflammatory activity or at least a pro-inflammatory activity
which is much less significant than that observed with the
metabolites emitted from arachidonic acid. Oral fatty acids could
also reinforce the defective cutaneous barrier of atopic dogs.
In another study relapses were more common during 2 months
in dogs treated with methylprednisolone than in dogs treated
with ciclosporin and lesions were less severe in the latter (pruritus
was identical). After 4 weeks of daily administration it is possible
to administer the drug only every other day in 39 % of the cases
and after 12 weeks every other day or twice a week in 22 % and
36 % of the cases respectively. In a recent study therapy was
discontinued in 6 to 24 months in 45 % of the cases because of
failures (22 %) or success (24 %) without relapses over a period
of 3 to 22 months. So a long-term treatment (several months) is
justified and then the treatment is stopped.
The omega-6/omega-3 ratio could be important according to an
in vitro study and should be 5 to 10. Recent in vitro studies show
that addition of omega-3 and GLA decrease the production of
mediators of inflammation by mast cells.
This molecule has become, despite its high cost, a very effective
symptomatic treatment of CAD, particularly in severe forms
(Figures 11 and 12). Its efficacy is dose-dependent but the assay
of its blood level has no value since it cannot predict the clinical
response. Secondary effects are limited and are mainly gastrointestinal, with more rarely gingival hyperplasia, verrucous lesions
or hypertrichosis. The long-term secondary effects known in
man (renal insufficiency, hypertension) have not been reported
in dogs. Last but not least ciclosporin does not enhance the risk
of secondary infections.
Doses are variable and empirical in the clinical studies. Amongst
them there are only eight double blind placebo controlled
studies, including three in cross-over. Perhaps high doses could
be necessary to get a result but studies using high doses of
omega-6 or omega-3 give variable results, with duration of
treatment from 6 to 16 weeks. Supplementation in EFA does
not take in account the intake from the diet in these studies,
that can be important and only the three cross-over studies
overcome this drawback of variability of dietary EFA intake but
their results are variable.
6 - Other non steroidal systemic anti-inflammatory/
antipruritic agents
– Anti-depressor and psychotropic drugs: Fluoxetine, an antidepressive agent which inhibits serotonin uptake, doxepin
and amitriptyline, tricyclic anti-depressive agents with a
antiH1 activity, appear to be moderately efficient giving
good results comparable to the “best” antihistamines (20 to
30 %). Dextromethorphan has no effect.
– Leukotriene inhibitors have been tried in a few clinical trials.
Zileuton and Zafirlukast were not very effective in placebo
controlled studies but tepolaxin showed a certain efficacy in
milder cases of CAD.
– Misoprostol, a prostaglandin E analog, has shown a moderate
More recently, clinical studies have been performed with
specific diets or with supplements added to standard diets
that show the beneficial effect of omega-3 with or without
GLA. A glucocorticoid sparing effect has also been shown.
The mechanism of action remains obscure since there is no
correlation between the EFA concentrations in the skin and
plasma and the clinical improvement.
In summary, the reaction of atopic dogs to fatty acids varies
273
How to treat atopic dermatitis in dogs - D. N. Carlotti
Fig. 11 Alopecia, lichenification and hyperpigmentation in a
severely affected atopic German shepherd.
Fig. 12 Same dog as illustrated in figure 11, six months after
initiation of control of microbial overgrowths, antiseborrhoeic
topical therapy and ciclosporin therapy.
effect, including in a randomized controlled study.
– Phosphodiesterase inhibitors have shown a moderate
efficacy in comparative (arophylline) or double blind placebo
controlled cross-over (pentoxyfilline) studies. Arophylline is
poorly tolerated. Papaverin is ineffective.
– Interferons: recombinant canine gamma interferon injections
showed a good-to-excellent efficacy to control skin lesions
or pruritus in about 80% of dogs with CAD and in a recent
study, we showed a good efficacy of a recombinant omega
interferon (rfeIFN-ω), comparable to ciclosporin [33].
– Various agents: an injectable formulation of fatty acid
copolymers, a phytotherapy preparation of Chinese herbs,
MS-antigen (a peptide extracted from urine of allergic
humans), aminopterine (an antifolate), have given interesting
results.
References
[1] Mueller RS, Bettenay SV (1996) Long-term Immunotherapy of 146
Dogs with Atopic Dermatitis - a Retrospective Study. Aust. Vet.
Practit., 26, 128-132.
[2] Pin D, Carlotti DN, Jasmin P, DeBoer DJ, Prélaud P (2006) Prospective
study of bacterial overgrowth syndrome in eight dogs. Vet.
Record., 158, 437-441.
[3] Guillot J, Bond R (1999) Malassezia pachydermatis: a review. Med.
Mycol., 37, 295-306.
[4] Carlotti DN, Jacobs DE (2000) Therapy, control and prevention of
flea allergy dermatitis in dogs and cats. Vet. Dermatol., 11, 8398.
[5] Olivry T et al (2007) Food for thought: pondering the relationship
between canine atopic dermatitis and cutaneous adverse reaction.
Vet. Dermatol., 18, 390-391.
[6] Chesney CJ (2001) Systematic review of evidence for the
prevalence of food sensitivity in dogs. Vet. Rec., 148, 445-448.
[7] Carlotti D.N., Bensignor E. Management of keratoseborrhoeic
disorders. Eur Journal Comp Anim Pract, 2002; 12: 123-133.
[8] Harvey RG, Harari J, Delauche AJ (2001) Ear diseases of the dog
and cat, London, Manson Publishing Ltd.
[9] Holm BR, Rest JR, Seewald W (2004) A prospective study of the
clinical findings, treatment and histopathology of 44 cases of
pyotraumatic dermatitis. Vet. Dermatol., 15, 369-376.
[10] Carlotti DN, Costargent F (1994) Analysis of positive skin-tests in
449 dogs with allergic dermatitis. Eur Journal Comp Anim Pract,
4, 52-59.
[11] Prelaud P, olivry T (1998) Etiopathogénie de la dermatite atopique
canine. Prat. Méd. Chir. Anim. Comp., 33 (numéro spécial), 315329.
[12] Swinnen C, Vroom M (2004) The clinical effect of environmental
control of house dust mites in 60 fouse dust mite-sensitive dogs.
Vet. Dermatol., 15, 31-36.
[13] Griffin CE, Hillier A (2001) The ACVD task force on canine atopic
dermatitis (XXIV): allergen-specific immunotherapy. Vet. Immunol.
Immunopathol., 81, 363-383.
[14] Loewenstein C, Mueller RS (2009) A review of allergen-specific
immunotherapy in human and veterinary medicine. Vet. Dermatol.,
20, 84-98.
Other treatments were considered as ineffective: erythromycin,
doxycycline, tetracycline-niacinamide, cyproheptadine, ascorbic
acid, tranilast, an homeopathic preparation, azathioprine and
proanthozone.
Conclusion: Combination therapy case
management
Long-term management of CAD is difficult. Therapy of
dermatoses which are related or secondary is essential. The
hygienic and clinical value of topicals designed for canine
dermatology should be underlined, as in human dermatology.
The treatment, as for all allergic dermatoses, shall act on the
pruritic threshold, by specific immunotherapy and symptomatic
treatments and can also include allergen eviction. It should be
remembered that placebo effect exists in canine medicine and is
around 9 % in pruritus due to CAD (less for lesions). This effect
must be taken in account in clinical studies.
Each case is different and deserves a “combination therapy”,
which associates treatment of complications, eventual allergen
eviction measures, allergen-specific immunotherapy and
symptomatic therapy. It is the key to success.
274
EJCAP - Vol. 19 - Issue 3 December 2009
[31] Olivry T, Mueller RS and the international task force on canine
atopic dermatitis (2003) Evidence-based veterinary dermatology:
a systematic review of the pharmacotherapy of canine atopic
dermatitis. Vet. Dermatol., 14, 121-146.
[32] Steffan J, Favrot C, Mueller R (2006) A systematic review and
meta-analysis of the efficacy and safety of cyclosporine for the
treatment of atopic dermatitis in dogs. Vet. Dermatol., 17, 3-16.
[33] Carlotti DN, Boulet M, Ducret J, Machicote G, Jasmin P, Reme
C, Albouy M (2009) The use of recombinant omega interferon
therapy in canine atopic dermatitis. A double-blind controlled
study. Vet. Dermatol. 20,405-411.
[15] Shida M, Kadoya M, Park SJ, Nishifuji K, Momoi Y, Iwasaki T (2004)
Allergen-specific immunotherapy induces Th1 shift in dogs with
atopic dermatitis. Vet. Immunol. Immunopathol. 102, 19-31.
[16] Hou C, Griffin C, Hill PB (2008) Dermatophagoides farinae-specific
IgG responses in atopic dogs undergoing allergen-specific
immunotherapy with aqueous vaccines. Vet. Dermatol., 19, 215220.
[17] Bollinger ME et al (1996) Cat antigen in homes with and without
cats may induce allergic symptoms. J. Allergy Clin. Immunol., 97,
907-914.
[18] Rosenbaum MR et al (1996) Effects of Mold Proteases on the
Biological Activity of Allergenic Pollen Extracts. Amer. J. Vet. Res.,
57, 1447-1452.
[19] Willemse T, van den Brom WE, Rijnberg A (1984) Effect of
hyposensitization on atopic dermatitis in dogs. J. Am. Vet. Med.
Assn., 184, 1277-1280.
[20] Willemse T, Bardagi M, Carlotti DN, Ferrer L, Fondati A,
Fontaine J, Leistra M, Noli C, Ordeix L, Scarampella F, Schleifer
S, Sinke J, Roosje P (2009) Dermatophagoides farinae–specific
immunotherapy in atopic dogs with hypersensitivity to multiple
allergens: a randomized, double blind, placebo-controlled study.
Vet. J., 180, 337-342.
[21] Mueller RS, Bettenay SV (2001) Evaluation of the safety of an
abbreviated course of injections of allergen extracts (rush
immunotherapy) for the treatment of dogs with atopic dermatitis.
Am. J. Vet. Res., 62, 307-310.
[22] Mueller RS, Veir J, Fieseler KV, DOW SW (2005) Use of
immunostimulatory liposome-nucleic acid complexes in allergenspecific immunotherapy of dogs with refractory atopic dermatitis
- a pilot study. Vet. Dermatol., 16, 61-68.
[23] Cochet-Faivre N, Prelaud P (2007) Monodose allergen-specific
immunotherapy for treatment of canine atopic dermatitis:
preliminary safety study. Vet. Dermatol., 18, 385-386 (abstract).
[24] Olivry T, Mueller RS and the international task force on canine
atopic dermatitis (2003) Evidence-based veterinary dermatology:
a systematic review of the pharmacotherapy of canine atopic
dermatitis. Vet. Dermatol., 14, 121-146.
[25] Olivry T, Foster AP, Mueller RS (2009) Interventions for Atopic
Dermatitis in Dogs: A Systematic Review of Randomized
Controlled Trials. Vet. Dermatol., in press.
[26] Nuttal T, Mueller R, Bensignor E, Verde M, Noli C, Schmidt V, Reme
C (2009) Efficacy of a 0.0584% hydrocortisone aceponate spray
in the lmanagement of canine atopic dermatitis: a randomised,
double blind, placebo-controlled trial. Vet. Dermatol., 20, 191198.
[27] Carlotti DN, Reme CA (2004) Efficacy of a soothing astringent
topical spray for the management of Malassezia pododermatitis
in dogs: a preliminary open-label clinical trial. Proc. BSAVA 47th
Annual Congress, Birmingham, 103.
[28] Löflath A, Von Voigts-Rhetz A, Jaeger K, Schmid M, Kuechenhoff
H, Mueller RS (2007) The efficacy of a commercial shampoo and
whirpooling in the treatment of canine pruritus – a double-blind,
randomized, placebo-controlled study. Vet. Dermatol., 18, 427431.
[29] Bourdeau P, Bruet V, Gremillet C (2007) Evaluation of
phytosphingosine-containing shampoo and microemulsion spray
in the clinical control of allergic dermatoses in dogs: preliminary
results of a multicentre study. Vet. Dermatol., 18, 177-178
(abstract).
[30] Deboer DJ, Griffin CE (2001) The ACVD task force on canine atopic
dermatitis (XXI): antihistamine pharmacotherapy. Vet. Immunol.
Immunopathol, 81, 323-329.
THE LEADING COMPANY IN ALLERGY TESTING
Artuvetrin Serum Test
®
Reliable allergy test
Comprehensive panels
including Malassezia
Easy to interpret results
Full technical support
and advice
Hyposensitisation
vaccine available
within 8 working
days
P.O.Box 612 . 8200 AP Lelystad . The Netherlands
Tel. 0031-320 267 900 . Fax: 0031-320 256 060
E-mail: [email protected]
W W W . A R T U V E T R I N . C O M
275
DERMATOLOGY
How to treat atopy in cats?
E. Vidémont (1), D. Pin(1)
SUMMARY
Therapy of atopic dermatitis (AD) can be a challenge to the clinician’s therapeutic skills and selecting the best treatment
plan for individual situations is an art. Cats diagnosed with AD are treated in a variety of ways depending upon
the severity of clinical signs, duration or owner preference. Treatment options include allergen avoidance, treatment
of aggravating factors, allergen specific immunotherapy (ASIT) and symptomatic therapy of pruritus. This article
presents an update of these different options.
and insect growth hormone regulators, and steam cleaning of
sleeping areas [24].
This paper was commissioned by FECAVA for
publication in EJCAP.
Treatment of aggravating factors and
disease
Introduction
Microbial proliferation
Although bacterial [24] and Malassezia [22] overgrowth are less
common in cats than in dogs, they can be observed in allergic
cats and cause additional pruritus. These complications should
be searched for by taking tape strip impressions and, treated, if
present, with appropriate antimicrobial or antifungal therapy.
Antiseptic shampoos, particularly those containing chlorhexidine,
could help prevent relapse. In cats, shampoos are rarely used
because cats have a reputation (often unjustified) for not liking
being washed. However, shampoos, when it is possible to apply
them easily, form an effective adjunctive therapy. Antiseptic
solutions can now be applied in a spray formulation. Canine
shampoos containing quaternary ammonium compounds and
phenols can be toxic in cats and must be avoided.
AD in cats is not well known and its pathophysiology is unclear.
Some authors consider feline atopy to be similar to the human
and canine form while others have obtained contradictory
findings. There may be particular differences relating to cats
but investigation of these has not been performed. There have
been very few controlled studies in cats. Such studies that have
been carried out must be examined critically partly because they
often involve only small numbers of cats and partly because
of differences in approach to diagnosis. For example, in some
studies, there is confusion between flea bite hypersensitivity and
AD. As in the dog, it is important to consider the hypersensitivity
threshold concept. Each animal has its own pruritic threshold,
the level of stimuli resulting in pruritus. Once this threshold
is reached, additional stimuli will increase pruritus and other
clinical signs. It is therefore important to reduce or eliminate
additional stimuli. Infections must be searched for and treated.
Strict flea control must be maintained.
Dry skin
Dry skin is associated with atopic dermatitis. The functional
integrity of the epidermis relies particularly on intercorneocyte
sheets of lipids. Disorders of epidermal lipid metabolism account
for the defect in barrier function in atopic dog [23]. If we assume
that a similar phenomenon occurs in the cat, several approaches
can be used to restore epidermal barrier function.
Allergen avoidance
In practice, only food allergens can really be avoided. Avoidance
of aeroallergens is only practical if the allergens concerned are in
a limited area from which the allergic cat can be excluded. The
most important allergens for cats in Europe are house dust mites
and although various measures aimed at reducing their number
can be recommended, these are only likely to be effective if
combined with other procedures: very regular ventilation of
the cats’ surroundings, frequent aeration of duvets, mattresses
and blankets, use of a vacuum cleaner fitted with special filters,
treatment of resting areas with a combination of insecticides
• Essential fatty acids (EFA)
The used of EFAs is proposed for several reasons:
- They seem to contribute to the restoration of skin barrier
function [23],
- They have been shown to exert anti-inflammatory effects
in various in vitro and in vivo models, and
- They seem to have positive effects on the quality and
luster of the hair coat.
1) Emilie Vidémont and Didier Pin, Unité Dermatologie, Ecole Nationale Vétérinaire de Lyon, France
E-mail: [email protected]
276
EJCAP - Vol. 19 - Issue 3 December 2009
EFA products generally contain a mixture of gamma linolenic
acid and eicosapentaenoic acid. EFAs can be administered in
food as a capsule, oil or spray. For several years, EFAs have also
been supplied in some dry pet foods. There are few reports on
the effectiveness of fatty acid supplements to control pruritus
in the cat [Table 1]. In several open trials [10, 11, 12, 19], cats
with pruritus, eosinophilic granuloma complex (EGC) and miliary
dermatitis secondary to flea bite hypersensitivity or atopy were
treated with various combinations of evening primrose oil and
fish oil. These studies suggest that cats respond favorably to EFA
with variable efficacy. A double-blinded study by Logas et al.
showed no significant difference between two groups of cats
receiving either evening primrose oil liquid or olive oil [15].
Side-effects of EFA are very uncommon (occasional vomiting)
but palatability is, often, considered to be poor.
To summarise, EFA supplementation may improve coat condition
but its true clinical efficacy remains uncertain.
been performed in feline atopic patients and most information
is anecdotal. The mechanism of action in both the canine and
feline atopic patient has not been fully elucidated.
For an effective response to ASIT, the relevant allergens must
be selected, typically by identification of high levels of allergenspecific IgE in the sera and/or by positive skin test results to the
allergen. One of the major problems in the cat is the low level
of accuracy associated with these tests. [see previous article in
this issue]
The injection schedule is borrowed from canine medicine
and depends on the company that prepares treatment. No
standardisation exists in cats. The schedule involves injecting
a gradually increasing amount of allergen over a period of
several weeks (induction phase). This is then followed by a
gradual reduction in the frequency of injections but leaving
the amount of allergen constant (maintenance phase). Current
recommendations [33] are to encourage owners to continue ASIT
for at least 1 year before discontinuing therapy. Improvement may
be monitored by the dose and frequency required of additional
medications and the pruritus scores that owners have assigned
to their pet during the course of the therapy. In cats that exhibit
only minimal to moderate improvement during the first year of
ASIT, the clinician and owner have to decide whether or not
continuing ASIT provides therapeutic benefit to the patient. In
patients that exhibit good to excellent response to ASIT after
6 months to 1 year, the recommendation would be to reduce
gradually the frequency of the injections over the subsequent
year. If, after one year, the cat’s allergies are controlled with no
clinical signs attributable to allergy or need for other medications,
the recommendation would be to discontinue the injections and
monitor the patient for recurrence of clinical signs. Although
immunotherapy is usually continued lifelong, it may, in a few
cases, be discontinued after some years without recurrence of
clinical signs.
• Moisturisers and emollients
They are useful in the treatment of dry skin. Products with
propylene glycol, glycerine and urea can be used in cats.
Psychogenetic factors
A link has been established in man between anxiety and atopy,
with stress aggravating the clinical signs. It is possible that a
similar link exists in the cat. Severe, prolonged pruritus can induce
a state of anxiety and behavioural problems. When cats have
extensive lesions, especially on the face, marking is decreased.
Moreover, owners are sometimes reluctant to stroke their pets.
If anxiety or behavioural problems are suspected, behavioural
therapy or treatment with pheromones or psychotropic drugs
may be given. Several sedating antihistamines also have anxiolytic
properties. It may be speculated that this is the reason for some
of the beneficial effects of this group of drugs in atopy.
Allergen-specific immunotherapy
Allergen-specific immunotherapy is defined as the practice of
administering gradually increasing quantities of an allergen
extract in order to reduce or eliminate the signs associated with
subsequent exposures to the causative allergen. Few studies have
Reported success rates [Table 2] range from 50 to 100 % in
feline atopic patients [3, 4, 9, 16, 25, 26]. However, a placebocontrolled trial demonstrating unequivocally that cats respond
to immunotherapy would be useful. In the majority of studies,
Tab. 1 Trials reporting treatment with EFA in management of feline AD.
Study
Product
Patients
Results
Harvey 1991 [10]
Evening Primrose oil + fish oil
(Efa-Vet 2 capsules)
8 cats with military dermatitis
6 cats good response with absence
of papules, decrease of pruritus and
improvement in coat condition
Harvey 1993 [12]
Evening primrose oil (6 cats) or
sunflower oil (5 cats)
11 cats with military dermatitis
Improvement of all cats, better
efficacy of evening primrose oil
Harvey 1993 [11]
Various combinations of
14 cats with military dermatitis
evening primrose oil and fish oil
Improvement with evening primrose
oil. No effect of fish oil alone
Miller 1993 [19]
DVM Derm Caps LiquidTM
1 mL/9.1 kg once daily 14 days
28 cats with various pruritic
dermatosis, military dermatitis
and EGC
Complete resolution in 13 cats
At least 50 % improvement in 3 cats
Logas 1993 [15]
Double-blinded study. Evening
Primrose oil versus olive oil
15 cats
No significant differences between
the two groups
277
How to treat atopy in cats? - E. Vidémont, D. Pin
Studies and their result on ASIT in the cat
Number of cats Response rate (%)
Reedy 1982 [26]
20
55 % response
McDougal 1986 [16]
13
69 % : good response
23 % : moderate response
8 % : bad response
Carlotti 1988 [4]
6
66 % excellent response
Prost 1992 [25]
28
78 % response
Bettenay 1996 [3]
29
Overall success rate of 50 %. Success rate decreases after 3
years of follow-up
Halliwell 1997 [9]
42
Improvement ranges from 53.3 % (hair loss) to 100 %
(linear granuloma) according to the dermatologic signs
Tab. 2 Trials reporting results of ASIT in the management of feline AD.
period evaluation is short, generally under a year and it is
interesting that success rate decreases when the follow-up
period is longer. In a study by Bettenay [3], success rate after
one year is similar to than in other studies but it decreases
significantly after 3 years of treatment.
It is unusual to rely on topical therapy alone because cats are
adept at grooming away topical products. Hydrocortisone
aceponate, now commercially available, could be used. Its rapid
penetration of the stratum corneum and metabolism in the skin
are interesting.
Side-effects are rare and include worsening of clinical signs
for a few hours to days, local reactions at injection site and
anaphylaxis. Increased pruritus or local reactions can usually be
managed by reducing the injection dose. The dose can later be
increased gradually after a period of stabilisation. Even though
life-threatening anaphylaxis is extremely rare, it is important to
educate owners about this possibility. Anaphylaxis occurs within
the first 30 to 60 minutes after the injection. Animals should
be monitored during this time. If vomiting, diarrhoea, dyspnoea
or collapse occur, the owner must seek immediate veterinary
emergency care. The risk of inducing fibrosarcoma has never
been investigated.
Injectable preparations are popular, especially with cats that
resent being given pills. Methylprednisolone acetate is often
successful at a dose of 20 mg (or 4 mg/kg) every two to three
weeks for a total of three injections [6]. Maintenance doses
may be given every six to 12 weeks. Unfortunately, an initial
beneficial response to injectable therapy can be followed by a
reduced response and, consequently, a reduction in the interval
between injections. Therefore, injectable methylprednisolone
acetate should not be a standard therapy. Prednisolone or
methylprednisolone are used orally at a dose of 1 to 2 mg/kg
per day. After seven days, the dose should be reduced by 50 per
cent for a further seven days followed by alternate day therapy
and a search for the minimal effective dose. Some cats can be
maintained on doses of 0.5-1 mg/kg on alternate day to alleviate
pruritus. Cats have unpredictable absorption or metabolism (to
the active form) of prednisone, which should not therefore be
used in this species. Other oral steroids that may be useful in
cases that fail to respond, or become resistant to the effects
of the previously mentioned steroids, include oral triamcinolone
(0.1-0.2 mg/kg/day) and dexamethasone (0.1-0.2 mg/kg/day).
Their long duration of action requires an administration only
every 3 days if they are used long-term [6].
Rush allergen specific immunotherapy (RIT) is a technique
of advancing an allergic patient to a maintenance dose of an
extract over a shorter period of time than that required for the
traditional induction period. RIT would minimise the owner’s
burden and may result in improved compliance. Typically, RIT
is given over 8 hours as opposed to 25 days usually needed for
induction. At present, RIT has been evaluated in 4 feline atopic
patients [32] and in an experimental model of feline asthma
[27]. Further studies are required.
Symptomatic therapy of pruritus
Intralesional injections of corticosteroid have been described for
severe refractory indolent ulcer (IU) and eosinophilic granuloma
(EG) but benefit remains unproven.
Therapeutic options include the use of glucocorticoids,
antihistamines, EFA and cyclosporin.
Although glucocorticoids are effective and safer in cats than
dogs, they are not without side-effects and often become
less effective with time. Adverse effects include polydipsia,
polyphagia, weight gain, diabetes mellitus, iatrogenic
hyperadrenocorticism with fragile skin syndrome and urinary
tract infections, dermatophytosis, demodicosis, and gastric
ulceration.
Glucocorticoids
Until recently, corticosteroids were the mainstay of therapy for
allergic cats.
Glucocorticoids can be administered by injection, orally or
topically.
278
EJCAP - Vol. 19 - Issue 3 December 2009
Drug
Clemastine fumarate
Hydroxyzine
hydrochloride
Mechanism of action
H1-blocker
antihistamine. Centrally
mediated, synergistic
with EFA
Stabilizes mast cell
membranes, centrally
mediated
Diphenhydramine
Dosage
0.34-0.68 mg/cat PO
BID
Comments
Study
Diarrhea, lethargy, fixed Miller 1994 [20]: 10
drug eruption
cats 0.68 mg/CT,
response in 5/10 cats
1-10 mg/kg PO BID or
TID
Behavioral changes
(hyperexcitability or
depression), teratogenic
Liquid form : alcohol
base that cats strongly
dislike
Miller 1990 [18]
Transient drowsiness,
unpalatable (extremely 26 cats 2 mg/cat every
bitter tasting)
12 hours. Excellent
response in 73 %
Polyphagia, behavioral
Scott 1998 [31]
changes, vocalization,
20 cats, 2 mg, q12h,
sedation, vomiting,
for 2 weeks. Good or
affectionate behavior
excellent response in 9
cats (side effects in 8
cats, severe in 3)
1-2 mg/kg BID to TID
Chlorpheniramine
maleate
Centrally mediated
2-4 mg/cat PO SID to
TID
Cyproheptadine
hydrochloride
H1-blocker
antihistamine and
serotonin antagonist
2 mg/cat PO BID
(1 mg/cat, q 24h, to 8
mg/cat, q8h)
Tab. 3 Trials reporting treatment with antihistamines in the management of feline AD.
Glucocorticoids can be considered a reasonable choice in animals
with mild seasonal pruritus of only a few months duration but
their long-term use should be undertaken with care.
CsA is not licensed for use in cats. It is available as a solution
or capsule. Dermatologists tend to use the microemulsion
concentrate which is presumed to provide better absorption. It
is not known if food affects the absorption of CsA in cats but
a majority of authors recommend giving CsA at least 2 hours
before or after meals. One study found no difference between
the two formulations, although cats given capsules received a
lower dose [34]. The liquid form allows more flexible dosing
but is bitter tasting. Initial doses vary between 3.6 to 13.3 mg/
kg but in the majority of cases are about 5 mg/kg or 25 mg/cat
once daily. CsA must be administrated once daily until complete
remission of clinical signs, then in an alternate day regimen for
least two months and eventually a twice weekly administration
for an unlimited duration. If it is stopped immediately after
remission of clinical signs, relapse will probably occur [8].
Therefore, it is important to prolong maintenance therapy by
increasing the interval between administrations and searching
for the minimal effective dose.
Antihistamines
Several antihistamines have been used in cats [Table 3]. There
are no placebo-controlled studies of antihistamines in cats, so
the dosages recommended are empirical and based on open
trials. Efficacy is often low and very variable with different
authors reporting a success rate of 20 to 73 % [6, 18, 20, 31].
Administer the antihistamine for at least three weeks before
evaluating a patient’s response. If effective, antihistamines must
usually be given once a day indefinitely. The success rate may be
increased by trying several different antihistamines sequentially
as patients may be responsive to one antihistamine but not to
another.
The advantage of antihistamines is the rare occurrence of
side-effects. The main side-effects are increased appetite and
sedation, although paradoxically, there can be hyperexcitability.
Gastrointestinal signs are uncommon. The frequent
administration (two to three times daily) limits their long-term
use in many feline patients.
In cats, successful use of CsA has been described principally in
small, open and uncontrolled trials [Table 4]. Efficacy is generally
very good. It is difficult however to compare the results of
studies because formulation, clinical signs and evaluation period
are different. Sometimes, the study period is too short [21],
generally one month. This could lead to a lower success rate
because remission of clinical signs may take longer than one
month. In one study, pruritus and EG were the clinical signs
which responded best, with a significant improvement seen
after 10 days of treatment and complete remission after 30
days. However, it took 60 days to obtain complete remission of
eosinophilic plaque (EP) lesions [8]. It is sometimes necessary to
administer the drug once daily for two or three months before
obtaining remission. Only one study compares the effects of
prednisolone and CsA on skin lesions and pruritus in a doubleblind pattern [36]. The effect of CsA is approximatively 70 % and
Antihistamines may be synergistic with glucocorticoids or EFAs.
Essential fatty acids (EFAs)
See part 3.
Cyclosporin A (CsA)
CsA is a potent inhibitor of cell-mediated immunity, and a
less potent inhibitor of humoral immunity. CsA also has a
variety of anti-inflammatory effects on leucocytes other than
lymphocytes, and on other types of cell, including keratinocytes
and endothelial cells [28].
279
How to treat atopy in cats? - E. Vidémont, D. Pin
Study
Guaguère 2000 [8]
Noli 2006 [21]
Vercelli 2006 [34]
Wisselink 2009 [36]
Protocol
Outcome
12 cats with ECG. 25 mg CsA/cat once By day 60, cats with EP and
daily (4.9-12.5 mg/kg/day) for 2 months EG were completely cured. In
2 cases, relapse by day 90. In
3 cases of indolent ulcer, only
partial regression
10 cats. 25 mg/cat once daily (3.6-8.3
Good to excellent
mg/kg/day), preferably on an empty
improvements was observed
stomach, for one month
in 40 % of cats for pruritus,
57 % of cats for alopecia, 60
% of cats for erythema and
50 % of cats for the total
lesions.
15 cats with EGC 5.8 – 13.3 mg/kg
Cure in all cats
Solution once daily or caps twice a
day, 2 h before or after meals, for one
month.Then CsA continued every other
day for 1 or 2 months until remission.
Maintenance regimen: twice a week
administration for an unlimited duration
Study period: 6 months
29 cats Oral therapy for 4 weeks with
No significant difference
either one capsule of CsA 5 mg/kg SID between the two groups.
(18 cats) or one capsule of prednisolone The effect of CsA is
approximatively 70 %
1 mg/kg SID (11 cats) 2h before meals
Side effects
Mild diarrhea in one cat,
which disappeared promptly
with symptomatic therapy
without the cessation of the
ciclosporin therapy
In one cat, capsules caused
diarrhea, disappeared with
liquid formulation
11 cats treated with CsA
involving intermittent
vomiting, diarrhea or loose
stools, hyperactivity, increased
appetite, polydipsia
Tab. 4 Trials reporting treatment with cyclosporin A in the management of feline AD.
no significant difference was found between the two groups.
prior to initiation of immunomodulatory therapy, as well as
during immunosuppressive therapy, might be helpful to detect
seroconversion. When seroconversion occurs, or significant rises
in toxoplasma antibody titres are observed in association with
developing clinical illness in cats which were seropositive prior
to initiation of immunosuppressive treatment, antitoxoplasma
chemotherapy should be started immediately to prevent acute
systemic toxoplasmosis.
The main disadvantage of CsA is its high cost. In cats, few adverse
reactions to CsA have been reported [29]. Gastrointestinal
signs (vomiting, diarrhoea and anorexia) are most frequently
reported. Other adverse events include salivation, headshaking,
intermittent soft faeces, gingival hyperplasia [14], hyperactivity,
increased appetite and polydipsia [36]. Vomiting can often be
overcome by giving the drug with a very small amount of food.
To minimise vomiting, the dose can be gradually increased or
metoclopramide can initially be given concomitantly.
These measures are difficult to apply in practice. It may be
helpful to evaluate serological antibody status of cats for both
A recent concern associated with CsA therapy is the increased
risk of developing systemic toxoplasmosis and viral diseases.
No publication exists at present concerning the association of
viral diseases such as feline immunodeficiency virus (FIV) and
feline leukemia virus (FeLV) with CsA treatment. In a study by
Vercelli, no clinical expression of viral disease was apparent
during the 6-month study period in the two cats found to be
FIV-positive before CsA therapy [34]. Therapeutic doses of
CsA have induced fatal toxoplasmosis in three cats following
renal transplant surgery [2], two cats with atopy [1, 13] and
one cat with immune-mediated haemolytic anaemia. Cats
can develop systemic toxoplasmosis either by reactivation of
latent infection or by primary infection. Precautions to consider
during immunomodulatory therapy would include feeding
only commercial cat food or other cooked foods, avoiding
raw meat, poultry, viscera or bones and preventing hunting
and scavenging. Monitoring of serological antibody status, for
both IgG and IgM class antibodies to Toxoplasma gondii, both
Tab. 5 General recommendations concerning the use of CsA in
management of feline CsA.
- Before treatment: Check for FIV/FeLV and toxoplasmosis
serological status
- In first intention: Microemulsion concentrate, capsules
giving at least 2 hours before or after meal
- Induction phase: One capsule of 25 mg/cat once daily
until complete remission of clinical signs (sometimes two
to three months)
- Maintenance regimen: Increasing intervals between
administrations and searching for the minimal effective
dose.
- Whole blood level of 250 to 500 ng/mL is recommended.
Whole blood levels higher than 1000 ng/mL can cause
side effects. Measuring blood CsA concentrations in cats
2 h after oral administration [17].
280
EJCAP - Vol. 19 - Issue 3 December 2009
Treatment
Dose
Mode of action
Side effects
Chlorambucil
0.1 to 0.2 mg/kg daily
or every other day, in
combination with steroids
DNA synthesis and
inhibition of rapidly
proliferating cells at all
stages of the cell cycle
Vomiting, diarrhea, anorexia and, more
importantly, bone marrow suppression
Gold salt therapy
Chrysotherapy
Sodium
aurothiomalate
1 mg/kg intramuscularly
every week, then every
month
variety of influences on
immune function including
neutrophil migration,
lymphocyte function and
immunoglobulin production
glomerulonephritis, bone marrow suppression,
thrombocytopenia and cutaneous eruption
Megestrol acetate
anti-inflammatory properties polyuria, polydispsia, mammary gland
hyperplasia, behavioral problems, potentially
irreversible diabetes mellitus, iatrogenic
hyperadrenocorticism and, possibly, mammary
neoplasia
Tab. 6 Some of old treatments recommended in the literature in the management of ECG and pruritus in cats.
[3]
FIV/FeLV and toxoplasmosis before starting CsA. However, the
risk seems to be low.
Others treatments
Several others treatments have been recommended in the
literature, especially for the management of EGC lesions. All
reports of these treatments are anecdotal with no proof of
efficacy.
[4]
[5]
[6]
Old treatments include chlorambucil, aurothioglucose and
progestagens [7]. These options are expensive, usually unlicensed,
require careful monitoring and are not always effective [Table
6]. More recently, amoxicillin-clavulanate [35], an analogue of
palmitolethanolamide called PLR-120 [30] and interferon α have
been proposed [5] but further studies are necessary to evaluate
these drugs.
[7]
[8]
[9]
Conclusion
[10]
Feline atopy is a disease recognised more frequently in
recent years and there have been many studies concerning
its management. In the majority of cases, a combination of
treatments is needed. Topical treatments are often useful. The
results of ASIT are very inconstant in cats. Antihistamines and
essential fatty acids may be synergistic with others drugs but
their efficacy is often low. Steroids, when used as long-term
maintenance therapy, are associated with several side-effects.
Cyclosporin may be a useful alternative therapy because it is safe
and effective in most cases. However, the existence of a new
antipruritic drug is no excuse for avoiding the difficult task of
establishing a definitive diagnosis in the itchy cat!
[11]
[12]
[13]
[14]
References
[15]
[1]
[16]
[2]
Barrs VR, Martin P, Beatty JA. Antemortem diagnosis and
treatment of toxoplasmosis in two cats on cyclosporin therapy.
Aust Vet J. 2006; 84: 30-35.
Bernsteen L, Gregory CR, Aronson LR, Lirtzman RA, Brummer
DG. Acute toxoplasmosis following renal transplantation in three
cats and a dog. J Am Vet Med Assoc. 1999; 215: 1123-1126.
[17]
281
Bettenay SV. Response of hyposensitization in 29 atopic cats.
In Advances in Veterinary Dermatology. Vol. 3. Eds : Kwochka
KW, Willemse T, Von Tscharner C. Butterworth and Heinemann,
Oxford, 1998. P 517-518.
Carlotti DN, Prost C. L’atopie feline. Point Vét. 1988; 20: 777784.
Fondati A. Feline eosinophilic skin diseases. In: Proceeding of the
18th annual congress of the ESVD-ECVD. Nice, France; 2002; p.
135-139.
Foster A. Diagnosing and treating feline atopy. Vet Med. 2002:
226-240.
Foster A. Clinical approach to feline eosinophilic granuloma
complex. In Pract. 2003: 2-9.
Guaguère E, Prélaud P. Efficacy of cyclosporine in the treatment of
12 cases of eosinophilic granuloma complex. Vet Dermatol. 2000;
11 (Suppl 1), S31.
Halliwell REW. Efficacity of hyposensitization in feline allergic
diseases based upon results of in vitro testing for allergen-specific
immunoglobulin E. J Am Anim Hosp Assoc. 1997; 33: 282-288.
Harvey RG. Management of feline military dermatitis by
supplementing the diet with essential fatty acids. Vet Rec. 1991;
128: 326-329.
Harvey RG. Effect of varying proportions of evening primrose oil
and fish oil on cats with crusting dermatosis (“military dermatitis”).
Vet Rec. 1993; 133: 208-211.
Harvey RG. A comparison of evening primrose oil and sunflower
oil for the management of papulocrustous dermatitis in cats. Vet
Rec. 1993; 133: 571-573.
Last RD, Suzuki Y, Manning T, Lindsay D, Galipeau L, Whitbread
TJ. A case of fatal systemic toxoplasmosis in a cat being treated
with cyclosporin A for feline atopy. Vet Dermatol. 2004; 15: 194198.
Latimer KS, Rakich PM, Purswell BJ, Kircher IM. Effects of
cyclosporine A administration in cats. Vet Immunol Immunopathol.
1986; 11: 161-173.
Logas DB, Kunkle GA. Double-blinded study examining the effects
of evening primrose oil on feline pruritis dermatitis. Vet Dermatol.
1993; 4: 181-184.
McDougal BJ. Allergy testing and hyposensitization for 3 common
feline dermatoses. Mod Vet Pract. 1986: 629-633.
Mehl ML, Kyles AE, Craigmill AL, Epstein S, Gregory CR.
Disposition of cyclosporine after intravenous and multi-dose oral
administration in cats. J Vet Pharmacol Therap. 2003; 26: 349354.
How to treat atopy in cats? - E. Vidémont, D. Pin
[18] Miller WH, Scott DW. Efficacy of chlorpheniramine maleate for
management of pruritus in cats. J Am Vet Med Assoc. 1990; 197:
67-70.
[19] Miller WH, Scott DW, Wellington JR. Efficacity of DVM Derm
Caps LiquidTM in the management of allergic and inflammatory
dermatoses of the cat. J Am Anim Hosp Assoc. 1993; 29: 37-40.
[20] Miller WH, Scott DW. Clemastine fumarate as an antipruritic
agent in pruritic cats: results of an open clinical trial. Can Vet J
.1994; 35: 502-504.
[21] Noli C, Scarampella F. Prospective open pilot study on the use
of ciclosporin for feline allergic skin disease. J Small Anim Pract.
2006; 47: 434-438.
[22] Ordeix L, Galeotti F, Scarampella F, Dedola C, Bardagi M, Romano
E, Fondati A. Malassezia spp. overgrowth in allergic cats. Vet
Dermatol. 2007; 18: 316-323.
[23] Piekutowska A, Pin D, Rème CA, Gatto H, Haftek M. Effects of
a topically applied preparation of epidermal lipids on the stratum
corneum barrier of atopic dogs. J Comp Pathol. 2008; 138: 197203.
[24] Prélaud P, Gilbert S. Atopic dermatitis. In: A practical guide to
feline dermatology. Eds Guaguère E, Prélaud P. Blackwell Science,
Oxford. 2000: 101-108.
[25] Prost C. Atopy in the cat: 28 cases. In: Proceeding of the Second
World Congress of Veterinay Dermatology. Montreal, Quebec,
Canada, 1992: 87.
[26] Reedy LM. Results of allergy testing and hyposensitization in
selected feline skin diseases. J Am Anim Hosp Assoc. 1982; 18:
618-623.
[27] Reinero CR, Byerly JR, Berghaus RD, Berghaus LJ, Schelegle ES,
Hyde DM, Gershwin LJ. Rush immunotherapy in an experimental
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
model of feline allergic asthma. Vet Immunol Immunopathol
2006; 110: 141-153.
Robson D. Review of the properties and mechanisms of action of
cyclosporine with an emphasis on dermatological therapy in dogs,
cats and people. Vet Rec. 2003; 152: 768-772.
Robson D. review of the pharmacokinetics, interactions and
adverse reactions of cyclosporine in people, dogs and cats. Vet
Rec. 2003; 152: 739-748.
Scarampella F, Abramo F, Noli C. Clinical and histological
evaluation of an analogue of palmitoythanolamide, PLR 120
(comicronized Palmidrol INN) in cats with eosinophilic granuloma
and eosinophilic plaque: a pilot study. Vet Dermatol. 2001; 12:
29-39.
Scott DW, Rothstein E, Beningo KE, Miller WH. Observations on
the use of cyproheptadine hydrochloride as an antipruritic agent
in allergic cats. Can Vet J. 1998; 39: 634-637.
Trimmer AM, Griffin CE, Boord MJ, Rosenkrantz WS. Rush allergen
specific immunotherapy protocol in feline atopic dermatitis: a pilot
study of four cats. Vet Dermatol. 2005; 16: 324-329.
Trimmer AM, Griffin CE, Rosenkrantz WS. Feline immunotherapy.
Clin Tech Small Anim Pract. 2006; 21: 157-161.
Vercelli A, Raviri G, Cornegliani L. The use of oral cyclosporin to
treat feline dermatoses : a retrospective analysis of 23 cases. Vet
Dermatol. 2006; 17: 201-206.
Wildermuth BE, Griffin CE, Rosenkrantz WS. Response of feline
eosinophilic cutaneous plaques and eosinophilic lip ulcers to
amoxicillin-clavulanate therapy. Vet Dermatol. 2009; Abstract.
223.
Wisselink MA, Willemse T. The efficacity of cyclosporine A in
cats with presumed atopic dermatitis: a double blind randomized
prednisolone-controlled study. Vet J. 2009; 180: 55-59
The big relief!
For
cats
and
dogs!
The effective approach to allergy in dogs and cats starts with the Artuvetrin® Serum Test;
the reliable allergy test that makes the allergen-specific IgE in the serum visible via the Fc region.
Based on the outcome of this test, we can provide you with an allergen-specific vaccine:
a big relief for allergy patients!
The authority on animal allergies
T E L . : + 3 1( 0 ) 3 2 0 - 2 6 7 9 0 0 - W W W. A R T U V E T R I N . C O M