1. health and fitness
2. disease

Ab s t ra c t s
Oral Abstracts
Leg and foot ulcers in patients with
collagen vascular disease
Afsaneh Alavi; Bizhan Bandarchi; R Gary Sibbald
University of Toronto, Toronto, ON
Background and objectives: Co-existing rheumatologic
disease occurs in up to 10-15% of specialized clinic patients
with lower extremity ulcers. There is a wide differential
diagnosis to these skin lesions that often creates difficult
diagnostic and treatment challenges. The etiology of these
leg ulcers includes vasculitis, hypercoagulable state due to
cryoglobulinemia or antiphospholipid antibody, panniculitis,
pyoderma gangrenosum, cutaneous calcification, often with
a coexisting arterial and venous component. Effective local
and systemic treatments have led to significant improvement in skin lesions and disease activity. .
Method: In this retrospective case series we followed over
20 patients with lower extremity ulcers associated with
connective tissue disorders. We compared the clinical and
pathological manifestations of the ulcers to determine their
relationship to the involvement of other organs or a consequence of the treatment of their underlying rheumatological
disease.
Conclusion: Connective tissue disorders may be associated with chronic relapsing lower extremity ulcers. There
are often several etiological factors associated with these
ulcers. Any ulcer that is not healing at the expected rate in
this patient population should be biopsied for underlying
etiological associations.
Patients seen in Ontario emergency
departments for diseases of skin
and subcutaneous tissue
Akerke T. Baibergenova; Neil H. Shear
University of Toronto, Toronto, ON
Rationale: There are only a few skin disorders that are
considered true emergencies and require rapid recognition
and treatment. To the best of our knowledge, there have
not been any studies on characteristics of patients visiting
emergency department (ED) with diseases of skin and subcutaneous tissues.
Objective: To understand characteristics of patients with
skin diseases who were seen in Ontario EDs.
Methods: We conducted a retrospective cohort study using
an administrative clinical database - National Ambulatory Care Records System (NACRS) collected by Canadian
Institute for Health Information (CIHI). Research population
included patients who visited Ontario EDs between April 1st,
2002 and March 31st, 2007 and had a principle diagnosis of
“Diseases of the skin and subcutaneous tissue” according to
the ICD-10: L00-L99.
Results: There were 866,976 ED visits due to skin conditions during a five year period. Various infections of skin and
subcutaneous tissue were major diagnostic category (52%
of all visits), followed by dermatitis (16.7%), and urticaria/
erythema (12.4%). Patients had relatively equal gender
distribution (females - 47.4%, males - 52.6%), with 23.3% of
all patients being younger that 20 years old. The majority of
patients were in non-urgent and semi-urgent category by
ED triage level (74.3%) with only 4% being eventually admitted inpatients. Interestingly, 84.4% patients indicated that
they had a family doctor.
Conclusion: Only a small minority of patients visiting
Ontario EDs with skin conditions had true emergencies.
Improving access to dermatological care is likely to largely
prevent ED visits due to minor skin conditions.
Erythropoietic protoporphyria:
the Sherbrooke experience
Janie Bertrand; Dominique Hanna
CHUS, Division of Dermatology, Department of Medicine, University of
Sherbrooke, Sherbrooke, QC
Introduction: Porphyrias result from the dysfunction of
enzymes in the heme biosynthesis. Erythropoietic Protoporphyria (EPP) is due to a deficiency of ferrochelatase, the last
enzyme of the pathway. It is the most frequent porphyria of
childhood, with most symptoms appearing early in life.
Methods: We describe three cases of EPP:
1. Our first patient is a 3 year-old boy who presented with
recurrent episodes of edema and erythema after sun
exposure. After many visits to the hospital, the diagnosis
a1
was suspected by a pediatrician and confirmed when we
evaluated the patient at 16 months of age.
2. The second case is a 15 year-old boy. He also had multiples visits at the emergency room during the summer
months. He complained of severe burning after sun
exposure. The diagnosis of EPP was made by another
pediatrician at 11 years of age.
3. The last case is a 27 year-old female who was sent to us
for acne. She was known for multiple sclerosis and celiac
disease. She also carried a diagnostic of “sun allergy”
since birth. Her symptoms were typical and we confirmed our diagnosis of EPP.
Results:
Case 1
Case 2
Case 3
Age at the
diagnosis
16 months
11 yo
27 yo
FEP (Ug FEP/
100cc RBC)
(32-62)
90-106
992
1991
Stool porphyrin
negative
negative
negative
Urine porphyrin
(Ug/dl) (0-200)
16.4
0
0
pending
pending
Mutation analysis mutation analysis showed an
unidentified FECH mutation by the
presence of low-expression IVS3
Conclusion: It is of a great interest to present three typical
cases of this rare entity with such a wide variability in the
patients’ ages at the time of diagnosis. It shows that a very
high index of suspicion is necessary.
The transmission of EPP is usually autosomal dominant but
it can also be recessive or secondary to a sporadic mutation. Life expectancy is normal but quality of life is greatly
affected. Treatment is mainly supportive, photoprotection
being the cornerstone of it.
None of the authors has any kind of conflict of interest.
A substituted trans-stilbene derivative
as a novel topical treatment for
psoriasis and atopic dermatitis
Robert Bissonnette; Michael Lyle; Yangsheng Wanggui; Bin
Li; Genhui Chen; Liren Tang; Youwen Zhou; John Webster
Introduction: As a new chemical entity, WBI-1001 is being
developed as a topical treatment for mild to moderate
psoriasis and atopic dermatitis (AD). In preclinical studies,
WBI-1001 was shown to inhibit inflammatory cytokines, and
T-cell viability and infiltration processes.
Methods: To assess the safety and efficacy of WBI-1001 in
patients with psoriasis or AD, two, double-blinded, placebocontrolled studies were conducted. In the Phase I dose
ascending study, 36 patients with plaque psoriasis were
recruited in groups of 6. Each group received 0.5, 1.0 or 2.0%
WBI-1001 cream either once or twice daily on one side of the
a2
body and the placebo on the other side. In the second study,
36 patients with AD were randomized (1:1:1) to receive
either 0.5 or 1.0% WBI-1001 cream or the placebo cream
twice daily. Patients were treated for 28 days.
Results and Conclusions: The 0.5% and 1.0% WBI-1001
treatment exhibited excellent skin tolerance. The 2.0% WBI1001 caused a few temporary, mild, skin-related adverse
events (AE) in the psoriasis study. The pharmacokinetic
studies showed that WBI-1001 was only minimally absorbed
and no evidence of WBI-1001 accumulation was detected
in the blood. In the psoriasis study, improvement in physician’s global assessment, induration, erythema and scaling
was more important on the side treated with WBI-1001 as
compared to the side treated with the placebo cream. In
the AD study patients randomized to 0.5 or 1.0% WBI-1001
showed statistically significant improvement of all the major
efficacy assessments including eczema area and severity
index, SCORAD, investigator’s global assessment, and body
surface area, when compared with placebo cream. In conclusion, WBI-1001 cream at 0.5% and 1.0% was well tolerated by
patients with psoriasis and AD, minimally absorbed into the
blood system and efficacious against both psoriasis and AD
as a novel, non-steroidal topical therapy.
Treatment of HIV-associated facial
lipoatrophy with injectable silicone oil
Alastair Carruthers; Jean Carruthers
University of British Columbia, Vancouver, BC
20 HIV positive individuals (18 male, 2 female) with facial
lipoatrophy (FLA) were treated with injectable silicone oil
(ISO). 1ml of ISO was injected into each cheek on each visit
to a maximum of 6 visits, (total 12ml per subject) by the
microdroplet technique. The subjects were then followed for
12 months. A questionnaire was completed at each visit.
All subjects had improvement in their FLA during the study
and this was maintained for the duration of the study.
Subjects responded positively to the change in their appearance. Side effects were related to the injection procedure
(pain on injection, bruising, swelling, redness) but no long
term sequelae were observed.
LIS is not approved by Health Canada for facial augmentation. The treaments for FLA which are approved will be
contrasted with ISO.
Keratinocyte/fibroblast
communication via exososmes
Claudia Chavez-Muñoz; Ruhanguiz Kilani; Aziz Ghahary
BC Professional Firefighters’ Burn and Wound Healing Research Lab, The
University of British Columbia, Vancouver, BC
Introduction: Previous studies have reported that many
growth factors and cytokines released by keratinocytes
interact with fibroblasts, modulating the expression of the
extracellular matrix (ECM). It is also known that the expression of ECM is key in the wound healing process. Previous
studies in our lab described for the first time the presence
of stratifin (14-3-3) in keratinocyte conditioned medium.
Stratifin is involved in a wide range of intracellular regulatory processes not expected to be found in the extracellular
environment. However, the function and mechanism of its
release has not been elucidated. In this study, we propose
a new concept of keratinocyte/fibroblat communication
through which some intracellular proteins such as stratifin
and the other 6 isoforms of 14-3-3 are released from keratinocytes by exosome externalization and functioning as
ECM modulating factors for fibroblasts.
Hypothesis: In the present study, we hypothesize that
stratifin can be released from keratinocyte through exosome
externalization and that possesses an MMP-1 stimulating
effect for fibroblasts.
Methods: Exosomes were purified from KCM and visualized
by using transmission electron microscopy. The presence
of stratifin and the other 14-3-3 isoforms were analyzed
and compared between differentiated and undifferentiated
keratinocyte lysate and their releasable exosomes, using
proteomics and western blot analysis.
Results: The results showed the presence of stratifin and
other 6 isoforms of 14-3-3 proteins in exosomes. Interestingly exosome associated stratifin and 14-3-3β isoform
showed an MMP-1 stimulating effect in fibroblasts. Further,
the results of the proteomic analysis confirmed the presence
of these proteins in the keratinocyte releasable exosomes.
Further, the 14-3-3 isoforms profile were different between
exosomes from differentiated and undifferentiated KCM.
Conclusions: In conclusion, exosomes from DK possess a
different 14-3-3 protein profile than UK. In addition to stratifin, other 14-3-3 isoforms also stimulate MMP-1 expression.
Clinical Significance: Exosomes have the potential to
be used as a delivery mechanism. This study shows that
keratinocyte exosomes contain anti-fibrogenic factors, with
the capacity to induce MMP-1 expression in fibroblasts. The
presence of these anti-fibrogenic factors in exosomes might
be the answer to reduce scar tissue formation and improve
hypertrophic scar.
Toll-like receptor 9 expression on skin stromal
cells is required for the topical adjuvant
effect of CpG oligodeoxoynucleotides
Wing-ki (Vicki) Cheng; Jan Dutz
Department of Dermatology & Skin Science, Faculty of Medicine, Child
& Family Research Institute, University of British Columbia, Vancouver, BC
Current vaccine technologies remain inadequate to counter
the risk of pandemics of viral infections. This is in part due
to the poor ability to induce effective antiviral immunity mediated by cytotoxic T lymphocytes (CTLs). We have
demonstrated that topical administration of immunostimulatory CpG oligodeoxynucleotide (ODN), a Toll-like receptor
9 (TLR9) agonist, induces potent, rapid, and durable antigen
(Agn)-specific CTL responses to locally injected protein Agn.
However, the subset of cells that are responding to this
adjuvant effect remains to be elucidated and the expression of TLR9 in the skin is controversial. This study aimed
to determine the expression of TLR9 by real time-PCR in
the skin and if TLR9 is required on stromal cells such as
keratinocytes for the topical adjuvant effect of CpG ODN in
vivo using C57BL/6 mice. Bone-barrow chimeric mice with
TLR9 deficient stromal cells but TLR9 sufficient (WT) bone
marrow derived cells were generated. Real time-PCR results
indicated that untreated WT mice expressed TLR9 compared
to TLR9 deficient mice in the skin. Tape stripping did not
up-regulate TLR9 expression in WT mice while CpG adjuvant up-regulated TLR9 expression in the skin. Topical CpG
treatment enhanced Agn-specific CTL responses in WT (TLR9
sufficient) but not stromal cell TLR9 deficient mice as indicated by the percent of OVA-specific CTLs amongst CD8+ T
cells in the spleen. Thus, skin stromal cell expression of TLR9
is required for the topical adjuvant effect of CpG to increase
the efficacy of vaccines. Topical CpG ODN is a potentially safe
and efficacious adjuvant to current vaccines. Third World
countries in particular might benefit from the results of this
study, as there is the potential to optimize vaccines without
reformulation.
The amazing vanishing Canadian dermatologist:
results from the 2006 CDA Member Survey
Eunice Chow; Gordon E. Searles
University of Alberta, Edmonton, AB
Introduction and Methods: The 2006 CDA Member Survey
tracked the Canadian Dermatology Workforce. Use of nondermatologist extenders, impact of financial burden on
practice style, and wait times was collected in the 2006 Survey. CDA members in 2006 were surveyed by mail. Follow-up
mailings were done for non-responders. Survey results were
compared to the 2001 Survey.
Results: Thirty-six percent (216/602) of Canadian dermatologists responded, (70 % in 2001). The national distribution
was identical between surveys. Median age increased to 55
years; 2/3 of dermatologists are male. Median retirement
age remained at 65 years. There is a shift from rural to urban
practice locations; 78% practice in private offices. 3/5 of
dermatologists do mainly medical dermatology, a decrease
between surveys. Pediatric dermatology decreased 10%,
surgical dermatology has increased 52% between surveys.
Fewer practitioners perform non-insured services, and half
as many perform research, hospital consultations, or teach
medical students. Financial debt burden had no impact on
selection of practice style. Median wait times for non-urgent
consultations doubled from 5 to 10 weeks; follow-up visits
increased from 4 to 5 weeks; non-insured consultations
increased from 4 to 5 weeks. The national median wait time
for a third-available consultation appointment was 42 days
(range 7 to 161 days). Seventeen percent of dermatologists
report using non-dermatologist extenders. Training programmes produce only 60% of new practitioners needed
to replace retirees over the next 5 years. Existing training
a3
programmes are at full capacity, and only the creation of
new programmes can expand training capacity.
Conclusions: While the face of Canadian Dermatology
shows a productive specialty committed to patient care,
teaching and research, the demographics of the Canadian
baby boom generation will have a major negative impact on
the effectiveness of Canadian dermatology in the service of
the Canadian population. The attrition rate predicted in the
2001 survey and validated by the 2006 survey spotlights the
critical imperative for the specialty to adapt to the future of
a shrinking workforce in the face of expanding demand for
its services.
Role of plasmacytoid dendritic cells
in adjuvent effect of topical CpG
Jennifer Cross; Jan Dutz
Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC
Dendritic cells (DCs) are a small, heterogeneous population
of antigen-presenting cells that are required for the initiation of primary immune responses. Epidermal Langerhans
cells and dermal DCs are two subsets of DCs that can be
identified in normal skin. Under inflammatory conditions
and in diseased states plasmacytoid dendritic cells (pDC) are
recruited and accumulate at sites of inflammation. Through
activation of TLR7 and/or TLR9, pDCs produce high levels
of type I interferon, which is key in antiviral defense. Work
in our lab has demonstrated that the topical application of
the TLR9 agonist CpG results in an adjuvant effect during
vaccination of mice with the model antigen ovalbumin. One
property of type I IFN is the ability to promote and maintain
CD8+ T cells responses thus, it was of interest to determine if
pDC recruitment and type I IFN production play a role in the
adjuvant effect of topical CpG.
Update on the safety of hair dyes
Jeff C. Donovan1 Erin M. Warshaw2 Maria K. Hordinsky2
1. University of Toronto, Toronto, ON; 2. University of Minnesota,
Minneapolis, MN, United States
Approximately 40 % of women, and a smaller percentage of
men, dye their hair. Hair dye use by children and teenagers is
also increasingly common. Dermatologists may be consulted for advice regarding the potential side effects of these
products. Here, we review three important potential side
effects of hair dyes: allergy, cancer and complications from
hair dye use in pregnancy.
Allergens in hair dyes may cause delayed contact hypersensitivity reactions as well as immediate contact urticaria.
Paraphenylenediamine (PPD) remains the most common
hair dye allergen, although other allergens such as 2,5diaminotoluene sulfate and 2-nitro-4-phenylenediamine
may are also be contributory for some patients. Severe, and
in some cases fatal, anaphylactic reactions have rarely been
reported with PPD. The incidence of contact dermatitis to
hair dye allergens may also be increasing.
a4
Multiple epidemiological studies have examined the association between use of hair dyes, especially permanent dyes,
and the risk of developing various types of cancer. While
most cancers do not appear to have an association with hair
dyes, a weak association may be present for hematopoietic
cancers such as non-Hodgkin lymphoma and multiple myeloma. There is a lack of evidence to adequately assess the
safety of hair dyes in pregnancy, although a small number
of studies have reported an increased incidence of certain
childhood malignancies as well as cardiac defects in children
of mothers who used hair dyes during pregnancy.
Hair dyes are important cosmetic agents for both men and
women. Continued evaluation of their long-term safety is
warranted.
The hair follicle is a reservoir for
skin langerhans cell precursors
Jeff C. Donovan1, 2 Florent Ginhoux2 Michel Abel2 Anthony
Bonito2 Marylene Leboeuf2 Tariq Dawoud2 Miriam Merad2
1. Division of Dermatology, University of Toronto, Toronto, ON;
2. Department of Gene and Cell Medicine, Mount Sinai School of
Medicine, New York, New York, USA
Introduction: As a new chemical entity, WBI-1001 is being
developed as a topical treatment for mild to moderate
psoriasis and atopic dermatitis (AD). In preclinical studies,
WBI-1001 was shown to inhibit inflammatory cytokines, and
T-cell viability and infiltration processes.
Methods: To assess the safety and efficacy of WBI-1001 in
patients with psoriasis or AD, two, double-blinded, placebocontrolled studies were conducted. In the Phase I dose
ascending study, 36 patients with plaque psoriasis were
recruited in groups of 6. Each group received 0.5, 1.0 or 2.0%
WBI-1001 cream either once or twice daily on one side of the
body and the placebo on the other side. In the second study,
36 patients with AD were randomized (1:1:1) to receive
either 0.5 or 1.0% WBI-1001 cream or the placebo cream
twice daily. Patients were treated for 28 days.
Results and Conclusions: The 0.5% and 1.0% WBI-1001
treatment exhibited excellent skin tolerance. The 2.0% WBI1001 caused a few temporary, mild, skin-related adverse
events (AE) in the psoriasis study. The pharmacokinetic
studies showed that WBI-1001 was only minimally absorbed
and no evidence of WBI-1001 accumulation was detected
in the blood. In the psoriasis study, improvement in physician’s global assessment, induration, erythema and scaling
was more important on the side treated with WBI-1001 as
compared to the side treated with the placebo cream. In
the AD study patients randomized to 0.5 or 1.0% WBI-1001
showed statistically significant improvement of all the major
efficacy assessments including eczema area and severity
index, SCORAD, investigator’s global assessment, and body
surface area, when compared with placebo cream. In conclusion, WBI-1001 cream at 0.5% and 1.0% was well tolerated by
patients with psoriasis and AD, minimally absorbed into the
blood system and efficacious against both psoriasis and AD
as a novel, non-steroidal topical therapy.
Cutaneous leishmaniasis
Yahya Dowlati
Center for Research and Training in Skin Diseases and Leprosy, Tehran
University of Medical Sciences, Tehran, , Iran
Leishmaniases are a group of diseases caused by several
species of the genus Leishmania, a protozoa transmitted by
the bite of a tiny insect vector, the sandfly. The four clinical
patterns of the disease in the human host are: cutaneous
leishmaniasis (CL), diffuse cutaneous leishmaniasis (DCL),
mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL).
The causative agents of CL in the Old World are L. major, L.
tropica, L. aethiopica, and rarely L. infantum. Clinically, the
disease is seen in dry and wet forms. The anthroponotic
cutaneous leishmaniasis (ACL), dry, urban or late ulcerative
form is generally attributed to L .tropica and the zoonotic
cutaneous leishmaniasis (ZCL), wet, rural, or early ulcerative form is caused by L .major. In human the initial sign of
infection is the appearance of an erythematous papule or
nodule at the feeding site of the insect. It develops into an
ulcer with a violaceous border which heals spontaneously in
several weeks to months, usually with scarring. ACL lesions
are usually more chronic and at the worst scenario, they can
develop into a long-lasting, destructive and disfiguring form,
known as recidivans leishnaniasis, which is very difficult to
treat.
In this presentation, the clinical features of cutaneous leishmaniasis will be reviewed and a clinical treatment guideline
based on a systematic review of published randomized
controlled trials will be provided.
Contact allergy to acrylates:
ten years of experience
Aaron M. Drucker1 Melanie D. Pratt2
1. Queen’s University School of Medicine, Kingston, ON; 2. Division of
Dermatology, University of Ottawa, Ottawa, ON
Introduction: Acrylates are present in a wide variety of
products and cause occupational and non-occupational
allergic contact dermatitis. Artificial nails, dental prostheses
and UV-curable inks are potential routes of exposure. We
sought to assess the significance of acrylate allergy in an
Ottawa outpatient contact dermatitis clinic.
Methods: Charts of patients visiting the Ottawa outpatient
contact dermatitis clinic from January 1998 - February 2008
were reviewed.
Results and conclusions: 47 patients were found to have
contact allergy to acrylates. The most common positive
allergens were hydroxyethyl methacrylate (HEMA) (30),
ethyl acrylate (EA) (28), methylmethacrylate (MMA) (25) and
ethyleneglycol dimethacrylate (20). Thirty-two of the 44
(73%) unequivocally positive patch tests would have been
discovered with the use of the 2 compounds (MMA, EA) in
the North American Contact Dermatitis Standard Screening Series, while 12 were found through expanded patch
testing. If HEMA were to be added to the series, it would
have found 8 additional cases. Artificial nails (14), dental
materials (9) and adhesives (5) were the most relevant
exposures. Occupational relevance was found in 24 cases,
including: dental workers (5), assemblers (5), aestheticians
(4) and auto mechanics (3). In conclusion, acrylates are an
important source of contact allergy. The standard screening
series identifies most cases of acrylate allergy, but may miss
a substantial number. Clinicians should be aware of acrylates as potential sources of allergy, even if initial screening is
negative.
Complementary medicine in Canadian
pediatric patients with atopic
dermatitis: a cross sectional survey
Aaron M. Drucker1 Fara Redlick2 Sam Cammisuli3, 4 Saul
Greenberg3, 4 Nhung T. C. Ho3, 4 Elena Pope3, 4 Hala Tamim5
Christine Webster3, 4 Jeanne Zeller3 Miriam Weinstein3, 4
1. School of Medicine, Queen’s University, Kingston, ON; 2. Women’s
College Hospital, Toronto, ON; 3. The Hospital for Sick Children, Toronto,
ON; 4. The University of Toronto, Toronto, ON; 5. York University,
Toronto, ON
Introduction: The use of complementary and alternative
medicine (CAM) is increasing among patients with atopic
dermatitis (AD), despite the lack of safety and efficacy data
for these treatments. Our objective was to determine what
proportion of AD patients use CAM, which CAM strategies
are being tried, which factors have contributed to decisionmaking regarding the use of CAM and if there are any
predictors of CAM use.
Methods: A detailed questionnaire was administered to
parents of children with AD attending clinic at an academic
paediatric dermatology center.
Results and conclusions: Two-hundred and six parents
participated in the study. Sixty eight percent of patients
had used CAM in the past, and 40% were using CAM at the
time of the survey. The most commonly used types of CAM
were vitamins and topical herbal preparations. When asked
about their motivations for using CAM, 66% of participants
stated they wished to “minimize their child’s symptoms”, 42%
wanted to “avoid the side-effects of conventional medicines”
and 42% wanted “to cure their child’s eczema.” When asked
about the safety of CAM, only 21.6% of respondents felt
that CAM was safer than conventional medicine, and 45% of
participants felt that CAM was “more natural” than conventional medicine. Forty-three percent of participants believed
CAM improved their child’s atopic dermatitis, while 71.4% of
participants felt that conventional medicine improved their
child’s AD. Patients with no family history of AD (OR 2.5, CI
1.3-4.7) and parents who believed that topical steroids thin
the skin (OR 2.2, CI 1.1-4.4) were more likely to use CAM. In
conclusion, parents felt that CAM was “more natural”, but less
efficacious compared to conventional medicine. CAM use
was more prevalent among children with no family history
of eczema and children whose parents believed that topical
steroids thin the skin.
a5
Hyperpigmentation disorders
in tropical Latin America
Rafael Falabella
Traveling has become an important activity of human
beings. Either because of leisure, business, administration,
education and so on, common people have frequent trips
within their native countries or abroad. And sometimes,
patients with skin disease may request treatment at their
destination points where such conditions are non prevalent,
sometimes provoking diagnostic difficulties. Pigmentation
disorders may also be such conditions.
Melanocytes in-vitro respond with dendricity or edema and
increased tyrosinase activity when exposed to PGE2, LTC4,
LTD4, LTE4, 12 HETE, TXB2, and in turn migration of melanocytes also occur if exposed to bFGF, ET-1 or TGF-alpha; these
cytokines and inflammatory mediators may be present in
many hyperpigmentation disorders of inflammatory origin,
and the clinical expression is increased skin darkening.
Moreover, autocrine and paracrine cytokine networks involving keratinocytes, fibroblasts and melanocytes may originate hyperpigmentation following inflammatory dermatoses.
Most hyperpigmentation disorders are similar around the
world. However some of them are more prevalent in tropical
areas, others are observed occasionally, and a few are almost
exclusively seen in the tropics. The purpose of this presentation is to review some of these dermatoses.
Post inflammatory hyperpigmentation, is characterized by
skin darkening following inflammatory skin conditions; the
manifestation of hyperpigmented areas usually have the
shapes of previous lesions and the intensity depends on
multiple factors including a possible genetic predisposition,
and ethnic skin is characteristic in the tropics.
Exogenous ochronosis is a less frequent pigmentation
disorder provoked by multi-therapy for melasma and
hyperpigmented lesions, mostly with hydroquinone derivatives at high concentrations. Typical micro-dots of pigment,
histologically observed within collagen bundles may be
observed. Fractional lasers may improve this condition.
Lichen-lupus usually manifests as diffuse and dark pigmentation of facial areas indistinguishable from that of dark
melasma; however, lesions not responding to therapy may
suggest this pathology, which may be difficult to treat with
antimalarials, topical corticosteroids and tretinoin.
Pigmented lichen planus is observed as wide, band-like, dark
pigmented macular lesions, characteristically non pruritic;
lesions are difficult to resolve even after potent topical steroid therapy.
Ashy dermatosis (erythema dyschromicum perstants),
consists of ill defined, asymptomatic macules of grayish
discoloration affecting trunk, face and upper extremities and
more evident on exposed areas. Although difficult to treat,
this condition may respond to clofazimine and dapsone.
Eruptive, macular, idiopathic pigmentation is a condition
with small 1-3 cm macules that develop in young individuals
a6
usually before the age of 20, without any related apparent
cause; lesions seem to resolve spontaneously after several
years.
Pinta (carate) is an almost historical pigment-related dermatosis caused by Treponema herrejoni that became uncommon after the antibiotic era, but it is observed from time to
time in tropical areas in patients who live in remote rural
areas. During a typical secondary stage the patient discloses
bluish hyperpigmented areas. Serological tests confirm the
diagnosis and penicillin is the therapy of choice.
In summary, although more commonly observed in tropical areas, hyperpigmentation disorders may be seen away
from the patient’s home. Dermatologists from other latitudes should be aware of these unusual manifestations not
observed in their daily practice.
Update on melanocyte
transplantation for vitiligo
Rafael Falabella
Melanocytes stimulated with appropriate medical treatment, migrate and repopulate depigmented defects. If
melanocytes are totally absent, repigmentation may not
take place, lesions become refractory and surgery may be
indicated in selected patients.
Vitiligo has two main clinical presentations:
a. Unilateral (segmental, asymmetric) affecting young
patients before the age of 20, with a rapid course until stabilization and without further depigmentation. This is the most
stable form responding well to surgical interventions, and
high rates of repigmentation are frequently achieved.
b. Bilateral vitiligo (non-segmental, symmetric) is a slow
developing form, and in around 50% of affected individuals
arrest of depigmentation occurs, allowing repigmentation
by surgery.
Five basic surgical methods have been described
1. Non-cultured melanocyte suspensions. With 0.25% trypsin
digestion of a donor skin sample during 2 hours at 37°C.,
epidermal cells, including melanocytes, separate and form
a cell suspension which is then prepared and “seeded” onto
recipient sites previously denuded by superficial dermabrasion. After healing, repigmentation takes place within the
following months.
2. Thin dermo-epidermal grafts. Very thin 0.1-0.3 mm dermoepidermal grafts are harvested with a suitable dermatome
from the donor site; the recipient site is prepared by removing the epidermis and papillary dermis with superficial
dermabrasion and the dermo-epidermal sheets are grafted
next to each other directly on the abraded recipient area.
Repigmentation is shortly achieved in the next weeks.
3. Epidermal grafting. This is a commonly used method
disclosing excellent repigmentation and absence of scarring. Grafts are harvested from donor sites in 2-4 hours with
diverse custom made suction devices. The depigmented
epidermis is removed from recipient sites by freezing with
liquid nitrogen, superficial dermabrasion, or ultrapulse CO2
laser. Grafting is done by transferring blister grafts onto the
recipient site. Repigmentation occurs gradually by melanocyte and pigment spread around grafts.
4. Minigrafting. This is a very simple method that has gained
much popularity in vitiligo surgery. Minigrafts are harvested
with a small 1.0 to 1.2 mm punch from donor sites and
placed on a non-adherent dressing moistened with normal
saline solution until grafting. Recipient sites are prepared by
perforating multiple recipient holes with a punch of similar
size at a distance of 3-4 mm from each other. Minigrafts are
transferred to the recipient sites and the area is covered
with Micropore® tape. Repigmentation occurs gradually by
coalescence around minigrafts.
5. In-vitro cultured epidermis and melanocyte suspensions.
From a small donor skin sample, an epidermal cell suspension is prepared by 0.25% trypsin digestion, which is seeded
in culture flasks with specific culture media. Thin epidermal
sheets are harvested from cultured flasks 3 weeks later and
transferred to recipient sites previously denuded superficially as with other methods. Pure melanocyte suspensions
may be cultured in a similar manner and spread onto the
recipient surface. Repigmentation is gradually achieved in
both types of grafts during the following months. The large
population of cells obtained is an advantage of this method.
In general, surgical methods constitute an important addition to the therapeutic armamentarium for vitiligo. Updated
results will be presented.
Actinic superficial folliculitis
in a 29 year old man
Lauren Fratesi; Nordau Kanigsberg; Steven Glassman
University of Ottawa, Ottawa, ON
Background: Actinic superficial folliculitis was first
described by Nieboer in 1985. Since then only 3 further
reports have been published. Characteristics of this disease
are monomorphous, superficial, follicular pustules that
appear 24-36 hours after exposure to sunlight. These usually
appear on the back, upper chest and shoulders annually
after the first exposure to sun of the year. The lesions resolve
on their own within 10 days. Recurrence occurs under similar
conditions after a latency period of at least 4 weeks.
Case: A 29 year old man presented to our clinic with a 5 year
history of an intermittent follicular rash. These eruptions
occur on his back and chest only when exposed to the sun,
with his shirt off. They develop 24-36 hours after the sun
exposure and resolve spontaneously after 5-7 days. The rash
begins with the year’s first exposure to the sun and becomes
less intense by the end of the summer. Photos are impressive, with follicular pustules grouped along his left flank.
Conclusion: According to our literature search, this is the
5th reported case of actinic superficial folliculitis. This will
be the first case in which provocative phototesting will be
done with and without the use of sunscreen. We will review
the clinical and pathological attributes of actinic superficial
folliculitis.
Fibroblast-keratinocyte cross talk: critical
role of cross-talking between epithelial
cells and fibroblasts in wound healing
Aziz Ghahary
BC Professional Firefighters’Burn and Wound Healing Research Lab. The
University of British Columbia, Vancouver, BC
Although, the promotion of healing in patients with nonhealing wounds is desirable, over healing processes such
as post-burn hypertrophic scarring and keloid are both
disfiguring and debilitating. Thus, an essential component
of wound healing is its timely cessation. Without it, there
can be a build up of excess and often a deleterious fibrotic
condition. In an attempt to identify and characterize any
keratinocyte derived anti-fibrogenic factors (KDAF) for
fibroblasts, we co-cultured fibroblasts with keratinocytes
and showed more than 10-fold increase in MMP-1 expression and activity in fibroblasts and that factor was identified
to be stratifin, also known as 14-3-3σ. During my presentation, compelling evidence will be provided to show that: 1)
There exist a cross-talking between epithelial and fibroblasts
using a co-culture system, 2) Keratinocytes release two sets
of ECM modulating factors that are important in controlling the healing process, 3) One set of this factors increases
the expression of MMP-1, 3, 8 and 24 in fibroblasts, 4) The
other set reduces the expression of type I and type III collagen in fibroblasts, 5) On the hand, fibroblasts release some
unknown factors that control the expression of keratinocyte
derived anti-fibrogenic factors (KDAF) and, 6) The expression
and activation of c-fos, c-jun and P38 MAPK are involved in
collagenase stimulatory effect of KDAF in fibroblasts. Finally
the mechanism by which these factors are released from
keratinocytes will also be discussed.
In conclusion. Identification and application of these naturally keratinocyte releasable factors in a clinical setting would
be critical in our understanding on how a dynamic healing
process is coming to end. We hope that identifying these
anti-fibrogenic factors at late stage of healing process,
would empower us to design a new strategy to improve and
even prevent scar formation in burn patients in the future.
Toll like receptor 7 is essential for
the induction of lupus like disease in
autoimmune prone NOD mice
Mehran Ghoreishi; Jan Dutz
Department of Dermatology & Skin Science, University of British
Columbia, Vancouver, BC
The role of environmental precipitants in autoimmunity
such as systemic lupus erythematosus (SLE) remains unclear.
Here we demonstrate that ultraviolet light B (UVB) with or
without topical application of synthetic Toll like receptor
(TLR) 7 ligand (imiquimod) induces SLE like disease in autoimmune prone non-obese diabetic (NOD) mice. Repeated
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weekly exposures of mice to UVB alone or combined with
topical imiquimod induced auto-antibodies against chromatin, dsDNA, sm-RNA or RNP detectable by direct immunofluoresence of HEP cells and antibody against desmoglein 3
(Dsg3) by ELISA. Apoptotic cells were significantly increased
in skin following UV irradiation. Following UV irradiation,
IFNa inducible gene MxA expression was detectable in skin
of treated mice with or without TLR-7 agonist. This treatment
resulted in glomerulonephritis measured by PAS staining
of glomeruli and proteinuria. Immune complex depositions
were detectable in dermo-epidermal junction, follicular epithelial cells and in glomeruli of kidney in 20% of experimental mice. High mobility group box 1 (HMGB1), a chromatin
protein, has been implicated in immune complex mediated
autoimmune pathogenesis. Extracellular HMGB1 expression
was noted in the dermis of skin after treatment with UVB
and imiquimod but not in normal control mice. Systemic
immune activation was detected following combination
(UVB and imiquimod) but not single therapy as evidenced
by IL-6 and TNF α production in serum. Combined treatment
induced up-regulation of TLR-7 in IgM positive peripheral
blood B cells. Intraperitoneal injection of pristane in mice
induces lupus by induction of chronic inflammation and
IFNa. Pristane injection resulted in accelerated autoantibody
production in NOD mice. IFNa production by DC is enhanced
by either TLR-7 or TLR-9 stimulation, and IFNa stimulates
antibody production. Combination of UV with TLR-9 agonist
CPG decreased autoantibody production in NOD mice. TLR-9
KO NOD mice treated with either pristane or UV showed
autoantibody production similar to or higher than NOD
mice. Chloroquine (an inhibitor of endosomal TLR-7 and
TLR-9) prevented UV mediated autoantibody production in
NOD mice. NOD mice deficient in MYD88, the adaptor molecule for both TLR-9 and TLR-7 signaling pathways, treated
with pristane did not develop autoantibodies. These studies
demonstrate that environmental factors combined with
inflammation induce autoimmune like disease and suggests
that TLR7 engagement (by either exogenous or endogenous
agonists) is essential.
Evidence for the expression of type I
interferons in scalp lesions of alopecia
lesions of alopecia areata
Mehran Ghoreishi; Magdalena Martinka; Jan P. Dutz
Dept of Dermatology & Skin Science, University of British Columbia,
Vancouver, BC
The exact mechanisms involved in the genesis of alopecia
areata (AA) remain unknown. T lymphocytes play an essential role in the hair follicle (HF) injury that occurs in AA. Type
1 interferons (IFNs) enhance a Th1 immune response and
recruit T-cells expressing CXCR3+. Little is known about
the role of Type1 IFNs and CXCR3+ cells in lesions of AA.
We examined the expression of IFNα inducible myxovirus
protein A (MxA) and CXCR3+ T cells in paraffin embedded
sections of scalp lesions from total of 8 patients with AA and
compared those with lesions from 2 discoid lupus erythematosus (DLE), 2 lichen planopilaris (LPP) and 2 androgenic
a8
alopecia (androgenic A). We observed strong expression of
MXA in follicular epithelial cells and epidermal keratinocytes
and appearance of CXCR3+ cells surrounding the bulbar
regions of HF in early AA similar to lesions from DLE and
LPP. In contrast, chronic (non-inflammatory) lesions of AA
and lesions of androgenic A failed to show the expression
of MXA or CXCR3. Granzyme B (GrB) and T-cell restricted
intracellular Ag1 (TiA-1) are both cytotoxic granule proteins
and induce apoptosis and tissue damage. Lesions of AA
showed expression of (TiA-1) but not GrB. In contrast, lesions
of scarring alopecia (DLE and LPP) demonstrated expression
of both TiA-1 and GrB cytotoxic molecules. Thus type 1 IFNmediated induction of Th1 inflammatory immune responses
and recruitment of CXCR3+ T cells may play role in early
lesions of AA. Furthermore, cytotoxic cells in AA lesions are
functionally different than in DLE or LPP.
A burning talk… Zoster and PHN
Lyn C. Guenther
The Guenther Dermatology Research Centre, The University of Western
Ontario, London, ON
Humans are the only known reservoir of the Varicella Zoster
virus (VZV). During the primary infection, varicella, viral
latency is established in sensory ganglia. Zoster occurs when
the virus is reactivated, often as a result of waning cellmediated immunity with increasing age or immunosuppression. Humoral and cell-mediated immunity are boosted with
re-exposure to the virus. The lifetime risk of zoster is approximately 30%.The diagnosis of zoster is usually made clinically.
A prodrome with pain, paresthesia, headache, malaise and
fever is common. Painful erythematous macules, papules
and vesicles on an erythematous base develop in a dermatomal and unilateral distribution, then crust over and heal.
PCR and viral culture can confirm the diagnosis. Individuals
over 50 years of age, or with severe prodrome, pain, or rash
should be treated with an antiviral (i.e. acyclovir, famciclovir, or valacyclovir). Acute pain may be treated with aspirin,
acetaminophen, NSAIDs, opioids, tricyclic antidepressants,
gabapentin and/or pregabalin. Postherpetic neuralgia (PHN),
a debilitating chronic neuropathic pain, occurs in approximately 10%. It is more common in older individuals, if there
was a prodrome, and when the eruption, subacute pain and
sensory abnormalities are greater. PHN pain may be continuous, paroxysmal, or evoked. It has a significant impact on
quality of life, affecting all activities of daily living. Pregabalin, gabapentin, tricyclic antidepressants, narcotics, topical
anesthetics and nerve blocks may offer some relief, although
PHN is often difficult to treat. The Shingles Prevention Study
showed that vaccination can halve the incidence of zoster,
decrease the severity and duration of zoster, and reduce
PHN at 3 months by 66.5% and at 6 months by 72.9%. The
vaccine is recommended for individuals > age 60 years
including those with a previous history of zoster. It may be
given concomitantly with the influenza vaccine.
Pseudopseudoporphyria
Richard M. Haber
University of Calgary, Calgary, AB
A 53 year old man with a history of chronic renal failure
treated with haemodialysis for ten years, presented with blisters, erosions and skin fragility on his hands of six months
duration.
The clinical diagnosis was porphyria cutanea tarda (PCT).
However this patient presented the interesting dilemma
of the differential diagnosis of true PCT, dialysis-induced
pseudoporphyria and drug-induced pseudoporphyria.
Skin biopsies showed a cell-poor subepidermal blister and
negative direct immunofluorescence. Erythrocyte protoporphyin was slightly elevated at 99 (Normal 10-70 umol/mol
Hb) and fecal porphyrins showed a minimal elevation in
coproporphyrin of 32 nmol/g (Normal <31) with a normal
protoporphyrin level.
He was anuric and urinary porphyrins could not be obtained.
One month prior to the onset of blistering, he had been
started on Naproxen for arthritis in his knees. The Naproxen
was stopped and the bullae, erosions and fragility cleared in
two weeks.
The final diagnosis was pseudoporphyria secondary to
Naproxen.
This case is presented because it illustrates the difficulty of
diagnosing a patient with clinical features of PCT in the setting of dialysis and chronic renal failure with anuria.
I have called this presentation Pseudopseudoporhyria as
he had two potential causes of pseudoporphyria but was
determined to have drug- induced pseudoporphyria rather
than dialysis-induced pseudoporphyria.
This presentation will review the differential diagnosis of
PCT- like skin changes in patients with chronic renal failure on dialysis. It will discuss the differential diagnosis of
pseudoporphyria and investigations for true PCT in an
anuric patient.
shown that the stress-response-kinase GCN2 is involved in
this selective apoptotic effect. However, the mechanism(s)
underlying selective GCN2 pathway activation in immune
cells is not known. It is showed that the protein IMPACT
homolog inhibits GCN2 activation and abolishes the expression of its downstream target gene CHOP. Here, we asked
the question of whether the expression of IMPACT protein in
immune and skin cells is differently regulated in response to
IDO-induced tryptophan deficient environment.
Objectives: 1) To study the expression of IMPACT protein
in IDO sensitive versus IDO resistant cell. 2) To study the
IMPACT regulation in response to IDO inducers such as IFN-γ.
Materials and Methods: IFN-γ treated IDO-expressing fibroblasts were co-cultured with bystander purified human CD3+
T cells, Jurkat cells, or primary skin cells such as fibroblasts or
keratinocytes. Expression of IMPACT was studied by Western
blot and RT-PCR analysis. The levels of total GCN2, phosphoGCN2 and CHOP were also studied by Western blot analysis.
Results: A significant expression of phospho-GCN2 and
CHOP was shown in immune cells, but not in skin cells,
co-cultured with IDO-expressing fibroblasts. The IMPACT
protein was highly and constitutively expressed in skin cells
both at the protein and messenger RNA level. The expression level of IMPACT protein was very low in CD3+ T cells and
it was undetectable in Jurkat cells. IMPACT expression level
in these cells was not dependent on either rich or amino
acid-deprived environment.
Conclusion: Our findings suggest for the first time that constitutive high IMPACT expression in non-immune cells might
act as a protective mechanism against IDO-induced GCN2
activation, therefore make them resistant to the amino aciddeprived environment caused by IDO expression.
Significance: This study revealed that IDO expression can
function as a local immunosuppressive factor to protect
the allograft skin without compromising skin cell viability.
On the other hand, using IDO inhibitors to treat different
types of cancer is already proven. Therefore, IMPACT inhibition may be considered as a good adjuvant therapy for
melanoma.
Higher expression of impact protein in
primary skin cells versus immune cells
might make them resistant to IDO effects
Photodermatoses: practical approach
to diagnosis and management
Darya Habibi1, 2 Reza B. Jalili1 Farshad Forouzandeh1
Christopher Ong2 Aziz Ghahary1
St John’s Institute of Dermatology, St Thomas’ Hospital, London, , UK
1. Burn and Wound Healing Research Lab, Department of Surgery,
University of British Columbia, Vancouver, BC; 2. Prostate Centre,
University of British Columbia, Vancouver, BC
Introduction: Indoleamine 2, 3-dioxygenase (IDO), a hemecontaining rate-limiting enzyme, catalyzes conversion of
tryptophan to kynurenine as the main tryptophan metabolite. It has been shown that IDO expression by trophoblasts
prevents fetal rejection by suppressing immune cells (mainly
T cells) function. We have previously demonstrated that
IDO expression selectively induces apoptosis in immune
cells rather than primary skin cells. We and others have also
John Hawk
The commonest photodermatoses are polymorphic light
eruption (PMLE) in the idiopathic, probably autoimmune
group, light-exacerbated seborrheic eczema and drug
photosensitivity. Also important are light-exacerbated acne
and the autoimmune actinic prurigo (AP), hydroa vacciniforme (HV), chronic actinic dermatitis (CAD) and solar
urticaria (SU).
PMLE is a common, sun-induced, papular, itchy, symmetrical
eruption of just some exposed sites, often sparing the face,
and affecting 10-20% of often young women in temperate
a9
areas. It develops over hours, lasts days and is a delayed-type
hypersensitivity response against ultraviolet radiation (UVR)altered skin molecules. These thereby become antigenic and
immunologically recognized because of genetically reduced
UVR-induced skin immunosuppression. Diagnosis is from
the history and presence of itchy papules, along with negative lupus and porphyrin testing.
Mild cases respond to high-protection, broad-spectrum sunscreens, while short oral steroid courses, say prednis(ol)one
25mg from first irritation for several days, or steroid injections, are effective for infrequent attacks. Otherwise, lowdose, prophylactic phototherapy thrice weekly for several
weeks in spring helps most patients for months by immunosuppressive activity, sometimes with long-term remission.
Rare severe disease may need azathioprine or cyclosporine.
Another common disorder with similar history is light-exacerbated seborrheic eczema, with eczema at characteristic
sites, along with a seborrheic eczema history and negative lupus and porphyrin testing. Treatment is surprisingly
successful with daily anti-eczema shampooing and careful
moisturizing, but if inadequate, with therapy as for PMLE.
A third, rarer condition with similar story is light-exacerbated
acne in subjects with previous acne. Diagnosis is from the
history of sunlight-induced, non-itchy papules in acne areas.
Antibiotics and sunscreens are ineffective, oral isotretinoin
being necessary, or oral steroids for occasional attacks.
AP is a persistent, excoriated, sometimes eczematised, eruption, mostly of exposed sites in children, and apparently a
genetically prolonged PMLE through the HLA type DRB1*04
(DR4), or subtype DRB1*0407. It responds to carefully administered thalidomide 50-100mg nocte, or sometimes phototherapy or oral immunosuppression.
HV resembles PMLE with permanent scarring. Treatment is
difficult, though sunscreens may help, and the condition
may resolve in adolescence.
CAD is a persistent eczematous, sometimes pseudolymphomatous, eruption of the exposed areas of older men
or younger atopics, and apparently an allergic contact
dermatitis-like reaction against skin photo-antigen, perhaps sometimes a DNA-like molecule. Diagnosis is from the
eczematous appearance, summer deterioration, and positive
irradiation and often patch tests, the latter frequently to
airborne allergens. Mild CAD responds to contact allergen
avoidance, high-protection, broad-spectrum sunscreens and
strong topical steroids, more severe cases to topical tacrolimus, intermittent oral steroids, phototherapy under highdose oral steroid cover, or azathioprine or cyclosporine.
SU is a type I allergic hypersensitivity against UVR-induced
cutaneous photo-antigen producing wealing over minutes
lasting hours. It develops spontaneously at any age, is
a10
diagnosed on history and irradiation testing, with normal lupus and porphyrin tests, and often responds to
high-dose non-sedating antihistamines, or less reliably
otherwise to phototherapy, plasmapheresis or intravenous
immunoglobulin.
Drug photosensitivity is mostly dealt with by non-dermatologists, but comprises sunburn-like or blistering reactions
or a burning sensation on exposure. Treatment is by drug
cessation or rarely evening dosing.
Screening for melanoma and non-melanoma
skin cancer with annual cutaneous
examination: reasons for non-compliance
Iman Hemmati2 Shannon D. Humphrey1 Katie Beleznay2
Jason Rivers1
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Faculty of Medicine, University of British
Columbia, Vancouver, BC
Background: Annual Cutaneous Examination (ACE) is recommended by many dermatologists as a screening method
for early detection of melanoma and non-melanoma skin
cancers in patients with increased risk for these lesions.
Objective: To explore patient compliance with a dermatologist’s recommendation for ACE and to characterize reasons
for non-compliance with this recommendation.
Methods: A retrospective chart review was performed for
patients seen by the same dermatologist over a 10-year
period with the diagnosis of either benign neoplasm of the
skin or melanoma. Charts were reviewed to determine if the
recommendation was made for ACE. Patients found to be
non-compliant with this recommendation were invited to
complete a survey exploring reasons for non-compliance.
Results: Nine hundred and fourteen charts were reviewed,
356 patients were targeted for ACE, and 215 of these
patients were found to be non-compliant. Questionnaires
were mailed to the non-compliant patients with a response
rate of 32%. Over half of respondents reported at least one
cutaneous examination since they saw the study dermatologist, and 26 % reported undergoing ACE. The most common
reasons cited for non-compliance were; 1) self-monitoring
of skin, 2) perceived lack of need for ACE, 3) being unaware
of the recommendation for ACE, and 4) uncertainty about
which physician would be responsible for follow-up. Thirteen percent of respondents were diagnosed with skin
cancer since they last saw the study dermatologist.
Conclusion: A failure to comprehend the recommendation
and importance of ACE is a significant reason for non-compliance. Strategies that emphasize the benefit of ACE may
improve this situation.
Carbon nanotube assisted laser
thermotherapy of skin cancers pilot proofof-principle study in a murine model
Naiyan Huang; Hequn Wang; Jianhua Zhao; Harvey Lui;
Mladen Korbelik; Haishan Zeng
The Laboratory for Advanced Medical Photonics (LAMP),
Photomedicine Institute, Department of Dermatology and Skin
Science, University of British Columbia & Vancouver Coastal Health
Research Institute and Cancer Imaging Department, BC Cancer
Research Center, Vancouver, BC
Background and Objective: Single-wall carbon nanotubes
(SWNTs) are a new type of nanomaterial with unique physicochemical properties and significant potential for medical
applications. SWNTs have strong Raman signals that facilitate convenient monitoring of their locations within tissue
thereby enabling non-invasive pharmacokinetic study.
SWNTs also have strong absorption to NIR light and can
translate this energy into heat. We hypothesize that intratumoral injected SWNT can absorb 785 nm NIR laser light and
generate significant local hyperthermia to destroy cancer
cells and eradicate tumors.
Materials and Methods: SWNTs are made water-soluble by
functionalizing with polyethylene glycol (PEG). The average diameter of the functionalized SWNTs is 4.3 nm and the
average length is 580 nm. A real-time Raman system was
developed in our lab that can obtain a Raman spectrum
within a few seconds. The device incorporates a 785 nm
diode laser with 1 W output. Animal model: C3H/HeN mice
were injected subcutaneously with 2 million mouse tumor
squamous cell carcinoma (SCCVII) cells. Seven days after
the implantation, the tumors reached the size used for the
testing (approximately 7 mm in largest diameter). Treatment: There were 4 groups of mice: control 1 (C1, no SWNT,
no laser), control 2 (C2, SWNT only), control 3 (C3, laser only)
and treatment (T, SWNT 1mg/ml, laser 200mW/cm2, 10 min).
The temperatures of the tumor in C3 and T groups were
monitored by an IR thermometer each minute before and
during laser irradiation. Tumor sizes were measured before
and at 2, 4, and 7 days after the start of the experiment
The Raman spectra from tumor, liver, lung, skin and kidney
were measured ex vivo. We measured 3 mice without SWNTs,
3 mice after 1 week, and 4 mice at 1 month after intratumoral injection of SWNTs.
Results: Tumor volume: The tumors in group T disappeared
2 days after treatment. In group C1, C2 and C3, tumors
continued to grow. The tumor volumes had no statistical difference between groups C1, C2 and C3 (ANOVA, P=0.0637).
However the tumor volumes of these 3 groups were statistical different from those of group T (ANOVA, P=0.0005).
Temperature: The temperature increased, on average, by
17.6°C in group T at the end of treatment; it increased by
9.2°C in group C3 (Paired t-test, P=0.00103).
SWNTs metabolism: The SWNTs had a strong peak at 1585
cm-1 and a medium peak at 1309 cm-1. These two peaks were
found in tumors both at 1 week and 1 month after intratumoral injection of SWNTs, but didn’t show up in kidney,
liver, lung, and skin. This suggests that SWNTs remained
localized only to the tumors.
Conclusions: Intratumoral injection of SWNTs followed by
785 nm NIR laser treatment increased the temperature in the
tumor by about 17°C and resulted in the eradication of skin
tumor in a murine model. SWNTs remained localized in the
tumor even 1 month after injection, but were not found in
other organs.
The expression of a cancer inflammation
marker correlates with melanoma
invasion and predicts poor survival in
stage III and stage IV melanoma
Helen Jiang1 Liren Tang2, 3 Wency Ip2, 3 Mingwan Su2, 3
Derek Dai2 Penelope Brasher4 Yaohua Y. Zhang2, 3
Yang Wang2, 3 David I. McLean2, 3, 5 Magdalena Martinka5
Gang Li2, 3, 5 Youwen Zhou2, 3, 5
1. Faculty of Medicine, University of British Columbia, Vancouver, BC;
2. Department of Dermatology and Skin Science, Faculty of Medicine,
University of British Columbia, Vancouver, BC; 3. Chieng Genomics
Center and Laboratory of Predictive Medicine and Therapeutics,
Vancouver Coastal Health Research Institute, Vancouver, BC; 4.
Center for Clinical Epidemiology and Evaluation, Vancouver Coastal
Health Research Institute, Vancouver, BC; 5. Skin tumor Group, British
Columbia Cancer Agency, Vancouver, BC; 6. Department of Pathology
and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC
Melanoma is one of the most aggressive and life-threatening
cancers due to its resistance to conventional treatments and
high metastatic potential. The current tumour-node-metastasis (TNM) staging system proposes that Breslow tumor
thickness and ulceration are the most powerful predictors
of survival for primary melanoma Stages I and II. However,
prediction of long term clinical outcomes for patients with
metastatic disease, either with lymph node involvement
(Stage III) or distant metastasis (Stage IV), currently remains
imprecise. Additional prognostic markers are urgently needed to improve the reliability of melanoma prognostication.
Tumor gene expression profiling has shown that among the
most up-regulated genes in metastatic melanoma are those
involved in the regulation of the extracellular matrix. Interestingly, in tumor biopsies from various stages of melanoma
examined through immunohistochemistry, we observed an
increased expression of an acute phase reactant protein with
extracellular protease activity. The objectives of this study
were to assess the correlation between protein expression
and melanoma progression, and to evaluate its clinical prognostic value.
Acute phase reactant protein levels are virtually absent in
normal nevi, dysplastic nevi and melanoma in situ but its
expression dramatically increases as lesions progressed to
primary and metastatic melanoma (P<0.001). The possibility
this protein contributes to melanoma invasion and metastasis was further examined in vitro using cultured MMRU
and KZ-28 melanoma cells. Down-regulation of this protein
through siRNA knockdown leads to decreased invasion into
Matrigel, but does not inhibit cell proliferation, migration,
or survival. The clinical correlation and prognostic utility
a11
of increased acute protein expression was subsequently
evaluated through Kaplan-Meier survival analyses with
biopsies and data from 159 patients with primary melanoma
and 51 patients with metastatic disease. Using a validated
3-point scoring system, stained lesions from these patients
were classified as exhibiting weak protein expression (score
of 0 or 1) or strong expression (score of 2 or 3). Increased
expression levels of this protein does not correlate with
worse 5-year overall and disease-specific survival in primary
melanoma patients (P>0.5). However, increased expression
strongly correlates with poorer overall survival (P=0.0229)
and disease-specific survival (P=0.0428) in metastatic melanoma. Patients with weakly stained biopsies experienced a
mean survival of 46.2 months compared to 14.9 months for
patients with strongly stained lesions. Furthermore, strong
protein expression is associated with worse survival specifically for patients with Stage III melanoma (P=0.0437). Taken
together, this acute phase reactant protein appears to contribute to melanoma invasion and metastasis and is a novel
prognostic marker for metastatic melanoma.
Varicella zoster virus in patients taking
TNF-α antagonists: is there a role for pretreatment screening and vaccination?
John Kraft1 Siobhan Ryan2
1. Division of Dermatology, University of Toronto, Toronto, ON; 2.
Division of Dermatology, Women’s College Hospital, Toronto, ON
Tumour necrosis factor alpha (TNF-α) antagonists
(adalimumab, etanercept, and infliximab) are increasingly
used in the treatment of inflammatory diseases such as
psoriasis. TNF-α antagonists increase the likelihood of some
infections and reactivation of latent infections, especially
Mycobacterium tuberculosis. It is standard practice to
ensure patients do not have latent tuberculosis, and if found
treated appropriately, prior to starting anti-TNF-α therapy. Initial screening is also done for viral hepatitis such as
Hepatitis B and C, as fulminant hepatitis has been reported
in patients started on anti-TNF-α who have chronic HBV. The
risk of other viral infections, such as varicella zoster virus
(VZV), is not as well-described.
We present two patients who developed zoster within
months of initiating etanercept therapy for psoriasis. Both
patients were males under 60 years of age with longstanding psoriasis. Usual screening investigations were done prior
to starting the TNF-α antagonist. Etanercept was dosed
at 50 mg sc 2 times per week. Both patients were treated
with antivirals within 72 hours of the first signs of the skin
lesions, and etanercept was stopped. The zoster resolved in
under three weeks with no sequelae, except minor scarring.
The etanercept was restarted and both patients have been
followed for over six additional months with no recurrence.
Neither patient had any immunosuppresion apart from
etanercept.
TNF-α normally inhibits the replication of VZV and VZV antigen expression and it has been shown that blocking TNF-α
completely inhibits this antiviral activity. A literature review
a12
suggests that the incidence of zoster and other viral illnesses
may be increased while on anti-TNF-α therapy, although to
a lesser extent than the likelihood of TB or HBV reactivation.
Cases of fatal disseminated VZV while on anti-TNF-α have
also been reported.
These cases highlight the need to review the current
evidence linking VZV and TNF-α antagonists and to discuss
whether or not patients should be warned specifically about
VZV, tested for the presence of varicella antibodies, and
offered a VZV vaccine prior to initiating anti-TNF-α therapy.
Repeat mechanical trauma to the
hands: the use of anti-impaction gloves
for treatment and prevention
Tiffany Kwok1, 2 Victoria Arrandale2, 3
Sandy Skotnicki-Grant2, 3
1. Schulich School of Medicine, University of Western Ontario, London,
ON; 2. James R. Nethercott Occupational Health Clinic, Occupational
Disease Specialty Program, St. Michael’s Hospital, Toronto, ON; 3.
University of Toronto, Toronto, ON
Background: Repeat mechanical trauma to the hands can
result in forms of irritant contact dermatitis known as hyperkeratotic hand dermatitis (HHD) and frictional hand dermatitis (FHD). These conditions can be chronic, debilitating
and refractory to many therapies. Unfortunately, reports on
the treatment and prevention of HHD and FHD are sparse.
We propose a strategy of using anti-impaction gloves filled
with gel or air, used in prevention of Hand and Arm Vibration Syndrome, as personal protective equipment for these
conditions.
Methods: We describe a case series of 11 patients who
presented to our occupational contact dermatitis clinic
between January 2004 to June 2008 with either HHD or
FHD. Demographic and occupational characteristics were
collected. Five were patch tested to the North American
Standard series and relevant occupational trays. All patients
were treated with anti-impaction gloves, tazarotene cream,
clobetasol ointment and followed for long-term outcome of
their job.
Results: Of the 11 patients evaluated, 9 had a diagnosis
of FHD and 2 were diagnosed with HHD. Patients spent an
average of 11.8 years in their occupation and a maximum of
2 years with active disease before reaching their diagnosis.
One patient had a history of psoriasis and none had a history
of atopy. Positive patch testing was found in 1 patient. All
patients with FHD were able to return to work with the use
of anti-impaction gloves, creams, and modified work duties
in some cases. Neither case of HHD resolved with treatment
and hand dermatitis remained chronic upon discontinuation
of work.
Conclusion: A return to work protocol consisting of antiimpact gloves, creams, and modified duties appears to
benefit individuals diagnosed with FHD but may not be
helpful in those diagnosed with HHD. This is the first study
to investigate anti-impaction gloves as a treatment for FHD.
As most case reports of FHD describe avoidance of frictional
trauma as a management solution, the results of this study
bring hope to prevention and management of FHD while
sustaining occupational-related frictional trauma.
A micrornaome analysis of cutaneous
squamous cell carcinomas
Lorie Kwong; Jennifer M. Tran; P. Régine Mydlarski
Department of Medicine, University of Calgary, Calgary, AB
Background: In recent years, microRNA (miRNA) has taken
center stage in cancer research. miRNAs are small, noncoding RNAs that act as translational inhibitors by downregulating gene expression. While certain miRNAs function
as oncogenes or tumor suppressors, their role in the process
of carcinogenesis remains unclear. An important challenge
therefore is to elucidate and understand the role of miRNAs
in normal and disease states. Herein, we investigate the
miRNA profile of cutaneous squamous cell carcinomas (SCC).
Objective: To compare the miRNA profile of normal human
keratinocytes (NHK) and cutaneous SCC cell lines.
Materials and Methods: Total miRNA was extracted from
NHK and SCC cell lines with a miRNeasy extraction kit
(Qiagen, Mississauga, ON). Using µParaflo® Biochip technology and the Sanger miRBase Release 12.0, a genome-wide
miRNA microarray assay was performed (LC Sciences, Houston, TX). All data were subject to multi-array normalization,
false discovery rate calculations and clustering analysis. An
unpaired t-test was employed to determine statistical significance (p-values of < 0.01). All findings were verified using
quantitative real time-polymerase chain reactions (qRT-PCR).
Results: A microRNAome analysis of NHK and SCC cell lines
revealed distinct miRNA profiles. Of 856 miRNAs studied, a
total of 72 miRNAs were significantly altered between the
normal and cancer cell lines. Of the 72 transcripts that were
statistically significant, 27 contained high signal intensities,
of which 12 miRNAs were up-regulated and 15 miRNAs were
down-regulated in SCCs. The significant, high signal intensity
findings were independently verified using qRT-PCR.
Conclusion: The identification of unique miRNA profiles
within NHK and SCC cell lines will allow our dataset to serve
as a roadmap for future studies of the microRNAome. While
many of the miRNAs identified remain uncharacterized, several have been implicated in the process of carcinogenesis.
For instance, miR-224, a marker of hepatocellular and renal
malignancies, targets apoptosis inhibitor 5 (API-5), resulting
in cellular proliferation and programmed cell death. Further,
miRNA-125b serves as a negative regulator of p53, a key
transcription factor involved in cell cycle regulation and
tumor suppression. Our data clearly suggests that miRNAs
are deregulated in skin cancer, are implicated in tumorigenesis and have the potential to provide useful prognostic
information. By understanding the transcriptional regulation
of miRNAs, molecular insight will be gained into the process
of skin cancer development. Ultimately, our findings will be
applied toward the development of diagnostic, prognostic
and therapeutic tools essential for the management of skin
cancer patients.
Unusual vulvar ulcers – a case
report and discussion
Christina Lam; Deana Funaro
University of Montreal, Montreal, QC
Vulvar lesions are a common reason for visiting a dermatologist. The list of differential diagnoses is extensive and it
is important to consider not only localized disease but the
implication of an underlying systemic condition as well. The
objective of this presentation is to highlight the importance
of keeping a broad list in mind and to discuss investigations
and treatment options for this diagnosis.
We report the case of a 47 year-old woman who presented
with a 6-month history of painful vulvar ulcers that bled
intermittently with no systemic symptoms. She was known
for diabetes insipidus, controlled with DDVAP for the last
15 years, and hypothyroidism. Initial cytology and cultures
were done and revealed no evidence of neoplasia with only
mixed inflammatory cells and no bacterial, fungal or parasitic infection. Biopsies were later performed and revealed
the following: granulation tissue heavily infiltrated by mixed
inflammatory cells and a different population of large cells
with eosinophilic cytoplasm and reniform nucleus. Immunohistochemistry studies were performed and showed intense
positivity of these cells for CD1a and protein S100. A final
diagnosis of Langerhans cell histiocytosis (LCH) was made.
Further systemic investigations were undertaken: chest X-ray
was normal; bone series was normal and MRI of the brain
showed normal pituitary stalk with an osteolytic bone lesion
of the occipital skull. Laboratory tests revealed a normal
blood count and biochemistry, but elevated prolactin and
decreased TSH.
The patient was started on a class 1 corticosteroid ointment
and the ulcers have decreased in depth. LCH can affect one
or many organs with the clinical course being quite variable;
therefore it is important to investigate for potential organ
involvement. Treatment for this disease is not well-defined
and depends on the degree and number of affected organs.
Multiphoton microscope development
for sin cancer detection and diagnosis
Anthony Lee1, 2 Hequn Wang2 Harvey Lui3
David I. MacLean3 Haishan Zeng1, 2
1. Department of Cancer Imaging, BC Cancer Research Centre,
Vancouver, BC; 2. Department of Physics, University of British Columbia,
Vancouver, BC; 3. Laboratory for Advanced Medical Photonics,
Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC
As skin cancer incidence increases, there is great impetus
to develop techniques to quickly and accurately detect
lesions in their early stages. Optical techniques hold promise
for this purpose and can be performed much faster than
biopsy. Furthermore, optical techniques have an additional
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advantage over biopsy of being non-invasive and nondestructive. Non-destructive techniques in particular are
essential for evaluating the natural progression of premalignant lesions and the effectiveness of chemopreventive/
therapeutic agents.
We present our progress and initial experiments using a
newly developed Multiphoton Microscopy (MPM) apparatus. This apparatus has been specifically designed for
dermatological use to detect and diagnose cancer. In MPM,
similar to Laser Scanning Confocal Microscopy (LSCM), a
laser excitation beam is scanned over the sample to create 2 dimensional images. However, MPM uses very short
pulse lasers (pulse duration ~100fs = 10-13s) as the excitation
source. Nonlinear, multiphoton signals are only generated at
the focus of the laser beam where the intensity is sufficiently
high. Hence, MPM is inherently capable of 3-dimensional
sectioning without the need for a light rejecting pinhole as
is the case for LSCM, enabling superior light collection ability
especially for highly scattering samples such as tissue. The
long wavelengths at which the short pulse lasers operate
(~800nm) are also ideal for tissue studies as they penetrate
deeper than shorter visible lasers. Additionally, there is
minimal linear absorption of tissue at 800nm and therefore
minimal thermal damage to the surrounding tissue.
Our new apparatus is a multimodal instrument capable
of simultaneously imaging two-photon fluorescence and
second harmonic generation signals at video rates, while
at the same time measuring the spectral characteristics of
the emitted fluorescence. The imaging capabilities of the
instrument should give clinicians the ability to perform in
vivo ‘optical’ biopsies, by examining cellular and structural
morphology without the removal of tissue. The spectral
characteristics of the emitted fluorescence will give indications to the chemical composition of the tissue that should
assist in determining disease. As we are also able to tune
the excitation laser wavelength, we can perform spectral
imaging of different cellular/structural fluorophores. We are
also equipping this instrument with confocal Raman spectral
and reflectance confocal imaging capabilities that should
give even more chemical specificity in the examined tissue.
Role of the tumor suppressor ING4 in
apoptosis and angiogenic potential
of human melanoma cells
Jun Li; Gang Li
Dept. of Dermatology and Skin Science, University of British Columbia,
Vancouver, Vancouver, BC
Objective: To evaluate the effect of ING4 on human melanoma cell apoptosis and angiogenic potential. The Inhibitor
of Growth (ING) family proteins are novel tumor suppressors
which are involved in various biological activities, including
regulation of transcription, cell cycle checkpoints, and DNA
repair. ING proteins contain several conserved domains, suggesting that they may share common biological functions.
ING4 was shown to diminish colony-forming efficiency,
suppress loss of contact inhibition, and arrest cell cycle at
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G2-M phase. We previously reported that ING4 expression
is decreased in malignant melanoma and the reduced ING4
expression is correlated with melanoma tumor thickness,
ulceration and poor patient survival. To further elucidate
the mechanism by which ING4 inhibits melanoma progression, we investigated the effect of ING4 overexpression on
apoptosis and angiogenic potential of melanoma cells. We
found that ING4 overexpression alone promotes morphologic changes associated with apoptosis, notably chromatin
fragmentation and the formation of apoptotic bodies. In
both wild-type p53 (MMRU) and mutant p53 (PMWK) melanoma cell lines, ING4 overexpression resulted in significantly
higher percentage of apoptotic cells when compared with
the empty vector. Overexpression of ING4 also enhanced
chemodrug-induced apoptosis in both MMRU and PMWK
melanoma cells. Furthermore, ING4 overexpression induced
UVB-mediated apoptosis in melanoma cells in the presence
or absence of functional p53, indicating that ING4 plays
an important role in cellular response to UV. Moreover, we
found that ING4 overexpression decreases the expression of
Interleukin-6 (IL-6) in melanoma cells at both transcriptional
and translational level, and suppresses the HIF-1α activity,
thus inhibits the growth of endothelial cell in vitro. Taken
together, our data suggest that reduced ING4 expression
leads to defects in the apoptotic pathways and enhanced
angiogenic potential of melanoma cells.
The impact of CXCR3/ligands in the
tumorigenesis of basal cell carcinomas
Blanche K.K. Lo; Mei Yu; David Zloty; Bryce Cowan;
Jerry Shapiro; Kevin J. McElwee
Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC
Basal cell carcinoma (BCC) is the most common malignancy
found in the Caucasian population. Recently, it has been
suggested that expression of CXCR3/ligands are associated with the progression of advanced-stage tumors,
such as malignant melanoma and ovarian carcinoma. Our
previous microarray analysis identified that selected CXC
chemokines were significantly upregulated in BCCs. We
hypothesized that CXC chemokines could be involved in
BCC development. In this study, real-time RT-PCR revealed
that chemokines CXCL9, 10, 11 and their receptor CXCR3
were significantly upregulated by 22.6-fold, 9.2-fold, 26.6fold, and 4.9-fold respectively in 17 BCC tissue samples as
compared to non-lesional skin epithelium. Double-labeling
immunohistochemistry revealed that CXCL10, CXCL11 and
CXCR3 colocalized with cytokeratin 17 (K17) in BCC keratinocytes; the expression of CXCR3 and its ligands was present in
the cells of the stromal region. In addition, the chemokines
and K17 were expressed in cultured human immortalized
HaCaT keratinocytes. In vitro functional assay of HaCaT cells
supplemented with CXCL11 peptides significantly increased
HaCaT cell proliferation and upregulated mRNA expression
of STAT1 and NFκB1. The expression of CXCR3 and its ligands in human BCC keratinocytes, and the keratinocyte cell
proliferation enhanced by CXCL11, suggest that CXCR3 and
its ligands may be important mediators for BCC growth via
autocrine and/or paracrine signaling. These chemokines may
be novel targets for the development of new treatments.
IDO may confer immune privilege
to basal cell carcinomas
Blanche K.K Lo1 Navkiran Sidhu1 David Zloty1 Reza B.
Jalili2 Aziz Ghahary1 Bryce Cowen1 Jerry Shapiro1 Kevin J.
McElwee1
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Department of Surgery, University of
British Columbia, Vancouver, BC
Basal cell carcinoma (BCC) is the most prevalent malignancy
found in the Caucasian population. It has been suggested
that immunoprotection may be involved in BCC tumorigenesis; however, the nature of putative immunoprotective
mechanisms has yet to be established. In this study, we
profiled the expression of genes associated with immune
privilege (IP) in BCCs by real-time RT-PCR using human
nodular BCC samples (n=10) as compared to non-lesional
skin epithelium control tissue (n=10). BCC samples exhibited
significant upregulation in 9 of 19 immunoregulatory genes
including IDO (1.96-fold). Immunohistochemistry (IHC) and
Western blot confirmed the IDO protein was present in relatively high concentrations in nodular BCCs. IDO was mainly
localized in the tumor nests while a weak, non-specific
staining was distributed in the stromal region of the BCC
biopsies. There was some immuno-labeling in the normal
skin biopsies, especially in hair follicle outer root sheath and
sebaceous glands. IDO proteins were present in the nonfollicular epithelium of both BCCs and control tissues. IDO in
BCCs had a 30kDa molecular weight which was smaller than
recombinant IDO (42kDa). In conclusion, the data suggest
BCCs may employ IP mechanisms to avoid targeting by the
host immune system. Of several differentially expressed IP
genes, IDO may be a key factor. The BCC cells synthesize
and release a truncated IDO protein. Further functional
assays of the BCC-derived IDO will be needed to determine
its immunosuppressive potency. The results may ultimately
shed light on the impact of IDO and other IP genes on BCC
growth.
Teledermatology as a means to
facilitate dermatological referral
Dave Ludwick; Charles Lortie; Christine Samoil - Schelstraete;
Jaggi Rao
University of Alberta Dermatology Centre, Edmonton, AB
Purpose: The purpose of the study was to determine if
Teledermatology, implemented in the context of an interdisciplinary team, can make the dermatology consultation
process easier while reducing wait times.
Methodology: A multidisciplinary teledermatology clinic
was created in a community with no practicing dermatologist, but with several family physicians belonging to a
Primary Care Network (PCN). Utilizing a secure, web-based,
store-and-forward teledermatology platform, an onsite primary care physician and nurse received twenty-eight dermatological consultation requests from nine PCN physicians. All
consultation requests were forwarded, with digital images of
the dermatological problem, to a University-based dermatologist working thirty kilometers away. Upon receiving the
teledermatologist’s impression and treatment suggestions,
subsequent patient care was implemented and follow-up
arranged. Patients were interviewed to understand their
experience. Referring physicians, the clinic physician and
nurse, as well as the teledermatologist were interviewed to
evaluate the advantages and drawbacks of the Teledermatology Clinic. Wait times, time intervals between appointments, and encounter durations were determined.
Results: Patients’ initial appointments occurred within one
week of referral. Necessary diagnostic procedures or treatment interventions were performed within one week of the
initial appointment. Convenience and minimized wait times
were common reasons patients expressed satisfaction with
the clinic. Referring practitioners were initially concerned
they would lose control of patients’ care. An easier referral
process and faster intakes met physician expectations. Reliable consult reports allowed referring physcians to maintain
control of care.
Conclusions: The asynchronous nature of store and forward Teledermatology improves timeliness of appointments because it avoids scheduling conflicts. Patients may
choose to derive a preliminary skin assessment and treatment plan via teledermatology rather than face-to-face
appointments with a specialist, as it has been shown to be
a more efficient and convenient. If necessary, patients may
then be triaged to visit a dermatologist’s office. In addition
to having their patients seen and treated faster, referring
physicians will refer patients to a teledermatology clinic to
mitigate any perceived legal risk that may arise if these cases
were managed without the direction of a board-certified
dermatologist.
A Canadian open-label trial of methyl
aminolevulinate (MAL) PDT for actinic
keratoses, superficial nonmelanoma skin
cancer: preliminary observations
Harvey Lui1, 3 Bernadette Policarpio1, 3 Jerry Tan2, 4
Sheetal Sapra5 Channy Muhn6, 7 Charles Lynde8, 9
Mariusz Sapijaszko10, 11
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. University of Western Ontario, London,
ON; 3. Vancouver Coastal Health Research Institute, Vancouver, BC; 4.
Windsor Clinical Research Inc, Windsor, ON; 5. Institute of Cosmetic
and Laser Surgery, Oakville, ON; 6. Department of Medicine, McMaster
University , Hamilton, ON; 7. Dermetics Centre for Advanced Skin Care
and Cosmetic Surgery, Burlington, ON; 8. Department of Medicine,
University of Toronto, Toronto, ON; 9. Lynderm Research, Markham,
ON; 10. Department of Medicine, Division of Dermatology, University
of Alberta, Edmonton, AB; 11. Western Canada Dermatology Institute,
Edmonton, AB
a15
Topical photodynamic therapy (PDT) has been accepted
as an important treatment option for superficial epithelial
carcinomas or their precursors. Methyl aminolevulinate
(MAL) in combination with red light-emitting diode (LED)
light has been approved in several international jurisdictions
for the treatment of superficial basal cell carcinoma (sBCC),
Bowen’s disease (BD) and actinic keratoses (AK). The aim of
this open-label multicenter study was to assess the efficacy
and safety of MAL-PDT for patients with either AKs and/or
histologically confirmed single or multiple primary sBCC
or BD. MAL cream (Metvix™, 160 mg/g) was applied for 3
hours, followed by illumination with a red LED system (peak
wavelength 630 ± 5 nm; Aktilite™ 128) for 7-10 minutes to
a fluence of 37 J/cm2. PDT was repeated after one week for
sBCC and BD. Lesions not showing complete response (CR)
were retreated at three months. Follow up visits were scheduled every 3 months. The Kaplan-Meier method was used to
estimate the proportion of lesions attaining CR at 6 months
by lesion type. 47 subjects (55% male with mean age 62
years) received treatment for 126 lesions between August
10, 2007 and October 8, 2008. 34 subjects with 63 lesions
(19 AKs, 36 sBCC, 8 Bowen’s disease) had at least 1 follow-up
evaluation by the time of the preliminary analysis. 32% of
these lesions underwent 2 PDT treatments. The 6-month CR
rate (95% CI) was 87% (67-98%) for AKs, 87% (69-97%) for
sBCC lesions, and 86% (54-99%) for BD lesions, respectively.
Temporary adverse effects included skin discomfort (79%)
and erythema (70%). Unsolicited adverse events reported
were wound discharge (1 subject) and purpura (1 subject).
Phosphodiesterase-5 inhibitors (PDE5I)
are useful for treating digital ischemia
and ulceration in secondary, but not
primary Raynaud’s phenomenon
Carrie B. Lynde1 Gordon Searles2
1. Faculty of Medicine, University of Toronto, Toronto, ON; 2. Dermatology & Cutaneous Sciences, University of Alberta, Edmonton, AB
Introduction: Raynaud’s phenomenon, either primary or
secondary, can cause digital vasospasm severe enough for
digital ischemia and ulceration. Calcium channel blockers
and intravenous prostacyclins are frequently ineffective
for patients. Vasomotor mediator modulation suggests a
potential benefit from PDE5Is in modulating the vasospasm
in Raynaud’s phenomena. We report the effectiveness of oral
tadalafil and sildenafil in patients with digital ischemia and
skin ulceration.
Methods: Retrospective review of patients in an officebased, university-affiliated medical dermatology practice
with Raynaud’s phenomenon treated with a PDE5I. Period
of review between January 1, 2005 and July 31, 2008. Main
outcome measured was more than 75% improvement in
patient symptoms, or complete healing of ulcerations following therapy.
Results: Nine patients with Raynaud’s phenomena were
treated with tadalafil (7 patients, 10 mg po twice weekly) or
sildenafil (2 patients, 50 mg po daily). Seven patients had
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digital ischemia secondary to systemic disease (systemic
sclerosis, 5; pulmonary vasculitis, 1; lupus vasculopathy,
1). Two patients had primary digital ischemia (primary
Raynaud’s, 1; chilblains, 1). Sixty-seven percent (6/9) of the
patients had digital ulceration (5 secondary, 1 primary).
Eighty-six percent (6/7) of patients with digital ischemia
secondary to a systemic disease achieved clinical outcome, while none of patients with primary digital ischemia
responded. Two of five ulceration patients with secondary
disease healed, whereas the one ulceration patient with
primary disease failed to heal. Mean follow-up from start of
drug administration was 1.2 years.
Three patients had adverse effects, necessitating one
withdrawal (anorexia, 1; headache, 1; vision disturbance, 1).
These occurred within one week of initiation of therapy.
Conclusions: In this retrospective case series, tadalafil and
sildenafil were effective, safe therapies for treatment of
digital ischemia and skin ulceration for patients with a systemic disease, but not for patients with primary disease. Our
experience demonstrates that tadalafil and sildenafil also
have a role in dermatology therapy.
Acknowledgements: Dr. Iren Kossintseva for her preliminary research.
Cutaneous leishmaniasis in Canadian
soldiers returning from Afghanistan
Jillian A. Macdonald1 Abigail B. Gradinger1
Melanie D. Pratt1, 2
1. University of Ottawa, Ottawa, ON; 2. The Ottawa Hospital, Ottawa, ON
Introduction: Leishmaniasis is a widespread vector-borne
parasitic infection involving the skin and mucous membranes. It can be classified geographically into New World
and Old. As a result of military personnel returning from
operations in these endemic areas manifestations of this
disease are being seen with increased frequency among
Canadian dermatology practices.
Objective: We sought to raise awareness of the varied clinical manifestations and diagnostic difficulties associated with
this uncommon and newly relevant disease in the Canadian
military population.
Methods: We performed a retrospective chart review on all
suspected cases of leishmaniasis presenting to either the
Infectious Disease clinic at the Ottawa Hospital or the senior
author’s Dermatology practice from June to December 2007.
Results: Of the twelve suspected cases the diagnosis was
confirmed in eight patients. One case proved to be dermatofibroma. In the three remaining cases, tissue biopsy was
non-confirmatory in two patients (tissue cultures and special
staining also negative), and the third declined investigation.
All lesions were cutaneous and occurred on the face and
extremities. The number of lesions ranged from one to five,
the morphology of which included plaques, papulonodular
lesions, and painless ulcerations. The only reported systemic
complaints were mild myalgias in one patient. Treatment
strategies included heat, cryotherapy, surgical excision,
fluconazole, miltefosine, and sodium stibogluconate. Spontaneous resolution occurred in a few lesions.
Discussion: The clinical manifestations of leishmaniasis seen
in the Canadian soldiers mirror the most common presentation of the disease in the Old World. The varied presentation
necessitates a wide differential diagnosis including cutaneous malignancies, inflammatory dermatoses, sarcoidosis,
and other infections. Diagnosis is commonly made on tissue
biopsy, with parasites visualized in approximately 70% of
cases. Tissue culture can be used to identify the species. Old
World leishmaniasis typically resolves spontaneously with
scarring. Indications for treatment include: chronic lesions,
cosmetically unacceptable lesions, large or multiple lesions,
mucosal disease, nodular lymphangitis, lesions in immunosuppressed patients and lesions over joints. Pentavalent
antimony is the first line therapy and can be administered
intravenously or intralesionally, however many alternatives
are available.
Hidradenitis suppurativa
Lynette J. Margesson
Dartmouth Medical School, Manchester, NH, USA
Hidradenitis suppurativa is a chronic, inflammatory, recurrent, debilitating, follicular skin disease which usually
presents with painful deep-seated inflamed lesions in the
apocrine-bearing skin of the body, most commonly the
axillary, inguinal and anogenital regions (2nd International
Conference on Hidradenitis Suppurativa March 5, 2009, San
Francisco, CA USA).
It is a common problem that significantly affects the lives
of patients. It is notoriously difficult to treat. The recurrent
crops of inflammatory acneiform lesions in inverse areas
are often mistaken for “boils” and treated as incorrectly as
infections. The lesions initially are transient and gradually
become more intransigent and lead to significant scarring
and disability.
This condition is not uncommon, affects as many as 1 in 25
of the general population and is 3-4 times more common in
women than men.
The importance of this condition is that it is too often
unrecognized and mismanaged by the medical community.
The patients are significantly impacted with painful recurrent debilitating lesions. They become discouraged by the
inadequacy of medical help, which is due in turn to a lack of
education in the medical community. The proper recognition and management of hidradenitis suppurativa is rarely
taught. It is an orphan disease, unclaimed and unloved. The
results are regrettable because the psychological impact on
patients is substantial, with major social personal and occupational problems. These patients are usually left to deal on
their own with scars, chronic draining malodorous fistulae,
depression and withdrawal from social interaction.
The etiology and pathogenesis is still debated. There is
apparently a defect in the follicular infundibulum, with
internal differentiation resulting in obstruction and rupture
with subsequent inflammation. Involvement of nearby apocrine glands is secondary. The inflammatory response results
from a foreign body reaction and lesions often heal with
subcutaneous fistulae, sinus formation and scarring/fibrosis.
Diagnostic criteria are:
A. Typical painful dermal nodules, abscesses, fistulae,
hypertrophic fistular scars
B. Typical localization axilla, groin, under breasts, buttocks
and perineum
C. Relapse with chronic recurrent lesions for more than 6
months.
This condition affects patients starting usually in the early
twenties but as early as puberty and can last into the fifties
or sixties but usually settles at menopause. Predisposing factors are genetic, obesity and hormones (still controversial).
This presentation will be an overview of the clinical presentations, diagnosis and management of this condition.
Management is based on Hurley’s clinical staging.
Hurley’s stage I - Abscess formation, single or multiple, without sinus tracts and cicatrisation. Managed by drug therapy.
Hurley’s stage II - Recurrent abscess with sinus tracts and
cicatrisation. Single and multiple widely separated lesions
managed with drug therapy and limited surgery.
Hurley’s stage III - Diffuse or near diffuse involvement or
multiple interconnecting tracts and abscesses across an
entire area. Treatment is mainly surgical.
Trends of nonmelanoma skin cancers from
1988 through 2007 in Alberta, Canada
Andrei I. Metelitsa1 Gordon Jung1 Douglas C. Dover2
Thomas G. Salopek1
1. Division of Dermatology and Cutaneous Sciences, University of
Alberta, Edmonton, AB; 2. Alberta Health and Wellness, Public Health
Division, Surveillance and Environmental Health, Edmonton, AB
Introduction: The highly morbid but potentially preventable nonmelanoma skin cancers (NMSC), primarily basal
and squamous cell carcinomas represent the most common
malignancy affecting Caucasian populations. Despite the
increasing availability of sun awareness education materials
and informational resources, the incidence of NMSC continues to increase globally in recent decades. The objective
of this study was to determine the trends of incidence of
NMSCs in Alberta and compare the results to available epidemiologic evidence from other Canadian provinces including British Columbia, Manitoba and New Brunswick.
Methods: A retrospective analysis of nearly 100,000 patients
diagnosed with NMSC from 1988 to 2007 inclusive was conducted with data retrieved from the Alberta Cancer Registry.
Only patients who are residents of Alberta were included in
the study. Information analyzed included the person’s age at
diagnosis, date of diagnosis, gender, and geographical location of residence in Alberta. Specific characteristics of the
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individual’s malignancy, including its anatomical location,
histological type, size, and thickness were also obtained.
Results and Conclusions: The analysis of the trends of
NMSC incidence rates in Alberta revealed higher incidence
rates in men than in women. Overall, there was an initial
rapid rise in the incidence rates from 1988 to mid 1990’s
with subsequent stabilization starting in 2000. Furthermore,
over 30% of the squamous cell carcinomas in our study were
found to be in-situ. These results differ from the previously
reported incidence rates in other Canadian provinces which
have all shown consistent increases in incidence of NMSC.
Our data suggests that the incidence rate has plateaued in
Alberta and that many of the cancers are potentially curable.
Nitric oxide: tool, weapon or both?
CC Miller
Faculty of Medicine, Division of Respiratory Care and Affiliated
with Division of Infectious Diseases, University of British Columbia,
Vancouver, BC
Known for decades as an air pollutant, nitric oxide (NO) has
recently been discovered as a vital endogenous direct acting and messenger molecule. NO has been shown to play a
critical role in various bodily functions, including the vasodilatation of smooth muscle, neurotransmission, regulation
of wound healing and immune responses to infection such
as bactericidal action directed toward various organisms. NO
is a lipophilic signaling molecule with a small stokes radius
that enables it to readily cross the plasma membrane into
the cytosol. It is hypothesized that the cellular messenger
regulatory (tool) and antimicrobial properties of this molecule (weapon), delivered in an exogenous gaseous form,
might easily enter the wound microorganism milieu and
be useful in optimizing the curing various wound diseases
with specific actions directed at reducing microbial burden,
reducing biofilms and improving endogenous debridement.
In summary, our group and others have found that gaseous NO acts as a potent non-specific microbicidal weapon
reducing bacterial load and viral infectivity. We have also
discovered that by mimicking the innate immune system’s
ability to produce high levels of NO, we can specifically
deliver the effective gNO antimicrobial dose exogenously
against wide range of bacterial, viral and parasitic infections
while acting as a tool to potentially ameliorate the negative
pathogenic inflammatory sequelae. Specifically, we have
shown that gaseous nitric oxide (gNO) is an effective and
rapidly acting antimicrobial agent against a broad range of
microbes at high supraphysiologic concentrations. We have
identified the mechanism of action by which NO is lethal
to bacteria but benign to host cells. gNO is currently being
evaluated for use in wounds associated with vascular disease, leishmaniasis, athlete’s foot and non-healing wounds
with methicillin resistant Stapyloccoccus aureus (MRSA).
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Pretibial angioplasia: a novel entity
encompassing the clinical features
of necrobiosis lipoidica and the
histopathology of venous insufficiency
Nisha Mistry1 H Chih-ho Hong1 Richard I. Crawford1, 2
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Department of Pathology and Laboratory
Medicine, University of British Columbia, Vancouver, BC
Background: Necrobiosis lipoidica is a condition of
unknown pathogenesis, which presents clinically as waxy
yellow-brown plaques surrounded by a raised violaceous
rim, most commonly occurring on the shins. Histopathology shows a palisading granulomatous inflammation with a
layered appearance, along with necrobiotic collagen. Venous
insufficiency occurs in a similar distribution, generally involving the legs bilaterally; however it has distinct pathologic
features. Dilated papillary dermal small blood vessels, hemosiderin and fibrosis are seen on pathology in these patients.
We present here a series of eight patients, who clinically
were suspected to have necrobiosis lipoidica, however on
pathology showed features of venous insufficiency.
Methods: Between 1997 and 2008 eight patients were identified by dermatopathology at St. Paul’s Hospital, Vancouver
to have had a clinical diagnosis of necrobiosis lipoidica and
histopathologic features of venous insufficiency. The charts
and pathology reports of these patients were reviewed.
Clinical information was extracted on demographic data,
disease states, morphologic and histopathologic features.
Results: The patient ages at time of biopsy ranged from
39 to 73 years. Only one of the eight patients was female.
Members of the group did have clinical diagnoses of diabetes, renal failure, venous disease or arterial disease. Most
patients had lesions on both anterior shins. The clinical
diagnosis was generally deemed to be necrobiosis lipoidica;
other differentials included morphea and Kaposi’s sarcoma;
in no cases did the lesions have a clinical resemblance to
venous insufficiency. All patients had features on pathology of venous insufficiency and no features of necrobiosis
lipoidica.
Conclusion: We put forth that this combination of clinical
features of necrobiosis lipoidica and histopathological
features of venous insufficiency represents a novel entity for
which we propose the name pretibial angioplasia.
Topical tretinoin treatment for confluent
and reticulate papillomatosis
Hyun Su Park; Sang Hoon Park; Un Ha Lee; Sang Jai Jang
Department of Dermatology, Sanggye Paik Hospital, Inje University
College of Medicine, Seoul, , Korea, Republic of (South Korea)
Introduction: Confluent and reticulate papillomatosis(CRP)
is a rare cutaneous disorder characterized by persistent,
scaling brown papules, patches, and plaques located on the
trunk, neck, axillae, and shoulders. It affects mostly adolescents or young adults and the cause of this disease is poorly
understood. Many different treatments with variable success
have been attempted and oral minocycline treatment is
highly effective in most patients with CRP. There was a report
of three cases of CRP responding to topical tretinoin, on the
contrary, other reports did not show benefit with topical
tretinoin treatment. And there have been no clinical studies
on the efficacy of topical tretinoin treatment for CRP in the
English literature.
Objectives: The purpose of this study was to evaluate the
efficacy and safety of topical tretinoin treatment for CRP.
Method: Six patients with CRP were treated with once
daily application of tretinoin 0.025% cream. The effectiveness of the treatment, recurrence, and adverse effects were
assessed. Assessments were conducted by two dermatologists based on clinical observation. Response to treatment
was evaluated at 2- or 3-week intervals according to clearance rates. The clearance rate was defined as the percentage of the cleared area relative to the whole of CRP lesion.
At every visit, all patients were asked about any symptoms
and difficulties associated with topical tretinoin treatment
to assess adverse effects. Follow-up was performed at
least 3 months after the cessation of the treatment. During
the posttreatment follow-up period, the information was
obtained by telephone if the patient could not return.
Results: Three men and three women were treated. The
mean age of the patients was 15.7 years (range, 11-18) and
the mean age at onset of the skin lesion was 12.8 years
(range, 3-18). The duration of disease varied from 3 months
to 8 years. Five of the six patients showed excellent response
to the treatment. They achieved 50% clearance or more
within 4 weeks and complete remission within 12 weeks.
Follow-up was performed 3-42 months after the cessation of
the treatment and none of the five patients recurred. One of
the six patients had improved slowly with topical tretinoin
treatment and achieved about 50% clearance at 8 weeks
from the start of the treatment. The patient stopped the
treatment voluntarily at 8 weeks and recurred. One of the six
patients complained of moderate erythema and irritation on
the treated lesion. Generally, adverse effects were minimal
to mild and were not associated with disabilities that interfered with the patients’ normal activities.
Limitation: This study included a small size and was neither
controlled nor double blinded.
Conclusion: We think topical tretinoin is an effective and
safe treatment modality for CRP and this treatment can be
an alternative modality to systemic treatment. The results
of this study can support that the etiology of CRP includes a
disorder of keratinization.
Laser speckle contrast: a novel in vivo
technique for measuring skin topography
Bernardita Policarpio1 Lioudmila Tchvialeva1 David I.
McLean1 Harvey Lui1 Haishan Zeng2 Tim K. Lee1
1. Vancouver Coastal Health Research Institute and University of British
Columbia, Vancouver, BC; 2. Cancer Control Research and Cancer
Imaging Departments, BC Cancer Agency, Vancouver, BC
Skin topography is of great interest for many dermatologists and skin scientists. We are developing a novel method
for in-vivo skin roughness measurement in about 5 msec
by analysing laser speckles. The purpose of this study is to
construct the instrument and evaluate its effectiveness.
A laser speckle imaging prototype was designed by
employing an open geometry scheme and two grayscale
CCD cameras without imaging lenses. Co- and cross- polarized speckle patterns were obtained from a blue diode laser
and then used to derive the contrast and the surface roughness (root-mean-square roughness) from the registered patterns. To validate the device, we used it to measure a group
of volunteers. The same skin location was measured thrice
and the average skin roughness was then computed.
We recruited 40 volunteers. The first group was 31 patients
who attended a skin clinic in the Skin Care Centre, Vancouver
General Hospital. We acquired the normal skin roughness of
the corresponding sites that required medical attention. The
second group was nine volunteers. The same spot of their
right dorsal hand and right volar forearm was measured.
When we compared all our measurements on various body
sites with the literature values, a reasonable correlation was
found (Pearson correlation coefficient = 0.64 and Spearman
correlation coefficient = 0.67). For the subgroup of 9, the
mean roughness measurement of the dorsal hand was 20±4
um while that of the volar forearm was 16±5 um. Results
showed a significant increase in skin roughness on the
dorsal hand as compared to the volar forearm (p=0.038). We
have demonstrated that our roughness measurements were
in agreement with published values; furthermore this instrument can detect a significant difference in the roughness
measurements between the dorsal hand and volar forearm.
The learning objective of the study is to describe the novel
in-vivo technique and to report the initial clinical test results.
Propranolol in the treatment of infantile
hemangioma: clinical observations
in 20 consecutive patients from
a vascular anomalies clinic
Julie Powell; Rita Sammour; Afshin Hatami;
Catherine C. McCuaig
CHU Sainte-Justine, Université de Montréal, Montreal, QC
Background: Problematic infantile hemangiomas (IH)
require treatment during the proliferative phase. There are
no rigorous evidence-based studies to guide therapy and
current medical therapeutic modalities have shown variable
efficacy with multiple potential side effects. Propranolol, a
a19
non selective beta-blocker has recently been reported efficient to control the growth of IH.
Objective: We sought to share our experience using propranolol for problematic IH and to evaluate the efficacy and
possible side effects of this new treatment modality.
Methods: A retrospective chart review analysis was performed in children treated with propranolol in our dermatology clinic between February and December 2008. 20
children with problematic IH received propranolol as an oral
solution on an outpatient basis with progressively increasing
dosage and close monitoring.
Results: Change in color and consistency was noted in all
IH in the first days of treatment. IH continued to improve
in color and thickness over the next weeks of treatment.
Regression of functional impairement and ulceration was
also noted in most patients. Propranolol was well tolerated
in the majority of patients.
Conclusion: Propranolol showed efficacy in controlling
the proliferative phase of problematic IH. It was overall well
tolerated. Potential explanations for its therapeutic effect
include: triggering apoptosis in endothelial cells, decreasing
expression of VEGF and HIF-1 a genes, inhibiting endothelial
cell proliferation and vasoconstriction. We believe that propranolol could be a first-line treatment for problematic IH.
Case of vulvar necrosis secondary to
antiphospholipid antibody (APA) syndrome
Kerri S. Purdy; Laura Finlayson
Dalhousie University, Halifax, NS
Antiphospholipid antibody syndrome is a disorder of hypercoagulation involving large or small vessels, often seen in
the context of systemic lupus erythematosus (SLE). Cutaneous manifestations are the presenting feature in a large
percentage of cases. We present a case of extensive skin
necrosis in the vulvar area.
AO, a 39 yo female with a history of SLE presented with a
one month history of vulvar “fullness”. On admission, a small
necrotic area in the vulva was noted with associated edema
extending to medial thigh. There was rapid progression of
the involved area over 24 hours. INR was 6.6 so warfarin was
held then restarted once INR normalized. She was seen by
multiple consultants and treated with antibiotics. The affected area continued to extend, involving the entire perineum
and lower abdomen. Histopathology revealed fibrin thrombi
within vessels. History revealed a prior episode of catastrophic APA syndrome with extensive skin necrosis in 2003.
The differential diagnosis included: coumadin necrosis, APA
syndrome, vasculitis, necrotizing infection or some combination of these. The patient was unable to tolerate anticoagulation due to multiple bleeding complications. Necrotic tissue
was eventually debrided, however, the patient unfortunately
passed away post-operatively.
This was a complicated case given recent modifications in
warfarin therapy and history of SLE. Initial consideration was
a20
given to a diagnosis of warfarin necrosis versus skin necrosis
associated with APA syndrome. It proved to be a diagnostic dilemma at times as these two entities share common
clinical and histopathologic features. Based on the clinical
history, we felt that this was more in keeping with APA
syndrome skin necrosis. It is uncommon for a patient to have
more than one episode of catastrophic skin necrosis secondary to APA syndrome, particularly when they are on longterm anticoagulation. The case also highlights the need for
early detection and prompt treatment of APA syndrome in
patients to attempt to prevent progression of skin necrosis.
In this particular case, definitive management was impossible due to significant bleeding complications.
Formulation and topical application
of a thermoreversible emulgel for the
management of hypertrophic scarring
Elham Rahmani-N; Reza Jalili; Aziz Ghahary
BC Professional Fire Fighters’ Burn & Wound Healing Research Lab.
Division of Plastic Surgery, University of British Columbia, Vancouver, BC
Introduction: Hypertrophic scarring is an important
clinical problem that lacks definitive treatment and results
in disfiguring and functional impairment. It was shown by
our group that stratifin stimulates the collagenase (MMP-1)
expression in dermal fibroblasts in vitro. We have also shown
that topical application of stratifin in a hydrogel formulation
reduces hypertrophic scarring in rabbit ear fibrotic model
in twice daily regimen. The goal of this study was to modify
the hydrogel formulation in order to enhance the dermal
penetration and also reduce the frequency of application.
To achieve this objective, we formulated an emulgel using a
thermoreversible emulsifier and fatty amines. We tested the
therapeutic efficacy of this formulation in vivo on the established fibrotic rabbit model.
Methods: Emulgel containing 0.01% stratifin was prepared
and applied once daily on 8 mm circular full thickness
wounds created on ventral side of New Zealand white rabbit
ears. Thereafter, the quality of wound healing and hypertrophic scar formation was evaluated.
Results: The thermoreversible emulgel formulation was
capable to create a protective film on the surface of wound,
moisturizing the wound while releasing the medication in
a sustained manner. The treatment was applied once daily
instead of twice daily. Wound assessments showed a significantly reduced scar hypertrophy in stratifin-treated wounds
compared to controls.
Discussion: In this clinically relevant rabbit model, wounds
treated with stratifin-containing emulgel demonstrated a
significant decrease in scar hypertrophy. This observation
may be the result of increased breakdown of extracellular
matrix components such as type-I collagen. The emulgel
solidified on wound bed and made a protective film at body
temperature due to thermoreversible characteristics. As a
result of using fatty amines in this formulation, the penetration of stratifin was enhanced, therefore, once daily application efficiently reduced scarring. The findings of this study
will ultimately be helpful in development of novel preventive strategies for hypertrophic scarring which are cost
effective and feasible for all burn patients and particularly
for children who are more susceptible to multiple painful
steroid injections or tight pressure garments. The learning
objectives in this study were to be familiar with development and application of topical anti-fibrogenic and wound
healing formulations and also to evaluate their therapeutic
effect using in vitro and in vivo models.
Exogenous gaseous nitric oxide effects on the
modulation of extra cellular matrix genes in
human dermal fibroblast and proliferation
and viability of human lymphocytes
Alireza Moeen Rezakhanlou1 Chris Miller2 Bevin McMullin3
Abdi Ghaffari1 Aziz Ghahary1
1. Department of Surgery, Wound Healing Research Lab, Vancouver
Coastal Health at Vancouver General Hospital, University of British
Columbia, Vancouver, BC; 2. Division of Infectious Diseases, Department
of Medicine, Vancouver Coastal Health at Vancouver General Hospital,
University of British Columbia, Vancouver, BC; 3. Respiratory Services,
Vancouver Coastal Health, Vancouver Coastal Health at Vancouver
General Hospital, University of British Columbia, Vancouver, BC
Nitric oxide (NO) molecule, synthesized by nitric oxide
synthase, is produced by various mammalian cell types.
NO plays a significant role in inflammation, infection and
wound healing processes. Gaseous nitric oxide (gNO), which
is produced by a chemical reaction, has several potential
clinical applications as an anti-microbial and wound healing
promoting agent. In this study, we investigated the role of
various concentration of gNO in expression of human extracellular matrix (ECM) protein genes in human fibroblasts by
microarray technicque. We also tested the effect of gNO on
the proliferation of human lymphocytes. The results showed
that, gNO induces the expression of several ECM genes such
as collagen type I alpha 1, collagen type V alpha 3, collagen
type VI alpha 1 and integrin and reduces matrix metalloproteinase 1 (MMP-1). This study further showed that gNO
inhibits lymphocytes proliferation without toxic effect. Taken
together, our findings support the potential application of
gNO as a wound healing promoting factor without any side
effect on local inflammatory cells.
Daily oral finasteride 5 mg improves
hidradenitis suppurativa in women.
Gordon E. Searles
University of Alberta, Edmonton, AB
Introduction: Hidradenitis suppurativa (HS) is a distressing
chronic disorder of apocrine glands leading to large furuncles in axillary, inframammary, and inguinal spaces. Women
are the most commonly afflicted. No satisfactory treatment
is currently available. Altered systemic and localized androgen activity appears to be one of the causes for HS. This
retrospective chart audit examined the effect of finasteride 5
mg daily on the incidence of HS.
Methods: Retrospective audit of all patients with HS in a
university-affiliated, community-based dermatology practice
treated with finasteride 5 mg daily. No men were considered for this audit. Demographic information, comorbid
conditions, presence of hyperandrogen states, and clinical
outcomes were recorded.
Results: Forty-one women were diagnosed with HS
between January 2006 and December 2008. The median
age was 38 years (range: 16 - 62 years). Median duration of
HS prior to treatment was 4 years (range: 1 - 30 years). 76%
had axillary; 59% had inframammary; and 83% had inguinal
involvement. Past treatments included oral antibiotics (54%),
oral contraception or peripheral androgen blockade (39%),
systemic retinoids (17%), and surgical excision (44%). All
patients audited had failed these treatments. 8/41 (20%) had
a demonstrated endocrine hyperandrogen state on serology
(Polycystic ovarian sydrome: 7; adrenal hyperplasia: 1).
33/42 (80%) of subjects reported subjective and objective (> 75%) improvement in the frequency and severity of
episodes. 24/42 (59%) remained asymptomatic for 8 to 23
months. Median time to clearance was 4 months (range:
2 to 10 months). Side effects were infrequent and mild,
consisting of menstrual irregularities (3/41; 7%) and breast
tenderness (5/41; 12%), with no withdrawals. Subjects who
failed to respond had extensive scarring or multiple incision & drainage procedures, which ultimately responded to
surgical extirpation.
Conclusions: While there are limitations on a single-practice
clinical audit, this study supports the clinical utility and
safety of finasteride 5 mg daily in the management of HS in
women. Best predictor of good clinical response is seen in
lesions that are not extensively scarred by previous drainage
procedures.
Cutaneous disease burden and
demographic characteristics of an urban
Canadian hiv dermatology practice
Jonathan L. Shapero; Jasmine T. Garrett; Gillian de Gannes
University of British Columbia, Department of Dermatology, Vancouver, BC
Background: The introduction of highly active antiretroviral
agents (HAART), and subsequent advancement of newer
agents and combination therapy has changed the frequency
of cutaneous disease in individuals carrying HIV.
Objective: The purpose of our study was to assess demographic characteristics, severity of immunosuppression,
and frequency of dermatologic disorders presenting to a
Canadian specialized HIV dermatology practice.
Methods: A cross sectional study was performed of 183
consecutive outpatient and inpatient consultations to a
single HIV dermatology practice between January 2007 to
December 2008.
Results: The average age of patients was 45 years. 163 (88%)
of the patients were male. The average CD4 count was 338
cells per microlitre (cpm). CD4 counts were 100 cpm or less
a21
in 18 patients. 46 of the patients seen were not on antiretroviral therapy.
Development and validation of a scale for acne
scar severity (SCAR-S) of the face and trunk
Multiple skin diseases were diagnosed in 120 patients
(66%). Verrucae was the most common diagnosis, seen in 29
patients. The second most common diagnosis was dermatophyte infection, seen in 27 patients. Other diagnoses were
atopic/eczematous dermatitis (21), seborrheic dermatitis
(14), folliculitis (8), rosacea (7) and psoriasis (6). There were 8
cases of Kaposi’s sarcoma, 5 of eosinophilic folliculitis, and a
single instance of oral hairy leukoplakia.
Jerry K.L. Tan1 Jing Tang1 Karen Fung1 Aditya K. Gupta1
D. Richard Thomas1 Sheetal Sapra1 Charles Lynde1 Yves
Poulin1 Wayne Gulliver1 Rolf J. Sebaldt1
Conclusions: Cutaneous infections were the most common diagnosis in this cross section. Classically described
HIV dermatoses occurred in a low frequency in this patient
group, which may reflect more successful management in
the modern antiretroviral era.
With a clinical suspicion of bullous
pemphigoid, is a skin biopsy for direct
immunofluorescence more likely to be
positive from lesional or perilesional skin?
Chris Sladden; Richard I. Crawford
UBC Department of Dermatology, Vancouver, BC
A skin biopsy for direct immunofluorescence (DIF) may show
differing sensitivity depending on whether it is taken from
lesional or perilesional skin, and this difference depends
upon the specific disease being biopsied. As of yet, there
is no scientific information to indicate whether lesional or
perilesional biopsies are more sensitive in the DIF diagnosis
of bullous pemphigoid (BP). The main objective of this study
was to assess the likelihood of a biopsy being diagnostic
when taken from lesional versus perilesional skin when
there is a clinical suspicion of BP.
Methods: This retrospective study reviewed all 1423 DIF
biopsies processed at St. Paul’s Hospital, Vancouver from the
period 1998 to 2008, including 260 specimens with a clinical
suspicion of BP. Each BP specimen was designated as either
lesional, perilesional or indeterminate. The biopsy results
were recorded as diagnostic of bullous pemphigoid, nondiagnostic, non-specific or supportive of another diagnosis.
Results: Of the 56 lesional biopsies, 28 (50%) showed a
positive result, while 10 of 45 (22%) perilesional biopsies and
19 of 159 (12%) indeterminate biopsies showed a positive
result.
Discussion: With a clinical suspicion of BP there was more
likelihood of a positive result if the biopsy was taken from
clinically or histologically lesional skin.
We would suggest that the highest yield on DIF biopsies for
BP would come from an intact lesional sample, or alternatively from a sample close enough to the lesion to contain
histologically identifiable lesional skin.
1. University of Western Ontario and Windsor Clinical Research Inc.,
Windsor, ON; 2. University of Western Ontario and Windsor Clinical
Research Inc., Windsor, ON; 3. Department of Mathematics & Statistics,
University of Windsor, Windsor, ON; 4. Division of Dermatology,
Department of Medicine, Sunnybrook Health Sciences Centre and
the University of Toronto, Toronto, Canada, and Mediprobe Research
Inc, London, ON; 5. Department of Dermatology and Skin Science,
University of British Columbia, Vancouver, BC; 6. Institute of Cosmetic
and Laser Surgery, Oakville, ON; 7. University of Toronto and Lynderm
Research Inc, Markham, ON; 8. Laval University and Centre de
Recherche Dermatologique du Quebec metropolitain, Quebec City,
QC; 9. Memorial University, St. John’s, Newfoundland; 10. McMaster
University and Clinforma Data Systems & Project Management, Fig.P
Software Incorporated, Hamilton, ON
Background: Although scarring is considered to be an
important component of overall acne severity, there are no
global scales for evaluation of acne scarring of the face and
trunk.
Objective: Our objective was to develop a global scale for
acne scar severity inclusive of the trunk and the face.
Methods: A 6-category global severity scale (SCAR-S) was
developed for assessment of acne scarring at each of the
face, chest and back. We evaluated SCAR-S against acne
severity and patient-reported scar severity.
Results: Of the 973 acne subjects in this study, 73% of
patients reported the presence of acne scars. Self-assessment of acne scarring was significantly associated with facial
SCAR-S and overall SCAR-S scores (p<.001) with R values
of 0.31 and 0.30, respectively. Acne scarring was observed
at the face in 87%, the back in 51% and the chest in 38%.
Clinically relevant scarring (SCAR-S > mild) at each of these
regions was 55%, 24%, and 14%, respectively. Acne severity significantly correlated with SCAR-S for all three regions
(Spearman’s correlation p<.001): back (r=0.612), chest
(r=0.548), and face (r=0.514). Duration of acne correlated
with both patient reported severity of acne scarring (r=
0.244) and overall SCAR-S scores (r=0.152). Clinically relevant
scarring increased with acne duration and peaked at 2-3
years.
Conclusion: SCAR-S is a practical, validated, global system
for acne scar evaluation and is clinically relevant in overall
severity grading of acne.
Deficiencies in treatment decision
support of psoriasis patients: Insufficient
information, inadequate decisional
skills and scarcity of physician time
Jerry Tan1 Dawn Stacey1 Benjamin Barankin2 Robert
Bissonnette3 Wayne Gulliver4 Christine Jackson5 Harvey
Lui6 Neil Shear7
1. University of Ottawa, Ottawa, ON; 2. The Dermatology Centre,
Toronto, ON; 3. Innovaderm Research Inc., Montreal, QC; 4. NewLab
a22
Research, St. John’s, NL; 5. Canadian Skin Patient Alliance, Ottawa, ON;
6. University of British Columbia, Dept Dermatology, Vancouver, BC; 7.
University of Toronto, Toronto, ON
Optimal treatment decisions require consideration of clinical
factors, scientific evidence, and patient preferences. We
sought to identify the decision-making needs of psoriasis
patients.
Patients with psoriasis from a Canadian consumer panel
were invited to participate in an online survey comprising 26
items on demographics, psoriasis history, role in treatment
decisions, decisional conflict, outcomes of treatment and
treatment awareness. After receiving ethics approval, the
survey was conducted between March-April 2008.
Of the 248 respondents (35% response rate) - mean age
was 52 years, 54% were female and 26% had BSA ≥ 3%.
Most were aware of topical (92%) and phototherapy (62%)
options, but few were aware of oral (26%) or injectable/
biologic (16%) treatments. Sixty-two percent had shared in
decision-making on previous psoriasis treatments with their
physicians. Their most frequently identified decision support
needs were: information on options, clarification of values,
access to physicians for discussion, and inadequacy in treatment decision-making skills. The following physician-specific
factors were perceived by patients to hinder decision
support: lack of physician time to stay abreast of treatment
information, lack of time to provide counseling, and inability
of physicians to access appropriate treatments.
Compared to those with milder psoriasis (n= 181), those
with BSA > 3% (n= 67) were more aware of oral (34% versus
23%; P = 0.08), injectable (28% versus 12%; P= 0.002) and
phototherapy (75% versus 59%; P= 0.02) options. They more
frequently indicated that the following were important in
supporting decision-making: the skill or ability to make
treatment decisions; and having information about what
other patients decide. A greater proportion of them preferred video and DVD as informational formats (29% versus
16%; P = 0.031).
Patient involvement in psoriasis treatment decision-making
is hindered by insufficient information, inadequate decisional skills and scarcity of physician time. More severely affected
patients require greater decision support.
Axillary granular parakeratosis: a
case report & literature review
Patricia Ting; Loretta Fiorillo; Ken Alanen
University of Alberta, Edmonton, AB
Introduction: We present a 62-year-old Caucasian lady
employed as an operating room nurse. This patient presented with an 8-week history of a progressive pruritic and
burning eruption in both axillae characterized by brown
keratotic papules in linear distribution. She did have a
history of contact dermatitis to carba chemicals (dithiocarbamates, diphenylguanidine), mercapto compounds,
thiomerosal, and thiurams, which she was avoiding. She
had used an underarm deodorant for several decades,
however, could not identify any new skin products she had
applied to the affected area in recent months. Past medical
history included non-insulin dependent type 2 diabetes,
hypothyroidism, hypercholesterolemia and depression,
all of which were controlled with medications. Prior to our
consultation, previous treatments with topical antibacterial
and antifungal creams as well as an oral antifungal were all
ineffective.
Methods: Clinical examination revealed multiple brown
hyperkeratotic papules coalescent into vegetative linear
plaques in both axillae. There was also some mild fissuring
in the axillary creases, but no discharge or foul odor. The
remainder of the skin exam was unremarkable. We performed a 4 mm punch biopsy of the axillary eruption.
Results: Histopathological analysis demonstrated a thickened stratum corneum with confluent parakeratosis and
conspicuous small basaloid granules. There was no evidence
of dysplasia of the keratinocytes. Periodic Acid-Schiff (PAS)
was negative for yeast and fungal elements.
Conclusion: Axillary granular parakeratosis is a rare disorder of keratinization condition of unknown etiology. Other
intertriginous sites such as the groin, inter/sub mammary,
abdomen and lower truncal areas are less frequently
involved. The clinical and histological features, differential
diagnoses, and proposed pathophysiological mechanisms
for granular parakeratosis are reviewed.
The role of GW bodies in cutaneous
squamous cell carcinomas
Jennifer M. Tran; Joanna J. Moser; Andrea K. Bruecks;
Marvin J. Fritzler; P. Régine Mydlarski
Department of Medicine, University of Calgary, Calgary, AB
Background: In 2002, unique cytoplasmic compartments
were identified and termed GW bodies (GWBs), also known
as processing bodies (P-bodies). GWBs were named after
the GW182 protein, an mRNA-binding protein that resides
within these macromolecular foci. By storing specific subsets
of mRNAs and microRNAs (miRNAs), degrading mRNAs,
participating in RNA interference (RNAi) and controlling the
events of cell cycle and cell proliferation, GWBs may serve
as important regulatory sites for normal, inflammatory and
malignant skin disease. Herein, we investigate the role of
GWBs in the most common form of cancer worldwide, nonmelanoma skin cancer.
Objectives: 1) To characterize the GWBs in normal human
skin and cutaneous squamous cell carcinoma (SCC) tissues;
and 2) to study the proteomic components of GWBs within
normal human keratinocyte (NHK) and SCC cell lines.
Materials and Methods: To investigate the presence and
distribution patterns of GWBs in normal human skin and
cutaneous SCCs, paraffin-embedded skin sections were
treated with an antigen retrieval method and stained with
mouse monoclonal antibodies to the recombinant GW182
protein. Using indirect immunofluorescence (IIF) techniques,
the GWBs of NHK and SCC cell lines were quantified with
a23
ImageJ software. To determine whether the GWBs within
these cell lines contain proteins involved in mRNA degradation and RNAi, colocalization studies were performed using
antibodies to Ge-1 (also known as RCD8 or Hedls), Dcp1a,
Xrn1, LSm4, Ago2 and dicer. The protein expression of various GWB components were then compared using immunoprecipitated GWBs from NHK and SCC cell lines.
Results: In the epidermis and cutaneous appendages,
GWBs were most prominent in the stratum basale and the
outer root sheath (ORS) of the hair follicle, notably the bulge
region. Colocalization studies with keratin 15, a known marker of cutaneous stem cells, confirmed that GWBs localize to
bulge cells, known progenitors of cutaneous SCCs. In tissue
sections, GWBs were most prominent in poorly differentiated SCCs. An abundance of GWBs were also noted in SCC as
compared to NHK cell lines.
A select group of proteins involved in mRNA degradation and RNAi were found to colocalize with keratinocyte
and SCC GWBs. In NHK (and SCC) cell lines, approximately
85.17% (78.19%), 78.12% (66.18%), 18.95% (23.40%), 12.57%
(42.99%), 11.45% (8.75%) and 2.49% (11.76%) of GWBs
costained with antibodies to Ge-1, Dcp1a, Xrn1, LSm4, Ago2
and dicer, respectively. Using immunoprecipitated GWBs
from NHK and SCC cell lines, distinct protein patterns for
NHKs and SCCs were confirmed by western blot analysis.
Conclusions: Preliminary data suggest that cutaneous
GWBs are involved in both mRNA degradation and RNAi
pathways. While skin GWBs may be preferentially involved in
mRNA degradation, the association of GWBs with other proteins may be transient and cell cycle-dependent. The GWBs
of NHK and SCC cells are clearly dynamic structures which
play important regulatory roles in both normal human skin
and non-melanoma skin cancer.
Case 2: A 52-year-old woman had a history of systemic LE
since the age of 16 diagnosed at age 21, with neuropsychiatric lupus and myotonic seizures, controlled on azathioprine,
prednisone, lamotrigine, citalopram, phenobarbital, risperidone and omeprazole. She developed a psoriasiform
variant of subacute cutaneous lupus erythematosus and
was treated with hydroxychloroquine 400 mg daily. After 3
weeks, she experienced worsening of her neuropsychiatric
symptoms, with depression, nightmares, myoclonic jerks
and vocalization. These symptoms resolved upon discontinuation of hydroxychloroquine. Quinacrine 100 mg daily
induced identical symptoms within 5 days; she has tolerated
chloroquine without complication.
There are scattered published reports of acute mania due to
antimalarial therapy but none in the dermatology literature
within the past 20 years. Although the incidence of such
psychiatric complications in unclear, we recommend close
observation of patients for behavioral changes that suggest
antimalarial-induced psychiatric disorders.
In vivo confocal Raman spectroscopy for skin
disease detection and characterization —
preliminary results from a Murine tumor model
Hequn Wang1, 2, 3 Naiyan Huang1, 2, 3 Jianhua Zhao1, 2, 3
Harvey Lui1, 2, 3 Mladen Korbelik1, 2, 3 Haishan Zeng1, 2, 3
1. The Laboratory for Advanced Medical Photonics (LAMP),
Photomedicine Institute, Department of Dermatology and Skin
Science, University of British Columbia, Vancouver, BC; 2. Vancouver
Coastal Health Research Institute, Vancouver, BC; 3. Cancer Imaging
Department, BC Cancer Research Center, Vancouver, BC
Results and conclusions:
Background and Objective: One in five individuals living in
North America now develops skin cancer sometime during
their life. Skin biopsy, which is time-consuming and results
in scarring, remains the gold standard for diagnosis. Optical
techniques may potentially obviate many of the problems that traditional biopsy methods suffer from and offer
physicians a non-invasive high-resolution morphological
and biochemical analysis of lesions in real time. The confocal principle provides a powerful method for performing
non-invasive, depth-resolved tissue evaluation because of its
optical sectioning capability. Raman spectroscopy measures molecular vibrations and can provide fingerprint-type
specific signatures for molecular identification. Our objective is to combine these two complementary techniques to
achieve non-invasive, depth-resolved biochemical analysis
of the skin in vivo for improving skin cancer detection and
evaluation.
Case 1: A 20-year-old woman with a one-year history of
discoid LE unresponsive to a 6-month course of hydroxychloroquine 400 mg, azathioprine and low-dose prednisone
presented 4 days after the addition of quinacrine with signs
and symptoms of acute mania requiring admission to the
Psychiatric Service. Urgent MRI examination ruled out the
possibility of lupus cerebritis. She had a past history of
Materials and Methods: A confocal Raman spectrometer
system with a special probe for reducing involuntary body
movements has been built for depth-resolved biochemical
analysis of the skin in vivo. The system consists of a 785nm
near-infrared laser, a spatial filter system, a dichroic mirror, a
water-immersion objective, a collection fiber, and a spectrograph. The skin of 24 anesthetized mice bearing squamous
Antimalarial-induced psychiatric disorders
Cristian Vera-Kellet1, 2 Richard Crawford1 Jan Dutz1
1. Department of Dermatology and Skin Science University of British
Columbia, Vancouver, BC; 2. Department of Dermatology. Pontificia
Universidad Catolica de Chile, Santiago, , Chile
Introduction: Psychiatric disorders due to hydroxychloroquine and quinacrine therapy represent an infrequent, but
serious, complication and may be poorly appreciated by
dermatologists despite the frequent use of these drugs.
Methods: Case description and literature review. We
describe two patients with lupus erythematosus (LE),
who developed psychiatric disorders after starting either
hydroxychloroquine or quinacrine.
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depression at age 16. Symptoms improved after quinacrine
discontinuation.
cell carcinoma (SCC) subcutaneous tumors was scanned
axially from the stratum corneum to mid dermis. Sites on
both normal skin and the tumor were measured. After this,
the skin from the measurement sites was excised and H&E
stained. The fluorescence backgrounds of the raw spectra
were removed using Vancouver Raman Algorithm. And all
the processed spectra were normalized according to the
area under curve and then evaluated by principal component analysis with leave-one-out cross validation.
Results and Conclusions: The axial resolution of the system
within tissue was 14.8 microns and the lateral resolution
was estimated to be 4.5 microns. Raman spectra with good
signal-to-noise ratio were obtained within 15 seconds under
27-mW of excitation light exposure to the skin surface.
Raman spectra of mouse epidermis and dermis differed
significantly. Obvious changes in Raman spectra for both the
epidermal and dermal layers were also evident between normal and tumor-bearing skin and could be differentiated with
high diagnostic sensitivity (91%) and specificity (86%). We
are aiming to now combine this spectrometer system with
a confocal imaging module in the near future to not only
improve the non-invasive clinical diagnosis of skin cancers,
but also help delineate their margins.
Identification of pathogenetic gene
changes in sezary syndrome
Yang Wang1, 5 Mingwan Su1 Xiaoyan Jiang3, 4 Youwen Zhou1, 2
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Skin Oncology Group, British Columbia
Cancer Agency, Vancouver, BC; 3. Terry Fox Laboratory, British Columbia
Cancer Agency, Vancouver, BC; 4. Department of Medical Genetics,
University of British Columbia, Vancouver, BC; 5. Department of
Dermatology and Venerology, Peking University First Hospital, Bejing, ,
P.R. China
Sezary syndrome (SS) is an aggressive leukemic form of
cutaneous T cell lymphoma, which is characterized by the
hall mark Sezary cells with cerebriform nucleus in peripheral
blood. To date, the molecular basis for the unique nuclear
architecture and its link to Sezary cell behavioral features
have not been elucidated.
To identify pathogenic gene expression changes in Sezary
cells, CD4+ T cells from peripheral blood of 6 SS patients, 9
healthy donors, 2 Sezary cell lines and 1 non Sezary T cell
line were screened by Whole Human Genome Oligo Microarrays for differential gene expression profiles. 191 genes
were found to be aberrantly expressed in Sezary cells. Those
genes are involved in inflammatory response, cleavage of
cytoskeletal proteins, dissembly of cell structures, and other
biological functions which can be related to the malignant
transformation of Sezary cells.
Interestingly, we found that special AT rich binding protein
1(SATB1), which is a chromatin organizer in nucleus, was
consistently and specifically down regulated in Sezary cells.
Western blot and immunofluorescence validated its low
expression in Sezary cell nucleus. As a global gene organizer
involved in multiple cancers, SATB1 may contribute to the
altered nuclear structure and the development of many of
the gene expression changes observed in the Sezary cells.
Clinical significance and knowledge translation: This pilot
study will lead to new knowledge on the pathogenesis of
Sezary syndrome and potentially point to new directions for
the development of selective therapies for Sezary syndrome,
which currently does not have a cure.
Field cellular defects in vitiligo vulgaris
S. Wei1, 2 Y. Wang1, 2 M. Gao1, 2 M.W. Su1, 2 A. Xu1, 2 H. Lui1, 2
X. Zhang1, 2 Y. Zhou1, 2
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Institute of Dermatology, Anhui Medical
University, , , China
Vitiligo is the most common depigmenting disorder, with a
prevalence ranging from 0.1-4 % in worldwide. It can cause
severe distress and disfigurement in the affected individuals.
The pathogenesis is unclear. In order to provide additional
clues to vitiligo pathogenesis, we had performed large scale
gene expression analyses on the lesional skin in vitiligo, and
discovered that a group of membrane bound proteins previously unknown to melanocyte structure or function were
specifically and consistently decreased in vitiligo-affected
skin biopsies. Cellular localization using immunohistochemistry stains as well as immunofluorescence has determined
that these molecules were normally present in dermal, nonmelanocytic cells, where as these cells were absent in vitiligo
lesions, parallel to the demise of melanocytes. Therefore,
we propose that previously unknown non-melanocytic cell
death is present in vitiligo lesional skin. Significance: These
findings have extended the cellular defects to involve additional cell types in vitiligo skin, suggesting that vitiligo is a
more complex disease than previously perceived.
Automatic identification of
dermoscopic structures
Paul Wighton1, 2, 3 Tim K. Lee1, 2, 3 David I. McLean2
Harvey Lui2, 3 M. Stella Atkins1
1. School of Computing Science, Simon Fraser University, Burnaby,
BC; 2. Photomedicine Institute, Department of Dermatology and
Skin Science, University of British Columbia and Vancouver Coastal
Health Research Institute, Vancouver, BC; 3. Cancer Control Research
Program and Cancer Imaging Department, BC Cancer Research Centre,
Vancouver, BC
Dermoscopy is an established practice in dermatology that
improves clinical diagnostic accuracy. However the ability
to accurately identify dermoscopic structures is a necessary precondition to its effective use. In fact, dermoscopy
has been shown to decrease accuracy when the individual
is insufficiently trained. Additionally, a study has shown
that even amongst experts (individuals experienced in the
use of dermoscopy who have either published or lectured
on the topic) interobserver agreement is poor. The same
study, however found that diagnosis by consensus improves
accuracy. We believe that a further increase in clinical
diagnostic accuracy can be realized through dermoscopy by
a25
1) explicitly defining dermoscopic structures 2) improving
consensus and 3) improving training methods.
We define a statistical framework that is sufficiently general
to explicitly define all dermoscopic structures. We demonstrate the framework’s ability to learn the dermoscopic structure ‘pigment network’ and differentiate between typical
and atypical variants. We also use the newly learnt definition
to create visualizations showing location/type of pigment
network along with the associated certainty.
Our dataset consists of 94 images from an atlas of dermoscopy that are labeled as having either an ‘absent’, ‘regular’
or ‘irregular’ pigment network. Locational information is
not specified; only that it occurs somewhere in the image.
We begin by performing various pixel-wise measurements
on these images such as filter-bank convolutions, wavelet
decompositions, etc. Multivariate distributions over these
measurements are then constructed and maximum likelihood estimation is used to label unseen images. The system
can detect pigment networks with 89% accuracy. It also
identifies the type of pigment network with 73% accuracy.
In conclusion, our framework seems to be a promising technique for the automatic identification and visualization of
dermoscopic structures in skin lesions. We believe that this
research not only has the potential to create tools to aid the
dermatologist, but also to improve training methods and
build consensus amongst experts.
Incidence and anatomic location of
cutaneous melanoma in central Canada
over a 50-year period: 1956–2005
Marni C. Wiseman1 Alain A. Demers2, 3 Zoann Nugent2
Regan Guilgoyle4 Deepak Pruthi2, 5
1. Dept. of Internal Medicine, Section of Dermatology, Section of
Hematology and Oncology, University of Manitoba, Winnipeg, MB;
2. Department of Epidemiology and Cancer Registry, CancerCare
Manitoba, Winnipeg, MB; 3. Department of Community Health
Sciences, University of Manitoba, Winnipeg, MB; 4. Dept. of Surgery,
Section of Plastic Surgery, University of Edmonton, Edmonton, AB; 5.
Faculty of Medicine, University of Manitoba, Winnipeg, MB
Background: Incidence rates of cutaneous malignant melanoma (CMM) have increased worldwide. Long-term studies
examining rates and anatomic site-specific incidence on a
population-based level are infrequent.
Methods: Using population-based data, all first diagnses
of CMMs reported between 1956 and 2005 were identified.
Age-specific rates, age-standardized incidence rates, and
anatomic sites were recorded.
Results: Incidence rates of CMM slowed for each sex beginning in 1981 for females and 1992 for males. Annual peercent change (APC) reveal decreasing rates among males less
than <40 [1992-2005:-5.3% (P=0.03)] and females <40
a26
[1987-2005:-1.8% (P=0.15)]. Similarly, middle-aged individuals (age 40-59) also had diminished APCs [males 19922005: 0.6 (P=0.65); females 1983-05: -0.3% (P=0.68)]. The
APCs for older males and women (60-79 and 80+) continue
to increase. Anatomic site specific analyses revealed that the
trunk was the most frequent site of CMM for young males
(<60) whereas the lower extremities were the most common
among young (<60) females; however, the rates are slowing
but lack statistical significance. Among those aged 60 and
above, the rates for each anatomical site increased.
Conclusion: The rates of CMM are slowing; however, this
change is confined to younger individuals. Anatomic sitespecific CMMs are changing; rates among the older continue
to increase for both sexes.
Tumor suppressor ING1b maintains genomic
stability upon UV-induced replication stress
Ronald PC Wong; Leon H. Lin; David W. Chen; Gang Li
Department of Dermatology and Skin Science, Jack Bell Research
Center, Vancouver Coastal Health Research Institute, University of
British Columbia, Vancouver, BC
Genomic instability plays an important role in cancer
development. Human genome is susceptible to genetic
alterations such as chromosome rearrangement during replication. Individuals with genetic defects in genes involved
in DNA replication and repair pathways are predisposed to
cancers. Ultraviolet (UV) irradiation is the major environmental risk factor for skin cancers. UV lesions present on
DNA template block progress of replication fork. Prolonged
stalling of replication leads to genomic instability and contributes to cancer development.
Tumor suppressor ING1b has been shown to be reduced or
mislocalized in various cancers. It is shown to be involved
in UV response, but the exact role has not been elucidated.
In this study, we found that depletion of physiological level
of ING1b sensitized cells to UV. ING1b depleted cells exhibited a prolonged S phase arrest and defect in recovery from
UV-induced replication blockage. Moreover, ING1b depletion increased H2AX phosphorylation, which is a hallmark
for DNA double strand breaks, and formation of aberrant
chromosome structures after UV irradiation. Interestingly,
ING1b knockdown did not affect activation of S phase
checkpoint after UV including Chk1 phosphorylation, ATR
binding to chromatin and association of ATR with replication
stalled sites. However, ING1b was required for efficient PCNA
monoubiquitination, indicating that ING1b may be involved
in lesion bypass mechanism. We herein describe a novel
tumor suppressive function of ING1b in the maintenance of
genomic stability after UV irradiation.
This study leads to a better understanding of the mechanism
involved in preserving genomic stability. It has implications
in developing new strategies for skin cancer prevention and
detection.
Skin cancer detection using noninvasive in
vivo Raman spectroscopy - preliminary results
Posters
Jianhua Zhao1, 2, 3 Haishan Zeng1, 2, 3 David I. McLean1, 2, 3
Harvey Lui1, 2, 3
Combination of split skin grafting
and excimer laser for the treatment
of chronic stable localized vitiligo
1. The Laboratory for Advanced Medical Photonics, Photomedicine
Institute, Department of Dermatology and Skin Science, University of
British Columbia, Vancouver, BC; 2. Vancouver Coastal Health Research
Institute, Vancouver, BC; 3. Cancer Imaging Department, British
Columbia Cancer Research Centre, Vancouver, BC
Background: As a non-invasive optical technique Raman
spectroscopy can assess molecular structures and conformations within biological tissue. We have developed
a rapid real-time Raman spectrometer system with data
acquisition times of less than 1 second suitable for clinical
measurement.
Methods and Patients: Patients with benign and/or malignant skin lesions were recruited. Both the lesional skin and
its surrounding normal skin were measured using a real-time
Raman spectrometer. Two hundred fifty six (256) cases were
included in this study, of which there were 24 cases of basal
cell carcinoma (BCC), 49 cases of squamous cell carcinoma
(SCC), 37 cases of malignant melanoma (MM), 24 cases of
actinic keratosis (AK), 53 cases of seborrbeic keratosis (SK),
32 cases of atypical nevus (AN), 22 cases of compound
nevus (CN), 25 cases of intradermal nevus (IN), and 23 cases
of junctional nevus (JN). Based on clinical relevance, the
patients were divided into two categories for analysis: (1)
skin cancer (BCC, SCC, MM, AK) versus benign lesions (SK,
AN, CN, IN, JN); (2) MM versus benign pigmented lesions
(SK, AN, CN, IN, JN). The Raman spectra were analyzed using
multivariate partial least squares regression and linear discriminant analysis.
Results and Conclusions: Lesional skin and normal skin
have distinctive spectral features. Statistical analysis demonstrated that skin cancers could be very well discriminated
from benign skin lesions (AUC of the ROC curve = 0.906,
optimal sensitivity = 91%, optimal specificity = 75%); and
malignant melanoma from benign pigmented lesions (AUC
of the ROC curve = 0.930, optimal sensitivity = 97%, optimal
specificity = 78%). The results demonstrated that real-time
clinical Raman spectroscopy is technically feasible and
capable of assisting with non-invasive skin cancer diagnosis.
Nawaf Al-Mutairi
Faculty of Medicine, Kuwait University, Kuwait, Farwaniya, Kuwait
Background: Refractory and stable lesions of vitiligo may be
unresponsive to medical treatment. Surgical treatment can
restore normal pigmentation in selected patients. However,
residual achromic areas may be seen even after surgical
correction.
Objective: To evaluate the efficacy of additional excimer
laser for completely restoring the achromic defects after split
skin grafting for correction of leucoderma.
Methods: Five patients with chronic stable localized vitiligo
not responding to topical treatments were treated with
split skin grafting. Two weeks after the surgery the treated
area was exposed to excimer laser twice a week to treat the
achromic areas left after the grafting.
Results: Depigmentation was 100% restored in all the
patients within 16 weeks after grafting and after 6-16 sessions of excimer laser. The patients have been under follow
up without treatment for 1-2.5 years without any relapse.
Conclusion: Surgical methods followed by excimer laser
may be helpful in restoring complete repigmentation of
depigmented defects. In cases, where residual achromia,
after split skin grafting is still present.
A review of cutaneous manifestation
of Hepatitis C (HCV) infection and a
case report of large vessel vasculitis
associated with HCV infection
Afsaneh Alavi; Gregory Choy; Kaveh G. Shojania;
R Gary Sibbald
University of Toronto, Toronto, ON
We report a 47 year old lady presenting with a right leg pain
secondary to femoro-popliteal obstruction. The underlying
etiology was established as chronic hepatitis C infection.
Hepatitis C virus (HCV) infects an estimated 170 million
individuals world wide. Extra-hepatic manifestations of HCV
infection include cutaneous immune complex mediated
(mixed cryoglobulinemia, Sjogren’s associated vasculitis)
or non-immune complex injury including lichen planus
and porphyria cutaneous tarda. In addition, there are other
misc. dermatologic manifestations seen with an increased
frequency with HCV: pruritus, urticaria, prurigo nodularis,
and erythema nodosum. Screening for viral hepatitis should
be considered in patients with conditions that have been
associated with both HBV and HCV infection.
Case: Most patients with acute and chronic HCV infection
are asymptomatic. HCV infection is a progressive disease
a27
with 20-30% mortality and extra-hepatic manifestations
are often the first clues to underlying HCV infection. This
case presented clinically as a leg pain and claudication for 3
weeks duration associated with absence of pulse. Her past
history was significant for hypertension diagnosed three
years ago. Her only risk factor for contraction of hepatitis
C was a blood transfusion received in Taiwan following the
birth of a baby girl. She had a successful embolectomy in
the hospital and the vessel biopsy revealed a lymphocytic
vasculitis with radiological exam confirming the presence of
large vessel involvement and femoropoliteal occlusion.
Conclusion: There are many dermatologic manifestations of
Hepatitis C. Early diagnosis and treatment of HCV improve
prognosis of the disease. This abstract reviewed the common cutaneous manifestations of HCV and highlights the
need to consider hepatitis C as a potential etiologic factor
in all patients with cutaneous manifestations related to HCV
including large vessel vasculitis. This case reinforces the
need to test for viral hepatitis screening inl patients presenting with cutaneous vasculitis even in the abscence of
cryoglobulinemia.
Cultural sensitive educational approach
to address global wound care needs
Afsaneh Alavi; Kevin Woo; R Gary Sibbald
University of Toronto, toronto, ON
Wounds are common in various regions of the world due to
genetics, life style, cultural preferences, and available resources. Provision of quality wound care presents an ever-growing challenge for health care professionals, patients and
their families. However, the knowledge and skills to manage
complex wounds are lacking leading to exceedingly high
mortality and morbidity such as lower limb amputation.
To meet this challenge, an international interprofessional
wound care course (IIWCC) has been established to facilitate
wound care knowledge uptake since 1999 at the University
of Toronto. Over the last 10 years this innovative program
has successfully educated health care professionals about
wound care in Canada and around the world. This course
was recently adapted for the Middle East with a key objective to improve the quality of wound care with a special focus
on reducing the lower limb amputation rate for persons with
diabetes.
.The design of this international curriculum requires education styles and knowledge transfer skills that are sensitive
to cultural diversity. International students have different
expectations and the faculty needs to reflect on their experience in this journey to adapt new teaching methods to a
different student population. To ensure individuals’ educational needs were met, the students were interviewed at the
beginning and the end of the course and faculty were asked
to complete a survey about their experience in the courses
a28
The objectives of this study are to review taped the student
interviews and faculty surveys balancing their needs and
expectations with improved patient care and health care
system change. The common themes will be identified in the
3 courses from University of Toronto (IIWCC in Tehran, Iran,
-Riyadh Saudi Arabia and Toronto, Canada).
The identification of barriers (social, economic and cultural)
can potentially improve the outcomes of international educational programs. .
Thyroid problem in patients with chronic
wounds treated topically with povidone iodine
Afsaneh Alavi1 Marjorie Fierheller2 R Gary Sibbald1
1. University of Toronto, Toronto, ON; 2. Wound Care Clinic, Mississauga, ON
Background and objectives: All chronic wounds contain
bacteria either colonized or infected. Idoine and its components have been broadly used since 1811 for the prevention
of infection and the topical treatment of wounds. This poster
describes 3 patients with iodine-induced hypothyroidism.
They all had large chronic wounds treated with long term
topical povidone-iodine.
Methods: Thyroid dysfunction was induced in three patients
with chronic wounds (A 34 year old female with panniculitis,
a 65 year old man with lung cancer and a Claggett window
and a 68 year old man with diabetic foot ulcer) associated
with topical treatment with povidone iodine. The patients
had no history of thyroid disease before topical treatment
with iodine. In all patients a marked increase in circulating thyroid hormones was noticed after topical daily use
of povidone iodine. After discontinuing use of topical
povidone iodine, circulating thyroid hormones returned to
normal values within weeks.
Discussion: Antiseptics destroy or inhibit microorganism
growth in or on living tissue and the rational for widely use
of antiseptics is prevention of infection along with low risk
of resistance. There is some debate of the role of iodine in
wound healing. In some studies povidone iodine was found
to cause no inhibition on wound reepithelialisation and it
has been shown to increase revascularization. Povidone
iodine is generally safe but cases of thyroid dysfunction
induced by povidone iodine have been reported.
Conclusion: Patients treated with long term povidone iodine administration to chronic wounds should be monitored
on a regular basis for thyroid dysfunction and observed carefully for any clinical manifestations of thyroid disease.
Subcutaneous panniculitis-like T-cell
lymphoma (SPTCL) with interface changes
Bizhan Bandarchi1 Afsaneh Alavi1 Judit Zobovitz1
Lingle Ma2 Golnar Rasty3
1. University of Toronto, Department of Pathology, Toronto, ON; 2.
University of Michigan, Michigan, MI, United States; 3. University of
Toronto, Toronto, ON
Background: SPTCL is a rare primary T-cell lymphoma,
which usually presents as erythematous subcutaneous
nodules on extremities. In many cases it is associated with
a rapidly aggressive behavior. Hemophagocytic syndrome
can occur in up to 50% of cases. Epidermal and superficial
dermal involvement may sometimes occur but is rare.
Design: A 56 year-old Chinese male presented with erythematous swelling of thigh and arm. Original diagnosis
was “panniculitis” not responding to treatment. Meanwhile
patient lost 20 pounds. Four months later the lesions of
thigh became ulcerated with deep soft tissue involvement.
Subsequent biopsies were performed for additional studies.
Result: Biopsies from leg and arm revealed erythema multiforme-like changes (interface changes). Dermis revealed
superficial perivascular lymphohistiocytic inflammation
with exocytosis predominantly composed of small mature
lymphocytes. Subcutaneous tissue showed an infiltrate of
atypical lymphocytes involving subcutaneous septae and fat
lobules with extensive fat necrosis, rimming of adipocytes,
karyorrhexis and phagocytosis of nuclear debris. Occasional
plasma cells and eosinophils were identified. The atypical
lymphocytes were CD3+, CD4+ cells and CD8- T-cells. However, CD4+ cells were low in number. CD5+ and CD7+ T-cells
were markedly decreased and CD56 was positive. CD68
highlighted presence of numerous histiocytes, giant cells
and vague granuloma formation. Molecular analysis on arm
nodule showed TCR γ gene rearrangement; however, analysis on leg lesion showed only TCR γ gene rearrangement.
In-situ hybridization showed foci of Eber positivity.
Conclusion: Majority of SPTCLs reveal only deep dermal and
subcutaneous involvement with only rare epidermal involvement of various types. In this case, epidermis revealed
interface dermatitis (erythema multiforme-like changes).
TCR gene rearrangement observed, however, there was also
positivity for EBV possibly indicating EBV+ variant of SPTCL.
Although majority of SPTCL are CD4- and CD8+, our case
revealed more CD4 positivity. Even though overlapping
features between SPTCL and γ T-cell lymphoma observed,
however EBV positivity is unusual for the latter.
A case series of metal prostheses allergy
Jennifer Beecker; Melanie Pratt
University of Ottawa, Ottawa, ON
Three cases of systemic contact allergic dermatitis from
metal prostheses are presented. The low incidence of
allergic contact dermatitis to metal prostheses is surprising,
especially given the frequency of metal allergy, particularly
nickel and cobalt, in the general population. Even patients
with known metal allergy often do not react to their metal
prosthesis.
The first example of metal prosthesis allergy is a nickel-allergic patient who received a femoral artery nitinol stent for
peripheral vascular disease. A recalcitrant systemic contact
dermatitis developed, requiring ex-plantation of the device.
This is the first reported case of a systemic nickel contact
dermatitis secondary to peripheral artery stenting.
A second patient presented after a hip prostheses replacement. The hip was replaced with a cobalt-chromium-molybdenum alloy prosthesis. A localized, then systemic, contact
dermatitis ensued. It was resistant to treatment, requiring
oral steroids for control. The patient was strongly patch test
positive to cobalt.
A third patient had documented severe nickel and cobalt
allergy. She received a knee replacement using a cobalt
alloy as there were a lack of other robust metal options. She
developed persistent systemic contact dermatitis.
Contact allergic dermatitis from metal in joint prostheses is
rare although both joint prostheses and metal allergy are
common in the general population. There is controversy
around whether patch testing is required in patients who are
about to receive metal prostheses. This series suggests that
a history of metal allergy should be elicited before a prostheses is placed. If there is a history of severe allergy and the
patch testing is positive for metals, there may be a higher
probability of systemic contact dermatitis in these patients.
Harlequin ichthyosis: case report
of an nine-year-old survivor
Jennifer Beecker; James Walker
University of Ottawa, Ottawa, ON
Harlequin ichthyosis, an autosomal recessive disease, was
uniformly fatal prior to the first use of systemic retinoids in
1984.
Our female patient was born to consanguineous Somalian
parents. Ultrasound at 35 weeks showed polyhydramnios,
flat forehead, flat nose, micrognathia, and short digits.
Caesarian-section was done at 38 weeks for failure to
progress. At delivery, she was noted to have diffusely thick,
firm, inelastic skin with symmetrical fissuring, ectropion,
eclabium, ainhum-like constrictions, as well as ear and nasal
deformities.
During her first few days of life she required aggressive
fluid and electrolyte management, sepsis prophylaxis and
debridement of legs and feet because of compromised
blood flow. Treatment included a high humidity environment, petrolatum to the body, lacrilube to eyes.
Her parents made the decision to do whatever possible to
save their daughter, as they had already experienced a number of spontaneous abortions and were childless. Acitretin
1.5mg a day was prescribed. The most prominent challenges were poor weight gain, contractures, constrictions and
spontaneous limb amputation.
She has required further amputations, prostheses, and
cardiac surgery. Attempts to taper her acitretin caused
severe exacerbations in her skin. Interestingly, her lipids
have remained below normal despite continuous acitretin
treatment.
A loss-of-function mutation in the ABC transporter gene
ABCA12 is now known to cause this disease.
Initially, there were discussions around the ethics of treating
a child with such severe deformities and a negligible chance
of survival. She is now a happy child attending school.
a29
Pemphigus herpetiformis
Yousef Binamer; Elizabeth O’Brien ; Kevin Watters;
Therese El helou
McGill University, Montreal, QC
Pemphigus herpetiformis (PH) is an uncommon variant of
Pemphigus vulgaris that was described by Jablonska et al
in 1975. It combines clinical features of dermatitis herpetiformis and some of the histological features of pemphigus
vulgaris. Clinically, it is characterized by the presence of
tense blisters, usually on the trunk, which are arranged in a
herpetiform pattern, with or without mucosal involvement.
Histologically, it is characterized by intraepidermal blisters,
with eosinophilic spongiosis or neutrophilic infiltrate, or
both, with or without acantholysis. Direct immunofluorescence (DIF) reveals IgG deposition in the upper or/and
lower parts of the epidermis. Indirect immunofluorescence
reveals IgG anti-epithelial cell surface autoantibodies in
most of patients. IgG antibodies are against desmoglein 3
mainly and to a lesser extent desmoglein 1. PH has a benign
course although there are some reports that it might change
into other forms of pemphigus during the disease course. It
responds very well to dapsone, as well as low doses of oral
prednisone or other immunosuppressive medications.
We report the case of a 71-year-old female diagnosed on
December 2007 with endometrial carcinoma with vascular
invasion, stage 1C, treated with surgery and radiotherapy.
She presented to dermatology clinic with pruritic tense
blisters on the trunk, clinically suggestive of bullous pemphigoid. Skin biopsy showed eosinophilic spongiosis with a
large intraepidermal vesicle containing numerous eosinophils without acantholysis. DIF revealed moderate granular
deposition in intercellular spaces in the lower half of the
epidermis against IgG, strong granular fluorescence with
C3and negative for IgM, IgA.
We are reporting this case to alert the audience to consider
unusual forms of pemphigus vulgaris in patients with vesiculobullous lesions.
Alitretinoin relieves signs and symptoms
of severe chronic hand eczema
Robert Bissonnette1 Kim Papp2 Norm Wasel3
Juergen Maares4 Thomas C. Brown4
1. Innovaderm Research, Montreal, QC; 2. Probity Medical Reseach,
Waterloo, ON; 3. Stratica Medical and University of Alberta, Edmonton,
AL; 4. Basilea Pharmaceutica Ltd. , Basel, Switzerland
Objectives: To assess the effect of oral alitretinoin (9-cis
retinoic acid) on the modified Total Lesion Symptom
Score (mTLSS) and its individual components in patients
with severe chronic hand eczema refractory to topical
corticosteroids.
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Methods: A total of 1032 patients with severe chronic hand
eczema refractory to topical corticosteroids received oral
alitretinoin 10 mg, 30 mg or placebo once daily for 12 to
24 weeks in a randomized double-blind trial. Disease signs
and symptoms (erythema, desquamation, hyperkeratosis,
vesicles, edema, fissures, and pruritis/pain) were rated by
physicians on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe), and the mTLSS was calculated as the sum
of assigned scores.
Results: Median within-patient changes in mTLSS from
baseline to Week 24 were -75%, -56%, and -39% for alitretinoin 30mg, 10mg and placebo respectively; with significant differences (p<0.001) between active drug and placebo
groups. Dose dependent decreases were seen in all 7 components of the scale, with pruritus/pain, fissures, and hyperkeratosis having the most rapid and marked improvements.
The smallest differences were observed for vesicles, which
were also the least severe at baseline. Among responding
patients, substantial improvement in all components was
observed after 4 to 8 weeks of therapy.
Conclusion: Oral alitretinoin led to dose-dependent
improvement in all signs and symptoms of severe chronic
hand eczema, with the most rapid and marked changes observed for symptoms (pruritus/pain), fissures, and
hyperkeratosis.
Treatment of palmoplantar
psoriasis with infliximab
Robert Bissonnette1 Yves Poulin2 Lyn Guenther3
Charles Lynde4 Chantal Bolduc1 Simon Nigen1
1. Innovaderm Research Inc., Montreal, QC; 2. Centre de Recherche
Dermatologique du Québec Métropolitain, Sainte-Foy, QC; 3. The
Guenther Dermatology Research Center, London, ON; 4. The Lynde
Centre For Dermatology, Markham, ON
Introduction: Palmoplantar psoriasis is a very difficult to
treat variant of psoriasis. Topical treatments and phototherapy often yield disappointing results. Infliximab, a monoclonal antibody against tumor necrosis factor alpha, is one
of the most efficacious treatment for plaque psoriasis. The
efficacy of infliximab in the treatment of palmoplantar psoriasis has never been studied.
Methods: Patients with non-pustular palmoplantar psoriasis affecting at least 10% of the palms and soles and with
a palmoplantar psoriasis area severity index (PPASI) of at
least 8 were recruited. Patients were randomized (1:1) to
receive infliximab at 5 mg/kg or placebo at week 0, 2 and 6.
Patients randomized to placebo received infliximab at week
14, 16 and 20 whereas patients randomized to infliximab
received additional infliximab infusions at week 14 and week
22. PPASI, percentage of palms and soles area affected by
psoriasis and DLQI were performed at every visit. Safety was
assessed by physical examinations, routine chemistry and
hematology tests and adverse events evaluation.
Results: The study is now closed for enrolment and a total
of 24 patients were randomized. Overall, infliximab has been
well tolerated thus far, with no serious infusion reactions
noted. Two serious adverse events were reported: one case
of hepatitis and one case of sternal fracture following a car
accident. The study is still blinded and the last patient last
visit will take place in February 2009.
Conclusions: This study will provide efficacy and safety
information on the treatment of palmoplantar psoriasis with
infliximab. Preliminary results will be presented.
A case of Cushing’s Syndrome after
intralesional injection of triamcinolone
acetonide for the management of periorbital
hemangioma in a pediatric patient
Marie-Michèle Blouin; Isabelle Auger
Université Laval, Quebec, QC
Introduction: The use of intralesional corticosteroids to
manage periorbital hemangiomas is controversial. Serious complications have been reported in the litterature
including atrophy, necrosis and ophthalmic and retinal
artery occlusion. Cushing syndrome following intralesional
injection is a rare side effect due to hypothalamic-pituitaryadrenal axis suppression.
acute eczematous dermatitis on her face, neck and upper
body 24-48 hours, peaking at 72 hours after receiving
parenteral corticosteroids (Solumedrol, Solucortef and
Prednisone) for an asthma exacerbation. Previously on
several occasions after receiving parenteral corticosteroids
in the emergency department for asthma exacerbations, the
patient experienced marked deterioration of her respiratory status, requiring admission to the intensive care unit.
However the question of possible steroid allergy was never
raised.
The patient underwent patch testing to different steroid
series for which she tested negative. Intradermal tests with
1mg each of Solumedrol, Solucortef and Prednisone into her
arms was performed. At 30 minutes the patient developed
shortness of breath, wheezing and bronchospasm. At 72
hours she presented with an acute eczematous reaction. A
month later, the patient developed both type 1 and type IV
hypersensitivity reactions to intradermal testing with 1mg of
Decadron.
Method: We report the case of a young 6 weeks old boy
who developed Cushing’s syndrome 3 months following
a single treatment with 40 mg triamcinolone acetonide
injected into a periorbital hemangioma to correct secondary
ptosis and astigmatism. Features of Cushing syndrome and a
completely suppressed hypothalamic-pituitary-adrenal axis
were present for up to 10 months after treatment. Fortunately, no serious complications happened before diagnosis
of adrenal suppression neither during the one year followup except for a mild psycho-motor delay which the patient
recovered completely.
Discussion: This patient developed both immediate and
delayed hypersensitivity reactions to parenteral, oral and
inhaled group A, B and C corticosteroids. This case demonstrates a possible continuum of immunologic reactivity from
type I hypersensitivity to type IV delayed hypersensitivity.
Conclusion: Dosages of intralesional streroids recommended for adults are not adequate for children and adrenal
suppression as a potential outcome should be kept in mind
after treatment.
1. Private Practice, Eastern Health, St. John’s, NL; 2. Lymphedema Nurse
Co-ordinator, Eastern Health, St. John’s, NL; 3. Wound Care Nurse,
Eastern Health, St. John’s, NL
An unusual case of both immediate
and delayed hypersensitivities to
parenteral corticosteroids
Maude Boulanger; Lauren Fratesi; Melanie Pratt
University of Ottawa, Ottawa, ON
Introduction: Type I and type IV hypersensitivity reactions
occur through distinct routes. Immediate (type I) hypersensitivity is IgE antibody-mediated whereas delayed (type
IV) is T cell-mediated. In type 1 hypersensitivity reactions
re-exposure to the allergen leads to cross-linking of the IgE
and release of mediators (e.g. histamine) causing clinical
symptoms ranging from urticaria to severe bronchoconstriction. In type IV hypersensitivity reactions, a second contact
with the antigen induces T-helper cells to release lymphokines which induce inflammation and activate macrophages,
which in turn release mediators causing erythema, eczema
and pruritus. We present a case of simultaneous immediate
and delayed hypersensitivity to parenteral corticosteroids.
Case Presentation: A 33 year-old female known to have
high-risk asthma and ulcerative colitis, presented with an
Coban-2-layer compression: an effective
treatment for lymphedema
Tracey D. Brown-Maher1 Martina Reddick2 Margo Cashin3
Barbara Moyst3
Lymphedema is the abnormal collection of protein-rich fluid
in the interstitial spaces due to a defect in the lymphatic
drainage network. It results in edema to the affected limb
and predisposes patients to infection, cellulitis and lymphangitis. There are two types: primary and secondary lymphedema. Primary lymphedema is present at birth, but may
not be clinically evident until later in life. Secondary lymphedema is due to an acquired dysfunction of otherwise normal
lymphatics. Lymphedema is progressive and deforming,
and can be both physically and psychologically debilitating.
Treatment of lymphedema is chronic and difficult. Previous
treatments have included inelastic bandages which have to
be changed frequently and are cumbersome. Compliance is
therefore poor.
We treated three patients with significant secondary lymphedema (present for years) with the Coban-2-Layer compression system. Coban-2-Layer is a new inelastic compression
dressing that is used for venous leg ulcers, and has been
reported to be effective with lymphedema. The dressings
were changed once-twice weekly. Two patients were able
to start wearing compression stockings within two-three
months. The other patient had more significant lymphedema (was unable to walk initially) and has had a decrease in
his lymphedema by approximately fifty percent. All patients
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reported the Coban-2-layer was easy to use and comfortable, and were extremely satisfied with their improvement.
All reported a dramatic improvement in their quality of life.
A Carney Complex case
We suggest that the Coban-2-Layer is an effective and safe
treatment option for chronic lymphedema and should be
employed as a first-line option.
1. CHUS, Division of Dermatology, Department of Medicine,
Sherbrooke, QC; 2. CHUS, Department of Pathology, Sherbrooke
University, Sherbrooke, QC; 3. CHUS, Division of Urology, Department
of Surgery, Sherbrooke University, Sherbrooke, QC
The future of psoriasis care
Wayne Carey Kim A. Papp Stewart Adams Lorne
Albrecht4 Benjamin Barankin5 Kirk Barber6 Marc Bourcier7
Lyn Guenther8 Wayne Gulliver9
1
2
3
1. Siena Medical Research Corporation, Westmount, QC; 2. Probity
Medical Research Inc., Waterloo, ON; 3. Adams Dermatology, Calgary,
AB; 4. Guildford Dermatology, Surrey, BC; 5. The Dermatology Centre
, Toronto, ON; 6. Kirk Barber Research, Calgary, AB; 7. Sherbrooke
University, Sherbrooke, QC; 8. The Guenther Dermatology Research
Centre, London, ON; 9. Memorial University of Newfoundland and
NewLab Clinical Research Inc., St. John’s, NL; 10. University of British
Columbia, Vancouver, BC
Introduction: The recently developed Canadian Guidelines
for the management of plaque psoriasis offer a comprehensive, evidence-based evaluation of treatment options for
this life-long, chronic skin disorder. The Guidelines advocate
a patient-centred approach in which physicians are encouraged to explore all appropriate options, in an attempt to
identify treatments that will not only work for the patient,
but those the patient will work with long term. The range
of anti-psoriatic treatments available in Canada has already
expanded since the Guidelines were completed, and it can
be expected to expand further in the near future.
Methods: Trial registry searches and Medline searches using
the terms “psoriasis” and “therapeutic” for the years 20082009 were conducted to expand and update the overview of
emerging therapies provided in the Guidelines.
Results: New formulations of existing drugs, such as foams
for delivery of corticosteroids or other topical agents, can
be expected to reach the Canadian market. Emerging
compounds with phase 3 data include voclosporine (a
calcineurin inhibitor, related to cyclosporine) and becocalcidiol (a vitamin D analogue, related to calcipotriol).
Agents with novel mechanisms of action include the CYP26
inhibitors rambazole and talarozole, which increase tissue
accumulation of all-trans retinoic acid. New biologics include
ustekinumab and ABT-874, which target the interleukin
12/23 pathway thought to drive autoimmune inflammation
in psoriasis. The new evidence base presented here includes
randomized control trials testing the drugs against placebo
and, in some cases, providing direct head-to-head comparisons between treatments.
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Conclusions: Innovations affecting psoriasis care take several forms: 1) new formulations of currently available drugs;
2) later-generation molecules structurally similar to existing
anti-psoriatic drugs; and 3) products with novel mechanisms
of action. The data supporting novel agents is frequently
of a higher level and, in many cases, yields more ambitious
treatment targets, than many older therapies reviewed in
the Guidelines.
Jérôme Coulombe1 Bruno Maynard1 Dominique Hanna1
Michel Carmel3 Edmond Rizcallah2
Background: Carney complex is a rare autosomal dominant disorder characterized by a heterozygous germline
mutation of the PRKAR1A gene. It is associated with specific
cutaneous signs (lentigines, blue nevi, cutaneous myxomas),
cardiac and endocrine abnormalities and breast/testicular
tumors.
Methods: We describe a 49 year-old male with Carney complex and a possible positive family history. The patient had
previous excisions of neck, thorax and groin cysts. The histology revealed myxomas and that were noted by his urologist
on examination for a para scrotal mass.
Results: The examination confirmed periorificial lentigines
around the lips and eyes, a para scrotal mass of 2,5 x 3,5 cm,
but no blue nevi. The investigations for Sertoli cell tumor,
cardiac myxoma and endocrine malfunction were negative.
The excision of the para scrotal mass revealed a multilobulated myxoma.
Conclusions: Carney complex is a rare genetic disorder with
heterogeneous manifestations where cutaneous findings
are a hallmark. Recognition of those signs is important to
prevent debilitating endocrine disorders or possibly fatal
cardiac complications. In our case only major cutaneous
criteria were found.
None of the authors has any kind of conflict of interests
Paraneoplastic acrokeratosis of Bazex
Sandra Davar1 Edmond Rizcallah2 Bruno Maynard1
Dominique Hanna1
1. CHUS, Division of Dermatology, Department of Medicine, Université
de Sherbrooke, Sherbrooke, QC; 2. CHUS, Division of Pathology,
Department of Medicine, Université de Sherbrooke, Sherbrooke, QC
Introduction: Paraneoplastic acrokeratosis of Bazex is a
rare skin disorder characterized by acral psoriasiform lesions
associated with an underlying neoplasm occurring in the
aerodigestive tract.
Methods: A 60 year old male patient with an acral psoriasiform eruption for over a year presented with a sensitive
cervical mass that was evolving for 3 weeks. Dermatologic
examination revealed a symmetrical violaceous, scaly eruption on the helices, forehead, nose and cheeks. Moreover,
hyperkeratotic plaques on the knees, palmoplantar keratoderma and onychodystrophy were observed. Laryngeal
biopsies and a PET scan were performed.
Results: The biopsies were consistent with a squamous cell
carcinoma of the hypopharynx and the PET scan showed
metastastic jugulo-digastric lymphadenopathy involvement. The patient is on chemotherapy and will receive
radiotherapy.
Conclusion: Bazex syndrome is a specific marker of mucosal
squamous cell carcinoma of the aerodigestive tract. In 70%
of the cases reported in the literature, the syndrome precedes the discovery of the neoplasm by 11 months.
Scalp prostheses and camouflaging
agents for patients with hair Loss
Jeff C. Donovan1 Ron L. Shapiro2, 3 Paul V. Shapiro2
Matt Zupan2 Maria K. Hordinsky3
1. University of Toronto, Toronto, ON; 2. Shapiro Medical Group,
Minneapolis, MN, United States; 3. University of Minnesota,
Minneapolis, MN, United States
Hair loss is common for men and women, and may have
a significant psychosocial impact. Although a variety of
medical and surgical treatment options are available, many
patients will seek advice from their physicians regarding
additional options for hiding or reducing the appearance
of hair loss with use of hair prostheses or hair camouflaging
agents. These may be used concurrently with treatment
or even in lieu of treatment by some individuals. Here, we
provide an overview of current products to hide or reduce
the appearance of hair loss. We discuss the manufacture,
costs, advantages and disadvantages of the wide range of
available products.
Scalp prostheses, which include wigs and hairpieces and
extensions, may be made from human hair or synthetic fibers. Prostheses made of human hair are more expensive than
synthetic ones, but have the advantage of being more durable and can be colored, heat styled and chemically treated.
Options for eyebrow camouflage include use of pencils,
tattoos and glue-on eyebrows. Human and synthetic fibers,
as well as tattoos, can be used for eyelash replacement.
Hair camouflaging agents include fibers, powder cakes,
sprays and lotions. Products such as Toppik (fiber), DermMatch (powder cake), ProTHIK (spray), and COUVRé (lotion)
are among the more popular products on the current market in North America. These products are available in many
different colors to match an individual’s existing hair color.
Use of these products requires a minimal density of hair fibers on the scalp to produce a natural look.
Knowledge of the wide range of products available to cover
scalp, eyebrow and eyelash hair loss may not only better
equip the physician to answer questions from concerned
patients, but may also provide additional options to help
these patients best cope with their hair loss.
Allergic contact dermatitis
from dimethylfumarate after
contact with Chinese sofa
Joseph Doumit; Melanie Pratt
Ottawa Hospital, Ottawa, ON
Dimethylfumarate has been successfully used in the treatment of psoriasis. Despite its clinical use, cutaneous contact
to this molecule may cause contact dermatitis. We report a
case in which skin exposure to a sofa containing dimethylfumarate made by a Chinese furniture manufacturer resulted
in a severe pruritic papulovesicular eczematous dermatitis to
the sites of contact to the sofa. The patient was patch tested
with serial dilutions of dimethylfumarate which elicited positive reactions to the allergen.
A novel aspect in the physiopathology
of psoriasis : LTs and PAF induce Th17
lymphocytes through activation of
monocyte-derived langerhans cells
Anne-Marie Drolet2, 1 Dominique Hanna2 Bruno Maynard2
Jana Stankova1 Marek Rola-Pleszczynski1
1. Division of Allergy and Immunology, Université de Sherbrooke,
Sherbrooke, QC; 2. Division of Dermatology, Université de Sherbrooke,
Sherbrooke, QC
Introduction: Leukotrienes (LTs) and Platelet-Activating
Factor (PAF) have been reported in increased concentration
in psoriatic skin. T helper (Th) cells producing IL-17 (Th17)
have been shown to play a major role in psoriasis. Th17 cells
express RORγt transcription factor and IL-23 is essential for
their expansion. IL-23 is now a target for therapy.
Objective: The aim of this study is to determine whether
PAF and/or leukotrienes can induce Th17 cells by stimulating IL-23 production in Langerhans cells and initiating RORγt
expression in Th cells. A comparison between healthy and
psoriatic individuals will be performed.
Methods: Monocyte-derived Langerhans cells (LCs) were
produced by culturing them with GM-CSF, IL-4 and TGF-β
for 5 days. They were then stimulated with graded concentrations of LTs (LTB4, LTD4) or PAF. IL-23 mRNA levels were
measured by RT-PCR. Moreover, LCs were co-cultured with
autologous anti-CD3- and anti-CD28-activated T cells in the
presence of PAF or LTs. After 10 days, these co-cultures were
analysed for the presence of RORγt in CD4+ T cells by FACS
analysis. Also, skin biopsies of healthy and psoriatic subjects
were analysed by immunofluorescence for the expression of
RORγt, PAF receptor and LTB4 receptor (BLT1).
Results: PAF-stimulated LCs showed a 3-fold increase in
the levels of IL-23 mRNA, whereas LTB4-stimulated LCs
showed a 2-fold increase with maximal effects at 4 hours.
Following co-culture of PAF-stimulated LCs with activated
lymphocytes, activated CD4+ lymphocytes showed a 4-fold
increase of RORγt expression compared to controls at PAF
concentrations of 10-1000 pM. Similarly, CD4+ T cells cocultured with LTB4-stimulated LCs showed a doubling of
a33
RORγt expression. The comparison of PAF and leukotrienes
receptors expression between healthy and psoriatic subjects
and their responses in terms of Th17 production will be
discussed.
Conclusion: Our data suggest that eicosanoids (mainly PAF)
can stimulate LCs to produce IL-23, which in contact with
activated CD4+ T cells triggers the development of Th17.
This may constitute a previously unknown stimulus for psoriasis and a potential therapeutic target.
Efficacy and safety of imiquimod 5%
cream in plaque type morphea
Loretta Fiorillo; Melody Cheung-Lee ; Marlene T. Dytoc
University of Alberta, Edmonton, AB
Methods: We enrolled in two Canadian centers adult
patients with histological-confirmed plaque-type morphea. Each patient applied imiquimod 5% cream daily for 9
months to a representative plaque and a placebo cream to
a separate plaque, if present. Treatment efficacy was measured using three assessment tools: DIET score, histology, and
ultrasound evaluation. Patients were seen at baseline and
every three months for 12 months. All adverse effects were
recorded.
Results: 25 patients were enrolled in the study. 22/25
patients had two or more follow-up visits. Eight patients
had only one morphea lesion. Eleven patients had incomplete ultrasound follow-up assessments. Thirteen patients
consented to baseline and follow-up biopsies of imiquimodtreated lesions.
A change in DIET scores was noted for both imiquimod and
placebo treated lesions at all follow-up intervals. However,
the p-values were much smaller for the imiquimod group
than the placebo group. Histological changes were also statistically significant for imiquimod treated lesions at followup biopsies. Ultrasound results were ambiguous, possibly
reflecting the lack of standardization of this modality for
evaluation of skin thickness.
Nine patients developed adverse reactions. Four developed
local irritation and redness. One developed infection with
Pseudomonas aureuginosa. Two patients developed ulcerations, one healed within two weeks and the other within
two months. One of the ulcers was secondarily infected by
Staphylococcus aureus. Both infections were successfully
treated with antibiotics. Two patients developed hypopigmented macules at site of contact with imiquimod. Both
resolved spontaneously. There were no systemic side effects.
Patient self-evaluations were obtained from ten patients,
seven of whom reported clinical improvement, the remainder reported no change.
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Subacute cutaneous lupus erythematosus
associated with rabeprazole
Steven J. Glassman
University of Ottawa, Ottawa, ON
The role of oral medication in the pathogenesis of subacute cutaneous lupus erythematosus has probably been
underestimated. Several drug classes has been implicated,
including antihypertensives, diuretics and antifungals, and
more recently proton pump inhibitors. A case of severe
SCLE, almost erythrodermic, is presented, where rabeprazole
is thought to have been of major significance.
A 41-year-old man presented with a pruritic and burning
rash, exacerbated by sun exposure, for three months. He had
been taking rabeprazole 20mg daily for approximately nine
months for gastroesophageal reflux disease. Examination
revealed annular erythematous and edematous plaques in
a partly photosensitive distribution. Skin biopsy showed
a vacuolar interface dermatitis with focal compacted
orthokeratosis consistent with cutaneous lupus erythematosus. Antinuclear antibody (ANA) was initially negative
but anti-Ro/SSA antibodies were high positive. A dagnosis
of subacute cutaneous lupus erythematosus was made,
and the rabeprazole was implicated and discontinued.
The patient was treated with oral prednisone 40mg daily
and hydroxychloroquine 200mg twice daily, together with
potent topical corticosteroids and high-factor sunscreens.
Skin lesions extended to the rest of his trunk and his extremities over the following two weeks, almost to the extent of
erythroderma, but then began to regress. On one occasion
the patient inadvertently took a dose of esomeprazole for
heartburn, and noted an immediate flare of the rash. Treatment was continued for six months and the prednisone
tapered. Ten months after onset he remained disease-free
and off all medication.
The exact role of rabeprazole in this case remains uncertain, but given that proton pump inhibitors are increasingly
recognized as possible triggers of drug-induced SCLE it
seems prudent to discontinue this class of medication if
possible in such a clinical setting. The mechanisms by which
drugs induce or worsen SCLE are not known, but it has been
postulated that such drugs or their metabolites shift Ro/
SSA antigens from the nucleus to the cell surface, thereby
facilitating the generation of autoantibodies. Genetic factors
are also considered important in both idiopathic and druginduced SCLE.
Ustekinumab in the treatment
of psoriatic arthritis
Alice B. Gottlieb1 Alan Mendelsohn2 Yaung-Kaung Shen2
Rodion Kunynetz4 Arthur Kavanaugh3
1. Tufts Medical Center, Boston, MA, United States; 2. Centocor Research
and Development, Inc., Malvern, PA, United States; 3. University of
California, San Diego, LaJolla, CA, United States; 4. Assistant profession
of dermatology at a university, Barrie, ON
Purpose: To evaluate individual ACR components in
ustekinumab(UST)-treated PsA pts.
Methods: Pts were randomized to UST90mg/63mg (n=76)
at wks0,1,2, and 3, followed by PBO at wks12 and 16, or PBO
at wks0,1,2, and 3, followed by UST 63mg at wks12 and 16
(n=70). The primary endpoint was ACR20 improvement at
wk12. Percentage improvement from baseline(BL) of individual ACR components(swollen joint count [SJC],tender joint
count [TJC], pt assessment of disease activity [VAS,0-10cm],
physicians global assessment [PGA], pt assessment of pain
score [VAS,0-10cm], pt assessment function [HAQ], and CRP)
were calculated.
Results: At wk12,statistically significant improvements in
TJC, pt pain, pt disease assessment, PGA, and HAQ in UST vs
PBO-treated pts and trends towards greater improvement
in UST groups vs PBO in SJC and CRP were observed. In pts
with BL CRP >0.8mg/dL, median improvement in CRP for
UST was 48.1%(n=22) vs 22.2% for PBO (n=27; p=0.021).
Beyond wk12, pts achieved maximal median percent
improvement in SJC and TJC (75.0% and 70.5%,respectively)
by wk20.Gradual decreases in improvement were noted during dose-free follow-up through wk36. In UST-randomized
pts, maximum reduction in HAQ achieved at wk16(median
-0.38); at wks24 and 36, the median change from BL was
-0.25 and -0.13.In pts initially randomized to PBO who then
received doses of UST at wks12 and 16, the median percent improvement in SJC and TJC at wk24 was 66.7%, and
57.1%,respectively. At wk 36, PBO crossover results were
60% and 43.5%,respectively. The greatest median reduction in median SJC and TJC in the PBO crossover group was
achieved at wk28 (16 wks following induction;73.3% and
63.6%,respectively). The median change from BL in HAQ disability score was -0.25 at wk24 and -0.13 at wk36.
Conclusions: UST significantly reduced 5 of 7 ACR component scores at wk 12. No significant change in the median
CRP scores was observed at wk12 due to low values at BL;in
patients with BL CRP >0.8mg/dL, a significant reduction in
CRP was observed.
Granulomatous vasculitis in
Crohn’s Disease: a clinicopathologic
correlate of two unusual cases
Peter j. Green; Ariel Burns; Noreen Walsh
Dalhousie University, halifax, NS
Crohn’s disease (CD) is a chronic inflammatory gastrointestinal (GI) tract disease often demonstrating non-caseating
granulomas. Cutaneous manifestations occur in 14-44%
of CD patients, with the most common being erythema
nodosum and pyoderma gangrenosum. Other reported
mucocutaneous associations include erythema multiforme,
apthous stomatitis and polyarteritis nodosa. A rare cutaneous finding is a sterile granulomatous infiltrate not contiguous with the GI tract, termed ‘metastatic’ Crohn’s disease
(MCD). Infrequently reported since it was first described in
1965, MCD’s clinical presentation is diverse. Most common
are ulcerated and non-ulcerated plaques and nodules on the
extremities and genital ulcers and swelling. Lesions may be
solitary or multiple. The most common histologic presentation is a superficial and deep granulomatous inflammatory
infiltrate, often accompanied by an eosinophil-rich mixed
perivascular infiltrate, and more rarely by lichenoid and
vasculitic granulomas. Granulomatous vasculitis may be a
specific clinically entity with distinct corresponding histopathologic findings within the spectrum of MCD.
Here we report two patients with CD and skin lesions characterized histopathologically by granulomatous vasculitis. A
29 year old female with a 20 year history of terminal ileal and
left-sided/rectal CD, presented with mild GI flaring and focal,
tender eroded and ulcerated nodules near the left lateral
malleolus. Histologically, prominent dermal and superficial
subcutaneous inflammation was present with a vasocentric infiltrate of mononuclear and multinucleated histiocytes. Fibrinoid change was seen in vessel walls. Lesions
responded to combined prednisone and injected triamcinolone. A male, age 35, with ileal and perianal CD for 15 years,
presented with inactive GI disease and two tender indurated
erythematous plaques on the left lower leg with punched
out centers . Biopsy showed vasculitis of small and medium
sized vessels in the dermis and subcutis. The fibrinoid
change of vessel walls was associated with granulomatous,
neutrophilic and lymphocytic inflammation. The lesions
improved with prednisone and injection with triamcinolone.
These two cases represent the rarely described phenomenon of cutaneous granulomatous vasculitis in CD.
Fact or fiction: does the non-HIV/AIDS
immunosuppressed patient really
need PJP prophylaxis?
Parbeer S. Grewal; Alain Brassard
University of Alberta, Edmonton, AB
Background: Pneumocystis jiroveci pneumonia (PJP) is a
potentially fatal fungal infection occurring in immunocompromised patients. There has been a lot of controversy and
conflicting reports in the literature regarding the role of
prophylactic treatment in the non-HIV/AIDS immunosuppressed population.
Objective: To determine whether or not PJP prophylaxis is
required in the non-HIV/AIDS immunosuppressed patient,
and if so, the optimal prophylactic therapy.
Methods: A thorough literature review, with the appropriate
MeSH terms, was conducted using PubMed, Medline and
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The Cochrane Database. A number of cases describing PJP
in patients with various systemic diseases and immunosuppressive medications, along with a Cochrane review, were
highlighted.
Results: Although there are a number of case reports in
the literature, the only collagen vascular disease with an
increased incidence of PJP is Wegner’s granulomatosis. Oral
trimethoprim-sulfamethoxazole (TMP-SMX) continues to be
the prophylaxis of choice for PJP.
Conclusions: Response to alitretinoin treatment was dose
dependent and
Conclusion: There is currently no evidence to recommend
PJP prophylaxis in the non- HIV/AIDS immunosuppressed
population. If the physician does decide to use prophylaxis
they should always weigh the benefits with the potential
risks. Further studies are needed to better quantify the risk of
developing PJP while on immunosuppressive medications.
significantly superior to placebo, when assessed by either
the physician or the patient. The high correlation between
the patient and physician evaluations in this study is noteworthy. The consistency of results obtained with the PGA
and PaGA supports the use of a categorical scale of severity
instead of an estimated degree of improvement, and the
non-ambiguous endpoint of ‘clear’ or ‘almost clear’ hands.
Comparability of physician and patient
assessments of disease following treatment
with alitretinoin in chronic hand eczema
Voclosporin (ISA247) pharmacokineticpharmacodynamic (PK-PD) profile—
results from ESSENCE study
Lynn Guenther1 Charles Lynde2 Les Rosoph3
Juergen Maares4 Thomas C. Brown4
Wayne Gulliver1 Robert Bissonnette2 Yves Poulin3
Aditya Gupta4 Patrick Mayo5 Richard Langley6
1. The Guenther Dermatology Research Centre, London, ON; 2.
Lynde Centre for Dermatology, Markham, ON; 3. Probity Medical
Research North Bay Dermatology Centre, North Bay, ON; 4. Basilea
Pharmaceutica Ltd. , Basel, Switzerland
1. NewLab Clinical Research Inc., St. John’s, NL; 2. Innovaderm Research
Inc, Montreal, QC; 3. Centre de Recherche Dermatologique du Quebec
Metropolitain, Quebec City, QC; 4. Mediprobe Research Inc., London,
ON; 5. Isotechnika Inc, Edmonton, AB; 6. Eastern Canada Cutaneous
Research Associates, Halifax, NS
Background: Alitretinoin (9-cis retinoic acid), has demonstrated efficacy in the treatment of severe chronic hand
eczema. Studies have shown that, when compared with
their physicians, eczema patients tend to rate their disease
as being more severe, whilst, following treatment, physicians
tend to assign higher disease improvement ratings than
patients.
Objectives: To assess the consistency of results obtained
using the Physician’s Global Assessment (PGA - based on an
integrated clinical picture of signs, symptoms and extent of
disease) and the Patients Global Assessment (PaGA - which
involves patients selecting a description that summarizes
their perception of treatment effects) to quantify the efficacy
of oral alitretinoin in patients with severe chronic hand
eczema.
Methods: Patients with severe chronic hand eczema were
recruited to a prospective randomized, double-blind, placebo controlled, parallel-group, multicenter study. Eligible
patients were required to have had chronic hand eczema for
at least 6 months and be refractory to topical corticosteroids
prior to entering the study. A total of 1,032 patients were
randomized 2:2:1 to alitretinoin 10 mg, 30 mg, or placebo
once daily for 12 to 24 weeks. Responses were defined by
physicians and patients, respectively, as a PGA and PaGA rating of ‘clear’ or ‘almost clear’.
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Results: Response rates as determined by PGA and PaGA
were 47.7% and 39.9% in the 30 mg alitretinoin group
(p<0.001 compared to placebo), 27.5% and 24.2% in the 10
mg group (p=0.004 compared to placebo), and 16.7% and
15.1% in the placebo group. The correlation coefficient for all
PGA and PaGA ratings at end of treatment was 0.785.
Introduction: Cyclosporine (CsA) is an efficacious agent in
plaque psoriasis, but suffers from dose-limiting toxicities.
Voclosporin (VCS) is a next generation calcineurin inhibitor
with increased potency, an improved PK-PD relationship and
a wider therapeutic window. Data from a previous Canadian
phase 3 trial showed that 91% of the reduction in Psoriasis
Area and Severity Index (PASI) scores could be attributed
to the trough concentrations of VCS during the study. The
Phase 3 ESSENCE study, which is both placebo and CsA controlled, has just completed.
Methods: A total of 642 patients (Canada, Germany and
Poland) were enrolled in the 60 week ESSENCE study.
Subjects were randomized to one of 3 treatment groups in
3:1:1 ratio (VCS 0.4 mg/kg bid, placebo, CsA 1.5 mg/kg bid,
respectively) for 12 weeks after which the placebo group
was converted to 0.4 mg/kg bid. After 60 weeks, all patients
were followed for an additional 12 weeks after discontinuation of treatment. Achieving “clear” or “almost clear” in the
Static Physician’s Global Assessment (SPGA) score after
12 weeks was the primary efficacy endpoint. A subset of
patients also participated in a PK-PD study at weeks 4, 12
and 24 to determine various PK-PD parameters.
Results and Conclusions: Blinded interim results demonstrate an acceptable pharmacodynamic response using the
calcineurin assay. Utilization of PK-PD information may allow
for improved patient management. Presentation of the
unblinded PK-PD data will take place at CDA’s 84th Annual
Conference.
Acute generalized exanthematous
pustulosis (AGEP) simulating toxic
epidermal necrolysis (TEN)
Richard M. Haber
University of Calgary, Calgary, AB
A 25 year old man was admitted to ICU with multiple
gunshot wounds and resulting abdominal trauma. He was
treated prophylactically prior to laparotomy with Tazocin
(Piperacillin and Tazobactam) IV.
Twenty-four hours later, he developed blisters on his feet
and then rapid development of diffuse blistering on his back
with a positive Nikolsky sign. As well, blistering occurred on
his upper and lower extremities and abdomen.
He also developed diffuse erythema on his arms, chest and
abdomen with multiple non-follicular pustules. There was no
mucosal involvement.
The initial clinical diagnosis was TEN with AGEP and staph
scalded skin in the differential diagnosis.
Skin biopsy was taken from a pustule on the chest and a
bulla on the abdomen.
The pustule biopsy showed a subcorneal vesicle with
neutrophils and eosinophils in the dermis. The bulla biopsy
showed an intraepidermal blister with neutrophils and
eosinophils in the dermis. Both biopsies were felt to represent AGEP with no evidence of TEN.
Treatment with IV Solucortef and good wound care brought
about slow resolution of the skin lesions over two weeks
with resolution without scarring and only some residual
post-inflammatory hyperpigmentation of the lower legs.
To my knowledge, this only the fourth report of AGEP mimicking TEN. It is important for dermatologists to recognize
that AGEP can simulate TEN because of the difference in
prognosis and treatment of the two conditions.
Keeping an eye on ocular melanoma
Tatyana Hamilton; Catherine Van Raamsdonk
University of British Columbia, Vancouver, BC
Introduction: Molecular mechanisms responsible for
ocular melanomas and other intradermal melanocytic proliferations such as blue nevi and nevus of Ota have not been
previously identified. Using a forward genetic screen, mice
with germline activating mutations of the heterotrimeric G
protein a-subunit GNAQ were found to harbour increased
numbers of intradermal melanocyes, resulting in hyperpigmented phenotype. GNAQ belongs to a class of G-protein
a-subunits involved in mediating signals between G-proteincoupled receptors (GPCR) and downstream effectors.
Results: A genetic screen of biopsy samples identified
GNAQ mutations in 24 of 29 blue nevi, 1 of 2 malignant blue
nevi, and 22 of 48 uveal melanomas. All mutations occurred
exclusively in codon 209 in the Ras-like domain and resulted
in constitutive activation, turning GNAQ into a dominant
acting oncogene. There results demonstrate an alternative
route to MAP kinase activation in melanocytic neoplasia.
Introduction of the Gln209Leu mutation activated the MAP
kinase pathway growth-signalling cascade and transformed
immortalized normal human melanocytes. Moreover, suppression of GNAQ transcripts in an ocular melanoma cell
line by RNA interference led to diminished cell growth and
apoptosis.
Conclusions: Uveal melanoma is a highly aggressive cancer
without any effective treatment options once it metastasizes. These latest molecular findings open a new approach
to ocular melanomas. The presence of a recurrent mutational hot spot in the GNAQ oncogene identifies signalling
components downstream of GNAQ as potential therapeutic
targets.
Interaction between ritonavir and
inhaled or intralesional steroids
Christina Han1 Richard I. Crawford1, 2
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Department of Pathology and Laboratory
Medicine, University of British Columbia, Vancouver, BC
Introduction: The interaction between inhaled fluticasone
and ritonavir causing adrenal suppression is well-documented in the medical literature. However, the use of other
local corticosteroids, namely intralesional or topical, causing
adrenal suppression in patients on antiretrovirals has not
been previously reported. Awareness of this drug interaction
is important for all dermatologists treating patients on antiretroviral therapies.
Methods: We describe two cases of adrenal suppression
during concurrent use of localized corticosteroid and an
antiretroviral regimen, which includes ritonavir, a protease
inhibitor.
Case 1: A 50-year-old man on long-term antiretroviral
therapy presents with a three month history of mild steroid acne and matted telangiectases over his upper torso. A
skin biopsy is consistent with sterile folliculitis. A search for
causes of corticosteroid excess reveals an inhaled steroid,
fluticasone, for asthma. Testing reveals a depressed AM cortisol level indicating suppression of endogenous adrenocorticoid production. The puffer is discontinued and lab testing
returns to normal.
Case 2: A 49-year-old man with previous success on intralesional steroids for his recalcitrant psoriasis of his elbows and
knees requests intralesional triamcinolone while on antiretrovirals. A normal baseline AM cortisol level is measured.
However, after three standard treatments of triamcinolone, it
is re-checked and found to be suppressed.
A systematic literature review is also included to evaluate
this interaction.
Results and Conclusion: A recent literature review reveals
several cases of iatrogenic adrenal suppression during
concomitant ritonavir and inhaled or intranasal fluticasone
similarly illustrated to our first case. To our knowledge, our
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latter case represents the first case of endogenous adrenal
suppression from intralesional steroid use in a patient on
ritonavir. Ritonavir increases the systemic bioavailability of
corticosteroids by inhibiting cytochrome-P450- isoenzyme3A4 leading to glucocorticoid excess and ultimately, adrenal
suppression. Thus, this drug interaction and its adverse
effect on the adrenocorticoid axis must be considered in
patients on ritonavir, even when small standard doses of
local corticosteroids are used.
Additionally, no adverse interactions have yet been documented with the use of topical corticosteroids and antiretroviral treatment. This combination represents an area that
warrants further study.
A review of electron microscopy in
dermatologic diagnosis: a current
case of progressive mucinous
histiocytosis as an example
Iman Hemmati1 W Alastair McLeod2 Richard I. Crawford2, 3
1. Faculty of Medicine, University of British Columbia, Vancouver, BC;
2. Department of Dermatology and Skin Science, Universtiy of British
Columbia, Vancouver, BC; 3. Department of Pathology and Laboratory
Medicine, University of British Columbia, Vancouver, BC
Introduction: once an important tool in dermatologic
diagnosis, electron microscopy has been largely replaced
by immunohistochemistry and immunofluorescence
techniques today, particularly within the realms of bullous
disorders, pigmented disorders and viral diseases. However,
electron microscopy occasionally still plays a crucial role in
diagnosis of dermatological conditions. We report a case of
progressive mucinous histiocytosis (PMH) as an example of
a dermatological disorder that requires electron microscopy
for its diagnosis.
Methods: A 60-year-old woman presented to our clinic with
a history of small, sharply demarcated, skin-coloured papules ranging from 2-5 mm in diameter distributed over arms,
forearms and dorsal hands. The results of light microscopy,
immunohistochemical studies and clinical examination
were inconclusive. Another biopsy for electron microscopy
showed characteristic features of PMH
Conclusion: this case demonstrates that, although electron
microscopy has almost entirely been replaced by immunohistochemical and immunofluorescence techniques for
dermatologic diagnosis, a dermatopathology service does
still need to have access to electron microscopy for diagnostic purposes in order to successfully diagnose a small
number of rare conditions.
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A rare presentation of Kaposi sarcoma
Anna A. Hinek; Sheila Au; Sunil Kalia; Richard Crawford
Department of Dermatology, University of British Columbia, Vancouver,
BC
Kaposi sarcoma (KS) is a vascular neoplasm, with human
herpesvirus-8 playing a key etiologic role. We present a rare
presentation of KS in the context of advanced HIV disease.
A 27-year-old HIV positive female (CD4 count=190, viral
load=133 000 copies/mL), with a known history of KS of
the cervical lymph nodes, was admitted to hospital with a
history of acute facial and leg edema. Examination revealed
a patient whose entire face was swollen beyond recognition. She had highly indurated neck, cheek, and upper chest
plaques. Her legs and feet were also strikingly edematous
with multiple tense and weeping bullae on the feet. Examination of the proximal thighs, groin and labia revealed firm,
violaceous induration and swelling. The abdomen, back
and arms were thin and spared, revealing her underlying
cachectic state. Biopsies of the neck and thigh plaques
were diagnostic of KS. The patient was started on liposomal
doxorubicin, with improvement of her cutaneous infiltration
and swelling.
KS has a propensity for lymphatic invasion, which can result
in outflow obstruction. Areas with reduced collateral support are most at risk. External compression of lymphatics by
skin lesions may also cause obstruction. This case demonstrates the classic features of KS lymphedema as described
in the literature: localized edema of the face, legs and genitals, with infiltration and ecchymosis-like discoloration of
the proximal skin. This presentation of KS is difficult to treat.
Chemotherapy, antiretrovirals, compression, physiotherapy,
and occasionally surgery may be required to ameliorate the
significant physical impairment of this invasive disease.
Baboon syndrome induced by
surgical skin staples
Marie-Claude Houle; Nathalie Provost
Université de Montréal, Montréal, QC
This is the case of a 56 year-old woman presenting for an
acute pruritic eruption two days after a laparoscopic surgery.
Her eruption constituted of eczematous plaques symmetrically distributed on the axillae, inner thighs and buttocks and
around each surgical skin staple used to close the wounds.
Upon questioning, she revealed having had very important
skin reactions to metal buttons, earrings and bracelets in the
past. Thereafter, the diagnosis of probable Baboon syndrome, or systemic contact dermatitis, to nickel was done.
The patient was treated with 25 mg prednisone x 6 days and
the eruption rapidly resolved.
Who cares for acne patients? An examination
of the United States National Provider
distribution for acne care 2003–2005
Nayla Idriss April W. Armstrong Hagit Bergman
2
2
1
1. Harvard School of Public Health, Newton, MA, United States;
2. UC Davis, California, CA, United States
Background: Acne is one of the most common reasons
patients seek dermatological care in the United States. Given
an apparent shortage of the dermatology workforce, nondermatologist physicians have been providing direct care for
patients presenting with acne. In this study, we investigated
the state of national provider distribution for acne from
2003 through 2005 and analyzed patient characteristics that
are predictive of obtaining acne care from a dermatologist
versus a non-dermatologist physician.
Methods: We compiled provider data from the National
Ambulatory Medical Care Survey (NAMCS) and National
Hospital Ambulatory Medical Care Survey (NHAMCS) during years 2003 through 2005. Using a weighted sample
of 6,661,592 patients whose visit code contained acne,
we examined the proportion of acne encounters seen by
dermatologists and non-dermatologist physicians during
this period. To determine patient demographic predictors
for seeing a dermatologist versus a non-dermatologist
physician, we performed univariate analysis of demographic
factors and constructed a multivariable regression model
controlling for known confounders.
Results: During 2003 through 2005, 64.6% of patients seeking acne care saw a dermatologist, and 35.4% patients saw
a non-dermatologist physician. Among non-dermatologist
physicians, pediatricians provided care to nearly 16% of
all acne patients, followed by general/family practitioners
(12%), internal medicine physicians (5.4%), and OB/GYN
physicians (1%). Having acne as the primary diagnosis for
the encounter (OR 11.99, 95% CI [6.51, 22.06]) and being
prescribed isotretinoin (OR 10.95, 95% CI [1.92, 62.37])
significantly predicted the odds of seeing a dermatologist
for acne care. In contrast, factors that significantly decreased
the odds of seeing a dermatologist included age less than
18 years (OR 0.14), Hispanic or Latino ethnicity (OR 0.34),
obtaining medical care in the Midwest (OR 0.43) or West
region of the country (OR 0.42), and having Medicaid/SCHIP
(State Children’s Health Insurance Program) insurance (OR
0.21) Of note, being female or white was not associated with
increased odds of seeing a dermatologist.
Conclusions: Non-dermatologist physicians, especially
pediatricians, family practitioners, internists, and OB/GYN
physicians, appear to play a critical role in caring for patients
with acne.
Keratoderma blenorrhagicum
Sara-Elizabeth Jean; Linda Moreau
McGill University, Montreal, QC
Introduction: Reiter’s syndrome is traditionally used to
describe the triad of urethritis, conjunctivitis and arthritis.
More recently, this historical eponym has been gradually
replaced in favor of reactive arthritis. Dermatological
manifestations of reactive arthritis include keratoderma
blenorrhagicum, psoriasiform eruptions, balanitis circinatum
and oral ulcers. We describe a case of keratoderma blenorrhagicum in an elderly woman who had had a recent urinary
tract infection.
Methods: An 86-year-old woman presented to our clinic
with a two-week history of progressive onset asymptomatic lesions on her soles and a rash on the dorsum of her
right big toe. This eruption occurred while she was treated
with adalimumab for a severe and deforming rheumatoid
arthritis. She denied genito-urinary or systemic symptoms,
nor did she have a flare up of her rheumatologic condition.
Physical examination revealed numerous monomorphic 4
to 6 mm keratotic firm orange-erythematous round papules
involving the soles symmetrically. A very well demarcated
psoriasiform erythematous plaque with silvery scale was
covering the dorsum of her right big toe. Nails were spared.
Throat examination was unremarkable. There were no signs
of synovitis.
Results: Histopathologic examination of a skin punch
biopsy demonstrated a psoriasiform epidermal hyperplasia with neutrophilic exocytosis. PAS and gram stains were
negative for fungi and bacteria respectively. Review of this
patient’s chart revealed a recent positive urine culture for
Escherichia Coli.
Conclusion: Keratoderma blenorrhagicum is a rare manifestation of reactive arthritis. Our patient displayed characteristic physical and histopathology findings of this clinical
entity. However, her clinical presentation is atypical because
the eruption was not accompanied by the usual asymmetric inflammatory arthritis as previously described in the
literature. We hypothesize that our patient had this unusual
presentation because of the attenuating effect of the antitumor-necrosis factor treatment that she was on for her
debilitating rheumatoid arthritis.
Botulinum toxin type A (BOTOX®)
treatment for Raynaud’s and other novel
dermatologic therapeutic applications
Irèn Kossintseva1 Benjamin Barankin2 David Zloty1
1. University of British Columbia, Vancouver, BC; 2. The Dermatology
Centre, Toronto, ON
The etiology of Raynaud’s disease is complex, but both
vasospasm and nociception play a major role. BoNTA inhibits
noradrenaline-mediated sympathetic vasoconstriction, thus
improving perfusion of digits by opening up the vasculature
and allowing for better oxygenation. It concurrently inhibits
a39
pain-stimulating neuropeptides (substance P, Calcitonin
Gene-Related peptide and glutamate) thus interfering with
nociception, both peripheral and central sensitization, and
decreasing swelling and inflammation. BoNTA therefore
presents a successful and safer alternative to surgical digital
artery sympathectomy. Here we also present practical tips
on assessment and injection parameters for BoNTA administration in the treatment of Raynaud’s disease.
Furthermore, BoNTA’s complex pharmaco-physiology which
targets cholinergic (motor and sweat), autonomic (vasodilator and vasoconstrictor), inflammatory and nociceptive
(Substance P, CGRP, glutamate) aspects allows for other
extensive dermatologic applications. By targeting hypersecretion, BoNTA injection has shown success in the treatment
of not just hyperhydrosis, but also other conditions made
worse by increased sweating such as Frey’s Syndrome, localized unilateral hyperhidrosis, Ross’ syndrome, pomphylox,
inverse psoriasis, parotid fistulas, and Hailey-Hailey disease.
BoNTA’s anti-nociceptive properties have been used in the
aid of treatment of multiple cutaneous piloleiomyomas as
well as of notalgia paresthetica.
The 2008 Eczema Awareness Support and
Education (EASE) program patient survey
Paul F. Kuzel; Marlene T. Dytoc
Department of Dermatology, Faculty of Medicine, University of Alberta,
Edmonton, AB
Paul Kuzel - Medical Student; Dr. Marlene Dytoc, MD - CDA
member, Sponsor
The 2008 Eczema Awareness Support and Education (EASE)
Program patient survey, the latest such survey since 2005,
revealed several key trends over a broad range of eczemarelated topics.
A non-randomized, voluntary online survey was conducted
between October 27 and November 30, 2008. Responses
were obtained from 417 Canadians who personally suffer
from, or have a child or spouse who suffers from, eczema.
Emotional factors were the most common reported cause of
eczema flare-ups. Family physicians are playing an increasing role in the diagnosis and treatment of eczema, with 47%
of respondents having first heard about eczema from their
family physician (up 8% from 2005). Family physicians were
reported as the most common source of eczema health
information (63%). However, the quality of information
received from doctors was rated as fair or poor by 61% of
suffers; only 2% classified it as excellent or very good. There
were clear differences amongst English and French speaking
respondents, specifically in their level of satisfaction with
information obtained from family physicians, as well as in
the amount French and English speaking Canadians relied
on dermatologists as compared to family physicians as a
source of information. Differences between the sexes were
apparent. Women were generally more proactive in seeking out eczema health information, and made up 86% of
respondents to this survey. Topical steroid therapy was the
a40
most common treatment being used (67%). 25% of sufferers
use topical tacrolimus, while the use of topical pimecrolimus was 11% lower. Half of all adults and 38% of children
indicated that no treatment was improving their condition.
When prescribed a medication to treat their eczema, less
than one third of respondents received some form of counselling, while 56% were unaware of the topical calcineurin
inhibitor class of drugs. A key finding of this survey is the
need for improved communication and patient education
by physicians.
Scrofuloderma and chronic
immunosuppressive therapy
Angela Law2 Brandon G. Howell1 Cheryl Rosen3
1. University of Toronto Dermatology Resident, Toronto, ON; 2.
University of British Columbia, Vancouver, BC; 3. University of Toronto,
Toronto, ON
Background: Scrofuloderma is a form of TB arising from
the subcutis that results in breakdown of skin and tissue
overlying a tuberculous focus-often an infected lymph node
or area of bone. This form of cutaneous TB has remained
relatively uncommon in industrialized countries.
Objective: To describe a case of scrofuloderma of the chest
in a patient on chronic immunosuppressive therapy, and
provide a brief review of tuberculosis.
Methods and results: A 72-year-old lady with a longstanding history of polymyalgia rheumatica (PMR) was on systemic prednisone therapy for the past 7 years. She presented
with a 9-month history of an inflamed, fistulizing mass on
her anterior chest wall and diffuse lymphadenopathy. A
combination of skin biopsy and AFB culture from the aspirate of the fistulizing mass and the axillary lymph node gave
rise to the diagnosis of disseminated TB with cutaneous TB
(scrofuloderma variant).
Conclusion: This case report illustrates that uncommon
forms of cutaneous TB must be considered in patients who
present with fistulizing wounds, especially in the setting of
chronic immunosuppressive therapy. It is important to consider the possibility of reactivating latent TB when starting
immunosuppressive regimens for chronic disease.
Segmental neurofibromatosis
Mark Lupin1 Doug Sawyer1,2 Patrizia E. Moccia1
1. Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC; 2. Vancouver Island Health Authority, Victoria,
BC
Segmental Neurofibromatosis is a subtype of Neurofibromatosis type 1 (NF-1) in which the disease features are limited
to one segment of the body. Patients may present with
café-au-lait macules, neurofibromas, or both. Distribution is
most often unilateral, but may be bilateral. Patients do not
typically have a family history of neurofibromatosis. This disorder is rare, with a reported incidence of 1/36 000 to 1/40
000. We present a case of a 42-year-old Caucasian female
with a unilateral grouping of isolated neurofibromas of the
neck. We review the literature on diagnosis and genetics of
Segmental NF-1, as well as discuss management of painful
or cosmetically unappealing neurofibromas.
Immune responses to pneumococcal
vaccine in adults with chronic plaque
psoriasis treated with alefacept
Charles W. Lynde1 James Krell2 Neil Korman3
Barbara Mathes4
1. Lynde Centre for Dermatology, Markham, ON; 2. Total Skin & Beauty
Dermatology Center, Birmingham, AL, United States; 3. University
Hospitals of Cleveland, Cleveland, OH, United States; 4. University of
Pennsylvania, Philadelphia, PA, United States
Background: Alefacept is a fully human fusion protein with
a mechanism of action that could, in principle, affect the
ability of patients to mount an immune response to vaccines. This open-label, phase IV multicenter study assessed
the ability of patients with chronic plaque psoriasis (CPP)
receiving alefacept to mount an immunological response to
a pneumococcal vaccine.
Methods: Adult patients with CPP involving >5% body
surface area were treated with a standard 12-week course
of alefacept (15 mg intramuscularly once a week). At Week
6, patients were administered a 23-valent polysaccharide
pneumococcal vaccine. Anti-pneumococcal antibodies were
measured at Weeks 0 (baseline), 6 (pre-challenge), 9, 12 and
33. The primary endpoint was the percentage and number
of patients who demonstrated a ≥2-fold increase from Week
6 to Week 12 in antibody titer for ≥2 of the 5 pneumococcal antigens (9V, 14, 18C, 19F and 23F). Efficacy and safety
assessments were performed at all visits.
Results: Of the 43 patients enrolled, 40 completed Week
14 and 32 completed Week 33. At Week 12, doubling of
antibody titers against ≥2 of the 5 primary pneumococcal antigens was observed in 36 patients with 24 patients
demonstrating quadrupling of titers compared with Week
6. At Week 33, 25 patients had 2-fold increases in antibody
levels and 15 had 4-fold increases compared with Week 6.
At baseline, 38 of 42 patients had moderate or worse CPP
based on Physician’s Global Assessment. After alefacept
treatment, only 14 patients remained in this group; 28
patients improved to mild-to-moderate or better with 3
patients achieving almost clear status. Adverse events (AE)
were observed in 21 patients and were similar to those seen
in previous studies, with the majority being mild or moderate in intensity. No serious AE were reported.
Conclusions: Alefacept was well tolerated. The safety and
efficacy of alefacept was similar to published results. In adult
patients with CPP treated with alefacept, 85.7% were successfully able to mount an immune response to pneumococcal vaccine.
Alitretinoin re-induces response in
relapsed chronic hand eczema patients
Charles Lynde1 Robert Bissonnette2 Lynn Guenther3
Thomas C. Brown4 Juergen Maares4
1. Lynde Centre for Dermatology, Markham, ON; 2. Innovaderm
Research, Montreal, QC; 3. The Guenther Dermatology Research Centre,
London, ON; 4. Basilea Pharmaceutica Ltd. , Basel, , Switzerland
Objectives: To assess the efficacy and safety of a 12- to 24week course of oral alitretinoin (9-cis retinoic acid) 10 mg
or 30 mg in patients with severe steroid refractory chronic
hand eczema previously treated with alitretinoin or placebo.
Methods: Chronic hand eczema patients who participated
in an earlier clinical trial (receiving alitretinoin 10 mg or 30
mg) who either failed to respond or responded and relapsed
within 24 weeks, were enrolled. Response was defined as a
Physician’s Global Assessment rating of ‘clear’ or ‘almost clear’
at the end of therapy. Responding patients who relapsed
(N=117) were re-randomized in a double-blind fashion to
either their previous treatment (10 mg or 30 mg alitretinoin
daily) or to placebo. Non-responding patients (N=243)
received 30 mg of alitretinoin. Treatment was for 12 to 24
weeks.
Results: Relapsed patients treated with alitretinoin 30 mg or
10 mg had higher response rates than those re-randomized
to placebo (79.6% vs. 8.3% and 47.6% vs. 10.0%, respectively). Among previous non-responders the response rate
was 47.3%. Alitretinoin was well tolerated, with the adverse
event profile similar to that of the initial treatment course,
and consistent with known retinoid class effects.
Conclusions: Patients with chronic hand eczema who
respond to alitretinoin and later relapse, can regain response
with a further 12 to 24 week course of alitretinoin, with the
highest response rate achieved in the 30 mg group. Prolonged treatment with oral alitretinoin 30 mg led to further
responses. No late-arising adverse reactions were observed
with re-treatment or prolonged treatment.
Made in Canada: development of voclosporin
(ISA247) for the treatment of psoriasis
Charles Lynde1 Neil Shear3 Lyn Guenther4 Kim Papp5
Robert Foster2 Richard Langley6
1. Lynderm Research Inc, Markham, ON; 2. Isotechnika Inc, Edmonton,
AB; 3. Sunnybrook Dermatology Clinic, Toronto, ON; 4. Guenther
Dermatology Research Centre, London, ON; 5. Probity Medical
Research, Waterloo, ON; 6. Eastern Canada Cutaneous Research
Associates, Halifax, NS
Background: Calcineurin inhibitor (CNi) based therapies are
effective in the treatment of plaque psoriasis. Cyclosporine
(CsA), a first-generation CNi, is efficacious, but has doselimiting adverse events. Using a pharmacodynamic measure
(calcineurin inhibition) to more accurately evaluate efficacy,
voclosporin (VCS) was developed by Isotechnika, a Canadian
company, to provide a drug with similar efficacy to CsA, but
improved PK-PD and safety profiles.
a41
Drug Development Pathway: A Canadian Phase 3 study
demonstrated that VCS was efficacious and that blood
concentrations correlated strongly with mean percentage
reduction in psoriasis area and severity index (PASI). In the
phase 3 randomized, multicentre, double-blind ESSENCE
study, the efficacy and safety of VCS was compared to placebo and an active comparator, cyclosporine. Comparison
with the CNi cyclosporine provided a proper assessment of
benefit/risk ratio. Safety, efficacy and PK-PD results from the
ESSENCE trial are currently blinded, but will be available for
CDA’s 84th Annual Conference.
Conclusions: A single cycle of rituximab 1g on days 1
and 15 is an effective treatment for pemphigus. Our study
showed that the dose of prednisone can be significantly
decreased and other medications such as IVIG can either be
decreased or discontinued. We did not observe any serious
adverse effects during the 6-month follow-up period. Further observation is needed to determine whether a second
cycle of rituximab may be needed in patients having flares at
6 to 9 months after the first cycle.
Conclusions: VCS has been assessed for the treatment of
psoriasis during a Phase 2a trial, a Canadian Phase 3 trial,
and a Canadian/European Phase 3 trial in which Canadian
sites participated. Canadian dermatologists have played a
primary role in the development of this drug, not only acting
as Investigators and sitting on Steering Committees, but also
acting as impartial adjudicators on Data Monitoring Committees. Voclosporin is an example of the lead role Canadian
Dermatology can play in drug development from Phase 1-3.
Loukia-Maria Mitsos4 Judith Simoneau-Roy5 Pierre-Hugues
Fortier3 Edmond Rizcallah 2 Dominique Hanna4
Effect of a single cycle of rituximab
for recalcitrant pemphigus
Setsuko Matsukura; Sandra P. Knowles; Scott Walsh;
Neil H. Shear
Sunnybrook Health Sciences Centre, Department of Dermatology,
Toronto, ON
Background: There is increasing evidence that a single cycle
of rituximab (375 mg/m2 body surface area once weekly for
four weeks) is efficacious in patients with severe pemphigus.
The approved protocol for rituximab in rheumatoid arthritis
is a 1g on days 1 and 15. We hypothesized that the latter
protocol would also be effective in pemphigus.
Methods: Nine patients (mean age 41.3 ±SD 11.5yr) with
severe recalcitrant pemphigus were administered rituximab
between January and August 2008. Eight patients had
pemphigus vulgaris and one had pemphigus foliaceus.
Two patients had skin lesions on more than 50% of BSA.
Eight patients were treated with high doses of prednisone (58.1mg/d ±49.7). Immunosuppressive agents used
included mycophenolate mofetil (8 patients), azathioprine
(1 patient), methotrexate (1 patient), and cyclophosphamide
(1 patient.).Intravenous immunoglobulin (IVIG) was administered in six patients. Rituximab 1g was infused on days 1 and
15. Each patient was observed for a minimum of six months.
Results: Re-epithelialization of at least 50% of affected areas
occurred in all patients between 4 and 16 weeks (7.5 weeks
±3.1). A moderate flare was observed in 1 patient on his face
at 5 months. 50% of patients had IVIG discontinued (two
at 3 months and one at 5 months). A 39% decrease in the
mean dose of prednisone was observed at one month (35.1
mg ±22.3,), 67% at 3 months (21.7 mg±11.9), and 74% at 6
months (15.23 mg±3.7). There were no serious infections or
other adverse effects observed during the 6-month followup period.
a42
A mouth that leads to a diagnosis of MEN 2B
1. Sherbrooke University, Sherbrooke, QC; 2. Department of Pathology,
Sherbrooke, QC; 3. Division of ENT, Department of Surgery, Sherbrooke,
QC; 4. Division of Dermatology, Department of Medicine, Sherbrooke, QC;
5. Division of Endocrinology, Department of Pediatrics, Sherbrooke, QC
Background: Multiple endocrine neoplasia type 2B (MEN2B)
is a rare disorder characterized by highly malignant medullary thyroid carcinomas, pheochromocytomas, multiple
mucosal neuromas, intestinal ganglioneuromas and marfanoid habitus. This syndrome is caused by a germ line
mutation in the RET proto-oncogene and the inheritance is
usually autosomal dominant.
Methods: We describe the case of a 13 year old boy with no
past medical history and no family history who was referred
by his dentist for an 8 year history of oral tumors previously
misdiagnosed as fibromas. The patient presented multiple
soft and painless papules and nodules on the lips, palate,
tongue, and oral mucosa. The rest of the cutaneous and
physical examination were unremarkable.
Results: Biopsy results of the oral papules confirmed the
diagnosis of neuromas. A CT scan of the neck and abdomen
revealed 2 thyroid nodules, multiple cervical adenopathies and a nodule in proximity to the inferior vena cava
suggesting ganglioneuromatosis vs pheocromocytoma.
Biochemical evaluation revealed normal catecholamine and
TSH levels but elevated calcitonin (196 ng/L; N= 0-10) and
CEA levels (7.8 µg/L; N= 0-2.5).
The patient underwent total thyroidectomy with bilateral
neck and central node dissection for local disease control.
Histopathology results revealed medullary thyroid carcinoma with 3 /45 positive nodes. Sequencing of the patient’s
RET proto-oncogene showed a Met918Thr de novo gain of
function mutation.
Conclusions: Men2B is a rare genetic polyendocrinapathy
caused by activating germ-line mutations in the RET protooncogene. The diagnosis of MEN2B is often delayed at
which time medullary thyroid carcinoma may be regionally
advanced or metastatic. Early diagnosis and treatment of
these patients is essential for this aggressive tumor. Surgery
is the only definitive therapy. Clinical trials for tyrosine kinase inhibitors may provide hope for patients with advanced
MEN 2B syndrome.
NAPSDERM: NAtional Psoriasis
Survey for DERMatologists
Kristin Noiles1 Ronald Vender2
1. McMaster Medicine, Hamilton, ON; 2. Dermatrials Research,
Hamilton, ON
Background: With the increasing use of biologic agents
to treat psoriasis, certain private and public agencies may
require information on specific characteristics of a patient’s
psoriasis. We have created a survey in the hopes of determining which aspects of psoriasis are used or documented
most frequently by dermatologists across Canada in diagnosing and managing clinic patients.
Methods: A survey was created and faxed to dermatologists across Canada. Dermatologists who indicated that they
treated psoriasis in their clinical practices were subsequently
asked to select the various aspects of a patient’s psoriasis
that they routinely document. The options included the following: body surface area (BSA), Psoriasis Area and Severity
Index (PASI), Dermatology Life Quality Index (DLQI), Physician’s Global Assessment (PGA), redness, thickness, scale,
nail involvement, scalp involvement, genital involvement,
and intertriginous involvement.
Results and Conclusions: The results on this national
survey along with the accompanying implications will be
presented at the 2009 CDA conference in Vancouver.
Are excipients really inert ingredients? A
review of adverse reactions to excipients in
oral dermatologic medications in Canada
Kristin Noiles Ronald Vender
1
2
1. McMaster Medicine, Hamilton, ON; 2. Dermatrials Research,
Hamilton, ON
Background: Pharmaceutical excipients comprise all of the
components of medications other than the active ingredients. Conventionally, excipients have been regarded as inert
or inactive ingredients. However, along with technological
and economic advancements in the pharmaceutical industry, the definition of excipient has evolved from a simple
pharmacologically inert substance to a crucial adjuvant
which both guarantees and optimizes the characteristics of
a medication. While several literature reviews have discussed
the role of excipients in drug-related reactions, no manuscript has focused specifically on those found in oral dermatologic medications.
Methods: The Compendium of Pharmaceuticals and Specialties (CPS) was used to reference the inert ingredients
found in oral dermatologic medications. Excipients were
reported, categorized, and charted for each medication.
Additional charts were created specifying which medications are gluten-, dye-, or lactose- free. An extensive literature review was subsequently conducted using PubMed and
MEDLINE to document known adverse reactions to these
excipients.
Results and Conclusions: As excipients are generally
selected for their low toxicity, adverse reactions are both
mild and infrequent when compared to the overall prevalence of drug reactions. However, despite the infrequent
occurrence of reactions to excipients, they still must be
considered during the investigation and management of a
patient with a potential drug reaction. Furthermore, attention should also be given to patients with certain metabolic
disorders, enzyme deficiencies, or acquired diseases as well
as to patients with known allergies or sensitivities as they
will be more likely to react to these inert ingredients. This
manuscript serves as a reference guide for dermatologists
to aid in prescribing medications to individuals with known
sensitivities and to assist in working up patients with suspected reactions to inert ingredients.
Biologic survival
Kristin Noiles1 Ronald Vender2
1. McMaster Medicine, Hamilton, ON; 2. Dermatrials Research,
Hamilton, ON
Background: The results of long-term studies on the efficacy and safety profiles of the biologics for patients with
psoriasis are starting to appear in the literature. Not only are
the results promising for the biologics as a whole, but the
high number of patients remaining in these clinical trials
after extended periods of time may also reflect additional
benefits of the biologics. This manuscript aims to compare
rates of attrition for the various biologic therapies in pivotal
clinical trials. This is also known as biologic survival.
Methods: An in-depth literature review was conducted
using PubMed and MEDLINE. Randomized, controlled trials
utilizing biologic agents as monotherapy for the treatment
of psoriasis were analyzed for patient numbers over time.
Studies which provided data on patient retention for at least
24 weeks were selected, graphed and compared. Reasons
for discontinuation were listed for each study. For the studies using various dosing regimens, intrastudy attrition rates
were also compared.
Results and Conclusions: Nineteen trials were selected,
graphed and charted to compare attrition rates of the various biologic therapies. Due to limited data with regards to
patient numbers as well as to differences in sample sizes,
study designs, dosing regimens and study durations, only
preliminary conclusions can be drawn. However, given the
data available, etanercept appears to be associated with the
lowest rate of discontinuation over longer periods of time in
clinical trials. This may be due to superior efficacy and to a
decreased likelihood of experiencing adverse events.
a43
Psoriasis registries: useful data collection tools
Kim A. Papp Robert Bissonnette Marc Chevrier
Carin Binder4 Lyn Guenther5, 6
1
2
3
1. Probity Medical Research, Waterloo, ON; 2. Innovaderm Research
, Montréal, QC; 3. Centocor Ortho Biotech Services LLC, Horsham,
PA, United States; 4. Janssen-Ortho Inc, Tornto, ON; 5. Professor of
Dermatology, University of Western Ontario, London, ON; 6. Medical
Director, The Guenther Dermatology Research Centre, London, ON
Introduction: There are currently many ongoing multicenter North American “registries” of patients with psoriasis
These “registries” are prospective cohort studies often
centered on safety surveillance. A key challenge facing these
registries is providing optimal context to assess risks and
outcomes.
Methods: Design of current or recently completed multicenter industry sponsored “registries” for plaque psoriasis in
North America was collected from government-sponsored
web sites and public poster presentations as of March 2009.
Scope of activity was summarized including: length of
observation, outcomes/safety measures, inclusion/exclusion criteria, data source (e.g., dermatology practice vs
pharmacy), specific product vs disease-based and interval vs
cross-sectional data collection.
Results: North American plaque psoriasis multi-center
registries include : RESTORE;AWARE;OBSERVE;ATLAS;ESPRI
T and PSOLAR. The RESTORE, AWARE, OBSERVE and ESPRIT
studies are designed to collect data on patients treated with
efalizumab, alefacept, etanercept or adlimumab respectively. Some (e.g, OBSERVE, ESPRIT) limit patients to those
matching label criteria or address specific observations (e.g.,
ATLAS, malignancy/ infection in alefacept-exposed patients).
PSOLAR (PSOriasis Longitudinal Assessment and Registry)
reflects a disease-based inclusion criteria sampling multiple
therapies for psoriasis patients currently taking (or eligible
for) systemic therapy including biologics. The studies exhibit
variable periods of observation. None offers a randomized
control group, and all have bias based on participation
and channeling of therapy. Data are collected primarily by
dermatology centers. .
Conclusion: Registries of plaque psoriasis in North America
vary in objective and approach, and are usually productspecific. Registries may capture events and outcomes associated with long-term exposure or unusual clinical course.
PSOLAR allows a proportion of patients to be observed on
treatments other than the sponsor’s biologic. Some studies
have excluded patients that do not conform to the product
label limiting the population under analysis.
a44
A Canadian survey evaluating the
practice patterns in the management of
moderate to severe plaque psoriasis
Kim A. Papp1 Norman Wasel2 Yves Poulin3 Robin Andrew4
Elisa Fraquelli5 Daphne Chan 4
1. Probity Medical Research, Waterloo, ON; 2. Stratica Medical,
Edmonton, AB; 3. Université Laval, Quebec, QC; 4. Medical Affairs,
Janssen-Ortho, Toronto, ON; 5. Business Information-Janssen-Ortho,
Toronto, ON
Introduction: Psoriasis is a chronic autoimmune disease
associated with substantial physical, psychosocial and
economic burden. This study evaluated the variability of
Canadian practice patterns and management of moderateto-severe psoriasis.
Methods: An online patient survey was conducted using a
consumer panel. Eligible respondents reported a diagnosis
of psoriasis by a physician, had at least moderate disease
within the past 5 years and met at least one of the following
criteria: 1) ≥3% BSA affected, 2) psoriasis on a sensitive area
(hands, feet, scalp, face, genitals), or 3) currently receiving
prescription oral and/or injectable medication or photo/
light therapy for their psoriasis.
Results and Conclusions: 514 of 3845 eligible patients completed the questionnaire (mean age: 49.7yrs; male/female
ratio 1:2). Initial diagnosis was made predominantly by GP/
FPs (63%) followed by Dermatologists (34%) in most provinces except Quebec, where initial diagnosis was primarily
by Dermatologists (57%). Fifty-nine percent of respondents
were followed by GP/FPs for regular disease management
and respondents (41%) were likely to visit a GP/FP at a time
of sudden worsening. Quebec respondents were more likely
to visit their Dermatologists for ongoing disease management (55%) relative to the remainder of Canada (30%). Most
patients were currently treated with prescribed (61%) or OTC
topicals (33%). Those currently treated with injectables (5%),
photo/light therapy (7%) or orals (8%) were most likely managed by Dermatologists (71%, 74% and 42%) and tended to
be ‘very satisfied’ with their care (43%) compared to those on
topicals (18%). Twenty-eight percent of those followed by
Dermatologists (n=185) were ‘very satisfied’ with their management compared to 17% followed by a GP/FP (n=303).
The diagnosis and treatment of psoriasis in a sample of Canadians reporting moderate-to-severe disease reveals much
variability. A better understanding of the flow of patient care
within the medical community will likely improve overall
disease management and patient outcomes.
Two-step dosing of subcutaneous ustekinumab
by body weight provides similar efficacy
in heavier and lighter weight patients
with moderate-to-severe psoriasis
Kim A. Papp1 Newman Yeilding2 Yuhua Wang2 Mark
Lebwohl3
1. K Papp Clinical Research Inc, Waterloo, ON; 2. Biostatistics,Centocor
Research and Development Inc, Malvern, PA, United States; 3. Mount
Sinai School of Medicine, New York, NY, United States
Objectives: Efficacy of fixed-dose biologics may be affected
by weight with lower response rates in heavier patients. We
evaluated the impact of weight on ustekinumab efficacy
and determined whether weight should be considered in
dose selection.
Methods: PHOENIX 1 and 2 evaluated ustekinumab in
patients with moderate-to-severe plaque psoriasis (≥10% of
total body surface area and PASI score ≥12) who were candidates for phototherapy/systemic therapy. Patients were
randomized to subcutaneous ustekinumab 45-or 90mg at
wks0 and 4 and then q12wks or placebo with crossover to
ustekinumab at wk12. Prespecified efficacy analyses were
conducted by weight categories in 10-kg increments at
steady-state drug levels.
Results: 664 patients were randomized to ustekinumab
45mg and 667 to ustekinumab 90mg. Mean baseline
weights were 93.9kg and 91.0kg in PHOENIX 1 and 2,
respectively. Based on the analysis by weight categories in
10-kg increments, a dose-response was most evident for
the subpopulation of patients >100kg with Week 28 PASI75
response about 20 percentage points higher in the 90mg
than in 45mg group (74.2% [155/209] and 54.6% [107/196]
for 90mg and 45mg groups, respectively). In patients
≤100kg, response rates were similar between the groups
(PASI75: 80.8% [350/433] and 76.9% [347/451] for the 90mg
and 45mg groups, respectively). Pharmacokinetics paralleled
efficacy findings with median ustekinumab serum concentrations in patients weighing >100kg in the 90mg group
similar to those in patients weighing ≤100kg in the 45mg
group. An impact of weight on safety was not apparent
(54.7% versus 54.5% of patients had > 1 adverse event in the
≤100kg and >100kg weight subgroups, respectively).
Conclusion: Two-step dosing of ustekinumab (45mg
for patients weighing ≤100kg and 90mg for those
weighing>100kg) provides comparable efficacy and pharmacokinetic exposure in both heavier and lighter weight
patients. This two-step dosing approach optimizes efficacy
and dosing convenience while minimizing serum drug
exposure.
Malignancies in ustekinumab-treated
psoriasis patients: comparisons to the
general United States population
Kim A. Papp2, 1 Gerald G. Krueger3 Malcolm Rustin4
Eugene Healy5 Newman Yeilding6 Philipe Szapary6
Ming-Chun Hsu6 Kristian Reich7
1. Probity Medical Research, Waterloo, ON; 2. K Papp Clinical Research
Inc, Waterloo, ON; 3. University Of Utah Health Sciences Centre,, Salt
Lake City, UT, United States; 4. Royal Free Hospital, London, , United
Kingdom; 5. University of Southhampton, Southhapton, , United
Kingdom; 6. Immunology, Centocor Research and Development Inc,
Malvern, PA, United States; 7. Dermatologikum Hamburg, Hamburg, ,
Germany
Background: Ustekinumab is a fully human IL-12/23 monoclonal antibody developed for the treatment of moderateto-severe psoriasis. The impact of blocking IL-12 and IL-23 on
malignancy risk has not been established.
Objective: To evaluate malignancy rates in ustekinumab
psoriasis clinical trials.
Methods: The incidences of nonmelanoma skin cancers
(NMSCs) and other malignancies (noncutaneous malignancies) were evaluated in patients with moderate-to-severe
plaque psoriasis treated in Phase 2/3 trials of ustekinumab.
Rates of noncutaneous malignancies were compared to
rates in the general population using the US National Institutes of Health Surveillance, Epidemiology, and End Results
database (2000-2004).
Results: 2266 patients were treated with ustekinumab
for up to 1.5years (total of 2251 patient-years [P-Y] of
follow-up). In the placebo-controlled period, the incidence
of noncutaneous malignancies was 0.25 per 100 P-Y for
ustekinumab-treated patients (1 patient in 406P-Y) compared with 0.57 per 100 P-Y for placebo-treated patients (1
patient in 177P-Y). The incidence of NMSC was 0.74 per 100
P-Y for ustekinumab-treated patients (3 patients in 406P-Y)
compared with 1.13 per 100 P-Y for placebo-treated patients
(2 patients in 176P-Y). In the controlled and non-controlled
portions of trials, the incidence of noncutaneous malignancies was 0.36 per 100 P-Y for ustekinumab-treated patients
(8 patients in 2249P-Y) and included: breast, colon, head and
neck, kidney, prostate, and thyroid cancers. The rate of noncutaneous malignancies in ustekinumab-treated patients
was comparable to the rate expected in the general population (standardized incidence ratio = 0.68 [95% confidence
interval: 0.29, 1.34]). The incidence of NMSC was 0.80 per
100 P-Y for ustekinumab-treated patients (18 patients in
2245P-Y).
Conclusions: In Phase 2/3 trials, rates of NMSC and noncutaneous malignancies were similar between ustekinumab and
placebo-treated psoriasis patients. Overall, the rate of noncutaneous malignancies was consistent with the expected
background rate in the general population. Follow-up
analyses are warranted after longer follow-up, and studies
are currently ongoing.
a45
Efficacy of Voclosporin (ISA247) for psoriasis
treatment—results from the ESSENCE study
Kim Papp1 Norman Wasel2 Rod Kunynetz3 Ian Landells4
Launa Aspeslet6 Vincent Ho5
1. Probity Medical Research, Waterloo, ON; 2. Stratica Medical,
Edmonton, AB; 3. Ultranova Skincare, Barrie, ON; 4. Nexus Clinical
Research, St. John’s, NL; 5. Skin Care Centre, Vancouver, BC; 6.
Isotechnika Inc, Edmonton, AB
Introduction: Calcineurin inhibitors (CNi) remain one of
the systemic therapies of choice for the treatment of severe
plaque psoriasis. Voclosporin (VCS) is a new, tight binding
CNi. The tighter binding and novel chemical structure results
in an improved pharmacokinetic and pharmacodynamic
profile, as well as a decreased adverse event profile, compared to a traditional CNi. ESSENCE is a 3-arm trial of VCS
compared to placebo and cyclosporine (CsA) in moderate
to severe plaque psoriasis patients. This study design with
a placebo and an active comparator arm allows for proper
assessment of benefit/risk ratio.
Methods: total of 642 patients (Canada, Germany and
Poland) were enrolled in the 60 week ESSENCE study.
Subjects were randomized to one of 3 treatment groups in
3:1:1 ratio (VCS 0.4 mg/kg bid, placebo, CsA 1.5 mg/kg bid,
respectively) for 12 weeks after which the placebo group
was converted to 0.4 mg/kg bid. After 60 weeks, all patients
were followed for an additional 12 weeks after discontinuation of treatment. Achieving “clear” or “almost clear” in the
Static Physician’s Global Assessment (SPGA) score after
12 weeks was the primary efficacy endpoint. Secondary
efficacy endpoints and Quality of Life assessments were also
collected on all study subjects. Patients were also closely
monitored for changes in renal function, hypertension and
hyperlipidemia.
Results and Conclusions: The head-to-head design of
ESSENCE (CsA and placebo control groups) provides a direct
comparison of safety and efficacy. Presentation of the final
unblinded efficacy data for the current study will take place
at CDA’s 84th Annual Conference.
Measuring skin topography
using laser speckles
Bernardita Policarpio1 Lioudmila Tchvialeva1 David I.
McLean1 Harvey Lui1, 2 Haishan Zeng1, 2 Tim K. Lee1, 2
1. Vancouver Coastal Health Research Institute and University of British
Columbia, Vancouver, BC; 2. BC Cancer Agency, Vancouver, BC
Skin topography is of great interest for many dermatologists and skin scientists. We are developing a novel method
for in-vivo skin roughness measurement in about 5 msec
by analysing laser speckles. The purpose of this study is to
construct the instrument and evaluate its effectiveness.
A laser speckle imaging prototype was designed by
employing an open geometry scheme and two grayscale
CCD cameras without imaging lenses. Co- and cross- polarized speckle patterns were obtained from a blue diode
laser and then used to derive the contrast and the surface
a46
roughness (root-mean-square roughness) from the registered patterns. To validate the device, we used it to measure
a group of volunteers. The same skin location was measured
thrice and the average skin roughness was then computed.
We recruited 40 volunteers. The first group was 31 patients
who attended a skin clinic in the Skin Care Centre, Vancouver
General Hospital. We acquired the normal skin roughness
of the corresponding sites that required medical attention.
The second group was nine volunteers. The same spot of
their right dorsal hand and right volar forearm was measured. When we compared all our measurements on various
body sites with the literature values, a reasonable correlation was found (Pearson correlation coefficient = 0.64 and
Spearman correlation coefficient = 0.67). For the subgroup
of 9, the mean roughness measurement of the dorsal hand
was 20±4 um while that of the volar forearm was 16±5 um.
Results showed a significant increase in skin roughness on
the dorsal hand as compared to the volar forearm (p=0.038).
We have demonstrated that our roughness measurements
were in agreement with published values; furthermore, this
instrument can detect a significant difference in the roughness measurements between the dorsal hand and volar
forearm.
Consistency of ustekinumab response
across different body regions and PASI
components for the treatment of moderateto-severe psoriasis: results from the
PHOENIX 1 and PHOENIX 2 trials
Yves Poulin1 Robert Matheson2 Philippe Szapary3 Shu li3
Gerald Krueger4
1. Université Laval, hopital Hotel-Dieu de Québec et Centre
Dermatologique du Québec métropolitain, Québec, QC; 2. Oregon
Medical Research Center, Portland, OR, Portland, OR, États-Unis; 3.
Centocor Research and Development, Inc., Malvern, PA, États-Unis; 4.
University of Utah Health Sciences Center, Salt Lake City, UT, États-Unis
Objective: To describe the efficacy of ustekinumab across
body regions and in individual component of the PASI in
psoriasis patients.
Methods: In PHOENIX 1 (n=766) and PHOENIX 2 (n=1230),
patients with moderate-to-severe plaque psoriasis (≥10%
of total BSA and PASI score ≥12) who were candidates for
phototherapy or systemic therapy were randomized to subcutaneous ustekinumab 45mg or 90mg, or placebo, at wks 0
and 4. The primary endpoint was the proportion of patients
achieving at least 75% improvement from baseline in the
PASI (PASI75) score at wk12. PASI response was assessed for
the head, trunk, upper extremities, lower extremities and in
each of the PASI components.
Results: At wk12, higher proportions of patients treated
with ustekinumab 45mg and 90mg achieved PASI75
response vs. placebo (PHOENIX 1:67.1%,66.4% vs.3.7% and
PHOENIX 2:66.7%,75.7% vs 3.7% for the 45mg,90mg,and
placebo groups,respectively (p<0.001,all comparisons). The
proportions of patients in the combined ustekinumab vs.
placebo groups achieving at least 75% improvement for
each body region were: 74.2% vs. 13.7% for the head, 70.3%
vs. 4.8% for the trunk, 69.0% vs. 3.9% for the upper extremities, and 63.2% vs. 3.9% for the lower extremities (PHOENIX
1) and 77.6% vs. 10.3% for the head, 73.3% vs. 6.0% for the
trunk, 72.4% vs. 2.9% for the upper extremities, and 68.8%
vs. 3.7% for the lower extremities (PHOENIX 2). The proportions of patients achieving at least 75% improvement for the
individual PASI components for the combined ustekinumab
vs placebo groups in each of the trials were: 66.9% vs 2.7%
for induration, 66.9% vs. 4.3% for scaling, and 64.8% vs. 2.7%
for erythema (PHOENIX 1) and 73.3% vs. 3.7% for induration,
72.8% vs. 3.7% for scaling, and 69.0% vs. 4.1% for erythema
(PHOENIX 2).
Conclusion: Ustekinumab provides a consistent response
across all evaluated body regions and in each component of
the PASI score.
A Canadian survey evaluating the
burden of co-morbidities in patients with
moderate-to-severe plaque psoriasis
Yves Poulin1 Norman Wasel2, 1 Kim Papp3 Elisa Fraquelli4
Robin Andrew4 Daphne Chan4
1. Université Laval, hopital Hotel-Dieu de Québec et Centre
Dermatologique du Québec métropolitain, Québec, QC; 2. Stratica
Medical, Edmonton, AB; 3. Probity Medical Research, Waterloo, ON; 4.
Janssen-Ortho, Toronto, ON
Introduction: Psoriasis is an autoimmune disease associated
with a high incidence of co-morbidities. The current study
evaluated the co-morbidities present in a Canadian population of moderate-to-severe plaque psoriasis patients.
Methods: An online survey was conducted using a Canadian consumer panel. Eligible respondents reported a
diagnosis of psoriasis by a physician, had at least moderate
disease within the past 5 years and met at least one of the
following criteria: 1) ≥ 3% body surface area (BSA) affected,
2) psoriasis on a sensitive area (i.e. hands, feet, scalp, face, or
genitals), or 3) currently receiving prescription oral and/or
injectable medication or phototherapy for their psoriasis.
Results and Conclusions: 514 of 3845 panellists were
eligible and completed the questionnaire. The majority
of respondents (65%) reported self-assessed ‘moderate’,
‘severe’ or ‘very severe’ psoriasis at the time of the survey,
with 75% of respondents diagnosed with ≥1 co-morbid
condition. Respondents most commonly reported obesity
(32%), high blood pressure (30%) and elevated cholesterol/
lipids (26%). Psoriatic arthritis (PsA) was diagnosed in 23% of
respondents. Severity of PsA was reported to be ‘severe’ or
‘very severe’ in 17% of PsA respondents, and increased with
greater BSA involvement (9%, 19% and 30% for BSA of 0-2%,
3%+, and 10%+). Mental health conditions such as depression (19%), anxiety (18%) and insomnia/sleep disorders
(18%) were also prevalent. There was no significant correlation found between the number of co-morbid conditions
and psoriasis disease severity (-0.036).
Psoriasis is associated with significant co-morbidities. Our
results corroborate other studies and suggest a need to
assess the cutaneous and associated systemic inflammation
linked with psoriasis, in addition to the physical, metabolic
and psychological effects.
Soluble biomarkers differentiate
psoriatic arthritis from psoriasis
Cheryl F. Rosen; Vinod Chandran; Hua Shen; Fawnda
Pellett; Sutha Shanmujarajah; Catherine T. Schentag;
Richard J. Cook; Dafna D. Gladman
Toronto Western Hospital, Toronto, ON
Introduction: Serum biomarkers may be helpful in screening patients with psoriasis for psoriatic arthritis (PsA). We
sought to identify serum biomarkers for psoriasis and PsA.
Methods: Fifty-two patients with psoriasis vulgaris, 26 of
whom had PsA, and 26 controls were recruited. Patients with
psoriasis and PsA were matched for age, sex and psoriasis
duration; controls were matched for age and sex. None of
the patients were on biologic agents. Patients’ serum samples were analyzed for the following biomarkers using ELISA
kits: Interleukin (IL)-12, IL-12 p40, IL-17, Tumour Necrosis
Factor Super Family member 14 (TNFSF14), Matrix Metalloproteinase (MMP)-3, Receptor Activator for Nuclear Factor
κ B Ligand (RANKL), Osteoprotegrin (OPG), Cartilage oligomeric protein (COMP), C-propeptide of type II collagen (CPII),
Col2-3/4(long mono) (C2C) and Col2-3/4(short) (C1-2C) neoepitopes, and highly sensitive C - reactive protein (hsCRP).
Results and Conclusions: Compared to controls, patients
with psoriasis and/or PsA had elevated TNFSF14 [OR 1.007,
95% CI (1.000, 1.014), p<0.05] and elevated COMP [OR 1.001,
95% CI (1.000, 1.002), P< 0.05] and a decreased C2C [OR 0.96
95%CI (0.939, 0.982) P<0.001] on multivariate analysis. We
then investigated biomarkers for PsA in patients with psoriatic disease. The 26 PsA patients (PsA duration of 11.4 years,
mean actively inflamed joint count 16, swollen joint count
5) were compared to 26 patients who had psoriasis alone.
Patients with PsA, on multivariate analysis, had elevated
MMP-3 [OR 1.32, 95% CI (1.033,1.686)], OPG [OR 1.011, 95%
CI (1.002,1.021)], CPII [OR 1.016, 95% CI (1.004,1.028)], hsCRP
[OR 1.001, 95% CI (1.000,1.001)] (all p<0.05) which were
independently associated with PsA, whereas elevated C2C
[OR 0.925, 95% CI (0.857,0.999), P<0.05] was associated with
reduced risk. This pilot study indicates that TNFSF14, COMP
and C2C are soluble biomarkers of psoriatic disease, whereas
MMP-3, OPG, CPII, and hsCRP are biomarkers for PsA in
patients with psoriasis.
A Canadian case report of erythema
nodosum leprosum successfully treated
with prednisone and thalidomide
Mélissa Saber; Nathalie Provost
CHUM University of Montreal, Montreal, QC
Introduction: Erythema nodosum leprosum (ENL) is a
disease rarely encountered in Canada. It is characterized by
multiple remissions and recurrences, often requires long-
a47
term treatment and can result in debilitating sequelae. This
poster presentation aims to promote rapid recognition and
adequate therapy for ENL.
Methods: Case report of an ENL. The clinical and histopathological features, treatment provided and response to
treatment are detailed in this poster presentation.
Results and Conclusions: A 39 year-old male patient receiving treatment for borderline lepromatous leprosy came to
our dermatology service with painful cutaneous lesions on
the face and limbs, bilateral paresthesia of the 4th and 5th
fingers and systemic symptoms. A diagnosis of ENL was
suspected and confirmed by skin biopsy. Prednisone 40
mg qd for a week, followed by 60 mg qd for another week,
reduced the lesions by 80% and the pain by 50%. While
prednisone 60 mg qd was continued for one more week and
then stopped, thalidomide was started at a dose of 300 mg
qd for four weeks and then reduced to 250 mg qd for two
weeks, which led to complete resolution. At the 7½-month
follow-up, the patient remained completely asymptomatic.
Although ENL is a rare disease in Canada, it is important to
recognize and treat it promptly.
An atypical dermatopathological
presentation of Sweet’s Syndrome
Jakub Sawicki1 Jadranka Jambrosic2 Ronald Vender3
1. Queen’s University, Kingston, ON; 2. University of Toronto, Toronto,
ON; 3. McMaster University, Hamilton, ON
Acute febrile neutrophilic dermatosis, also known as Sweet’s
Syndrome, is a rare condition characterized by an eruption
of tender erythematous nodules and plaques in the presence of fever and neutrophilia. It presents in one of three
forms: classical (usually associated with an upper respiratory
or gastrointestinal infection, inflammatory bowel disease,
or pregnancy), malignancy-related, or drug-induced. The
standard histopathological features of Sweet’s Syndrome
include papillary dermal edema and an infiltrate of mature
neutrophils in the superficial dermis. In addition, swelling
of endothelial cells, dilatation of small blood vessels and
leukocytoclasia are frequently present. Epidermal involvement is unusual.
We report a unique case that clinically resembles classical
Sweet’s Syndrome, but is histologically atypical. A 17 year
old male with a five-day history of fever presents with an
erythematous, nodular, vescicular bullous eruption covering most of his body, as well as a concurrent streptococcal
throat infection. Pathology from a lesional biopsy reported
an acute neutrophilic infiltrate with papillary dermal edema
associated with a large number of neutrophils. Along with
this typical histological presentation of Sweet’s Syndrome,
epidermal hyperplasia and several intraepidermal pustules
were present. No organisms were isolated from the lesions,
nor were immunoglobulins G,A,M or complement present
under immunofluorescence. The patient was treated with
oral prednisone and clobetasol propionate spray which led
a48
to complete resolution of lesions within 48 hours. To date,
only a handful of cases with epidermal involvement were
published among the several hundred reports of patients
with Sweet’s Syndrome since it was first described in 1964.
When vasculitis hides something else...
Pascale St-Amour; Nicolas Aubut; Éric Gagné;
Marie-Marthe Thibeault
CHUQ - Hôtel-Dieu de Québec, Québec, QC
Introduction: The spectrum of clinical manifestations of
cutaneous vasculitis is quite broad. When a granulomatous
pattern of vascular inflammation is observed, the differential
diagnosis has to include all of the following entities: Wegener granulomatosis, Churg-Strauss syndrome, polyarteritis
nodosa, lymphomatoid granulomatosis, metastatic Crohn’s
disease and infections.
Methods: We report a case of a 66-year old female presenting in March 2009 with inferior limbs purpura. The
eruption evolved a few weeks later into purpuric and furonculoid nodules on the arms, thighs and legs. Articular pain
and swelling of the wrists, knees and ankles also appeared
shortly afterwards.
The patient had low-grade non-Hodgkin lymphoma since
2003 and got her last chemotherapy cycle at the end of
2007. She was treated in 2004 for a c-ANCA positive glomerulonephritis. She underwent splenectomy in early 2008.
A skin biopsy was performed at the first visit. Granulomatous
vasculitis was objectivable upon histopathological exam. A
thorough work-up for excluding common causes of vasculitis yielded no result. Cultures were initially negative for
micro-organisms. Given the persistance of the eruption, a
second skin biopsy was performed in May. This time, a pattern of mixed inflammation (exsudative and granulomatous)
was seen. There was however a totally unexpected finding:
presence of numerous atypical mycobacteria. Skin, blood
and synovial fluid cultures were all positive for mycobacteria
at that time.
The causal organism was formally identified as Mycobacterium haemophilum. A triple therapy was initiated, consisting
of rifampicin, clarithromycin and ciprofloxacin. Synovitis
quickly improved but a new cutaneous nodule appeared
in September, which was again biopsied. Mycobacterium
haemophilum was still isolated in the skin cultures despite
ongoing antibiotic therapy.
Conclusion: Mycobacterium haemophilum is one sub-type
of atypical mycobacteria. It is difficult to grow in cultures,
requiring ferric ions and a temperature of 30°C. Concomitant
immunosuppression is the rule. Clinical manifestations are
non-specific and consist of pustules and nodules that can
ulcerate. Sepsis, septic arthritis and osteomyelitis are common complications. Cutaneous mycobacteriosis must be
considered in the differential diagnosis of vasculitis associated with a granulomatous pattern.
Unusual case of proximal calciphylaxis
without renal failure
Monica Stanciu; Angélique Gagné-Henley;
Marie-Claude Dionne; Geneviève Thérien
Université Laval, Quebec, QC
Calciphylaxis is a rare syndrome of vascular calcification with
subsequent cutaneous and tissue necrosis. It usually manifests as a complication of end-stage renal failure, affecting
1-4% of long-term dialysis patients. Very exceptionally, it can
occur without chronic renal failure.
Calciphylaxis is characterized by exquisitely painful indurated plaques with a violet livedoid border and central necrosis.
It can progress to necrotic non-healing ulcers. The mortality
is very high and approaches 80% in the presence of ulceration. Calcium deposits can be demonstrated histologically
within the blood vessel walls in the dermis and the subcutaneous tissue. Therapeutic options include calcium-restricted
diet, aggressive wound care with debridement and, as
recently published, sodium thiosulfate.
We present a case of a 31 year-old woman with extensive
proximal, ulcerated calciphylaxis without associated chronic
renal failure. Our patient had quite a few risk factors associated with the pathogenesis of calciphylaxis such as obesity,
malnutrition and a transient episode of acute renal failure. She was successfully treated with sodium thiosulfate,
extensive wound debridement (more than 30% total body
surface) and subsequent skin grafts. The patient has miraculously survived to this often fatal condition.
Nevus lipomatosus: case report
and literature review
Zaki A. Taher1 Charlene Hunter2 Ken Alanen1 Andrew Lin1
1. Division of Dermatology University of Alberta, Edmonton, AB; 2.
Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB
Background: Nevus lipomatosus cutaneous superficialis
(NCLS) is a rare skin disorder with distinct clinical and histopathologic findings.
Objective: To increase awareness of the clinical and histopathologic features of NCLS, in order to facilitate its recognition and diagnosis.
Methods: The clinical and histopathologic features of a
patient with NCLS, and results of a literature review are
presented.
Results: A 30 year old woman presented with asymptomatic
lesions on the left lower back since age 12. Physical exam
showed several clustered, soft, brownish, 1-2 cm papules
on the left lower back. Lateral to these lesions, there is a
skin colored, non-tender, 8 by 5 cm soft swelling. Clinical
diagnosis included neurofibromatosis, lipomas, and nevus
lipomatosus. Biopsy showed features most in keeping with
irritated nevus lipmatosus. Excision was offered, but the
patient declined. Literature search shows that NCLS presents
as soft, clustered papulonodules, usually present at birth
or appearing in childhood or adolescence, often affecting
pelvic girdle area and upper thighs. Biopsy shows mature fat
cells in the dermis.
Conclusions: NLCS is a rare, benign condition that presents
as grouped, soft, papoulonodules, often involving the hips
and upper thighs.
A Substituted trans-stilbene derivative
as a novel topical treatment for
psoriasis and atopic dermatitis
Liren Tang1 Robert Bissonnette2 Michael Lyle1 Yangsheng
Wanggui1 Bin Li1 Genhui Chen1 John Webster1
1. Welichem Biotech Inc., Burnaby, BC; 2. Innovaderm Research Inc.,
Montreal, QC
Introduction: As a new chemical entity, WBI-1001 is being
developed as a topical treatment for mild to moderate
psoriasis and atopic dermatitis (AD). In preclinical studies,
WBI-1001 was shown to inhibit inflammatory cytokines, and
T-cell viability and infiltration processes.
Methods: To assess the safety and efficacy of WBI-1001 in
patients with psoriasis or AD, two, double-blinded, placebocontrolled studies were conducted. In the Phase I dose
ascending study, 36 patients with plaque psoriasis were
recruited in groups of 6. Each group received 0.5, 1.0 or 2.0%
WBI-1001 cream either once or twice daily on one side of the
body and the placebo on the other side. In the second study,
36 patients with AD were randomized (1:1:1) to receive
either 0.5 or 1.0% WBI-1001 cream or the placebo cream
twice daily. Patients were treated for 28 days.
Results and Conclusions: The 0.5% and 1.0% WBI-1001
treatment exhibited excellent skin tolerance. The 2.0% WBI1001 caused a few temporary, mild, skin-related adverse
events (AE) in the psoriasis study. The pharmacokinetic
studies showed that WBI-1001 was only minimally absorbed
and no evidence of WBI-1001 accumulation was detected
in the blood. In the psoriasis study, improvement in physician’s global assessment, induration, erythema and scaling
was more important on the side treated with WBI-1001 as
compared to the side treated with the placebo cream. In
the AD study patients randomized to 0.5 or 1.0% WBI-1001
showed statistically significant improvement of all the major
efficacy assessments including eczema area and severity
index, SCORAD, investigator’s global assessment, and body
surface area, when compared with placebo cream. In conclusion, WBI-1001 cream at 0.5% and 1.0% was well tolerated by
patients with psoriasis and AD, minimally absorbed into the
blood system and efficacious against both psoriasis and AD
as a novel, non-steroidal topical therapy.
a49
Successful treatment of digital necrosis
associated with CREST Syndrome using
Intravenous Immunoglobulin (IVIG)
Mimi Thériault; Marilyn Caron; Martin Gilbert
CHA-Hôpital de L’Enfant Jésus; Centre de Dermatologie Maizerets,
Quebec City, QC
Introduction: CREST syndrome, a limited form of Progressive Systemic Sclerosis, is an autoimmune connective tissue
disease of unknown etiology. It is caracterized by calcinosis,
Raynaud’s phenomenon, esophageal dismotility, sclerodactyly and telangiectasia. The clinical manifestations of this
disease can be very debilitating and painful, especially ulcers
and necrosis of the extremities.
Methods and results: We describe the case of a 62 year-old
female with a seven-year history of CREST Syndrome. She
had been presenting chronic ulcers and mild necrosis of
some digits for several years. They were treated with local
and systemic treatments, including pentoxifylline, amlodipine, Illoprost perfusions and topical patches of nitroglycerine. Those ulcers were partially controlled until the beginning of 2008. Despite those treatments, the necrosis of the
left middle fingertip ulcer worsened to the point that an
amputation seemed inevitable. Knowing that autoimmune
disease are being treated with Intravenous Immunoglobulin (IVIG) , this treatment was tried at a starting dose of
0.5g/kg/d in a 4-day protocol once a month for 6 months.
A spectacular clinical improvement was noted after the
second treatment and almost completely healed at the 5th
treatment.
Conclusion: Intractable ulcer and digital necrosis are
frequently found in systemic sclerosis, but are rarely seen in
CREST Syndrome. Many treatment options were described
for this condition. Recently, a case of digital dystrophic calcifications, but without any necrosis, was successfully treated
with IVIG. To our knowledge, no other case of digital necrosis
associated with CREST Syndrome showing notable improvement with the use of IVIG has been described.
A case of congenital aggressive systemic
mastocytosis with c-kit mutation
Diane Tran1 Janie Bujold1 Francine Caron2 Jean Bernard2
Isabelle Auger2
1. Hotel Dieu de Québec, Quebec, QC; 2. Centre Hospitalier de
L’Université Laval, Chul, Quebec, QC
Mastocytosis is defined as an abnormal proliferation of mast
cells in tissues. A mutation in c-kit proto-oncogene plays an
important role in both cutaneous and systemic mastocytosis
pathogenesis by inducing mast cells growth and preventing
their apoptosis. Imatinib, a tyrosine kinase inhibitor specific
to c-kit receptor, has recently been tried in the treatment of
this disease.
We describe the case of a baby girl who presented at birth
an erythroderma with bullæ. She also had respiratory
distress, hepatosplenomegaly, thrombocytopenia, bilateral
a50
cephalematomas and a peri-aortic mass. On examination,
the rash corresponded to diffusely infiltrated erythematous
to brownish plaques showing urtication on pressure. Skin,
liver and bone marrow biopsies revealed characteristic mast
cell infiltration. The elevated serum tryptase levels as well
as positive c-kit mutation were consistent with systemic
mastocytosis. The child further developed portal hypertension, esophageal varicose veins, ascite, osteopenia and
growth delay. The initial treatment included H1 and H2
antihistamines, ketotifen, cromoglycate and systemic glucocorticoids. Since the patient did not improve after 6 weeks
of high doses prednisone, a cytoreductive therapy was
considered. Because of its inhibitory effect on c-kit receptor,
a treatment with imatinib was introduced. Unfortunately,
the patient worsened with treatment, possibly because of an
allergic reaction, and it had to be stopped.
Reports of such severe systemic mastocytosis in child
carrying c-kit mutation are rare. We have to keep in mind
that tyrosine kinase inhibitors represent an interesting
therapeutic option in mastocytosis implying c-kit mutation.
Among alternative treatments, remain interferon α-2b and
cladribine.
Dose-dependent time to response with oral
alitretinoin in severe chronic hand eczema
Ronald B. Vender1 Kim Papp3 Yves Poulin2 T C. Brown4
1. Dermatrials Reserach , Hamilton, ON; 2. Universite Laval, Quebec City,
QC; 3. Probity Medical Reseach, Waterloo, ON; 4. Basilea Pharmaceutica
Ltd., Basel, , Switzerland
Background: Alitretinoin (9-cis retinoic acid) has been
demonstrated to induce clinically significant responses in
patients with severe chronic hand eczema refractory to
topical corticosteroids, where ‘response’ was defined as
a Physician’s Global Assessment (PGA) rating of ‘clear’ or
‘almost clear’.
Objectives: This study compared the effects of two different
doses of alitretinoin on ‘time-to-response’ in patients with
severe chronic hand eczema refractory to topical corticosteroids. Time to response was defined as the time taken to
achieve the first PGA rating of ‘Clear’ or ‘Almost clear’.
Methods: A total of 1032 patients received oral alitretinoin
at doses of either 10 mg (N=418) or 30 mg (N=409), or
placebo (N=205) given once daily for 12 to 24 weeks in a
double-blind, randomized, placebo-controlled, multicentre
trial.
Results: Response rates at the end of therapy were 48%,
28%, and 17% for patients receiving alitretinoin 30 mg, 10
mg, and placebo, respectively. Median time to response was
significantly shorter in patients receiving alitretinoin 30 mg
(85 days) compared with 10 mg (171 days; p<0.001; log-rank
test).
Conclusions: Consistent with other studies, this trial showed
that oral alitretinoin induces clinically significant responses
in a high percentage of patients with severe chronic hand
eczema who are refractory to potent topical corticosteroids.
Both dosing regimens were effective, with the 30 mg dose
inducing a significantly more rapid response in a larger number of patients.
In vivo confocal Raman spectroscopy for skin
disease detection and characterization—
preliminary results from a Murine tumor model
Hequn Wang1 Naiyan Huang1 Jianhua Zhao1 Harvey Lui2
Mladen Korbelik1 Haishan Zeng1
1. BC Cancer Research Center, Vancouver, BC; 2. Photomedicine
Institute, Department of Dermatology and Skin Science, University of
British Columbia, Vancouver, BC
Background and Objective: The confocal principle provides
a powerful method for performing non-invasive, depthresolved tissue evaluation because of its optical sectioning
capability. Raman spectroscopy measures molecular vibrations and can provide fingerprint-type specific signatures for
molecular identification. Our objective is to combine these
two complementary techniques to achieve non-invasive,
depth-resolved biochemical analysis of the skin in vivo for
improving skin cancer detection and evaluation.
Materials and Methods: A confocal Raman spectrometer
system with a special probe for reducing involuntary body
movements has been built for depth-resolved biochemical analysis of the skin in vivo. The skin of 15 anesthetized
mice bearing squamous cell carcinoma (SCC) subcutaneous
tumors was scanned axially from the stratum corneum to
mid dermis. After this, the skin from the measurement sites
was excised and H&E stained.
Results and Conclusions: The axial resolution of the system
within tissue was be 12.6 microns. Raman spectra with good
signal-to-noise ratio were obtained within 15 seconds under
27-mW of excitation light exposure to the skin surface.
Raman spectra of mouse epidermis and dermis differed significantly. Obvious changes in Raman spectra for the dermal
layers were also evident between normal and tumor-bearing
skin. We are aiming to now combine this spectrometer system combined with a confocal imaging module in the near
future to not only improve the non-invasive clinical diagnosis of skin cancers, but also help delineate their margins.
Towards explicit definitions of
dermoscopic structures
Paul Wighton1, 2, 3 Tim K. Lee1, 2, 3 David I. McLean2, 3
Harvey Lui2, 3 M. Stella Atkins1
1. School of Computing Science, Simon Fraser University, Burnaby,
BC; 2. Photomedicine Institute, Department of Dermatology and
Skin Science, University of British Columbia and Vancouver Coastal
Health Research Institute, Vancouver, BC; 3. Cancer Control Research
Program and Cancer Imaging Department, BC Cancer Research Centre,
Vancouver, BC
Dermoscopy is an established practice in dermatology that
improves clinical diagnostic accuracy. However the ability
to accurately identify dermoscopic structures is a necessary
precondition to its effective use. In fact, dermoscopy has
been shown to decrease accuracy when the individual is
insufficiently trained. Additionally, a study has shown that
even amongst experts (individuals experienced in the use
of dermoscopy who have either published or lectured on
the topic) interobserver agreement is poor. The same study,
however found that diagnosis by consensus improves accuracy. We believe that a further increase in clinical diagnostic
accuracy can be realized through dermoscopy by 1) explicitly defining dermoscopic structures 2) improving consensus
and 3) improving training methods.
We define a statistical framework that is sufficiently general
to explicitly define all dermoscopic structures. We demonstrate the framework’s ability to learn the dermoscopic structure ‘pigment network’ and differentiate between typical
and atypical variants. We also use the newly learnt definition
to create visualizations showing location/type of pigmentary
network along with the associated certainty.
Our dataset consists of 94 images from an atlas of dermoscopy that are labeled as having either an ‘absent’, ‘regular’
or ‘irregular’ pigment network. Locational information is
not specified, only that it occurs somewhere in the image.
We begin by performing various pixel-wise measurements
on these images such as filter-bank convolutions, wavelet
decompositions, etc. Multivariate distributions over these
measurements are then constructed and maximum likelihood estimation is used to label unseen images. The system
can detect pigment networks with 87% accuracy. It also
identifies the type of pigment network with 72% accuracy.
In conclusion, our framework seems to be a promising technique for the automatic identification and visualization of
dermoscopic structures in skin lesions. We believe that this
research not only has the potential to create tools to aid the
dermatologist, but also to improve training methods and
build consensus amongst experts.
Mucosal ulceration in two infants:
an uncommon presentation of
primary immunodeficiency
Monika Winnicki; Rola Al Dhaybi; Julie Powell
CHU Sainte-Justine, University of Montreal, Montreal, QC
Introduction: Primary immunodeficiency (PID) is a group
of diseases affecting innate and acquired immunity. Prompt
recognition and treatment can be life-saving. Dermatologic
features of PID can include severe dermatitis, morbilliform
eruption, recurrent skin infections, granulomatous lesions
and mucosal ulceration in some patients. We report two
patients under the age of 2 years presenting with oral or
genital aphthae as the first manifestation of two primary
immunodeficiency diseases.
Methods: The medical charts of each patient were reviewed.
The approach to investigation of mucosal ulceration in
children is presented along with a review of dermatologic
manifestations of PID.
Results and Discussion: A 12-month-old female patient
presented to the emergency department with fever and a
a51
1.5 cm ulceration of the right labia majora. Routine blood
testing revealed decreased WBC (4.20 x 10^9/L) and neutrophil counts (0.2 x 10^9/L). Bacterial culture of the ulcer
revealed Pseudomonas aeruginosa while viral cultures and
serology were negative. A diagnosis of autoimmune neutropenia was made with rapid healing of the ulcer after institution of G-CSF.
An otherwise healthy 5-month-old female patient presented
to our service with recurrent painful, sublingual and palatine
aphthae. Routine blood testing revealed a decreased WBC
count (4.21 x 10^9/L) and lymphopenia (1.3 x 10^9/L). She
had recently been suffering from diarrhea and cough and
Pneumocystis carinii infection was subsequently diagnosed.
Further testing lead to the diagnosis of severe combined
immunodeficiency disease (SCID). The patient has since
received bone marrow transplantation.
Oral and genital ulcerations are uncommon in the pediatric
population. Causes include infection with Candida, HSV and
EBV, aphthosis, periodic fever syndromes, Crohn’s disease
and Behçet disease. Mucosal ulceration can also be the
initial clue to an immunodeficiency disorder in young children. Awareness of this presentation of PID is crucial to avoid
delay in diagnosis and institution of life-saving treatment.
Basosquamous cell carcinoma of the
nasal septum – a case report
Joyce W. Wong; Jeremy Man; Alain Brassard
University Dermatology Center, University of Alberta, Edmonton, AB
Basosquamous cell carcinoma (BSCC) is most frequently
found on the face and ears. However, squamous cell carcinoma (SCC) is more common than BSCC when the nasal
septum is involved. The distinction is important since it has
been suggested that BSCC has greater propensity for pulmonary metastasis than SCC. Unfortunately, experience with
the management of BSCC of the nasal septum is limited.
We present a case of a 61-year-old man who presented with
a nodule on his nasal bridge, which had grown rapidly in
size. MRI with gadolinium contrast showed a mass in the
nasal septal region that invaded underlying cortical bone.
Bilateral adenopathy of the neck was also detected. A modified radical neck dissection was completed along with a
total rhinectomy, an anterior craniofacial resection and a
total anterior maxillectomy. As a result of positive margins,
adjuvant chemotherapy and radiotherapy were completed
thereafter and the patient is now faring well.
BSCC is now viewed as a distinct entity with its own defining histological features, which include infiltrating nests
of basaloid cells that have little basophilic cytoplasm and
uniform nuclei that palisade at the periphery of the nests;
within these nests are squamous cells, which have more
eosinophilic cytoplasm and may contain intercellular
bridges. There was significant growth as well as invasion into
surrounding areas. This emphasizes the fact that BSCC is a
rare, histologically distinct entity that is aggressive in nature.
Accurate diagnosis is essential for effective management.
a52
Surgery in combination with chemo and radiotherapy seem
to be effective in managing basosquamous carcinoma of the
nasal septum, but long-term follow-up is required.
Pityriasis rubra pilaris: tumor
necrosis factor alpha production and
response to adalimumab therapy
Yaohua Y. Zhang1 Youwen Zhou1
1. University of British Columbia, Vancouver, BC; 2. Department of
Dermatology, Huashan Hospital, Shanghai, , China
Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder which has many clinical and histological similarities to psoriasis. Although the treatment of PRP remains
challenging, many therapies effective for psoriasis have
shown efficacy for pityriasis rubra pilaris, including acitretin
and methotrexate. Recently, several reports have indicated
the efficacy of tumor necrosis factor (TNF) inhibiting agents,
such as inflixmab or etanercept, either as mono or as combined therapies, for the treatment of PRP. Here we report a
patient with type I PRP that was refractory to conventional
therapies responding to adalimumab therapy, the newest
TNF inhibiting agent approved for the treatment of psoriasis.
Of note, this patient’s pre-treatment skin biopsies demonstrated significant up-regulation of TNF messenger RNA in
lesional skin biopsies compared with the normal perilesional
skin sample. This finding, together with the documented
clinical efficacy of TNF-blocking agents, strongly suggests
that TNF plays important role in the pathogenesis of PRP.
Skin Cancer detection using noninvasive in vivo
Raman Spectroscopy – preliminary results
Jianhua Zhao; Haishan Zeng; David I. McLean; Harvey Lui
Department of Dermatology and Skin Science, University of British
Columbia, Vancouver, BC
Background: As a non-invasive optical technique Raman
spectroscopy can assess molecular structures and conformations within biological tissue. We have developed a
rapid real-time Raman spectrometer system with measurement times of less than 1 second suitable for clinical
measurement.
Methods and Patients: Patients with benign and/or malignant skin lesions were recruited. Both the lesional skin and
its surrounding normal skin were measured using real-time
Raman spectrometer. Two hundred fifty six (256) cases were
included in this study, of which there were 24 cases of basal
cell carcinoma (BCC), 49 cases of squamous cell carcinoma
(SCC), 37 cases of malignant melanoma (MM), 24 cases of
actinic keratosis (AK), 53 cases of seborrbeic keratosis (SK),
32 cases of atypical nevus (AN), 22 cases of compound
nevus (CN), 25 cases of intradermal nevus (IN), and 23 cases
of junctional nevus (JN). Based on clinical relevance, the
patients were divided into two categories for analysis: (1)
skin cancer (BCC, SCC, MM, AK) versus benign lesions (SK,
AN, CN, IN, JN); (2) MM versus benign pigmented lesions
(SK, AN, CN, IN, JN). The Raman spectra were analyzed using
multivariate partial least squares regression and linear discriminant analysis.
Results and Conclusions: Lesional skin and normal skin
have distinctive spectral features. Statistical analysis demonstrated that skin cancers could be very well discriminated
from benign skin lesions (AUC of the ROC curve = 0.906,
optimal sensitivity = 91%, optimal specificity = 75%); and
malignant melanoma from benign pigmented lesions (AUC
of the ROC curve = 0.930, optimal sensitivity = 97%, optimal
specificity = 78%). The results demonstrated that real-time
bedside Raman spectroscopy is both technically feasible and
capable of assisting with non-invasive skin cancer diagnosis.
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n
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Abel, Michel ......................................................................... a4
Brown, Thomas C. ....................................... a30, a36, a41, a50
Al Dhaybi, Rola .................................................................. a51
Bujold, Janie ....................................................................... a50
Alanen, Ken ................................................................ a23, a49
Cammisuli, Sam . .................................................................. a5
Albrecht, Lorne ................................................................... a32
Carmel, Michel ................................................................... a32
Armstrong, April W. ........................................................... a39
Caron, Marilyn . .................................................................. a50
Aspeslet, Launa . ................................................................. a46
Carruthers, Jean .................................................................... a2
Au, Sheila ........................................................................... a38
Chan , Daphne ................................................................... a44
Auger, Isabelle ............................................................ a31, a50
Chandran, Vinod ................................................................. a47
Bandarchi, Bizhan . ....................................................... a1, a28
Chen, David W. ................................................................... a26
Barber, Kirk ........................................................................ a32
Cheng, Wing-ki (Vicki) . ...................................................... a3
Beleznay, Katie ................................................................... a10
Chevrier, Marc .................................................................... a44
Bernard, Jean ...................................................................... a50
Choy, Gregory . ................................................................... a27
Binamer, Yousef . ................................................................ a30
Coulombe, Jérôme .............................................................. a32
Bissonnette, Robert ................. a2, a22, a30, a36, a41, a44, a49
Crawford, Richard ............................... a18, a22, a24, a37, a38
Bolduc, Chantal .................................................................. a30
Dai, Derek ........................................................................... a11
Boulanger, Maude . ............................................................. a31
Dawoud, Tariq . ..................................................................... a4
Brasher, Penelope ............................................................... a11
Demers, Alain A. . ............................................................... a26
Brown-Maher, Tracey D. .................................................... a31
Donovan, Jeff C. .......................................................... a4, a33
Adams, Stewart ................................................................... a32
Bruecks, Andrea K. ............................................................. a23
Al-Mutairi, Nawaf .............................................................. a27
Burns, Ariel ......................................................................... a35
Alavi, Afsaneh ....................................................... a1, a27, a28
Carey, Wayne ...................................................................... a32
Andrew, Robin ............................................................ a44, a47
Caron, Francine . ................................................................. a50
Arrandale, Victoria . ............................................................ a12
Carruthers, Alastair ............................................................... a2
Atkins, M. Stella ......................................................... a25, a51
Cashin, Margo . ................................................................... a31
Aubut, Nicolas .................................................................... a48
Chan, Daphne ..................................................................... a47
Baibergenova, Akerke T. . ..................................................... a1
Chavez-Muñoz, Claudia ....................................................... a2
Barankin, Benjamin ............................................. a22, a32, a39
Chen, Genhui ................................................................ a2, a49
Beecker, Jennifer . ............................................................... a29
Cheung-Lee , Melody ........................................................ a34
Bergman, Hagit ................................................................... a39
Chow, Eunice ........................................................................ a3
Bertrand, Janie ...................................................................... a1
Cook, Richard J. ................................................................. a47
Binder, Carin . .................................................................... a44
Cowen, Bryce ............................................................. a14, a15
Blouin, Marie-Michèle . ...................................................... a31
Cross, Jennifer ...................................................................... a4
Bonito, Anthony . .................................................................. a4
Davar, Sandra . .................................................................... a32
Bourcier, Marc .................................................................. , a32
de Gannes, Gillian .............................................................. a21
Brassard, Alain . .......................................................... a35, a52
Dionne, Marie-Claude ........................................................ a49
Doumit, Joseph ................................................................... a33
Han, Christina ..................................................................... a37
Dowlati, Yahya . .................................................................... a5
Hatami, Afshin .................................................................... a19
Dover, Douglas C. . ............................................................. a17
Drolet, Anne-Marie ............................................................. a33
Drucker, Aaron M. ................................................................ a5
Dutz, Jan ...................................................... a3, a4, a7, a8, a24
Dytoc, Marlene T. ....................................................... a34, a40
El helou , therese . .............................................................. a30
Falabella, Rafael ................................................................... a6
Fierheller, Marjorie ............................................................. a28
Finlayson, Laura ................................................................. a20
Fiorillo, Loretta ........................................................... a23, a34
Forouzandeh, Farshad ........................................................... a9
Fortier, Pierre-Hugues . ...................................................... a42
Foster, Robert . .................................................................... a41
Fraquelli, Elisa .......................................................... a44, a47
Fratesi, Lauren .............................................................. a7, a31
Fritzler, Marvin J. ............................................................... a23
Funaro, Deana ..................................................................... a13
Fung, Karen ........................................................................ a22
Gagné-Henley, Angélique .................................................. a49
Hanna, Dominique ......................................... a1, a32, a33, a42
Hawk, John ........................................................................... a9
Healy, Eugene .................................................................... a45
Hemmati, Iman ........................................................... a10, a38
Hinek, Anna A. ................................................................... a38
Ho, Nhung T. C. .................................................................... a5
Ho, Vincent ......................................................................... a46
Hong, H Chih-ho ................................................................ a18
Hordinsky, Maria K. ..................................................... a4, a33
Houle, Marie-Claude .......................................................... a38
Howell, Brandon G. ............................................................ a40
Hsu, Ming-Chun ................................................................. a45
Huang, Naiyan ..................................................... a11, a24, a51
Humphrey, Shannon D. . ..................................................... a10
Hunter, Charlene ................................................................ a49
Idriss, Nayla ........................................................................ a39
Ip, Wency ............................................................................ a11
Jackson, Christine ............................................................... a22
Jalili, Reza . ............................................................ a9, a15, a20
Gagné, Éric ......................................................................... a48
Jambrosic, Jadranka ............................................................ a48
Garrett, Jasmine T. .............................................................. a21
Jean, Sara-Elizabeth . .......................................................... a39
Gao, M. ............................................................................... a25
Ghaffari, Abdi ..................................................................... a21
Ghahary, Aziz . ................................... a2, a7, a9, a15, a20, a21
Ghoreishi, Mehran .......................................................... a7, a8
Gilbert, Martin .................................................................... a50
Ginhoux, Florent ................................................................... a4
Gladman, Dafna D. ............................................................. a47
Glassman, Steven J. ...................................................... a7, a34
Gottlieb, Alice B. ................................................................ a35
Gradinger, Abigail B. .......................................................... a16
Green, Peter j. ..................................................................... a35
Greenberg, Saul .................................................................... a5
Grewal, Parbeer S. .............................................................. a35
Guenther, Lyn ................................ a8, a30, a32, a36, a41, a44
Guilgoyle, Regan ................................................................ a26
Gulliver, Wayne ................................................. , a22, a32, a36
Gupta, Aditya K. ......................................................... a22, a36
Haber, Richard M. . ....................................................... a9, a37
Habibi, Darya . ...................................................................... a9
Hamilton, Tatyana . ............................................................. a37
Jang, Sang Jai . .................................................................... a18
Jiang, Helen ........................................................................ a11
Jiang, Xiaoyan .................................................................... a25
Jung, Gordon . ..................................................................... a17
Kalia, Sunil ......................................................................... a38
Kanigsberg, Nordau .............................................................. a7
Kavanaugh, Arthur . ............................................................ a35
Kilani, Ruhanguiz ................................................................. a2
Knowles, Sandra P. ............................................................. a42
Korbelik, Mladen ................................................. a11, a24, a51
Korman, Neil ...................................................................... a41
Kossintseva, Irèn . .............................................................. a39
Kraft, John .......................................................................... a12
Krell, James ........................................................................ a41
Krueger, Gerald G. . .................................................... a45, a46
Kunynetz, Rod ............................................................ a35, a46
Kuzel, Paul F. ...................................................................... a40
Kwok, Tiffany ..................................................................... a12
Kwong, Lorie ...................................................................... a13
Lam, Christina .................................................................... a13
a55
Landells, Ian ....................................................................... a46
Miller, CC ........................................................................... a18
Law, Angela ........................................................................ a40
Mistry, Nisha . ..................................................................... a18
Langley, Richard ......................................................... a36, a41
Leboeuf, Marylene . .............................................................. a4
Lebwohl, Mark ................................................................... a45
Lee, Anthony . ..................................................................... a13
Lee, Tim K. .................................................. a19, a25, a46, a51
Lee, Un Ha .......................................................................... a18
Li, Bin ........................................................................... a2, a49
Li, Gang ............................................................... a11, a14, a26
Li, Jun ................................................................................. a14
li, Shu .................................................................................. a46
Lin, Andrew ........................................................................ a49
Lin, Leon H. . ...................................................................... a26
Lo, Blanche K.K ......................................................... a14, a15
Lortie, Charles .................................................................... a15
Ludwick, Dave . .................................................................. a15
Lui, Harvey ................................. a11, a13, a15, a19, a22, a24,
............................................................... a25, a27, a46, a51, a52
Lupin, Mark ........................................................................ a40
Lyle, Michael ................................................................ a2, a49
Lynde, Carrie B. . ................................................................ a16
Lynde, Charles ..................................... a15, a22, a30, a36, a41
Ma, Lingle . ......................................................................... a28
Maares, Juergen ................................................... a30, a36, a41
Macdonald, Jillian A. .......................................................... a16
MacLean, David I. .............................................................. a13
Man, Jeremy ....................................................................... a52
Margesson, Lynette J. ....................................................... , a17
Martinka, Magdalena ..................................................... a8, a11
Mathes, Barbara .................................................................. a41
Matheson, Robert . ............................................................. a46
Matsukura, Setsuko . ........................................................... a42
Maynard, Bruno .......................................................... a32, a33
Mayo, Patrick . .................................................................... a36
McCuaig, Catherine C. ....................................................... a19
McElwee, Kevin J. . .................................................... a14, a15
McLean, David I. .................. a11, a19, a25, a27, a46, a51, a52
McLeod, W Alastair . .......................................................... a38
McMullin, Bevin . ............................................................... a21
Mendelsohn, Alan ............................................................... a35
Merad, Miriam ...................................................................... a4
Metelitsa, Andrei I. ............................................................. a17
a56
Miller, Chris ........................................................................ a21
Mitsos, Loukia-Maria ......................................................... a42
Moccia, Patrizia E. . ............................................................ a40
Moreau, Linda . ................................................................... a39
Moser, Joanna J. . ............................................................... a23
Moyst, Barbara ................................................................... a31
Muhn, Channy .................................................................... a15
Mydlarski, P. Régine ................................................... a13, a23
Nigen, Simon ...................................................................... a30
Noiles, Kristin ..................................................................... a43
Nugent, Zoann .................................................................... a26
O’Brien , Elizabeth ............................................................. a30
Ong, Christopher . ................................................................. a9
Papp, Kim ..................... a30, a32, a41, a44, a45, a46, a47, a50
Park, Hyun Su ..................................................................... a18
Park, Sang Hoon ................................................................. a18
Pellett, Fawnda ................................................................... a47
Policarpio, Bernardita .......................................... a15, a19, a46
Pope, Elena ........................................................................... a5
Poulin, Yves .......................... a22, a30, a36, a44, a46, a47, a50
Powell, Julie . .............................................................. a19, a51
Pratt, Melanie . ....................................... a5, a16, a29, a31, a33
Provost, Nathalie . ....................................................... a38, a47
Pruthi, Deepak .................................................................... a26
Purdy, Kerri S. .................................................................... a20
Rahmani-N, Elham ............................................................. a20
Rao, Jaggi ........................................................................... a15
Rasty, Golnar ...................................................................... a28
Reddick, Martina ................................................................ a31
Redlick, Fara ......................................................................... a5
Reich, Kristian ................................................................... a45
Rezakhanlou, Alireza Moeen .............................................. a21
Rivers, Jason ....................................................................... a10
Rizcallah , Edmond . .................................................. a32, a42
Rola-Pleszczynski, Marek .................................................. a33
Rosen, Cheryl F. . ........................................................ a40, a47
Rosoph, Les ........................................................................ a36
Rustin, Malcolm ................................................................. a45
Ryan, Siobhan ..................................................................... a12
Saber, Mélissa ..................................................................... a47
Salopek, Thomas G. ............................................................ a17
Sammour, Rita ................................................................... a19
Ting, Patricia . ..................................................................... a23
Sapijaszko, Mariusz ........................................................... a15
Tran, Jennifer M. . ....................................................... a13, a23
Samoil - Schelstraete, Christine . ........................................ a15
Sapra, Sheetal . ............................................................ a15, a22
Sawicki, Jakub .................................................................... a48
Sawyer, Doug . .................................................................... a40
Schentag, Catherine T. ........................................................ a47
Searles, Gordon E. ........................................................ a3, a21
Searles, Gordon . ................................................................. a16
Sebaldt, Rolf J. . .................................................................. a22
Tran, Diane ......................................................................... a50
Van Raamsdonk, Catherine . ............................................... a37
Vender, Ronald B. ................................................ a43, a48, a50
Vera-Kellet, Cristian ........................................................... a24
Walker, James ..................................................................... a29
Walsh, Noreen . ................................................................... a35
Walsh, Scott ....................................................................... a42
Wang, Hequn ............................................... a11, a13, a24, a51
Shanmujarajah, Sutha ......................................................... a47
Wang, Y. .............................................................................. a25
Shapiro, Jerry .............................................................. a14, a15
Wang, Yuhua ...................................................................... a45
Shapero, Jonathan L. . ......................................................... a21
Shapiro, Paul V. . ................................................................. a33
Shapiro, Ron L. ................................................................... a33
Shear, Neil . .................................................... a1, a22, a41, a42
Shen, Hua . ......................................................................... a47
Shen, Yaung-Kaung ............................................................ a35
Shojania, Kaveh G. ............................................................. a27
Sibbald, R Gary ..................................................... a1, a27, a28
Sidhu, Navkiran .................................................................. a15
Simoneau-Roy, Judith ......................................................... a42
Skotnicki-Grant, Sandy . ..................................................... a12
Sladden, Chris ..................................................................... a22
St-Amour, Pascale . ............................................................. a48
Stacey, Dawn ...................................................................... a22
Stanciu, Monica .................................................................. a49
Stankova, Jana .................................................................... a33
Su, M.W. ...................................................................... a11, a25
Szapary, Philipe .......................................................... a45, a46
Taher, Zaki A. ..................................................................... a49
Tamim, Hala . ........................................................................ a5
Tan, Jerry K.L. .................................................................... a22
Tan, Jerry .................................................................... a15, a22
Tang, Jing . .......................................................................... a22
Wang, Yang .................................................................. a11, a25
Wanggui, Yangsheng . ................................................... a2, a49
Warshaw, Erin M. ................................................................. a4
Wasel, Norman . ........................................... a30, a44, a46, a47
Watters, Kevin .................................................................... a30
Webster, Christine ................................................................. a5
Webster, John ................................................................ a2, a49
Wei, S. ................................................................................. a25
Weinstein, Miriam ................................................................ a5
Wighton, Paul ............................................................. a25, a51
Winnicki, Monika ............................................................... a51
Wiseman, Marni C. ............................................................. a26
Wong, Joyce W. .................................................................. a52
Wong, Ronald PC ............................................................... a26
Woo, Kevin ......................................................................... a28
Xu, A. .................................................................................. a25
Yeilding, Newman .............................................................. a45
Yu, Mei ............................................................................... a14
Zeller, Jeanne ........................................................................ a5
Zeng, Haishan ............... a11, a13, a19, a24, a27, a46, a51, a52
Zhang, X. ............................................................................ a25
Zhang, Yaohua Y. ......................................................... a11, a52
Zhao, Jianhua ....................................... a11, a24, a27, a51, a52
Tang, Liren ............................................................. a2, a11, a49
Zhou, Y. . ............................................................................. a25
Thériault, Mimi ................................................................... a50
Zloty, David ......................................................... a14, a15, a39
Thibeault, Marie-Marthe . ................................................... a48
Zupan, Matt . ....................................................................... a33
Tchvialeva, Lioudmila ............................................... a19, a46
Thérien, Geneviève ............................................................. a49
Thomas, D. Richard ............................................................ a22
Zhou, Youwen ................................................ a2, a11, a25, a52
Zobovitz, Judit .................................................................... a28
a57