1. health and fitness
2. disease

Elephantiasis nostras verrucosa: An institutional
analysis of 21 cases
Steven M. Dean, DO, FACP,a Matthew J. Zirwas, MD,b and Anthony Vander Horst, BA, BS, MAc
Columbus, Ohio
Background: Previous reports regarding elephantiasis nostras verrucosa (ENV) have been typically limited
to 3 or fewer patients.
Objectives: We sought to statistically ascertain what demographic features and clinical variables are
associated with ENV.
Methods: A retrospective chart review of 21 patients with ENV from 2006 to 2008 was performed and
statistically analyzed.
Results: All 21 patients were obese (morbid obesity in 91%) with a mean body mass index of 55.8. The
average maximal calf circumference was 63.7 cm. Concurrent chronic venous insufficiency was identified
in 15 patients (71%). ENV was predominantly bilateral (86%) and typically involved the calves (81%).
Proximal cutaneous involvement (thighs 19%/abdomen 9.5%) was less common. Eighteen (86%) related a
history of lower extremity cellulitis/lymphangitis and/or manifested soft-tissue infection upon presentation.
Multisegmental ENV was statistically more likely in setting of a higher body mass index (P = .02), larger calf
circumference (P = .01), multiple lymphedema risk factors (P = .05), ulcerations (P \ .001), and nodules
(P \ .001). Calf circumference was significantly and proportionally linked to developing lower extremity
ulcerations (P = .02). Ulcerations and nodules were significantly prone to occur concomitantly (P = .05).
Nodules appeared more likely to exist in the presence of a higher body mass index (P = .06) and multiple
lymphedema risk factors (P = .06).
Limitations: The statistical conclusions were potentially inhibited by the relatively small cohort. The study
was retrospective.
Conclusions: Our data confirm the association among obesity, soft-tissue infection, and ENV. Chronic
venous insufficiency may be an underappreciated risk factor in the genesis of ENV. ( J Am Acad Dermatol
2011;64:1104-10.)
Key words: edema; elephantiasis; elephantiasis nostras verrucosa; lymphedema.
E
lephantiasis nostras verrucosa (ENV) is an
uncommon and singular array of dermatologic manifestations that can complicate
chronic lymphedema. Characteristic cutaneous signs
include profound hyperkeratosis, dermal fibrosis,
and lichenification, and a verrucous and papillomatous eruption with a cobblestone-like appearance
From the Departments of Cardiovascular Medicinea and Dermatology,b Ohio State University College of Medicine; and Quantitative Research, Evaluation, and Measurement, Ohio State
University School of Educational Policy and Leadership.c
Funding sources: None.
Conflicts of interest: None declared.
Accepted for publication April 29, 2010.
Reprint requests: Steven M. Dean, DO, FACP, Department of
Cardiovascular Medicine, Ohio State University College of
1104
Abbreviations used:
BMI: body mass index
CVI: chronic venous insufficiency
ENV: elephantiasis nostras verrucosa
Medicine, 200 Davis Heart and Lung Research Institute, 473
W 12 Ave, Columbus, OH 43210. E-mail: steven.dean@osumc.
edu.
Published online March 28, 2011.
0190-9622/$36.00
ª 2010 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2010.04.047
Dean, Zirwas, and Horst 1105
J AM ACAD DERMATOL
VOLUME 64, NUMBER 6
(Fig 1). The aforementioned array of dermatologic
assess for both acute and chronic recanalized deep
findings usually occurs in the presence of severe,
venous thrombosis and venous incompetence.
fibrotic edema that resists pitting. Recurrent cellulitis,
Routinely obtained laboratory studies included:
tumors, previous surgery or trauma, obesity, congescomprehensive chemistry profile, complete blood
tive heart failure, and radiation are purported risk
cell count, thyroid-stimulating hormone, free
factors for ENV. However, concrete data regarding
thyroxine-4, and urinalysis. When clinically approprithe epidemiology of this disorder are limited to
ate, a transthoracic echocardiogram was obtained
information attained from
with attention to the right
isolated case reports typically
ventricular and pulmonary arCAPSULE SUMMARY
involving 3 or fewer patients.
tery systolic pressures.
In an attempt to further
Morbid obesity and soft-tissue infection
elucidate the potential unRESULTS
are the predominant risk factors for
derlying risk factors for
The sample of 21 patients
elephantiasis nostras verrucosa (ENV).
this disfiguring condition, an
identified with ENV was
ENV is principally bilateral and typically
analysis of 21 affected pacomposed of 14 men and 7
involves the calves. Proximal cutaneous
tients was undertaken from
women. The mean age of
involvement (thighs/abdomen) is less
a university outpatient vascustudy participants and avercommon.
lar medicine clinic.
age duration of lymphedema
was 54 years (range: 26-77
Chronic venous insufficiency was present
METHODS
years) and 11 years, respecin 71% of cases of ENV and often
An assessment of 21 patively. All patients had bilatmanifested as concurrent stasis
tients clinically given the dieral lymphedema. Although
dermatitis, lipodermatosclerosis,
agnosis of lower extremity
one individual underwent a
ulcerations, or a combination of these.
ENV (2006-2008) was underbelow-knee
amputation
Venous hypertension may be an
taken at a university vascular
1
year
before
presentation,
underappreciated risk factor for ENV.
medicine clinic. The diagnohe described a long-standing
sis of ENV was made by recpresurgical history of bilatognizing the cutaneous characteristics in the setting
eral ENV.
of stage III lymphedema. All patients were examined
The mean BMI was 55.8 (range: 34.6-79.1). All
by a vascular medicine specialist certified by the
study patients met criteria for obesity (BMI $ 30
American Board of Vascular Medicine. Cutaneous
kg/m2) with 19 of the 21 patients (91%) fulfilling the
criteria for morbid obesity (BMI $ 40). The average
biopsy specimens were not routinely obtained.
maximal calf circumference was 63.7 cm (range:
Demographic data (age, gender, body mass index
43.2-106.7 cm).
[BMI]) were acquired. Lymphedema-related clinical
Characteristic ENV skin manifestations were revariables reviewed included: etiology, limb involvecorded in 18 of the 21 patients (86%) in a bilateral
ment (unilateral/bilateral), maximal calf circumferfashion. In the 3 patients (14%) with unilateral ENV,
ence (centimeters), and duration of swelling.
the more swollen extremity was affected. All patients
Patients were queried regarding a history of cellulitis
manifested cobblestone-like plaques and papules
and carefully inspected for evidence of acute softwith associated hyperkeratosis. Eleven patients
tissue infection.
(52%) with ENV had associated nodules as well.
Recorded ENV-associated clinical findings reThe distribution of ENV cutaneous pathology is
corded included: lesion distribution (toes, feet,
outlined in Fig 2. Acute (n = 3) or previous (n = 8)
calves, thighs, abdomen, or a combination of these)
lower extremity venous stasis/lymphostatic ulceraand lesion type (papules, plaques, nodules).
tions were identified in 11 patients (52%). Eighteen
A papule was defined as an elevated solid lesion
of the patients (86%) related a history of cellulitis
up to 0.5 cm in diameter. A plaque was defined as a
and/or manifested skin infection at the time of their
circumscribed, plateaulike elevation above the skin
examination.
surface, often formed by the confluence of papules.
Fifteen patients (71%) manifested concurrent
A nodule was defined as a circumscribed, elevated,
CVI according to the ClinicaleEtiologiceAnatomice
solid lesion greater than 0.5 cm in diameter.
Pathophysiologic classification criteria (Fig 3). Seven
The ClinicaleEtiologiceAnatomicePathophysiologic
of the 15 cases of clinically overt venous hypertension
classification criteria were used to grade any associwere corroborated by ultrasonographically docuated physical findings of chronic venous insufficiency
mented reflux. Superficial reflux within the bilateral
(CVI).1 Bilateral lower extremity venous duplex
ultrasonography was performed on all patients to
above- and below-knee great saphenous vein was
d
d
d
1106 Dean, Zirwas, and Horst
J AM ACAD DERMATOL
JUNE 2011
Fig 1. A 58-year-old obese man with classic skin findings
of bilateral lower extremity elephantiasis nostras verrucosa
including an admixture of plaques, papules, and nodules
with a cobblestoned and mossy appearance in a multisegmental distribution (toes/feet/calves).
identified in 7 cases with associated bilateral distal
medial calf perforating vein reflux in two patients. No
evidence of acute or chronic deep venous thrombosis
was identified.
Echocardiography documented mild to moderate
pulmonary hypertension (right ventricular systolic
pressure = 50-60 mm Hg) with normal left ventricular
systolic function in 3 patients (14%).
Statistical analysis
Two types of correlations were reported. Pearson
correlations for the continuous by continuous
variables (age, BMI, average maximal calf circumference, lymphedema duration). The Pearson correlation was reported when both the column and row
variables had a (P) identifier. The remaining data
were assessed via Spearman correlations for the
categorical by categorical variables. Significant results were defined at a level of significance of .05.
Table I illustrates the statistical analyses of the
aforementioned variables. Not surprisingly, there
was a statistically significant (R = 0.79, P \ .001)
relationship between the BMI and maximal (mean)
calf circumference, with the calf circumference increasing roughly in proportion to BMI. Nearing
statistical significance (R = 0.42, P = .06), a moderately positive relationship between BMI and the
presence of nodules existed, suggesting a correlation
between degree of obesity and risk for developing
nodules. Finally, a significant correlation (R = 0.51,
P = .02) between the BMI and anatomic distribution
of ENV was identified. With increasing BMI, more
areas of the lower extremity were affected by the
cutaneous changes of ENV (henceforth referred to as
multisegmental cutaneous involvement).
As maximal calf circumference increased, patients
were significantly more likely to incur both skin
ulcerations (R = 0.52, P = .02) and multisegmental
cutaneous involvement (R = 0.54, P = .01).
The duration of lymphedema did not significantly
correlate with complications of ENV such as nodules,
ulcerations, or distribution.
Men with ENV were more likely than women to
have associated CVI (R = e0.67, P \.001).
As the number of underlying risk factors (cellulitis, obesity, and pulmonary hypertension) for ENV
increased, patients were significantly more likely to
develop multisegmental cutaneous pathology
(R = 0.44, P = .05). In addition, patients with multiple
risk factors were probably more likely to develop
nodules (R = 0.42, P = .06) although this relationship
did not meet statistical significance.
Lower extremity ulcerations (R = 0.62, P \ .001)
and nodules (R = 0.77, P \ .001) were statistically
more likely to exist in the presence of multisegmental cutaneous involvement. In addition, nodules and
ulcerations were significantly prone to occur concurrently (R = 0.43, P = .05).
A significant inverse correlation was identified
between age and the two variables BMI and maximal
calf circumference. For instance, younger patients
had both larger calves (R = e0.525, P \ .015)
and higher BMIs (R = e0.43, P = .051) than older
patients.
None of the patients had severe hypoalbuminemia, chronic liver disease, or end-stage renal disease.
Patients with a history of hypothyroidism were
euthyroid via thyroid-stimulating hormone and free
thyroxine-4 testing at the time of their assessment.
No cases of Graves disease were identified.
DISCUSSION
ENV is an uncommon, potentially disfiguring, and
sometimes grotesque constellation of dermatologic
sequelae of chronic lymphatic obstruction.
Alternative terms for this disorder include ‘‘lymphostatic verrucosa,’’ ‘‘lymphostatic papillomatosis cutis,’’ ‘‘elephantiasis crurum papillaris et verrucosa,’’
and ‘‘mossy foot and/or leg.’’ Although morphologically comparable with classic filarial elephantiasis
(eg, Wuchereria or Brugia species), ENV is a separate, nonparasitic mediated disorder. Semantically,
the adjective ‘‘nostras’’ indicates ‘‘from our region’’
(temperate zone); consequently, nonfilarial elephantiasis or ENV is nosologically differentiated from
classic tropical helminthic elephantiasis.
In his seminal 1934 work, Castellani2 classified
elephantiasis into 4 subtypes: (1) elephantiasis tropica,
J AM ACAD DERMATOL
Dean, Zirwas, and Horst 1107
VOLUME 64, NUMBER 6
Fig 2. Distribution of elephantiasis nostras verrucosa (ENV) cutaneous pathology.
Fig 3. Chronic venous insufficiency subtypes in setting of elephantiasis nostras verrucosa
according to ClinicaleEtiologiceAnatomicePathophysiologic classification criteria.
caused by filariasis (eg, Wuchereria species); (2)
elephantiasis nostras, secondary to recurrent bacterial
cellulitis/lymphangitis; (3) elephantiasis symptomatica, caused by diverse conditions such as tuberculosis, syphilis, fungi, neoplasms, and surgery; and (4)
elephantiasis congenita, in association with Milroy
and Meige disease. However, more recent literature
includes the aforementioned causes of elephantiasis
symptomatica within the definition of ENV.3,4
Similarly, an argument could also be constructed for
including patients with elephantiasis congenita and
lymphostatic verrucosis within the ENV definition.
1108 Dean, Zirwas, and Horst
J AM ACAD DERMATOL
JUNE 2011
Table I. Statistical analysis of variables associated with elephantiasis nostras verrucosa
BMI (P)
BMI (P)
Corr
sig
Calf (P)
Corr
sig
Duration (P)
Corr
sig
Gender
Corr
sig
Etiology
Corr
sig
Age (P)
Corr
sig
Nodule
Corr
sig
Ulcers
Corr
sig
CVI
Corr
sig
Dist
Corr
sig
Calf (P)
Duration (P)
Gender
Etiology
Age (P)
Nodule
Ulcers
CVI
Dist
1
0.76
.00
1
0.07
.78
0.08
.72
1
0.18
.43
0.11
.64
0.15
.51
1
0.27
.23
0.30
.19
0.21
.36
0.06
.80
1
0.60
.00
0.58
.01
0.31
.17
0.16
.49
0.00
1.00
1
0.42
.06
0.29
.20
0.29
.20
0.07
.77
0.42
.06
0.00
1.00
1
0.24
.29
0.52
.02
0.21
.37
0.13
.56
0.25
.26
0.05
.84
0.43
.05
1
0.19
.41
0.04
.85
0.22
.34
0.67
.00
0.31
.17
0.01
.97
0.03
.90
0.24
.29
1
0.51
.02
0.54
.01
0.06
.80
0.01
.97
0.44
.05
0.20
.38
0.77
.00
0.62
.00
0.14
.54
1
BMI, Body mass index; Corr, correlation; CVI, chronic venous insufficiency; Dist, distribution; sig, significance.
Two types of correlations were reported. Pearson correlation (P) was used for continuous by continuous variables (BMI, maximal calf
circumference, lymphedema duration, and age). Remaining results were reported via Spearman correlations for categorical by categorical
variables. For results that show significance at 95% confidence level, both correlation coefficient (r) and P value (sig) are bolded.
Regardless of the aforementioned subtype, the
theory of Castellani5 suggests that all forms of
elephantiasis share a common pathogenic mechanism. Specifically, recurrent streptococcal (less often
staphylococcal) lymphangitis is the ultimate precipitant of elephantiasis. Even in the setting of filariasis,
Castellani5 proposed that parasitic burden traumatizes the lymphatic vessels, thereby allowing
secondary bacterial lymphangitis to provoke elephantiasis. The precipitating events in ENV are
speculative but are probably a result of occult or
clinically manifest disruption of the skin barrier from
cutaneous fissures, erosions, ulcerations, and/or
tinea-associated interdigital fissures. Consequently,
a nidus for bacterial infection is created.
With each bacterial infection, increasing lymphatic stasis ensues with progressive accumulation
of proteins, lymphocytes, and cellular metabolites.
Fibroblasts proliferate and collagen is deposited with
subsequent epidermal, dermal, and subcutaneous
thickening. Consequently, the limb becomes progressively swollen and increasingly susceptible to
additional bouts of soft-tissue infection. Attendant
local immune dysfunction further increases susceptibility to cellulitis. Because of this vicious cycle of
swelling and infection, classic ENV eventuates. Our
data support the role of recurrent soft-tissue infection
in the genesis of ENV, as 86% of the patients
presented with either acute lower extremity cellulitis
or described a history of soft-tissue infection.
However, the association between recurrent cellulitis and ENV does not appear absolute because 14% of
the patients had no history of infection. Case reports
of ENV evolving in the absence of cellulitis or
lymphangitis exist.6
Our study highlights the importance of two lesser
appreciated factors in the setting of ENV, specifically
obesity and CVI. All 21 patients were obese with 91%
J AM ACAD DERMATOL
Dean, Zirwas, and Horst 1109
VOLUME 64, NUMBER 6
of them meeting criteria for morbid obesity (BMI $
40). The mean BMI was an astounding 55.8 with an
average maximal calf circumference of a remarkable
63.7 cm (25 in). Although several studies have illustrated that obesity enhances the risk of postmastectomy lymphedema,7,8 an explicit association between
obesity and lower extremity lymphedema has not
been well documented in the medical literature. In a
2008 article, deidentified data from 17 wound care
centers within the United States (approximately 15,000
patients) documented a 74% prevalence of lower
extremity lymphedema in morbidly obese patients.9
The pathophysiological mechanisms that link
obesity and lymphedema are speculative but may
involve structural lymphatic changes in the interstitium, impaired diaphragmatic movement, increased
abdominal pressure, and/or arteriovenous proliferation within oxygen-demanding fat tissue without
proportional lymphatic proliferation. A definite answer as to what provokes ENV to develop in the
setting of obesity and lymphedema is cryptic, although our data support the theory of Castellani5 that
superimposed soft-tissue infection may be causative.
Multiple small case reports (n = # 2 patients) of
patients with ENV have documented the potentially
culpable combination of obesity and recurrent cellulitis, lymphangitis, or both.3,10-12
Obesity is often implicated as a risk factor for
CVI; consequently, it is not surprising that 15 of
our patients (71%) manifested clinical (and often
ultrasonographic) signs of venous hypertension.
Many
patients
displayed
more
advanced
ClinicaleEtiologiceAnatomicePathophysiologic
features, as evidenced by stasis pigmentation (IVa) in
14 (67%) and chronic stasis-associated sclerosing
panniculitis/lipodermatosclerosis (IVb) in 9 (43%).
The relationship between lymphedema and CVI
has been noted by other authors via various objective
tests13-16 or clinical observation.17,18 CVI may be an
underrecognized factor in the pathogenesis of ENV.
Curiously, we uncovered a significant inverse
relationship between age and the variables BMI
and maximal calf circumference. Younger patients
were more obese with larger calves. This converse
association may simply reflect the recent increasing
mean BMI in the United States. For example, the
percentage of male subjects with a BMI greater than
or equal to 30 kg/m2 in the original (1948-1953),
offspring
(1971-1975),
and
third-generation
(2002-2005) cohorts of the Framingham Heart
Study was 12%, 15%, and 26%, respectively.19
Because of the paucity of reported cases, no
evidence-based medicine exists to guide therapy of
ENV. Management is based on limited data from case
reports. Treatment includes traditional modalities
used in lymphedema, including skin hygiene, limb
elevation, manual lymphatic drainage/complete decongestive therapy, compression bandages, graduated support stockings, and sequential intermittent
lymphatic pumping. Two case reports documented
attenuation in both leg swelling and skin changes
with the use of sequential lymphatic pumping.17,20
Considering that obesity and cellulitis appear closely
linked to ENV, weight loss and infection control are
paramount clinical goals. Both topical and systemic
retinoids have been successfully used to mitigate the
cutaneous manifestations of ENV.6,21 Two case reports illustrated favorable results with the use of
scalpel debridement.22,23 In one of these surgical
reports, adjunctive dermabrasion with a motorpowered grinder was used.22 A lymphaticovenular
anastomosis effectively reduced limb swelling and
skin lesions in one patient with ENV.24 As a last
resort, amputation is sometimes required.12,25
Conclusion
We have reported the largest series to date on the
combined cutaneous and vascular malady ENV. In a
statistical fashion, our data illustrate how many
pathophysiological variables interact in this disfiguring disorder.
ENV was predominantly a distal disorder (81%)
that affected the calves (either in isolation or in
combination with the feet and toes) and was typically bilateral (86%). Proximal involvement of the
thigh and abdominal wall occurred in only 19% and
10% of the patients, respectively. Multisegmental
cutaneous pathology was statistically more likely to
occur in the presence of a higher BMI, larger calf
circumference, multiple risk factors (eg, cellulitis,
obesity, pulmonary hypertension, or a combination
of these), ulcerations, and nodules. Calf circumference was significantly and proportionally linked to
developing lower extremity ulcerations. Nodules
and ulcerations were significantly prone to occur
simultaneously. An elevated BMI and multiple risk
factors appeared to increase the chance of manifesting nodules but these relationships fell short of being
statistically significant (P = .06), probably because of
an inadequate sample size. Although severe obesity
and soft-tissue infection appeared inexorably linked
in the genesis of ENV, associated CVI may have been
an underappreciated participant in causation as well.
As the proportion of obese patients in the United
States increases, the probability of developing both
lymphedema and its disfiguring sequel, ENV, is
expected to increase as well. Our facility will continue to enroll patients in an ENV database in an
effort to obtain more information on this distinct and
unfortunate condition.
1110 Dean, Zirwas, and Horst
J AM ACAD DERMATOL
JUNE 2011
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