Multiple Facial Seborrheic Keratoses - like lesions in a young adult with epidermodysplasia verruciformis
Henry Foong FRCP, Ipoh, Malaysia (1)
Andrew Carlson MD, FRCPC, Albany, NY, USA (2)
on May 27, 2005
(1) Consultant Dermatologist, Foong Skin Specialist Clinic, Ipoh, Malaysia
(2) Associate Professor, Divisions
of Dermatopathology and Dermatology
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by disseminated infection by human papillomavirus (HPV) and malignant transformation of the lesions in about half of the patients. Two phenotypes of EV have been described according to their propensity to develop malignant tumors. The benign form of EV presents a singular type of lesions comprised of flat warts widely disseminated. The malignant form of EV is highly polymorphic and presents as malignant skin tumors, predominantly basal and squamous cell carcinomas, on sun-exposed sites. The seborrheic keratosis-like (SK) lesions in patients of EV have been reported to be associated with the malignant phenotype. In this work, we documented the behavior of SK-like lesions in nine patients with EV, through clinical observations as well as histological and immunohistochemical findings. We suggest that the HPV infection may promote the occurrence of SK-like lesions in EV patients. Despite the fact that we did not observe any malignant transformation of these lesions in our series of patients, this possibility was not completely excluded.
Kwon OS, Hwang EJ, Bae JH, Park HE, Lee JC, Youn JI, Chung JH. Seborrheic keratosis in the Korean males: causative role of sunlight. Photodermatol Photoimmunol Photomed. 2003 Apr;19(2):73-80.
BACKGROUND/PURPOSE: Seborrheic keratoses (SKs) are common epidermal
tumors in the white population over 40 years. The etiology of SKs
is not well known; however, exposure to sunlight was suggested to
play a role in the development of them. To our knowledge, no well-designed
study has been undertaken in order to investigate the clinical characteristics
of SKs in a brown-skinned Korean population. The aim of this study
was to assess the prevalence and clinical features of SKs in the Korean
males and to investigate the possible relationship of SKs with sun
exposure and possible risk factors of developing SKs. METHODS: A total
of consecutive 303 male volunteers, aged 40-70 years, were recruited
from general community and public health centres. Each volunteer was
interviewed regarding demographic data, sunlight sensitivity, lifetime
cumulative sun exposure and smoking history. Skin examination was
performed except for scalp, buttocks and genitals. All SKs were recorded
about the anatomical distribution, the size of each lesion measured
with a caliber, color and morphology. RESULTS: The mean overall prevalence
of SKs in the Korean males, aged 40-70 years was 88.1%. A considerable
increase in the prevalence of SKs was shown from 78.9% at 40 years
to 93.9% at 50 years and 98.7% in those over 60 years. The mean number
of lesions per person was 5.5 at 40 years, 9.2 at 50 years and 13.4
at 60 years. Seborrheic keratoses were considerably more frequent
on exposed areas (0.47 +/- 0.06/percentage of body surface area, BSA)
than partly exposed areas (0.04 +/- 0.01/percentage of BSA). The majority
of lesions were concentrated on the face (0.98 +/- 0.09/percentage
of BSA) and on the dorsum of each hand (0.51 +/- 0.08/percentage of
BSA). The size of each lesion on exposed areas also became significantly
larger by decade significantly (P < 0.01). The estimated area covered
by SKs per percentage of BSA on exposed areas was 5.7-fold larger
than that on partly exposed areas at 40 years, 11.2-fold larger at
50 years and 18.3-fold larger at 60 years. Aging by decade showed
a 2.08-fold increased risk for SKs (n > or = 6) (95% CI, 1.07-4.08)
at 50 years and a 3.47-fold risk (95% CI, 1.67-7.20) at 60 years on
exposed areas compared with the 40-year age group, for developing
many SKs (n > or = 6). Lifetime cumulative sunlight exposure of
more than 6 h per day was associated with a 2.28-fold higher risk
of SKs than a sun exposure of less than 3 h per day. A tendency for
an odds ratio value reduction was found on increasing Fitzpatrick
skin types I-III to VI, V; however, this was without statistical significance.
CONCLUSIONS: Seborrheic keratoses are common in the Korean males,
aged 40-70 years, and may be a major pigmentary problem. Both aging
and cumulative sunlight exposure were found to be independent contributory
Li YH, Chen G, Dong XP, Chen HD. Detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in nongenital seborrhoeic keratosis Br J Dermatol. 2004 Nov;151(5):1060-5.
BACKGROUND: DNA of epidermodysplasia verruciformis (EV)-associated
human papillomaviruses (HPVs) has been widely detected in lesions
of malignant skin tumours, benign tumours and other proliferative
diseases of epithelial origin. OBJECTIVES: To investigate the presence
of EV-associated HPV DNA in nongenital seborrhoeic keratosis (SK)
and to elucidate the prevalence of distinct HPV genotypes. METHODS:
We investigated HPV DNA in 55 nongenital SK biopsies, which were compared
with 48 normal skin biopsies (healthy controls) using a nested polymerase
chain reaction (PCR) using consensus primers CP65/CP70 and CP66/CP69.
The positive PCR products were retracted and used to prepare recombination
clones with T-vector. Distinct clones were analysed with endonucleases,
and HPV genotypes were identified by direct sequencing. RESULTS: EV-associated
HPV DNA was detected in 42 of 55 (76%) nongenital SK biopsies vs.
only 13 of 48 (27%) healthy controls (chi2 = 22.087; P < 0.005).
The prevalence was higher in patients with more than five lesions
than in those with only one lesion (P < 0.05). Ten distinct HPV
genotypes were detected in the nongenital SK biopsies: HPV 20, 23,
5, renal transplant recipient (RTR) X7, HPV 17, 37, 17b, RTRX4, RTRX4b
and strain SK3. HPV 20 was found in 26 of 42 (62%) positive specimens,
followed by HPV 23 (11 of 42, 26%) and HPV 5 (six of 42, 14%). Existence
of multiple HPV genotypes was observed in 12 of 42 (29%) positive
specimens. In healthy controls, five genotypes of EV-associated HPV
(HPV 20, 23, 5, 17 and RTRX4) were detected, with the same predominant
genotype of HPV 20 (five of 13, 38%). Several distinct HPV genotypes
were found to coexist in four of 13 (31%) positive specimens. CONCLUSIONS:
This study provides some evidence that EV-associated HPVs might play
a part in the pathogenesis of nongenital SK.
Tomasini C, Aloi F, Pippione M. Seborrheic keratosis-like lesions in epidermodysplasia verruciformis. J Cutan Pathol. 1993 Jun;20(3):237-41.
A light microscopic study of 6 verrucous lesions with clinical features of seborrheic keratoses (SK) occurring on sun-exposed skin of 4 patients with epidermodysplasia verruciformis (EV) was performed. We observed the typical histological findings of SK in all cases. In addition, koilocytotic effects suggestive of EV were observed in the upper prickle layer and stratum granulosum. In 2 lesions, we also noted bowenoid changes suggesting possible early malignant transformation. Immunohistochemical study confirmed the presence of HPV in these lesions
Ramoz N, Taieb A, Rueda LA, Montoya LS, Bouadjar B, Favre M, Orth G. Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformis with two susceptibility loci mapped to chromosome regions 2p21-p24 and 17q25.J Invest Dermatol. 2000 Jun;114(6):1148-53.
Epidermodysplasia verruciformis is a rare genodermatosis associated
with a high risk of skin cancer. This condition is characterized by
an abnormal susceptibility to specific related human papillomavirus
genotypes, including the oncogenic HPV5. Epidermodysplasia verruciformis
is usually considered as an autosomal recessive disease. We recently
mapped a susceptibility locus for epidermodysplasia verruciformis
(EV1) to chromosome 17qter within the 1 cM interval between markers
D17S939 and D17S802. We report here the genotyping for 10 microsatellite
markers spanning 29 cM around EV1 in two consanguineous epidermodysplasia
verruciformis families from Colombia (C2) and France (F1) comprising
five patients and two patients, respectively. Using homozygosity mapping,
linkage with 17qter markers was observed for family C2 only. Multipoint
linkage analysis yielded maximum multipoint LOD-score values above
10 between markers D17S1839 and D17S802 encompassing the EV1 locus.
A genome-wide search performed in family F1 yielded evidence for linkage
between epidermodysplasia verruciformis and the chromosomal 2p marker
D2S365. Nine additional microsatellite markers spanning 15 cM in this
region were analyzed. Assuming an autosomal recessive inheritance
with a complete penetrance, the expected maximum two-point LOD-score
value of 1.8 was obtained for three markers and multipoint linkage
analysis yielded a maximum LOD-score value of 3. 51 between markers
D2S2144 and D2S392. Haplotype analysis allowed to map a candidate
region for a second epidermodysplasia verruciformis susceptibility
locus (EV2) within the 8 cM interval between markers D2S171 and D2S2347
of the 2p21-p24 region. In contrast, linkage with 2p markers was excluded
for family C2 and for the three families in which we mapped EV1 previously.
The disclosure of two susceptibility loci for epidermodysplasia verruciformis
provides evidence for a nonallelic heterogeneity in this disease.
Sullivan, M.; Ellis, F. A. : Epidermodysplasia verruciformis (Lewandowsky and Lutz). Arch. Derm. Syph. 40: 422-432, 1939.
Anadolu et al. Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a. J Am Acad Dermatol 2001;45:296-9.
Epidermodysplasia verruciformis (EV) is an autosomal recessive disease characterized by the lifelong eruption of disseminated verrucae-like lesions. Numerous treatment modalities have been used to treat EV without benefit. Recently, retinoid and interferon therapies have been found to be of value in the treatment of EV. We present a case of EV that was treated with a combination of acitretin and interferon alfa-2a.