Multiple Facial Seborrheic Keratoses - like lesions in a young adult with epidermodysplasia verruciformis

presented by

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
Albany Medical College, Albany, NY, USA




Roncalli de Oliveira W, Neto CF, Rady PL, Tyring SK.Seborrheic Keratosis-like lesions in patients with epidermodysplasia verruciformis. J Dermatol. 2003 Jan;30(1):48-53.

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 factors.

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.

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