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Four familial cases of epidermodysplasia verruciformis: Mother and three sons

  • Author(s): Robati, Reza Mahmoud
  • Marefat, Afsaneh
  • Saeedi, Marjan
  • Rahmati-Roodsari, Mohammad
  • Asadi-Kani, Zahra
  • et al.
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Four familial cases of epidermodysplasia verruciformis: Mother and three sons
Reza Mahmoud Robati MD, Afsaneh Marefat MD, Marjan Saeedi MD, Mohammad Rahmati-Roodsari MD, Zahra Asadi-Kani MD
Dermatology Online Journal 15 (4): 8

Skin Research Center, Shahid Beheshti University, M.C. Shohada-e Tajrish Hospital, Tehran, Iran. rmrobati@gmail.com

Abstract

Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. In this report, we present three Iranian brothers and their mother with extensive seborrheic keratosis-like (SK-like) viral warts. Initial facial lesions developed in the first decade and disseminated with time. The patients showed SK-like viral warts characterized by dark brown or black pigmented proliferative lesions with hyperkeratotic surfaces. The histopathological findings were consistent with the diagnosis of EV. There are few reports of familial epidermodysplasia verruciformis especially in a mother and her three sons.



Introduction

Epidermodysplasia verruciformis (EV) is an inherited disorder in which there is widespread and persistent infection with HPV, giving rise to a characteristic combination of plane warts, pityriasis versicolor-like lesions and reddish plaques. Malignant change is very common but metastasis is rare. The cutaneous lesions of EV first appear in childhood and are highly polymorphic. Multiple squamous cell carcinomas (SCC) of the skin develop subsequently on sun-exposed sites in about half of the patients. Benign cutaneous findings include polymorphic lesions such as pityriasis versicolor-like (PV-like) macules, flat warts and red macules. Epidermodysplasia verruciformis is believed to be an autosomal recessive disease [1, 2]. Two susceptibility loci, EV1 and EV2, have been mapped with EV1 containing the characterized EVER1/TCM6 and EVER2/TCM8 genes [3].


Report

In this report, we present three Iranian brothers (ages 10, 16, and 25), and their 55-year-old mother with extensive seborrheic keratosis-like (SK-like) viral warts. Initial facial lesions developed in the first decade and disseminated with time. Pityriasis versicolor-like brown scaly macules resembling pityriasis versicolor were observed on the trunk and neck. (Fig. 1) The patients showed SK-like viral warts characterized by dark brown or black pigmented proliferative lesions with hyperkeratotic surfaces. (Fig. 2)


Figure 1Figure 2
Figure 1. PV-like brown scaly macules resembling pityriasis versicolor were observed on the trunk in the 25 year old brother.

Figure 2. Seborrheic keratosis-like viral warts characterized by dark brown or black pigmented proliferative lesions with hyperkeratotic surfaces on the trunk in the mother.

Figure 3
Figure 3. Facial SK-like lesions were dark and warty in 10-year-old brother.

Facial SK-like warty lesions were dark and plaque-like. (Fig. 3) Hyperkeratotic warty lesions on dorsal aspect of hands were present in all patients. (Figs. 4 & 5)

There was no history of skin cancer in the mother and she mentioned no history of similar cutaneous lesions or skin malignancy in her relatives. Routine laboratory tests were all negative or within normal ranges. The patients showed no decrease in the number of CD8+ T-cells as described previously for EV. They are all HIV-negative.


Figure 4Figure 5
Figure 4. Hyperkeratotic warty lesions on dorsal aspect of hands were present in all patients.

Figure 5. Hyperkeratotic warty lesions on dorsal aspect of hands were present in three patients (closer view).

Skin biopsies were taken from one SK-like wart and histopathologic evaluation of the warty lesion revealed hyperkeratosis and hypergranulosis with vacuolation and koiliocytes consistent with HPV infection. The lesion showed mild to moderate dysplasia in the epidermis. (Fig. 6) The dermatopathological findings were consistent with the diagnosis of EV.


Figure 6Figure 7
Figure 6. Histopathological view: Hyperkeratosis and hypergranulosis with vacuolation and koiliocytes and moderate dysplasia in the epidermis (H&E x40)

Figure 7. Histopathological view: Koiliocytes and moderate dysplasia in the epidermis (H&E x100)

Discussion

Epidermodysplasia verruciformis is a genodermatosis characterized by disseminated HPV infection, malignant conversion, and immunological abnormalities. This is an example of genetic predisposition of squamous cell carcinoma of viral origin and it has been regarded as a model of cutaneous HPV oncogenesis [4]. EV has no particular racial predisposition or geographical preference [5]. The first lesions to appear are flat warts, localized to the dorsal hands and fingers. A few years later, pityriasis versicolor-like lesions, characteristic of EV, will develop [6].

Epidermodysplasia verruciformis-associated HPV types include 3 and 10 (both characteristic of plane wart in non-EV patients) as well as types more distinctive to EV such as 5, 8, 9, 12, 14, 15, and 17. Individual EV patients frequently express several HPV types in their lesions and the most commonly recognized HPV types identified depend on the molecular techniques used [7].

Squamous cell carcinoma (SCC) develops in 30-60 percent of EV patients on sun-exposed surfaces, frequently beginning between 20 and 40 years of age. Most of EV-associated SCCs are related to HPV types 5 and 8, although HPV types 14 and 47 may also be important. Epidermodysplasia verruciformis patients who have a lower production of interleukin-10 are predisposed to develop SCC. Epidermodysplasia verruciformis-associated SCCs may be quite locally destructive but rarely metastasize. Actinic keratoses, Bowen disease, and basal cell carcinomas are further potential complications. Extracutaneous malignancies have infrequently been associated with EV. Epidermodysplasia verruciformis patients have impaired cell-mediated immunity and EV-like lesions have been reported in various immunosuppressed states including HIV [8].

Classical inherited EV may be caused by autosomal recessive defects in EVER1/TCM6 or EVER2/TCM8, both of which are positioned on chromosome 17 and encode integral membrane proteins of unknown significance in the endoplasmic reticulum [3]. Another susceptibility locus has been mapped to chromosome 2, although the exact gene defect is still unknown. Reports of several other pedigrees with classical EV have suggested the presence of an X-linked recessive form of transmission [9].

Although the most common form of EV is sporadic [9], there have been some reports of familial EV. One report from India introduced 14 members of an EV pedigree among 41 individuals across several generations, with second degree consanguinity [10]. Another from Turkey reported a 22-year-old Turkish male and his 45-year-old mother with extensive seborrheic keratosis-like (SK-like) viral warts with no family history of EV [11]. The third report from Brazil introduced thirteen patients (seven male and six female). Eleven were the product of consanguineous marriages, all first cousin marriages. Ten patients had at least one sibling involved. Three patients (23%) were mentally retarded [4]. The fourth report of familial EV was from China and presented two families with EV: the first family consisted of 6 EV patients and 23 normal individuals and the second family included 2 EV patients and 12 normal individuals [12].

Herein, we report four familial cases of EV in a mother and her three sons, all of whom manifested with bizarre SK-like warty growths and a PV-like eruption. Another prominent point of our report was the lack of consanguinity between parents and involvement of all the three children. In this regard, we suggest that EV should be included in the differential diagnosis of any eruptive warty papular and plaque type lesions with familial involvement.

References

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