Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.

The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.

STK4 deficiency and epidermodysplasia verruciformis-like lesions: A case report.

Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as epidermodysplasia verruciformis-like lesions (EVLL). Herein, we describe a 17-year-old male patient born from consanguineous parents presenting with recurrent respiratory infections, verruciform plaques, poikiloderma, chronic benign lymphoproliferation, and Sjögren syndrome with suspected interstitial lymphocytic pneumonia.

Acquired Epidermodysplasia Verruciformis in the Setting of Renal Transplant.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare dermatologic condition that is clinically characterized by flat, cutaneous, verrucous papules, pityriasis versicolor-like lesions, and similar lichenoid papules. There are 2 forms of EV: a classic inherited genodermatosis and a secondary acquired form. EV predisposes individuals to infections with certain types of human papillomavirus virus and subsequently increases the risk of cutaneous squamous cell carcinoma. The acquired form occurs in immunosuppressed patients, particularly in patients infected with HIV; however, it has also been described in patients who have undergone stem cell and solid organ transplantation. We report an additional case of renal transplantation and immunosuppressive therapy-associated acquired EV (AEV) in a 78-year-old man with multiple flesh-colored to violaceous, flat-topped papules distributed on the face and trunk clinically mimicking lichen planus. Biopsy was typical for that of EV, demonstrating enlarged keratinocytes with a blue-gray cytoplasm, a thickened granular layer, acanthosis, and hyperkeratosis. Herein, we discuss an unusual presentation of an AEV-mimicking lichen planus with review of the literature.

Novel dermoscopic features of pityriasis versicolor-like macules in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) manifests early in childhood as pityriasis versicolor (PV)-like macules on sun-exposed sites such as the face. These hypopigmented lesions closely resemble commoner pediatric dermatoses such as PV or pityriasis alba. In this report of two cases, we describe the distinguishing dermoscopic features of PV-like macules in EV. Unfocused dotted vessels in a hypopigmented or erythematous background with whitish scales and pigment diluted vellus hairs on dermoscopy should raise the suspicion of EV in children presenting with PV-like lesions.

Diagnosis of epidermodysplasia verruciformis: Two cases highlighting the role of direct HPV L1 gene sequencing.

Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by the development of multiple flat warts with the potential for malignant transformation. Patients are susceptible to human papillomavirus (HPV) infection that develops in a background of either a genetic or acquired immunodeficiency predisposing patients to infection with specific HPV types that are ubiquitous but generally non-pathogenic in healthy individuals. There is no standard clinical methodology for determining the causative HPV from patients with suspected EV. Here, we report the diagnostic workup of two EV cases and describe the use of L1 gene Sanger sequencing as a specific method to accurately identify the causative HPV genotype and confirm the diagnosis of EV.

New biomarkers of human papillomavirus infection in epidermodysplasia verruciformis.

The cause of epidermodysplasia verruciformis is infection by human papillomavirus, usually types 5 or 8, and it exhibits a high potential for malignant transformation. The diagnostic histologic features of epidermodysplasia verruciformis are not always present and can be mimicked by non-viral diseases. The purpose of this study was to interrogate such lesions for new potential biomarkers to aid in the diagnostic accuracy. HPV DNA was high copy and localized to the upper half of the lesion in cells with cytologic features that included perinuclear halos, blue-grey cytoplasm, and hyper/parakeratosis. Serial section analyses demonstrated that there was increased expression of importin-ß, exportin-5, Mcl1, p16, Ki67 and PDL1 in 13/13 epidermodysplasia verruciformis lesions. Each of these proteins localized primarily to the less differentiated cells in the parabasal aspect of the lesion. Only Ki67 and exportin-5 were expressed in the normal epithelia, though much less so, in 13/13 aged matched controls. It is concluded that the host response to HPV 5/8 infection in epidermodysplasia verruciformis includes the up regulation of several proteins including p16, Ki67, importin-ß, exportin-5, Mcl1, and PDL1. Thus, these proteins may serve as new biomarkers of this disease that can aid in cases that are equivocal for epidermodysplasia verruciformis on histologic examination.

Multiple flat-topped scaly violaceous papules.

Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis characterized by susceptibility to beta-genus human papillomavirus (HPV) infection. Owing to TMC6/EVER1 and TMC8/EVER2 mutations that lead to abnormal transmembrane channels in the endoplasmic reticulum involved in immunological pathways, keratinocytes cannot combat infection from non-pathogenic HPV strains. Mutations involving RHOH, MST-1, CORO1A, and IL-7 have also been associated with EV in patients without TMC6 or TMC8 mutations. We highlight a 27-year-old man with multiple violaceous flat-topped papules with scale and irregular borders distributed on his chest, extremities, abdomen, and back. The striking physical examination and the subsequent biopsy findings of enlarged nests of cells in the granular and spinous layers with blue-gray cytoplasm and keratohyaline granules confirmed the diagnosis. We conclude with a brief discussion on the differential diagnosis, which includes confluent and reticulated papillomatosis, Darier disease, and disseminated superficial actinic porokeratosis.

Epidermodysplasia Verruciformis-like HPV Infection of the Vulva in Immunosuppressed Women.

The vast majority of vulvar human papilloma virus infections are produced by α human papilloma viruses and consist of exophytic or flat warts and classic or "usual" vulvar intraepithelial neoplasia. This report details 2 examples of epidermodysplasia verruciformis-like lesions of the vulva in women who were immunosuppressed. The most consistent morphologic feature was the presence of abnormal mature keratinocytes with large pale open nuclei with small nucleoli and eosinophilic cytoplasm, situated in the upper epithelial layers. In addition to these features, which are commonly seen in epidermodysplasia verruciformis-associated lesions, 1 case displayed in addition more extensively distributed abnormal nuclei, including involvement of both the upper epithelial strata and the epithelial/stromal interface. Both lesions were associated with ß-papilloma virus type 5. The unique aspects of epidermodysplasia verruciformis-like lesions relative to the more common human papilloma virus infections of the vulva are highlighted and these cases illustrate the range of epithelial distribution that might be encountered in lesions involving the vulvar mucosa.

[Cutaneous infections: Pathologist's role in unusual or atypical situations]. / Infections cutanées : place du pathologiste dans les situations inhabituelles ou atypiques.

In infectious pathology, the gold standard consists of the detection of the pathogen within the sample. Identification of the pathogen is often difficult despite the presence of few and inexpensive tools, such, as special stain, immunohistochemistry, or in situ hybridization specific of the pathogen. In infectious pathology, there are morphological signs, which can guide us towards an etiology. We present some clinicopathological examples illustrating rare or unusual situations in cutaneous infectious pathology.

Acquired Epidermodysplasia Verruciformis and Its Relationship to Immunosuppressive Therapy: Report of a Case and Review of the Literature.

INTRODUCTION: Epidermodysplasia verruciformis (EV) is a rare inherited dermatosis characterized by increased susceptibility to human papilloma virus infection. Acquired EV occurs in patients with compromised cell-mediated immunity, such as patients with HIV and transplant recipients. Optimal management of acquired EV has not yet been established, as cases are rare and are due to a variety of underlying conditions. Additionally, no distinctions have been made between different immunosuppressive medications and their respective link to EV. METHODS AND RESULTS: We report a patient with systemic lupus erythematosus who developed EV while on azathioprine and prednisone. The patient's lesions resolved completely after she was switched from azathioprine to mycophenolate mofetil. Her lesions recurred when her immunosuppressive regimen was again changed from mycophenolate mofetil to methotrexate. A review of the literature revealed azathioprine to be related to other cases of acquired EV. DISCUSSION: This case indicates a possible link between specific immunosuppressive drugs and the development of EV, allowing for new EV treatment considerations. In this case and previous cases, azathioprine is indicated as being particularly linked with the development of EV, while mycophenolate mofetil may be an immunosuppressive option that is less likely to induce EV in patients predisposed to this condition. J Drugs Dermatol. 2017;16(7):701-704.

Acquired Epidermodysplasia Verruciformis Associated with Human Papilloma Virus Type 14 in a Small Bowel Transplanted Child--A Case Report.

A 3-year-old African American girl taking sirolimus and tacrolimus for a small bowel transplantation presented with hypopigmented macules and papules throughout her trunk. A biopsy diagnosed epidermodysplasia verruciformis (EV) that was found to be associated with human papillomavirus (HPV) type 14 according to polymerase chain reaction analysis. There are few cases of acquired EV in the setting of organ transplantation. Although there is no standardized treatment for acquired EV, prevention and surveillance for transformation to squamous cell carcinoma are primary concerns.

Epidermodysplasia Verruciformis (Lewandowsky and Lutz's Dysplasia).

A woman in her twenties, with a non-consanguineous marriage, presented to the dermatology clinic with asymptomatic lesions on her face, neck, trunk, and extremities for the past 12 years. The general physical and systemic examination was unremarkable. Cutaneous examination revealed multiple hypopigmented to a few hyperpigmented, slightly scaly tinea versicolor-like macules distributed predominantly on the neck, upper portion of the back, and distal parts of the extremities (Figures 1-5). There were muultiple, slightly erythematous to violaceous flat-topped wart-like papules and plaques were discovered on the arms (Figures 1 and 2), with seborrheic keratosis-like lesions on the face (Figure 5). Baseline investigations, such as complete blood count (CBC), liver function test (LFT), kidney function test (KFT), and plasma glucose levels, were normal. Serologic tests conducted for human immunodeficiency virus (HIV)-1 and HIV-2, and hepatitis B and C were nonreactive. Skin lesion potassium hydroxide (KOH) examination from tinea versicolor-like lesions was negative for fungal elements. Skin biopsies were performed from tinea versicolor-like macules present on the upper portion of the back, flat wart-like plaque on the dorsum of the left hand, and hyperpigmented scaly plaque in the extensor area of the left leg. Histopathologic examination revealed parakeratosis, hyperkeratosis, and acanthosis with swollen keratinocytes, bluish-gray cytoplasm, and rounded nuclei with prominent nucleoli. No dysplastic changes/atypia or mitotic figures (Figures 6 and 7), plus occasional perinuclear halo (a vacuolated area that surrounds the nucleus), were observed. Following clinicopathologic correlation, the patient was diagnosed with epidermodysplasia verruciformis (EV, or Lewandowsky and Lutz's dysplasia).