Human Polyomavirus 6 Detected in Cases of Eosinophilic Pustular Folliculitis.

BACKGROUND: Human polyomaviruses (HPyVs) have been associated with several cutaneous inflammatory conditions. More investigation is needed to identify further presentations of cutaneous pathology associated with HPyVs. Our aim was to investigate the possible association of skin-tropic HPyVs with folliculitis, particularly eosinophilic pustular folliculitis (EPF). METHODS: This study included 55 Japanese patients, comprising 13 patients with EPF and 42 patients with suppurative folliculitis. HPyV DNAs were detected by quantitative polymerase chain reaction. Expression of viral antigen and geographically related viral genotypes were also assessed. RESULTS: Human polyomavirus 6 (HPyV6) DNA was found in 9 of 13 (69%) patients with EPF, a rate significantly higher than that found in suppurative folliculitis (1/42; 2%). Of the 7 HPyV6 DNA-positive EPF specimens analyzed, 4 were positive for HPyV6 small tumor antigen. All the HPyV6 strains detected in this study were of the Asian/Japanese genotype. CONCLUSIONS: The predominant detection of HPyV6 DNA and the expression of viral antigen suggest a possible association between HPyV6 infection and EPF in a subset of patients. Worldwide studies are warranted to determine whether Asian/Japanese genotype HPyV6 is associated preferentially with the incidence and pathogenesis of this eosinophil-related skin disease that has an ethnic predilection for the East Asian population.

Covid-19 pandemic and the skin.

In the beginning of the COVID-19 outbreak, skin manifestations, if present, were not paid enough attention. Then, the focus moved toward the impact of the prolonged use of personal protective measures in both healthcare workers and patients. In the meantime, attention is increasingly paid to dermatology as a result of the concern for certain groups of dermatologic patients, including those whose condition may worsen by the thorough disinfection measures and those treated with immunosuppressants or immunomodulators. Following patients with psoriasis on biological therapy, as well as other inflammatory and autoimmune cutaneous disorders such as atopic dermatitis, pemphigus, pemphigoid diseases, and skin cancer provoked the interest of dermatologists. Finally, an intriguing question to the dermatologic society was whether skin changes during COVID-19 infection exist and what could be their diagnostic or prognostic value. Here, we summarize skin conditions during the COVID-19 pandemic, patient information, and expert recommendations and give an overview about the registries launched to document skin changes during COVID-19, as well as details about certain patient groups infected with SARS-CoV-2, for example, psoriasis, atopic dermatitis, and autoimmune bullous diseases.

Mantle cell lymphoma presenting with exaggerated skin reaction to insect bites.

We present the case of a 62-year-old African-American woman with medical history of hypertension and hyperlipidaemia who presented to dermatology clinic for 'bug bites'. Skin examination showed resolving bullae on the shins and postinflammatory pigment changes. Histopathology showed eosinophilic spongiosis and direct immunofluorescence (DIF) was negative for IgG, IgM, IgA and C3. After returning to clinic with recurrent severe bullous eruptions, the patient presented with anaemia, lymphocytosis, posterior cervical lymphadenopathy and weight loss. An exuberant bite reaction in the setting of lymphoma was suspected. Further workup with haematology revealed elevated IgG level and total protein levels. Flow cytometry showed a B cell lymphoma subtype. Extensive imaging was positive for diffuse lymphadenopathy, with accompanying evidence of Ebstein-Barr virus infection. Our case highlights the importance of considering exuberant arthropod bite reaction in the setting of undiagnosed lymphoma in a patient with bullous eruption and negative DIF.

Atypical Gianotti-Crosti syndrome

Abstract: We report the case of a male 22-month-old child, with atypical presentation of Gianotti-Crosti syndrome after infection with Epstein-Barr virus.

Generalized pustular psoriasis associated with Epstein-Barr virus.

Generalized pustular psoriasis (GPP) is a rare and severe variant of psoriasis. We report a case of a 79-year-old woman who presented with generalized pustular psoriasis and significant Epstein-Barr virus (EBV) viraemia. Serial measurements of EBV DNA showed a correlation with the deterioration in her clinical condition. We speculate that EBV reactivation triggered the development of GPP, and propose that further investigation is required into the association between EBV and GPP.

Chronic active Epstein-Barr virus infection-associated hydroa vacciniforme-like eruption and Behçet's-like orogenital ulcers.

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: a histopathological and immunohistochemical comparative study.

BACKGROUND: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF). OBJECTIVE: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF). METHODS: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions). RESULTS: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients. LIMITATIONS: Only quantitative differences and not qualitative differences were found. CONCLUSIONS: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found.

Purpuric macules with vesiculobullous lesions: a novel manifestation of Chikungunya.

BACKGROUND: Chikungunya (CHIK) is an emerging viral disease with a myriad of cutaneous manifestations. AIMS: The aim of our study was to document the morphology and evolution of skin lesions in cases presenting with fever, purpuric macules and vesiculobullous lesions, to confirm its causative relationship with CHIK, and to investigate further in order to delineate possible mechanisms of bulla formation in these cases. MATERIALS AND METHODS: A prospective, descriptive hospital-based study was carried out at a tertiary health care centre in Kerala. A total of 10 patients were enrolled in the study and investigated. RESULTS: All cases had morbilliform eruption prior to onset of purpuric macules. Eight cases developed vesiculobullous lesions that arose either de novo or over a part or whole of the purpuric macules. Skin lesions resolved within an average of 7.6 days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from the bullae showed lymphocytes in most cases along with acantholytic cells, necrotic keratinocytes or occasional neutrophils. Skin biopsy showed intraepidermal or subepidermal bullae. Immunohistochemistry revealed predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was good with supportive management alone. DISCUSSION: The clinical features in our cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK affected infants. Based on the current evidence, we hypothesize that at least 2 mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte necrosis followed by a cytotoxic immune response, and possible modulation of rash by drugs. CONCLUSION: With severe epidemics of CHIK spreading from Asia and Africa to the Western hemisphere, we must consider bullous CHIK as a differential diagnosis in cases with fever and purpuric and vesiculobullous lesions.

Severe bullous skin lesions associated with Chikungunya virus infection in small infants.

INTRODUCTION: The aim of this study was to describe a pediatric case series of Chikungunya infection associated with extensive bullous skin lesions, a severe and unknown form of the disease, during the 2005-2006 outbreak in La Réunion Island. MATERIALS AND METHODS: Retrospective descriptive hospital-based study in children presenting blisters > or = 10% of total body surface area with laboratory-confirmed Chikungunya infection. RESULTS: Eight boys and five girls with a mean age of 3.4 months were included. Blistering began after an average of 2 days after onset of fever and affected 21.5% (10% to 35%) of the total body surface area. Reverse transcription-polymerase chain reaction of blister fluid (n = 5) was positive with a mean viral load sometimes higher than in concurrent serum. Histopathologic examination (n = 10) showed intraepidermal blisters. Hospitalization and repeated dressing changes under general anesthesia were required. No death occurred. On follow-up, long term repigmentation was excellent with sometimes cosmetic sequelae. CONCLUSION: Chikungunya should be included in the differential diagnosis of febrile blistering dermatoses in small infants in epidemic areas.

Occult herpes simplex virus colonization of bullous dermatitides.

BACKGROUND: Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease, superficial pemphigus), Darier disease, and Grover transient acantholytic dermatosis, as well as other vesiculo-bullous disorders, including bullous pemphigoid, epidermolysis bullosa, and atopic dermatitis, are prone to florid infections by herpes simplex virus (HSV)-I and -II, and, more rarely, by varicella-zoster virus (VZV). As these infections are difficult to recognize clinically and histologically, their frequency remains unknown. A possible occult viral colonization has never been documented in these disorders. The manner in which the primary bullous disorders are contaminated by herpesviridae remains unclear. OBJECTIVE: To retrospectively assess the possible presence of HSV and VZV in a series of biopsies of acantholytic disorders and bullous pemphigoid. METHOD: The typical alpha-herpesviridae-related cytopathic signs were searched for by conventional microscopy in skin biopsies of patients with bullous pemphigoid (n = 20), pemphigus vulgaris (n = 19), Darier disease (n = 18), chronic benign familial pemphigus (n = 3), and Grover transient acantholytic dermatosis (n = 3). Immunohistochemistry (IHC) targeted specific HSV-I, HSV-II, and VZV antigens. Polymerase chain reaction (PCR) was used for detecting HSV- and VZV-specific DNA sequences. RESULTS: No cytopathic signs suggestive of HSV or VZV infection were detected. However, IHC revealed HSV antigens in Darier disease (1/18, HSV-I), Grover transient acantholytic dermatosis (1/3, HSV-I), pemphigus vulgaris (1/19, HSV-I), and bullous pemphigoid (2/20, HSV-I and HSV-II). In these IHC-positive cases, PCR amplified specific HSV primers in Darier disease (1/18), pemphigus vulgaris (1/19), and bullous pemphigoid (1/20). VZV antigens and nucleic acids were never identified. The HSV antigens were nearly always restricted to the upper part of the granular layer and thus differed from the usual HSV distribution during cutaneous infection. Negative and positive controls yielded consistently positive and negative results, respectively. CONCLUSION: This report shows for the first time that clinically and histologically occult HSV colonization may occur in Darier disease, Grover transient acantholytic disease, pemphigus vulgaris, and bullous pemphigoid. Given the frequent use of immunosuppressive treatments for primary bullous disorders, greater awareness of HSV colonization and infection is recommended in these patients.

Orf-induced immunobullous disease: A distinct autoimmune blistering disorder.

BACKGROUND: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described. OBJECTIVES: Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases. METHODS: Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes. RESULTS: Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen. LIMITATIONS: We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified. CONCLUSIONS: Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.

Herpes zoster in the ulnar nerve distribution.

Varicella zoster is a ubiquitous virus which usually affects school-aged children as Chicken Pox. While the initial disease is self-limiting and seldom severe, the virus remains in the body. It lies dormant in the dorsal root ganglia and reactivation may occur years later with variable presentations as Herpes Zoster, or Shingles. While Shingles is common, it rarely presents exclusively in the upper extremity. It is important that hand surgeons recognize the possibility of zoster infection, with or without a rash, when evaluating the onset of neuralgia in a dermatomal distribution in the upper limb. Early diagnosis allows rapid and appropriate treatment, with a lower risk of complications. We report on a case of Herpes Zoster isolated to the ulnar nerve distribution in a young woman.

Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

Characterization of Epstein-Barr virus (EBV)-positive NK cells isolated from hydroa vacciniforme-like eruptions.

Recently, the involvement of Epstein-Barr virus (EBV) in hydroa vacciniforme (HV)-like eruptions has been suggested. To elucidate the role of EBV in this disease, we isolated EBV-infected cell clones from peripheral blood mononuclear cells (PBMC) and the skin lesions of a patient with HV-like eruptions; cells isolated from PBMC were designated SNK-12, and those from the eruption SNK-11. Both cells expressed CD16, CD56, and HLA-DR and had germline configurations of the T-cell receptor and the immunoglobulin genes, indicating that the cell clones were of NK cell lineage. The analysis of EBV terminal repeats indicated that the cells were monoclonal, had identical clonality, and originated from EBV-positive cells in the PBMC and eruption. Both clones expressed EBNA-1, but not EBNA-2. Although LMP-1 was weakly detected in SNK-11, no LMP-1 was detected in SNK-12. Interestingly, EBV-infected cells required less IL-2 for in vitro growth in the later phase of this disease and this appeared to correlate with the expression of LMP-1, suggesting that the proliferative capacity of the EBV-positive NK cells increased during the time course of the disease, and LMP-1 expression might be responsible for that. This is the first report of the isolation of EBV-infected cells from the skin lesions of HV-like eruptions and strongly suggests that the HV-like eruption in the patient was caused by clonal NK cells with latent EBV infection.

[Eruptive pseudoangiomatosis in an adult renal transplant recipient]. / Pseudo-angiomatose éruptive chez un adulte transplanté rénal.

BACKGROUND: In 1969, Cherry et al. described four children with acute onset angioma-like papules with spontaneous regression during an acute viral infection. Similar cases, called eruptive pseudoangiomatosis, have been reported since and considered to be a viral exanthema. We observed a similar eruption in a 48-year-old male kidney transplant recipient. CASE REPORT: One month after kidney transplantation, the patient rapidly developed macules and papules on the trunk. He had unexplained fever 15 days before the eruption. A biopsy specimen revealed dermal blood vessels surrounded by lymphoid infiltrate. Serology tests were unable to identify any virus. The lesions resolved spontaneously within 15 days. DISCUSSION: In our patient, eruptive pseudoangiomatosis was diagnosed on the basis of the clinical and histological features and the disease course. This case demonstrates that the entity is not limited to children. Further cases should be studied to determine the precise pathogenics of this uncommon entity.

Detection of human herpesvirus 8 DNA in pemphigus and chronic blistering skin diseases.

Increased incidences of Kaposi's sarcoma and lymphoid malignancies have been observed in patients with pemphigus, and the human herpesvirus 8 (HHV-8) is very strongly associated with these tumors. Because the virus may be one of the triggering factors of pemphigus, we undertook this study to screen for the presence of HHV-8 in chronic blistering skin diseases including pemphigus. A total of 45 paraffin-embedded specimens were studied using nested polymerase chain reaction (PCR) with primers to amplify a 160-base pair HHV-8 fragment. HHV-8 DNA could be detected in 7 of 9 patients with pemphigus vulagris, and 1 of 2 with pemphigus foliaceus. All specimens of other blistering skin diseases were negative for HHV-8. On sequencing PCR products, the sequences were almost identical with the prototypic sequence for HHV-8, and a few base- pair substitutions at 1086C-T and 1139A-C were detected. The results of our study suggests that HHV-8 might have trophism for pemphigus lesions. Further studies including comparison of HHV-8 DNA load in both lesional and normal skin in the same patient, serological and animal studies would be helpful to study the relationship between HHV-8 and pemphigus.

Herpes simplex virus type 2 infection in a 5-year-old boy presenting with recurrent chest wall vesicles and a possible history of herpes encephalitis.

A 5-year-old hyperkinetic but otherwise healthy child presented with recurrent irritable vesicles and erosions of the anterior chest wall; they have been apparent since the age of 15 months. Wound swab cultures yielded herpes simplex virus type-2 (HSV-2) and Western blot serology showed past exposure to both HSV-1 and HSV-2. Skin biopsy results further supported a herpes virus infection. Magnetic resonance imaging of the brain showed right temporal lobe atrophy. An evaluation showed no evidence of sexual abuse in the patient but a Western blot assay of the mother's serum for HSV-2 was positive, while the father's was negative. In view of the diagnosis of HSV-2 infection in such a young patient, the possible routes of transmission and the time of acquisition of infection were explored. We believe the most likely route of infection in this child was postnatal, through intimate contact with the mother.