Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases

BACKGROUND: There are many reports of patients with a severe hydroa vacciniforme (HV)-like eruption in which cutaneous lesions occur in both sun-exposed and non-exposed areas, unlike in true HV. Several patients have died from a malignant haematological neoplasm. In most cases, a latent Epstein-Barr virus (EBV) infection has been detected in the skin lesions. OBJECTIVES: To describe the clinical and laboratory features of six additional patients with an EBV-associated HV-like eruption. METHODS: The clinical, histological and immunohistochemical features were reviewed. T-cell receptor gamma gene rearrangements were studied using polymerase chain reaction (PCR) and heteroduplex analysis. In-situ hybridization was performed to detect mRNA for EBV in skin biopsy specimens. PCR was performed to screen for EBV infection in the skin lesions of three patients and blood of two patients. Photoprovocation with repeated ultraviolet (UV) A exposure was performed in three patients. RESULTS: The severity of the skin lesions and the clinical course varied among the patients. Skin lesions were induced by repeated UVA exposure in three patients and a latent EBV infection was demonstrated in the photoprovoked lesions. CONCLUSIONS: Three different clinical courses were found in six patients with an HV-like eruption associated with chronic EBV infection: (i) spontaneous remission; (ii) clearing after photoprotection; and (iii) continuous recurrence irrespective of sun exposure. It is possible that there are two patterns of HV-like eruption associated with chronic EBV infection. One is characterized by recurrent necrotic papulovesicles of the face and the other by nodules and facial swelling. It was demonstrated that the skin lesions could be triggered by repeated UVA exposure in the patients showing recurrent necrotic papulovesicles of the face.     

Familial hydroa vacciniforme

Hydroa vacciniforme is a rare, idiopathic photodermatosis with an onset in childhood and characterized by acute vesiculation, crusting and scarring following sun exposure. Familial cases are extremely rare with only one previous report. We report a brother and sister, both of whom have developed hydroa vacciniforme.     

种痘样水疱病12例临床及病理分析

目的：分析12例种痘样水疱病患儿的临床，病理特征。方法：回顾分析12例种痘样水疱病患儿的临床资料和组织病理检查结果。结果：12例种痘样水疱病患儿男5例，女7例，平均发病年龄4.3岁，病程1-13年。12例均有暴露部位的丘疱疹、水疱、坏死、结痂及痘疮样瘢痕；其中1例伴有非暴露部位皮肤受累，1例伴有指间关节变形，1例皮损出现时伴有低热。病理表现为表皮内多房性水疱，真皮浅层中等至大量淋巴细胞浸润，并可伴有表皮、真皮坏死。结论：种痘样水疱病典型皮损为水疱，丘疱疹和痘疮样瘢痕，重型可出现皮肤肿胀，皮损亦可累及非暴露部位皮肤。     

Epstein–Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long‐term follow‐up

Background Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein–Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T‐cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long‐term follow‐up. Objectives To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV. Methods Repeated tests for EBV DNA blood load using real‐time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long‐term follow‐up. Skin samples from phototest‐induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty‐five patients with other photosensitive disorders were included as controls. Results The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0·001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest‐induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest‐induced lesions, but not in the surrounding normal skin. Conclusion EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV.     

Severe hydroa vacciniforme-like eruptions confined to sun-exposed areas

A 15-year-old boy presented with vesiculopapular eruptions confined to sun-exposed areas from the age of 3. Histopathological examination of biopsy specimens of repetitive UVA-irradiated areas revealed reticular degeneration of the epidermis, and dermal infiltrates in the photoinduced lesions showed a latent Epstein-Barr virus (EBV) infection. At the age of 21, the number of skin lesions had increased, and his anti-EBV antibody titers revealed an abnormal profile: an undetectable anti-EBV nuclear antigen antibody titer despite a detectable antiviral capsid antigen IgG antibody titer. No infectious mononucleosis-like symptoms, such as prolonged or intermittent fever, lymphoadenopathy, or liver damage were evident up till then. Severe hydroa vacciniforme (HV)-like eruptions were diagnosed considering the increased number of the skin lesions with increasing age and the unusual anti-EBV antibody titers, in addition to the histopathological findings. In the same year, he suddenly developed high fever and died from disseminated intravascular coagulation syndrome without any spontaneous regression of the skin lesions. In this patient with severe HV-like eruptions, the skin lesions had been confined to sun-exposed areas until his death, and the photo-provocation test showed a positive reaction. Severe HV-like eruptions may have clinical features suggestive of HV.     

Factors influencing the photo-reproduction of hydroa vacciniforme lesions

Hydroa vacciniforme vesicles can be reproduced experimentaly with repetitive UVA irradiations, but this photo-reproduction is not constant. The aim of this study was to search for the factors that influence photo-reproduction. To reproduce hydroa vacciniforme lesions six patients underwent repetitive UVA and polychromatic irradiations on the back. In four patients out of six, UVA irradiation with high doses induced papulo-vesicular lesions. Photo-induced lesions were very close to those induced by sunlight. Photo-reproduction failed when phototesting was done after or shortly before remission. Therefore, the absence of photo-reproduction appears to be a good prognostic factor.     

Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection

Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.     

Hydroa vacciniforme-like eruptions in a patient with chronic active EB virus infection

We report a case of chronic active Epstein-Barr (EB) virus infection (CAEBV) associated with skin eruptions mimicking hydroa vacciniforme (HV) in a 4-year-old boy. The patient had repeated episodes of vesiculo-necrotic eruptions on the face, scalp, and bilateral forearms one year before the first visit to our department. General symptoms including fever, hepatosplenomegaly, abnormal liver function, and cervical lymph node swelling were noted three months before the first visit. At the first visit, small, bean-sized, erythemic papules with central necrosis were observed on the face and anterior chest wall. Thumb-sized ulcers with crust were present on the bilateral forearms. Histopathological examination of an erythematous lesion in the submandibular area revealed parakeratosis with a thick crust, mild spongiosis in the epidermis, and a dense infiltration of lymphoid cells into the dermis and perivascular space. Laboratory examination showed EBNA x 40, EBV VCA IgG x 1,280, and EBV DNA (PCR) 8 x 10(4). EBV-encoded small nuclear RNA (EBER) positive cells were detected in the dermis by an in situ hybridization (ISH) method. Large granular lymphocytes (65%) with the NK cell phenotype were found in the peripheral blood. A real time PCR method showed 171,741 copies/ micro g DNA in CD 16 positive cells. Although latent EBV infection-associated eruptions have been documented, detailed skin manifestations in CAEBV are less well known.     

Epstein-Barr virus-associated recurrent necrotic papulovesicles with repeated bacterial infections ending in sepsis and death: consideration of the relationship between Epstein-Barr virus infection and immune defect

The disease of Epstein-Barr virus (EBV) -associated recurrent necrotic papulovesicles is a distinct clinicopathologic entity different from classic hydroa vacciniforme (HV). A few patients have been reported as atypical HV with systemic involvement, development of lymphoma, and poor prognosis. We describe a patient with recurrent necrotic papulovesicles and multiple varioliform scars in both sun-exposed and covered areas. In contrast to cases of previously reported atypical HV, our patient suffered from repeated bacterial infections on various sites ending in sepsis and death, but without malignant transformation. EBV was detected in the lymphoid cells from the skin lesions by anti-latent membrane protein (LMP) antibody and in situ hybridization. We suggest that the repeated bacterial infections in this case raise the possibility of an association of EBV infection with increased susceptibility to bacterial infections.     

Systemic lupus erythematosus induced by Epstein-Barr virus infection

We report a 22-year-old woman who developed systemic lupus erythematosus (SLE) immediately after an Epstein-Barr virus (EBV)-induced mononucleosis infection. The link between these two conditions has long been suspected. The close temporal relationship, the course of the pathological events and the development of immunological changes in this case provide further evidence supporting the hypothesis that EBV infection could work as a trigger in some cases of SLE, particularly if the patient is genetically susceptible.     

Quality of life assessment and disease experience of patient members of a web-based hydroa vacciniforme support group

Background/Purpose: Hydroa vacciniforme (HV) is a rare photodermatosis that primarily affects children. It is characterized by photodistributed vesicles that heal with scarring. The purposes of this study are to perform the initial investigation into the effect of HV on quality of life (QoL) and gain insight into disease diagnosis and management.
Methods: Using the listserv from a web-based, international HV support group, either the Dermatology Life Quality Index (DLQI) or the Children's DLQI (CDLQI), and an HV-specific questionnaire were administered.
Results: Fifteen HV patients participated, nine (60%) males and six (40%) females. Median age at onset was 7 years, and 11/15 (73%) were younger than 18 years. The majority of patients were Caucasian (73%). Children cited life quality as being negatively impacted by an inability to play outdoors while adults noted QoL influences due to limitations on clothing choices. The mean CLDLQI and DLQI scores, 12.1 and 8.5, respectively, suggest a higher negative QoL impact than previously reported indices for generalized eczema, atopic dermatitis, and psoriasis.
Conclusion: When compared with other dermatoses, HV appears to have an equal or greater impact on patients' QoL. Dermatologists should be aware of the psychosociologic impact of this disease, especially on young HV patients.     

Epstein-Barr virus-associated T-cell lymphoma: a case of eyelid swelling and intramuscular infiltration mimicking dermatomyositis

Association with Epstein-Barr virus (EBV) infection has been noted in various types of cutaneous lymphoproliferative disorders. We report a 57-year-old Japanese woman with T-cell lymphoma mimicking dermatomyositis that was associated with chronic active EBV infection. She presented with low-grade fever, bilateral erythematous swellings on the eyelids, and necrotic papules on the face. Serum creatine kinase levels were elevated and a diffuse reticular shadow was detected in both lung fields. The infiltrate of atypical lymphocytes found in skin and muscle, which contained EBV-encoded small nuclear RNA-1 and EBV, was also detected in the CD4+ peripheral blood cells. Treatment with prednisolone resolved her lesions with no relapse for 3 years, after which there was a recurrence in her left lung. Combination chemotherapy was not effective against the lung lesion and she died with multiple organ failure 2 months after the recurrence.     

Purpuric lesions induced by UVA1 spectrum (340–400 nm) phototesting in an adult with persistent and severe hydroa vacciniforme

A 28‐year‐old man had presented a severe photosensitivity since his infancy. In March 2008, the clinical examination showed large crusts on the dorsum of his hands, on the edge of his ears with destruction of the underlying cartilage, and on his nose and cheeks. He also presented erythematosus fibrous scars on the temples. The diagnosis of hydroa vaccinforme was made. Phototesting including repeated UVA1 phototest was strongly positive with purpuric lesions from day 7 to day 10 and hypertrophic scars at day 67. A sequential histological study of the UVA1 triggered lesions was performed and showed bullous cleavage, dense inflammatory infiltrate in the whole dermis with numerous neutrophilic cells, nuclear dusts, superficial focal thrombosis of small blood vessels at day 10. We report an unusual case of hydroa vaccinforme with purpuric lesions leading to fibrous scars and with important infiltration of neutrophils in the dermis of the photoinduced lesions.     

Epstein-Barr virus-positive blastoid nasal T/natural killer-cell lymphoma in a caucasian

T/natural killer (NK)-cell lymphoma is a subtype of non-Hodgkin's lymphoma, with frequent cutaneous involvement; it follows an aggressive course. Most cases are reported in Asia, and typically present with nasopharyngeal involvement. There is a distinct variant known as blastoid T/NK-cell lymphoma, which affects elderly, non-Asian patients, with absence of nasal involvement. We report a middle-aged caucasian man who had blastoid T/NK-cell lymphoma with nasal involvement.     

Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome

Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32-year-old-man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle-shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.