Severe Hydroa Vacciniforme Research Articles

Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein-Barr Virus Infection.

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

A reactivation signal, BZLF1 expression, is a prognostic marker for severe hydroa vacciniforme and hypersensitivity to mosquito bites

A reactivation signal, BZLF1 expression, is a prognostic marker for severe hydroa vacciniforme and hypersensitivity to mosquito bites

Oculomucosal and gastrointestinal involvement in Epstein-Barr virus-associated hydroa vacciniforme

In a series of patients with Epstein-Barr virus (EBV)-associated hydroa vacciniforme (HV) and related disorders, we reviewed the incidence of oculomucosal and gastrointestinal involvement. Of 63 patients with EBV-related HV and/or hypersensitivity to mosquito bites (HMB), 11 patients (17.5%) presented with mucosal lesions such as aphthous stomatitis and ulcerative gingivitis, 3 patients (4.8%) had ocular symptoms including iritis, conjunctival hyperemia and corneal erosions, and 2 patients (3.2%) presented with severe HV complicated gastrointestinal involvement. Oculomucosal lesions are sometimes complicated in patients with EBV-related HV and HMB, and gastrointestinal involvement may occur in the severe form.

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.

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.

Pathogenic Link Between Hydroa Vacciniforme and Epstein-Barr Virus–Associated Hematologic Disorders

To determine the pathogenic association of latent Epstein-Barr virus (EBV) infections with both typical hydroa vacciniforme (HV) and severe HV-like eruptions, and to survey the complications and outcomes of patients. Case series. Twenty-nine patients with HV or severe HV-like eruptions. In situ hybridization and immunostaining of biopsy specimens; extraction of DNA samples from cutaneous lesions and/or peripheral blood mononuclear cells for EBV DNA assay. Clinicopathologic manifestations, hematologic findings, complications, and outcomes; presence of latent EBV infection. T cells positive for EBV-encoded small nuclear RNA (EBER) were detected, to various degrees, in cutaneous infiltrates in 28 (97%) of 29 patients, including all 6 patients with definite HV with a positive phototest reaction, 11 of 12 patients with probable HV without evidence of photosensitivity, and all 11 patients with severe HV associated with systemic symptoms. In addition to EBER-positive T cells, many cytotoxic T lymphocytes expressing T-cell intracellular antigen 1 and granzyme B were present in the cutaneous lesions. Natural killer (NK) cells were absent or at a background level. The UV-induced cutaneous lesions showed histopathologic findings consistent with those of HV, containing many EBER-positive cells. Although no hematologic abnormalities were found in the definite and probable HV groups, the amounts of EBV DNA were increased in the peripheral blood mononuclear cells. By contrast, the severe HV group had markedly increased levels of EBV DNA associated with NK-cell lymphocytosis, and complications including chronic active EBV infection, hypersensitivity to mosquito bites, and hemophagocytic syndrome. Five patients with severe disease died of EBV-associated NK/T-cell lymphomas or hemophagocytic syndrome 2 to 14 years after onset. Both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T-cell lymphoproliferative disorders with a frequently fatal outcome.

Photoprovocation in the Patients with an EBV Associated Hydroa Vacciniforme‐Like Eruption

There are many reports of patients with a severe hydroa vacciniforme (HV)‐like eruption. The cutaneous lesions occur both in sun‐exposed and nonexposed areas in these patients unlike a true HV. In most cases, a latent Epstein‐Barr virus (EBV) infection has been detected in the skin lesions of these patients. We performed the photo‐provocation test in five patients with an EBV associated HV‐like eruption. The photoprovocation tests were caried out using the UVA delivered by a SUPUVASUN 3000 light source. A 5x 5 sqaure cm area on the buttock was irradiated three or four times at 24 hour intervals. A skin biopsy was obtained from the lesional skin and photo‐provoked lesion in all five patients. H&E staining and immunohistochemical staining were performed. In situ hybridization was also performed to detect mRNA for EBV in the skin biopsy specimens. Skin lesions were induced by repetitive UVA exposure in all five patients. The severity of the phtoprovoked lesion showed correlation with that of the clinical features. The immunohistologic findings of photo‐provoked skin lesions were similar to those of original skin lesions. A latent EBV infection was also demonstrated in the photo‐provoked lesion.

Edematous, scarring vasculitic panniculitis: A new multisystemic disease with malignant potential

Background : Hydroa vacciniforme (HV) is a disease of unknown origin characterized by erythema, vesicles, necrosis, and varicelliform scars in light-exposed skin. Systemic involvement is absent. A few patients have been reported with “severe HV” with systemic involvement, development of non-Hodgkin's lymphoma, and a poor prognosis. Objective : Our purpose was to characterize and differentiate our patients' disease from HV. Methods : We performed a retrospective clinicopathologic study of 14 children previously diagnosed as having “severe HV”. Results : The extension and severity of the cutaneous lesions, fever, wasting, failure to thrive, hepatosplenomegaly, vasculitis, panniculitis, and potential development of lymphoma are features that clearly differentiate edematous scarring vasculitic panniculitis from HV. Conclusion : Edematous scarring vasculitic panniculitis is a novel multisystemic disease with malignant potential that is not related to classic HV.