Hypersensitivity to Mosquito Bites Conceals Clonal Lymphoproliferation of Epstein‐Barr Viral DNA‐positive Natural Killer Cells

Ishihara, Shigehiko; Ohshima, Koichi; Tokura, Y.; Yabuta, Reiko; Imaishi, Hidenori; Wakiguchi, Hiroshi; Kurashige, Takanobu; Kishimoto, Hiroshi; Katayama, Ichiro; Okada, Shintaro; Kawa‐Ha, Keisei

doi:10.1111/j.1349-7006.1997.tb00305.x

Cited by 70 publications

(60 citation statements)

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“…[21][22][23] In this syndrome, CD4 + T cells stimulated by mosquito antigens may reactivate latent EpsteinBarr virus infection in NK/T cells and contribute to their unregulated expansion within inflammatory skin lesions and in the peripheral circulation. [24][25][26][27][28] A significant proportion of these patients die of Epstein-Barr virus-positive NK/T-cell lymphoma or hemophagocytic syndrome. [21][22][23]29 A comparable scenario can be proposed regarding the possible role of insect bites as a triggering factor in the presentation of ALCL.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Lamant¹,

Pileri²,

Sabattini³

et al. 2009

Haematologica

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BackgroundSkin involvement is frequent in ALK-positive anaplastic large cell lymphomas. The role of an insect bite as a triggering event has been postulated but not well documented. Design and MethodsWe retrospectively investigated five cases of ALK-positive anaplastic large cell lymphoma who presented with skin lesions occurring after an insect bite. Biopsies were immunostained with antibodies against CD30, ALK, T-and B-cell antigens. ResultsPersistent skin lesions developed after solitary insect bites in three patients and after multiple bites in two. Regional lymphadenopathy developed within weeks after the bite in three cases. In four cases the correct diagnosis was delayed due to misinterpretation of the findings as a reactive infiltrate in the skin (n=2) or lymph nodes (n=2); all cases subsequently showed small numbers of cells with nuclear and cytoplasmic staining for ALK. The final diagnoses were lymphohistiocytic variant (n=3) and composite common/small cell type (n=2) anaplastic large cell lymphoma. The patients were treated and three were alive at the last follow-up. Two patients died, one of pneumonia and the other of disseminated disease. ConclusionsIn these cases the sequence of events between the insect bites and the occurrence of both skin lesions and satellite lymphadenopathy suggest a direct relationship between the bite and the presentation with anaplastic large cell lymphoma. We postulate that insect bite-associated antigens could result in an influx of T lymphocytes, some bearing the t(2;5). The subsequent release of cytokines at the site of the bite could act as a 'second hit', eliciting activation of the latter cells, which would then express the oncogenic NPM-ALK protein and undergo uncontrolled proliferation.Key words: ALK-positive ALCL, NPM-ALK, skin involvement. Haematologica. 2010;95:449-455. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Lamant L, Pileri S, Sabattini E, Brugières L, Jaffe ES, and Delsol G. Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases. Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

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Section: Discussionmentioning

confidence: 99%

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Lamant¹,

Pileri²,

Sabattini³

et al. 2009

Haematologica

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“…Caution should be exercised in diagnosing CAEBV initially in the presence of these diseases. Skin lesions such as hypersensitivity to mosquito bites were characteristic in some patients with CAEBV who may suffer from the granular lymphocyte proliferative disorder or clonal T-cell lymphoproliferation [21,[24][25][26], and various cutaneous manifestations, including hydroa vacciniforme-like eruptions, were recently reported to be associated with T-cell or NK-cell LPDs having chronic activated EBV infections [27].…”

Section: Clinical Featuresmentioning

confidence: 99%

Proposed guidelines for diagnosing chronic active Epstein‐Barr virus infection

et al. 2005

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Since the initial report of unusual manifestations possibly associated with chronic active Epstein‐Barr virus (EBV) infection (CAEBV), nearly three decades have passed. During this period, reported cases with this entity have dramatically increased in the world. Additionally, recent development of diagnostic procedures, including molecular biological and immunological techniques, have provided us with the ability to define certain diseases, especially malignant disorders. Guidelines, derived mainly from the current literature and recent experiences with CAEBV in Japan, for diagnosing CAEBV are proposed to clarify this enigmatic disease. Am. J. Hematol. 80:64–69, 2005. © 2005 Wiley‐Liss, Inc.

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“…Patients with hypersensitivity to mosquito bites tend to develop HPS, and their prognosis is very poor. 5 Typical hydroa vacciniforme is defined by photosensitivity, childhood onset, resolution by early adult life, and histologic epidermal necrosis with lymphocyte infiltration. However, the atypical form presents with fever, liver dysfunction, edematous swelling of the face, unusual skin lesions, and progression to subcutaneous lymphoma accompanied by HPS.…”

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confidence: 99%

Unrelated bone marrow transplantation for Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease

Okamura

Kishimoto

Inoue

et al. 2003

Bone Marrow Transplant

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Summary:Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders, including chronic active EBV infection, EBV-associated hemophagocytic syndrome, hypersensitivity to mosquito bites, hydroa vacciniforme, aggressive NK-cell leukemia, and nasal/nasal-type NKcell lymphoma. In most instances, these disorders are refractory to conventional treatments and have a poor prognosis. Here, we report a new treatment strategy for EBV-associated T/NK-cell LPD, consisting of immunochemotherapy, intensive combination chemotherapy, and stem cell transplantation. The five patients studied, two with T-cell and three with NK-cell LPD, lacked a human leukocyte antigen-matched, related donor, and therefore received bone marrow grafts from HLA-matched, unrelated donors. The preconditioning regimen consisted of total-body irradiation (12 Gy), etoposide (900 mg/m 2 ), and cyclophosphamide (120 mg/kg) or melphalan (210 mg/m 2 ). All patients had residual LPD by a quantitative PCR technique prior to transplantation. After unrelated bone marrow transplantation (UBMT), four of the five patients remain in continuous complete remission at a median of 19 months, without detectable EBV-DNA in peripheral blood. Thus, UBMT appears to be a reasonable option for the treatment of patients with EBV-associated T/NK-cell LPD. Detection of EBV-DNA by PCR offers an important tool for assessing minimal residual disease in patients with EBV-associated T/NK-cell LPD.

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Hypersensitivity to Mosquito Bites Conceals Clonal Lymphoproliferation of Epstein‐Barr Viral DNA‐positive Natural Killer Cells

Cited by 70 publications

References 19 publications

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Cutaneous presentation of ALK-positive anaplastic large cell lymphoma following insect bites: evidence for an association in five cases

Proposed guidelines for diagnosing chronic active Epstein‐Barr virus infection

Unrelated bone marrow transplantation for Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease

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