P0908 - When Mosquito Bite Allergy with Epstein-Barr Virus Infection Requires Hematopoietic Stem Cell Transplant

Introduction:
Epstein-Barr virus (EBV) can present with varied clinical patterns. In acute infection, common symptoms include fever, malaise, and lymphadenopathy. However, chronic EBV can also cause lymphoproliferative disorders and malignancy.

Case Description:
A 5-year-old boy with history of nasal allergies and asthma presented with fever to 104 degrees Fahrenheit, exudative tonsillitis, oral sores, and moderate cervical lymphadenopathy. Rapid strep test was negative. One month later, he developed fever with severe local reactions to mosquito bites, each with >5 cm of erythema, induration, and bulla that ulcerated after rupture (Figures1&2). Afterward, he continued to have periodic high fevers for 4 days at a time over the course of 3 months, often accompanied by mouth ulcers and body rash.

Laboratory results were significant for normal CBC and differential, ESR elevated to 67mm/hr (normal <10), CRP elevated to 33mg/L (normal <3), IgE elevated to 12,093 kU/L (normal <307), with normal IgG, IgA, IgM levels. EBV quantitative PCR was elevated to over 5,000,000 copies/mL.

Peripheral blood mononuclear cells were stained and sorted into populations of B-cells, T-cells and NK-cells. Lymphocyte subset analysis demonstrated elevated percentage of NK-cells: CD16/56 (67%; 4435cells/mcL). Upon further testing, an oligoclonal NK-cell population in the bone marrow was found. Preliminary sorting found EBV infection primarily in NK-cells instead of B-cells.

Discussion:
Given extensive mosquito bite reactions with fever and NK-cell proliferation, diagnosis of EBV-associated NK-cell lymphoproliferative disease with hypersensitivity to mosquito bites (EBV-T/NK LPD-HMB) was made. Elevated inflammatory cytokines, NK-cell infection, and elevated serum IgE supported this diagnosis. This condition is rarely seen in the United States but has been described in Asia. Notably, our patient’s mother was of Asian descent.

EBV infection of T- and/or NK- cells can lead to chronic active EBV infection (CAEBV), which can progress to liver failure, hemophagocytic lymphohistiocytosis, organ dysfunction, or malignancy.

Treatment options in the literature are typically multi-step, with initial acute control achieved through immunochemotherapy (steroids, cyclosporine A, etoposide), followed by multi-drug chemotherapy. The only curative treatment is allogenic hematopoietic stem cell transplant (HSCT). Given the potential sequelae of CAEBV, HSCT was pursued.

The patient received HSCT from a 10/10 HLA matched sibling donor, with initial complete reconstitution of donor derived B-cells, granulocytes, and NK-cells. His EBV viremia decreased by 2 logs. He has since remained clinically well and returned to school.

Conclusion: Although rare, EBV-T/NK LPD should be suspected in patients presenting with hypersensitivity to mosquito bites (HMB) if accompanied by systemic inflammation. It is important to sort lymphocytes to determine which cell types are infected. Clinicians should closely monitor HMB patients for possible sequelae of lymphoproliferative disease or hematologic malignancies.

As this condition may rapidly progress and has high mortality, curative allogenic HSCT should be pursued as soon as possible.