EBV-related lymphoproliferative disease in Wiskott-Aldrich Syndrome patient

Abstract

CaseWiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. DiscussionWe present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.