Combined B Cell Aplasia and Hypereosinophilia as a Complication of Lamotrigine Therapy

BackgroundAlthough drug rash with eosinophilia and systemic symptoms (DRESS) and anticonvulsant hypersensitivity syndrome are well-known complications of anti-seizure medications (ASMs), lesser-known immunologic complications, including B cell loss and hypogammaglobulinemia, have been reported. Historically, the etiology and natural history of ASM-induced B cell injury have been incompletely understood.CaseAn otherwise healthy 20-year-old female with minimal infectious history presented with acute fatigue, fever, and upper respiratory tract infection symptoms. She had initiated lamotrigine therapy two months prior. One week after symptom onset, she developed severe abdominal pain and presented emergently to an outside hospital. Imaging demonstrated acute splenic infarction, with labs notable for leukocytosis, eosinophilia, lymphocytosis, near-absent B cells, and borderline low IgG. She was initiated on enoxaparin, but within five days developed a second splenic infarction and new maculopapular rash. The patient transitioned to rivaroxaban and was discharged home. The patient’s condition progressed to include cough, mucositis, diarrhea, and unintentional weight loss, prompting admission for expedited workup.Labs demonstrated new hypereosinophilia, with complete B cell aplasia and progressive immunoglobulin loss. Endoscopy revealed absent B cells and plasma cells throughout the small and large intestine. Bone marrow biopsy demonstrated near-complete loss of B cell precursors and mature B cells alike, with rare detectable plasma cells. Cytokine studies demonstrated elevated sIL-2R, CXCL9, IL-5, and IL-13. PET-CT was without evidence of malignancy. Whole genome sequencing (WGS) was negative for variants concerning inborn errors of immunity, but revealed a likely pathogenic heterozygous SLC4A1 variant compatible with hereditary spherocytosis. An extensive infectious disease workup was negative.The patient tapered off lamotrigine, initiated immunoglobulin replacement, and completed two doses of mepolizumab, with significant symptomatic improvement. In the months following discharge, the patient has demonstrated recovery of B cell counts with evidence of emerging class switching and humoral output, without recurrence of eosinophilia.DiscussionDrug hypersensitivity syndromes, B cell loss, and hypogammaglobulinemia may occur following ASM therapy. This case demonstrates for the first time that the mechanism may involve loss of developmentally diverse B cell populations, including precursors, mature B cells, and plasma cells across multiple compartments. Importantly, we observed B cell recovery after discontinuation of lamotrigine, suggesting that this loss may be reversible.