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Papers of the Week

2022 Feb




Varicella-Zoster Reactivation in a Non-immunized Elderly Multiple Sclerosis Patient While on Delayed-Release Dimethyl Fumarate With Grade 2 Lymphopenia and Profoundly Low CD4+ and CD8+ Cell Counts: A Case Report.


Increased susceptibility to opportunistic infections (OI) in multiple sclerosis (MS) patients is a real concern amongst neurologists when using disease-modifying therapies (DMTs). DMTs used in modulating or suppressing the immune system for MS management may risk the patient with lymphocytopenia, raising the possibility of OI; however, this lymphopenia may contemplate as a biomarker for drug response, degree of immunomodulation, and drug compliance. The OI could be reactivation of varicella-zoster, progressive multifocal leukoencephalopathy (PML) induced by John Cunningham virus (JC virus), infection, cryptococcal meningitis, atypical mycobacteria, and many more. We present a non-immunized case of varicella-zoster reactivation with dimethyl fumarate (DMF) therapy. Surprisingly, the patient's lymphocyte count trend during her previous follow-up visits remained in the range of normal to grade 1 lymphopenia but with her current flared-up rash presentation, she had a profoundly low CD8+ and CD4+ cell counts (CD8+ cell count << CD4+ cell counts) despite an absolute lymphocyte (ALC) level far above 500 cells/µl; in fact, it was 13.6% higher when compared to her last quarterly levels. Controlled trials with DMF claimed no serious infection even with a lymphopenia range of 500-800 cells/µl, which is untrue in real clinics and it would be wise and reasonable to follow the lymphocyte subsets along with ALC to prevent potential opportunistic infections. Recently, comprehensive strategies were evolved to mitigate OI risk for MS patients while on DMTs. These were not only limited to lymphocyte threshold monitoring but extended to address features in terms of screening recommendation, vaccination advice, the need for antibiotic prophylaxis, neuroimaging, laboratory checkups, medication dosing, and behavioral modifications. Our patient was not immunized with zoster vaccine and, unfortunately, DMF has no proper structured guidelines regarding vaccination against OI prevention as other few DMTs have. Our case could suggest that MS patients need proper vaccination guidelines from the Centers for Disease Control and Prevention (CDC) before starting DMF.