Aggressive Herpes Zoster in Young Patients With Multiple Sclerosis Under Dimethyl Fumarate

Dimethyl fumarate (DMF), approved for relapsing-remitting multiple sclerosis (RRMS), exerts immune-mediated mechanisms crucial for T-cell survival and migration, preferentially reducing CD8 + T cells. 1 Although baseline absolute lymphocyte count (ALC) is considered the most critical predictor of developing lymphopenia, 2 it was recently concluded that lymphocyte subset monitoring is not required for safety vigilance because T-cell subset reduction does not increase risks for serious infections.3 We present 2 young patients with RRMS, under DMF treatment, negative for HIV and SARS-CoV-2 (by RT-PCR in nasal swab) and with normal follow-up white blood cell (WBC)/ALC counts, who developed severe herpes zoster (HZ) infection with normal ALC but low CD8 + and high CD56 bright natural killer (NK) cells, and discuss the potential significance of T-cell immunophenotyping in HZ manifestation. Patient 1A 23-year-old woman was seen at age 16 years with acute cerebellar ataxia and trigeminal neuralgia.MRI showed nonenhancing T2-hyperintense periventricular and subtentorial lesions and CSF oligoclonal bands.Anti-AQP4 and anti-MOG antibodies were negative.After 6 months, new T2-hyperintense, enhancing, periventricular lesions developed and was started on interferon beta-1a with excellent response.Because of new enhancing cervical and thoracic demyelinating MRI lesions, she was started on DMF 240 mg BID 2 years ago.In March, during the first peak of COVID-19, she presented with an aggressive, blistering rash extending from the right side of back to the chest (figure), typical of HZ with positive anti-varicella-zoster virus (VZV) antibodies.She reported chickenpox in childhood.DMF was discontinued, and 1-week treatment with brivudine (bromovinyldeoxyuridine) began followed by valaciclovir 1,000 mg TID for 20 days, tapered to 500 mg daily.Her WBC and ALC counts were normal but had low CD3 + , very low CD8 + , lownormal CD4 + T cells, and very high NK cells (table).After 2 months, the rash improved.Repeated MRI of the brain and cervical spine was stable.She was started on glatiramer acetate 40 mg 3 times/wk.After 3 months, CD3 + , CD4 + , and CD8 + T subsets remain still low (table ).Although SARS-CoV-2-PCR was negative and always asymptomatic, she had antibodies to SARS-CoV-2-spike protein when tested 10 months after the HZ manifestation.