High CD4+:CD8+ ratios with herpes zoster infections in patients with multiple sclerosis on dimethyl fumarate

Abstract

Background: Dimethyl fumarate (DMF) depletes CD8+ and CD4+ T cells, and cases of herpes zoster (HZ) in patients with multiple sclerosis (MS) on DMF have been documented. Objectives: To evaluate lymphocyte subsets in patients with MS who developed HZ on DMF (Tecfidera) compared to matched controls who did not develop HZ. Methods: We used linear mixed-effects models to test for differences in white blood cell count, lymphocyte percentage, absolute lymphocyte count, CD3+ percentage, absolute CD3+ count, CD4+ percentage, absolute CD4+ count, CD8+ percentage, absolute CD8+ count, and CD4+:CD8+ ratio over time in HZ and non-HZ groups. Results: Eighteen patients developed HZ while on DMF. The linear mixed-effects model for CD4+:CD8+ ratio showed a significant difference between the HZ and non-HZ groups ( p = 0.033). CD4+:CD8+ ratio decreased over time in the HZ group and increased over time in the non-HZ group. Conclusion: Patients with MS who develop HZ while on DMF have high CD4+:CD8+ ratios, suggesting an imbalance of CD4+ and CD8+ cells that may put a patient at risk for developing HZ while on DMF. This result emphasizes the need for lymphocyte subset monitoring (including CD4+:CD8+ ratios) on DMF, as well as vaccination prior to DMF initiation.

CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases

“…When the CD4/CD8 ratio is less than the turning point of 2, the risk of developing HZ in AIRD patients gradually increases as the CD4/CD8 ratio decreases. Another study has also demonstrated that changes in the CD4/CD8 ratio may elevate the risk of HZ occurrence in patients with MS, which was consistent with our study 28 . Therefore, changes in T-lymphocyte subsets should be detected during clinical workup and treatment; in particular, changes in the CD4/CD8 ratio should be emphasized.…”

“…An interesting study by Balshi et al 28 suggests that patients with multiple sclerosis (MS) who develop HZ while on dimethyl fumarate (DMF) have high CD4/CD8 ratio. MS is a chronic neurological disease that affects the central nervous system, and the efficacy of DMF in the treatment of MS has been confirmed.…”

Reactivation of Herpes Zoster in a Young Patient With Multiple Sclerosis Under Dimethyl Fumarate Treatment and Normal Lymphocyte Subsets Count: A Case Report

“…Another case demonstrated a significant decrease in CD8+ and CD4+ T lymphocytes in a patient receiving DMF, suggesting a potential link between DMF-induced lymphopenia and VZV reactivation with disseminated zoster [ 27 ]. Furthermore, a recent study found elevated CD4+/CD8+ ratios in patients with MS on DMF who developed HZ [ 28 ]. Additionally, a case of progressive multifocal leukoencephalopathy in DMF-treated patients without severe lymphopenia underscores the need for vigilance [ 29 ] as does the case of HSV encephalitis in a lymphopenic DMF-treated patient with MS, highlighting the potential implications of DMF-related lymphopenia for viral immunity [ 30 ].…”