Case Study: Herpes Zoster in Patients With MS Treated With Dimethyl Fumarate

Varicella zoster (chickenpox) virus, illustration. The virus consists of a lipid membrane envelope with glycoproteins, a protective capsid holding the nucleic acid. VZV is a virus from the Herpesviridae family, the causative agent of chickenpox and shingles. In severe cases VZV may cause complications, such as pneumonia and encephalitis.
This case study examines 2 patients with relapsing remitting multiple sclerosis, under dimethyl fumarate treatment, who developed severe herpes zoster infection.

A reduction of CD8+ T-cells coupled with increased natural killer (NK) cells associated with dimethyl fumarate (DMF) therapy for multiple sclerosis (MS) may have important implications for patients who become infected with herpes zoster (HZ), according to case report findings published in Neurology: Neuroimmunology and Neuroinflammation.

Patient 1 was a woman who was 23 years old. At age 16, she presented with acute cerebellar ataxia and trigeminal neuralgia, prompting a magnetic resonance imaging (MRI) assessment. The patient was found to have T2-hyperintense periventricular subtentorial lesions and developed additional enhancing lesions at 6 months.

After therapy with interferon b-1a, the patient showed satisfactory response. Providers started her on 240 mg twice daily DMF due to enhancing cervical and thoracic demyelinating lesions.

After 2 years on DMF, in March of 2020 the patient presented with a blistering rash from the right side of the back to the chest. This pattern is typically observed among patients with HZ with positive anti-varicella-zoster virus antibodies.

DMF was discontinued and providers administered 1 week of brivudine, followed by valaciclovir at 1000 mg, 3 times daily for 20 days which was tapered to 500 mg daily. Laboratory analysis indicated the patient had normal white blood cell count, absolute lymphocyte count, low to normal CD4+ T cells, high NK cells, and low CD3+ and CD8+ T-cells.

The rash improved following 2 months, after which time the patient was started on 40 mg glatiramer acetate 3 times per week. At 3 months, CD3+, CD4+, and CD8+ T-cells remained low and no lesion exacerbations were observed.

Patient 2 was a man who was 42 years old. At age 28, he presented with acute numbness of the right arm and dysuria. An MRI indicated multiple T2-hyperintense, periventricular, subcortical, and cervical lesions. The patient was treated with glatiramer acetate but was switched to 240 mg twice daily DMF after 2 relapses.

After 2 years on DMF, the patient presented in October of 2020 with an aggressive blistering rash from the left side of the back to the chest, similar to patient 1.

Laboratory analysis indicated the patient had grade-1 lymphocytopenia, low CD3+ and CD8+ T-cells, high NK cells, and increased CD4+ and CD19+ T-cells.

Providers discontinued the patient’s DMF and administered therapy of brivudine for 2 weeks, followed by 1000 mg, 3 times daily valaciclovir for 30 days which was tapered to 500 mg daily. At 1 month, the rash improved, CD3+ and CD8+ T-cells remained low, and NK cells remained high. MRI detected a new enhancing demyelinating cervical lesion, and the patient was treated with corticosteroids.

Study researchers concluded, “Our cases highlight that T-cell subset monitoring may still have a role during DMF therapy and that the combination of low CD8[+]/ high NK requires attention.” The combination of high NK cells with low CD8+ T-cells may be a risk factor for severe HZ infection.


Anagnostouli MC, Velonakis G, Dalakas MC. Aggressive Herpes Zoster in Young PatientsWith Multiple Sclerosis Under Dimethyl Fumarate. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1017. doi:10.1212/NXI.0000000000001017