Severe multiple sclerosis reactivation during prolonged lymphopenia after dimethyl fumarate discontinuation

Background Delayed‐release dimethyl fumarate ( DMF ) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. Case presentation We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36‐year‐old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta‐1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF . The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. Conclusions Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a “wait and see.” A different immunotherapeutic strategy such as an anti‐B therapeutic approach could be considered.