Patients treated with Dimethyl fumarate are at risk for opportunistic infections with and without severe lymphocytopenia


Patients receiving Dimethyl fumarate ( DMF ) are at risk for opportunistic infections even without severe lymphocytopenia.

An additional patient with progressive multifocal leukoencephalopathy ( PML ) and the immune reconstitution inflammatory syndrome after DMF treatment with only a modest case of lymphocytopenia was reported recently.

Because the number of patients treated with Dimethyl fumarate has increased rapidly since the approval of delayed-release Dimethyl fumarate as first-line treatment for relapsing–remitting multiple sclerosis, progressive multifocal leukoencephalopathy or other opportunistic infections may develop in more patients.

Safety monitoring of patients treated with Dimethyl fumarate is crucial, because opportunistic infections can occur in patients without severe lymphocytopenia.
Further studies concerning safety monitoring and new methods for identification of patients at risk are therefore urgently needed.

Case A

Researchers have reported a 23-year-old male patient with psoriasis who was treated with DMF ( Fagron ). After 2 months of treatment, fever, skin lesions unrelated to psoriasis, and cervical, axillary, and inguinal lymphadenopathy developed.

Histopathological findings were consistent with herpesvirus infection. Polymerase-chain-reaction testing confirmed the diagnosis of varicella–zoster virus ( VZV ) infection; serologic testing was positive for IgM antibodies to varicella–zoster virus, but there was no IgG response.

The patient had no documented lymphocytopenia. Because his medical history mentioned chickenpox during childhood, researchers made the diagnosis of generalized VZV infection.

The DMF treatment may have reactivated the VZV infection in this patient, because the infection developed 2 months after the initiation of treatment, he never received ultraviolet-light therapy, and he did not use topical glucocorticoids.

This case suggests that patients treated with DMF may have an increased risk of viral infection, even in the absence of lymphocytopenia.

Case B

Dimethyl fumarate has been shown to reduce specific lymphocyte subpopulations even when total lymphocyte counts exceed 500 cells per cubic millimeter. It appears, therefore, that in spite of normal lymphocyte counts, patients receiving Dimethyl fumarate may be at risk for infections.

A human herpesvirus 8–related Kaposi's sarcoma developed in a patient with psoriasis who was receiving DMF treatment and who had normal total lymphocyte counts but low counts of CD4+ and CD8+ lymphocytes.

Thus, it may be important to assess cell counts of specific lymphocyte subsets during treatment with Dimethyl fumarate. Measurement of intracellular ATP concentrations in CD4+ lymphocytes has been suggested to monitor for decreased CD4+-mediated immunity during treatment with Dimethyl fumarate.
Low levels of intracellular ATP in CD4+ lymphocytes were detected in a patient in whom DMF-related progressive multifocal leukoencephalopathy developed. ( Xagena )

Source: The New England Journal of Medicine, 2015

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