Fatal PML in a patient treated with compounded dimethyl fumarate with only modest lymphocytopenia

      Background: Since the 1950s fumaric acid esters (FAEs) have been used to treat psoriasis and in 2013 dimethyl fumarate (DMF) was approved as treatment for multiple sclerosis. FAEs have immunomodulatory and immunosuppressive effects and although they lead to a reduction of peripheral blood lymphocyte counts, opportunistic infections appear to be very rare. However, since 2013 several cases of progressive multifocal leukoencephalopathy (PML) were reported in patients with sustained and severe lymphocytopenia. Recently, two PML cases without severe lymphocytopenia were also reported.
      Objective: Present the case of a psoriasis patient with PML after two years treatment with Psorinovo (DMF compounding pharmacy, Mierlo-Hout, the Netherlands). (Nieuwkamp et al, NJEM 2015; 372:1474-1476)
      Patients and methods: In June 2012 a 64 year old Dutch woman with psoriasis started treatment with Psorinovo 240 mg t.i.d. Since July 2013 the dose was reduced to 240 mg b.i.d. She received no other systemic immunosuppressive treatment and was seronegative for HIV. During the treatment period, her total leukocyte counts remained within normal range.
      Results: In July 2014 the patient developed progressive apraxia. Due to atypical CT and MRI imaging findings, no history of leukocytopenia and negative JC virus PCR in CSF, PML was rejected and the diagnosis of atypical ischemic stroke was made and Psorinovo was stopped. Her condition continued to deteriorate and MRI images were suggestive of PML-IRIS. Posthumously the diagnosis PML was established by PCR and immunohistochemistry.
      Conclusion: Physicians should be alert for PML in patients treated with FAEs, both in lymphocytopenic and non-lymphocytopenic patients.