Progressive multifocal leukoencephalopathy in a patient with systemic mastocytosis treated with cladribine

•PML has recently been associated with several immune therapies utilized in multiple sclerosis (MS), a disorder with autoreactive T-cells.•Cladribine is an effective drug against MS, but may cause prolonged depression of the CD4 counts.•This is the second published PML case associated with the use of cladribine.•The present case adds concern that all potent agents against MS, aimed to deplete/inhibit autoreactive lymphocytes, also increase the risk of PML.

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML.Case descriptionA 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis. Cladribine treatment was initiated and regarded effective, but the course was complicated with bouts of severe anemia and recurrent episodes of salmonella associated gastroenteritis. His lymphocyte count fell to 0.1 × 109/L at its lowest level, but gradually rose. Despite this, in the 6 month wake of the last dose of cladribine given, the patient experienced herpetic stomatitis, had CMV present in blood, and ultimately developed the neurological symptoms. An MRI scan revealed a lesion in the right cerebellar hemisphere compatible with PML, and PCR analysis of the CSF showed positive for JCPyV DNA with a load of 323 950 copies/ml. No pathological cells were seen on CSF flow cytometry. The CD4/CD8-ratio was 0.45 (160 CD4+ cells/mm3 and 360 CD8+ cells/mm3). The patient passed away 3 weeks later.ConclusionPML may be the consequence of prolonged lymphopenia due to the use of cladribine.