A case of developing progressive multifocal leukoencephalopathy while using rituximab and mycophenolate mofetil in refractory systemic lupus erythematosus

Abstract

Progressive multifocal leukoencephalopathy (PML) is a central nervous system infection caused by John Cunningham (JC) virus reactivation in an immunocompromised patient. PML has various neurologic symptoms and has very poor prognosis. A 36-year-old man developed transverse myelitis and had a psychiatric disorder at the age of 26. He was diagnosed with systemic lupus erythematosus (SLE) and neuropsychiatric SLE (NPSLE), on the basis of leukopenia and presence of anti-DNA and anti-nuclear antibodies. Treatment with glucocorticoid (GC) was started, and remission was introduced. Six months before PML onset, his condition was complicated with hemophagocytic lymphohistiocytosis (HLH) due to exacerbation of SLE. Remission re-induction therapy by GC, cyclosporine-A, intravenous cyclophosphamide, and rituximab (RTX) was initiated and HLH improved. However, interleukin-6 levels of the cerebrospinal fluid (CSF) continued to rise. We thought that the disease activity of NPSLE worsened; thus, we introduced mycophenolate mofetil (MMF) 4 months before the PML onset. He developed progressive dysarthria and right hemiplegia. He was diagnosed with PML via magnetic resonance imaging and JC virus polymerase chain reaction in CSF. Considering that immunosuppressants, including RTX and MMF, are precipitating factors of PML, we discussed the RTX removal using plasma exchange (PEx), but we did not introduce PEx, because it was expected that the concentration of RTX was already lowered when he was diagnosed with PML. Treatment for PML with mefloquine and mirtazapine saved his life, but severe residual disabilities remained. This is the first report of a patient who developed PML during combination therapy with RTX and MMF.

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis

“…One example is the reactivation of the John Cunningham virus leading to progressive multifocal leukoencephalopathy, which has been reported in patients with autoimmune diseases. Patients must be informed of the risk of such adverse events with rituximab therapy [159,160]. Additionally, long-term rituximab therapy is related to hypogammaglobulinemia.…”

The Use of Antimalarial Drugs against Viral Infection

“…In many cases, MQ was combined with mirtazapine, an antidepressant that, acting on the 5-HT2A serotonin receptor, is able to inhibit JCPyV entry into glial cells, preventing the diffusion of the infection in oligodendrocytes. The outcomes of this treatment are controversial, leading to the resolution of the infection, with a claimed effect of MQ and mirtazapine treatment [86,87,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105], and to the resolution of the infection probably due to other factors [96,[106][107][108][109] or to the death of the patient, which was not always directly related to the unsuccessful therapy [87,96,[110][111][112][113][114][115][116]. In one case, the suspension of the therapy was necessary due to the side effects [117].…”

Longitudinal Analysis of Disease Burden in Refractory and Nonrefractory Generalized Myasthenia Gravis in the United States

“… 16 Rituximab may also be associated with chronic B-cell depletion. 19 , 20 Other issues associated with the management of refractory gMG are the very slow response to some ISTs 21 and the often “trial and error” nature of treatment. 22…”