Prevalence of progressive multifocal leukoencephalopathy (PML) in adults and children with systemic lupus erythematosus

Abstract

ObjectiveTo define the risk of progressive multifocal leukoencephalopathy (PML) in SLE.MethodsThis is a retrospective observational study to evaluate PML cases in patients with SLE admitted to two large academic hospitals. Using electronic medical record (EMR) data, International Classification of Diseases (ICD) codes identified PML cases among patients with SLE, rheumatoid arthritis (RA) (controls), had renal transplant and with HIV. Medication exposure was reviewed.ResultsA total of 5409 Columbia University Medical Center (CUMC) patients and 2046 Northwell Health patients were identified using one ICD code for SLE. Of 7455 patients, three had an ICD code for PML. On EMR review, however, PML was substantiated in only one fatal SLE case with significant immunosuppressant use and severe lymphopenia (<0.5 cells x 109/L); one patient was evaluated for PML but cerebrospinal fluid (CSF) was negative for JC virus and improved with treatment of central nervous system (CNS) lupus. EMR data were very limited for the third patient and diagnosis could not be confirmed. None of the 13 342 patients with RA ICD codes had PML. Of the 5409 patients with an SLE ICD code at CUMC, 212 also had a renal transplant ICD code, and 83 had concomitant HIV/AIDS. Based on inpatient pharmacy records of 5409 hospitalised patients at CUMC, 59.2% were treated with steroids, and 16.09% with immunosuppressants (7.76% mycophenolate, 3.42% cyclophosphamide, 2.88% azathioprine and 2.03% rituximab). No patients with paediatric SLE (pSLE) (n=538) had PML. The combined prevalence of PML in hospitalised patients with SLE at the two hospitals was 13–27/100 000 patients.ConclusionAmong 7455 adult patients with SLE ICD codes, there were two PML cases, with only one confirmed case associated with severe lymphopenia and immunosuppressants, corresponding to a prevalence of 13–27 per 100 000 patients. No PML cases in pSLE were found. A high index of suspicion in patients with SLE and CNS manifestations is required for the prompt diagnosis of PML.

Progressive Multifocal Leukoencephalopathy Misdiagnosed as Neuropsychiatric Systemic Lupus Erythematosus With a Catastrophic Outcome

“…Children with SLE, as compared to adult patients, may have a lesser risk for PML despite being immunocompromised from medications or active SLE. It has been observed that PML associated with autoimmune disorders had a more favorable prognosis when compared with PML caused by other disorders such as HIV or malignancy 9…”

B-Cell-Directed Therapies: A New Era in Multiple Sclerosis Treatment

“…No cases of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus, which is mostly seen with natalizumab treatment, 89,90 have been recorded in MS patients treated with rituximab, and the frequency of PML in non-neurologic patients treated with rituximab seems to range around 1:4000; however, usually these patients have received multiple immunosuppressants. 91,92 Finally, an added advantage of rituximab is its relatively low cost (biosimilars are also available); however, its off-label prescription is complex and time-consuming for physicians. While open questions remain about optimal dosing and frequency strategies, a common tactic is 2 × 500 or 1000 mg, in a 14-day period, and repeat dosing of 500–1000 mg every 6 months or yearly.…”

Immunosuppression-related neurological disorders in kidney transplantation

“…Reports of PML cases in patients treated with Rituximab have raised concerns about its use in renal transplant recipients, since the risk seems to be higher in patients treated with multiple immunosuppressive drugs [28]. However, the incidence of this potentially fatal complication seems to be very low both in patients with autoimmune disorders and in renal transplant recipients [29,30]. Alemtuzumab is a humanized anti-CD52 monoclonal antibody that is used as induction or anti-rejection therapy in renal transplant recipients.…”