A27: Polyomavirus Excretion in Children with Rheumatic Diseases on Immunosuppressive Therapy

Background/Purpose: Biologic therapies have revolutionized the care and outcome of children with rheumatic diseases. However, the long term risks associated with these therapies remain unclear. For example, the occurrence of Progressive Multifocal Leukoencephalopathy (PML), caused by reactivation of the JC poly-omavirus (JCV), in patients treated with Rituximab is a major concern. PML has also been reported with Infliximab and other non-biologic immunosuppressive therapies. Human BK polyomavirus (BKV) results in allograft loss in kidney transplant recipients. While primary infection with the polyoma viruses occurs in childhood and is usually asymptomatic, the factors associated with reactivation and clinical disease remain unclear. Given the devastating and frequently fatal nature of PML, identification of specific risk factors may be useful prior to initiating immunosuppressive therapy and in long term surveillance. Methods: Thirty-three subjects with various rheumatologic diseases were prospectively enrolled from the Pediatric Rheumatology Clinic in a study of polyoma-virus excretion in patients with secondary immune compromise. Serial urine specimens were collected at each visit and stored at −70°C. Total nucleic acids were extracted and used to detect genome equivalents/milliliter urine (GE/mL), using real-time quantitative PCR for BKV and JCV. The lower limit of detection (LLOD) was 102 genomes/ml for BKV and JCV. Data forms about the patients' medications and clinical status were completed at each visit. Results: The underlying rheumatologic diagnosis was JIA in 16 patients (48.4%), SLE in 5 patients (15.1%), IBD-related arthritis in 5 patients (15.1%) and other conditions in 7 patients. Biologic therapies included Etanercept (n=8), Infliximab (n=4), adalimumab (n=1), multiple anti-TNF agents sequentially (n=2) and Rituximab (n=1). Non-biologic therapies included cortico-steroids, methotrexate, hydroxychloroquine, mycophenolate mofetil, azathioprine, cyclo-sporine and intravenous gammaglobulin. All patients on biologic therapies were also on a non-biologic disease-modifying agent. Urinary polyomavirus excretion was found in 17 of 33 (51.5%) patients and in 40 of 114 specimens (35.1%). Of these patients, 10 were BK excretors, 5 were JC excretors and 2 had BK and JC viruria at various times. Corticosteroid therapy was associated with polyomavirus excretion in 11 of the 33 patients. Among patients on biologic therapies, 8 of 15 (53.3%) were excretors, including 2 patients with JC virus excretion. On the other hand, among patients who were solely on non-biologic agents, 8 of 18 were excretors (44.4%). Conclusion: Our data indicate that there is an increased prevalence of reactivation of polyoma viruses as evidenced by viruria in patients with rheumatic diseases on biologic and non-biologic immunosuppressive therapies. An improved understanding of the factors associated with polyomavirus reactivation will be useful in pharmacosurveillance during long term therapy with immunosuppressive agents and may facilitate early diagnosis and therapy of polyomavirus-related diseases.