AB1513 SIROLIMUS INDUCED INFLAMMATORY ARTHROPATHY

Abstract

BackgroundSirolimus is a non-calcineurin immunosuppressant commonly used in patients with organ transplantation to prevent rejection. While various inflammatory syndromes have been described post-sirolimus use, it is uncommon to have inflammatory arthritis to sirolimus1. We present a patient who developed significant joint inflammation following sirolimus use.ResultsOur patient is a 39 year old gentleman who had a heart transplant in 1992 following dilated cardiomyopathy. He was switched to sirolimus after concerns about chronic kidney disease and graft vascular disease. Six weeks later, he developed bilateral foot pain and swelling which prevented him from weight bearing. He had an MRI which showed significant bone marrow oedema in the midfoot tarsal bone and basal metatarsals. He then had a nuclear scan which showed highly increased and symmetrical uptake in both mid feet affecting the cuneiform and second, third and fourth bases of the metatarsals. The appearances showed increased osteoblastic activity with increased vascularity which was more in keeping with bone inflammation/infection and no osteonecrosis. His C-reactive protein was elevated at 148. This improved to 30 after cessation of the sirolimus. Blood cultures were negative.Of significance in his history, he also suffers from gout and has had previous monoarthritic flares involving his wrist, elbow and index finger. However, he was placed on febuxostat 80 mg in 2018 with excellent response. His serology was negative for anti-CCP and Rheumatoid factor. His urate levels were controlled at 374. He was also found to be HLA-B27 positive, but there was no evidence of inflammatory back pain.He was placed on a tapering course of prednisolone and coupled with the cessation of the Sirolimus, his pain and swelling resolved. In follow-up clinic appointments, he remained in remission from his inflammatory arthritis and did not require any additional treatment but continued on Mycophenolate Mofetil and Ciclosporin for his cardiac transplant.ConclusionThere are many studies investigating the use of sirolimus as an anti-inflammatory agent in autoimmune conditions such as rheumatoid arthritis2 and inflammatory bowel disease3. The mechanisms include down regulation of IL-17 and IL-63.However, the induction of an inflammatory arthritis by sirolimus can paradoxically occur as sirolimus causes a reduction in the STAT 3 and the anti-inflammatory cytokine IL-103. There has been raised levels of IL-6 and TNFα in serum of patients with inflammatory sequelae post sirolimus therapy1. This disequilibrium of inflammatory cascade is related to the ability of Sirolimus to inhibit mammalian target of rapamycin (mTOR) which then subsequently modulates these effects4. In general, these pro-inflammatory sequelae are mild and tend to resolve after cessation of the drug1. Although our patient had severe arthritic manifestations which required steroid therapy, his symptoms were transient after removal of Sirolimus.References[1]Buron F, Malvezzi P, Villar E, Chauvet C, Janbon B, et al. (2013) Profiling Sirolimus-Induced Inflammatory Syndrome: A Prospective Tricentric Observational Study. PLOS ONE 8(1): e53078[2]Wang J, Zhang SX, Hu FY, Zheng XJ, Cheng T, Yu NN, Yang WX, Gao C, Wen HY, Li XF. Sirolimus Treatment in Patients with Refractory Rheumatoid Arthritis: A Double-Arm, Open-Label, phase 1/2 Trial. Arthritis Rheumatol, 2018:70 (suppl 10).[3]Yin H, Li X, Zhang B, et al. Sirolimus ameliorates inflammatory responses by switching the regulatory T/T helper type 17 profile in murine colitis. Immunology. 2013;139(4):494-502.[4]T Weichhart, G. Costantino, M. Poglitsch, M. Rosner, M. Zeyda, KM. Stuhlmeier, T Kolbe, TM. Stulnig, WH. Horl, M Hengstschlager, M. Muller, and MD. Saemann. The TSC-mTOR Signaling Pathway Regulates the Innate Inflammatory Response. Immunity Volume 29, Issue 4, 17 October 2008, Pages 565-577Disclosure of InterestsNone declared