S3256 An Uncommon Side Effect of JAK Inhibitors

Introduction: Janus kinase (JAK) family are intracellular enzymes involved in the immune-related intracellular transduction of signals from extracellular cytokines via receptors. JAK inhibitors therefore suppress immune system, leading to life-threatening infection. Upadacitinib and tofacitinib are approved for treating adults with moderate to severe ulcerative colitis (UC) who have not responded to anti-TNF agents. We are reporting a case of Fournier’s gangrene in a patient taking upadacitinib. Case Description/Methods: 51-year-old man with prior medical history of rheumatoid arthritis (RA) on upadacinitib came to ED with complaint of scrotal swelling and discomfort in perineum for 1 week associated with subjective fever and chills. He denied any trauma or any surgery. He was on steroids for RA until 3 months ago when he was switched to rinvoq. He is a mechanic by profession, not sexually active and not on any other medication except updacitinib. Examination revealed swollen penis, testes and discoloration of the perineum with foul smelling drainage. He was tachycardic at 115 and had temp of 100.8 with leukocytosis of 24000, CRP of 24.5 mg/d. He was nondiabetic (hbA1c 5.6). CT abd pelvis w/ IV contrast showed marked scrotal wall thickening with air in the subcutaneous tissue, extends into the penile shaft and suprapubic tissue, findings suspicious for Fournier’s gangrene. He was started on linezolid and meropenem. General surgery and urology took him to OR and found to have necrotic skin of the genitalia involving the phallus, left scrotum up to the left inguinal canal. Infection tracks from the left perianal area up to the perineum into the scrotum. Incision and drainage were performed. OR gram stain and culture grew polymicrobial with no evidence of MRSA. He was on linezolid and meropenem for 5 days and deescalated to levofloxacin with outpatient follow-up with rheumatology. Leukocytosis and CRP trended down to normal. Final impression was Fournier’s gangrene secondary to Rinvoq in absence of other risk factors. Discussion: Necrotizing fasciitis of the perineum, aka Fournier gangrene (FG) is a form of polymicrobial infection. Major risk factors include diabetes, trauma, immunosuppression, surgery and obesity. In our case, patient did not have any risk factors except being on updacitinib. JAK inhibitors are approved for certain autoimmune diseases including UC. Therefore, gastroenterologist should be aware of adverse effects including FG which is rarely reported and after reviewing literature, this is the second case being reported.