Infliximab Induced Anterior Uveitis in a Patient With Ulcerative Colitis

Abstract

Tumor necrosis factor alpha (TNF-α) antagonists are increasingly used to treat Crohn's disease (CD), ulcerative colitis (UC), and rheumatologic conditions including psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. Sepsis, reactivation tuberculosis, lymphoma, and drug-induced lupus are serious but uncommon adverse events associated with use of Infliximab. However, less frequent reactions are emerging as Infliximab use has increased. In this case, we present a 49 year-old male with left-sided UC who developed anterior uveitis following escalation of Infliximab therapy. Since his diagnosis of UC in 1992, the patient had been poorly controlled on various forms of mesalamine (5-ASA) therapy and often required intermittent courses of steroids for acute flares. In 2011, the patient was placed on steroids for a UC flare and associated polyarthralgias, but transitioned to 6-mercaptopurine (6-MP) for maintenance therapy. The patient was in clinical remission, but 6-MP was discontinued secondary to hepatotoxicity and pancytopenia. A decision was made to initiate Infliximab therapy at 5 mg/kg every eight weeks, which maintained the patient in clinical remission for eight months. He then developed arthralgias, fatigue and elevation in inflammatory markers in between Infliximab infusions. In response to these breakthrough symptoms, his dose was increased to 10 mg/kg every eight weeks. Upon initial administration of Infliximab at 10 mg/kg, he developed acute onset of bilateral conjunctival hyperemia and chemosis. He experienced bilateral eye pain, photophobia, and blurry vision consistent with uveitis that persisted for two weeks and resolved without treatment. Prior to his second escalated dose of infliximab, he was pretreated with 100 mg intravenous hydrocortisone in addition to acetaminophen and diphenhydramine. During his infliximab infusion, he experienced unilateral chemosis and hyperemia without acute eye pain, changes in vision, or photophobia. Ophthalmologic consultation confirmed a diagnosis of uveitis, but pretreatment with hydrocortisone may have decreased the severity of uveitis causing a milder version of the previous attack. The patient was started on ocular steroids with plans to pre-treat him with prednisone three days prior to his next infliximab dose. Our patient's flares of uveitis occurred upon increasing his Infliximab dose, and then recurred upon receiving that same elevated dose. This strongly suggests that his uveitis was caused by the higher dose of Infliximab. TNF-α blockade is typically used to treat uveitis flares associated with inflammatory bowel disease. Paradoxical reactions have been reported describing anterior uveitis following therapy with Etanercept, but less commonly with therapy with Infliximab. The proposed mechanism is that peripheral TNF-α blockade may increase T-cell reactivity leading to inflammation in the eye, or may participate in demyelination of the optic nerve causing neuritis. These infrequent adverse reactions are described sporadically in rheumatologic conditions but are not described in association with inflammatory bowel disease. With increasing use of TNF-α blockade for the treatment of UC and CD, it is important to consider and recognize anterior uveitis as a possible reaction following induction and escalation of TNF-α blockade therapy. Potential treatment options include reduction in infusion rate, dose-adjustment, pretreatment with steroids, or treatment with an alternate TNF-α antagonist.