Infliximab Induced Systemic Lupus Erythematosus: A Case Report

Abstract

A 41-year-old Hispanic female was diagnosed with Crohn's disease in 1998, and was treated with Mesalamine and 6 Mercaptopurine. She also required the use of prednisone for 6-8 weeks at least once a year. Her disease was complicated by perianal fistulae and recurrent perianal abscesses. In 2001, she was started on Infliximab (5 mg/kg) every 8 weeks. However, it was stopped in 2003 for financial reasons. She continued to use 5 ASA and 6-mercaptopurine. In addition, prednisone and Flagyl were used for treatment of acute flare-ups. Infliximab was restarted in January 2009 due to frequent flare-up and inability to control perianal disease. In April 2009, the patient presented to the clinic complaining of right toe pain and swelling, and this was preceded with multiple episodes of large and small joint pain and swelling, with lower extremity tingling. She denied skin rashes, oral ulcers, or photosensitivity. The physical exam was remarkable for right toe swelling and tenderness with normal range of motion. Serology was positive for ANA (1:320), mildly elevated anti DsDNA (1:20), increased anti-B2 lipoprotein antibodies (29.4), low C4 and mildly decreased C3. Anti-Smith, anti SSA, anti SSB, anti RNP and anti-histone antibodies were negative. Rheumatoid factor and urinalysis were normal. Correlation of the history, examination, and laboratory findings in the context of patient's exposure to infliximab, the diagnosis of TNF-alpha antagonist induced Lupus syndrome (TAILS) was made. Treatment included stopping infliximab. Patient was started on hydroxychloroquine (200 mg twice daily). Arthralgia resolved 6 months after stopping infliximab. Her symptoms of lower extremity tingling also partially resolved with gabapentin in 12 months. Serology and complement levels were found to be normal. Discussion: The occurrence of TAILS is estimated to be 0.5-1% with infliximab, and etanercept being the most common agents. Onset of symptoms ranges from 10 days to 54 months after exposure. In our patient, symptoms started 3 months after restarting infliximab. Presenting symptoms can widely vary involving musculoskeletal system, neuropathy, and neuropsychiatric disorders. Arthritis is the most common presenting disorder. Peripheral neuropathy was found in 5 out of 32 patients receiving infliximab, and neuropsychiatric symptoms developed in 3% of patients receiving either infliximab or etanercept. Our patient presented with arthralgia, arthritis and peripheral neuropathy. Anti-neutrophil antibodies were found to be positive in the majority of patients and in our patient as well. In a prospective controlled study, only 20% of patients receiving infliximab were positive for anti-double stranded DNA, and it was mildly elevated in our patient. Anti-histone antibodies are positive in 95% of patients with drug induced lupus, and only in 17-57% of patients with TAILS. Anti-histone antibodies were negative in our patient. Resolution of symptoms was found in most of the patients after stopping the drug in 3 weeks to 6 months. Our patient's arthritis resolved after 6 months, and it required the addition of hydroxychloroquine. Peripheral neuropathy required more time to resolve (12 months).