Background:Interferon-α (IFN-α) is known for its antiviral and antiproliferative effects, used mainly for the treatment of chronic hepatitis C infection [1]. Immunomodulatory effects have been reported in patients treated with IFN-α, including hematological, immunological, rheumatological and dermatological disorders [2]. In fact, IFN-α may lead to the induction or exacerbation of autoimmune diseases such as psoriasis, systemic lupus erythematosus, and rarely rheumatoid arthritis (RA).Objectives:We report the case of a Caucasian who developed anticyclic citrullinated peptide antibody (anti-CCP)-positive RA following treatment of chronic hepatitis C infection with pegylated IFN-α2a.Methods:A 57-year-old women was diagnosed of chronic hepatitis C infection after detection of abnormal liver function. She has a genotype Ib with a high viral load: RNA was 100,000 UI/ml. Liver histology showed advanced fibrosis and portal fibrosis (A3 F4 according to metavir score). A history of blood transfusion was found. The patient was placed on a 24-week course of PEGylated -IFN-α2a 180 µg weekly and a 1000 mg daily dose of ribavirin. After two months of antiviral treatment, she developed symmetrical polyarthritis, with pain and edema in the wrists, elbows, shoulders and metacarpophalangeal joints, associated with prolonged morning stiffness. The musculoskeletal examination was notable for active synovitis of the proximal phalangeal joints, metacarpophalangeal joints, wrists, elbows. Distal interphalangeal joints were spared. She had no musculoskeletal symptoms prior to antiviral therapy. Review of systems was otherwise unremarkable. X-ray showed no remarkable findings. Ultrasonography of the hands revealed diffuse synovitis as well as tenosynovitis of the ulnar extensor tendons in both wrists. Laboratory results revealed a normal C-reactive protein, elevated liver enzymes: ALAT (alanin-aminotransferase) 119,ASAT (aspartat-aminotransferase) 66, Gamma-GT 203 and undetectable cryoglobulins. Anti-CCP was 21 IU/ml (negative < 20 IU/ml), antinuclear antibodies were positive 1280 (negative<160), rheumatoid factor was 192 (normal < 30 IU/ml).A diagnosis of rheumatoid arthritis (RA) was made on the basis of clinical and ultra-sonographic evidence as well as Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity. Moreover, an autoimmune thyroiditis was found that evolved into hypothyroidism treated with thyroxine.Results:The patient developed a sustained virological response as evidenced by persistent undetectable HCV RNA and normal aminotransferase activities. Upon completion of a 12-week course of antiviral therapy, The rheumatoid syndrome disappeared after cessation of IFN therapy. By that time, antinuclear antibodies were in a titre of 1 /180, rheumatoid factor and Anti-CCP were negative.Conclusion:The present case suggests that biological agents, affecting the cytokine network, may work as triggering factors for the development of RA in previously predisposed individuals. Screening for RF and anti-CCP may be considered before treating with IFN. In addition, a close surveillance for the occurrence of autoimmune phenomena during and after treatment should be worthy, for early diagnosis and adequate clinical management.References:[1]DARICE YANG,DANIEL ARKFELDandTSE-LING FONG TreatmentforChronic Hepatitis C Infection.DevelopmentofAnti-CCP-positive Rheumatoid Arthritis Following Pegylated Interferon-alpha. J Rheumatol 2010;37;1777Volume 37, no. 8. 2a[2]Okanoue T, Sakamoto S, Itoh Y, Minami M, Yasui K, Sakamoto M, et al. Side effects of high-dose interferon therapy for chronic hepatitis C. J Hepatol 1996;25:283-91.Disclosure of Interests:None declared
Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy?
