Association of rheumatoid arthritis and primary biliary cirrhosis treated with rituximab

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Association of rheumatoid arthritis and primary biliary cirrhosis treated with rituximab

A 60-year-old woman was diagnosed with primary biliary cirrhosis (PBC) in 2004. The diagnosis was based on the pathology of a liver biopsy that revealed signs of nonsuppurative cholangitis without fibrosis or cirrhosis and on laboratory tests showing high levels of alkaline phosphatase (four times the upper normal limit) and gamma-glutamyltransferase (three times the upper normal limit); positive type 2 antimitochondrial antibodies (1:640) serological tests were negative for hepatitis B and C. She was treated with ursodeoxycholic acid (UDCA) at a dose of 12mg/kg (600mg/day), with partial regression of her hepatic disorder. One year later, our patient presented with a deforming polyarthritis of her small and large joints. A physical examination on admission found synovitis in nine joints, seven painful joints, bilateral ulnar deviation hand deformities, Z-thumb deformity, and a limitation of motion in her wrists, shoulders and left hip

The most likely diagnosis of this presentation is

  • Rheumatoid Arthritis
  • Polyarthritis
  • Osteoporosis
  • Gout

Introduction

The association of primary biliary cirrhosis (PBC) with rheumatoid arthritis (RA) is exceptional, and the true prevalence of PBC in RA is not well known.1 This may impose several therapeutic and diagnostic challenges. In both diseases, it was observed that B cells played a prominent role in pathogenesis.2 We describe an unusual case of a patient with PBC and RA treated with rituximab.

Medical History

He had treated with ursodeoxycholic acid (UDCA) at a dose of 12mg/kg (600mg/day), with partial regression of her hepatic disorder. One year later, our patient presented with a deforming polyarthritis of her small and large joints.

Examination

Laboratory tests showed that our patient had an inflammatory syndrome with an erythrocyte sedimentation rate of 81mm at the first hour and a C-reactive protein level of 14mg/L. Her rheumatoid factor was positive at 143IU/L, and she had an anti-citrullinated protein antibody level of 798UI/mL. Radiographs showed erosions of her metacarpophalangeal and metatarsophalangeal joints, bilateral carpus and tarsus, atlantoaxial dislocation, and left coxitis. Based on this clinical, biological and radiological evidence, a diagnosis of active and severe RA was made.

Management

The patient was treated with a low dose of methotrexate (MTX; 7.5mg/week) associated with rituximab (two doses of 1000mg separated by two weeks), which demonstrated good efficiency in her arthritis after five months of follow-up (Disease Activity score-28 of 2.8), but her abnormal liver function tests persisted.

Discussion

The studies suggest that the prevalence of RA in PBC patients is between 1.8% and 5.6%. 3 The association between PBC and RA has raised questions about the hepatotoxicity of RA drug. 4 In this case, we examined the effects on safety and immunological selective B-cell depletion using rituximab (an anti-cluster of differentiation 20 monoclonal antibody) with low-dose MTX in a patient with PBC and RA. In our patient, we used a small amount of MTX (7.5mg/week) combined with two doses of 1000mg of rituximab, two weeks apart. After five months of follow-up, we observed a good clinical and biological response of her RA although there were persistent abnormalities in her liver tests. Another two cases have been reported where the patients were treated with etanercept and MTX 4mg/week, obtaining a significant improvement in disease activity and liver function, maintained one year after starting etanercept. 5,6  Further studies are needed to determine the relationship between these two diseases; in particular, an investigation of PBC occurrence in large RA patient cohorts is needed.

Learning

B cells seem to play a major role in the pathogenesis of both rheumatoid arthritis and primary biliary cirrhosis. Additional studies are necessary to better determine the therapeutic role of rituximab in both diseases.

Reference

  1. Caramella C, Avouac J, Sogni P, Puéchal X, Kahan A, Allanore Y: Association between rheumatoid arthritis and primary biliary cirrhosis. Joint Bone Spine 2007, 74:279–281.
  2. Tsuda M, Moritoki Y, Lian ZX, Zhang W, Yoshida K, et al : Biochemical and immunologic effects of rituximab in patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Hepatology 2012, 55:512–521
  3. Marasini B, Gagetta M, Rossi V, Ferrari P: Rheumatic disorders and primary biliary cirrhosis: an appraisal of 170 Italian patients. Ann Rheum Dis 2001, 60:1046–1049
  4. Bach N, Bodian C, Bodenheimer H, Croen E, Berk P, et al: Methotrexate therapy for primary biliary cirrhosis. Am J Gastroenterol 2003, 98:187–193.
  5. Kubo S, Iwata S, Saito K, Tanaka Y: Successful treatment of primary biliary cirrhosis with etanercept in a patient with rheumatoid arthritis. Joint Bone Spine 2011, 78:535–536.
  6. Ogata A, Terabe F, Nakanishi K, Kawai M, Kuwahara Y, Hirano T, Arimitsu J, Hagihara K, Shima Y, Narazaki M, Tanaka T, Kawase I: Etanercept improved primary biliary cirrhosis associated with rheumatoid arthritis. Joint Bone Spine 2009, 76:104–116.
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