Successful treatment with infliximab of refractory rheumatoid arthritis in a male with ‘GDF5 brachydactyly’

Abstract

GDF5 (growth diVerentiation factor-5, also known as cartilage-derived morphogenetic protein-1, CDMP1) is a secretable molecule that participates in skeletal morphogenesis [1]. In humans, homozygous and compound heterozygous GDF5 mutations cause acromesomelic chondrodysplasia (Hunter-Thompson and Grebe type), and heterozygous mutations can lead to a wide range of phenotypes, from brachydactyly type C (BDC) to no discernible clinical and radiological Wndings at all [2–4]. Recently, GDF5 has been reported to be a susceptible gene for osteoarthritis in Asian populations [5]. Here we describe a case of severe RA accompanied by brachydactyly caused by a GDF5 mutation. The Japanese male patient was born in 1939. He was noted to have short second, third and Wfth Wngers in bilateral hands shortly after birth. His elder brother also has short Wngers. None of his family has been aVected with arthritis. The patient’s joint disease started in January 1997 with a swollen and tender left shoulder. Subsequently, he developed polyarthritis involving bilateral shoulders, wrists, knees, ankles and Wnger joints accompanied with typical morning stiVness. Rheumatoid nodules were not observed. Rheumatoid factor was positive with a high titer. Diagnosis of RA was made according to the criteria of the American College of Rheumatology, and he was initially treated with nonsteroidal anti-inXammatory drugs and low dose corticosteroid (5 mg of predonisolone daily). Then, he was referred to our hospital in January 1998. X-ray examination of his hands revealed shortness of middle phalanx of bilateral second, third and Wfth Wngers, which is a typical feature of BDC. Periarticular osteoporosis was consistent with early RA. Osteoarthritis was not remarkable (Fig. 1). Neither sulfasalazine nor buccillamine was found to be eVective in this case and C-reactive protein concentration was kept at high levels and Xuctuated between 6 and 10 mg/dl. Methotrexate was next subscribed, but prematurely discontinued due to interstitial pneumonia. Subsequently, azathioprine and minocycline were administrated with only minimal eVects. Bilateral knee joints were severely swollen and joint aspiration and intra-articular administration of steroids were frequently needed. Disease activity was persistently high, and joint damage progressed. Therefore, we decided to employ inXiximab that had just