LETTERS TO THE EDITOR Peripheral Arthritis Caused by Mycobacterium avium- intracellulare in a Patient With Ankylosing Spondylitis To the Editor: W e read with interest the report by Lee who described an unusual case of My- cobacteria avium complex (MAC)-induced pleurisy in a patient with amyopathic dermato- myositis and interstitial lung disease following prolonged immunosuppressive therapy. 1 We would like to present a patient with a two-year history of ankylosing spondylitis (AS) who developed Mycobacterium avium-intracellu- lare arthritis of the left ankle after immunosup- pressive therapy. In March 2006, a 33-year-old Asian male was diagnosed with AS after he pre- sented with lower back pain that had per- sisted for more than 3 months, with bilateral grade III sacroiliitis and positive HLA-B27. Thereafter, he started to receive therapy con- sisting of nonsteroidal anti-inflammatory drugs (NSAIDs) and sulfasalazine. Four months be- fore his admission, pain and swelling with tenderness over the left ankle occurred, and he visited a clinic for an examination. At the clinic, he received an increased dosage of NSAIDs and sulfasalazine under the suspi- cion of AS flare up with peripheral arthritis. After one month, the arthritis with low-grade fever persisted. Treatment with methotrexate was commenced to control the peripheral arthritis, and this treatment was combined with NSAIDs and sulfasalazine. After 3 months, swelling over the left ankle with limitation of movement and intermittent low- grade fever was still noted. He was admitted to our hospital for further survey of mono- arthritis. There was swelling and local heat with tenderness over the left ankle but no significant signs of arthritis in the other joints. The patient denied having history of pulmo- nary tuberculosis and other medical illness. A complete blood count revealed 6360 WBC/ mm 3 , 76% neutrophils, 24% lymphocytes, 13 g/dL hematoglobin, 180,000 platelets/mm 3 , an erythrocyte sedimentation ratio 100 mm/h (N  25), and 7.48 mg/dL C-reactive protein (N  0.5). Liver and renal function tests were both normal. An immunologic study revealed the patient to be negative for rheumatoid factor and antinuclear antibody. Bacterial and TB cultures from sputum were negative. Serologic tests for viruses, includ- ing CMV, EBV and HIV, were also nega- tive. A chest x-ray was normal. Plain film of the left ankle showed mild sclerotic change of the subtalar joint with bony erosion of the calcaneus, suggesting inflammatory arthritis. Magnetic resonance imaging (MRI) revealed synovial thickening with several hypointense nodules in the talus, subtalar joint, and around the posterior tibialis tendon on T1- weighted images; these nodules showed hy- perintensity on T2-weighted images. The MRI diagnosis of septic arthritis with ab- scesses was suggested. Subsequently, 1 mL turbid synovial fluid was aspired under ultra- sound-guided arthrocentesis. Although ini- tial bacterial culture and acid-fast stain for tuberculosis of the synovial fluid were neg- ative, surgical debridement and biopsy of the left ankle was still performed under the sus- picion of septic arthritis. The pathologic tests revealed acute necrotizing inflammation with multiple foci of calcification of soft tissue surrounding granulomas and a few multinu- cleated giant cells. One month later, M. avium- intracellulare was identified from a soft tissue culture. The patient was treated with 1000 mg clarithromycin, 800 mg ethambutol, and 300 mg rifabutin daily and has shown a good clin- ical response. Extraspinal manifestations in patients with AS include peripheral arthritis, enthesi- tis, acute anterior uveitis, and pulmonary and cardiac involvement. Approximately 10% of the patients have significant peripheral arthri- tis. 2 The pathogens in nontuberculosis myco- bacterial (NTM) infections include MAC, M. fortuitum, M. kansasii, M. mariunum, and M. xenopi with a prevalence rate of 1.8 cases per 100,000. 3 The most common type of NTM is MAC. Most patients with MAC infection have pulmonary or disseminated diseases. Most NTM pulmonary infections give rise to variable chest radiographic findings with posi- tive sputum and blood cultures. Rarely, pa- tients have only skeletal involvement and there are no significant systemic symptoms. MRI or computed tomography may help to localize lesions. In immunocompromised subjects, such as HIV-positive patients or these receiv- ing immunosuppressive treatments, there ap- pears to be an increased risk of developing this opportunistic infection. NTM septic arthritis can occur in those patients with rheumatic diseases, including systemic lupus erythemato- sus, polymyositis, and rheumatoid arthritis, be- cause these patients receive immunosuppres- sive drug treatment over a long term. 4–7 These immunosuppressive drugs include azathoprine, oral corticosteroids, intra-articular corticoste- roids, cyclosporine, and biologic agents. 8 Our patient is receiving long-term medication of sulfasalazine. Sulfasalazine has many anti-inflammatory and immuno- suppressive properties including inhibition of prostaglandin and leukotriene synthesis, free radical scavenging, immunosuppressive activity, impairment of white cell adhesion and function, inhibition of cytokine synthe- sis. This case seems to be an increased risk of developing this opportunistic infection due to receiving immunosuppressive treatments. However, no M. avium-intracellulare was detected in the initial culture of synovial fluid aspirate. Significant pulmonary symp- toms or image finding were not found in our case. A synovial biopsy was required to confirm the infection. In patients with AS, peripheral arthritis including that of the knees, wrists, ankles and feet, can develop during the course of the disease. The indolent nature of tuberculous bone and joint disease may lead to delayed or missed diagnosis because rheumatologists easily suspect AS flare with peripheral arthritis. Deng-Ho Yang, MD Division of Rheumatology/Immunology/ Allergy Department of Internal Medicine Armed-Forces Taichung General Hospital Taichung, Taiwan Division of Rheumatology/Immunology/ Allergy Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Wei-Chou Chang, MD Department of Radiology Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Ming-Fang Cheng, MD Department of Pathology Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Jenn-Haung Lai, PhD Deh-Ming Chang, PhD Chen-Hung Chen, MD* Division of Rheumatology/Immunology/ Allergy Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan *deng6263@pchome.com.tw REFERENCES 1. Lee HT, Su WJ, Chou TY, et al. Mycobacteria avium complex-induced pleurisy in a patient with amyopathic dermatomyositis and interstitial lung disease after prolonged immunosuppressive ther- apy. J Clin Rheumatol. 2009;15:193–194. 2. Collantes E, Zarco P, Munoz E, et al. Disease pattern of spondyloarthropathies in Spain: description of the first national registry (REGISPONSER)-extended re- port. Rheumatology. 2007;46:1309 –1315. 3. O’Brien RJ, Geiter LJ, Snider DE Jr. The epide- miology of nontuberculous mycobacterial disease JCR: Journal of Clinical Rheumatology • Volume 15, Number 6, September 2009 323