Recurrent multifocal Mycobacterium kansasii infection in an immunosuppressed patient with myelodysplasia and relapsing polychondritis

N. Benton1, S. Musaad2, R. Vaughan3 and L. McLean1,2

Departments of 1 Rheumatology and 3 Microbiology, Auckland Hospital and 2 Department of Molecular Medicine, University of Auckland, Auckland, New Zealand

Correspondence to: L. McLean, Clinical Immunology and Analgesia, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. E-mail: Lachy_McLean{at}merck.com

SIR, Atypical infections are a common complication of immunosupression. Musculoskeletal sepsis presents particular challenges when the clinical course of the infection is unusual or could be confused with the primary diagnosis, the organism is atypical, and comorbidity imposes limits on treatment. Mycobacterial infections are not limited to the biological TNF-{alpha} antagonists or to Mycobacterium tuberculosis. A 69-yr-old Caucasian man was admitted under our rheumatology service with right ankle and heel pain. Over a 4-week period this had worsened to the extent that he was unable to weight-bear and required narcotic analgesics. There was diffuse soft tissue swelling of the ankle and a tender erythematous area over the right lateral malleolus. He looked unwell and was febrile (38.6°C). His significant past history included relapsing polychondritis, which featured peripheral joint synovitis. He had an excellent response to prednisone at an initial dose of 60 mg daily but was unable to taper this below 20 mg without flares in his arthritis, and an attempt to introduce azathioprine was unsuccessful because of a marked cutaneous reaction. Haematological monitoring revealed a progressive decline in leucocyte, red cell and platelet counts, and a bone marrow biopsy showed a myelodysplastic syndrome for which he subsequently became transfusion-dependent and which complicated further attempts to introduce steroid-sparing agents.

Approximately 2 yr prior to the index admission he presented with a 1-month history of intermittent fever as high as 39.0°C, unplanned weight loss of 9 kg, worsening bilateral knee and ankle arthritis, and enlarging soft-tissue swellings overlying the bridge of the nose and the right third MCP joint. A 5 mm superficial ulcer had developed over the affected MCP, with no history of local trauma recalled. There was no lymphadenopathy. He had no respiratory symptoms or abnormal clinical signs, and a chest radiograph was normal. Six sets of blood cultures and a urine culture were negative, and aspirates of the knees were sterile. Swabs from the skin lesion overlying the MCP showed a mild neutrophil infiltrate and a slow growing acid-fast bacillus initially suggestive of Mycobacterium marinum but later identified as M. kansasii (see below). In vitro antibiotic sensitivities included rifampicin, ethambutol, ciprofloxacin and clarithromycin. He was a retired engineer and could not identify any source of environmental exposure to atypical mycobacteria. Six months of treatment with rifampicin 600 mg and ethambutol 800 mg daily had been associated with complete clinical resolution of the nasal and MCP lesions, and his arthritis improved in phase with this.

Three months after finishing the antimycobacterial therapy he presented again with fever, severe polyarticular arthritis and new peripheral skin lesions. Turbid green fluid was aspirated from a fluctuant subcutaneous lesion overlying the left second MCP joint, which had been clinically uninvolved in the prior presentation, and acid-fast bacilli (AFB; 1–10 per high-power field) were seen on direct microscopy. On this occasion the rifampicin/ethambutol antimycobacterial regimen was associated with intolerable nausea and was changed to ciprofloxacin 500 mg twice daily and clarithromycin 500 mg twice daily for a period of 12 months, finishing 2 months prior to the current presentation.

On the current presentation, plain radiographs of the affected ankle were unremarkable (Fig. 1a and b). Aspiration of the right ankle joint and a skin biopsy of the erythematous area did not show AFB, and mycobacterial cultures were negative. However, magnetic resonance imaging (MRI) showed appearances in keeping with a bone abscess (Fig. 1c and d). A calcaneal biopsy confirmed AFB within the aspirated material and he was recommenced on ciprofloxacin and clarithromycin. Mycobacterial cultures on this occasion indicated that the causative organism was M. kansasii, based on the microscopic appearance of a long bacillus with a typical beading appearance and photochromogenic properties with colonies of the organism turning bright yellow on exposure to light. Sequencing of the organism's 16S rRNA and 65 kDa heat shock protein gene regions showed complete homology with sequence AF480601 for M. kansasii. Following this episode the ciprofloxacin/clarithromycin regimen was continued indefinitely. Two months later he was able to discontinue narcotic analgesics and was walking without aids.



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FIG. 1. Imaging studies at the second clinical recurrence. Anteroposterior (a) and lateral (b) radiographs. Coronal (c) and sagittal (d) T2-weighted MRI with gadolinium contrast.

 
This case of twice-recurrent and multifocal infection with an atypical organism is very unusual. M. kansasii is a rare cause of musculoskeletal infection, with only 11 previous documented cases, and recent case reports have reviewed this limited literature [1, 2]. In our patient the definitive identification of the organism was obtained at sequence level. Multifocal M. kansasii infection has previously been reported in patients with acquired immunodeficiency syndrome [3]. It is likely that the clinical septic episodes at different sites and on widely separated occasions in this patient represent foci that were established during systemic dissemination prior to the initial presentation, and which were not eliminated despite the first two courses of antimycobacterial therapy (6 and 12 months respectively), which had been deemed successful because of clinical resolution of the lesions. Because of this patient's advanced (transfusion-dependent) myelodysplastic syndrome and the high doses of systemic corticosteroids needed to control his polychondritis and arthritis, he was significantly immunosuppressed. Guidelines for the treatment of atypical mycobacterial infection in immunosuppressed subjects emphasize extended therapy [4, 5]. Although a large prospective study of pulmonary M. kansasii demonstrated almost complete success using a 9-month regimen of rifampicin and ethambutol [6], the evidence base for treating extrapulmonary disease is limited. In the context of HIV/AIDS, multidrug therapy of disseminated atypical mycobacterial infection is usually lifelong.

This case illustrates the difficulties in diagnosing and treating atypical mycobacterial infection associated with immunosuppression and adds to the very limited experience with musculoskeletal M. kansasii infection. An extended course of antimycobacterial therapy had been perceived as greatly reducing the chances of further musculoskeletal sepsis. With hindsight, his antimycobacterial regimen should have been continued indefinitely from the time of his initial presentation.

The authors have declared no conflicts of interest.

References

  1. Bernard L, Vincent V, Lortholary O et al. Mycobacterium kansasii septic arthritis: French retrospective study of 5 years and review. Clin Infect Dis 1999;29:1455–60.[CrossRef][ISI][Medline]
  2. Nakamura T, Yamamura Y, Tsuruta T, Tomoda K, Sakaguchi M, Tsukano M. Mycobacterium kansasii arthritis of the foot in a patient with systemic lupus erythematosus. Intern Med 2001;40:1045–9.[ISI][Medline]
  3. Capdevila O, Zurita A, Domingo E et al. Multiple cranial osteolytic lesions due to Mycobacterium kansasii in a patient with AIDS. Scand J Infect Dis 1998;30:305–6.[CrossRef][ISI][Medline]
  4. Scientific Assembly on Microbiology, Tuberculosis, and Pulmonary Infections, American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Resp Crit Care Med 1997;156:S1–25.[ISI][Medline]
  5. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society. Management of opportunist mycobacterial infections: Joint Tuberculosis Committee guidelines 1999. Thorax 2000; 55:210–8.[Free Full Text]
  6. British Thoracic Society. Mycobacterium kansasii pulmonary infection: a prospective study of the results of nine months of treatment with rifampicin and ethambutol. Thorax 1994;49:442–5.[Abstract]
Accepted 28 June 2004





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