Mycobacterium intracellulare Pulmonary Disease with Endobronchial Caseation in a Patient Treated with Methotrexate
A 58-year old woman was admitted to our hospital with a two month history of a worsening productive cough, fatigue and fever. The patient had a 20 year history of RA involving primarily her hands and wrists, and her disease had become refractory to multiple non-steroidal anti-inflammatory drugs over the past several years. Three year ago, the patient had commenced treatment with MTX at a dose of 12.5 mg per week with concomitant acetaminophen 650 mg twice daily. She had achieved control with these medications. She has never had a similar respiratory problem before. She also complained of mild chest pain, shortness of breath, night sweats and anorexia. The shortness of breath was progressive in nature and it was aggravated by strenuous activities and it subsided when taking a rest.\nOn physical examination, the patient appeared chronically ill. She was appropriately alert and oriented. She has a body temperature of 37.8℃ and regular heart rhythm with a rate of 80 beats/min. Her blood pressure was 140/80 mm Hg and the respiratory rate was 25 breaths/min. The respiratory system examination was entirely normal except for bibasilar crackles noted on auscultation.\nAt the time of presentation a complete blood cell count showed a hemoglobin level of 10.9 g/dL and a white blood cell of 6,380 cells/mm3 with 74% neutrophils, and 20% lymphocytes. The other laboratory results were as follows: the erythrocyte sedimentation rate was 28 mm/hr, the C-reactive protein was 6.33 mg/dL, the RA factor was 27.7 IU/mL and the anti nuclear antibody, the anti-neutrophil cytoplasmic antibodies and the anti-ds-DNA were all negative. The anti-human immunodeficiency virus (HIV) antibody was also negative. A chest X-ray revealed multifocal nodular consolidation and ill-defined nodules in both lungs, and this was more prominent in the mid-lung field of the right lung and there was no evidence of mediastinal lymphadenopathy (). Bronchoscopy at this time revealed diffuse actively caseating endobronchial lesions in the left main and left upper lobar bronchus (). The bronchial biopsy specimen from the left main bronchus showed granulomatous inflammation with caseating necrosis (). Ziehl-Neelsen staining of the bronchial washing fluid and expectorated sputum showed acid-fast bacilli (AFB). The polymerase chain reaction test for the specific sequences of M. tuberculosis was negative.\nThe MTX was discontinued. Her RA was treated with hydroxychloroquine sulfate 100 mg twice daily, nambumetone 500 mg twice daily and acetaminophen 650 mg twice daily. She was empirically treated with isonizid (300 mg/day), rifampin (600 mg/day), ethambutol (800 mg/day), and pyrazinamide (1,500 mg/day) for tuberculosis pending the AFB culture results. Subsequently, the fever and cough subsided, and the fatigue and shortness of breath regressed. After 6 weeks, the mycobacterium culture of the sputum and bronchial washing fluid yielded M. intracellurare. The isonizid and pyrazinamide were discontinued. Antimycobacterial therapy was continued with rifampicin, ethambutol, and clarithromycin (500 mg twice daily) for 18 months with a good response. Follow up bronchoscopy after 2 months of therapy revealed that the actively caseating endobronchial lesion had completely resolved. At the return visits 3 and 6 months later, the patient was able to do most of her daily activities without respiratory symptoms, and she well tolerated the antimycobacterial medications without any adverse reactions. The chest X-ray checked at the end of the treatment showed normal findings.\nAt eight months after completing the antimycobacterial medications, the patient was still totally free of respiratory symptoms and the sputum culture for AFB was negative.