Nontuberculous Mycobacterium Infection and Tumor Necrosis Factor-α Antagonists

To the Editor: Mycobacterium haemophilum is an aerobic, slowgrowing microorganism with optimal growth at 30°C to 32°C. It has a unique requirement for ferric iron–containing compounds (1), from which it acquired its name (i.e., haemophilum). Infections with M. haemophilum are rare, but cervicofacial lymphadenitis caused by M. haemophilum has been described in children (2). Besides cervicofacial lymphadenitis, extrapulmonary signs of M. haemophilum disease include subcutaneous noduli, arthritis, and osteomyelitis, which generally affect immunocompromised patients (3). Recently, 2 cases of cutaneous M. haemophilum infections after alemtuzumab treatment were reported (4). A small number of pulmonary M. haemophilum infections associated with AIDS or solid organ or bone marrow transplantation have been described (1). We report pulmonary M. haemophilum infection in a woman who had been immunosuppressed by tumor necrosis factor-α antagonist (TNF-αA) (adalimumab) treatment for rheumatoid arthritis. A 72-year-old woman with a history of rheumatoid arthritis and obstructive sleep apnea syndrome had signs and symptoms of fatigue, mild fever episodes, and a nonproductive cough 9 months after treatment for rheumatoid arthritis had begun with methotrexate (MTX) and TNF-αA. Physical examination was unremarkable except for a body temperature of 38.9°C. Laboratory testing showed an increased erythrocyte sedimentation rate (ESR) (77 mm/h), an increased Creactive protein (CRP) level (60 mg/L), a normal leukocyte count (8,500 cells/ μL), and relative monocytosis (12%). HIV serologic testing results were negative. Chest radiograph showed an infiltrate in the right upper lobe. Chest computed tomography confirmed this finding and showed lymphadenopathy in the right hilus and mediastinum. Notably, the tuberculin skin test result was negative at screening before she began the TNF-αA treatment, but was now positive (20 mm), suggesting mycobacterial infection. Auramine and Ziehl-Neelsen staining of sputum and bronchoalveolar liquids showed no acid-fast bacilli, and M. tuberculosis infection was not confirmed by PCR or culture. Eventually, a mediastinal lymph node biopsy was taken by endoscopic ultrasound guidance. Granulomatous inflammation and acid-fast bacilli were seen by microscopy. Corresponding cultures yielded a strain identified as M. haemophilum at the Netherlands National Institute for Public Health and the Environment (RIVM) by using the Inno-LiPA Mycobacteria v2 reverse line blot assay (Innogenetics, Ghent, Belgium). Strain identity was confirmed by sequencing of the complete 16S rDNA gene, which was identical to that of M. haemophilum available in the GenBank sequence database (National Center for Biotechnology Information; www.ncbi.nlm.nih.gov; accession no. X88923). The RIVM performed drug susceptibility testing by using a modified agar dilution method (5). Middlebrook 7H10 media were enriched with 10% sheep blood hemolyzed by 1:1 dilution with water and subsequent freezing–thawing. Historic drug susceptibility data was reviewed (Table). Initially, adalimumab was discontinued, and our patient was treated with isoniazid, ethambutol, rifampin, and pyrazinimide because M. tuberculosis infection was suspected. After identification of M. haemophilum, our patient was treated with rifampin and azithromycin. A total treatment duration of 10 months resulted in complete resolution of the