Etanercept or Mycobacterium Lung Injury?

Abstract

We have significant questions regarding the recent report “Lung Injury Linked to Etanercept Injury” (November 2002). 1 Peno-Green L Lluberas G Kingsley T et al. Lung injury linked to etanercept therapy. Chest. 2002; 122: 1858-1860 Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar The authors’ final diagnosis was drug-induced lung injury due to etanercept, but we suggest that the data are more consistent with either hypersensitivity pneumonitis or miliary infection, both probably related to Mycobacterium avium complex. The clinical presentation, pathology, findings of loosely cohesive noncaseating granulomas, and resolution after administration of prednisone therapy are consistent with hypersensitivity pneumonitis, possibly in response to inhaled Mycobacterium avium-intracellulare complex (MAC). Hypersensitivity pneumonitis associated with exposures to nontuberculous mycobacteria has been associated with exposures in hot tubs 2 Embil J Warren P Yakrus M et al. Pulmonary illness associated with exposure to Mycobacterium-avium complex in hot tub water. Chest. 1997; 111: 813-816 Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar or to metalworking fluids. No environmental or occupational history was provided in the case description. Had the patient used a hot tub or had other potential exposures? Alternatively, the multifocal pulmonary lesions and noncaseating granulomas in the skin lesions are also consistent with disseminated mycobacterial infection. There was no mention of special stains or cultures of the skin lesions, which would have been helpful in establishing this diagnosis. The authors did not address reports of reactivation tuberculosis associated with tumor necrosis factor (TNF)-α inhibitors. Although most cases have been associated with infliximab, 3 Keane J Gershon S Wise RP et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001; 345: 1098-1104 Crossref PubMed Scopus (3279) Google Scholar etanercept has been associated with 11 cases of tuberculosis, 3 of which (27%) were disseminated, and 5 of which (45%) were fatal. 4 Day R. Adverse reactions to TNF-alpha inhibitors in rheumatoid arthritis. Lancet. 2002; 359: 540-541 Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Of note, etanercept has been associated with eight cases of nontuberculous mycobacterial disease as well. 5 Cush JJ Matteson EL FDA advisory committee reviews safety of TNF inhibitors: ACR Hotline. Atlanta, GA: American College of Rheumatology. 2001; Google Scholar Could miliary MAC resolve without antibiotic therapy? Yes, based on analogy to the involution of MAC with reconstitution of immunity in AIDS or hairy-cell leukemia.