We read with interest the Case Study from Van Ingen et al. in which they describe a pulmonary Mycobacterium szulgai infection in a patient receiving anti-tumor necrosis factor (TNF) therapy. Their report highlights an emerging and heretofore poorly recognized serious infection that can occur under conditions of TNF blockade. With this Article Response, we wish to alert clinicians of the updated nontuberculous mycobacterium (NTM) diagnostic criteria, and suggest that NTM disease is probably under-recognized in the setting of TNF blockade.
In this case, NTM was not diagnosed in the patient until 18 months after his initial presentation and first bronchoscopy yielded M. szulgai. Because NTM are environmental organisms and can colonize airway surfaces (and contaminate cultures), previous guidelines mandated that patients have multiple respiratory samples positive for NTM, or one positive sample along with evidence of tissue invasion, before meeting diagnostic criteria for pulmonary disease. These 1997 criteria were cumbersome and could be difficult to apply to individual patients as some of the criteria relied upon quantitative cultures, a practice infrequently employed by clinical laboratories (1). With the recent issue of 2007 guidelines from the American Thoracic Society and Infectious Diseases Society of America, the diagnostic criteria have been updated and simplified (2,3). With a decade of additional experience, it is apparent that NTM pulmonary disease can be diagnosed earlier within the right clinical setting. Patient's with underlying lung architectural abnormalities from rheumatoid arthritis, sjogren's syndrome, chronic obstructive pulmonary disease, tuberculosis, bronchiectasis, and others are at risk for NTM. In the setting of symptoms and chest computed tomography (CT) findings of fibronodular opacities or cavitary disease, a patient with one positive culture from bronchoalveolar lavage (or two positive cultures from sputum) now meet diagnostic criteria. Had these criteria been in place at the time of this patient's first presentation, he would have met the case definition at that time, presumably been started on antibiotic therapy, and potentially spared from some of the lung damage apparent on subsequent CT scans.
Lastly, the authors correctly state that reports of TB during anti-TNF therapy are more numerous than NTM (4). Although they propose several potential explanations for this, we believe NTM is under-recognized relative to TB. In contrast to TB, NTM disease is not reportable within the US, is more difficult to diagnose, and frequently goes unrecognized for months to years before being identified. These factors could alone explain the greater recognition of TB in the anti-TNF setting. We recently queried a national network of Infectious Diseases specialists in the US (the Emerging Infection Network) asking for recent infections associated with anti-TNF therapy (unpublished data). To date, we've received more reports of NTM disease (n=35) than TB (n=12). It might be that in areas of low TB prevalence, NTM in the anti-TNF setting is more common than TB and more common than we currently think. For now, due to lack of study, the epidemiology of NTM is poorly understood, and definitive epidemiologic studies are needed.
References
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Winthrop, K., Daley, C. & Griffith, D. Nontuberuclous mycobacterial disease: updated diagnostic criteria for an under-recognized infectious complication of anti-tumor necrosis factor therapy. Nat Rev Rheumatol 3, E1 (2007). https://doi.org/10.1038/ncprheum0621
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DOI: https://doi.org/10.1038/ncprheum0621
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