Biological Agents and the Risk of Mycobacterial Disease: A Primary Care Concern


Dr Rutecki is professor of medicine at the University of South Alabama College of Medicine in Mobile. He is also a member of the editorial board of CONSULTANT.

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Which patients who are receiving biological therapy are at greatest risk for mycobacterial infections?

Tuberculosis (TB) is uncommon in the United States, especially when rates here are compared with those in endemic locations, such as Cambodia, Thailand, Kenya, Malawi, and Cameroon.1 In fact, in the United States, non-tuberculous mycobacterial (NTM) disease is now more prevalent than TB.2

How might these facts impact primary care practice? Immunity against either Mycobacterium tuberculosis or NTM infections relies on the body’s production of tumor necrosis factor (TNF), interferon, and interleukin. Contemporary aggressive treatment of crippling arthritides (e.g., rheumatoid arthritis [RA] and psoriatic arthritis) liberally utilizes the so-called “biologicals”—agents that may be associated with activation of latent mycobacterial infections through attenuation of TNF and other protective responses. How can primary care physicians increase their vigilance for those patients who take biologicals and may be at increased risk? This month’s “Top Paper” offers some helpful pointers.2


First, in regard to TB, the results of skin tests (either Mantoux or purified protein derivative [PPD]) can be false-negative in 20% to 25% of patients with active TB who are not simultaneously infected with HIV. How does this fact change the approach to screening? Higher-risk patients, that is, persons from endemic areas or those exposed as a result of travel, may be better served by the QuantiFERON-TB Gold test, which is more sensitive in persons with RA from TB-endemic areas.

A second important point regarding TB was clarified. Treatment of latent TB in these same patients
requires isoniazid (for 6 to 9 months), but the regimen should also include a second agent, rifampin, for 4 months. Dr Iseman2 cautioned that while patients are receiving biological therapy, they might require more than one course of therapy for latent TB.


NTM infections are especially troublesome in this population because they often present subtly. These infections may be either pulmonary or extrapulmonary. Anti-TNF agents can be associated with serious NTM disease. 

Which patients are particularly at risk? Those with chronic obstructive pulmonary disease, silicosis, cystic fibrosis, gastroesophageal reflux disease, and lung diseases associated with the primary disease being treated with biologicals, such as RA, are considered at high risk. Another valuable caveat was offered in this context: otherwise healthy white women who are slender and taller than average seem predisposed to NTM infection as well. In addition, if patients complain of a chronic cough or have a history of recurrent pneumonia, or if they have an abnormal chest radiograph or
CT scan, a specialist should evaluate them before they commence biological therapies. Of the many risk factors for NTM infection, bronchiectasis seems to be the most prominent. 

Dr Iseman’s article clarified my thinking about a substantive primary care role in co-managing patients with my rheumatology colleagues. Much of his content that addressed NTM infection was new to me. I will be more attentive to his suggestions in a primary care practice increasingly populated with patients who are receiving biological therapies.■


1. Bonnet MM, Pinoges LL, Varaine FF, et al. Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden. AIDS. 2006;20:1275-1279.
2. Iseman MD. Mycobacterial infections in the era of modern biologic agents. Am J Med Sci.2011;341:278-280.

Dr Rutecki reports that he has no relevant financial relationships to disclose.