PORTLAND, Ore. - Patients with suspicious, productive coughs should be worked up to rule out atypical mycobacterial infections before they are treated with tumor necrosis factor inhibitors, even if their chest x-rays and tuberculosis tests are negative, according to Dr. Kevin Winthrop.
"These biologics seem to promote mycobacterial growth; you have to be careful an infection isn’t hiding," he said at the annual meeting of the Society for Pediatric Dermatology.
Chest x-rays are not sensitive enough to pick up infection by Micobacterium avium and other nontuberculous mycobacteria (NTM), which are twice as likely to cause pulmonary infection in the United States as M. tuberculosis is, Dr. Winthrop of the division of infectious diseases at Oregon Health and Science University, Portland, said in a later interview.
Chest computed tomography and sputum culture are typically needed to make the diagnosis.
It's important information for dermatologists because tumor necrosis factor (TNF) inhibitors are being used “more and more in dermatology,” he said.
Adalimumab, etanercept, and infliximab are indicated for plaque psoriasis; those and other TNF inhibitors have been tried off label for many ailments with dermatologic manifestations, including Behçet’s disease, Crohn’s disease, dermatomyositis, and scleroderma (J. Cutan. Med. Surg. 2005;9:296-302).
Black boxes on product labels warn that TNF inhibition increases the risk of TB, but the risk of NTM infection is not similarly emphasized.
Dr. Winthrop and his colleagues identified 105 anti-TNF therapy–associated NTM infections in FDA’s MedWatch database between 1999 and 2006; 56% were pulmonary, 26% skin and soft tissue, 9% bone and joint, and 8% disseminated. There was one eye infection; overall, M. avium caused half of the infections (Emerg. Infect. Dis. 2009:15:1556-61).
Most of the patients were older women treated for rheumatoid arthritis; only a few of the cases were associated with psoriasis therapy, but TNF inhibitors were not indicated for psoriasis during most of the study period.
Seventy-three infections in the MedWatch database were associated with infliximab, 25 with etanercept, and 7 with adalimumab.
"Use of infliximab may pose a greater risk for NTM disease. If true, the risk could be caused by the drug itself or differences in the characteristics of patients given infliximab relative to users of the other anti-TNF-alpha compounds," Dr. Winthrop and his colleagues wrote.
"Infliximab users were more likely to be concomitantly using methotrexate at the time of diagnosis," they said.
During his presentation at the annual meeting, Dr. Winthrop said he suspects the number of anti-TNF–associated NTM infections is "much lower" in psoriasis than in rheumatoid arthritis, which can affect the lungs and increase susceptibility to opportunistic infection by nontuberculous mycobacteria, which are ubiquitous in soil and water.
He and his colleagues noted in their report, however, that MedWatch – a voluntary reporting system – likely underestimated the incidence of TNF blocker–associated NTM infection.
A large, epidemiologic safety study of TNF inhibitors and other biologics is underway, and should further define the risks of NTM infections in dermatology patients, said Dr. Winthrop, a coinvestigator in the project. Results could begin to be published in 2011.
He said M. avium is most likely to infect the lungs, while Micobacterium abscessus, Micobacterium chelonae, Micobacterium marinum, and Micobacterium fortuitum are more likely to infect skin and soft tissue.
Micobacterium kansasii is a likely pathogen of both skin and lung in the Southern United States, he said.
As with pulmonary infections, NTM skin infections are difficult to diagnose; diagnosis typically requires a punch biopsy along with a culture or polymerase chain reaction analysis.
NTM infections do not typically respond to TB antibiotics; other antibiotics must be used in combination, Dr. Winthrop said.
Pulmonary infections typically are treated for 18 months, longer than for TB, because NTM infections are generally less susceptible to antibiotics.
Disclosures: Dr. Winthrop said he has no conflicts of interests.