Non-TB mycobacteria in endobronchial lesions similar to cervical adenitis

June 2007

Consider pulmonary nontuberculosis mycobacteria in otherwise healthy children who present with new-onset wheezing or stridor nonresponsive to bronchodilator therapy, according to Alexandra F. Freeman, MD.

Freeman, a staff clinician at the National Institute of Allergy and Infectious Diseases for the NIH and an assistant professor of pediatric infectious diseases at Georgetown University Hospital in Washington, and colleagues analyzed five otherwise healthy children diagnosed with pulmonary nontuberculosis mycobacteria disease for cystic fibrosis transmembrane mutations and immunologic abnormalities.

The researchers found no mutations or abnormalities, according to Freeman, who suggests clinicians be cognizant of pulmonary nontuberculosis mycobacteria when presented with children with certain symptoms.

“Pulmonary mycobacteria disease can effect otherwise healthy children in causing enlarged lymph nodes in the chest that are similar to the enlarged lymph nodes in the neck of healthy children who have nontuberculosis mycobacteria disease,” Freeman told Infectious Diseases in Children.

It is important to obtain a biopsy or culture first to rule out a malignancy or tuberculosis, she said.

Freeman and colleagues presented the data at The Pediatric Academic Societies’ Annual Meeting in Toronto.

Presentation and treatment

Although nontuberculosis mycobacteria is not uncommon, it usually manifests in the neck and is usually treated with removal, according to Freeman.

“These children, for whatever reason, are getting the diseases in the lymph nodes next to their lungs, and then that causes compression of the lungs, which leads to problems,” Freeman said.

Freeman and colleagues analyzed five children aged 12 months to 2.5 years who all appeared immunocompetent and were otherwise healthy.

One of the children, a 12-month-old boy, was asymptomatic, but the four other children presented with new-onset wheezing or stridor.

The asymptomatic child received a tuberculin skin test during a well-child visit, which led to his diagnosis.

All of the children in the study had hilar lymph nodes and/or endobronchial lesions that caused bronchial obstruction, according to the researchers.

“What was interesting, [the children] all presented in a similar fashion: very little in terms of systemic symptoms like fever and weight loss, but they all presented with stridor or wheezing that was unresponsive to therapy. They were all similar ages with similar findings on their chest computed tomographies,” Freeman said.

Researchers performed immunologic studies which included a complete blood cell count, serum quantitative immunoglobulins, flow cytometry for lymphocyte phenotyping and interferon-gamma reception expression, and cytokine analysis measured interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, interferon-g, IL-1b and IL-12 with peripheral blood mononuclear cell at rest and following the stimulation with PHA, PHA+IL-12, LPS and LPS+IFN-g.

The laboratory responses were normal, according to the researchers. One of the children had a mildly decreased serum immunoglobulin G, but cytokine analysis found no clear abnormalities.

The researchers cultured Mycobacterium abscessus from one of the children, M. avium complex from two children and M. avium-intracellulare from two children; they treated all of the children with anti-mycobacterial therapy.

The researchers said the mycobacterial disease found in these children resembles the disease most commonly appearing as cervical adenitis in young, healthy children. However, exposure may be associated with these children with enlarged hilar lymph nodes with inhalation, as opposed to enlarged neck lymph nodes, which are probably associated with ingestion of mycobacteria through contaminated soil or water, Freeman said.

Freeman said that pulmonary nontuberculosis mycobacteria disease is increasingly seen among adults, especially in older women. However, in adults the disease is of the parenchyma of the lung and seems to have a higher incidence of mutations in the cystic fibrosis transmembrane regulator gene.

The researchers found no higher incidence of cystic fibrosis transmembrane regulator mutations among these children, however, Freeman said.

Treatment

After obtaining the biopsy and ruling out other etiologies, Freeman recommended antibiotic therapy for the children. However, the length and effectiveness of multiple combinations remains unknown, she said.

The children they analyzed all responded well, but the sample was too small of a group to determine the best therapy option.

“Just keep this in your differential. If you see someone with enlarged hilar lymph nodes that is in the toddler-age group, in addition to thinking about TB or malignancy, nontuberculosis mycobacteria should be considered, and extensive immunologic evaluation in otherwise healthy children is not necessary,” Freeman said.

Follow-up lasted from two to eight years; the researchers found no disseminated mycobacterial disease, opportunistic infection or immunodeficiencies in any of the children.

For more information:

• Freeman AF, Demidowich A, Rubio TT, et al. Pulmonary nontuberculosis mycobacterial infections in otherwise healthy children. Presented at: The Pediatric Academic Societies’ Annual Meeting. May 5-8, 2007; Toronto.