Mediastinal nontuberculous mycobacteria as a cause of pediatric airway obstruction

1. Introduction 

Nontuberculous mycobacterial (NTM) lymphadenitis is a common clinical scenario in the head and neck in immunocompetent children. The presentation of NTM infections as pulmonary disease is rare, with only 43 cases reported in the literature since 1930 [1]. Mandatory reporting of NTM is not required in United States, so exact data on incidence is not available. However the incidence of NTM is estimated to be 1–1.8 cases per 100,000 people in United States [2]. The Center for Disease Control and Prevention reported that one-third of mycobacterial cases isolated in U.S. were NTM, from 1979 to 1980 [3], [4]. The ratio of tuberculosis (TB) to NTM isolates declined from 3.2:1 between 1976 and 1981 to 1:1.6 between 1986 and 1991 [5]. The prevalence of TB has declined in the developed world and the relative proportion of mycobacterial disease due to NTM has increased [6].

Nontuberculous mycobacteria are ubiquitous in the environment and commonly reside in soil. Mycobacterium avium intracellulare has been cultured from household hot tap water [7]. NTM is considered endemic to certain geographic areas particularly mid and south western United States [8].

It is thought that the frequency of head and neck NTM in young children, typically toddlers, is due to the ease with which they encounter NTM organisms in their environment and their propensity to interact with their world through their oral cavity.

2. Case presentation 

A previously healthy 16-month-old male presented to the Pediatric Pulmonary clinic with 3 months of wheezing which had progressed to biphasic stridor. Initial assessment with a chest radiograph showed some left perihilar density. He was initially treated with a brief course of azithromycin with little improvement. Wheezing continued to worsen despite subsequent trials of albuterol, prednisone and antibiotics. The atypical history and non-resolving symptoms prompted a referral to the Pediatric Otolaryngology service for evaluation of a potential airway foreign body. At bronchoscopy (Fig. 1) a mass partially obstructing right main stem bronchus was found. Chest CT scan showed a 3.1cm×1.8cm heterogeneous subcarinal/azygoesophageal recess mass (Fig. 2) and a prominent 1.1cm×0.8cm left hilar lymph node. Mediastinoscopy and video assisted thoracoscopic surgery was performed by Pediatric Surgery to assess the nature of the mass. The intraoperative findings revealed a densely matted mass adherent to right main stem bronchus and a biopsy was taken. Histopathology showed necrotizing granulomatous lymphadenitis but AFB and fungal smears were negative.

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Fig. 1. Initial bronchoscopy showing NTM carinal and right main stem bronchial mass.

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Fig. 2. CT chest with contrast. Arrow indicates mass at carina with compression of both bronchial airways.

Empiric treatment for tuberculosis, tularemia and atypical mycobacteria was initiated. Subsequent cultures grew Mycobacterium avium intracellulare and the treatment was streamlined to clarithromycin, ciprofloxacin and rifampin for a 12-month course. The patient completed the treatment without complications. Follow-up interval bronchoscopies were performed at 3-month intervals and these showed gradual resolution of the granulomatous mass (Fig. 3, Fig. 4), with near total resolution of the mass at 12 months. Airway obstruction, stridor and wheezing resolved quickly after instigation of therapy without any further sequelae. Follow-up with the patient now at 1 year after completion of therapy reveals no indication of recurrent disease.

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Fig. 3. Bronchoscopy at 3 months showing some improvement.

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Fig. 4. Bronchoscopy at 9 months showing near complete resolution.

3. Discussion 

Endobronchial obstruction due to NTM lymphadenitis is rare. Knowledge of this clinical entity is important as the overall incidence of NTM infections is rising [9], [10], [11], [12]. Therapeutic approaches to these patients vary from surgical treatment, to combined medical and surgical therapy, to medical therapy alone with antibiotics and antituberculous drugs. The optimum management of immunocompetent children with NTM infections has not been clearly defined. The majority of studies are retrospective, do not specifically look at immunocompetent children, or include multiple antibiotic regimes as well as surgery, all of which further complicate a unifying management modality. Surgery is the usual treatment of choice for patients with head and neck lymphadenitis [13]. Fergusson and Simpson [14] noted that the time interval between surgery and healing was shorter for patients who had primary excision (median 3 weeks) compared to patients who received I&D/curettage (6 weeks). They also found a primary cure rate for curettage of 86% compared to 92% for excision [14]. The experience with pediatric cervical lymphadenitis from NTM may be applicable to intrathoracic disease in children but the experience with thoracic disease is much smaller. Surgical excision of localized pulmonary disease has been shown to have a role in the management of select cases where access is surgically possible and associated with low morbidity. Arguments against surgery have included the difficulty of excising an inflammatory mass proximal to critical structures, the risk of operative and anesthetic morbidity and mortality and the risk of disseminating disease throughout the thoracic cavity.

The beneficial effect of corticosteroids on tuberculosis in children with bronchial obstruction has been reported in several studies [15], [16]. Bronchoscopy has been advocated as a useful tool in the assessment of response to treatment in children with bronchial obstruction secondary to tuberculosis, and should also be considered in atypical mycobacterial disease [17]. The treatment of atypical mycobacterial infections has dramatically improved with the availability of new macrolides and rifabutin [18]. However there is little published data on the use and effects of these antibiotics in children. Clarithromycin has been shown to be of benefit in patients with AIDS and disseminated Mycobacterium avium complex [19], [20]. In retrospective studies antibiotics alone have shown to be effective for the treatment of cervical lymphadenitis [21]. The combination therapy of clarithromycin, ethambutol and rifabutin has been suggested as the optimum therapy for atypical mycobacterial pulmonary disease but randomized controlled studies are lacking [22], [23]. Some studies have shown that the use of antibiotic therapy can be an adjunct to surgery in treating and controlling disease [24]. The appropriate duration of the antibiotic therapy is dependent on the clinical response. However based on experiences with childhood tuberculosis, drug treatment of atypical mycobacterial pulmonary disease should probably be prescribed for 6–12 months. Close observation for recurrence after cessation of therapy is essential.

An overlying theme in all of the studies on pulmonary NTM is that all children with atypical mycobacterial pulmonary disease should have their immune function investigated including HIV status.

Additionally, owing to the increasing frequency and difficulty in the treatment of Mycobacterium avium complex pulmonary disease, it seems advisable to make it a reportable condition based on reasonable microbiological, radiographical and clinical criteria such as those recommended by American Thoracic Society [25].

4. Conclusion 

Pediatricians, pulmonologists and otolaryngologists should be increasingly aware of NTM in the differential diagnosis of persistent pulmonary disease or airway obstruction in previously healthy children. Further studies are required to establish the optimum treatment for these patients. Management currently requires a tailored approach individualized for the patient and location of the disease process to include surgery, medical therapy or a combination of medical and surgical management depending on the location. Serial bronchoscopy can be helpful to follow the course of the disease when endotracheal disease is present.