International Journal of Pediatric Otorhinolaryngology 55 (2000) 65 – 68 www.elsevier.com/locate/ijporl
Case report
Isolated endobronchial atypical mycobacterium in a child: a case report and review of the literature David A. Litman a, Udayan K. Shah a,*, Bruce R. Pawel b a Di6ision of Pediatric Otolaryngology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104 -4399, USA, and the Department of Otorhinolaryngology — Head & Neck Surgery, Uni6ersity of Pennsyl6ania School of Medicine, Philadelphia, PA, USA b Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Received 4 January 2000; received in revised form 24 June 2000; accepted 25 June 2000
Abstract Isolated endobronchial lesions caused by Mycobacterium a6ium are rare, especially in the pediatric population. We share the case of a 10-month-old boy who, after 1 week of cough and low-grade fever, had a radiographic examination showing endobronchial obstruction. At bronchoscopy, a granuloma of the left bronchus intermedius was found. Histopathologic examination revealed necrotizing granulomatous inflammation. Kinyoun Acid Fast stain revealed acid fast bacilli. Cultures were positive for M. a6ium. Current treatment options and controversies are presented. The roles of antibiotics and steroids in preventing progressive disease are discussed. The need for serial bronchoscopy and the potential benefits of surgical resection are discussed. Isolated endobronchial M. a6ium infection remains a rare and challenging problem. The paucity of clinical experience, and variation in patient presentation, obligates a high index of suspicion, and frequent follow-up with bronchoscopic examination and pulmonary assessment, for the child diagnosed with isolated endobronchial atypical mycobacterial infection. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Airway obstruction; Bronchoscopy; Atypical mycobacterium; Granuloma
Presented at the 27th Annual Meeting of the Society for Ear, Nose and Throat Advances in Children, Williamsburg, VA, 4 December 1999. * Corresponding author. Present address: Division of Pediatric Otolaryngology, The Children’s Hospital of Philadelphia, Richard D. Wood Building, 1st Floor, 34th and Civic Center Boulevard, Philadelphia, PA 19104-4399, USA. Tel: + 1-2155903054; fax: + 1-215-5903986. E-mail address:
[email protected] (U.K. Shah).
1. Introduction Mycobacterium a6ium is the second most common cause of mycobacterial infection after tuberculosis [1]. It is currently believed to represent 80% of all non-tuberculous mycobacterial infections [2]. The organism is commonly found in soil, house dust, and water. Pulmonary infection is
0165-5876/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 0 ) 0 0 3 8 1 - 5
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probably caused by inhalation of aerosolized particles [1]. This has historically been noted to occur in adults with chronic pulmonary disease [3]. The incidence of pulmonary infection by M. a6ium is considered to be increasing [3 – 5]. The source of the increase is unclear and the true magnitude of the rise is difficult to ascertain, as M. a6ium is not a reportable disease [4]. Additionally, the organism is responsible for a variety of disease presentations including granulomatous neck disease,
otologic manifestations, and pulmonary disease [6,7]. However, there has been an increasing number of reports of previously healthy pediatric patients afflicted with isolated atypical mycobacterial pulmonary infection [1,2,8,9]. Lack of experience with this disease entity, combined with an increasing incidence of pediatric pulmonary infections, make it imperative to investigate current theories regarding the proper management of atypical mycobacterial infection.
2. Case presentation
Fig. 1. Chest radiograph. Air is trapped in the left lung, indicating endobronchial obstruction.
A 10-month-old male presented to his primary care physician with 1 week of cough, wheezing, and fever. A chest X-ray was obtained revealing air trapping of the left lung, consistent with endobronchial obstruction (Fig. 1). This was confirmed at bronchoscopy, where granulation tissue was seen, obstructing the left mainstem bronchus. The granulation tissue was removed with surgical forceps and sent for culture and histologic examination. Histology revealed necrotizing granulomatous inflammation (Fig. 2), and rare mycobacterial organisms were demonstrated histologically with the Kinyoun Acid Fast stain. Oral isoniazid therapy was started for the patient. Repeat bronchoscopy 10 days later revealed complete resolution of the granuloma. A post-operative chest radiograph demonstrated no evidence of disease. Isoniazid was discontinued at that time, as further work-up including sputum cultures and purified protein derivative (PPD) placement failed to demonstrate evidence of tuberculosis. Cultures at 8 weeks grew M. a6ium sensitive to oral clarithromycin, which was started. The patient remains asymptomatic at 4 months follow-up, with a chest radiograph confirming resolved endobronchial disease.
3. Discussion
Fig. 2. Histopathologic evaluation of left bronchial granuloma. Necrotizing granuloma is seen (hematoxylin and eosin stain, 10×).
M. a6ium has long been recognized as a source of cervical lymphadenitis in the pediatric population [1]. Pulmonary disease resulting from atypical mycobacterial infection is rare in young patients.
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However, the literature has brought attention to several cases of pediatric pulmonary atypical mycobaterium in recent years [1,3,8,9]. This parallels the overall rising incidence of M. a6ium infections. Lack of experience with this manifestation of the disease leads to clinical challenges in diagnosis, management, and predicting prognosis. The diagnosis of M. a6ium pulmonary disease is extremely difficult, especially in the pediatric patient [8]. Diagnosis depends on a high degree of suspicion on the part of the caregiver. Signs and symptoms can be variable and non-specific. They include chronic cough, wheezing, fatigue, dyspnea, fever, and weight loss [4]. There is also a wide range of radiographic findings including isolated pulmonary nodules, mediastinal lymphadenopathy, parenchymal infiltrates, or bronchial obstruction [4,8]. Diagnosis is hampered both by the non-specific signs and symptoms, and the overlap of the presentation with that of tuberculosis. An occasionally positive PPD can further lead to diagnostic confusion [1]. The non-specific presentation of this disease makes obtaining positive cultures essential. Diagnostic criteria recommended by the American Thoracic Society are the following. 1. If three sputum/bronchial wash results are available from the previous 12 months: 1.1. three positive cultures with negative acid fast bacilli (AFB) smear results; or 1.2. two positive cultures and one positive AFB smear. 2. If only one bronchial wash is available: 2.1. Positive culture with a 2 + , 3 + , or 4 + AFB smear or 2 + , 3 +, or 4 + growth on solid media. 3. If sputum/bronchial wash evaluations are nondiagnostic or another disease cannot be excluded: 3.1. transbronchial or lung biopsy yielding a non-tuberculous mycobacterium (NTM); or 3.2. biopsy showing mycobacterial histiopathologic features (granulomatous inflammation and/or AFB) and one or more sputum or bronchial washings are positive for a NTM, even in low numbers [4].
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Positive cultures are notoriously difficult to obtain in the pediatric patient. It has been suggested that the presented criteria may need to be altered when dealing with children, as only 30–50% of patients will have a positive culture on three consecutive morning gastric aspirates [8]. Although bronchoalveolar lavage has increased the rates of diagnosis in adults, the same has not proven to be the case in pediatric patients [8]. Bronchoscopic findings are similarly difficult to interpret. The differential diagnosis of necrotizing granulomatous inflammation within the bronchi includes atypical mycobacterial infection, tuberculosis, fungal infections, brucellosis, and meliodosis. This broad differential emphasizes the importance of tissue biopsy for culture and histopathologic evaluation of an obstructing bronchial granuloma. Controversy exists regarding treatment options for the disease. Surgical excision for cervical lymphadenitis is nearly always curative for M. a6ium [2]. Because of this experience and the high level of drug resistance in atypical mycobaterial isolates, some recommend early surgical resection [3]. Such resections range in degree, depending on the extent of disease. Options include lobectomy, segmentectomy, wedge resection, or even pneumonectomy [5,10]. Most recently, Shiraishi et al. demonstrated 97% and 88% relapse free rates at 5 and 10 years, respectively, when surgical resection was combined with pre- and post-operative drug therapy [5]. Reservations against surgery have included the difficulty of excising an inflammatory mass that is proximal to critical structures, the risk of operative and anesthetic mortality, and the risk of disseminating the organism throughout the thoracic cavity [2]. Recently, success has also been obtained using aggressive antimycobacterial medications. This involves a three- to four-drug regimen that includes ethambutol, rifabutin and clarithromycin [8]. Therapy is continued until the patient is culture negative on therapy for at least 1 year [4]. In our patient, limited surgical resection combined with medical therapy has resulted in a clinically stable condition, with no evidence of airway obstruction at 4 months follow-up. He remains on clarithromycin and will be examined
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in the office at 3-month intervals, and by serial chest radiographs at 6 and 12 months post-bronchoscopy. Repeat bronchoscopy will be performed if there is either clinical or radiographic suspicion of recurrence. This approach is similar to that presented by Piediamonte et al., who reported a 9-month-old child presenting with wheezing and fever [2]. The symptoms progressed to bronchial obstruction, caused by endobronchial granulation tissue that was resected with both laser and forceps. The child required three procedures to treat recurrent granulomatous obstruction. Re-examination at 2 months revealed only mild bronchomalacia at the site of the granuloma. As in our patient, this demonstrates the successful management of endobronchial mycobacterium with medical therapy and limited surgical intervention. The proper management of isolated endobronchial atypical mycobacterium remains unclear. Currently, good outcomes have been demonstrated with early surgical intervention combined with aggressive drug therapy. At endoscopy, the integrity of the bronchial wall must be confirmed, as atypical mycobacterial bronchial granulomas may have mediastinal components (R. Ward, personal communication, 4 December 1999). A computed tomography scan with contrast would be required to determine the extent of such disease. New drug regimens might reduce the need for future surgery. Caution is needed as pulmonary M. a6ium infection can be an indolent disease. Lack of experience with long-term medical management of these patients requires close monitoring for signs or symptoms of recurrence.
4. Conclusion Isolated endobronchial M. a6ium infection remains a challenging problem. The paucity of clin-
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ical experience, and variation in patient presentation, obligates a high index of suspicion and frequent follow-up for the child diagnosed with this rare disorder.
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