Abstract
Objectives:
To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection.
Methods:
Case report and review of the literature.
Results:
A 68-year-old female with history of prior smoking, gastroesophageal reflux disease, asthma, bronchiectasis, and tracheobronchomalacia presented with a 3-month history of shortness of breath, exertional inspiratory stridor, and hoarseness. Flexible laryngoscopy demonstrated ulceration of medial aspect of right vocal fold and subglottic tissue abnormality with crusting and ulceration extending through the upper trachea. Microdirect laryngoscopy with tissue biopsies and carbon dioxide (CO2) laser ablation of disease completed, and intraoperative culture revealed positive Aspergillus and acid-fast bacilli with Mycobacterium abscessus (type of NTM). Patient began antimicrobial treatment of cefoxitin, imipenem, amikacin, azithromycin, clofazimine, and itraconazole. Fourteen months after initial presentation, patient developed subglottic stenosis with limited extension into the proximal trachea prompting CO2 laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis.
Conclusion:
Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.
Keywords
Introduction
Nontuberculous mycobacteria (NTM) or “atypical mycobacteria” is a rare cause of disease in humans. Progressive disease caused by NTM is uncommon, with disease burden falling on immunocompromised patients or those with structural lung disease. 1 While NTM infection most commonly involves the pulmonary system, prior studies have documented head and neck involvement.2 -8 Laryngeal NTM infections are exceedingly rare. Failure to consider an atypical mycobacterial infection in the differential diagnosis when presented with an ulcerative, exophytic mass may result in insufficient tissue evaluation, delayed diagnosis, and disease progression. We present a patient with the first case of NTM infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection.
Case Report
A 68-year-old female with history of prior smoking, gastroesophageal reflux disease, asthma, bronchiectasis, and tracheobronchomalacia presented with a 3-month history of shortness of breath, exertional inspiratory stridor, and hoarseness. She was on sublingual immunotherapy for allergies. Her lung disease was managed with a bronchodilator and steroid inhaler. She was being followed by pulmonology for sputum cultures positive for Pseudomonas requiring antibiotics. Additionally, the patient had a right lower lung nodule that was worked-up for possible malignancy. During her fiberoptic bronchoscopy with lung tissue biopsy and bronchoalveolar lavage (BAL), culture results were positive for NTM which required 1 month of antimycobacterial treatment 2 years prior to initial presentation (Table 1). This was notably her only intubation. Serial repeated acid-fast bacillus (AFB) sputum cultures were negative at the time of presentation. Prior flexible laryngoscopy demonstrated edematous vocal folds and subglottic eschar, and she was subsequently referred for laryngology evaluation.
Timeline of patient’s medical and surgical management including culture and pathology results.
Abbreviations: IP, initial presentation; OR, operating room; BAL, bronchoalveolar lavage; MAC, Mycobacterium avium complex; MABc, Mycobacterium abscessus; TVFs, true vocal folds; MDL, microdirect laryngoscopy; CO2, carbon dioxide; AFB, acid-fast bacilli; GMS, Grocott methenamine stain; IV, intravenous; PAS, Periodic acid-Schiff; mm, millimeters.
Office tracheoscopy in the laryngology clinic demonstrated ulceration of medial aspect of right vocal fold, and subglottic tissue abnormality with crusting and ulceration extending through the upper trachea (Figure 1A-D). Diagnostic work-up was notable for an airway obstruction on spirometry (peak expiratory flow 3.48 L/s, peak inspiratory flow 2.04 L/s). Neck computed tomography (CT) with contrast showed irregular narrowing below the level of vocal folds at level of cricoid (Figure 2).
Laryngoscopy demonstrating (A) ulceration of medial aspect of right vocal fold, and (B) subglottic tissue abnormality with crusting and ulceration extending through (C) upper trachea (D) lower trachea. Repeat laryngoscopy 14 months later demonstrating (E) healthy supraglottic tissue, (F) area of subglottic stenosis immediately below level of vocal cords, (G) upper and (H) lower trachea with signs of disease clearance.
Axial CT neck with contrast demonstrating irregular soft-tissue narrowing below level of vocal folds at level of cricoid extending approximately 9 mm into the airway.
The patient underwent microdirect laryngoscopy (MDL) with tissue biopsies and carbon dioxide (CO2) laser ablation of disease. At this point, wedge resections of the disease were performed to provide the patient with an adequate airway while pathology was obtained. Care was taken to leave tissue bridges between to avoid causing a stenosis. Pathology demonstrated acutely inflamed and ulcerated tissue without malignancy. Cultures were not obtained. Her dyspnea resolved, but the hoarseness and subglottic irregularity persisted post-operatively. The patient underwent MDL with biopsy approximately 2 months later with both pathology and culture results positive for Mycobacterium abscessus (MABc). Under management of the infectious disease team, the patient was treated with 2 months of IV cefoxitin, imipenem, and amikacin followed by 24 months of oral azithromycin, clofazimine, and inhaled amikacin. Three months later, patient presented with subglottic crusting on office tracheoscopy prompting a repeat MDL with both tissue biopsy and microbiology culture. Pathology demonstrated focally necrotic tracheal mucosa with inflammation and fungal microorganisms (Figure 3). Tissue culture was positive for fungus (Aspergillus fumigatus) and MABc.
Intraoperative pathology demonstrated focally necrotic trachea mucosa with inflammation and fungal microorganisms (high magnification 600x, Periodic Acid-Schiff [PAS] stain).
Afterward, the patient was asymptomatic until she returned 9 months later with mild dyspnea. Neck CT and in-office tracheoscopy were concerning for mucosal irregularity of the subglottis and upper trachea (Figure 1E-H). The patient was taken to the operating room for MDL and biopsies, 14 months after initial presentation, which showed subglottic stenosis with limited extension into the proximal trachea. AFB cultures were negative from this procedure. One month later, patient underwent CO2 laser incision, balloon dilation, and steroid injection of the subglottic stenosis.
At her 1-month follow-up appointment, she had a stable voice and mild dyspnea with exertion. Flexible laryngoscopy demonstrated a significantly improved airway; the area of prior subglottic stenosis remained well dilated extending to cervical trachea, and there was no sign of vocal fold ulceration or infection. Tracheomalacia was noted on office tracheoscopy. She was kept on antimicrobial therapy for an additional 8 months and remains disease free with a patent airway.
Discussion
NTM infections are increasing globally and are difficult to treat due to the inherent antibiotic resistance of these bacteria. The growing number of NTM cases is tied to multiple factors including: advancing age of the global population, lung diseases, immunosuppression, and broad-spectrum antibiotic therapy.2,9 The symptoms of NTM infection are generally nonspecific with patients presenting with chronic cough, hemoptysis, fatigue, or malaise. Lung involvement including indolent nodular or cavitating pneumonitis is the most common site of NTM infection. 5 NTM infection is frequently associated with bronchiectasis and other structural lung diseases, with NTM lung involvement further complicating preexisting disease. 8 Extrapulmonary NTM disease more commonly includes lymphadenitis, soft tissue infection, and bacteremia.5,8 Laryngeal NTM involvement is rare with only 7 prior studies reporting cases.2 -8 The limited mention of any tracheal involvement in NTM disease comes from one study describing tracheobronchial lesions found on bronchoscopy. 10 Our case demonstrates possible complications, such as subglottic stenosis, from treatment of NTM infection.
Following successful diagnosis and treatment of laryngeal NTM, most of the literature describes complete resolution of disease without complications.2 -4,6 -8 This was not the case for our patient with laryngeal and cervical tracheal NTM disease. Although she initially improved, she developed subglottic stenosis that required dilation. Of note, our patient had subsequent positive AFB culture 3 months into treatment, and the first negative AFB culture came 11 months into treatment. Although we do not fully know the natural timeline for an expected clearance of AFB positivity in NTM infections, the World Health Organization considers positive AFB sputum smears in pulmonary tuberculosis after 5 months of treatment to be treatment failure. 11 Hussin et al reported a case of delayed dysphagia due to hypopharyngeal stenosis following treatment of laryngopharyngeal (lingual surface epiglottis, right hypopharynx) NTM treatment. 5 The stenosis was successfully treated with tracheostomy, laser excision of hypopharyngeal stenosis, application of mitomycin C, and delayed decannulation. Likely risk factors for development in this case and ours include multiple procedures, surgical debridement and excision, multiple subsite involvement, and underlying prolonged inflammation from NTM infection as indicated by persistent positive AFB cultures.
Etiology of an ulcerative, exophytic laryngeal lesion can include malignancy, infection, or autoimmune condition. Tissue sampling is crucial in determining the cause of laryngeal lesions. Prior cases of laryngeal NTM provide various timelines and delays in achieving a final diagnosis, as biopsy may demonstrate nonspecific necrotic or inflammatory tissue.2,4,5 Delay in diagnosis due to repeated procedures increases risk of disease progression. Obtaining additional information than tissue histopathology results, either with in the form of tissue culture and/or PCR analysis, is crucial in the prompt diagnosis of laryngeal NTM.2,4,5
The treatment of NTM infection includes prolonged, multiagent therapy. Obtaining 12 months of negative AFB cultures and imaging stability are the goals of therapy. 12 Patients with macrolide-sensitive NTM infection initially receive a 3-drug combination – a macrolide (azithromycin or clarithromycin), rifampin, and ethambutol. Patients with more severe infections receive a parenteral aminoglycoside (eg, amikacin) for the initial 8-12 weeks of therapy. For mild disease or patients who cannot tolerate the 3-drug combination, a 2-drug combination—a macrolide and ethambutol—is a possibility. In macrolide resistance infections, the following combination is suggested: ethambutol, rifamycin or rifabutin, clofazimine, and a parenteral aminoglycoside. 13 Although a prior study 6 saw resolution of symptoms associated with NTM infection following 6 months of initiating antibiotic therapy, our case demonstrated nonlinear improvement with months of improvement followed by symptom recurrence and eventual development of subglottic stenosis. Our recommendations would be: (1) to obtain 12 months of negative AFB cultures and (2) monitor for recurrent NTM infection and/or sequelae for at least 2 years following completion of treatment.
In the case we presented, our patient had multiple risk factors for NTM infection including structural lung disease, Pseudomonas colonization, chronic steroid use, and prior NTM positivity.2,6,8 NTM infections should be considered when evaluating laryngotracheal lesions, especially in patients with risk factors for opportunistic infections. Prompt diagnosis of NTM infections is critical as this infection is contagious and progressive symptoms can lead to long-term sequelae. Diagnosis was delayed due to a low suspicion for NTM and by not completing a tissue culture or PCR analysis. Delay in diagnosis may result in permanent vocal fold and/or airway damage. Multiple subsite involvement of NTM infection may increase risk of disease sequelae including airway stenosis. Patients with laryngeal NTM should be monitored at least for the duration of antibiotic regimen to ensure no further complications develop.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics Statement
All authors have seen and approved the manuscript.
