Acquired tracheoesophageal fistula in disseminated Mycobacterium avium complex associated with anti-interferon-gamma autoantibodies

Abstract

We describe a case of a 30-year-old previously healthy woman who presented to our hospital with a 2-month history of fevers, tender lymphadenopathy, dysphagia, globus sensation and occasional haematemesis. Further evaluation revealed cervicothoracic adenopathy and a subcarinal mass with oesophageal involvement. Imaging showed a transesophageal fistula at the level of the carina with contrast extravasation to the left main bronchus. Our patient was diagnosed with disseminated Mycobacterium avium complex (MAC) based on acid-fast bacillus noted on sputum cultures and nodal biopsies. Further investigation revealed anti-interferon-gamma autoantibodies as a possible predisposing factor for the disseminated MAC infection. This case demonstrates the importance of a broad differential diagnoses in a patient presenting with unexplained cervicothoracic lymphadenopathy, fever and dysphagia. Although acquired tracheoesophageal fistulae are uncommon, it should be considered in the clinical setting of globus sensation, haemoptysis and dysphagia. Furthermore, our case highlights a rare predisposition to disseminated Mycobacterium infection.

Background

Bronchoesophageal fistula and tracheoesophageal fistula (TEF) are abnormal anatomic connections between the oesophagus and the airways. The congenital variant is well documented in children, but TEFs are an uncommon presentation in adults, where a significant proportion is secondary to malignancy. Less commonly, these can be due to iatrogenic causes such as prolonged endotracheal intubation and surgical or endoscopic interventions. Cases of bronchopleural fistula formation due to Mycobacterium tuberculosis (TB) have been described in the literature. However, disseminated Mycobacterium avium complex (MAC) infection with diffuse lymphadenopathy resulting in a TEF is rare.¹ After an extensive literature review, we were unable to identify reports of a TEF secondary to disseminated MAC infection in a patient with interferon-gamma autoantibodies.

Case presentation

A 30-year-old apparently healthy Asian woman presented to our hospital with 2 months of fevers, chills, weight loss and dysphagia in the setting of tender cervical lymphadenopathy. She had travelled to the Philippines 6 months prior to presentation, but had no history of sick contacts, tobacco or alcohol use. There was no family history of autoimmune, rheumatologic diseases or malignancy. She was on no medication other than Tylenol and ibuprofen, which were started within the month of presentation for pain and fevers, and had no known allergies to medications. Vital signs on admission were temperature of 37.9°C, heart rate of 109 beats/min, blood pressure 105/73 mm Hg and respiratory rate 22 breaths/min with an oxygen saturation of 99% on room air. Other significant physical examination findings included scalp, anterior and posterior cervical, supraclavicular, axillary and inguinal tender lymphadenopathy. The rest of the physical examination was normal.

Investigations

CT scan of the chest (figures 1 and 2), abdomen and pelvis showed cervicothoracic adenopathy with a subcarinal mass involving the oesophagus as well as multiple lytic lesions involving both iliac wings, right sixth rib and soft tissue extension into the pleural space. The findings were thought to be compatible with metastatic disease from an unknown primary. Initial differential diagnoses included oesophageal carcinoma, melanoma or other thoracic malignancies. Lymph node aspirates were negative for malignancy, but were positive for MAC by DNA probe; blood and sputum cultures grew MAC. Her hospital course was complicated by pneumonia, worsening dysphagia and aspiration, which raised concerns for fistula formation. An oesophagram (figure 3) demonstrated a TEF at the level of the carina with contrast opacification of the left main bronchus, as well as narrowing of the thoracic oesophagus in the subcarinal area, which corresponded with necrotic lymph nodes seen on CT scan (figures 1 and 2). Esophagogastroduodenoscopy (EGD, figure 4) showed a moderate-sized area of extrinsic compression and a fistula in the middle third of the oesophagus. An 18×mm×12.3 cm WallFlex covered stent was placed under fluoroscopic guidance (figure 5).

Figure 1.

CT scan showing 31×18 mm subcarinal mass with near obliteration of the oesophageal lumen.

Figure 2.

CT scan showing right paratracheal lymph node measuring 14×26 mm.

Figure 3.

Tracheoesophageal fistula (TEF) at the level of the carina with narrowing of the thoracic oesophagus in the subcarinal area, which corresponds with necrotic lymph nodes seen in figures 1 and 2.

Figure 4.

Fistula in the middle third of the oesophagus, at 25 cm from the incisors.

Figure 5.

Placement of an 18 mm×12.3 cm WallFlex covered stent, the proximal portion 19 cm from the incisors.

Differential diagnoses

Differential diagnoses at presentation included oesophageal carcinoma, melanoma and lymphoma associated with diffuse lymphadenopathy and infection. Lymph node biopsies showed acute inflammation and atypical cells favouring a reactive process. Flow cytometry did not reveal evidence of malignancy, cultures of the aspirate confirmed MAC.

An aggressive infection was also high on the differential. HIV testing was negative and CD4 count was 485. Human T-lymphotropic virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, blastomycosis, chlamydia and gonorrhoeae were negative. Blood, sputum and nodal aspirate cultures were positive for MAC. Further evaluation of disseminated non-tuberculous mycobacteria in our non-immunocompromised patient included testing for anti-interferon-gamma autoantibodies, which was positive.

A fistulous tract was suspected in the setting of dysphagia, aspiration pneumonia and episodes of small-volume haematemesis. Initial evaluation by speech therapy and a barium swallow was non-confirmatory. Further workup with an oesophagram and an upper GI endoscopy confirmed the clinical suspicion (figures 3 and 4).

Treatment

The TEF was treated with placement of an 18 mm×12.3 cm WallFlex covered stent with proximal and distal clips to prevent stent migration under fluoroscopy. A CT scan of the thorax with oral contrast following the procedure showed no extravasation of contrast from the oesophagus. A repeat EGD 3 weeks later with stent removal showed an 8 mm fistula in the upper third of the oesophagus. Endoscopic suturing was performed in a continuous fashion under direct visualisation. Post suturing follow-up oesophagram showed a persistent oesophageal bronchial fistula with thin barium extending into the left main bronchus. (figure 6). An 18 mm×15.3 cm WallFlex covered stent (figure 7) was replaced and a nasojejunal tube was placed for nutritional support. The patient was then accepted to a specialised care centre for further management of the disseminated MAC infection and follow-up gastroenterological care.

Figure 6.

An 8 mm fistula is seen in the upper third of the oesophagus.

Figure 7.

An 18 mm×15.3 cm WallFlex covered stent is placed, covering the tracheo-esophageal fistula (TEF) (yellow arrow).

Outcome and follow-up

On follow-up 9 months after discharge, the patient is status post a jejunostomy tube and is tube-feed dependent. She underwent multiple EGDs with stent placements and trial removals, but the TEF persisted. Unfortunately, she has failed conventional polypharmacy therapy with multiple antimicrobials. Given the disease burden and the lack of improvement, there is no immediate plan for surgery to repair the TEF. For now, she remains on a conservative treatment plan.

Discussion

TEF and bronchoesophageal fistula in adults are uncommon. They are often acquired and secondary to malignancy involving the oesophagus or adjacent structures such as lymph nodes, or due to iatrogenic causes such as prolonged endotracheal intubation or manual surgical manipulation.² Infections such as tuberculosis, while less common, can also cause TEFs.¹ To our knowledge, there are no reported cases of disseminated MAC with a background of anti-interferon-gamma autoantibodies causing TEFs.

Diagnosis of TEF begins with a history and further evaluation for clinical manifestations of frequent coughing with oral intake suggestive of aspiration. It is important to evaluate underlying conditions that could predispose to TEF formation such as malignancy. Ultimately, radiographic evaluation with barium swallow or oesophagram, and endoscopy (EGD) are key to the diagnosis.

Treatment of TEF includes interventional endoscopy with stenting to seal the fistula and prevent liquid/solid into the airway with resulting risk of pneumonia and other pulmonary complications.^{3 4} A single stent in the oesophagus can allow most patients to resume their diet following the intervention.⁴

Our approach with this patient differed given her poor response to the endoscopic intervention. Another management option is surgical. Our patient had a disseminated infection, which complicated her treatment course. While the ultimate goal is to correct the TEF, this cannot be done without treating the underlying infection that caused the fistula as a result of the necrotic lymphadenopathy.

Disseminated MAC infection is typically seen in immunocompromised patients. However, it has been reported in patients with autoimmune diseases. A thorough infectious disease evaluation was negative. As such we suspected anti-interferon-gamma autoantibodies. Patients with anti-interferon-gamma autoantibodies are vulnerable to a multitude of infections, including disseminated MAC. Unfortunately, non-tuberculous MAC infections tend to have a high incidence of drug resistance.^{5 6}

Learning points.

• Tracheoesophageal fistula (TEF) and bronchoesophageal fistula have non-specific symptoms. The diagnosis should be suspected in patients with both clinical manifestations and a pertinent medical history that increases the risk of TEF formation.

• The current main treatment of choice in patients with TEF is endoscopic stent placement to seal the fistula to prevent passage of food particles and fluid from the oesophagus to the airways.

• Common causes of acquired TEF in adults include: malignancy, trauma (prolonged endotracheal intubation) and disseminated infections.

• Disseminated non-tuberculous Mycobacterium avium complex infections are often due to AIDS. However, in patients who are not immunocompromised, an autoimmune condition must be considered—such as anti-interferon-gamma autoantibodies.