*From the Division of Pulmonary Sciences and Critical Care Medicine and the Division of Gastroenterology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO.
Correspondence to: William Janssen, MD, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Box C-272, Denver, CO 80262; e-mail: William.Janssen@uchsc.edu.
A 47-year-old, African-American man presented to the emergency department complaining of 3 weeks of cough, fever, and night sweats. The cough was productive of white sputum and progressive in nature. The patient also noted 3 days of severe dyspnea and several episodes of posttussive syncope. He had fatigue and malaise but no other symptoms. Doxycycline prescribed 4 days prior had not alleviated the symptoms.
The patient had a 12-year history of ulcerative colitis for which he had required hospitalization on several occasions. A recent colonoscopy demonstrated active disease. His current medications included oral mesalamine and doxycycline. He was a former smoker but quit 3 years prior. He denied recent travel and had no risk factors for tuberculosis. There was no family history of GI or pulmonary disease.
Physical examination was notable for a temperature of 38.2°C and a respiratory rate of 28 breaths/min. The patient appeared anxious, was in moderate respiratory distress, and was using accessory respiratory muscles. The ears, nose, oropharynx, and neck were normal. High-pitched breath sounds were present on inspiration and exhalation. Percussion was normal, and there was no egophony. No skin lesions were present. The remainder of his examination was unremarkable.
Initial laboratory evaluation demonstrated a WBC count of 13,500/μL, a hematocrit of 40%, and a platelet count of 738,000/μL. Serum electrolytes and liver function test results were normal. The patient was admitted to the ICU. Methylprednisolone and ampicillin/sulbactam were administered IV. A chest radiograph (Fig 1
) and a bedside flow-volume loop (Fig 2
) were obtained.
Although the patient has had respiratory symptoms for 3 weeks, he now appears quite ill and is exhibiting stridor. Stridor that occurs during inspiration suggests extrathoracic airway obstruction, while expiratory stridor usually indicates an intrathoracic process. In this case, stridor occurs during both inspiration and expiration, suggesting either that the lesion involves both intrathoracic and extrathoracic structures, or that a high-grade fixed obstruction is present.
The chest radiograph demonstrates narrowing of the trachea. No parenchymal lung disease is present. The flow-volume loop has flattening of the inspiratory and expiratory limbs, confirming a fixed upper-airway obstruction. The inspiratory and expiratory flow rates are extremely low. Assuming that the patient was able to cooperate and has normal muscle strength, the degree of obstruction is severe.
Fever and the rapidly progressive nature of the illness are suggestive of infection. Laryngotracheobronchitis (croup) most often occurs in children and is caused primarily by respiratory viruses. Adults with croup may experience hoarseness, but airway compromise would be unusual. A secondary bacterial infection is possible and would explain a sudden worsening in the patient’s condition. Tuberculosis and disseminated histoplasmosis can cause laryngotracheitis, but the patient has no risk factors for tuberculosis and has not traveled. Sputum cultures, Gram stain, and acid-fast stains should be obtained.
Noninfectious etiologies must also be considered. Wegener granulomatosis, sarcoidosis, and relapsing polychondritis can each present with subglottic and tracheal involvement. Wegener granulomatosis and sarcoidosis cause concentric narrowing of the trachea. In contrast, the posterior tracheal membrane (which is noncartilaginous) is spared in relapsing polychondritis. Therefore, a CT scan of the chest would be helpful. The chest radiograph demonstrates normal lung fields and no hilar adenopathy, making sarcoidosis unlikely. More than 90% of patients with sarcoidosis have lung involvement. Isolated tracheal involvement would be unusual.
Examination of the ears, nose, throat, and skin is normal. Destruction of the nasal and auricular cartilage would point toward relapsing polychondritis, while sinusitis is often seen with Wegener granulomatosis. Nodules, ulcers, and palpable purpura can be seen with both Wegener granulomatosis and relapsing polychondritis. The absence extrapulmonary findings makes Wegener granulomatosis and relapsing polychondritis less likely diagnoses but does not rule them out. Serum antinuclear and anti-neutrophil cytoplasmic antibodies (ANCAs) should be obtained.
The key to the diagnosis is in the medical history. The patient has long-standing ulcerative colitis. Inflammatory bowel disease can affect the upper and lower airways and can present in acute fashion with subglottic stenosis and tracheitis. It is interesting that the patient is a former smoker because smoking may prevent GI manifestations of ulcerative colitis. In contrast, tobacco smoke may exacerbate GI disease in Crohn disease.
It is unlikely that a diagnosis will be obtained without an invasive procedure. However, bronchoscopy at this juncture could compromise the airway. Empiric treatment with antibiotics and corticosteroids should be continued, and bronchoscopy should be performed only if the patient requires endotracheal intubation, or once his condition is more stable.
Close monitoring of the airway is paramount. Anesthesia and surgical services should be involved early in the course. If the patient exhibits further deterioration, endotracheal intubation should be performed immediately, preferably in the controlled setting of the operating room. Heliox may also be of benefit in this patient. Normally, there is turbulent airflow in the large airways. Administration of a mixture of helium and oxygen (usually in an 80:20 or 70:30 helium-to-oxygen ratio) will decrease the density of inhaled gas, facilitate laminar airflow, and decrease work of breathing.
Although extraintestinal disease was recognized as a complication of ulcerative colitis > 75 years ago,1only recently have the pulmonary manifestations been acknowledged.2 The true prevalence of pulmonary disease in ulcerative colitis is unknown. Patient registries document significant pulmonary disease in < 1% of patients.2–3 In contrast, pulmonary function abnormalities (including decreased diffusion capacity, increased residual volume, and increased functional residual capacity) are present in up to 50% of patients with ulcerative colitis.4–5 This is not surprising given that the GI tract and lungs derive from a common embryonic origin.
Virtually any part of the respiratory system can be involved in ulcerative colitis, including the large and small airways, parenchyma, pleura, and vasculature (Table 1
). Chronic bronchitis, bronchiectasis, and bronchiolitis represent the most common clinical-pathologic patterns of involvement.6–7 Tracheal disease is rare and has been reported in 11 previous cases (Table 2
On average, patients had ulcerative colitis for > 10 years before tracheitis developed. Tracheitis was the presenting feature in two patients. All patients had relatively severe inflammatory bowel disease. Five patients underwent colectomy prior to airway involvement developing. The remainder had active GI disease coinciding with the onset of tracheal involvement.
Based on the acuity of symptoms, patients can be classified into two groups. One half of the patients presented in acute fashion with severe cough and wheezing followed by hoarseness, stridor, and impending respiratory distress. The remainder had cough and/or wheezing that lasted for weeks to months. Hoarseness and stridor eventually developed in two of these patients, necessitating emergent therapy.
High fever and purulent sputum are common in fulminant cases. Bronchoscopic examination demonstrates severe tracheal narrowing with 50 to 80% reduction in the tracheal diameter. Friable hemorrhagic tissue and a cobblestone-appearing mucosa may be seen in the larynx, trachea, and bronchi. Biopsies demonstrate exuberant inflammation with granulation tissue containing abundant plasma cells, lymphocytes, and neutrophils.
In all cases in which treatment is reported, systemic corticosteroids were administered. Rapid improvement was seen in all patients, including two of whom who required endotracheal intubation. One patient had a subacute presentation with mild-to-moderate improvement in symptoms following corticosteroids.8 Bronchial dilation was attempted, resulting in tracheal rupture and death.
This adverse event highlights the importance of early recognition and treatment of inflammatory bowel-related lung disease. Large airways disease appears to be extremely responsive to corticosteroids.6–7,9–10 When disease is minor, inhaled corticosteroids can provide significant amelioration of symptoms and may be the only therapy necessary. In severe cases, systemic corticosteroids are required but can quickly be tapered to lower doses and eventually transitioned to inhaled corticosteroids.6 Delayed treatment may result in irreversible airway fibrosis and stricture.8
Small airways disease is more difficult to treat.6–7 Inhaled steroids appear to have little effect, and oral corticosteroids are often required. Despite high doses, improvement may be minimal or modest. Lung transplantation has been required in at least one case.7
Several authors2,6–7,11–12 have suggested that colonic surgery is a risk factor for development of pulmonary disease. This may reflect inflammation targeted at sites of common embryonal origin. Further supporting this concept are parallel flares of pulmonary and colonic inflammation11–12 and cases of concomitant bronchial and biliary involvement.8,13–14 Patients with ulcerative colitis are prone for acquiring sclerosing cholangitis,15–16 and the histopathology of sclerosing cholangitis and ulcerative colitis related-airways disease is remarkably similar.17 The biliary tree and lungs both develop as extensions of the embryonic gut. Thus, colonic and biliary surgery should be avoided in patients with ulcerative colitis related-lung disease.
Tobacco use may protect against development of lung disease in patients with ulcerative colitis. Smoking history has been documented in at least 55 patients with ulcerative colitis-related pulmonary disease.2,7–8,10–11,18–21 Forty-three patients had never smoked, and 11 patients were former smokers. Only one patient with respiratory disease was a current smoker.19 A similar relationship between tobacco use and the activity of intestinal disease is well established and may be mediated in part through nicotine.22–23 In contrast, smoking appears to have an adverse effect on the clinical course of Crohn disease.24–26 The reasons for this are unknown but may provide further insight into the relationship between inflammatory bowel disease and the lungs.
It is essential to rule out Wegener granulomatosis prior to making the diagnosis of ulcerative colitis or Crohn-related lung disease. The pulmonary manifestations of Wegener granulomatosis include cavitary nodules and laryngotracheal stenosis/ulceration. Similar findings can be seen in patients with inflammatory bowel disease. Additionally, Wegener granulomatosis can involve the colon, presenting with active colitis.27 ANCA levels are often elevated in ulcerative colitis; however, the antibodies with ulcerative colitis are typically antimyeloperoxidase antibodies (perinuclear ANCA), whereas those of Wegener granulomatosis are antiproteinase 3 antibodies (cytoplasmic ANCA). Histopathology remains the “gold standard” for differentiating inflammatory bowel disease from Wegener granulomatosis.
In summary, pulmonary disease is common in patients with ulcerative colitis and is largely underrecognized. Large airway disease is most common and includes bronchiectasis, bronchitis, tracheitis, and subglottic stenosis and tracheal stenosis. Forms of small airway and parenchymal involvement include bronchiolitis, organizing pneumonia, bronchiolitis obliterans, and interstitial fibrosis. Systemic corticosteroids are highly effective for large airways disease, while inhaled corticosteroids may be helpful for maintenance therapy. A high index of suspicion is required in nonsmokers with a history of severe or active colitis; these patients are at highest risk for ulcerative colitis-related lung disease. The patient presented here highlights these risk factors as well as the importance of early diagnosis and aggressive treatment of ulcerative colitis-related lung disease.
A CT scan of the chest demonstrated circumferential tracheal narrowing. Sputum cultures and stains for acid-fast bacilli were negative. The patient improved rapidly on corticosteroids and antibiotics. After 3 days, there was resolution of the fever and marked improvement in cough and dyspnea. Fiberoptic bronchoscopy demonstrated diffuse concentric narrowing of the trachea and studding of the mucosa with multiple small nodules (Fig 3
). Endotracheal biopsies revealed ulceration of the squamous and glandular mucosa, submucosal necrosis, and acute inflammation (Fig 4
). Culture and stain findings for bacteria, fungus, and acid-fast bacilli were negative. Viral polymerase chain reaction was negative, as were antinuclear antibody and ANCA.
The patient was given a diagnosis of ulcerative colitis-related tracheobronchitis. Antibiotics were discontinued, and the patient was discharged receiving oral prednisone. A flow-volume loop 5 days after discharge was completely normal (Fig 5
). Prednisone was discontinued after 4 months, and inhaled fluticasone was started. Severe tracheobronchitis recurred when the patient stopped the fluticasone. He exhibited a prompt response to systemic corticosteroids and has done well for > 2 years receiving inhaled fluticasone.
Abbreviation: ANCA = anti-neutrophil cytoplasmic antibody
The authors have no conflicts of interest to disclose.
NA = not available.
Two-step presentation with cough, dyspnea, and tracheal inflammation without narrowing. The patient had partial remission followed by tracheal stenosis 20 months later.
Minimal improvement with systemic steroids. Endobronchial dilation led to initial improvement followed by recurrence of symptoms over 1 year; repeat endobronchial dilation complicated by tracheal rupture and death.
Airway involvement part of initial presentation.
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