Case 4 -
Suppurative Bronchiectasis with Secondary Organizing Pneumonia as a
Pulmonary Manifestation of Inflammatory Bowel Disease
Samuel A. Yousem
University of Pittsburgh
Click on each slide thumbnail image for an enlarged view
A 30-year-old Black woman presented with a progressive shortness of breath
and productive cough over the last six months associated with chest radiographs showing a bilateral
reticulonodular pattern with bronchiectasis, greatest in the left lower lobe. Repeated cultures of
sputum were negative. Past medical history is pertinent only for a history of ulcerative colitis for
which she had a colectomy in 1994. Pulmonary function studies showed predominantly obstructive lung
disease. A diagnostic thoracoscopic biopsy was performed (Case contributed by Michael D. Kanzer, MD,
Christiana Care Health Services, Newark, Delaware).
Case 4 - Figure 1 - Low magnification demonstrated suppurative bronchiectasis with peribronchiolar lymphoid hyperplasia and air space consolidation.
Case 4 - Figure 2 - The bronchi and bronchioles had a luminal fibrinopurulent exudate with submucosal chronic inflammation.
Case 4 - Figure 3 - The airways were intensely inflamed with neutrophil migration into the epithelium.
Case 4 - Figure 4 - The airways were intensely inflamed with neutrophil migration into the epithelium.
Case 4 - Figure 5 - The distal lung parenchyma showed an organizing pneumonia with obstructive changes.
Diagnosis: Suppurative bronchiectasis with secondary organizing pneumonia as a pulmonary
manifestation of inflammatory bowel disease (ulcerative colitis).
Inflammatory bowel disease (IRB) is associated with a constellation of
extra-intestinal manifestations affecting a variety of organs and organ systems. Pleuropulmonary disease
occurs infrequently (<1%) and may be associated with other extra-intestinal involvement including
cutaneous lesions, pericholangitis, and ocular inflammation. Most forms of pulmonary disease are seen in
association with ulcerative colitis (90%), although Crohn's disease and celiac sprue contribute
approximately 10% of cases.
The forms of pulmonary disease that have been associated with inflammatory bowel disease are wide:
Table 1: Pulmonary Manifestations of Inflammatory Bowel Disease
In essence they can be divided into seven different patterns beginning with upper
respiratory/large airway inflammatory processes taking the form primarily of tracheitis/tracheal stenosis
and chronic bronchitis/bronchiectasis. Such large airway disease is often accompanied by, but may also
be restricted to, small airway injury in the form of bronchiolitis and bronchiolitis obliterans. Other
forms of disease fall within the categories of interstitial lung disease (predominantly organizing
pneumonia), airspace disease (predominantly eosinophilic pneumonia), pleural disease (serositis), and
nodular disease (necrobiotic non-granulomatous suppurative nodules). The discussion for this case will
focus on airway disease as a manifestation of ulcerative colitis.
- Tracheal stenosis
- Large airway disease
- Chronic bronchitis
- Bronchiectasis (usually suppurative)
- Colobronchial fistula (CD)
- Small airway disease
- Chronic bronchiolitis
- Bronchiolitis obliterans/constrictive bronchiolitis
- ILD - patterns
- Organizing pneumonia
- Non-specific interstitial pneumonia – cellular type
- Desquamative interstitial pneumonia
- "Lymphocytic alveolitis" (?NSIP in CD)
- Non-necrotizing granulomatous interstitial pneumonia (CD)
- Airspace disease
- Eosinophilic pneumonia/alveolitis (R/0 drugs)
- Acute pneumonia (usually secondary to bronchiectasis)
- Nodular disease
- Necrobiotic non-granulomatous suppurative nodules ("pulmonary pyoderma gangrenosum")
- Pleural disease
- Serositis – pleuritis/pericarditis
- Overlap syndromes/associations
- IBD and sarcoidosis
- IBD and emphysema (esp. alpha/antitrypsin deficiency)
- IBD and pulmonary thromboemboli
- IBD and pulmonary vasculitis (? role of pANCA)
Pleuropulmonary disease is predominantly found in middle aged women, often with the ulcerative colitis
(UC) or Crohn's disease (CD) in a quiescent phase (60%) or in individuals who have had a prior
proctocolectomy (20%). Patients are usually non-smokers and produce chronic copious mucopurulent
secretions to the point of bronchorrhea, with a significant negative impact on life style. These changes
are accompanied by obstructive pulmonary function studies with chest x-rays showing proximal
bronchiectasis with tram line and ring shadows, predominantly localized to the lower lobes. High
resolution CT scans show bronchiectasis often associated with small airway inflammatory cuffing with
mucoid impaction and a "tree and bud" appearance. Patchy alveolar opacities may be seen.
Bronchoalveolar lavage shows a predominantly neutrophilic infiltrate and culture studies are negative.
On bronchoscopy, there is marked diffuse erythema of the airways associated with narrowing and bulging of
the airway mucosa with a distinctive and striking tortuosity.
The histopathology of large airway inflammation in the setting of inflammatory bowel disease has been
predominantly reported in ulcerative colitis. The histologic features are largely non-specific with
biopsies of the airway showing squamous metaplasia associated with a greater than expected submucosal
inflammatory infiltrate of lymphocytes and plasma cells. A superficial infiltrate of neutrophils is also
noted often with an intra-epithelial component ("pulmonary crypt abscesses"). Involvement of the minor
salivary glands has also been observed and is relatively unusual in most cases of non-IBD
bronchiectasis. By report, the presence of reactive germinal centers and lymphoid follicles is less
common as well. With large airway inflammation, secondary distal changes in the pulmonary parenchyma may
occur, including a patchy acute non-infectious bronchopneumonia, as well as foci of airspace organization
(organizing pneumonia). In some instances, large nodular regions of suppuration, resembling abscesses
("pulmonary pyoderma gangrenosum") may be seen in association with bronchiectasis or as isolated events.
In all of these instances, special stains and culture studies are essential to exclude primary or
secondary bacterial, fungal, and mycobacterial infection.
Accompanying the large airway disease, or occurring independently, is small airway disease.
Non-cicatricial forms of chronic bronchiolitis lack signs and symptoms of suppuration instead presenting
with progressive shortness of breath, dyspnea, cough and obstructive PFTs. With prolonged injury
–primary or secondary to large airway damage – the small airways become scarred and fibrotic. Such
instances of bronchiolitis obliterans/constrictive bronchiolitis are usually fatal.
From a therapeutic perspective, the treatment of the large airway disease is accomplished successfully
through aggressive use of aerosolized steroids. In recalcitrant cases, success has been reported with
repeated BALs using steroid laced fluid. If unsuccessful with such topical treatment, systemic therapy
has been successful. When the patient has developed bronchiectasis however, management is difficult,
both because of recurrent disease activity and secondary infection. It should also be noted that
proctocolectomy is not recommended for abrogation of pulmonary disease and in fact, reports have
indicated that the development of pulmonary disease is more likely in individuals who have had such
The pathogenesis of inflammatory bowel disease associated pleuropulmonary injury is controversial and
has not been extensively investigated. Certainly the "shared antigen" theory is most popular with an
argument that the common embryogenesis of the lung and gastrointestinal system allows certain shared
antigens (P40 antigen) to enable both sites to "share" the immunologic injury. A second theory is
similar to the one used for Goodpasture's syndrome in that immune complexes with accompanying complement
deposition selectively deposit within the intestines, hepatobiliary system, and lung (e.g. pANCA). A
third theory relates to a presumption of common exposure to offending inhaled and ingested antigens that
initiate simultaneous organ specific injury.
As noted previously, the vast majority of pulmonary injury associated with IBD is related to
ulcerative colitis. Crohn's disease affects the lung to a lesser extent although often with
non-infectious suppurative bronchitis/bronchiolitis and organizing pneumonia (OP). With bronchiolitis
and OP, the presence of non-necrotizing granulomas or isolated giant cells are often seen and may mimic
hypersensitivity pneumonitis. Exclusion of infection, drug induced lung disease, and hypersensitivity
pneumonitis is essential before attributing the inflammatory activity to CD.
The differential diagnosis of bronchiectasis occurring in the setting of inflammatory bowel disease is
wide. Certainly, one needs to exclude the possibility of infection by repeated cultures and appropriate
serologic studies. Second, drug induced lung disease always should be excluded, particularly since many
of these patients are treated with drugs that have pulmonotoxic affects (sulfasalazine, mesalamine, and
methotrexate). Finally, Wegener's granulomatosis, with a predominant bronchiolocentric quality needs to
be excluded because of the association with ANCAs. The presence of necrotizing granulomatous process
with a destructive vasculitis and C-ANCA positivity, however, has not been reported in this group of
inflammatory bowel associated conditions.
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