Case 4 -

Suppurative Bronchiectasis with Secondary Organizing Pneumonia as a Pulmonary Manifestation of Inflammatory Bowel Disease Samuel A. Yousem University of Pittsburgh Pittsburgh, PA

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Clinical History 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). Discussion: 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 Trachea/Epiglottis Epiglottitis/tracheitis Tracheal stenosis Large airway disease Chronic bronchitis Bronchiectasis (usually suppurative) Colobronchial fistula (CD) Small airway disease Chronic bronchiolitis Bronchiolitis obliterans/constrictive bronchiolitis Panbronchiolitis 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") Amyloidoma 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) 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. 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 procedures. 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. Selected References Butland RJ, Cole P, Citron KM, et al.: Chronic bronchial suppuration and inflammatory bowel disease. Quarterly Journal of Medicine 1981:63-75 Camus P, Colby TV: The lung in inflammatory bowel disease. European Respiratory Journal 2000, 15:5-10 Camus P, Piard F, Ashcroft T, et al.: The lung in inflammatory bowel disease. Medicine 1993, 72:151-184 Casey MB, Tazelaar HD, Myers JL, et al.: Noninfectious lung pathology in patients with Crohn's disease. American Journal of Surgical Pathology 2003, 27:213-219 Greenstein AJ, Janowitz HD, Sachar DB, et al.: The extra-intestinal complications of Crohn's Disease and ulcerative colitis: a study of 700 patients. Medicine 1976, 55:401-412 Higenbottam T, Cochrane GM, Clark TJ, et al.: Bronchial disease in ulcerative colitis. Thorax 1980, 35:581-585 Isenberg JI, Goldstein H, Korn AR, et al.: Pulmonary vasculitis - an uncommon complication of ulcerative colitis. The New England Journal of Medicine 1968:1376-1377 Kraft SC, Earle RH, Roesler M, et al.: Unexplained bronchopulmonary disease with inflammatory bowel disease. Archives of Internal Medicine 1976, 136:454-459 Kuzela L, Vavrecka A, Prikazska M, et al.: Pulmonary complications in patients with inflammatory bowel disease. Hepato-Gastroenterology 1999:1714-1719 Moles KW, Varghese G, Hayes JR: Pulmonary involvement in ulcerative colitis. British Journal of Disease of the Chest 1988, 82:79-83 Spira A, Grossman R, Balter M: Large airway disease associated with inflammatory bowel disease. Chest 1998, 113:1723-1726 Storch I, Sachar D, Katz S: Pulmonary manifestations of inflammatory bowel disease. Inflammatory Bowel Diseases 2003, 9:104-115 Swinburn CR, Jackson GJ, Cobden I, et al.: Bronchiolitis obliterans organizing pneumonia in a patient with ulcerative colitis. Thorax 1988, 43:735-736 Tzanakis N, Samiou M, Bouros D, et al.: Small airways function in patients with inflammatory bowel disease. American Journal of Respiratory Critical Care Medicine 1998, 157:382-386