Case 5 -

Severe, Acute, and Chronic Bronchiolitis with Bronchiolectasis Associated with Extensive Organizing Endogenous Lipoid Pneumonia; and Rare Non-necrotizing Granulomas Henry D. Tazelaar and Marie-Christine Aubry

PDF File (3.6 MB) Clinical History A 58-year-old man with a history of sarcoidosis presented with persistent cough and symptoms of bronchitis. These had been recurrent over the past ten years and developed approximately six months following a diagnosis of Crohn's disease of the colon. Throughout the past ten years, he has had a persistent cough productive of five to eight teaspoons of thick, tan, yellow, "chunky" sputum and has had numerous hospitalizations for pulmonary infections with fever and chills. He underwent an open lung biopsy because his sputum was growing aspergillus and the possibility of invasive aspergillosis was raised. Slides illustrating Case 5 are in the accompanying PDF of the Powerpoint presentation. Diagnosis: Severe, acute, and chronic bronchiolitis with bronchiolectasis associated with extensive organizing endogenous lipoid pneumonia; and rare non-necrotizing granulomas. The features are consistent with lung disease occurring in association with inflammatory bowel disease (Crohn's disease). Discussion Sections show those features outlined in the diagnosis. The presence of airway dilatation is best appreciated by comparing the airway diameter to that of its adjacent vessel. They should be about the same size. In this case, the bronchioles are three to four times the size of the adjacent arteries. Although one cannot make a diagnosis of bronchiectasis the small airway changes suggest that bronchiectasis may be present. Patients with inflammatory bowel disease (IBD) may have a variety of extra intestinal manifestations, including arthritis, ankylosing spondylitis, erythema nodosum, pyoderma gangrenosum, dermatitis, aphthous stomatitis, conjunctivitis, episcleritis, uveitis, hepatitis, pericholangitis, sclerosing cholangitis, primary biliary cirrhosis, pancreatitis, thyroiditis, pyelitis, and pericarditis. Pulmonary complications also occur and although more common in ulcerative colitis, have also been reported in Crohn's disease. The landmark article was published by Camus, et. al., in 1993. They summarized the results of 33 patients with inflammatory bowel disease, predominantly ulcerative colitis (n=27). A number of features emerged from this study. Most patients (84%) developed respiratory involvement following the onset of IBD by nine years (range one week to 36 years). The bowel disease activity at the time of the respiratory illness was variable, many having inactive disease or being post-colectomy. In only 10% was the inflammatory bowel disease active. In a few patients, severe bronchopulmonary involvement developed suddenly and unexpectedly a few days or weeks following proctocolectomy. Rarely, the bowel disease and lung symptoms developed concurrently and in four patients the bronchopulmonary disease developed prior to the IBD. The patterns of pulmonary involvement can be divided into those which consisted predominately of airway disease (60%), interstitial lung disease (35%), parenchymal nodules (5%). (See Table 1). Large airway involvement, as seen in this case, is characterized histologically by the presence of remarkably airway centered disease. The submucosa usually contains a dense cuff of lymphocytes and plasma cells. Occasionally, neutrophils may be present. The mucosa sometimes shows squamous metaplasia. In lobectomy specimens, where large airway involvement can be better appreciated, the inflammatory infiltrate often involves bronchial submucosal glands. Usually, germinal centers are absent from the lymphoid aggregates, an overall pattern unusual for ordinary bronchiectasis. Mucous stasis, as seen in this case, may also be prominent The current case also shows a fairly dramatic endogenous lipoid pneumonia, a manifestation of this patient's inability to adequately clear his secretions. In biopsies lacking bronchi, similar changes may be identified in bronchioles. While some may show simply a chronic bronchiolitis without fibrosis, luminal, and mural fibrosis have also been reported. Such cases could be classified as showing bronchiolitis obliterans (without the organizing pneumonia). In our recent review of eight patients with noninfectious pulmonary complications associated with Crohn's disease (Casey et. al.), the bronchiolitis has taken two forms; one, a chronic bronchiolitis with non- necrotizing granulomatous inflammation within bronchiolar walls and second, a more acute bronchiolitis with bronchopneumonia-like features in the surrounding pulmonary parenchyma. The interstitial changes associated with IBD have been variable and have been classified as bronchiolitis obliterans organizing pneumonia (BOOP), with or without giant cells and non-necrotizing granulomas, nonspecific interstitial pneumonia (NSIP), and eosinophilic pneumonia. Camus, et. al., have commented that the BOOP associated with IBD may be associated with a distinctive marked septal edema which is infiltrated by chronic inflammatory cells and modest numbers of eosinophils, not characteristic of idiopathic BOOP. Table 1 Patterns of thoracic involvement in inflammatory bowel disease * Pattern of involvement Camus 1993 % of total Lit review % total Subglottic stenosis 3 9.4 3 5.3 Chronic bronchitis 6 18.8 12 21.0 Chronic bronchial suppuration 3 9.4 4 7.0 Bronchiectasis 6 18.8 14 24.6 Chronic bronchiolitis 2 6.3 1 1.8 Bronchiolitis obliterans organizing pneumonia 6 18.8 5 8.8 Interstitial lung disease 1 3.1 15 26.3 Pulmonary infiltrates and eosinophilia 3 9.4 0 --- Necrobiotic nodules - neutrophilic infiltrates 2 6.3 3 5.3 Serositis 32 100 57 100 Myocarditis 0 --- 10 24.4 Pericarditis 0 --- 15 36.6 Pleural effusion 0 --- 4 9.6 Pleuropericarditis 1 --- 12 29.3 Total 1 --- 41 100 * from Camus P et al, 1993 Cases associated with eosinophilic pneumonia show airspace, septal, and pleural involvement. The septae may also show marked edematous thickening similar to that seen in cases of BOOP described above. Nonspecific interstitial pneumonia is characterized by temporal and spatial homogeneity of both inflammation and fibrosis (if present). A complete description of this entity and its significance is beyond the scope of this course and handout. Necrobiotic nodules have been described as resembling necrotic granulomas. Early nodules appear to consist of dense airspace accumulations of neutrophils and a fibrinous exudate. These nodules may then undergo central necrosis and cavitation. There is some resemblance of these nodules to infectious and noninfectious granulomas, particularly Wegener's, but they have a notable absence of giant cells and vasculitis. These nodules have been described as being reminiscent of dermal pyoderma gangrenosum. Table 2 summarizes our recent experience and the published literature on pulmonary involvement with Crohn's disease. Although there is some overlap, respiratory involvement may differ in patients with ulcerative colitis and Crohn's disease. For instance, necrobiotic nodules have not been reported in Crohn's disease. Conversely, diseases know to occur in conjunction with Crohn's disease, such as granulomatous involvement of the larynx, trachea, and bronchi have not been reported in patients with ulcerative colitis. Interestingly, both have been reported to be associated with pulmonary sarcoidosis, which this patient had in the past. Whether the pulmonary granuloma seen in patients with inflammatory bowel disease is true sarcoid or a distinct granulomatous process remains unclear. Table 2. Spectrum of Pulmonary Changes Associated with Crohn's Disease Chronic Bronchiolitis with Granulomas Acute bronchiolitis with Bronchopneumonia-like features Non-specific interstitial pneumonia (± giant cells) BOOP with rare granulomas and/or giant cells The differential diagnosis for lung disease associated with IBD is fairly lengthy depending on the exact pattern of involvement. Infection always needs to be excluded with special stains and cultures, particularly because many patients may be on immunosuppressive therapy. The other main possibility to consider is a drug reaction. Drugs used to treat IBD, particularly sulfasalazine and 5-ASA, have been associated with a variety of histologic patterns. Sulfasalazine can cause eosinophilic pneumonia, or chronic interstitial pneumonia not otherwise specified i.e. nonspecific interstitial pneumonia; desquamative interstitial pneumonia, BOOP, diffuse alveolar damage, and hypersensitivity pneumonitis. Although the current patient was not on any medication other than steroids at the time of the biopsy, predominantly airway centered disease as seen in this case is unlikely to be due to drugs. Since bronchiectasis and bronchiolectasis are usually secondary, when a pathologic diagnosis is made the clinical differential will depend on whether the process is focal or diffuse. See Table 3. Table 3: Bronchiectasis: Clinical Associations Localized (Focal) Bronchial "obstruction" Recurrent Pneumonia Middle lobe syndrome (right/lingula) Endobronchial tumor Foreign body MAC-associated Diffuse bronchiectasis Chronic aspiration Recurrent pneumonia Cystic fibrosis Hypogammaglobulemia Immotile cilia Kartagener's Syndrojme Yellow nail syndrome Inflammatory bowel disease MAC associated Allergic bronchopulmonary fungal disease Idiopathic Congenital: Mounier-Kuhn's syndrome In this older adult patient, the combination of airway dilatation, and non-necrotizing granulomatous inflammation makes mycobacterium-avium complex (MAC) airway disease the most realistic differential diagnostic consideration. MAC-associated airway disease typically occurs in elderly women. When it occurs in the right middle lobe or lingula it has been the Lady Windermere syndrome. Whether bronchiectasis is the primary process or a result of chronic MAC infection is not clear. 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