Metastatic Crohn's Disease of the Lung

Abstract

Crohn's disease (CD) may affect any segment of the gastrointestinal tract(1). Extraintestinal lesions, although rare, are by no means uncommon (2). Overt pulmonary abnormalities of CD in adults (3) have been described in a few reports. These comprise: granulomatous lung disease, interstitial fibrosis, and acute alveolitis (3). In contrast, latent pulmonary changes(alveolar lymphocytosis, activation of alveolar macrophages, and abnormal pulmonary function tests) seem to be frequent in Crohn's disease(4). In children, three cases with metastatic granulomatous lung CD have been reported by the Birmingham group(5,6). We describe another case of pulmonary Cd, diagnosed for the first time by endoscopy with endobronchial granulomata as the dominant lung lesion. CASE REPORT A 15-year-old, malnourished girl had a 3-month history of exercise-induced dyspnea, cough, anorexia, malaise, recurring vomiting, abdominal pain, occasional febrile episodes, and hair loss. Her stools were intermittently loose and bulky. She had experienced growth failure from the age of 12. On admission, she was pale and ill, below the 3rd percentile for height and weight. Late inspiratory crackles were heard over the right upper chest. Finger clubbing, slight pretibial edema, and an absence of pubertal signs were present as well. Investigations Laboratory investigations showed erythrocyte sedimentation rate, 40 mm/hour; hemoglobin concentration, 104 g/l; and leukocyte count, 9.2 × 109/l. Urinalysis was normal. Total serum protein concentration was 42 g/l, and serum albumin was 24 g/l. Sweat chloride concentration, stool chromatography for sugars, duodenal juice, and stool microscopy for parasites, liver function test, serum iron concentration, blood urea nitrogen, serum electrolyte levels, α1-antitrypsin activity, and serum immunoglobulins were all normal or negative. Fecal fat excretion was within normal limits (4.2 g/24 hours). Serum angiotensin-converting enzyme activity was normal at 14.1 U/l (normal range, 5-33 U/l). Results of a Kveim test were negative and a Mantoux test with three tuberculin units of purified protein derivative caused 9 mm of hyperemia. It should be mentioned that this child had been immunized regularly against tuberculosis. Chest radiograph showed central density of the right middle lobe with a minor interlobar effusion(Fig. 1). There was no hilar adenopathy. An upper gastrointestinal series with small bowel follow-through revealed stenosis at the duodenojejunal flexure, a narrowed first jejunal loop with thickened walls, penetrating ulcers, and blind fistulas (Fig. 1). The distal ileum was grossly abnormal, with thickened walls, a nodular surface, and ulcers (Fig. 1). A barium enema and contrast study showed distortion and contraction of the ileocecal region with ulcerations. Fiberoptic esophagogastroduodenoscopy demonstrated pale duodenal mucosa with reduced circular folds. At colonoscopy, the cecum and the terminal ileum were observed to be abnormal. Small aphthoid ulcers, irregular erosions, and wide and superficial mucosal ulcers were seen.FIG. 1: (A) Chest radiograph demonstrates right parahilar parenchymal consolidation with pleural interlobar affection. (B) Duodenojejunal flexure is distorted. There are deep penetrating ulcers of the first loop of the jejunum.(C) Terminal ileum is tubular, with numerous mucosal ulcers. Note segmental bowel narrowing.At bronchoscopy, multiple whitish mucosal elevations were seen at the beginning of the intermediate bronchus, and a biopsy was obtained immediately. Cytology of bronchoalveolar aspirate showed increased percentages of lymphocytes (23.1%; normal, <7%), eosinophils (16.9%; normal, <1%), and neutrophils (8.9%; normal, <5%). Acid- and alcohol-fast bacilli staining and culture of bronchoalveolar aspirates for mycobacteria were all negative. Pulmonary function tests excluded a restrictive disorder, with vital capacity of 87.7% and total lung capacity of 89.9% of predictive values. Transfer factor for carbon monoxide(79%) and coefficient of diffusion (109%) were not reduced. Pathologic Findings Histologic analysis of multiple endobronchial mucosal biopsies showed signs of chronic mucosal inflammation with subepithelial noncaseating and epithelioid granulomas (Fig. 2). Stains for acid- and alcohol-fast bacilli and fungi were negative in all of these specimens. In histologic analysis, duodenal mucosal biopsy specimens demonstrated patchy enteropathy with foci of subtotal villous atrophy, diffuse mononuclear cell infiltration of the lamina propria, and foci of subepithelial hyperplastic lymphoid follicles. Mucosal histologic study of the cecum and terminal ileum indicated chronic inflammatory infiltrate with lymphocytes and plasmocytes, lymphoid hyperplasia, fissures, edema, and fibrosis. Granulomas were not seen.FIG. 2: Study of endoscopic bronchial biopsy specimen demonstrates subepithelial infiltration with lymphocytes and plasma cells. There is subepithelial granulomatous formation consisting of epithelial cells and lymphocytes (arrow).Clinical Progress A course of antituberculosis drugs (isoniazid, rifampicin, pyrazinamide) was discontinued after 8 weeks, when all bacteriologic cultures proved to be negative. Clinical response to chemotherapy was unsatisfactory. The patient's further treatment consisted of 1.5 mg/kg oral prednisolone daily, 2 g sulphasalazine daily, and vitamin and microelement supplementations. All symptoms and laboratory abnormalities completely resolved during the next 2 months, and she gained 11 kg. She was eventually discharged 4 months after admission, eating a normal diet and taking 10 mg of prednisolone on alternate days, and sulphasalazine. Pulmonary symptoms almost subsided; no major changes were noted in chest radiographs. DISCUSSION Crohn's disease (CD) is considered a systemic disorder, predominantly affecting the gastrointestinal tract, but manifesting a wide variety of extraintestinal associations (7). These encompass more than 130 systemic manifestations (7). Their recognition is important because they may precede clinically apparent intestinal symptoms or may account for predominant morbidity. Traditionally, joint, skin, eye, mouth, and hepatobiliary inflammation are the most frequent systemic inflammatory conditions of CD, which affects predominantly the large bowel(2,8). In patients with inflammatory bowel disease, clinically significant pulmonary manifestations are rare. Most of these patients with respiratory or pleuropericardial disease have ulcerative colitis rather than CD(7). It has been demonstrated that a high proportion of adults with CD have increased alveolar lymphocytes (4). This may indicate CD-associated alveolar lymphocyte alveolitis, which is a characteristic feature of pulmonary granulomatous disorders seen in sarcoidosis, hypersensitivity pneumonitis, and berylliosis(7). Abnormal results in pulmonary function tests recorded in adult patients with CD do not seem to be related to alveolar lymphocytosis. The clinical significance and the natural history of latent CD of the lung remains to be determined. Overt respiratory involvement of CD consists mainly of granulomatous airway disease, interstitial inflammation, and fibrosis(3). It seems that CD-associated granulomatous involvement of the bronchial tree is prevalent (3). This raises differential diagnostic questions of dividing intrapulmonary manifestations of CD from extrapulmonary, intestinal involvement of sarcoidosis (9). Low serum angiotensin activity and negative Kveim results may help to discern these two entities. The similarities between sarcoidosis and CD, which include unknown cause, noncaseating epithelioid granulomas, and tendency toward fibrosis and shared complications such as erythema nodosum, uveitis, and arthritis, have prompted some investigators to consider these two entities less distinct with overlapping symptoms (10). We were able to demonstrate for the first time endobronchial changes of CD by endoscopy and mucosal biopsy. These findings, combined with Kveim test results and serum angiotensin-converting enzyme measurement, were sufficient for diagnosis of CD of the lung. It seems that more routine bronchoscopy in all CD cases with suspected clinical or radiologic chest abnormality will enable us to determine the true incidence of CD of the lung. Acknowledgment: The authors thank Professor Dr. Ian W. Booth for his help with the manuscript and for his constant support.