Secondary Logo

Journal Logo

Case Reports

Severe Crohn Disease of the Lung Following Colectomy

Mahgoub, Linda EO*; Puntis, John WL*; Chetcuti, Philip AJ; Sugarman, Ian D

Author Information
Journal of Pediatric Gastroenterology and Nutrition: October 2007 - Volume 45 - Issue 4 - p 477-479
doi: 10.1097/MPG.0b013e318031c7f0
  • Free


Inflammatory bowel disease (IBD) presents in childhood in 15% to 25% of patients (1) and is associated with a wide variety of extraintestinal complications including pulmonary disease. We report a child with Crohn disease (CD) who became increasingly breathless 18 months following colectomy. Investigations showed this to be due to severe pulmonary inflammation confirmed on biopsy to be CD of the lung.


A 5-year-old boy was referred with a 7-month history of bloody diarrhea and abdominal pain together with weight loss and lethargy. There was no significant past medical or family history. On examination he was pale and unwell with height on the 25th centile and weight between the 25th and 50th centiles; the perianal skin was reddened and oedematous. Investigations revealed increased inflammatory markers (C-reactive protein, 25 mg/L; platelets, 557 × 109/L), anemia (hemoglobin, 97 g/L), and low serum albumin level (28 mg/L); stool cultures were negative for pathogens.

The clinical impression was of CD. Although a technetium-labeled white blood cell scan showed no evidence of active IBD, upper gastrointestinal endoscopy demonstrated superficial duodenitis, and colonoscopy revealed an extensive ulcerative proctocolitis with inflammatory changes throughout the large intestine. Histological findings included acute and chronic inflammatory cell infiltration, most severe in the rectum, with scattered crypt abscesses. Several well-formed noncaseating granulomas were identified at all levels of the colon and in the terminal ileum, thereby confirming the diagnosis of CD. Treatment was initiated with an exclusion diet and sulfasalazine 200 mg 4 times daily. He showed little clinical response and prednisolone 2 mg/kg each day was added. Occasional steroid therapy was then required over the next 2.5 years for control of recurrent bloody diarrhea. He remained generally well, attended school, and reported minimal symptoms; however, height velocity was far less than expected and repeat colonoscopy was performed to establish disease activity. Again this revealed a markedly inflamed and oedematous colonic mucosa with contact bleeding. In addition, he was found to have a colonic fistula and therefore underwent laparotomy, subtotal colectomy, ileostomy, and mucous fistula formation. He was weaned from treatment and showed catch-up in height with resolution of all of his symptoms over the next year.

Eighteen months after surgery he was readmitted with a 4-month history of weight loss (to <0.4th centile), cough, and increasing breathlessness. On clinical examination he was tachypneic and unwell, requiring oxygen to maintain normal saturations. Auscultation revealed widespread bilateral crepitations. Chest radiography showed extensive airspace shadowing and several ring shadows. High-resolution computed tomography demonstrated changes consistent with interstitial lung disease (Fig. 1). On abdominal ultrasound examination there was no evidence of abnormal small bowel thickening, and no evidence of CD was found on upper gastrointestinal endoscopy.

FIG. 1:
High-resolution CT demonstrates changes consistent with interstitial lung disease.

Serum antibodies against respiratory viral pathogens and toxocara were negative. Allergic bronchopulmonary aspergillosis and hypersensitivity pneumonitis were ruled out. Serum angiotensin-converting enzyme was within the reference range and tests of neutrophil function including the nitroblue tetrazolium test were normal. Lung function tests were not done at this time because of his poor general condition. Bronchoscopy was unremarkable and bronchoalveolar lavage and lung biopsy were negative for immunofluorescence culture or acid-fast bacilli, as was polymerase chain reaction for mycobacterium, fungi, pneumocystis, and aspergillosis. Histological examination of lung tissue showed noncaseating epithelioid granulomatous inflammation throughout the pulmonary parenchyma with lymphocytic interstitial pneumonitis and focal scarring, consistent with a diagnosis of CD of the lung (Fig. 2).

FIG. 2:
Lung biopsy shows noncaseating epithelioid granulomatous inflammation.

Treatment was commenced with daily prednisolone starting at 60 mg and tapering to 5 mg after 3 months. Seven months later there was only moderate improvement in respiratory status, and therefore azathioprine 50 mg (2 mg/kg) daily was added (later increased to 3 mg/kg). Despite treatment with azathioprine and prednisolone, there has been little overall improvement in his clinical status in the past 2 years. He is still experiencing exercise-induced hypoxia and requires gastrostomy feeding to maintain nutritional status, and has developed finger clubbing and right ventricular hypertrophy. A trial of infliximab therapy has not improved his lung function and lung transplantation is being considered as a future treatment option.


There is a wide clinical spectrum of pulmonary involvement in CD. It may be asymptomatic with incidental abnormal lung function test results and reduced carbon monoxide transfer factor or it may present with marked respiratory symptoms and signs. It has sometimes been reported as a presenting feature of CD (2,3). As far as we are aware, this is the first report of severe CD of the lung appearing in childhood long after complete surgical resection of inflamed bowel.

Respiratory system involvement in CD includes bronchial hyper responsiveness, lymphocytic alveolitis, chronic bronchitis, subglottic stenosis, severe chronic bronchial suppuration, bronchiectasis, bronchiolitis obliterans organizing pneumonia, pulmonary infiltrates with peripheral eosinophilia, granulomatous and nongranulomatous interstitial lung disease, and pleuritis (4–8). Bronchial hyperresponsiveness occurs in a high proportion of children and adolescent subjects with CD (71%) even in the absence of clinical, radiological, and functional evidence of airway disease (4). The overall prevalence of respiratory complications in IBD remains to be clearly defined. One study suggested they occurred in as few as 0.4% of patients (9), but this may be an underestimation (10,11). Lung involvement occurs less frequently in CD than ulcerative colitis (12,2). Although asymptomatic pulmonary involvement in CD has been widely reported (7), symptomatic lung disease appears uncommon (2) and occurs mainly in adults.

The pathogenesis also remains obscure, and some patients have increased pulmonary permeability when measured by clearance of inhaled technetium-99m diethylenetriaminepentaacetic acid (12). It is possible that a common antigenic stimulus results in the pulmonary and intestinal manifestations of CD (13). Circulating immune complexes and complement deposition may also be involved (14). Colectomy has been implicated as a risk factor for the development of pulmonary disease (11). Camus et al (7) found that airway involvement in IBD was more common after colectomy; some of these patients also demonstrated worsening of existing lung disease (7). The common embryologic origin of the lungs and gastrointestinal tract from the primitive foregut and the similarity in the immune systems in pulmonary and intestinal mucosa may mean that, after colectomy, the lungs become a target for the abnormal inflammatory response (11). Our patient developed symptomatic lung disease more than 1 year after colectomy and in the absence of evidence of active gastrointestinal CD. This suggests an ongoing inflammatory process independent of bowel disease activity. Although he remained free of respiratory symptoms for almost 1 year after medical treatment had been discontinued, it is also possible that steroid withdrawal permitted progression of what was originally a subclinical respiratory pathological process.

The differential diagnosis includes chronic granulomatous disease, sarcoidosis, Wegener granulomatosis, pulmonary emboli, and drug-induced pulmonary fibrosis. Chronic granulomatous disease was excluded by the negative nitroblue tetrazolium test results and sarcoidosis is ruled out by the normal angiotensin-converting enzyme level (15). In addition, sarcoidosis is rare in childhood and gastrointestinal involvement is uncommon (2). The lung biopsy from our patient was also more consistent with CD, and the granuloma distribution was atypical for pulmonary sarcoidosis; however, sarcoidosis and IBD may occasionally occur together (14). Wegener granulomatosis is a cause of lung disease and is also associated with IBD (14,16,17). More than half of all patients with Wegener granulomatosis have lung parenchymal involvement and bronchoscopic abnormalities (18). In our patient there were no bronchoscopic abnormalities and no histological evidence of vasculitis. Pulmonary emboli may arise in IBD (14), but radiological and histological findings in our patient would not be consistent with this diagnosis. Drug-induced pulmonary fibrosis (usually associated with eosinophilia and lung infiltrates) from sulfasalazine appears unlikely not only on histological grounds but also because this treatment was withdrawn 14 months before appearance of the respiratory symptoms. Granulomatous interstitial pneumonitis is a mesalamine-induced lung lesion; this rare adverse reaction has recently been reported in a child. It is dose-related and responds to drug withdrawal (19).

Treatment for pulmonary involvement in IBD usually relies on corticosteroids (7,11) and can be effective when there is evidence of large airway disease (more so when inhaled than given by mouth). In some refractory cases, benefit has been achieved by local bronchoscopic delivery of steroid therapy (16). Among 33 patients with pulmonary complications of IBD, 2 had debilitating bronchiectasis and were listed for lung transplantation. Four patients died from complications of sulfasalazine-induced lung fibrosis or interstitial lung disease, one of whom was a child (7). Successful use of anti-tumor necrosis factor treatment for “metastatic” CD has been reported (20,21). A recent publication details how CD of the lung was treated successfully with a single infusion of infliximab leading to remarkable clinical and radiographic improvement (22). Our patient did not benefit from this therapy, and clearly illustrates that severe extraintestinal manifestation of CD may occur a long time after complete resection of diseased bowel, underlining the need for careful follow-up.


The authors thank Dr Catherine Cullinane, Consultant Paediatric Histopathologist, St James University Hospital, for her interpretation of the histological features of tissue samples.


1. Kim SC, Ferry GD. Inflammatory bowel diseases in paediatric and adolescent patients: clinical, therapeutic, and psychosocial considerations. Gastroenterology 2004; 126:1550–1560.
2. Al-Binali AM, Scott B, Al-Garni A, et al. Granulomatous pulmonary disease in a child: an unusual presentation of Crohn's disease. Pediatr Pulmonol 2003; 36:76–80.
3. Valletta E, Bertini M, Sette L, et al. Early bronchopulmonary involvement in Crohn disease: a case report. BMC Gastroenterol 2001; 1:13.
4. Mansi A, Cucchiara S, Greco L, et al. Bronchial hyperresponsiveness in children and adolescents with Crohn's disease. Am J Respir Crit Care Med 2000; 161:1051–1054.
5. Munck A, Murciano D, Pariente R, et al. Latent pulmonary function abnormalities in children with Crohn's disease. Eur Respir J 1995; 8:377–380.
6. Fraser RS, Colman N, Muller NL, et al. Connective tissue diseases. In: Fraser RS, Muller NL, Colman N, et al. (eds). Fraser and Pare's Diagnosis of Diseases of the Chest, 4th ed. Philadelphia: WB Saunders; 1999: 1473–5.
7. Camus P, Piard F, Ashcroft T, et al. The lung in inflammatory bowel disease. Medicine (Baltimore) 1993; 72:151–183.
8. Hotermans G, Benard A, Guenanen H, et al. Nongranulomatous interstitial lung disease in Crohn's disease. Eur Respir J 1996; 9:380–382.
9. Rodgers BH, Dark LM, Kirsner YB. The epidemiologic and demographic characteristics of inflammatory bowel disease: analysis of a computerized file of 1400 patients. J Crohn Dis 1971; 24:743–773.
10. Xia K, Wolf J, Friedman S, et al. Granulomatous tracheo-bronchitis associated with Crohn's disease. Med Gen Med 2004; 6:18.
11. Mahadeva R, Walsh G, Flower CDR, et al. Clinical and radiological characteristics of lung disease in inflammatory bowel disease. Eur Respir J 2000; 15:41–48.
12. Adenis A, Colombel JF, Lecouffe P, et al. Increased pulmonary and intestinal permeability in Crohn's disease. Gut 1992; 33:678–682.
13. Calder CJ, Lacy D, Raafat F, et al. Crohn's disease with pulmonary involvement in a 3 year old boy. Gut 1993; 34:1636–1638.
14. Storch I, Sachar D, Katz S. Pulmonary manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2003; 9:104–115.
15. Letzia C, D'Ambrosio C, Agostini D, et al. Serum angiotensin converting enzyme activity in Crohn's disease and UC. Ital J Gastroenterol 1993; 25:23–25.
16. Camus P, Colby T. The lung in inflammatory lung disease. Eur Respir J 2000; 15:5–10.
17. Morris M, Cole D, Allan P. Pulmonary disease associated with inflammatory bowel disease. Clin Pulmon Med 2005; 12:246–257.
18. Prince J, Duhamel D, Levin D, et al. Nonneoplastic lesions of the tracheobronchial wall: radiologic findings with bronchoscopic correlation. Radiographics 2002; 22:215–230.
19. Kohli R, Melin-Aldana H, Sentongo T. Mesalamine-induced pneumonitis during therapy for chronic inflammatory bowel disease: a paediatric case report. J Pediatr Gastroenterol Nutr 2005; 41:479–482.
20. Van Dullemen HM, de Jong E, Slors F, et al. Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, Ca2: report of two cases. Dis Col Rect 1998; 41:98–102.
21. Gill K, Mahadevan U. Infliximab for the treatment of metastatic hepatic and pulmonary Crohn's disease. Inflamm Bowel Dis 2005; 11:210–212.
22. Alrashid AI, Brown RD, Mihalov ML, et al. Crohn's disease involving the lung: resolution with infliximab. Dig Dis Sci 2001; 46:1736–1739.
© 2007 Lippincott Williams & Wilkins, Inc.