Akobeng, Anthony K.; Miller, Victor; Thomas, Adrian G.
Department of Paediatric Gastroenterology, Booth Hall Children's Hospital, Manchester, United Kingdom
Received May 20, 1998; revised August 24, 1998; accepted August 26, 1998.
Address correspondence and reprint requests to Dr. Anthony K. Akobeng, Department of Paediatric Gastroenterology, Booth Hall Children's Hospital, Charlestown Road, Blackley, Manchester, UK M9 7AA.
Inflammatory bowel disease (IBD) is associated with a wide variety of extraintestinal manifestations. Symptomatic pulmonary involvement is rare, although asymptomatic abnormalities of lung function tests have been reported to be common in patients with Crohn's disease. Suppurative lung disease, as an extraintestinal manifestation of IBD, has rarely been described. We report a 9-year-old boy with a long-standing history of unexplained bronchiectasis who experienced weight loss, bloody diarrhoea, and lethargy. Subsequent investigations confirmed a diagnosis of intestinal Crohn's disease. We discuss the rare association between chronic suppurative lung disease and inflammatory bowel disease. Other pulmonary manifestations of inflammatory bowel disease are mentioned, and the possible pathogenesis of pulmonary disorders in inflammatory bowel disease is discussed.
A 4-week-old boy had initial symptoms of right upper lobe pneumonia, diarrhoea, and failure to thrive. He was treated with antibiotics, and findings in investigations for failure to thrive were normal. A jejunal biopsy specimen obtained at 1 year of age because of recurrent diarrhoea and failure to thrive showed low lactase activity, and a lactose-free diet was prescribed. His diarrhoea subsequently settled and his weight improved.
His respiratory symptoms of breathlessness, cough, and wheeze did not respond to treatment, and chest radiographs showed a persistent consolidation in the right upper lobe. Several investigations including repeated sweat tests, genetic analysis for cystic fibrosis, Mantoux tests, repeated sputum cultures for acid-fast bacilli, α1-antitrypsin levels, and a barium contrast study did not reveal a cause for his lung disease. Bronchoscopy performed at the age of 3 years showed collapse and consolidation of the right upper lobe with no foreign body. Despite intensive antibiotic treatment and physiotherapy, he continued to have persistent collapse and consolidation, and a right upper lobectomy was performed at the age of 4 years. His respiratory symptoms persisted, however, and a bronchography performed at the age of 5 years revealed bronchiectasis of the left lower lobe. By the age of 6 years, he had extensive bilateral bronchiectasis, and he was treated with various bronchodilators, antibiotics, and physiotherapy with little effect. He was noted to have hepatomegaly and hypoproteinaemia at the age of 7 years and analysis of a liver specimen showed very mild microvesicular fatty changes.
Bloody diarrhoea, weight loss and lethargy developed when he was 9 years old. Investigations at this time showed elevated erythrocyte sedimentation rate of 43 mm in the first hour, and a raised orosomucoid level of 3550 mg/l. He had positive serum mitochondrial antibodies. Colonoscopy showed macroscopic inflammation throughout the colon and histologic analysis of a mucosal specimen confirmed active pancolitis with features of chronicity. A small bowel enema examination showed irregularity and asymmetry of the mucosa of the terminal ileum consistent with Crohn's disease. He has since been treated with intermittent courses of oral steroids.
Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the bowel whose causes are not known (1). Extraintestinal manifestations may be seen in approximately 25% to 35% of patients (2) and usually involve the skin, joints, and liver. Extraintestinal involvement has also been described in other organs such as the brain (3), genitals (4), kidneys (5), and bone (6).
Symptomatic pulmonary involvement is rare, although some studies suggest that latent abnormal pulmonary function tests, in the absence of symptoms, are common in patients with both Crohn's disease (7,8) and ulcerative colitis (8). Lymphocyte alveolitis, a frequent feature in granulomatous interstitial conditions of the lung such as sarcoidosis, has been described in Crohn's disease (7,9). Wallaert et al. (10) and Bonniere et al. (7) have demonstrated that alveolar macrophages obtained through bronchoalveolar lavage in patients with Crohn's disease show increased production of superoxide anion, an oxygen free radical. The half-time clearance of inhaled technetium-99m diethylene triamine pentacetate (99mTc-DTPA) from lung to blood has been found to be decreased in patients with Crohn's disease compared with that in healthy control subjects, suggesting increased pulmonary permeability (11). This situation is analogous to the increased intestinal permeability that is seen in Crohn's disease and may mean a generalised increase in epithelial permeability in the disease. Munck et al. and his colleagues (12) recently studied lung function abnormalities in children with Crohn's disease. They demonstrated a significant decrease in lung transfer factor for carbon monoxide during the active phase of the disease, compared with periods of remission. The clinical significance of all these latent changes is unclear.
Our patient has Crohn's disease and bilateral bronchiectasis. Although Calder et al. (13) and Puntis et al. (14) have described two children with Crohn's disease and granulomatous disease of the lung, we know of no reported association between chronic bronchial suppuration and inflammatory bowel disease in a child. There have, however, been a few reports of such an association in adult patients with inflammatory bowel disease (15-17). In a recent review, Spira et al. (18) reported five adult patients with IBD-associated bronchiectasis. Three of them experienced significant improvements in their respiratory symptoms after treatment with oral or inhaled corticosteroids.
In view of the time relationships of the bowel and pulmonary symptoms in our patient, it is important to consider whether the association represents the chance occurrence of two unrelated disorders. Pulmonary involvement in inflammatory bowel disease is recognised to occur either before, after, or concurrently with the onset of bowel disease (13). Butland et al. (15) reported two women aged 45 and 26 years whose inflammatory bowel diseases were preceded by suppurative lung conditions by 38 and 15 years, respectively. The unexplained cause of our patients' bronchiectasis, despite extensive investigations, makes a link with inflammatory bowel disease more likely in him. The presence of serum mitochondrial antibodies is also consistent with the reported high incidence of autoantibodies in patients with IBD and bronchial suppuration (15,16). The early age of onset of his respiratory symptoms may make it appear unlikely for these symptoms to be related to Crohn's disease which, is primarily a disease of older children and young adults. Crohn's disease has been reported in infants, however. Mezoff et al. (19) described a male infant who had bloody diarrhoea at the age of 4 weeks and in whom Crohn's disease was subsequently diagnosed.
The cause of bronchopulmonary changes seen in IBD is unclear but may have an underlying immunologic basis (13). Serum autoantibodies have been reported in patients with IBD and suppurative lung disease (15,16), and our patient had positive mitochondrial antibodies. In their series, Butland et al. (15) detected antinuclear antibodies in six, and smooth muscle antibodies in five of seven patients with chronic suppurative lung disease and IBD. They also found circulating immune complexes in two of the patients. The local immune system in the gut is known to share many similar features with that in the lung (13). It has therefore been suggested that, during early infancy, similar antigens could sensitise both the gut and bronchia-associated lymphoid tissues, thus making the mucosa of both organs susceptible to an allergic inflammatory response when they are exposed to a common unidentified environmental agent in the future (16).
In conclusion, suppurative lung disease is a rare complication which should be considered in patients with IBD in whom persistent and unexplained respiratory symptoms develop. An early diagnosis is important, because oral or inhaled corticosteroids can lead to significant improvements in respiratory symptoms.
1. Seidman EG. Epidemiology and current etiological concepts. In: Levine JL, Pettei MJ eds. Monographs in clinical pediatrics: inflammatory bowel disease in children and adolescents.
Switzerland: Harwood Academic Publishers, 1995:1-14.
2. Hyams JS. Extraintestinal manifestations of inflammatory bowel disease in children. J Pediatr Gastroenterol Nutr
3. Akobeng AK, Miller V, Thomas AG. Epilepsy and Crohn's disease in children. J Pediatr Gastroenterol Nutr
4. Polysangam T, Heubi JE, Eisen D, et al. Cutaneous Crohn's disease in children. J Am Acad Dermatol
5. Weinstein T, Pettei M. Extraintestinal complications. In: Levine JJ, Pettei MJ, eds. Monographs in clinical pediatrics: Inflammatory bowel disease in children and adolescents.
Switzerland: Harwood Academic Publishers, 1995;67-80.
6. Cowan FJ, Warner JT, Dunstan FDJ, et al. Inflammatory bowel disease and predisposition to osteopenia. Arch Dis Child
7. Bonniere P, Wallaert B, Cortot A, et al. Latent pulmonary involvement in Crohn's disease: Biological, functional, bronchoalveolar lavage and scintigraphic studies. Gut
8. Sommer H, Schmidt MM Gruber KD. Pulmonary functional disorders in ulcerative colitis and Crohn's disease. Dtsch Med Wochenschr
9. Wallaert B, Colombel JF, Tonnel AB, et al. Evidence of lymphocyte alveolitis in Crohn's disease. Chest
10. Wallaert B, Aerts C, Bonniere P et al. Superoxide anion generation by alveolar macrophages in Crohn's disease. N Engl J Med
11. Adenis A, Colombel JF, Lecouffe P, et al. Increased pulmonary and intestinal permeability in Crohn's disease. Gut
12. Munck A, Murciano D, Pariente R, et al. Latent pulmonary abnormalities in children with Crohn's disease. Eur Respir J
13. Calder CJ, Lacy D, Raafat F, et al. Crohn's disease with pulmonary involvement in a 3 year old child. Gut
14. Puntis JW, Tarlow MJ, Raafat F, Booth IW. Crohn's disease of the lung. Arch Dis Child
15. Butland RJA, Cole P, Citron KM, Turner-Warwick M. Chronic bronchial suppuration and inflammatory bowel disease. Q J Med
16. Gibb WRG, Dhillon DP, Zilkha KJ, Cole PJ. Bronchiectasis with ulcerative colitis and myelopathy. Thorax
17. Kraft SC, Earle RH, Roesler M, Esterly JR. Unexplained bronchopulmonary disease with inflammatory bowel disease. Arch Intern Med
18. Spira A, Grossman R, Balter M. Large airway disease associated with inflammatory bowel disease. Chest
19. Mezof AG, Cohen MB, Maisel SK, Farrell MK. Crohn's disease in an infant with central nervous system thrombosis and protein-losing enteropathy. J Pediatr
© 1999 Lippincott Williams & Wilkins, Inc.