Clin J Gastroenterol (2014) 7:155–158 DOI 10.1007/s12328-014-0473-7
CASE REPORT
Pulmonary involvement: a rare extraintestinal manifestation of ulcerative colitis Jun Nishikawa • Ayumu Hosokawa • Hiroshi Mihara • Ryuji Hayashi • Shigeharu Miwa • Tatsuhiko Kane • Sohachi Nanjo • Takayuki Ando • Haruka Fujinami • Shinya Kajiura • Masami Minemura • Toshiro Sugiyama
Received: 3 December 2013 / Accepted: 22 February 2014 / Published online: 13 March 2014 Ó Springer Japan 2014
Abstract Ulcerative colitis (UC) is associated with a number of extraintestinal manifestations (EIMs) that may affect most organ systems. Among the EIMs, those involving the lung are rare. We report a case of pulmonary involvement and pyoderma gangrenosum in a patient with refractory UC. A chest computed tomography showed multiple nodular infiltrates in bilateral lungs. The patient had no respiratory symptoms. No infectious agents were detected. A transbronchial biopsy specimen showed nonspecific features. Prednisolone was initiated with significant improvement in the patient’s abdominal symptoms and pyoderma gangrenosum. Subsequent imaging after steroid therapy showed improvement of the pulmonary infiltrates. The patient’s abdominal symptoms relapsed when prednisolone was tapered. The patient subsequently received a proctocolectomy. Chest radiographs have shown resolution of pulmonary infiltrates. Because pulmonary involvement follows an independent course and a proctocolectomy may not be protective against a recurrence of
J. Nishikawa (&) A. Hosokawa H. Mihara T. Kane S. Nanjo T. Ando H. Fujinami S. Kajiura M. Minemura T. Sugiyama Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan e-mail: [email protected] R. Hayashi First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan S. Miwa Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
pulmonary involvement, a careful follow-up should be continued. Keywords Ulcerative colitis Inflammatory bowel disease Pulmonary involvement Extraintestinal manifestation
Introduction Ulcerative colitis (UC) is associated with a number of extraintestinal manifestations (EIMs) that may affect most organ systems. EIMs are significant cause of morbidity and may be distressing for the patients. Among the EIMs, those involving the lung are rare. We report a case of pulmonary involvement in a patient with UC.
Case report A 21-year-old man with an 8-year history of UC was admitted because of exacerbation of symptoms. When he presented, he was having five bowel movements per day, intermittent rectal bleeding and mild abdominal pain. He also had pyoderma gangrenosum as an EIM of UC. Medication history included mesalazine, multiple courses of steroids, and five infliximab infusions. Azathioprine was withdrawn due to liver injury. He was a non-smoker and had no history of respiratory disease. On admission, a physical examination revealed his body temperature to be 38.1 °C, and oxygen saturation to be 98 % while breathing ambient air. His lungs were clear on auscultation. His abdomen was soft, and mildly tender to palpation in the left lower quadrant. Pyoderma gangrenosum, a tender erythematous papule, was present on his right lower limb. His
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Fig. 1 Chest X-ray images of the patient. a Three weeks prior to the admission; b at admission
white blood cell count was 12,100/lL (75 % neutrophils), red blood cell count was 481 9 104/lL, hemoglobin was 11.7 g/dL and platelet count was 51.1 9 104/lL. Peripheral eosinophilia was absent. C-reactive protein was 6.9 mg/ dL. Liver and renal function test results were normal, and cytomegalovirus-pp65 antigenemia test results were negative. Rheumatoid factor, antinuclear antibodies, and proteinase-3 anti-neutrophil antibody test results were also negative. A colonoscopy revealed moderately active extensive UC. No pathogens or Clostridium difficile toxin could be detected in stools. A chest X-ray revealed bilateral infiltrates in the apex regions that had not been identified 3 weeks prior to this admission (Fig. 1a, b). The computed tomography showed multiple peripheral infiltrates in bilateral lungs (Fig. 2). He denied any cough or dyspnea. Routine bacterial, fungal, and mycobacterial cultures of sputum were negative. A skin test for tuberculosis was also negative. He was prescribed an empiric course of antibiotics, with no improvement in the chest X-ray results or fever. A bronchoscopy with transbronchial biopsy was performed. A brushing cytology specimen revealed bronchial columnar cells, and pulmonary macrophages, but no malignant cells. Gram stain and cultures for bacteria were negative and special stains for fungi and mycobacteria were negative as well. A biopsy specimen showed nonspecific features of fibrin deposition and mixed infiltrates with prominent neutrophils and other inflammatory cells in the alveolar spaces (Fig. 3a, b). There was no evidence of vasculitis. His clinical presentation, radiographs and pathology findings were consistent with organizing pneumonia. Prednisolone (50 mg daily) was initiated with significant improvement in the patient’s abdominal symptoms and pyoderma gangrenosum. Subsequent imaging after steroid therapy showed improvement of the pulmonary infiltrates (Fig. 4). His abdominal symptoms relapsed when prednisolone was tapered to 15 mg. He subsequently
123
Fig. 2 Chest computed tomography showing bilateral multiple pulmonary infiltrations
received a proctocolectomy, and chest radiographs have shown resolution of pulmonary infiltrates.
Discussion The overall incidence of EIMs in patients with inflammatory bowel disease has been reported to range from 6 to
Clin J Gastroenterol (2014) 7:155–158
157
Fig. 3 A transbronchial biopsy specimen showed nonspecific feature of fibrin deposition and a mixed infiltrate with prominent neutrophils and other inflammatory cells. (Hematoxylin and eosin stain, a 9100, b 9400)
47 % [1, 2]. EIMs of UC include those related to the disease activity (arthritis, erythema nodosum, and ocular involvement). Others are nonspecific disorders that follow an independent course (hepatobiliary, osteoporosis, and amyloidosis). Pulmonary involvement and pyoderma gangrenosum belong to a nonspecific category that is not linked to active inflammation. Although EIMs of UC are common, clinically evident pulmonary involvement is rare. Pulmonary involvement in UC may reflect the common embryonic origin of both the gastrointestinal tract and the bronchial tree [3]; both the colonic and respiratory epithelia are of foregut origin. In addition, both gut-associated and bronchus-associated lymphoid tissues play important roles in the host mucosal defense. The similarity in the mucosal
Fig. 4 Chest computed tomography after steroid therapy showing resolution of pulmonary infiltrates
immune systems may cause inflammation at two different sites. In addition, aberrant homing of activated T-cells into the lungs from the primary sites of chronic inflammation may occur [4].
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158
It remains difficult to determine whether pulmonary lesions are secondary to the drugs or to the underlying disease process. The most common pulmonary abnormalities of inflammatory bowel disease are drug-induced pulmonary disease that occurs in patients treated with a 5-aminosalicylic acid (5ASA). The diagnosis of druginduced pulmonary disease is confirmed by resolution of the lesions with discontinuation of the offending drug. The most common 5ASA-related condition is eosinophilic pneumonia, which is defined as an infiltration of the lungs with or without excessive eosinophils in the peripheral blood. Reactions related to 5ASA usually occur after 2 to 6 months of therapy [5]. Infliximab also has been reported to cause life-threatening pulmonary toxicity [6]. Patients treated with immunosuppressants such as azathioprine, tacrolimus, and infliximab are susceptible to various opportunistic infections [7]. However, our patient had concomitant pyoderma gangrenosum and pulmonary lesions that resolved after steroid therapy without withdrawal of any medications. In addition, no infectious agents were detected, although a large number of microorganisms appear to be refractory to cultivation [8]. Although we cannot completely exclude other factors such as infections or drug-induced processes, we propose that the patient’s pulmonary lesions were EIMs of UC. Pulmonary diseases in patients with UC can be classified as airway diseases or parenchymal diseases according to the site of involvement within the respiratory system. Airway diseases include bronchiectasis, chronic bronchitis and asthma. Parenchymal diseases include organizing pneumonia interstitial lung disease and eosinophilic pneumonitis. Organizing pneumonia is the most reported parenchymal disease of inflammatory bowel disease and may present acutely or subacutely with fever, dyspnea and cough [3, 9]. Radiographic findings can present patchy ground-glass opacities, often with consolidation. The infiltrate tends to show peripheral distribution. In general, pulmonary lesions of UC seem to respond well to steroids [9, 10]. Recent studies suggest that exposure of genetically susceptible individuals to environmental antigens may stimulate uncontrolled inflammation leading to UC. The presence of one EIM appears to confer a higher likelihood of developing other manifestations [11]. This is probably a result of genetic susceptibility and environmental factors that also play an important role in the pathogenesis of EIM [12]. In addition, patients with EIMs have a higher risk of following a refractory clinical course. Because pulmonary involvement follows an independent course and a proctocolectomy may not be protective against a recurrence of pulmonary involvement, a careful follow-up should be continued [13, 14].
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Clin J Gastroenterol (2014) 7:155–158
In conclusion, pulmonary involvement in UC is rare. Early recognition and management of EIMs is important to prevent significant morbidity. Disclosures Conflict of Interest: Jun Nishikawa, Hiroshi Mihara, Ryuji Hayashi, Shigeharu Miwa, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa and Toshiro Sugiyama declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from all patients for being included in the study.
References 1. Bernstein CN, Blanchard JF, Rawsthorne P, et al. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96:1116–22. 2. Mendoza JL, Lana R, Taxonera C, et al. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis. Med Clin (Barc). 2001;125:297–300. 3. Black H, Mendoza M, Murin S. Thoracic manifestations of inflammatory bowel disease. Chest. 2007;131:524–32. 4. Birring SS, Brightling CE, Symon FA, et al. Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis. Thorax. 2003;58:1066–70. 5. Storch I, Sachar D, Katz S. Pulmonary manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 2003;9:104–15. 6. Heraganahally SS, Au V, Kondru S, et al. Pulmonary toxicity associated with infliximab therapy for ulcerative colitis. Intern Med J. 2009;39:629–30. 7. Tasaka S, Tokuda H. Pneumocystis jirovecii pneumonia in nonHIV-infected patients in the era of novel immunosuppressive therapies. J Infect Chemother. 2012;18:793–806. 8. Nishikawa J, Kudo T, Sakata S, et al. Diversity of mucosaassociated microbiota in active and inactive ulcerative colitis. Scand J Gastroenterol. 2009;44:180–6. 9. Basseri B, Enayati P, Marchevsky A, Papadakis KA. Pulmonary manifestations of inflammatory bowel disease: case presentations and review. J Crohns Colitis. 2010;4:390–7. 10. Bayraktaroglu S, Basoglu O, Ceylan N, et al. A rare extraintestinal manifestation of ulcerative colitis: tracheobronchitis associated with ulcerative colitis. J Crohns Colitis. 2010;4:679–82. 11. Rankin GB, Watts HD, Melnyk CS, et al. National cooperative Crohn’s disease study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77:914–20. 12. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and role of HLA genes. Gastroenterology. 2002;123:714–8. 13. Kelly MG, Frizelle FA, Thornley PT, et al. Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis? Int J Colorectal Dis. 2006;21:754–7. 14. Camus P, Piard F, Ashcroft T, et al. The lung in inflammatory bowel disease. Medicine (Baltimore). 1993;72:151–83.
CASE REPORT
Pulmonary involvement: a rare extraintestinal manifestation of ulcerative colitis Jun Nishikawa • Ayumu Hosokawa • Hiroshi Mihara • Ryuji Hayashi • Shigeharu Miwa • Tatsuhiko Kane • Sohachi Nanjo • Takayuki Ando • Haruka Fujinami • Shinya Kajiura • Masami Minemura • Toshiro Sugiyama
Received: 3 December 2013 / Accepted: 22 February 2014 / Published online: 13 March 2014 Ó Springer Japan 2014
Abstract Ulcerative colitis (UC) is associated with a number of extraintestinal manifestations (EIMs) that may affect most organ systems. Among the EIMs, those involving the lung are rare. We report a case of pulmonary involvement and pyoderma gangrenosum in a patient with refractory UC. A chest computed tomography showed multiple nodular infiltrates in bilateral lungs. The patient had no respiratory symptoms. No infectious agents were detected. A transbronchial biopsy specimen showed nonspecific features. Prednisolone was initiated with significant improvement in the patient’s abdominal symptoms and pyoderma gangrenosum. Subsequent imaging after steroid therapy showed improvement of the pulmonary infiltrates. The patient’s abdominal symptoms relapsed when prednisolone was tapered. The patient subsequently received a proctocolectomy. Chest radiographs have shown resolution of pulmonary infiltrates. Because pulmonary involvement follows an independent course and a proctocolectomy may not be protective against a recurrence of
J. Nishikawa (&) A. Hosokawa H. Mihara T. Kane S. Nanjo T. Ando H. Fujinami S. Kajiura M. Minemura T. Sugiyama Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan e-mail: [email protected] R. Hayashi First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan S. Miwa Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
pulmonary involvement, a careful follow-up should be continued. Keywords Ulcerative colitis Inflammatory bowel disease Pulmonary involvement Extraintestinal manifestation
Introduction Ulcerative colitis (UC) is associated with a number of extraintestinal manifestations (EIMs) that may affect most organ systems. EIMs are significant cause of morbidity and may be distressing for the patients. Among the EIMs, those involving the lung are rare. We report a case of pulmonary involvement in a patient with UC.
Case report A 21-year-old man with an 8-year history of UC was admitted because of exacerbation of symptoms. When he presented, he was having five bowel movements per day, intermittent rectal bleeding and mild abdominal pain. He also had pyoderma gangrenosum as an EIM of UC. Medication history included mesalazine, multiple courses of steroids, and five infliximab infusions. Azathioprine was withdrawn due to liver injury. He was a non-smoker and had no history of respiratory disease. On admission, a physical examination revealed his body temperature to be 38.1 °C, and oxygen saturation to be 98 % while breathing ambient air. His lungs were clear on auscultation. His abdomen was soft, and mildly tender to palpation in the left lower quadrant. Pyoderma gangrenosum, a tender erythematous papule, was present on his right lower limb. His
123
156
Clin J Gastroenterol (2014) 7:155–158
Fig. 1 Chest X-ray images of the patient. a Three weeks prior to the admission; b at admission
white blood cell count was 12,100/lL (75 % neutrophils), red blood cell count was 481 9 104/lL, hemoglobin was 11.7 g/dL and platelet count was 51.1 9 104/lL. Peripheral eosinophilia was absent. C-reactive protein was 6.9 mg/ dL. Liver and renal function test results were normal, and cytomegalovirus-pp65 antigenemia test results were negative. Rheumatoid factor, antinuclear antibodies, and proteinase-3 anti-neutrophil antibody test results were also negative. A colonoscopy revealed moderately active extensive UC. No pathogens or Clostridium difficile toxin could be detected in stools. A chest X-ray revealed bilateral infiltrates in the apex regions that had not been identified 3 weeks prior to this admission (Fig. 1a, b). The computed tomography showed multiple peripheral infiltrates in bilateral lungs (Fig. 2). He denied any cough or dyspnea. Routine bacterial, fungal, and mycobacterial cultures of sputum were negative. A skin test for tuberculosis was also negative. He was prescribed an empiric course of antibiotics, with no improvement in the chest X-ray results or fever. A bronchoscopy with transbronchial biopsy was performed. A brushing cytology specimen revealed bronchial columnar cells, and pulmonary macrophages, but no malignant cells. Gram stain and cultures for bacteria were negative and special stains for fungi and mycobacteria were negative as well. A biopsy specimen showed nonspecific features of fibrin deposition and mixed infiltrates with prominent neutrophils and other inflammatory cells in the alveolar spaces (Fig. 3a, b). There was no evidence of vasculitis. His clinical presentation, radiographs and pathology findings were consistent with organizing pneumonia. Prednisolone (50 mg daily) was initiated with significant improvement in the patient’s abdominal symptoms and pyoderma gangrenosum. Subsequent imaging after steroid therapy showed improvement of the pulmonary infiltrates (Fig. 4). His abdominal symptoms relapsed when prednisolone was tapered to 15 mg. He subsequently
123
Fig. 2 Chest computed tomography showing bilateral multiple pulmonary infiltrations
received a proctocolectomy, and chest radiographs have shown resolution of pulmonary infiltrates.
Discussion The overall incidence of EIMs in patients with inflammatory bowel disease has been reported to range from 6 to
Clin J Gastroenterol (2014) 7:155–158
157
Fig. 3 A transbronchial biopsy specimen showed nonspecific feature of fibrin deposition and a mixed infiltrate with prominent neutrophils and other inflammatory cells. (Hematoxylin and eosin stain, a 9100, b 9400)
47 % [1, 2]. EIMs of UC include those related to the disease activity (arthritis, erythema nodosum, and ocular involvement). Others are nonspecific disorders that follow an independent course (hepatobiliary, osteoporosis, and amyloidosis). Pulmonary involvement and pyoderma gangrenosum belong to a nonspecific category that is not linked to active inflammation. Although EIMs of UC are common, clinically evident pulmonary involvement is rare. Pulmonary involvement in UC may reflect the common embryonic origin of both the gastrointestinal tract and the bronchial tree [3]; both the colonic and respiratory epithelia are of foregut origin. In addition, both gut-associated and bronchus-associated lymphoid tissues play important roles in the host mucosal defense. The similarity in the mucosal
Fig. 4 Chest computed tomography after steroid therapy showing resolution of pulmonary infiltrates
immune systems may cause inflammation at two different sites. In addition, aberrant homing of activated T-cells into the lungs from the primary sites of chronic inflammation may occur [4].
123
158
It remains difficult to determine whether pulmonary lesions are secondary to the drugs or to the underlying disease process. The most common pulmonary abnormalities of inflammatory bowel disease are drug-induced pulmonary disease that occurs in patients treated with a 5-aminosalicylic acid (5ASA). The diagnosis of druginduced pulmonary disease is confirmed by resolution of the lesions with discontinuation of the offending drug. The most common 5ASA-related condition is eosinophilic pneumonia, which is defined as an infiltration of the lungs with or without excessive eosinophils in the peripheral blood. Reactions related to 5ASA usually occur after 2 to 6 months of therapy [5]. Infliximab also has been reported to cause life-threatening pulmonary toxicity [6]. Patients treated with immunosuppressants such as azathioprine, tacrolimus, and infliximab are susceptible to various opportunistic infections [7]. However, our patient had concomitant pyoderma gangrenosum and pulmonary lesions that resolved after steroid therapy without withdrawal of any medications. In addition, no infectious agents were detected, although a large number of microorganisms appear to be refractory to cultivation [8]. Although we cannot completely exclude other factors such as infections or drug-induced processes, we propose that the patient’s pulmonary lesions were EIMs of UC. Pulmonary diseases in patients with UC can be classified as airway diseases or parenchymal diseases according to the site of involvement within the respiratory system. Airway diseases include bronchiectasis, chronic bronchitis and asthma. Parenchymal diseases include organizing pneumonia interstitial lung disease and eosinophilic pneumonitis. Organizing pneumonia is the most reported parenchymal disease of inflammatory bowel disease and may present acutely or subacutely with fever, dyspnea and cough [3, 9]. Radiographic findings can present patchy ground-glass opacities, often with consolidation. The infiltrate tends to show peripheral distribution. In general, pulmonary lesions of UC seem to respond well to steroids [9, 10]. Recent studies suggest that exposure of genetically susceptible individuals to environmental antigens may stimulate uncontrolled inflammation leading to UC. The presence of one EIM appears to confer a higher likelihood of developing other manifestations [11]. This is probably a result of genetic susceptibility and environmental factors that also play an important role in the pathogenesis of EIM [12]. In addition, patients with EIMs have a higher risk of following a refractory clinical course. Because pulmonary involvement follows an independent course and a proctocolectomy may not be protective against a recurrence of pulmonary involvement, a careful follow-up should be continued [13, 14].
123
Clin J Gastroenterol (2014) 7:155–158
In conclusion, pulmonary involvement in UC is rare. Early recognition and management of EIMs is important to prevent significant morbidity. Disclosures Conflict of Interest: Jun Nishikawa, Hiroshi Mihara, Ryuji Hayashi, Shigeharu Miwa, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa and Toshiro Sugiyama declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from all patients for being included in the study.
References 1. Bernstein CN, Blanchard JF, Rawsthorne P, et al. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96:1116–22. 2. Mendoza JL, Lana R, Taxonera C, et al. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis. Med Clin (Barc). 2001;125:297–300. 3. Black H, Mendoza M, Murin S. Thoracic manifestations of inflammatory bowel disease. Chest. 2007;131:524–32. 4. Birring SS, Brightling CE, Symon FA, et al. Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis. Thorax. 2003;58:1066–70. 5. Storch I, Sachar D, Katz S. Pulmonary manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 2003;9:104–15. 6. Heraganahally SS, Au V, Kondru S, et al. Pulmonary toxicity associated with infliximab therapy for ulcerative colitis. Intern Med J. 2009;39:629–30. 7. Tasaka S, Tokuda H. Pneumocystis jirovecii pneumonia in nonHIV-infected patients in the era of novel immunosuppressive therapies. J Infect Chemother. 2012;18:793–806. 8. Nishikawa J, Kudo T, Sakata S, et al. Diversity of mucosaassociated microbiota in active and inactive ulcerative colitis. Scand J Gastroenterol. 2009;44:180–6. 9. Basseri B, Enayati P, Marchevsky A, Papadakis KA. Pulmonary manifestations of inflammatory bowel disease: case presentations and review. J Crohns Colitis. 2010;4:390–7. 10. Bayraktaroglu S, Basoglu O, Ceylan N, et al. A rare extraintestinal manifestation of ulcerative colitis: tracheobronchitis associated with ulcerative colitis. J Crohns Colitis. 2010;4:679–82. 11. Rankin GB, Watts HD, Melnyk CS, et al. National cooperative Crohn’s disease study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77:914–20. 12. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and role of HLA genes. Gastroenterology. 2002;123:714–8. 13. Kelly MG, Frizelle FA, Thornley PT, et al. Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis? Int J Colorectal Dis. 2006;21:754–7. 14. Camus P, Piard F, Ashcroft T, et al. The lung in inflammatory bowel disease. Medicine (Baltimore). 1993;72:151–83.
