C a r d i o p u l m o n a r y I m a g i n g P i c t o r i a l E s s ay

Betancourt et al. Inflammatory Bowel Disease Cardiopulmonary Imaging Pictorial Essay

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Thoracic Manifestations of Inammatory Bowel Disease

Sonia L. Betancourt 1 Diana Palacio1 Carlos A. Jimenez 2 Santiago Martinez 3 Edith M. Marom1
Betancourt SL, Palacio D, Jimenez CA, Martinez S, Marom EM

OBJECTIVE. The purpose of this article is to present the spectrum of inammatory bowel disease manifestations in the chest, including the airways, lung parenchyma, pulmonary vasculature, and serosal surfaces. CONCLUSION. The spectrum of inammatory bowel disease manifestations in the chest is broad, and the manifestations may mimic other diseases. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. ver the past few decades, the incidence of inammatory bowel disease (IBD) has risen in industrialized countries [1]. IBD, namely Crohn disease and ulcerative colitis, has a variety of thoracic manifestations. Clinically encountered acute respiratory symptoms in patients with IBD are most commonly due to infection. It is thought that signicant respiratory symptoms from IBD pulmonary involvement are rare [1, 2]. However, such patients may in fact be underdiagnosed because respiratory involvement may precede presentation of bowel disease by months or years [3], and respiratory symptoms have even been described after total colectomy [4]. In a randomly selected group of 44 IBD patients, up to 48% had nonspecic respiratory symptoms, such as cough, shortness of breath, and wheezing, not attributable to infection [5]. Pulmonary function tests are suboptimal in patients with IBD in comparison with healthy control subjects and do not always correlate with IBD activity [57]. Finally, many patients who exhibit respiratory manifestations also exhibit other extraintestinal manifestations (e.g., arthritis, uveitis), suggesting a common pathophysiologic mechanism [8]. The pathogenesis of respiratory involvement in patients with IBD may be related to the shared embryonic origin of the respiratory and intestinal systems, both of which originate from the primitive foregut and are formed by columnar epithelium containing goblet cells, which secrete mucus. In theory, intestinal and respiratory abnormalities IBD patients could

Keywords: airway disease, inammatory bowel disease, parenchymal lung disease, pulmonary vascular disease, serositis DOI:10.2214/AJR.10.5353 Received July 14, 2010; accepted after revision January 17, 2011.
1 Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009. Address correspondence to S. L. Betancourt (slbetancourt@mdanderson.org). 2 Department of Pulmonary Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX. 3 Department of Radiology, Duke University Medical Center, Durham, NC.

WEB This is a Web exclusive article. AJR 2011; 197:W452W456 0361803X/11/1973W452 American Roentgen Ray Society

result from epithelial exposure to common antigens by inhalation and ingestion, leading to sensitization of the lymphoid tissue and inammation. Another theory is that respiratory involvement in IBD is due to inammatory mediators released by the bowel mucosa [4, 6]. A normal chest radiograph is seen in most symptomatic and asymptomatic IBD patients with thoracic involvement [2, 9]. High-resolution CT is more sensitive in showing pulmonary abnormalities and has shown an abnormality in 19 of 36 (53%) symptomatic and asymptomatic patients in one study [10]. Respiratory manifestations may involve the large and small airways, pulmonary vasculature, lung parenchyma, or serosal surface [6]. In contrast to other extraintestinal manifestations, pulmonary parenchymal IBD is seen more commonly with ulcerative colitis than Crohn disease, and large airway disease is strongly associated with ulcerative colitis [2, 3, 10]. Approximately 22% of IBD patients with symptomatic respiratory involvement will show bronchiectasis; 20%, chronic bronchitis; 18%, interstitial lung disease; 12%, cryptogenic organizing pneumonia (COP); and 6%, necrobiotic nodules [2]. It is important to recognize these manifestations because they may mimic other diseases, leading to incorrect treatment. For example, airway involvement by IBD should not be confused with typical or atypical infection. Lung parenchymal masslike lesions due to necrobiotic nodules in IBD patients should not be confused with fungal infection, malignancy, or Wegener granulomatosis. In such

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Inflammatory Bowel Disease cases, histologic conrmation is required to provide adequate treatment. Finally, respiratory abnormalities may be related to drugs taken for treatment of IBD, and these effects may resolve after discontinuation of IBD-specic medications [11]. However, in cases with persistent pulmonary abnormalities after the withdrawal of medication, a biopsy should be performed. Parenchymal, serosal, and airway disease often respond well to steroids. Thus, knowledge of the spectrum of IBD-related respiratory symptoms combined with a strong clinical suspicion will lead to early diagnosis. Airway Disease Airway inammation is the most common form of respiratory involvement in IBD patients, predominantly affecting the intermediate-sized central bronchi [6]. Bronchiectasis is seen in 66% of airway involvement, and the remainder manifest as chronic bronchitis, suppurative large airway disease without airway dilation, or acute bronchitis [6]. Chest radiographs may show increased interstitial markings or a tramline pattern or may appear normal [12]. CT ndings include diffuse concentric bronchial wall thickening with or without mucoid impaction and bronchiectasis cylindric, varicose, or cystic [12, 13] (Fig. 1). Small airway involvement is rarely encountered clinically [6]. Chest radiographs are usually normal or may show ill-dened reticulonodular or ground-glass opacities, poorly marginated pulmonary vessels, and/or large lung volumes because of air trapping. CT shows bronchiolar wall thickening, mucoid impaction, centrilobular ground-glass nodules, and mosaic attenuation because of air trapping (Fig. 2). Upper airway involvement, particularly tracheal involvement in the form of subglottic stenosis or diffuse tracheitis, is rare. Patients may present with hoarseness or stridor. The mucosa may exhibit a cobblestone appearance similar to that seen in affected intestines [14]. Chest radiographs and CT may show narrowing of any portion of the trachea, with circumferential tracheal wall thickening on CT (Fig. 3). Parenchymal Lung Disease Parenchymal lung disease is most commonly due to infection because IBD-related parenchymal disease is rare. When present, it is usually due to COP. Although COP may accompany pulmonary infection or occur as a manifestation of drug toxicity (Fig. 4), cases have been attributed to IBD itself [6, 8]. Chest radiographs show focal to diffuse peripheral predominant airspace opacities. CT shows scattered, nonsegmental, unilateral, or bilateral foci of consolidation, ill-dened centrilobular nodules, and large irregular nodules (Fig. 5). Other forms of parenchymal disease that may be related to IBD or drug toxicity are eosinophilic pneumonia and nonspecic interstitial pneumonitis. On CT, peripheral consolidation predominates in cases of eosinophilic pneumonia, whereas nonspecic interstitial pneumonitis shows ground-glass opacities, interlobular septal thickening, and irregular linear opacities [3, 15] (Figs. 6 and 7) Pulmonary necrobiotic nodules, histologically similar to those encountered in patients with rheumatoid arthritis, have also been seen in patients with IBD and should be differentiated from malignancy and infection. On imaging, these nodules are round and well dened; they can measure up to a few centimeters in diameter and may cavitate. An infectious origin should be excluded because necrobiotic nodules will respond to steroids but not to antibiotics [3]. Several entities may coexist with IBD and be linked to the disease. An example is sarcoidosis and IBD [6, 8]. Genetic susceptibility and cellular immunity impairment are theoretically common mechanisms involved in the pathogenesis of both sarcoidosis and IBD (Fig. 8), and they share similar dermatologic, ocular, and joint manifestations [2, 6]. Alpha-1 antitrypsin deciency has increased prevalence in patients with IBD, although evidence does not show a direct link [6, 8] Serositis Serositis is not associated with IBD activity. Pleural effusion is usually unilateral and exudative in nature (Fig. 9). When the pericardium is involved, it is usually not accompanied by pleural effusions [6]. Pulmonary Vascular Disease The incidence of thromboembolic events in IBD patients is three to four times higher than in age-matched control subjects. Up to one third of thromboembolic events in this population occur while IBD is quiescent, suggesting an unknown risk factor that is unrelated to treatment or disease activity [6] (Fig. 10). Conclusion With the increased use of CT, respiratory manifestations of IBD are more commonly encountered. The spectrum of pulmonary involvement is wide, but correct identication of the disease pattern on imaging studies will allow clinicians to administer adequate treatment and avoid destructive irreversible airway changes or pulmonary brosis. References
1. Loftus EV Jr. Clinical epidemiology of inammatory bowel disease: incidence, prevalence, and environmental inuences. Gastroenterology 2004; 126:15041517 2. Hoffmann RM, Kruis W. Rare extraintestinal manifestations of inammatory bowel disease. Inamm Bowel Dis 2004; 10:140147 3. Camus P, Colby TV. The lung in inammatory bowel disease. Eur Respir J 2000; 15:510 4. Spira A, Grossman R, Balter M. Large airway disease associated with inammatory bowel disease. Chest 1998; 113:17231726 5. Douglas JG, McDonald CF, Leslie MJ, Gillon J, Crompton GK, McHardy GJ. Respiratory impairment in inammatory bowel disease: does it vary with disease activity? Respir Med 1989; 83:389394 6. Black H, Mendoza M, Murin S. Thoracic manifestations of inammatory bowel disease. Chest 2007; 131:524532 7. Kuzela L, Vavrecka A, Prikazska M, et al. Pulmonary complications in patients with inammatory bowel disease. Hepatogastroenterology 1999; 46: 17141719 8. Storch I, Sachar D, Katz S. Pulmonary manifestations of inammatory bowel disease. Inamm Bowel Dis 2003; 9:104115 9. Raj AA, Birring SS, Green R, Grant A, de Caestecker J, Pavord ID. Prevalence of inammatory bowel disease in patients with airways disease. Respir Med 2008; 102:780785 10. Songr N, Songr Y, Tzn M, et al. Pulmonary function tests and high-resolution CT in the detection of pulmonary involvement in inammatory bowel disease. J Clin Gastroenterol 2003; 37:292298 11. Salerno SM, Ormseth EJ, Roth BJ, Meyer CA, Christensen ED, Dillard TA. Sulfasalazine pulmonary toxicity in ulcerative colitis mimicking clinical features of Wegeners granulomatosis. Chest 1996; 110:556559 12. Camus P, Piard F, Ashcroft T, Gal AA, Colby TV. The lung in inammatory bowel disease. Medicine (Baltimore) 1993; 72:151183 13. Garg K, Lynch DA, Newell JD. Inammatory airways disease in ulcerative colitis: CT and highresolution CT features. J Thorac Imaging 1993; 8:159163 14. Janssen WJ, Bierig LN, Beuther DA, Miller YE. Stridor in a 47-year-old man with inammatory bowel disease. Chest 2006; 129:11001106 15. Katzenstein AL, Myers JL. Idiopathic pulmonary brosis: clinical relevance of pathologic classication. Am J Respir Crit Care Med 1998; 157:13011315

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Fig. 1 44-year-old woman with cough and active ulcerative colitis. Contrast-enhanced chest CT scan at level of main bronchi shows diffuse bronchiectasis of intermediate airways.

Fig. 2 58-year-old man with ulcerative colitis and nonspecic respiratory symptoms. A and B, Unenhanced inspiratory chest CT scan ( A ) shows subtle bilateral centrilobular nodules (arrows ) and mosaic attenuation consistent with small airways disease. Air trapping is evident on expiratory view (B). After antibiotics were administered for 2 weeks but failed to resolve symptoms, steroidal therapy was initiated and resulted in dramatic clinical and radiographic response (not shown).

Fig. 3 33-year-old woman with Crohn disease who presented with stridor. (Courtesy of Boiselle P, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA) A, Unenhanced, volume-rendered chest CT scan shows focal area of subglottic stenosis (arrows ). B, Corresponding axial CT scan at level of stenosis shows asymmetric tracheal wall thickening (arrow ).

Fig. 4 37-year-old man with active ulcerative colitis treated with mesalamine. (Courtesy of Restrepo C, The University of Texas Health Science Center at San Antonio, San Antonio, TX) A, Frontal chest radiograph shows bilateral peripheral opacities (arrows ). B, Contrast-enhanced chest CT scan shows that opacities seen on chest radiograph are peripheral lenticular-shaped areas of consolidation. Biopsy (not shown) revealed ndings consistent with cryptogenic organizing pneumonia. Remission was achieved after discontinuation of mesalamine (antiinammatory agent), conrming diagnosis of mesalamine-induced organizing pneumonia.

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Inflammatory Bowel Disease

Fig. 5 30-year-old man with Crohn disease. A, Unenhanced chest CT scan shows bilateral pulmonary nodules, some of which show groundglass opacity, surrounded by ring of soft tissue (arrows ) that appears as reverse halo sign, which was initially described in cases of cryptogenic organizing pneumonia (COP) but is also seen with other entities, such as infection and vasculitis. B, Photomicrograph of biopsy specimen from larger nodule reveals severe peribronchiolar cellular inltration and granulation tissue in alveolar ducts and adjacent airspaces, consistent with COP associated with inammatory bowel disease (arrows ). (H and E, 40)

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Fig. 6 39-year-old woman with active ulcerative colitis. A, Frontal chest radiograph shows bilateral peripheral heterogeneous airspace opacities. B, Contrast-enhanced CT scan shows scattered peripheral predominant airspace disease. Transbronchial biopsy (not shown) revealed lling of alveoli with eosinophils and macrophages with foci of organizing pneumonia, consistent with eosinophilic pneumonia.

Fig. 7 66-year-old woman with ulcerative colitis who was hospitalized with cough, fever, and dyspnea. Axial CT scan of chest shows scattered ground-glass opacities and intralobular septal thickening with little traction bronchiectasis. Biopsy (not shown) was consistent with nonspecic interstitial pneumonia.

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Fig. 8 42-year-old woman with Crohn disease. A, Frontal chest radiograph shows symmetric bilateral mediastinal and hilar adenopathy. B and C, Contrast-enhanced chest CT scans conrm mediastinal and hilar adenopathy. Endobronchial biopsy (not shown) revealed noncaseating granulomas with negative fungal serologies and cultures, consistent with sarcoidosis.

Fig. 9 44-year-old afebrile man with ulcerative colitis and no additional comorbidities who presented with mild shortness of breath. Coronal reformation of contrast-enhanced chest CT image reveals left pleural effusion, no infection, and no pulmonary embolus. Effusion spontaneously resolved on routine follow-up chest radiographs (not shown).

Fig. 10 42-year-old man with active Crohn disease and acute shortness of breath. A and B, Axial ( A ) and sagittal reformation (B) contrast-enhanced chest CT scans show low-attenuation lling defect in segmental right lower lobe pulmonary artery (arrow ) consistent with pulmonary embolus. There is peripheral wedge-shaped consolidation (asterisk, A ), compatible with pulmonary infarct. Small pleural effusions are also present (arrowheads , A ).

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