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Crohn's disease

Crohn's disease is a chronic inflammatory disease of the digestive tract and it can involve any part of it, from the mouth to the anus. It typically affects the caecum and/or the terminal ileum as well as demarcated areas of large bowel, with other areas of the bowel being relatively unaffected. It is often associated with auto-immune disorders outside the bowel, such as aphthous stomatitis and rheumatoid arthritis. more...

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Crohn's disease should not be confused with a non-progressive and non-degenerative digestive disorder called irritable bowel syndrome (IBS), which is not an autoimmune disease. Ulcerative colitis is a sibling autoimmune disease to Crohn's but only impacts the colon while Crohn's can impact any part of the digestive tract. Furthermore, Crohn's tends to affect multiple layers of the bowel lining, which can lead to many additional and hard-to-treat complications.

Symptoms

Crohn's patients typically suffer from abdominal pain, chronic diarrhea and disrupted digestion, which may make it difficult for sufferers, particularly in the acute phase of the disease, to eat and/or digest food. The inflammation can be extremely painful and debilitating. Other common complications of Crohn's include fistulas of the colon, hemorrhoids, lipid absorption problems, and anemia. Bleeding is seen in 20% cases, against 98% cases in ulcerative colitis. Rectal bleeding may be serious and persistent, leading to anemia. Bruising of the shins, varying fever symptoms, varying levels of pain, and psychological damage is seen in many cases. Children with Crohn's disease may suffer delayed development and stunted growth.

Epidemiology

The disease typically first appears in young adults in their late teens and twenties, although it is not unknown for symptoms to first appear quite late in life. Additionally, there has been an increase in cases occurring in young children. Recent studies suggest that up to 30% of all newly diagnosed cases are in children and teens under the age of 18. Estimates suggest that up to 60,000 people in the UK (about 1 in 1200) and 1,000,000 Americans have the disease (around 1 in 300). Some ethnic groups (such as Ashkenazi Jews) have a significantly higher rate of prevalence than others. Increased rates of disease have also been noted in some families, leading to speculation of a possible genetic link (see below). Epidemiological research indicates that Crohn's belongs to the group of diseases of affluence. In other words, the incidence of the disease is much higher in industrialized countries than elsewhere. However, this finding may be associated with the fact that Crohn's symptoms are typically diagnosed over a long period of time, in order to establish a pattern; in countries where medical help is less available, it may be difficult to arrive at a diagnosis.

Smoking increases the risk of Crohn's disease. Some women find that their disease is exacerbated by taking oral contraceptives, while others find it can help keep their flare ups at bay.

Causes

Barrier problem and autoimmunity to the luminal flora

The efficacy of immunosuppression, as well as scanty reports of complete disease resolution after bone marrow transplant, is highly suggestive of an autoimmune pathogenesis. A definite epitope to which the autoimmunity is directed is unknown, which also hampers the search for a virus or other pathogen that could induce molecular mimicry.

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Crohn's disease of the esophagus
From Ear, Nose & Throat Journal, 6/1/04 by Liron Pantanowitz

Abstract

Crohn's disease of the esophagus is rare but is being detected more frequently because of the use of upper endoscopy. Clinicopathologic correlation is required to establish the correct diagnosis. We present a case of esophageal Crohn's disease and review the literature to demonstrate that esophageal involvement is usually associated with disease elsewhere in the gut.

Introduction

Crohn's disease of the esophagus is rare. However, because of more frequent use of upper endoscopy, foregut Crohn's disease has been shown to be more common than previously suspected. The estimated incidence in adult patients with Crohn's disease is 0.3 to 2%. (1) Esophageal involvement is more common in the pediatric population. (2-5) Therefore, upper endoscopy, together with multiple biopsies, is important not only in the evaluation of patients with Crohn's disease, but also in establishing the diagnosis. We present the endoscopic and pathologic findings of an illustrative case of esophageal Crohn's disease and review the relevant literature.

Case Report

A 42-year-old man with a history of chronic colitis presented with weight loss, dysphagia, and odynophagia. Upper endoscopy revealed continuous "cobblestoning" and linear ulcers of his esophageal mucosa (figure 1) in the distal 20-cm segment, and a normal stomach and duodenum. A mucosal biopsy revealed chronic active esophagitis (figure 2) with noncaseating granulomas and an absence of microorganisms on special stains, which supported a diagnosis of Crohn's disease. Biopsies of the gastric and duodenal mucosa were normal. Colonoscopic examination with biopsies through the colon and terminal ileum revealed changes consistent with Crohn's disease in the sigmoid colon and proximal transverse colon. This patient was treated with a proton pump inhibitor, a short course of prednisone, and a maintenance regimen that included azathioprine and mesalamine. His esophageal symptoms resolved.

[FIGURES 1-2 OMITTED]

Discussion

As illustrated by this case, most reported cases of Crohn's disease of the esophagus are associated with disease elsewhere in the gut. (6-8) Inflammation in the esophageal mucosa usually parallels that seen in other sites of the gastrointestinal tract. However, there are rare reports in which Crohn's disease presented primarily in the esophagus? n Patients with esophageal involvement usually complain of heartburn, odynophagia, dysphagia, and substernal or epigastric pain.

Endoscopic findings have been classified into an inflammatory stage (stage 1) followed by stenosis (stage 2) caused by chronic inflammation and/or fibrosis. Early changes include aphthous ulceration, which may extend up into the hypopharynx and oral cavity. Typically, the lower part of the esophagus is more severely affected. Although apthoid ulcers and a cobblestone pattern of the mucosa are characteristic appearances seen at endoscopy, esophageal changes more often are nonspecific (e.g., hyperemia, granularity, friability, mucosal fold thickening, and nodularity). Clinicopathologic correlation is therefore required. Endoscopic ultrasonography can help demonstrate transmural and adjacent soil tissue involvement. (12) Complications may include esophageal stenosis, obstruction, fistula formation, perforation and, rarely, the development of adenocarcinoma. (13-15) Severe disease may also mimic carcinoma. Thus, biopsies should be taken to exclude not only neoplasia, but also severe reflux esophagitis and infections.

Therapy is based largely on the administration of corticosteroids. (16-17) Concomitant use of a proton pump inhibitor or sucralfate may also provide partial relief of symptoms. Opportunistic infections involving the esophagus should always remain a consideration in immunosuppressed patients with Crohn's disease. More complicated and refractory disease may warrant endoscopic dilatation or surgical resection. For patients with steroid-resistant or steroid-dependent disease, the use of infliximab (a monoclonal antibody to TNF-[alpha] may help induce and sustain clinical remission, thus avoiding surgery. (18)

Conclusion

Involvement of the upper gastrointestinal tract by Crohn's disease is usually underdiagnosed. (19-21) Patients with a diagnosis of Crolm's disease and esophageal symptoms should undergo upper endoscopy with biopsies to establish the cause of their symptoms, If diagnostic findings such as granulomas are not to be missed, biopsies should be taken from both ulcers and normal-appearing mucosa. Treatment with acid suppression medications and a short course of steroids is warranted. Occasionally, immunomodulators or infliximab may help sustain clinical remission.

References

(1.) Geboes K, Janssens J, Rutgeerts P, Vantrappen G. Crohn's disease of the esophagus. J Clin Gastroentero1 1986;8:31-7.

(2.) Mashako MN, Cezard JP, Navarro J, et al. Crohn's disease lesions in the upper gastrointestinal tract: Correlation between clinical, radiological, endoscopic, and histological features in adolescents and children. J Pediatr Gastroenterol Nutr 1989;8:442-6.

(3.) Ruuska T, Vaajalahti P, Arajarvi R Maki M. Prospective evaluation of upper gastrointestinal mucosal lesions in children with ulcerative colitis and Crohn's disease. J Pediatr Gaslroenterol Nutr 1994;19: 181-6.

(4.) Abdullah BA, Gupta SK, Croffie JM, et al. The role of esophago-gastroduodenoscopy in the initial evaluation of childhood inflammatory bowel disease: A 7-year study. J Pediatr Gastroenterol Nutr 2002;35:636-40.

(5.) Ramaswamy K, Jacobson K, Jevon G, Israel D. Esophageal Crohn disease in children: A clinical spectrum. J Pediatr Gastroenterol Nutr 2003;36:454-8.

(6.) Taskin V, von Sohsten R, Singh B, et al. Crohn's disease of the esophagus. Am J Gastroenterol 1995;90:1000-1.

(7.) Rudolph I, Goldstein F, DiMarino AJ, Jr. Crohn's disease of the esophagus: Three cases and a literature review. Can J Gastroenterol 2001;15:117-22.

(8.) Ohta M, Konno H, Kamiya K, et al. Crohn's disease of the esophagus: Report of a case. Surg Today 2000;30:262-7.

(9.) Howden FM, Mills LR IV, Rubin PAL Crohn's disease of the esophagus. Am Surg 1994;60:656-60.

(10.) Gilmour HM. The oesophagus: Crohn's disease. In: Whitehead R, ed. Gastrointestinal and Oesophageal Pathology. 2nd ed. Edinburgh: Churchill Livingstone, 1995:459-60.

(11.) Naranjo-Rodriguez A, Solorzano-Peck G, Lopez-Rubio F, et al. Isolated oesophageal involvement of Crohn's disease. Eur J Gastroenterol Hepato1 2003; 15:1123-6.

(12.) Dancygier H, Frick B. Crohn's disease of the upper gastrointestinal tract. Endoscopy 1992;24:555-8.

(13.) Delpre G, Mor C, Avidor I, et al. Barrett's mucosa of distal esophagus with concomitant isolated Crohn's disease and intramucosal adenocarcinoma. Report of a case and analysis of the literature. Dig Dis Sci 1989;34:304-11.

(14.) Rholl JC, Yavorski RT, Cheney CP, Wong RK. Esophagogastric fistula: A complication of Crolm's disease--Case report and review of the literature. Am J Gastroentero1 1998;93:1381-3.

(15.) Knoblauch C, Netzer P, Scheurer U, Seibold F. Dysphagia in Crohn's disease: A diagnostic challenge. Dig Liver Dis 2002;34:660-4.

(16.) D'Haens G, Rutgeerts P, Geboes K, Vantrappen G. The natural history of esophageal Crohn's disease: Three patterns of evolution. Gastrointest Endosc 1994;40:296-300.

(17.) Borum ML, Albert MB. An unusual ease of esophageal Crohn's disease and a review of the literature. Dig Dis Sci 1997;42:4246.

(18.) Fefferman DS, Shah SA, Alsahlil M, et al. Successful treatment of refractory esophageal Crohn's disease with infliximab. Dig Dis Sci 2001;46:1733-5.

(19.) Schmidt-Sommerfeld E, Kirschner BS, Stephens JK. Endoscopic and histologic findings in the upper gastrointestinal tract of children with Crohn's disease. J Pediatr Gastroeterol Nutr 1990; 11:448454.

(20.) Reynolds HL, Jr., Stellato TA. Crohn's disease of the foregut. Surg Clin North Am 2001;81:117-35.

(21.) Decker GA, Loftus EV, Jr., Pasha TM et al Crohn's disease of the esophagus: Clinical features and outcomes, Inflamm Bowel Dis 2001;7:113-19.

From the Department of Pathology (Dr. Pantanowitz and Dr. Nasser) and the Department of Gastroenterology (Dr. Gelrud and Dr. Apstein), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.

Reprint requests: Liron Pantanowitz, MD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-4344; fax: (617) 667 7120; e-mail: lpantanowitz@hotmail.com

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