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Keywords:

  • Crohn's disease;
  • scalloping;
  • villous atrophy

Abstract

  1. Top of page
  2. Abstract
  3. Case Reports
  4. Discussion
  5. References

Scalloping of the duodenal mucosal folds is an endoscopic finding of small bowel mucosal pathology that is generally due to villous atrophy. Though it can be seen in many disease processes, it is most commonly associated with celiac disease. We report three patients with scalloping of duodenal folds and histologic confirmation of villous atrophy due to Crohn's disease. All patients had negative celiac serologies and two had positive markers for Crohn's disease (anti–Saccharomyces cerevisiae antibodies). Patients had either ileitis or ileocolitis in addition to duodenal abnormalities. These cases illustrate that scalloping can occur in the duodenum in Crohn's disease.

Sceliac disease and is thought to be a specific marker for calloping of duodenal mucosal folds was first described in this condition. 1,2 It has recently been identified in other diseases including tropical sprue, HIV enteropathy, HIV-related small intestinal opportunistic infections, giardiasis, and amyloidosis. 3,4 Scalloping is a marker of villous atrophy irrespective of cause. We report the endoscopic finding of scalloping of folds in the duodenum of three patients with Crohn's disease. Strictures and ulceration are the most common findings in the upper GI tract in Crohn's disease. 5 Villous atrophy, however, has been reported in about 20% of patients with inflammatory bowel disease. 6,7

Case Reports

  1. Top of page
  2. Abstract
  3. Case Reports
  4. Discussion
  5. References

Case 1

A 61-year-old female presented with a 1-year history of intermittent diarrhea and occasional rectal bleeding. Physical examination was normal. Routine blood tests were also normal. Anti-gliadin IgG, IgA, and endomysial antibodies were negative. Total IgA level was normal. Anti–Saccharomyces cerevisiae antibody (ASCA) IgA was positive, IgG negative. Upper gastrointestinal endoscopy revealed scalloping of duodenal folds (Fig. 1). Colonoscopy revealed patchy erythema and ulceration of the colon and ulceration of the terminal ileum.

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Figure FIGURE 1. Scalloping of duodenal mucosa.

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Histopathologic examination of the duodenal biopsies showed an increase in mucosal plasma cells, dilatation of villous lymphatics, and partial villous atrophy. Colonoscopic biopsies showed patchy increases of mucosal plasma cells, histiocytes, eosinophils, and lymphocytes, as well as acute cryptitis and occasional crypt abscesses. In the right colon there was a small granuloma composed of giant cells and epithelial histiocytes. Overall, the histologic appearance was consistent with Crohn's disease. Treatment with mesalamine resulted in resolution of symptoms. Repeat upper endoscopy showed marked improvement in scalloping of the duodenal folds with no further atrophy on biopsy.

Case 2

A 70-year-old female was admitted to the hospital because of an ankle fracture. On admission, atrial fibrillation was detected and anticoagulation considered. However, fecal occult blood was positive. She denied gastrointestinal symptoms apart from intermittent diarrhea. Routine laboratory values, including hematocrit, were normal. Upper gastrointestinal endoscopy revealed scalloped duodenal folds. This finding prompted us to measure antigliadin IgG and IgA antibodies as well as endomysial antibodies, which were all negative. Colonoscopy was normal, but examination of the terminal ileum revealed ulcerated mucosa.

Histopathologic examination of the ileal biopsies showed markedly inflamed granulation tissue from an ulcer base and an acute inflammatory exudate. Two microgranulomas were seen in the duodenal mucosa. One was located in the tip of a broadened inflamed villus (Fig. 2). Patchy increases of mucosal chronic inflammatory cells were associated with partial villous atrophy. The patient was diagnosed with Crohn's disease and treated with mesalamine. She improved clinically, but was lost to long-term follow-up and did not undergo repeat endoscopy to evaluate histopathologic improvement.

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Figure FIGURE 2. Crohn's disease of the duodenum. A microgranuloma surrounded by a mixed infiltrate of lymphocytes, plasma cells, and histiocytes is seen in an expanded and shortened villus.

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Case 3

A 23-year-old woman presented with a 4-year history of diarrhea. She was initially diagnosed with and treated for giardiasis. Diarrhea continued and was associated with a 40-lb weight loss. Celiac serologies including anti-gliadin, endomysial and transglutaminase antibodies were negative; however, a duodenal biopsy suggested celiac disease and a gluten-free diet was recommended. The patient was noncompliant with the diet because of continued anorexia and upper abdominal pain. On her normal diet, symptoms improved during the next several months and she gained 30 lbs. In the last trimester of her first pregnancy, the patient presented with recurrent diarrhea and weight loss. Upper gastrointestinal endoscopy revealed scalloping of the duodenal mucosa. Anti-gliadin IgG and IgA, endomysial antibodies, and tissue transglutaminase IgG and IgA antibodies were negative. Total IgA level was normal. ASCA IgG and IgA were positive. Colonoscopy revealed patchy erythema and erosions throughout the colon and ileum. Histopathologic examination of the duodenal biopsy showed a diffuse increase of mucosal chronic inflammatory cells, crypt hyperplasia, marked villous broadening, and partial villous atrophy (Fig. 3). One non-necrotizing granuloma was seen in a lymphoid aggregate. Colonoscopic biopsies showed multifocal cryptitis and rare crypt abscesses with intervening normal mucosa (Fig. 4). In the terminal ileum, an erosion overlying a lymphoid follicle was associated with a poorly formed granuloma.

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Figure FIGURE 3. Villous atrophy. The duodenal villi are broadened and shortened, lacteals in villous tips are distended, and the lamina propria is edematous and inflamed.

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Figure FIGURE 4. Crohn's disease of the colon. There is a patchy increase in chronic inflammatory cells including a loose aggregate of histiocytes next to a crypt abscess.

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The patient was diagnosed with Crohn's disease and was treated with prednisone and mesalamine. She improved symptomatically on this regimen. She was tapered off prednisone and started on mesalamine. A repeat upper endoscopy showed resolution of scalloped folds grossly. Biopsies showed no villous atrophy, but chronic inflammatory cells and crypt hyperplasia were apparent. The patient has been maintained on mesalamine alone.

Discussion

  1. Top of page
  2. Abstract
  3. Case Reports
  4. Discussion
  5. References

Scalloping of duodenal mucosal folds on endoscopic examination is most often a sign of villous atrophy secondary to celiac disease. 1,8 The three cases presented here demonstrate that this endoscopic finding is not specific for celiac disease. Each of our three patients had, in addition to scalloping on upper endoscopy, either ileitis or ileocolitis making a unifying diagnosis of Crohn's disease more likely. Pathologic examination of duodenal biopsies revealed mild villous atrophy, patchy inflammation, and granulomas. These findings are consistent with Crohn's disease. Two patients had positive serological markers (ASCA) supportive of the diagnosis of Crohn's disease. 9

The patients' clinical course and response to medication were also consistent with Crohn's disease. None of the patients had positive celiac serologies. Though patients with celiac disease may improve on steroids and immunosuppressive agents, the long-term follow-up of our patients showed histologic improvement without a gluten-free diet. These clinical scenarios and the follow-up biopsies make a diagnosis of celiac disease unlikely.

A recent paper identified scalloping as being one of the least sensitive markers for celiac disease (6%), but nevertheless highly specific (100%). 10 Most often, one sees loss or reduction of duodenal folds, scalloping of the Kerkring folds, and a mosaic duodenal mucosal pattern in celiac disease. The sensitivity of these findings is 50%, but they are highly specific (99%) with positive and negative predictive values of 60% and 99%, respectively. 11 Endoscopic markers of duodenal villous atrophy are not specific for celiac disease. They may suggest duodenal involvement with Crohn's disease in addition to tropical sprue, HIV enteropathy, Giardiasis, small intestinal opportunistic infections, and amyloidosis. 3

Crohn's disease may affect any part of the gastrointestinal tract. Early estimates of a 5% incidence of gastroduodenal involvement have been replaced by higher rates of up to 83%. 12 Better diagnostic procedures including upper endoscopy with biopsy have led to greater detection of proximal Crohn's disease. A retrospective histologic study by Wright and Riddell found that more than 75% of patients with Crohn's disease of the distal gastrointestinal tract have upper gastrointestinal abnormalities on biopsy. 6 Crohn's disease of the esophagus, stomach, and duodenum can occur in 5%–30% of patients with ileocolonic disease. 13

Patients with proximal disease may present with symptoms of anorexia, epigastric pain, dyspepsia, diarrhea, fever, weight loss, or a combination of these symptoms. 14 Upper gastrointestinal involvement with Crohn's disease is most commonly found in the antrum, duodenal bulb, and distal duodenum. Duodenal biopsy findings include villous atrophy (23%), focal inflammation (40%), intraepithelial lymphocytosis (22%), gastric metaplasia (18%), erosions (3%), and granulomas (1%). 15 Granulomatous inflammation, long considered to be the diagnostic histopathologic hallmark of gastroduodenal Crohn's disease, is actually only present in 6%–15% of biopsy specimens. 16 Changes classically associated with celiac disease, such as villous atrophy and intraepithelial lymphocytosis, are more common. 17

In Crohn's disease, endoscopic evaluation of the esophagus, stomach, and duodenum may show a variety of findings. The esophagus may have erosions, ulcers, or nodularity. 18 The antrum and duodenum may have granular mucosa with patchy erythema, friability, nodularity, or ulceration. The duodenum may have irregular, thickened folds or scalloped mucosa. 19 Stricture formation may be seen in the upper tract in severe cases.

Pathologic examination of the duodenal biopsies of these three patients showed an increase in chronic inflammatory cells, granulomas, villous atrophy, and crypt hypertrophy. Except for granulomas, each of these individual histologic findings is typically seen in celiac disease. In Crohn's duodenitis, however, changes are patchy, varying in intensity or alternating between normal and abnormal within a single biopsy or between separate biopsy pieces. Because the demonstration of patchiness is so crucial for arriving at the correct diagnosis, multiple biopsy specimens need to be taken.

Several case reports have described patients with celiac disease in addition to Crohn's disease or ulcerative colitis. 20–22 The diagnoses are based on a combination of serologies for celiac disease, histopathology, and response to therapy with either a gluten-free diet or steroids and 5-ASA compounds. The coexistence of celiac disease with other autoimmune disorders is commonly described, but the diagnosis of celiac disease and inflammatory bowel disease is infrequent. 22

In our three cases, serologic markers for both diseases proved to be useful. Tissue transglutaminase antibodies based on the ELISA assay are highly sensitive and specific for celiac disease. 23 In addition, immunoglobulin A autoantibodies to endomysium are close to 100% sensitive and specific for celiac disease. 24 Unfortunately, the disappearance of endomysial antibodies in treated celiac disease patients does not indicate histologic recovery. 25 It has been suggested as a tool for monitoring dietary compliance. In our three patients, this was not at issue.

Serological markers are helpful diagnostic tools to differentiate Crohn's disease from ulcerative colitis. Anti-Sacchromyces cerevisiae antibody has up to 60% sensitivity and 91% specificity for Crohn's disease. 26 The positive and negative predictive values are 88% and 68%, respectively. For perinuclear antineutrophil cytoplasmic antibodies (pANCA), the sensitivity, specificity, positive and negative predictive values are 50%, 95%, 69%, and 89%, respectively. 26 The specificity for these markers is high, but their low sensitivity makes them less useful. In combination with clinical scenarios and histopathologic confirmation, there is a greater diagnostic value. A retrospective study evaluated 37 patients with celiac disease by history (chronic diarrhea) and serology (87% EMA positive, 87% tTG positive) and found that 16 of the 37 patients were ASCA positive. 27 The presence of ASCA in the serum of patients with celiac disease can occur.

The type of inflammatory infiltrate in Crohn's disease is different from that in celiac disease. The concentration of chronic inflammatory cells are at the base of crypts rather than along the surface. The admixture of histiocytes, sometimes aggregating into ill-defined granulomas, and aggregates of neutrophils, sometimes associated with acute cryptitis, are features in favor of Crohn's disease. The study of Wright and Riddell suggests that intraepithelial lymphocytosis does not help to distinguish between Crohn's and celiac disease. Focal acute inflammation of the duodenal mucosa, in the absence of gastric Helicobacter pylori infection, was highly specific (92% specificity) for Crohn's disease, but was not found in our three cases. 6 Because H. pylori is a significant cause of gastritis, it must be excluded before focal acute inflammation can be attributed to Crohn's disease.

Scalloping of duodenal mucosal folds is most commonly seen as a result of celiac disease. These cases, however, illustrate that proximal Crohn's disease may manifest with this endoscopic appearance as well. Consequently, it is useful to correlate the finding of scalloping with clinical, histologic, and serologic data in making a specific diagnosis.

References

  1. Top of page
  2. Abstract
  3. Case Reports
  4. Discussion
  5. References