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1
Question:

A 32-year-old woman comes to the office due to postprandial abdominal pain and nausea.  The patient has no diarrhea, constipation, bloody stools, or vomiting.  Medical history is significant for rheumatoid arthritis.  The abdomen is mildly tender to palpation at the epigastrium but without distension or hepatosplenomegaly.  Laboratory studies reveal anemia.  A small gastric ulcer is seen during upper endoscopy, and biopsies are negative for Helicobacter pylori.  Biopsies of the duodenum reveal numerous intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia.  Based on these biopsy findings, this patient is at increased risk for developing which of the following conditions later in life?

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Explanation:

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Celiac disease

Pathogenesis

  • Gluten (gliadin) consumption → immune-mediated small intestine inflammation → chronic malabsorption

Symptoms

  • Abdominal pain
  • Diarrhea, flatulence & bloating
  • Failure to thrive (children) or weight loss
  • Iron deficiency anemia
  • Dermatitis herpetiformis

Diagnosis

  • Serology: tissue transglutaminase IgA, antiendomysial antibodies
  • Duodenal biopsy: intraepithelial lymphocytes, villous atrophy, crypt hyperplasia

Associated conditions

  • Autoimmune disorders (eg, type 1 diabetes)
  • Cancer risk: T-cell lymphoma

This patient's presentation (abdominal pain, anemia) and biopsy findings are suggestive of celiac disease, an immune-mediated disorder triggered by gluten, a protein found in wheat, barley, and rye.  Diarrhea is also common in celiac disease but may be absent.

Gliadin, a breakdown product of gluten, is primarily responsible for causing chronic inflammatory changes of the small bowel.  Classic histologic findings, which are most prominent in the proximal small bowel (eg, duodenum, proximal jejunum), include intraepithelial lymphocytosis, villous atrophy, and crypt hyperplasia.

Chronic lymphocytic recruitment and proliferation within the small-bowel mucosa predisposes to monoclonal T-cell expansion, putting these patients at risk for enteropathy-associated T-cell lymphoma.  This small-bowel cancer is usually very aggressive and has a poor prognosis despite chemotherapy.

(Choice A)  Angiodysplasias are dilated, tortuous veins that develop in the gastrointestinal tract, most commonly in the small bowel and cecum.  Risk factors include advanced age, chronic kidney disease, and aortic stenosis.  They have no association with celiac disease.

(Choice B)  In addition to small-bowel lymphoma, celiac disease is a risk factor for small-bowel adenocarcinoma.  Unlike ulcerative colitis, familial adenomatous polyposis, and Lynch syndrome, celiac disease does not predispose to colon adenocarcinoma.

(Choice C)  Portal vein thrombosis can create portal hypertension, predisposing to ascites and varices.  This can occur in patients with hypercoagulable conditions such as polycythemia vera, as well as those with cirrhosis and hepatocellular carcinoma.  Celiac disease does not predispose to portal vein thrombosis.

(Choice D)  Pyloric stenosis is a congenital disorder that results from pyloric smooth muscle hypertrophy and typically presents with profuse vomiting in infants.  It is not associated with celiac disease.

Educational objective:
Celiac disease, an immune-mediated disorder triggered by gluten, causes small intestinal intraepithelial lymphocytosis, villous atrophy, and crypt hyperplasia.  Monoclonal T-cell expansion can occur in the small-bowel mucosa of patients, leading to enteropathy-associated T-cell lymphoma.