A 16-year-old female had intermittent, nonspecific right upper quadrant abdominal pain for a period of one year. The episodes of pain would last approximately one week. The pain was nonradiating and there were no identifiable precipitating or relieving factors. Some of the episodes of abdominal pain were associated with severe headaches. She vomited on only one occasion but did suffer with occasional nausea. She denied weight loss. She was passing 1 to 2 stools per day which alternated between loose and firm. There was no hematochezia or melena. Her past medical history was unremarkable. There was no history of travel outside the United States. Family history was significant in that her father had been diagnosed with celiac disease. There was also a family history of migraine headaches and gallbladder disease. The patient was a dizygotic twin and her twin enjoyed good health. The patient was a competitive cross country runner and swimmer. Her menses were irregular during periods of intense training.
Her height was at the 80th percentile for age and sex, and her weight at the 60th percentile for age and sex. Her physical examination was completely normal. Upper gastrointestinal endoscopy was performed in order to evaluate her abdominal pain. Small intestinal biopsy findings are shown in Figures 1 and 2.
What is the most likely etiology for this patient's complaints?
- Celiac disease
- Crohn's disease
- Autoimmune enteritis
- Zollinger-Ellison syndrome
Answer: A. Celiac disease. Figure 1 is a biopsy of the descending duodenum demonstrating partial villus atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (×100). A higher magnification of the same specimen (see Fig. 2) reveals a stratified appearance of the enterocyte nuclei and a marked increase in intra-epithelial lymphocytes (×1000). The histological picture is that of partially treated celiac disease. It was learned that all of the family members were consuming a gluten-free diet when at home in deference to her father who had been diagnosed with celiac disease. She was found to have an elevated antiendomysial titer of greater than 1:40 and a positive antigliadin IgA antibody titer. Her antigliadin IgG titer was indeterminant. The institution of a strict gluten-free diet was followed by resolution of all symptoms.
Comment: Celiac disease is significantly more prevalent in first degree relatives of affected patients (up to 10% affected or 100 times the rate in the general population) with a concordance rate of 70% in monozygous twins. Certain HLA haplotypes appear to confer an increased susceptibility to celiac disease because of their role in antigen presentation to activated T cells. CD4T cells, thought to be important in the pathogenesis of celiac disease, are activated only when antigen is presented to them in complex with MHC HLA class II determinants (i.e., DR3, DR7, DR5, and DQ2) (1,2). First degree relatives of patients with celiac disease should be screened. Affected members in a "celiac" household may be receiving a predominantly gluten-free diet at home and display minimal symptoms of celiac disease. Establishing the diagnosis is important in these relatively asymptomatic patients because of the significantly increased long-term risk of small bowel lymphoma in untreated patients (3).
This case emphasizes the fact that the pathological diagnosis of celiac disease is based not only on the presence of villus atrophy but also on crypt hyperplasia, an increased number of intra-epithelial lymphocytes, and an increased number of plasma cells and lymphocytes in the lamina propria. The enterocyte nuclei may lose their basilar alignment and appear stratified. The differential diagnosis of partial villus atrophy in pediatric patients includes an infectious enteritis, intestinal stasis, tropical sprue, autoimmune enteropathy and Zollinger-Ellison syndrome (4).
1. Ottaway CA. Activated T cells and genetic restriction in celiac disease. J Pediatr Gastroenterol Nutr
2. Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis. Gastroenterology
3. Maths-Vliegen EM. Coeliac disease and lymphoma: Current status. Neth J Med
4. Petras RE. Nonneoplastic intestinal disease. In: Sternberg S (ed). Diagnostic Surgical Pathology
. New York: Raven Press Ltd, 1994, 1311-70.