Celiac Disease

Overview
  • Celiac Disease is an autoimmune disease which manifests with a characteristic mucosal histology and symptomology that is relieved upon removal of gluten from the diet.
Morphology
  • The classic histomorphology of celiac disease is atrophy or near total loss of small intestinal villi. Additionally, the intestinal Crypts of Lieberkuhn appear elongated and hyperplastic, likely in a compensatory attempt to replace continually destroyed intestinal villi. Celiac Disease is also characterized by inflammation with increased numbers of intraepithelial lymphocytes in the small intestine epithelium as well as lymphocytes and plasma cells within the small intestine lamina propria. Notably, these pathological changes are most visible in the duodenum and attenuate along the length of the small intestine as gluten becomes digested and destroyed. The most characteristic histological finding is a return to normal histology after removal of gluten from the diet.
Etiology
  • Development of celiac sprue is likely multifactorial and involves complex environmental, immune, and genetic interactions. The clear environmental contribution is the dietary presence of "Gliadin", a glycoprotein component of gluten found in wheat and barely. The pathology associated with celiac disease appears to be initiated by immune-mediated destruction of intestinal villi. Why and how the immune system inappropriately targets intestinal mucosa in the presence of gliadin is currently unclear although it does appear to occur only in genetically predisposed individuals as the disease is more common in whites and almost exclusively occurs in those possessing the HLA-B8 allele.
Clinical Consequences
  • The symptomology of celiac disease can manifest at any age and is characterized by diarrhea or steatorrhea. The diarrhea of celiac disease is likely multifactorial but mostly occurs due to reduced intestinal mucosal function and surface area resulting in malabsorption. However, a secretory diarrhea also contributes, likely arising from excessive fluid secretion by hyperplastic intestinal Crypts of Lieberkuhn. Over time, widespread nutritional deficiency can lead to failure to thrive in infants or weight loss in adults. However, in some cases disease may present as deficiency of a single nutrient without the presence of diarrhea. Finally, celiac disease is often co-morbid with dermatitis herpetiformis likely reflecting the patient's genetically deranged immunity.
Diagnosis
  • Definitive diagnosis of celiac disease is based on histological analysis of a patient's small intestine mucosa before and after dietary gluten restriction. If the characteristic histological changes remit with gluten restriction, then celiac disease is highly suspected, otherwise patients may be suffering from tropical sprue which possesses similar histological findings. Additionally, nearly 95% of patients possess anti-endomysial auto-antibodies which are specific to tissue transglutaminase involved in terminal protein digestion. However, these auto-antibodies are not thought to play a role in the pathogenesis of the disease but merely represent an epiphenomenon of deranged immunity.