Celiac Disease

Celiac disease is a small intestinal enteropathy, characterised by autoantibodies to tissue transglutaminase, resulting in hypersensitive immune response towards gluten and related proteins.

Synonyms: Celiac sprue, Non‐tropical sprue, Idiopathic sprue, Idiopathic steatorrhoea, Gluten-sensitive enteropathy.

Gluten: Found in foods produced from barley, rye, some varieties of oats and wheat (Mnemonic: BROW). It is a common additive to prepared foods and pharmaceuticals.

Epidemiology

• Global prevalence: 1.4%.
• Prevalence in first-degree relatives: 10-15%.

Etiology

Celiac disease is widely regarded as an autoimmune disease that occurs in genetically predisposed people.

Histocompatibility locus antigens HLA DQ2 and DQ8 are found in 25-30% of general population.

• Presence of one of the two haplotypes is necessary but not sufficient for developing celiac disease.
• Detection of these alleles is not useful for diagnosis, since, most carriers never develop celiac disease.
• Negative predictive value: More than 99%, very useful in ruling out celiac disease.

*Tissue transglutaminase deamidates glutamine residues of gluten-derived peptides, and facilitates their presentation by antigen-presenting cells.

Clinical Manifestations

Ranges from being asymptomatic to having isolated iron-deficiency anemia, and malabsorption of multiple nutrients.

• Common presenting complaints: Diarrhea, weight loss, and growth failure in children.
• Bloating and irregular bowel habits.
• Migraine headaches and ataxia.
• Osteoporosis, iron-deficiency anemia, and abnormal liver enzymes.

Associated Diseases

• Autoimmune disorders such as type 1 diabetes mellitus and autoimmune thyroid disease.
• Dermatitis herpetiformis, characterised by by a vesicular rash mediated by IgA deposits in the skin.
• Down syndrome and Turner syndrome -> Have an increased risk of celiac disease.

Mechanism of Diarrhea

• Villus atrophy in proximal small intestine, leads to steatorrhea from mucosal malabsorption.
• In addition, there is secretory component due to crypt hyperplasia and fluid hypersecretion from the crypt epithelium.

Diagnosis

• Initial Screening: Serum antibodies incl. tissue transglutaminase IgA, anti-endomysial and deamidated anti-gliadin antibodies.
• Serum IgA levels: To detect false-negative results that may occur due to IgA deficiency. Tissue transglutaminase IgG antibodies or deamidated antigliadin IgG antibodies are detectable and diagnostic in IgA-deficient patients.
• Confirmatory test: Endoscopy with small-intestinal biopsy.
• Family members of patients with celiac disease are screened if symptomatic.

Biopsy Findings

• Mucosal architectural changes: Villus atrophy, crypt hyperplasia, thickening of basement membrane under surface epithelium, and reduced number of goblet cells.
• Mucosal inflammation, incl. increased intraepithelial lymphocytes.
• Enterocyte changes: Cuboidal morphology, loss of basal nuclear orientation and cytoplasmic vacuoles.

Marsh Classification

The modified Marsh-Oberhuber classification categorises different types of celiac disease-related lesions and is used to quantify severity of disease involvement.

Image Source: https://www.mdpi.com/2077-0383/13/5/1382

Complications

• Refractory celiac disease.
• Enteropathy-associated T-cell lymphoma.
• Hyposplenism.
• Small-bowel adenocarcinoma.

Refractory Celiac Disease

• Found in about 10% of patients with persistent active disease.
• Characterised by ongoing diarrhea, weight loss and persistent villus atrophy on biopsy after 1 year of strict gluten-free diet.
• Also, the patients have negative celiac serology confirming adherence to gluten-free diet.
• Type 1 refractory celiac disease: Normal intraepithelial lymphocyte population.
• Type 2 refractory celiac disease: Clonal expansion of CD3+ intraepithelial lymphocytes that also contain a monoclonal rearrangement of the gamma chain of T-cell receptor. It has a worse prognosis, due to its association with T-cell lymphoma.

Treatment

The mainstay of treatment is institution of a strict gluten-free diet. Patients must be given rigorous dietary instruction from a dietician and adhere lifelong to a gluten-free diet.

Patients whose symptoms resolve after gluten-free diet

• Serologic follow-up to confirm compliance with the diet.
• Follow-up biopsy to document complete healing of villous atrophy.

Patient whose symptoms does not resolve after gluten-free diet

• The most common cause is nonadherence to diet or inadvertent gluten exposure.
• Biopsy, to determine the degree of disease activity and to rule out other causes and complications.
• If biopsy is negative, but, symptoms persist, other causes of abdominal pain and diarrhea associated with celiac disease are considered such as IBS, microscopic colitis, small-bowel bacterial overgrowth, and lactose/fructose intolerance.

References

• Harrison's Principles of Internal Medicine (21st edition), Joseph Loscalzo & Anthony S. Fauci & Dennis L. Kasper & Stephen Hauser & Dan Longo & J. Larry Jameson, The McGraw-Hill Companies.
• Coeliac disease: an update for pathologists B C Dickson, C J Streutker, and R Chetty J Clin Pathol. 2006 Oct; 59(10): 1008–1016, doi: 10.1136/jcp.2005.035345 PMCID: PMC1861744 PMID: 17021129
• The image used as cover photo is licensed under the Creative Commons Attribution-Share Alike 4.0 International license. Source: Wikimedia Commons. Author: www.scientificanimations.com

_{*This article is an excerpt from the above mentioned book and Medical Sutras does not make any ownership or affiliation claims.}