creation date: 2025-11-13 15:27
tags: Pathologies

Celiac Disease

Background

Definitions

Celiac disease, also known as gluten-sensitive enteropathy, is a immune-mediated inflammatory disease of the small intestine. This is characterized by a genetic predisposition and sensitivity to gluten and gluten-related proteins.

It should be noted that this is distinct from non-celiac gluten sensitivity or gluten intolerance.

Etiology and Pathogenesis

There is a genetic basis of celiac disease with a number of genes being associated with the disease. Celiac disease is also associated with other autoimmune disorders.

The environmental agent that triggers celiac-related inflammation is gliadin, a component of gluten found in wheat and related cereals.

The pathophysiology of celiac disease involves gliadin-reative T-cells in the lamina propria. Gliadin resists complete digestion in celiac disease and through deamination by tissue transglutaminase (tTG) become highly likely to bind to specific antigen-presenting cells with HLA-DQ2 or HLA-DQ8 markers.

Subsequent immune response results in:

CD4+ T cells releasing pro-inflammatory cytokines, driving inflammation, crypt hyperplasia, and destruction of intestinal villi
B cell production of autoantibodies
CD8+ T cells attack intestinal epithelial cells exacerbating damage

It should be noted that presence of HLA-DQ2 or HLA-DQ8 does not necessarily result in celiac disease. Factors that may trigger disease in susceptible individuals include:

Infections that alter immune response
Disruptions to gut microbiome (eg. following antibiotic use)
Physiological changes during pregnancy

Clinical Presentation

Signs & Symptoms

Classic manifestations consist of gastrointestinal findings:

Diarrhea with bulky, foul-smelling, floating stools (steatorrhea and flatulence)
Malabsorption (weight loss, severe anemia, neurologic disorders from deficiencies, osteopenia)

Extra-intestinal findings include:

Dermatitis herpetiformis - pathognomonic, even in absence of GI symptoms
Atrophic glossitis
Metabolic bone disorders
Hematologic (iron deficiency anemia, hyposplenism)
Elevated aminotransferases
Neuropsychiatric symptoms (headache, peripheral neuropathy, ataxia, epilepsy, depression, dysthymia, anxiety) - limited evidence

In children, presenting symptoms include:

Poor weight gain (decreased appetite, irritability, diarrhea)
Abdominal distension
Vomiting
Constipation

History & Physical Exam

History should focus on eliciting the severity of symptoms. It is important to consider atypical presentations.

A number of conditions are associated with celiac disease, including:

Type 1 diabetes mellitus
Thyroid disease (more hypothyroidism)
Atopic dermatitis
GERD
Eosinophilic esophagitis
IBD
Microscopic colitis
Liver disease
Pancreatitis
Menstrual / reproductive issues
Idiopathic pulmonary hemosiderosis
Cardiovascular disease (autoimmune myocarditis, idiopathic dilated cardiomyopathy)
Kidney disease

Physical examination should assess the abdomen as well as the various extra-intestinal sites of manifestations. Note that in atypical cases, gastrointestinal symptoms may be absent.

Diagnosis

Criteria

Diagnosis is based on pre-test probability for celiac disease and whether the patient is on a gluten-containing diet.

Testing should be performed while patients are on a gluten-containing diet.

For patients with low disease probability, identified by any of the following:

Absence of suggestive signs or symptoms of malabsorption (eg. significant chronic diarrhea/steatorrhea, weight loss)
Absence of family history of celiac disease
Chinese, Japanese, or sub-Saharan African descent

These patients should undergo serologic testing:

tTG-IgA + total IgA
If negative: tTG-IgG + DGP-IgG

If serologic testing are positive, disease should be confirmed with upper endoscopy and small bowel biopsy.

For patients with high celiac disease probability, identified by:

Highly suggestive clinical presentation
Risk factors for celiac disease (family history, T1DM, autoimmune thyroiditis, Down and Turner syndromes, pulmonary hemosiderosis)

These patients should have serologic evaluation and upper endoscopy with small bowel biopsy simultaneously.

Diagnosis is made by established presence of one of the following:

Increased intraepithelial lymphocytes with crypt hyperplasia, alone
Villous atrophy on biopsy with positive celiac serology

It should be noted that if upper endoscopy is not used, a high tTG IgA (>10x elevation over ULN) with positive endomysial antibody in a second sample can be diagnosed as likely celiac disease.

Evaluation with genetic testing for HLA-DQ2 and HLA-DQ8 may also be done following endoscopy but is rare.

Work-up

Screening
Screening for asymptomatic patients has not been shown to be beneficial. However, it can be considered if an asymptomatic patient has first-degree relatives with a confirmed diagnosis.

Differential

Common alternative diagnoses include:

Irritable bowel syndrome
Small intestinal bacterial overgrowth
Tropical sprue (histologically the same but malabsorption following extended tropical visit)
Lactose intolerance
Chronic pancreatitis
Microscopic colitis
Inflammatory bowel disease

Symptomatic response to gluten with no serologic or histologic evidence of celiac disease is described by non-celiac gluten sensitivity.

Red Flags / Complications

Complications of uncontrolled celiac disease include:

Malabsorption and nutritional deficiencies
Higher risk of gastrointestinal malignancies
Dermatitis herpetiformis
Peripheral neuropathy and ataxia
Psychiatric conditions (eg. depression, anxiety)
Reproductive problems
Risk of pneumococcal infections (even with control)

Management

Diet management
The cornerstone of treatment is gluten elimination from the diet. This generally involves education and consultation with a dietitian.

Generally, the following advice is given to all patients:

Avoid wheat, rye, and barley
Soybeans or tapioca flours, rice, corn, buckwheat, and potatoes are safe
Read labels on prepared foods as many additives may contain gluten
Distilled alcoholic beverages and vinegars, and wine are safe
Beers, ales, lagers, and malt vinegars should be avoided (may be exceptions)
Dairy products should be avoided if secondary lactose intolerance
Oats should be avoided due to contamination
Fibre supplementation may be required if constipation is induced

Most patients (70%) have noticeable improvement within 2 weeks but symptom burden should be monitored regularly.

Serologic testing should be done 6 and 12 months following diagnosis for response to the gluten-free diet.

Treatment of nutritional deficiencies
Patients should be tested for deficiencies of:

Vitamins (A, D, E, B12)
Folic acid
Ferritin and iron
Prothrombin time (as a measure of vitamin K deficiency)

Other deficiencies may occur based on severity of disease. Deficiencies should be repleted.

Follow-up
Should consist of monitoring symptoms, assessment of adherence to diet, and assessment of complications. Additionally, routine annual bloodwork should include:

MD Notes

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