Celiac disease

Pathogenesis: immune-inflammatory cascade

Inflammation in the small intestinal mucosa is triggered by dietary gluten intake. Pathogenesis can be divided into several sequential stages:

1. Antigen presentation. Gliadin peptides bind to major histocompatibility complex molecules (HLA-DQ2 or HLA-DQ8) and are presented to gluten-specific CD4+ T lymphocytes.
2. Cytokine aggression. Activated lymphocytes begin massive production of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and others). This leads to a direct destructive effect on intestinal epithelial cells.
3. Humoral response. Under the action of cytokines, B lymphocytes transform and begin synthesizing autoantibodies (Abs). Targets include gliadin itself, tissue transglutaminase (tTG), and endomysial structures. The entry of these antibodies into the systemic bloodstream enables serological diagnosis.

Clinical presentation and symptom evolution

There is no single pathognomonic symptom of celiac disease, and the clinical picture transforms significantly as the patient grows older.

In infants and toddlers, gastroenterological syndrome predominates. Manifestation typically occurs in the second half of life (1.5–2 months after the introduction of cereal complementary foods). Profuse foul-smelling stools (steatorrhea), flatulence, abdominal distension, and severe protein-energy malnutrition are characteristic. Psychoneurological shifts are observed: negativism, apathy, sleep disturbances.

In adolescents and adults, classic intestinal symptoms often recede into the background. Extraintestinal manifestations begin to prevail:

• Skin: dermatitis herpetiformis, vitiligo, alopecia, aphthous stomatitis.
• Musculoskeletal system: osteoporosis, arthralgia, tooth enamel defects.
• Hematology: iron-deficiency and vitamin B12-deficiency anemias refractory to oral therapy.
• Reproductive system: delayed puberty, infertility.

Stages of the disease and response to diet

Celiac disease proceeds with clear staging that directly depends on contact with the trigger:

• Latent period — the time from the first gluten consumption to clinical manifestation.
• Active period — development of the full clinical picture.
• Partial remission — achieved after 3–6 months of a strict gluten-free diet. Complaints disappear, specific antibody titers decrease, but biopsy signs of atrophic enteropathy persist.
• Complete remission — stated no earlier than 1–1.5 years of ideal adherence to the diet. Complete mucosal recovery occurs.

Comprehensive diagnostic algorithm

The diagnosis is not made based on a single symptom or test. Evaluation of four components is required:

1. Clinical block — presence of gluten-dependent symptoms.
2. Serological screening — search for blood IgA antibodies to tissue transglutaminase, endomysium, and deamidated gliadin peptides. Important: blood collection is performed strictly before gluten withdrawal, and the total IgA level is measured beforehand (to exclude false-negative results in selective IgA deficiency).
3. Morphological examination — the "gold standard". Biopsy of the jejunal or duodenal mucosa is performed. The triad is sought: villous atrophy, crypt hyperplasia, and intraepithelial lymphocytic infiltration (Marsh scale evaluation).
4. Genetic typing — detection of predisposing HLA-DQ2/DQ8 alleles.

Class and exam questions

What else to study on this topic

• Morphological classification of enteropathy according to the M.N. Marsh scale (grades 1–3)
• Refractory celiac disease phenomenon: causes of unresponsiveness to diet
• Differential diagnosis with wheat protein food allergy and cystic fibrosis
• The problem of "hidden gluten" in industrially manufactured products
• Risk groups for celiac disease (Down syndrome, type 1 diabetes mellitus, autoimmune thyroiditis)

Other topics in "Chapter 7. Digestive System Diseases"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.