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Coeliac Disease

Coeliac disease (British English) or celiac disease (American English) is an autoimmune disorder that leads to an abnormal reaction to gluten, a protein found in wheat, barley, and rye. It primarily affects the small intestine, causing various gastrointestinal and systemic symptoms.

The disease can manifest at any age and is often linked with other autoimmune disorders.

Biopsy of small bowel showing coeliac disease
Biopsy of small bowel showing coeliac disease manifested by blunting of villi, crypt hyperplasia, and lymphocyte infiltration of crypts

Signs and Symptoms

Classic symptoms include chronic diarrhoea, abdominal distension, and malabsorption, which can lead to weight loss and failure to thrive in children. However, many people, especially older children and adults, may present with non-classic symptoms or be asymptomatic.

Non-classic symptoms can include fatigue, anaemia, low bone mass, and other systemic signs. Coeliac disease can also be associated with dermatitis herpetiformis, an itchy skin condition.

Gastrointestinal symptoms are typical but can vary in severity:

  • Chronic diarrhoea
  • Abdominal pain and cramping
  • Bloating and abdominal distension
  • Mouth ulcers

Malabsorption-related issues include:

  • Weight loss and fatigue
  • Iron deficiency anaemia
  • Osteopenia and osteoporosis
  • Deficiencies in vitamins A, D, E, K, selenium, copper, and zinc

Miscellaneous symptoms and associated conditions may involve:

  • IgA deficiency
  • Growth failure and pubertal delay in children
  • Pregnancy complications
  • Hyposplenism
  • Depression and anxiety

Cause

Coeliac disease is triggered by an inflammatory reaction to gluten proteins, primarily gliadins and glutenins in wheat and similar proteins in barley and rye. A genetic predisposition is very important, with most patients carrying the HLA-DQ2 or HLA-DQ8 alleles.

The disease involves an abnormal immune response leading to autoantibody production, inflammatory reactions in the small intestine, and villous atrophy, resulting in nutrient malabsorption.

DQ α5-β2 -binding cleft with a deamidated gliadin peptide
DQ α5-β2 -binding cleft with a deamidated gliadin peptide (yellow), modified from PDB: 1S9V

Diagnosis

Diagnosing coeliac disease involves a combination of serological tests and intestinal biopsies. Blood tests for antibodies like anti-transglutaminase (anti-tTG) and anti-endomysial (EMA) antibodies are first-line investigations.

Genetic testing for HLA-DQ2 and HLA-DQ8 can support the diagnosis. An endoscopy with biopsy of the duodenum is very important for confirming the diagnosis, especially if blood tests are inconclusive.

Immunofluorescence staining pattern of endomysial antibodies
Immunofluorescence staining pattern of endomysial antibodies on a monkey oesophagus tissue sample

Treatment

The primary treatment for coeliac disease is a strict lifelong gluten-free diet, which leads to the recovery of the intestinal lining, improvement of symptoms, and reduction in complications. Compliance can be challenging due to the widespread presence of gluten in many foods, and patients may benefit from dietitian support.

In some cases, additional measures such as supplementation for nutrient deficiencies, low-FODMAP diets, or avoidance of certain additives in gluten-free products may be required. Vaccination against certain infections, particularly for hyposplenic patients, is also recommended.

Refractory coeliac disease, where symptoms persist despite a gluten-free diet, may require additional treatments such as steroids or immunosuppressants after ruling out gluten exposure and other conditions.

Epidemiology

Coeliac disease affects about 1 in 100 to 1 in 170 people worldwide, with varying prevalence across different regions. It is more common in people of European descent and slightly more prevalent in women.

Many cases remain undiagnosed due to the broad spectrum of symptoms and lack of awareness among healthcare providers.

HLA region of chromosome 6
HLA region of chromosome 6

History

The term "coeliac" originates from the Greek word "koiliakós," meaning abdominal. The disease was first described in ancient Greece and later in modern times by Samuel Gee in 1887.

Significant advancements in understanding and diagnosing coeliac disease occurred in the mid-20th century, including the identification of gluten as the triggering factor and the development of biopsy techniques for diagnosing villous atrophy.


Self-assessment MCQs (single best answer)

Which protein is responsible for triggering coeliac disease in genetically predisposed individuals?



What is the primary treatment for coeliac disease?



Which HLA alleles are most commonly associated with coeliac disease?



Which of the following symptoms is NOT typically associated with coeliac disease?



Which diagnostic test is considered the most definitive for diagnosing coeliac disease?



Which condition is coeliac disease commonly associated with?



Which symptom is a classic gastrointestinal manifestation of coeliac disease?



What histological finding is characteristic of coeliac disease in an intestinal biopsy?



Which autoimmune condition is a known complication of untreated coeliac disease?



What is the prevalence of coeliac disease in the general population?



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Brilliant videos, thank you.
WS

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