Coeliac disease typically presents in genetically predisposed individuals, often of European descent, with chronic diarrhoea, bloating, and weight loss; hallmarked histologically by villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis in the small bowel, and genetically associated with HLA-DQ2 or HLA-DQ8 haplotypes.
Description
Coeliac disease, also known as gluten-sensitive enteropathy, is a chronic autoimmune disorder that primarily affects the small intestine. It is characterised by an aberrant immune response to dietary gluten, a protein found in wheat, barley, and rye, which results in inflammation and damage to the small intestinal mucosa. It is among the most common gastrointestinal diseases, affecting about 1% of the general population.
Pathogenesis
Coeliac disease is an autoimmune disorder influenced by genetic and environmental factors, primarily induced by gluten ingestion in genetically susceptible individuals. Partially digested gluten peptides, such as gliadin, are deamidated by tissue transglutaminase (tTG), enhancing their affinity for HLA-DQ2 or HLA-DQ8 molecules present in the intestinal mucosa. This leads to a gliadin-specific T cell-mediated immune response (Type IV hypersensitivity reaction), resulting in intestinal inflammation and villous atrophy. Concurrently, these activated CD4+ T cells promote B cells to produce anti-tTG antibodies, contributing to the disease pathogenesis. This complex interplay between genetic susceptibility, immune response to gluten, and autoimmunity results in coeliac disease’s symptomatic malabsorption.
Subtype
- Classical coeliac disease: Characterised by signs and symptoms of malabsorption, including diarrhoea, steatorrhoea (fatty stools), and weight loss or growth failure in children.
- Non-classical coeliac disease: Patients may present with mild gastrointestinal symptoms without clear signs of malabsorption. Extraintestinal symptoms such as anaemia, osteoporosis, neurological complaints may be present.
- Silent coeliac disease: Patients are asymptomatic but have villous atrophy on duodenal biopsy.
Epidemiology, Risk Factors & Associations
- Affects approximately 1% of the general population, with higher prevalence in Western countries and among populations of European descent.
- More common in females (female-to-male ratio 2:1).
- Often seen in early childhood and in middle age (but can be present at any age)
- Strong familial predisposition (seen in 10% of affected first-degree relatives)
- Strong association with HLA-DQ2 (90-95%) or HLA-DQ8 (others)
- Increased risk with other autoimmune conditions such as type 1 diabetes, autoimmune thyroid disease, autoimmune liver disease, and Sjögren’s syndrome.
- Increased risk with IgA deficiency (10 to 20 times higher risk) – individuals may also present with non-classical symptoms of coeliac disease and could yield false negative results on standard serological tests.
- Strongly associated with dermatitis herpetiformis – a pruritic, blistering skin disease
Clinical Features
- Common features include diarrhoea, abdominal pain, bloating, and weight loss.
- Extraintestinal manifestations may include dermatitis herpetiformis, anaemia, osteoporosis, and neurological symptoms (e.g., ataxia, neuropathy).
Complications
- Malabsorption leading to nutritional deficiencies
- Small bowel intussusception
- Refractory coeliac disease
- Ulcerative jejunoileitis
- Splenic atrophy may occur due to chronic inflammation, autoimmunity, and malabsorption-related nutritional deficiencies
- Increased risk of malignancies like enteropathy-associated T-cell lymphoma (EATL) and small bowel adenocarcinoma.
Pathological Features
Histopathology
- Macroscopic: Jejunal dilatation and jejunisation of the ileal loops are characteristic features.
- Microscopic: Characterised by villous atrophy, crypt hyperplasia, and intraepithelial CD8+ T lymphocytosis in the small intestinal mucosa.
Serology
- High levels of antibodies: anti-tissue transglutaminase (most sensitive), anti-endomysial, and anti-deamidated gliadin peptide IgA or IgG. Commonly found in untreated coeliac disease.
Biochemistry
- May show signs of malabsorption (e.g., low iron, folate, or vitamin B12 levels).
Radiological Features
General Features
- Non-specific findings, often normal in early or mild disease.
- In advanced disease, can show features of malabsorption such as decreased bowel wall enhancement and loss of normal fold pattern in small bowel.
- Complications such as strictures, ulcers, and malignancy can also be detected.
- Jejunoileal fold pattern reversal: Refers to an increased number of ileal folds and a reduced number of jejunal folds (the opposite to normal). Highly specific sign indicating mucosal atrophy and compensatory changes.
US
- Increased bowel wall thickness may be noted.
CT
- Non-contrast: May show bowel wall thickening.
- Contrast-enhanced:
- Jejunoileal fold pattern reversal
- Small bowel dilatation
- Perienteric stranding
- Intussusceptions
- Prominent mesenteric lymph nodes which may cavitate with a fat-fluid level (low density)
- Submucosal fat deposition in chronic disease
- Splenic atrophy
MRI
- T1: Increased signal in the bowel wall and mesentery due to inflammation and oedema.
- T2:
- Jejunoileal fold pattern reversal
- Decreased signal due to fibrosis in chronic disease.
- T1 C+: Bowel wall enhancement can be variable.
- DWI/ADC: No specific findings.
FL
- Jejunoileal Fold Pattern Reversal
- Small Bowel Dilatation: Widening of the small intestine due to the accumulation of excess fluid, caused by inflammation and malabsorption.
- Dilution of Contrast: Barium contrast appears less dense and more diluted than normal due to increased fluid content in the intestines.
- Multiple Non-Obstructing Intussusceptions (Coiled Spring Appearance): Sections of the intestine telescope into adjacent parts without causing a complete blockage, seen as stacked rings on imaging.
- Moulage Sign: Jejunum appears smooth and featureless as if “cast in a mold” (French: casting/molding), due to severe mucosal atrophy.
- Mosaic Pattern: Patchy, irregular pattern in the bowel mucosa from villous atrophy and nodular changes.
- Flocculation: Clumping of the barium contrast within the bowel due to excessive secretions and mucus.
- Segmentation: Segmented appearance with alternating areas of normal and abnormal mucosa caused by irregular contractions and mucosal damage.
NM
- PET FDG: May show increased uptake in the bowel wall in active disease, as well as detection of complications (e.g., malignancy).
Grading and Staging
The Marsh classification is commonly used to categorise histological changes in coeliac disease, from Marsh 0 (normal) to Marsh 3C (marked villous atrophy).
Diagnosis
Diagnosis is typically based on a combination of serology (high antibody levels), histopathology (duodenal biopsy showing characteristic changes), and clinical response to a gluten-free diet.
Differential Diagnosis
- Irritable bowel syndrome: Characterised by chronic abdominal pain and changes in bowel habits. No histological abnormalities on duodenal biopsy.
- Inflammatory bowel disease: Can also cause diarrhoea and abdominal pain. However, typically demonstrates a different pattern of intestinal involvement and abnormalities on imaging.
- Tropical sprue: Causes similar symptoms and villous atrophy but typically occurs after travel to tropical regions. Response to antibiotics can differentiate from coeliac disease.
- Lymphoma: Eccentric soft tissue mass in bowel wall.
Management
The mainstay of management is a strict lifelong gluten-free diet, which leads to improvement of symptoms and histological changes in most patients. Referral to a dietitian is usually the first step after diagnosis. In cases of refractory coeliac disease or complications, further medical or surgical treatment may be necessary.