Download Coeliac Disease (CD)

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Coeliac Disease (CD)
By Dr. Zahoor
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Coeliac Disease
Coeliac Disease (Gluten Sensitive Enteropathy)
• Coeliac Disease (CD) is an immunologically mediated
disorder in which there is inflammation of mucosa of
the upper small bowel (duodenum and jejunum) that
improves when gluten is withdrawn from the diet and
relapses when gluten is reintroduced
• Up to 1% of population is affected
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Coeliac Disease
(Gluten Sensitive Enteropathy)
What is Gluten?
 Gluten is the protein content of the cereals,
present in Wheat, Barley, Rye and Oat
 Prolamins (seed protein) – damaging factors
Gliadin – from wheat
Hordeins – from Barley
Secalins – from Rye
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Rye
Barley
Oats
Wheat
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Coeliac Disease
(Gluten Sensitive Enteropathy)
• Gluten protein present in wheat, barley, rye can
not be digested by pepsin, chymotrypsin because
of their high glutamine and proline contents,
therefore, remain in the intestine lumen
triggering immune response
Immunology
• Gliadin peptides pass through epithelium in
small intestine and bind to antigen presenting
cells
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Coeliac Disease
(Gluten Sensitive Enteropathy)
• Antigens present in cells interact with CD4 Tcell ( T- helper cell) in the lamina propria
• These CD4 T-cell produce interferon and also
interact with B-cell to produce antibodies
• Gliadin peptide also causes release of
interleukin – 15 from entrocytes, activating
entroepethilial lymphocytes
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Coeliac Disease
(Gluten Sensitive Enteropathy)
• This inflammatory cascade releases
metalloproteinases and other mediators that
contribute to the VILLIOUS ATROPHY and
CRYPT HYPERPLASIA, which are typical of
Coeliac disease.
• Mucosa of proximal small bowel (duodenum and
jejunum) is predominantly affected. Mucosal
damage decreases towards ileum.
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Pathophysiology of Coeliac Disease
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Genetic Factors
• Increase incidence of Coeliac Disease occurs in
families but exact mode of inheritance is not
known
• Over 90% of patients will have HLA-DQ2
Environmental Factors
• Rota virus infection in infancy increases the risk
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Clinical Features
• Coeliac Disease can present at any age
• In infancy, it sometimes appears when gluten
containing foods are introduced
• In adult, peak age of diagnosis is 5th decade with
F > M. Many patients are asymptomatic (silent)
and come to attention because of routine blood
test e.g. raised MCV, or iron deficiency in
pregnancy
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Symptoms
• These are non-specific e.g. tiredness and malaise
associated with anaemia
GI Symptoms
• May be absent or mild
• Diarrhoea, Steatorrhea, abdominal pain and
weight loss – suggest more severe disease
• Mouth ulcer, angular stomatitis are frequent and
can be intermittent
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Coeliac Disease
(Gluten Sensitive Enteropathy)
• Neuropsychiatric symptoms of anxiety and
depression occur
Neurological symptoms
• Paraesthesia, Ataxia, Muscle weakness,
polyneuropathy occur
• Other Symptoms – Infertility
Rare complications
• Tetany
• Osteomalacia, Osteoporosis
• Gross mal nutrition with peripheral edema
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Association with other autoimmune disease
• There is increased incidence of autoimmune diseases
associated with CD, like
- Thyroid disease
- Type I Diabetes Mellitus
- Sjogren’s syndrome ( Rheumatoid arthritis , dry
eyes, dry mouth due to degeneration of lachrymal and
salivary glands )
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Other Associated Diseases with CD
• Inflammatory bowel disease
• Primary Biliary cirrhosis
• Chronic liver disease
• Interstitial lung disease
• Epilepsy
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Coeliac Disease
• Consider Differential Diagnosis
- Giardiasis
- Chronic pancreatitis
- Lactose intolerance
- Irritable bowel syndrome
- Crohn disease
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Diagnosis
• Small bowel biopsy
Histology
• Shows subtotal villous atrophy
• Crypt hyperplasia with inflammatory cells,
increased lymphocyte and plasma cells in the
lamina propria
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Diagram showing normal and subtotal villous atrophy
Normal Mucosa
Subtotal Villous Atrophy in CD
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Causes of Subtotal Villous Atrophy
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Diagnosis (cont)
Endoscopy
• Endoscopy shows absence of mucosal folds,
mosaic pattern of mucosal surface
Serology
• Endomysial and anti tissue transglutaminase
antibodies – sensitivity is more than 90%
• IgA antibodies
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Diagnosis
HLA typing
• HLA - DQ2 ( gene marker) is present in 90 - 95%
cases ( on chromosome-6 )
• HLA – DQ8 is present in about 8%
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Other investigation
• Folate deficiency is common and causes
macrocytosis (Vitamin B12 deficiency is rare)
• Iron deficiency is common
• Blood film may show microcytosis and
macrocytosis, hyper segmented
polymorphonueclear leukocytes
• Howell – Jolly bodies due to splenic atrophy
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Howell – Jolly bodies in a blood smear stained with Giemsa
Note: Howell-Jolly bodies are histological finding. It is basophilic nuclear
remanants (cluster of DNA) in circulating erythrocytes.
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Investigations (cont)
Biochemistry
• Low calcium and high phosphate – Osteomalacia
• Hypoalbuminaemia
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Investigation (cont)
Radiology
• Small bowel follow through may show dilatation
of small bowel with slow transit
• Bone densitometry (DXA) – should be
performed due to risk of Osteoporosis
• Capsule endoscopy
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Treatment and Management
• Gluten free diet for life
Elimination of wheat, barley, rye ,oats
NOTE – Diet produces clinical improvement within
days or weeks. Morphological improvement takes
months
• Replacement of minerals and vitamins
E.g. Iron, folic acid, calcium, vitamin D
• Pneumococcal vaccination – once every 5 years
(because of splenic atrophy)
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Complications
• Very rarely, T-cell lymphoma
• Ulcerative jejunitis – present with fever,
abdominal pain, perforation and bleeding
Diagnosis for these Complications
• MRI
• Laparoscopy with small bowel biopsy
• Barium studies
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Treatment for Ulcerative Jejunitis
• Steroids
• Immunosuppressive agents Azathioprine
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Coeliac Disease
(Gluten Sensitive Enteropathy)
Association with Coeliac Disease
• Dermatitis herpetiformis – blistering sub epidermal eruption of skin associated with
Coeliac disease. It is extremely itchy appears on
forearm, knees, buttocks and back.
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Dermatitis herpetiformis at the forearm, elbow region and on the hand
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