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CELIAC DISEASE

DEFINITION:

A malabsorptive disorder characterized by a permanent gluten-sensitive enteropathy resulting in malabsorption, failure to thrive, and gastrointestinal manifestations.

EPIDEMIOLOGY:

incidence: 20/100,000 (declining with peak in early 70's)
prevalence: 1/500-3000
age of onset:
- usually develops before age 2
risk factors:
- food - BROW (barley, rye, oats, wheat)
- sex - F > M (1.3-2.8:1)
- geographic
  - Western Ireland, Europe
  - diet - decreased duration of breast feeding
    - early introduction of gluten into diet
- immunologic
  - HLA types:
    - Class I antigen - HLA-B8 (60-90%)
    - " II " - " -DQw2 (80-100%)
    - " -DR3 or DR7 (70-80%)
  - infection with adenovirus type 12 (homology between viral peptide and gliadin peptide)
- genetic
  - monozygotic twins - 70% concordance
  - first degree relatives:
    - 10% prevalence rate of occult celiac disease
    - 2-5% risk of developing overt "

PATHOGENESIS:

Gluten is the major form of stored protein in wheat and gliadin is a glycoprotein extract from gluten and this latter component is toxic to the small bowel mucosa of those with celiac disease. The pathophysiology of gliadin-induced damage to the mucosa is unknown but there are at least three hypotheses:

1. Toxic

catablism of gliadin may produce a metabolite which causes direct injury to the enterocytes
excess gliadin directly binds to an abnormal receptor on the surface membrane of the enterocyte -> injury - an abnormal immunologic response to gliadin

Mild cases involve the proximal small bowel with distal spread to the whole small bowel in more severe cases. As the lesion is con-tinuous and not patchy, to make the diagnosis only the proximal small bowel needs to be biopsied.
When a gluten-free diet is initiated, the mucosal recovery progresses proximally so that the upper small bowel recovers last.

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

failure to thrive
diarrhea - chronic or recurrent, occasionally fulminant
flatulence +/- abdominal pain or vomiting
malabsorption signs and symptoms:
- protein
- fat
- others - vit. B12, iron

2. Musculoskeletal Manifestations

wasting: limbs & buttock with marked abdominal distension

3. Others

anasarca, anemia, apathetic, delayed puberty, hypotonic, irritable, mouth sores, pale, peripheral edema, rectal prolapse, smooth tongue, clubbing, dental enamal hypoplasia

INVESTIGATIONS:

1. For Malabsorption

see "Malabsortive Disorders"

2. Imaging Studies

upper GI may show intestinal dilatation and thickening of the mucosal folds

3. Biopsy

1. Duodenum or Jejunum

crypts - hyperplastic & elongated with decreased life span
villi - atrophy (total or subtotal) -> flat & blunted
mucous membrane inflammation
- lymphocytic infiltration of the epithelium by cyto-toxic/suppressor T cells
- plasma cell infiltration of the lamina propria
morphologic changes in surface enterocytes
- columnar -> cuboidal or flattened
- increased RNA content -> basophillic cytoplasm
- nuclear disarray
- poorly defined brush border
- decreased enzyme activity (i.e., disaccharidases)

4. Serum Screening

CBC, ferritin, folic acid
decreased albumin, calcium, magnesium, and iron

DIAGNOSIS:

1. Gluten Challenge

first advocated in 1970
3 biopsies:
- 1st - typical histologic findings on gluten diet
- 2nd - full recovery of the mucosa on gluten-free diet
  - at 2-3 months after start of gluten-free diet
- 3rd - histologic relapse on gluten diet
  - changes detectable within 2 months

2. Screening Tests

1. Absorption/Permeability Tests

D-xylose absorption test
Urinary lactulose-to-mannitol ratio

2. Serum Antibodies

antigliadin IgG and IgA
antireticulin "
antiendomysial IgA - connective tissue component

MANAGEMENT:

1. Dietary Management

1. Avoid

wheat, barley, rye, and ?oats
processed foods (wheat flour)

2. Prefer

rice, soya, corn flours
unprocessed foods

2. Follow-up

growth curves (declining weight and height are the most con-sistent features of Celiac)
nutritional deficiencies
long-term complications:
- esophageal carcinoma
- small bowel adenocarcinoma
- small bowel lymphoma

3. Natural History

exacerbations and remissions
long-term prognosis is excellent

4. Diseases Associated with Celiac Disease

dermatitis herpetiformis
IDDM
selective IgA deficiency

Pediatric Database - CELIAC DISEASE

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