celiac disease:
* is an immunologically mediated inflammatory disorder of the small bowel occuring in genetically susceptible individuals & lead to intolerance to wheat gluten , rye, barley & oats.
*its common worldwide but is more common in northern europe.
*50% of cases are asymptomatic , gluten peptides are deamidated by the enzyme tissue transglutaminase in the subepithelial layer.
They are then able to fit the antigen-binding on HLA-DQ2-positive antigen-presenting cells. Recognition by CD4+ T cells triggers a Th1 immune response with generation of pro-inflammatory cytokines (IL-1, IFN-? and TNF-?). Lymphocytes infiltrate the lamina propria, and increased intraepithelial lymphocytes (IEL), crypt hyperplasia and villous atrophy
Clinical features:
*Coeliac disease can present at any age.
* In infancy it occurs after weaning on to cereals and typically presents with diarrhoea, malabsorption and failure to thrive.
*In older children it may present with non-specific features such as delayed growth. Features of malnutrition are often found on examination and mild abdominal distension may be present. & short stature
* In adults peak onset is in the third or fourth decade and females are affected twice as often as males. Some patients have florid malabsorption while others develop non-specific symptoms such as tiredness, weight loss, folate deficiency or iron deficiency anaemia.
*Other recognized presentations include :
()oral ulceration, dyspepsia and bloating. ()under nutrition and increased risk of osteoporosis.
()abnormal coagulation due to vitamin K deficiency and are slightly at risk for abnormal bleeding
Disease associations of coeliac disease:
()Insulin-dependent diabetes mellitus (2-8%)
()Thyroid disease (5%)
()Primary biliary cirrhosis (3%)
()Sj?gren s syndrome (3%)
()IgA deficiency (2%)
()Pernicious anaemia
()Inflammatory bowel disease
()Sarcoidosis
()Myasthenia gravis
()Neurological complications: encephalopathy, cerebellar atrophy, peripheral neuropathy, epilepsy
()Dermatitis herpetiformis
()Down s syndrome
()Enteropathy-associated T-cell lymphoma
()Small bowel carcinoma
()Squamous carcinoma of oesophagus
()Ulcerative jejunitis
()Pancreatic insufficiency
()Microscopic colitis
()Splenic atrophy
investigations:
Duodenal biopsy :
Endoscopic small bowel biopsy is the gold standard.
The histological features are usually characteristic but other causes of villous :atrophy should also be considered
Important causes of subtotal villous atrophy
()Coeliac disease
()Tropical sprue
()Dermatitis herpetiformis
()Lymphoma
()AIDS enteropathy
()Giardiasis
()Hypogammaglobulinaemia
()Radiation
()Whipple s disease
()Zollinger-Ellison syndrome
Antibodies :
()IgA anti-endomysial antibodies are detectable by immunofluorescence in most untreated cases.
()IgG antibodies, however, must be analysed in patients with coexisting IgA deficiency.
()The tTG AB assay has replaced other blood tests in many countries as it is easier to perform, but are not a substitute for small bowel biopsy; they usually become negative with successful treatment.other
() microcytic or macrocytic anaemia from iron or folate deficiency .
() hyposplenism (target cells, spherocytes and Howell-Jolly bodies).
()Biochemical tests may reveal reduced concentrations of calcium, magnesium, total protein, albumin or vitamin D.
()Measurement of bone density should be considered to look for evidence of osteoporosis,Management
()The aims are to correct existing deficiencies of iron, folate, calcium and/or vitamin D,
() a life-long gluten-free diet. This requires the exclusion of wheat, rye, barley and initially oats,
()Regular monitoring of symptoms, weight and nutrition is essential.
() an excellent clinical response, with disappearance of circulating anti-endomysial antibodies, probably do not need to undergo repeat jejunal biopsies. These should be reserved for patients who do not symptomatically improve or whose antibodies remain persistently positive.
()Rarely, patients are refractory and require treatment with corticosteroids or immunosuppressive drugs to induce remission.
()if their diet is satisfactory, other conditions such as pancreatic insufficiency or microscopic colitis should be sought, as should complications of coeliac disease such as ulcerative jejunitis or enteropathy-associated T-cell lymphoma
Complications
1- A twofold increased risk of malignancy, particularly of enteropathy-associated T-cell lymphoma, small bowel carcinoma and squamous carcinoma of the oesophagus,
2- A few patients develop ulcerative jejuno-ileitis;
3- Osteoporosis and osteomalacia may occur in patients with long-standing, poorly controlled coeliac disease.
Dermatitis herpetiformis:
()This is characterised by crops of intensely itchy blisters over the elbows, knees, back and buttocks. .()Immunofluorescence shows granular or linear IgA deposition at the dermo-epidermal junction.
() Almost all patients have partial villous atrophy on jejunal biopsy, even though they usually have no gastrointestinal symptoms.
()In contrast, fewer than 10% of coeliac patients have evidence of dermatitis herpetiformis,
()The rash usually responds to a gluten-free diet but some patients require additional treatment with dapsone (100-150 mg daily).
Tropical sprue:
() is defined as chronic, progressive malabsorption in a patient from the tropics, associated with abnormalities of small intestinal structure and function.
() The disease occurs mainly in the West Indies and in Asia, including southern India, Malaysia and Indonesia.
Clinical features
() There is diarrhoea, abdominal distension, fever, anorexia, fatigue and weight loss.
() the features of megaloblastic anaemia (folic acid malabsorption) and ankle oedema, glossitis and stomatitis, are common.
() Remissions and relapses may occur.
Management :
() Tetracycline 250 mg 6-hourly for 28 days is the treatment of choice.
() In most patients pharmacological doses of folic acid (5 mg daily) improve symptoms and jejunal morphology.