Celiac disease

  • Celiac disease
    • also known as celiac sprue or gluten-sensitive enteropathy (MCQ)
    • It is an immune-mediated enteropathy  (MCQ)
    • triggered by the ingestion of gluten-containing cereals, such as wheat, rye, or barley, in genetically predisposed individuals. (MCQ)
    • alcohol-soluble fraction of gluten, gliadin, contains most of the disease-producing components.
    • Pathophysiology :
      • Gluten is digested by luminal and brush-border enzymes into amino acids and peptides
      • α-gliadin peptide that is resistant to degradation by gastric, pancreatic, and small intestinal proteases
      • Some gliadin peptides induce epithelial cells to express IL-15 (MCQ)
      • IL-15 triggers activation and proliferation of CD8+ intraepithelial lymphocytes that are induced to express NKG2D, a natural killer cell marker. (MCQ)
      • These lymphocytes become cytotoxic and kill enterocytes with surface MIC-A, an HLA class I–like protein expressed in response to stress. (MCQ)
      • NKG2D is the receptor for MIC-A.
      • resulting epithelial damage may contribute to the process by which other gliadin peptides cross the epithelium to be deamidated by tissue transglutaminase. (MCQ)
      • Deamidated gliadin peptides are then able to interact with HLA-DQ2 or HLA-DQ8 on antigen-presenting cells and be presented to CD4+ T cells. (MCQ)
      • These T cells produce cytokines that contribute to tissue damage and the characteristic mucosal pathology.
    • almost all people with celiac disease carry the class II HLA-DQ2 or HLA-DQ8 allele. (MCQ)
    • Celiac disease show association with (MCQ)
      • type 1 diabetes, thyroiditis ,Sjögren syndrome
      • ataxia, autism, depression , some forms of epilepsy
      • IgA nephropathy, Down syndrome, and Turner syndrome.
    • Biopsy
      • Why the specimens are taken  from the second portion of the duodenum or proximal jejunum(MCQ)
        • they are exposed to the highest concentrations of dietary gluten
      • Biopsy is generally diagnostic in celiac disease
      • Histopathology (MCQ)
        • increased numbers of intraepithelial CD8+ T lymphocytes (intraepithelial lymphocytosis)
        • crypt hyperplasia (MCQ)
        • villous atrophy (MCQ)
          • This loss of mucosal and brush-border surface area probably accounts for the malabsorption.
        • increased numbers of plasma cells, mast cells, and eosinophils, especially within the upper part of the lamina propria. (MCQ)
  • Clinical Features
    • presents most commonly between the ages of 30 and 60
    • Symptomatic adult celiac disease is often associated with anemia, chronic diarrhea, bloating, or chronic fatigue.
    • celiac disease is detected two- to threefold more commonly in women, perhaps because monthly menstrual bleeding increases the demand for iron and vitamins and accentuates the effects of impaired absorption. (MCQ)
    • Pediatric celiac disease,
      • classic symptoms
        • disease typically begins between ages of 6 and 24 months, after introduction of gluten to the diet (MCQ)
        • includes irritability, abdominal distention, anorexia, chronic diarrhea, failure to thrive, weight loss, or muscle wasting
      • nonclassic symptoms
        • present at older ages
        • with complaints of abdominal pain, nausea, vomiting, bloating, or constipation.
      •  Common extra-intestinal complaints include (MCQ)
        • arthritis or joint pain
        • seizure disorders
        • aphthous stomatitis
        • iron deficiency anemia
        • pubertal delay,
        • short stature
    • Dermatitis herpetiformis (MCQ)
      • characteristic itchy, blistering skin lesion
      • incidence of lymphocytic gastritis and lymphocytic colitis is also increased.
    • only treatment currently available is a gluten-free diet
    • long-term complications
      • anemia, female infertility
      • osteoporosis, and cancer
    • Noninvasive serologic tests
      • most sensitive tests are the presence of (MCQ)
        • IgA antibodies to tissue transglutaminase
        • IgA or IgG antibodies to deamidated gliadin.
      • Anti-endomysial antibodies (MCQ)
        • highly specific but less sensitive than other antibodies.
        • In cases with negative IgA tests, IgA deficiency, which is more common in celiac patients, should be ruled out.
        • If IgA deficiency is present, titers of IgG antibodies to tissue transglutaminase and deamidated gliadin should be measured.
    • The absence of HLA-DQ2 or HLA-DQ8 is useful for its high negative predictive value, but the presence of these alleles is not helpful in confirming the diagnosis.
    • Individuals with celiac disease have a higher than normal rate of malignancy
        • most common cancer is enteropathy-associated T-cell lymphoma (MCQ)
        • Small intestinal adenocarcinoma is also more frequent
    • When do you consider development of cancer in Whipples disease
        • when symptoms such as abdominal pain, diarrhea, and weight loss develop despite a strict gluten-free diet, cancer or refractory sprue, in which the response to a gluten-free diet is lost, must be considered
    • Tropical sprue
      • a malabsorption syndrome
      • Histologic changes of tropical sprue  vs celiac disease(MCQ)
        • total villous atrophy is uncommon
        • tropical sprue tends to involve the distal small bowel
        • folate or vitamin B12 deficiencies are more common in tropical sprue 
      • Malabsorption
        • Cause -overgrowth of aerobic enteric bacteria has been documented
        • broad-spectrum antibiotics usually effect rapid recovery.

    What is Gluten? Celiac Disease?
    The baking of wheat bread depends on its gluten content. Wheat has three layers: the bran, the nutrient-rich germ and the enrosperm filled with starch and proteins. The important proteins in wheat are glutens.
    Celiac Disease
    March 2009, Celiac Disease, digital video, 2:36 minutes. Position: writer/director/editor. A documentary about Celiac Disease. Winner of the 2009 Student Educational Video Award in the High School Documentary Category.
    Endoscopy of Celiac Disease
    Duodenal mucosa shows an irregular pattern there are decrease in intestinal microvilli and flattening of these.
    Gluten and Autoimmunity Explained in 20 Minutes
    Celiac Disease – Rife Frequencies
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