Celiac disease

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  • 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.


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