Term
| What are the important consequences of untreated Celiac disease? |
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Definition
1) Malabsorption of iron and vitamins (resulting in anemia)
2) Osteoporosis
3) Diarrhea |
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Term
| What are the 5 major factors involved in the pathogenesis of Celiac disease? |
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Definition
IgA mediated immune response to un-digestible alpha-gliadin fraction in genetically susceptible individuals, leading to small bowel damage and malabsorption
1) Genetic- HLA DQ2 or DQ8
2) Environment- gluten (gliadin and prolamin proteins)
3) Immune- IgA
4) Organ injury- chronic inflammation (small bowel primarily)
5) Nutritional deficiency (Iron, vitamine, minerals, later water and fat) |
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Term
True or False:
Exposure to gluten early in life increase risk of developing celiac disease. |
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Definition
True! Before 4 months
After 7 months, risk is lower |
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Term
| What is the genetic association with celiac disease and why does it influence pathogenesis? |
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Definition
HLA DQ2 (90%) and DQ8 (10%) encoded on short arm of chromosome 6, by CELIAC1 locus.
- MHC class II antigen presenting receptor that functions to distinguish self from non-self antigens (abnormal antigen reaction makes this really an autoimmune condition).
- Anti-gliadin antibodies bound to APCs with HLA DQ2 or 8 stimulate CD4+ T cells in lamina propria to produce inflammatory cytokines (IF-y)
- Anti-tTG (tissue transglutaminase) and Anti-Endomysial antibodies |
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Term
| What are the innate and adaptive immune mechanisms driving Celiac disease? |
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Definition
1) Innate
- In response to gliadin, IL-15 and activation of intraepithelial lymphocytes damage enterocytes directly
2) Humoral
- Anti-gliadin antibodies bound to APCs with HLA DQ2 or 8 stimulate CD4+ T cells in lamina propria to produce inflammatory cytokines (IF-y)
- Anti-tTG (tissue transglutaminase that deaminates gliadin) and Anti-Endomysial antibodies
- IgA is a byproduct of immune response (Diagnostic importance) |
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Term
| Why does small bowel injury occur in celiac disease? |
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Definition
1) Greatest in proximal small bowel (duodenum), related to nutrient deficiencies secondary to malabsorption from chronic inflammation and mucosal damage.
2) Fat soluble vitamins (ADEK), zinc, calcium and Iron (MOST COMMON) are usually deficient |
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Term
| What histological changes are associated with Celiac disease? |
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Definition
1) "Blunted duodenal villi" ***
2) Villus atrophy
3) Crypt hyperplasia
4) Inflammatory infiltrate
5) cuboidal enterocytes with loss of brush border and basal polarity of nuclei
6) Increased intra-epithelial lymphocytes |
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Term
| What are the clinical manifestations of celiac disease in adults, adolescents and children? |
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Definition
1) Children
- Abdominal distention, diarrhea and failure to thrive
2) Adolescents
- Short, neurological symptoms and anemia
3) Anemia (iron), Osteoporosis (calcium), Diarrhea (water/electrolytes), Weight loss/bloating (protein and carbs). |
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Term
| What are the clinical manifestations of celiac disease in adults, adolescents and children? |
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Definition
1) Children
- Abdominal distention, diarrhea and failure to thrive
2) Adolescents
- Short, neurological symptoms and anemia
3) Anemia (iron), Osteoporosis (calcium), Diarrhea (water/electrolytes), Weight loss/bloating (protein and carbs). |
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Term
| What are the important antibodies that can be measured for diagnostic purposes in presumed Celiac disease? |
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Definition
1) IgA endomysial Ab (100% specific and 90% sensitive)
- IF or ELISA of tTG
2) tTG autoantigen- intracellular enzyme that covalently binds glutamine to lysine (tTG:gliadin complexes form)
Since IgA deficiency is common, make sure to measure total IgA also! |
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Term
| What therapeutic options are available for celiac disease? |
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Definition
1) Stop eating gluten (wheat, barley or rice)!
2) Assessment and replacement of deficient nutrients |
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Term
What are potential explanations for lack of initial response to gluten-free diet in confirmed celiac cases (antibodies + biopsy)?
What about return GI symptoms in successfully treated patients? |
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Definition
MOST COMMON REASON IS DIET RELAPSE
1) Auto-immune enteropathy, which may evolve to collagenous colitis
2) Lymphoma of small bowel |
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Term
You perform a biopsy on a central american patient who presented with diarrhea, anemia and weight loss and who did not improve with a gluten-free diet.
You see scalloped duodenal folds and blunted villi.
Whats going on? |
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Definition
Villus atrophy that does not respond to dietary changes.
Tropical Sprue due to infection of small intestine
Give her antibiotics. |
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Term
| What is the association between celiac disease and cancer? |
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Definition
- 2X as likely to get cancer, with 50% of cancers being T-cell lymphomas.
- Adenocarcinoma of small bowel is also more common than rest of population. |
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Term
| Why do you often see pruritic, blistering skin lesion on the elbow, buttocks, knees, trunk and face of celiac patients? |
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Definition
Dermatitis herpetiformis
elbow> buttocks> knees> trunk>face
- Gluten binds IgA antibodies in circulation, obstructing small vessels.
**Speckled IgA deposits are found on IF of un-involved skin. If it is homogenous and linear, it is NOT CELIAC** |
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