Celiac Disease Flashcards
celiac disease (overview)
*an intestinal autoimmune disorder
*occurs in genetically susceptible individuals
*triggered by a specific dietary antigen (GLIADIN)
*mucosal inflammation causes destruction of villi -> malabsorption -> diarrhea & malnutrition
gluten
*complex wheat seed storage protein
*composed of glutenin + several gliadins (alpha, gamma, omega)
*analogous proteins present in rye, barley, oats
digestion of alpha-gliadin
*digested by gut proteases to form a highly immunogenic 33-residue “innate” peptide
*resistant to further proteolysis
*contains epitopes recognized by HLA-DQ2
*contains deamidation sequences (Q-L-P) recognized by tissue transglutaminase (tTG)
*enzyme modification further increased antigenicity
HLA-DQ2 and HLA-DQ8 in Celiac Disease
*upon binding alpha-gliadin -> activation of pathogenic CD4+ T cells in intestinal mucosa; also directs a humoral response against tTG
*almost ALL celiac disease pts carry either HLA-DQ2 or 8 BUT there are people with these HLAs that do not have celiac
which HLA types are implicated in celiac disease
HLA-DQ2
*HLA-DQ8
note - absence of either DQ2 or DQ8 is almost 100% negative predictive value for having celiac disease
histopathology of celiac disease
*intra-epithelial lymphocytes
*lamina propria infiltrate (lymphocytes, eosinophils, plasma cells)
*reduced villi/crypt ratio
*partial to total villous atrophy
*subepithelial collagen deposition
note - these findings are NOT pathognomonic for celiac but they support a diagnosis alongside the clinical picture
epidemiology of celiac disease
*about 1% of the population
*female:male ratio = 2:1
*prevalence in high-risk populations:
-first degree relative with celiac = 10x increased risk
-secondary degree relative with celiac = 2-5x risk
disorders associated with celiac disease
*Down syndrome
*Turner syndrome
*type I diabetes
*many other genetic and autoimmune disorders
clinical presentation of celiac disease
*can be latent, silent, or active
*malabsorption:
-DIARRHEA/STEATORRHEA
-cramping, bloating, gas
-vitamin deficiencies
-lactose intolerance (secondary)
*extra-intestinal manifestations:
-IRON DEFICIENCY ANEMIA
-edema
-growth retardation or arrest
-neuro sx, ataxia
diagnosis of celiac disease
*clinical suspicion (sx, iron deficiency anemia, weight loss, family history)
*serology: ANTI-TISSUE TRANSGLUTAMINASE IgA (anti-tTG)
*HLA genotyping for HLA-DQ2/DQ8 (+ is NOT diagnostic, but - rules it out)
*EGD appearance (scalloped folds; mosaic mucosa)
*intestinal biopsy (gold standard)
what is the diagnostic serology test used for celiac disease
anti-tissue transglutaminase (tTG) IgA
EGD appearance consistent with celiac disease
scalloped folds; mosaic mucosa
treatment of celiac disease
*lifelong gluten-free diet!
*initially - lactose-free diet, Lactaid
*measure and correct plasma vitamins & minerals:
-vitamin B12, folate
-vitamins A, D, E, K
-iron (ferritin levels)
-bone densitometry
*follow-up:
-symptomatic response, weight gain, vitamin levels
-serologies
-mucosal healing (repeat biopsy)
dermatitis herpetiformis
*affects 10-15% of patients with celiac disease
*papulo-vesicular rash
*intensely pruritic (itchy)
*back, buttocks, scalp, and extensor surfaces (forearms, elbows, knees)
*patients often may have no GI sx
*dx: IgA-tTG deposits seen in the upper dermis
*responds slowly to gluten elimination
*tx: rapid response to dapsone, sulfapyridine
celiac disease - potential causes of failure to respond to gluten free diet?
*non-compliance with strict gluten free diet
*ingestion of hidden sources of gluten (cross-contamination; meds, malt-derived products)
*associated conditions; misdiagnosis
*refractory sprue
