Pocket Pediatrics: The Massachusetts General Hospital for Children Handbook of Pediatrics (Pocket Notebook Series), 2 Ed.

CELIAC DISEASE

Definition (N Engl J Med 2007;357:1731)

• Autoimmune enteropathy caused by a reaction to gluten in the diet resulting in effacement of the small bowel absorptive surface with resultant malabsorption

Pathophysiology

• Gliadin is the alcohol-soluble portion of gluten, is poorly digested in humans, and can pass through epithelial barrier of intestines (2/2 genetic susceptibility or infection)

• Adaptive immune (CD4 + T cells) and innate immune (NK cells) systems recognize gliadin bound HLA class II; trigger inflam w/ villous injury and crypt hypertrophy

• Tissue transglutaminase (TTG) enzyme deaminates gliadin, increasing inflammation

Epidemiology (J Pediatr Gastroenterol Nutr 2004;39:S601)

• Prevalence reaches 1 in 100–250 in some countries; classically thought most prevalent in Caucasian population (European ancestry), but dz worldwide

Clinical Manifestations (Gastroenterology 2005;128:S68)

• Classic picture malabsorption w/ bulky stools, abd distention and flatus, FTT, muscle wasting and hypotonia presenting in first 6 mo to 2 yr of life

• Celiac crisis; now rare, acute explosive watery diarrhea and severe dehydration

• Silent disease; likely the large majority given prevalence rates

• Nonclassic sx; presents later (5–7 yo) w/ range sx, recurrent abd pain, N/V, constipation, aphthous ulcers, arthritis, skin dz (dermatitis herpetiformis), enamel defects, delayed puberty, short stature, or abnormal LFTs

• Syndrome of epilepsy w/ occipital calcifications and celiac disease

• Noted associations with other autoimmune diseases: DM type I, thyroiditis, Sjögren

• Down, Turner, (Williams pts w/ 3–10% prevalence of celiac)

Diagnostic Studies (N Engl J Med 2007;357:1731)

• European Society of Pediatric Gastroenterology and Nutrition requires a single small bowel bx w/ crypt hyperplasia, villous atrophy and intraepithelial lymphocytes as well as +

response to a gluten-free diet (Gastro 2005;128:S98)

• Limitations: Patchiness of disease (limitation of bx), lack of compliance w/ diet

• Villous atrophy also seen w/ Crohn’s, food allergy, HIV enteropathy, TB, giardia, intestinal lymphoma, CVID, and radiation enteritis

• May not need bx; Anti-TTG >100 U/mL w/ symptom improvement w/ gluten-free diet predicted 127 of 128 bx proven cases (J Pediatr Gastroenterol Nutr 2011;52:554)

• Most specific serologic marker is antiendomysial antibody; approaching 100%

• Combined sensitivity of anti-TTG and antiendomysial antibodies is >90%; TTG is less operator-dependent and cheaper; best single study to send

• Antigliadin antibodies not sensitive enough, except in <18 mo

• Assoc of HLA-DQ2/DQ8 & serologic markers w/ sens 98.8%, spec 96.2%,

(J Pediatr Gastroenterol Nutr 2011;52:729)

• Check IgA levels as IgA deficiency is 10× more common in celiac patients

• IgA deficiency has false negative anti-TTG and antiendomysial Abs; can check IgG

Treatment

• Eliminate all gluten (wheat, rye, and barley); very difficult, oats can be contaminated

Complications (N Engl J Med 2007;357:1731)

• Osteoporosis: Initially thought to be 2/2 vit D and Ca++ deficiency; now felt may be 2/2 associated inflammation as lifelong gluten-free diet is preventative

• Cancer: Overall rates are 2× rest of populations but decrease rate of breast CA

• Specifically ↑ risk of adenoCa of small intestine and enteropathy assoc T-cell lymphoma as adults; risk ↓ w/ diet adherence

• Refractory sprue: 5% w/ continued symptoms and histology regardless of diet

• Inc risk of enteropathy associated T-cell lymphoma if w/ clonal expansion