03/10/2014

Celiac Disease in 2014 CSGNA Annual conference Khurram Khan Gastroenterology, St Josephs Healthcare Assistant Professor, McMaster University [email protected]

Objectives • • • •

Overview of Celiac disease Highlights from recent guidelines Canadian labeling laws Gluten free diet in non-celiac patients

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History & Epidemiology • Celiac disease

– Gluten-sensitive enteropathy characterized by mucosal inflammation and malabsorption upon exposure to gluten

• Initial descriptions date to Greece 250 A.D.

– Koiliakos = suffering in the bowels – Reports translated to English by Francis Adams, coined the name “Celiacs”

• W.K. Dicke (1940’s)

– established association to gluten – noticed the condition in children improve during WWII food shortages and relapse after cereal supplies restored

• Large number of asymptomatic or atypical presentations  true prevalence elusive – Estimate: 1/120 to 1/300 (Europe/NA)

Presentation • Classically a disease of infants (child with life-threatening malabsorption) • Now presents later - ~10 – 40 year olds – due to longer breast-feeding, later intro of gluten in infant diet – >20% present over age 60yo

• Variable presentation – Classic GI symptoms • Diarrhea, steatorrhea, flatulence, bloating

– Consequences of malabsorption • Vit B - Growth failure, weightt loss, severe anemia, neurologic d/o • Vit D and calcium – osteopenia/osteoporosis, fractures

– Subclinical/non-specific • Fatigue, Fe deficiency, mild transaminitis

– Most common • Asymptomatic or Microcytic anemia

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MALIGNANCY MALABSORPTION ↓ GROWTH & DVT RHEUMATIC

NUTRITIONAL DEFICIENCIES LOW BIRTH WT INFANTS

NEUROPSYCHIATRIC

Diagnosis Symptoms/Signs • Who should be tested? – GI symptoms: • chronic diarrhea, malabsorption, wt loss, abdominal distension (gaseousness)

– Unexplained/non-specific Sx: • transaminitis, short stature, delayed puberty, iron deficiency anemia, recurrent fetal loss, infertility, neuropathy, enamal loss

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Diagnostic Approach • Perform tests on a gluten diet for >2-4wks • serology may otherwise be (-)ve • Ab remain ↑for 1-6months

• Begin with serology – 4 Abs: • • • •

IgA tissue transglutaminase (tTG) - ELISA IgA Endomesial (EMA) - immunofluorescence IgA/IgG antigliadin (AGA) – ELISA IgG deamidated gliadin peptides (DGP)

– Highest sensitivity/specificity:

(Hill, Gastro 2005)

• α-tTG IgA (Sn 90-98%; Sp 95-97%) • α-EMA IgA (Sn 85-98%; Sp 97-100%) • α-AGA – no longer used due to low sensitivity and specificity

Suggestive clinical features & (-)ve serology • Selective IgA deficiency – More common in celiacs than general population – IgA EMA and IgA tTG will be falsely (-)ve – Recommend: • Measure total IgA levels • If IgA levels are low  test for α-AGA Ab

• False (-)ve – Repeat serology or small bowel bx – HLA-DQ2 and/or DQ8 haplotype • >98% of celiacs vs. 40% of general population • Sn 90-95% but Sp only ~30% (↑NPV)

• Pt may not have celiac – Explore other causes of Sx and villous atrophy

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Diagnostic Approach • Small bowel bx with villous atrophy(gold std) – All pts with (+)ve α-EMA or α-tTG IgA • Or in patients with high pretest probability

– Multiple bx should be taken in the 2nd and 3rd part of duodenum • • • •

atrophy can be patchy avoids distortion from Brunner’s glands and duodenitis At least 4 increases probability of Dx At least 1 bx from bulb may increase yield Lebwohl B et al. Gastrointest Endosc 2011 Evans KE et al. Am J Gastroenterol 2011

Histology • Classic findings: – – – – –

villous atrophy crypt hyperplasia mucosal inflammation ↑ intraepithelial lymphocytes ↑ lymphocytic infiltration of lamina propria

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Diagnostic Approach • Dx presumed – concordance between the serology and bx

• Dx confirmed – resolution of Sx on gluten-free diet

• If Dx still uncertain – – consider gluten challenge after gluten-free period – monitor Sx and repeat bx – Caution – gliadin crisis in very sensitive patients

Can you get by without Bx? • European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) • Triple criteria to avoid biopsy in children – Characteristic symptoms – Anti-TTG >10x upper limit normal – Positive HLA-DQ2 Husby S et. al. J Pediatr Gastroenterol Nutr 2012

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Treatment • Gluten-free diet – “Gluten” = Etoh-soluble fraction of wheat proteins (ie. prolamins) – Principle sources of gluten: • Barley • Rye Janatuinen Gut 2002 • Oats • Wheat

Treatment • Dietary counseling to improve compliance • • • •

Avoid foods containing wheat, rye, and barley. Oats may be contaminated by gluten Lactose may not be tolerated well. Read labels carefully - additives (ie.stabilizers or emulsifiers) may contain gluten.

• Supplement nutritional deficiencies – Fe, folate, calcium, vitamin D (rarely other fat soluble vitamins) – Screen for Osteoporosis

• Pneumococcal vaccine – Celiac associated with hyposplenism (cause unknown)

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Monitoring response and compliance Clinical assessment not reliable, even with dietary history Serology normalization (50-66%) does not mean healing of villous atrophy Only 2/3 patients with healed mucosa have normal serology Mucosal healing may be slow (2/3 at 5 years) Why? Increased cost of GFD Lifestyle choices (eating out) Hidden sources of gluten Poor food labeling

Refractory celiac disease • Failure of strict gluten-free diet to restore normal intestinal architecture and function • Arbitrary period of 1 year of GFD before diagnosis • Significant morbidity and mortality due to malabsorption and malnutrition, even lead to death • The cause of refractory sprue is unknown. • Occurs in