Celiac Sprue

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Celiac Sprue

• December 19, 2005

2
Definitions

• celiac sprue is an immune disorder characterized
  by inflammation of the proximal small intestine
  induced by the ingestion of gluten
• also known as celiac disease and gluten-sensitive
  enteropathy

3
History

• recognized in the third century (Aretaeus of
  Cappadocia chronic diarrhea and atrophy of the
  body)
• 1600s - Dutch term sprouw means aphthous
  disease
• Dr. Samuel Gee (UK) in 1888 described the disease
  and made a link to the diet
• Dicke (Dutch pediatrician) linked sprue with
  wheat during grain shortages in the Netherlands
  during WWII
• 1940s water insoluble gluten moiety was causal
• 1950s small bowel pathology was characterized
• 1970s first immunoglobulin and autoantibody
  studies
• 1980s anti-endomysial antibodies and HLA class
  II associations (DQ2)
• 1990s tissue transglutaminase (tTG)

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Pathogenesis Environmental

• glutens are water-insoluble grain proteins
  (prolamins and glutenins)
• taxonomy of grains predicts their toxicity in
  patients

Gramineae
family
Triticum
Secale
Hordeum
Avena
Oryza
Zea
Sorghum
Pennisetum
genus
wheat
rye
barley
oats
rice
corn
sorghum
millet
grain
gliadin
secalin
hordein
avenin
oryzenin
zein
kafirin
panicin
gluten
immunologic cross-reactivity
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Pathogenesis Genetic

• concordance
• 8-18 in first degree relatives
• 70 in monozygotic twins
• association with certain HLA DQ haplotypes
• 95 of celiac patients are DQ2
• most of the remaining are DQ8
• sprue develops in a minority with DQ2
• 25-30 of Europeans are DQ2
• non-HLA linked gene(s) likely determinant

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Pathophysiology
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Pathology
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Classification

• classic (typical) celiac sprue
• fully expressed form of celiac sprue
• symptoms and signs of malabsorption (after breast
  milk weaning)
• atypical celiac sprue
• gluten-induced small bowel inflammation
• atypical symptoms (anemia, short stature, etc.)
• silent celiac sprue
• gluten-induced inflammation without symptoms or
  signs
• latent celiac sprue
• childhood sprue reverts to normal biopsy and does
  not recur when gluten is reintroduced (possibly
  re-develop celiac sprue later in life)
• sprue presents later, after earlier documented
  absence on gluten
• potential celiac sprue
• abnormal serology but sub-diagnostic biopsy
  (normal or ?IELs)
• genetic predisposition (DQ2 and/or strong family
  history)
• 50 probability of developing celiac sprue

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Epidemiology
celiac iceberg
16000
classic
atypical
silent
potential latent
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Clinical Presentation

• Childhood Presentation
• typical
• failure to thrive
• diarrhea/steatorrhea
• anorexia
• vomiting
• abdominal distension
• abdominal pain
• atypical
• aphthous ulcers
• short stature
• anemia
• rickets

• Adult Presentation
• typical
• diarrhea/steatorrhea (75-80)
• weight loss
• abdominal bloating/flatulence
• mild abdominal pain
• atypical
• anemia (85)
• osteoporosis (15-30)
• coagulopathy (10)
• aphthous ulcers
• infertility/menstrual abnormalities
• neurologic symptoms
• short stature
• weakness/myopathy

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Associated Conditions

• dermatitis herpetiformis
• rare in childhood seen in 10 of adult celiac
  patients
• very pruritic
• gt80 have at least silent or latent sprue, but
  only 10 of patients have intestinal symptoms
• still have 10-40x risk of lymphoma if untreated
• type I diabetes mellitus
• 3-6 of IDDM patients develop sprue (20x risk)
• 5 of sprue patients develop IDDM
• IgA deficiency
• seen in 10 of sprue patients (complicates
  diagnosis)
• IgA deficient persons have 10x prevalence of
  sprue
• thyroid disease (5 of sprue patients)
• autoimmune diseases (Sjögrens, SLE, PBC)
• hyposplenism (50 of sprue patients)
• microscopic colitis

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Dermatitis Herpetiformis
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Serologic Tests
Test Sensitivity Specificity PositivePredictiveValue NegativePredictiveValue
IgA endomysial antibody (indirect IF) 85-98 97-100 98-100 80-95
IgA tissue transglutaminase 90-98 94-97 91-95 96-98
IgA antigliadin antibody 75-90 82-95 28-100 65-100
IgG antigliadin antibody 69-85 73-90 20-95 41-88
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Diagnostic Approach
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Dietary Guidelines

• avoid all foods containing wheat, rye and barley
  gluten
• in Europe, look for gluten-free labels
• brand name foods differ from country to country
• avoid dairy products (until remission, 3-6
  months)
• avoid oats until initial remission, then less
  than 50-60 grams/day
• use only rice, corn, buckwheat, potato, soybean,
  sorghum or tapioca flour or starches
• read all labels and ingredients in processed
  foods condiments
• watch for gluten in medications, thickeners,
  emulsifiers and additives
• avoid all beers (lagers, ales stouts)
• wine, liqueurs, whiskey, brandy and most ciders
  are usually OK
• consider vitamin, calcium, iron and folate
  supplementation
• remember that medications can be malabsorbed as
  well
• remember that these restrictions are expensive
  and inconvenient

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Response to Diet Restrictions

• 70 of patients have symptomatic improvement
  within 2 weeks
• histologic improvement lags unpredictably
• may not be evident for 2-3 months
• associated with fall in antibody levels in 3
  months
• is commonly complete in children
• 50 of adults have only partial histologic
  resolution
• failure to respond is most often due to
  incomplete removal of dietary gluten
• with strict adherence
• 5 year survival rate equal to general population
• infant and child growth and development
  normalizes
• lower risk of SB lymphoma (back to normal in 5
  years)

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Complications

• refractory sprue
• unresponsive sprue (other causes excluded)
• may require immunosuppressive therapy or TPN
• up to 75 may have cryptic T-cell lymphoma
• collagenous sprue
• subset of refractory sprue with a poor response
  and prognosis
• ulcerative jejunoileitis (UJI)
• ulcers, strictures and severe symptoms (pain,
  bleeding, obstruction)
• high mortality (up to 33)
• higher risk of lymphoma (abnormal clones of
  T-cells)
• malignancy
• 3 incidence over 5 year study
• SB lymphoma (EATCL)
• T-cell origin and often multifocal
• accounts for half of malignancies in sprue
  patients (40x risk)
• occurs 20-40 years after presentation
• oropharyngeal and upper GI cancers

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Future Directions

• bio-engineering gluten-free grains
• developing a vaccine or directed therapy against
  tTG