Transcript Celiac Disease - Healthcare Professionals

Case Discussion
John F. Pohl MD
Assistant Professor of Pediatrics
Section of Pediatric Gastroenterology
Scott and White Hospital
Texas A&M Health Science Center
Temple, Texas
Dr. Pohl
Dr. Gupta
Pertinent History
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5 year old male with 2 year history of intermittent
vomiting of a cyclic nature (CVS?)
2 prior episodes of dehydration requiring
hospitalization.
Previous Giardia infection (pertinent?)
Brother with “wheat allergy” and Giardia
infection
Mother with IBS.
Father and paternal relatives with stomach
problems and wheat allergy.
Pertinent History
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Serum bicarbonate 16
Urine organic acid screen: Increased 3-hydroxybutyric
and acetoacetic acid consistent with physiologic ketosis
or disorder of fatty acid oxidation.
Urine analysis: Sp. gravity 1.032, pH 5.5, 4+ ketones,
negative blood / glucose / protein / nitrite / leukocyte
esterase / bilirubin. 0 RBCs, 0 WBCs, 0 bacteria.
MRI: Scattered areas of increased signal intensity on the
FLAIR images particularly noted in the subcortical white
matter regions.
During the work-up, an upper endoscopy was performed.
Duodenum
Normal appearing
villi
Duodenum
Lymphoid aggregate
Increased inflammatory
cells in crypt region
Shortened villi
Giardia
Follow-up
Patient’s brother was known to have celiac sprue.
 Patient’s father, although never officially tested,
had gone on a strict wheat free diet and had
resolution of symptoms.
 This patient’s celiac titer:
Anti-endomysial antibody 1 : 80 (normal <1:5)
Tissue transglutaminase antibody 1.1 (normal <1)
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Introduction
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AKA, “Sprue” or “gluten-sensitive enteropathy”
First described around 200 AD.
“Sprue” was used in 18th century (Dutch,
“aphthous disease”).
Samuel Gee: “On the Coeliac Affection” (1888).
Dicke and Der Kamer: Identified alcohol soluble
fraction of wheat gluten (gliadin) and similar
residues in related barley, rye, and oats as being
the damaging agents (1950-53).
Definition of Celiac Disease
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Permanent intolerance to dietary wheat gliadins.
Produces intestinal lesions in geneticallysusceptible individuals.
Immunologic and genetic basis.
Relatively common.
Has an broad phenotype:
IBS / chronic diarrhea
Kwashiorkor, ascites, FTT
Epidemiology
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Prevalence seems to have changed.
1950 – 1970: Prevalence increased (or ↑d use of
endoscopic biopsy?)
1970 – Present: Large decline in prevalence in
Europe. WHY?
3.
Prolonged breast feeding
Low allergen formula
Less AGE in infants
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Age at which diagnosis is made is increasing.
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IBS / chronic diarrhea
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Kwashiorkor, ascites, FTT
Epidemiology
Old data of US incidence – 1:6000.
 Recent large scale serologic screen of blood
donors in United States – 1:250
 Maki and Collin (1997): The “celiac iceberg”
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Diagnosed CD
Latent CD
Pathogenesis – Family history
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Prevalence in 1st degree relatives up to 10%
(screening of relatives is ESSENTIAL).
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Concordance in monozygotic twins: 75%.
Pathogenesis - Immunity
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Celiac is an immune mediated small bowel
enteropathy.
 Due to gluten-sensitive T-cells.
 Increased numbers of CD8 T-lymphocytes in
mucosa
Pathogenesis - Immunity
Gliadin protein fraction of wheat, rye, barley, and probably oats
Class II HLA APC cells
T-cells (lamina propria)
Antigen
Mucosal
injury
T-cell &
Macrophage
proliferation
↑ IL-2,
cytokines, IL-6,
TNF 
Early Presentation
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Classically presents at 6-18 m of age once gluten
is introduced.
Chronic diarrhea / rectal prolapse
FTT
“Celiac crisis” – diarrhea with dehydration
“Celiac personality”
Kwashiorkor
Developmental delay
Constipation (<10%)
Bruising, rickets, hematoma formation
Celiac Disease
From Atlas of Pediatric Physical Diagnosis, 2nd ed., BJ Zitelli editor. Mosby-Wolfe, 1992.
Late Presentation
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School age or later (even adulthood)
 Mild, chronic diarrhea
 Occasional constipation
 Lactose intolerance
 Dental enamel hypoplasia
 Kwashiorkor less likely
 Osteopenia / osteoporosis
 Short stature
 Unexplained microcytic (Fe) / macrocytic (folic acid)
anemia
 Can be asymptomatic!
“Atypical” Presentation
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Unexplained short stature
Aphthous stomatitis
Enamel hypoplasia
Infertility
Unexplained anemia
Unexplained ↑SGOT/SGPT (cirrhosis / AIH)
Osteoporosis
Alopecia
Peripheral neuropathy / central CNS changes
Lymphoma
Laboratory Features
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Gliadin IgA/IgG
Reticulin IgA
Increased rate of
Endomysial IgA
Giardia
Tissue Transglutaminase IgA
3-5% of celiac patients are IgA deficient!
IgA deficiency: False-negatives
None of the tests have 100% sensitivity and
specificity (false-negatives / false-positives).
Laboratory Features
Antigliadin antibody
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Antigliadin IgG: sens. 90-100%, spec. 60%.
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Antigliadin IgA: sens. 60-100%, spec. 86-100%
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Ab titers and sensitivity of IgG and IgA tend to
decrease as patient’s age increases (>3yrs old).
Laboratory Features
Antiendomysium antibody (IgA)
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Sensitivity: close to 100%
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Specificity: close to 100%
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Antibody to unknown antigen
Laboratory Features
Tissue transglutaminase antibody (TTG)
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Probably the sole autoantigen recognized by the
antiendomysium Ab.
 High affinity for gliadin proteins
 Almost 100% sensitivity and specificity
 Now the antibody test of choice.
Diagnostic Testing
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Once antibody tests positive, duodenal biopsy is
key to diagnosis (absolute 100% sensitivity and
specificity).
Hyperplastic crypts
Increased mitotic figures
Villi flattened / gone
Dense lymphocytic infiltrate with plasma cells
Disaccharidases: Brush border hydrolases are
decreased, especially lactase (lactose intolerance).
Diagnostic Test
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There is a spectrum of insult…
Absent villi
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Villi present
There is always a lymphocytic infiltrate that goes
away with dietary manipulation.
Endoscopic Celiac Disease
Untreated Celiac Disease
Treated Celiac Disease
Treatment
Removal of gluten is essential!
Treatment
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Behavioral disturbances resolve quickly.
Immediate weight gain with complete correction
in one year.
Developmental delay corrects in 1-2 months.
Stools return to normal in a few weeks.
Abdominal distention resolves in a few months.
Villi resume normal architecture in one year.
“Safe” gluten intake < 50mg/day
A dedicated nutritionist is imperative.
Treatment
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Gluten challenge (older diagnostic criteria)
Done after 6 years of age.
Done to confirm long-lasting nature of disease
(adopted in 1970).
Allow 5-10 g gluten daily (2 pieces of bread) for
1-12 months once patient is healthy.
Problem with technique: 3 procedures to confirm
diagnosis.
ESPGAN (1990): revised diagnostic criteria for
celiac.
Treatment
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New criteria (children > 2 yrs):
Histologically similar to celiac disease at time of
diagnosis.
Clinical recovery is evident after gluten removal.
Ab levels return to normal after diet restriction.
If these criteria cannot be fulfilled, classic gluten
challenge is necessary.
Careful! Over half of relapsing patients are only
detected by biopsy alone (they look normal).
Associated Diseases
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Higher incidence of autoimmune diseases overall
than the normal population.
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May be due to the shared HLA haplotypes
between diseases.
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Seems to be related to duration of gluten exposure.
Associated Diseases
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Hemochromatosis
 Type I Diabetes Mellitus
 Autoimmune thyroid disease
 Addison disease
 Autoimmune thrombocytopenia
 Sarcoidosis
 Autoimmune hepatitis
 CNS disease (seizures, CNS calcifications)
 Dermatitis herpetiformis
 Primary biliary cirrhosis
 Lymphoma (risk 25-125X risk of general pop.)
 Trisomy 21 (4-17% with celiac disease)
IDDM
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Barera, et al, Pediatr, 2002 (Italy)
Investigated prevalence of celiac disease in
pediatric patients (8.6 ±4.6 yrs) with IDDM.
60% -- had celiac disease at time of IDDM
diagnosis.
Prevalence of celiac disease approximately 20X
higher than general population.
SHOULD WE SCREEN OUR DIABETICS???
What about the MRI changes in this patient?
Another Example of CNS Findings
Calcification
Celiac Disease and CNS Findings
PRESENTATIONS:
 Headaches / migraines
CVS?
 Cerebellar ataxia
 Epilepsy
 Myoclonic ataxia
 Neuropathies
 Dementia
 Ischemic stroke
 Tic disorders
 Learning disabilities / ADHD
Celiac Disease and CNS Findings
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Celiac patients on a gluten diet demonstrate
cerebral hypoperfusion (via PET scan
measurement).
 Increased thrombotic potential (mainly described
in case reports; etiology unclear).
 CNS disease is seen in other AUTOIMMUNE GI
diseases (Crohn’s, UC).
 Antibodies in celiac disease may affect voltagegated calcium and potassium channels as well as
glutamate receptors in the CNS.
Celiac Disease and CNS Findings
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What benefit exists with gluten-free diet?
 Improvement only seen in those patients with
transient infantile hypotonia and migraine
headaches
Pediatrics. 2004 Jun;113(6):1672-6.
Range of neurologic disorders in patients with celiac disease.
Zelnik N, Pacht A, Obeid R, Lerner A.
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Case in Point: Our patient improved considerably
over time as he was placed on a gluten-free diet.
Did the patient have CVS due to migraine disease?
Bottom Line…
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Celiac disease is more common than we realize.
Any child with FTT, chronic diarrhea, or IBS (esp.
diarrhea predominant) should be screened.
The phenotypic presentation is changing.
Ab tests have excellent sensitivity and specificity
(esp. EMA and tTG).
Gluten free diet is mandatory and curative.
Keep in mind high risk of other autoimmune
disorders with celiac disease.
Screen 1st degree relatives.
The End
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Proceed to the post test
 Down load the post test
 Complete the post test
 Return the post test to Dr. Sandra Oliver
407 I TAMUII
Post test question 1
1. Individuals with celiac disease may
experience which of the following:
A. Constipation
B. Weakness
C. Weight gain
 Hyperactivity
Post test question 2
2. Pathology of Celiac disease includes:
A. Villous atrophy
B. Hypoplasia of the crypts of Lieberkuhn
C. Decreased plasma cell infiltration of the
lamina propria
D. Increased brush border hydrolases
Post test question 3
3. Treatment of celiac disease includes
removal of which of the following?
A. Wheat and buckwheat
B. Rye and corn
C. Rice and potatoe
D. Oats and barley
Post test question 4
4. Prognosis for celiac disease includes all of
the following except:
A. Increased risk for adenocarcinoma of the
small bowel
B. Increased risk for cardiovascular disease.
C. Increased risk for lymphoma
D. Increased risk for osteoporosis
Thank you!
Scott & White Memorial Hospital and Clinic
Texas A&M University Health Science Center