Transcript Celiac Disease - DFWCeliac.org

Celiac Disease
Jeffrey Fine, MD
)
Celiac
disease

Autoimmune disorder with a prevalence of approximately 0.5
to 1 percent in the United States. (1 in every 100-200 persons)

Inappropriate immune response to the dietary protein gluten,
which is found in rye, wheat, and barley.

After absorption in the small intestine these proteins interact
with the antigen-presenting cells in the lamina propria causing
an inflammatory reaction that targets the mucosa of the small
intestine in genetically sensitive people.

Manifestations range from no symptoms to overt
malabsorption with involvement of multiple organ systems and
an increased risk of some malignancies.
Genetics

Most all patients with celiac disease express human leukocyte antigen
(HLA)-DQ2 or HLA-DQ8, which facilitate the immune response against gluten
protein

Concordance rates of 70 to 75 % among monozygotic twins and 5 to 22 %
among first-degree relatives.

Genome wide associations (GWAS) identified -8 new genes,7/8 contained
immune related genes and 4/8 loci share other autoimmune /inflammatory
disorders –one of SNP associated w/ Crohn’s
Diagnosis

Classic Celiac Disease –occurs 5% -easy to make

Atypical -Difficult to make

The Great Masquerader
Phenotype

Grade 1
Typical symptoms

Grade 2
Mild

Grade 3
symptoms
Asymptomatic
T -lymphocyte associated protein cytotoxic T-lymphocyte antigen 4
Polymorphism (CTLA-4+49 A/G) genotype on Chromosome 2 q33
Epigenic Factors

Adenovirus/Enteric Infections

Stressors

Surgery
Prevalence among
Risk Factors for Celiac Disease
Dermatitis herpetiformis
100
First-degree relative with
5 to 22
celiac disease
Autoimmune thyroid disease
1.5 to 14
Down syndrome
5 to 12
Turner's syndrome
2 to 10
Type 1 diabetes mellitus
10
Children
3 to 8
Adults
2 to 5
Dermatitis Herpetiformis
Signs and Symptoms

Classic

Diarrhea

Fatigue

Borborygmus

Abdominal pain

Weight loss

Abdominal distention

Flatulence
Up to 38 % Asymptomatic

Atypical

Osteopenia/ osteoporosis

Abnormal liver function

Vomiting

Folate /Iron-deficiency anemia

Neurologic dysfunction

Brain Fog/ dementia

Constipation

Nausea

Esophageal reflux
Test selectively as part of the medical evaluation when
symptoms could be secondary to celiac disease:

Autoimmune thyroid disease

Selective immunoglobulin A deficiency

Cerebellar ataxia

Short stature (in children)

First- or second-degree relative with
celiac disease

Sjögren's syndrome

Turner's syndrome

Irritable bowel syndrome

Type 1 diabetes mellitus

Peripheral neuropathy

Unexplained delayed puberty

Recurrent migraine

Unexplained recurrent fetal loss/Infertility

Refractory Crohn’s Disease

Seizures

Psoriasis
SEROLOGY

Serum IGA and IgA tissue transglutaminase (tTG) antibodies. Sensitivity and
specificity > 95%.

Do Deaminated Antigliadin antibodies DE –AGA IgG And IgA and do TTG IGG
as well.

Testing for gliadin antibodies is no longer recommended because of the low
sensitivity and specificity for celiac disease , but should be considered for gluten
sensitivity.

TTG is less costly because it uses an enzyme-linked immunosorbent assay;

When the prevalence is low, as in the general U.S. population, the risk of a
false-positive result is high

Confirmatory testing, including small bowel biopsy, is advised.
TESTING

Serologic Testing

Stool Testing
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Genetic HLA Testing

Endoscopy , Pill Endoscopy and SB series
SMALL BOWEL BIOPSY

Required to confirm the diagnosis of celiac disease for most patients.

Should be considered in patients with negative serologic test results
who are at high risk or in whom the physician strongly suspects
celiac disease.

Mucosal changes may vary from partial to total villous atrophy, or
may be characterized by subtle crypt lengthening or increased
epithelial lymphocytes.

To avoid false-negative results on endoscopic biopsy, most
authorities recommend obtaining at least four tissue samples, which
increases the sensitivity of the test.
ENDOSCOPIC FINDING

Scalloped folds

Decrease in Kerckring folds

Mucosal fissuring

Flattened folds

Normal appearing
Normal small intestine
Celiac Disease
Normal villi
Villous atrophy
BENIGN COMPLICATIONS

Small bowel adenomatous polyps

Identified on sbft, vce or enteroscopy
MALIGNANT COMPLICATIONS

Enteropathy –type Intestinal T cell Lymphoma - 30-40x ^ if GFD, 70x if not

Other Lymphomas 23x

Small Bowel Adenocarcinomas -80x

Head and Neck cancer-23x
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Esophageal Squamous Cell cancers 23x

Other cancers ^ risk
TREATMENT

Avoidance of food products that contain gluten proteins.

It is essential that the diagnosis be confirmed before submitting patients to this
therapy.

Key elements to successful treatment include the motivation of the patient, the
attentiveness of the physician to comorbidities that need to be addressed.

Formal consultation with a trained dietitian is necessary.

The dietitian plays a vital role in helping the patient successfully adapt to the
necessary behavioral changes and may provide much of the required follow-up.

National celiac disease support organizations can provide patients invaluable
resources for information and support
.
COMORBIDITIES
 Thyroid
dysfunction
 Deficiencies in
folic acid, vitamin B12, fat-soluble vitamins
, calcium, magnesium, copper ,zinc and iron
 Osteoporosis
 Increased mortality
due to increased risk of malignancy
Non-Hodgkin's lymphoma (3-6x more likely)
 Oropharyngeal , esophageal, and small intestinal adenocarcinoma.

Vitamin and Mineral Deficiencies

Vitamin D and other Fat soluble Vitamins
Folate and B12

Calcium, Magnesium , Copper and Zinc

.
Follow-up

Antibody levels return to normal within 12 months of starting a
gluten-free diet.

A repeat small bowel biopsy three to four months after
initiation of a gluten-free diet is not necessary if the patient
responds appropriately to therapy.

If the patient does not respond as expected despite adherence
to a gluten-free diet, the physician should consider diseases
that may mimic celiac disease vs refractory sprue

.
Screening

Screening an asymptomatic patient for celiac disease must be
weighed against the psychological, emotional, and economic impact
of a false positive result

Also, it would necessitate further evaluation with small bowel
biopsy.

The need to follow a strict diet indefinitely can adversely affect the
patient's perceived quality of life.

Routine screening of the general population is not recommended.
But should be considered

Persons at high risk for celiac disease who exhibit any level of
symptoms, appropriate testing is indicated.
Special Topics

FERTILITY

PROBIOTICS

NON IMMUNE GLUTEN SENSITIVITY

REFRACTORY SPRUE
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MY PARADIGM

NEW TESTING
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POTENTIAL THERAPIES
Fertility in Celiac Disease

Delayed menses/ Premature Menopause
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Amenorrhea
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Recurrent abortions
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Relative Infertility Women and Men
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Low birth weight babies
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Increased Perinatal Mortality
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Poor Outcomes of Fertility may be corrected GFD – minimum 6-9 mos
Probiotics

Good bacteria such as lactobacillus and bifidiobacterium decrease on gluten
free diet

Pathogenic bacteria proliferated

RX : probiotic should be taken-lactobacillus and bifidiobacterium 10 billion
CFUS to start daily
Differential Diagnosis of Celiac Disease

Anorexia nervosa

Irritable bowel syndrome

Autoimmune enteropathy

Ischemic enteritis

Bacterial overgrowth

Lactose intolerance

Collagenous sprue

Pancreatic insufficiency

Crohn's disease- co-exist

Soy protein intolerance

Giardiasis

Tropical sprue

Human immunodeficiency
virus enteropathy

Tuberculosis
Hypogammaglobulinemia


Whipple's disease
Infective gastroenteritis


Zollinger-Ellison syndrome
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Intestinal lymphoma
Non Immune Gluten Sensitivity

This is Real !

Antigenic nature of gliadin

Zonulin –protein suggested to increase intestinal permeability- “Leaky Gut”
DQ1 alleles are GS genes subtype DQ5, 6
DQ2subtype DQ2, DQ3 st7,8,9
As are Celiac Genes
Refractory Celiac Disease

RCD 1-IELS w/ polyclonal and have nl Phenotype

RCD 2 abberant IELS and monoclonality

50% Develop Enteropathy Associated Lymphoma
CELIAC DISEASE
IgA and IGG tissue transglutaminase and ,DeAGA antibodies , IgA and IGG
levels
and IgA and IGG endomysial antibodies are appropriate
first-line serologic tests to rule in celiac disease.
If negative I do enterolab’s stool for AGA if positive
I do HLA testing , small bowel biopsy and a pill cam
IF I BELIEVE THEY HAVE CELIAC DISEASE- Check labs for CBC, CMP ,25 D b12, ,
TSH, Minerals and vitamin testing, Bone Dexa and follow lifelong
New Testing on Horizon

Not clinically available

Measuring –serum levels of Th-2 Cytokines IL-4 and 10 and inflammatory
cytokines IL-1a,1B and 8- correlates w/ IGA –TTG titres

Galectin -10 –lysophospholipase in WBC associated in gut epithelium
correlates w/ Histology
T -lymphocyte associated protein cytotoxic T-lymphocyte antigen 4
Polymorphism sCTLA-4-gene higher in celiac disease and other auto immune
disease
Potential Therapies

Breast feed, delay/decrease infant gluten exposure Farrell RJ, JAMA 2005

Predigest Gluten Molecules – endopetidases

Genetic Modified Wheat Strains – for better?

Inhibit Zonulin - AT-1001- larazotide- in Phase 2 trials

Immunotherapy

Anti-interferon-gamma and TNF alpha
Potential Therapies

Anti-TTG blockers

Anti-HLA DR2/DR8
Questions

www.drfoodsensitivity.com
Reference

Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Disease. American Family
Physician. December 15, 2007: 1795-1802.

Enterolab website and HLA info from Gluten Seminar

Fasano, A ,Zonulin Physiol Rev 91, 151-175,2011

Tennyson C, Lewis S and Green P, New and Developing Therapies for Celiac
disease, Therap Adv Gastroenterol. 2009 Sept 2(5): 303-309

Advances in Celiac Disease 2011, Curr Opin Gastroenterol. 2011;27(2):112118. © 2011 Lippincott Williams & Wilkins
References

Advances in Coelic Disease, Alimentary Pharmacology &
Therapeutics. 2012;35(7):768-781. © 2012 Blackwell Publishing
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