تشخیص

Celiac disease is an immune mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals

Celiac disease most affects people of Noethen Europe

It has been also doumented in Hispanics, Indians, Sudanese, Chinese and Middle East people

The most common period of presentation is between

6 mon-2yr of age

Celiac Disease in Iran

The prevalence of Celiac Disease among 2000 Iranian blood donors is one of the highest in the world (1:166).

Celiac Disease is a common finding among patients labelled as irritable bowel syndrome (11%).

Gastrointestinal (“classical”)

Non-gastrointestinal (“atypical”)

Asymptomatic

In assiciation with other conditions and mostly with:

    Autoimmune disorders

     some syndromes

Celiac Disease Associated Disorders

Type 1 diabetes(3-10%)

Hashimoto,s thyroiditis

(4-8%)

Autoimmune hepatitis

(6-8%)

Adrenal failure

Down syndrome(4-19%)

Williams syndrome2-4%)

Turner syndrome(4-8%)

IgA deficiency(7%)

Diarrhea

FTT

Vomiting

Anorexia

These children are irritable, unhappy,

They are not interested in food

Pallor

Abdominal distension

Large bulky stool suggestive of constipation

Digital clubbing

Non Gastrointestinal Manifestations
of Celiac Disease
most common age of presentation: older children and adult

Dermatitis herpetiform

Dental enamel hypoplasia

Osteopenia/Osteoprosis

Short stature ~ 10%

Delayed puberty

Iron deficiency anemia

Resistant to oral Fe (5-8%)

Hepatitis(9% adult with high ALT,AST) have silent celiac disease

Arthritis

Epilepsy with occipital calcifications

Non Gastrointestinal Manifestations
of Celiac Disease

Selective IgA deficiency

Diabetes mellitus

Chronic rheumatoid arthritis

Thyroiditis

Hypothyroidism

Addison disease

Pernicious anemia

Alopecia

Lymphocyte gastritis

Pancreatic insufficiency

Silent                                               latent

Latent: no symptoms, normal mucosa

May show positive serology identified by following in time

These individuals will develop at some point in time mucosal changes (+/- symptoms).

Silent: no or minimal symptoms,”damaged” mucosa and positive serology

Identified by screening asymptomatic individuals from groups at risk such: 1st degree relatives, down syndrome , type 1 dibetes patients etc.

Screening tests for malabsorption may be normal

Microcytic or macrocytic anemia

    (target cells, Howel-jolly bodies, Heinz bodies,  siderocytes, irregular & cescent cells)

hypoproteinemia

Antigliadin antibodies (AGA)

Antiendomysial antibodies(EMA)

Anti tissue transglutaminase antibodies(TTG)

HLA typing

Role of serological tests:

Identify symptomatic individuals who need a biopsy

Screening of asymptomatic “at risk” individuals

Supportive evidence for the diagnosis

Monitoring dietary compliance

 Antiglidin IgG antibodies (sensitivity 86%)

Antiglidin IgA antibodies (sensitivity 95.5%)

Advantages

Relatively cheap & easy to perform

Disadvantages

Poor sensitivity & specifity

False positive for antigliadin antibodies:

Cow,s milk protein, crohn disease, IgA nephropathy, eosinophilic enteritis, tropical sprue, dermatitis herpetiform

Atiendomysial antibodies

IgA based antibodies

advantages

 (sensitivity 100%, specifity 98%)

Pv+ and ng- predictive value for antiendomysial antibody together with antigliadin antibody = 100%

Disadvantages

False negative in young children

Operator dependent

Expensive & time consuming

Tissue transglutaminase Ig A

advantages

 (specifity 95-98% & sensitivity 92-94%)

Relatively cheap

Disadvantages

Fase negative in young children

False negative in IgA deficiency

Possibly less specific than EMA

IgG tTG ELISA

 (in celiac patients with IgA deficiency)

Serlogic Markers

Tissue TG are available for:

Screening asymptomatic patients with type 1 diabetes, history of 1st degree relative with type 1 diabetes,and a family member with CD( ppv  = 70-83% for biopsy evidence of CD

Serological Test Comparison

Serum IgA level

Individuals with IgA deficiency are at increased risk for CD.

 IgA deficient individuals will have negative EMA-IgA,TTG-IgA

consider IgG based tests (EMA-IgG, &TTG-IgG) in IgA deficiency

ESPGAN recommendation
1969

Diagnosis should be confirmed by showing that the small bowel biopsy returned to normal 1-2yr after starting a gluten free diet and then rechallenge the patient with a gluten diet and repeat the biopsy to demonstrate the return the intestinal lesion.

ESPGAN Recommendation
now

For children > 2 yr is not necessary to rechallenge if the gluten free diet has produced resolution of symptoms & normalized the specific celiac disease serologies (EMAs, ab to Ttg)

For children <2 yr & when the diagnosis is in question, a rechallenge is recommended

The gold standard for diagnosis of CD is histologic confirmation

Genetic predisposition

Environmental triggers

       Dietary

       Non dietary?

HLA alleles associated with
Celiac Disease

DQ2 found in 95% of celiac patients

DQ8 found in remaining patients

DQ2 found in 30% of general population

Value of HLA Testing

High negative predictive value

Negativity for DQ2/DQ8 exclude diagnosis of celiac disease

Strong HLA association(B8,DR7, DR3, DQW2,)

98% patients HLA-DQ2, also found in 20-30% of controle

10% of patients have an affected 1st degree relative.

Concordance in monozygotic tweens is 70%

Concordance in HLA identical siblings 30-40% suggesting other genes involved.

Treatment

Only trearment for Celiac Disease is a gluten free diet(GFD)

- strict, lifelong diet

- Avoid

    Weat

     Rye

     Barly

Prognosis

Within 1 wk of starting therapy:

Improvement of mood , appetite and lessening of diarrhea

Older and extremely ill children

Teenagers

Development of malignancy

No complications from long term gluten free diet treatment are recognized