Food Allergy &Food Intolerance

Diagnostic algorithm for Celiac Disease

Dr Ashok Rattan, MD, MAMSChief Operating Officer & Medical Director,

Star Metropolis Clinical LabDubai, Sharjah, Abu Dhabi

Diagnostic Algorithm for Celiac Disease

Food Allergy Vs Food intolerance

Definition of Food Allergy ?

Definition of Food AllergyFood allergy has no universally accepted

definition. The NIAID has suggestedthat food allergy be defined as

•“Adverse immune response that occurs reproducibly on exposure to a given food and is distinct from other adverse responses to food, such as, food intolerance, pharmacologic reactions or toxin mediated reactions”

ATOPYType 1Hypersensitivity

Signs & Symptoms of Food Allergy

Possible

Food allergy & “Intolerance”Type of Reaction Cause Food InvolvedAllergy Atophy, IgE mediated Eggs, Milk, Wheat, Fish,

Shellfish, Nut, Peanuts, Soya

Pharmacological Absorption of certain amines from food

Fermented food (cheese, red wine, sausages) fish

Enzyme defects Failure of normal enzymatic breakdown after absorption

Methanol, Lactose

Irritant Reflux Strong spices

Toxic Toxins Some shellfish, Mushroom, badly stored food

Chemicals MSD, Sulfites Chinese food, dry fruits

Celiac disease IgG to Gliadin, auto-immune

Wheat, Maize, Rye

Psychological Emotional reaction to food

Food proteins are recognized as “foreign”

Food specific IgG production and formation ofantigen/antibody complexes

Complexes are deposited in tissues and activateComplement

Complement and macrophages stimulate Inflammation

Delayed reaction and may last for days

Food Allergy

Food Intolerance

Signs & Symptoms of Food Intolerance

Class 0 No allergic reaction against tested food. No restriction is necessary.

Classes 1-2 Means that there is a low to moderate allergic reaction against tested food. These have to be avoided for 12

weeks.

Class 3 There is a major allergy type III against the tested foods. Strict avoidance for

6 months.

Class 4 There is a major allergy type III against the tested foods. Strict avoidance for

1 year.

30

Improvement of symptoms (%) after omitting allergenic food

Study, 2002-2008; evaluated by Mediveritas Institiute for Medical Studies, Munich

Celiac Disease

• Samuel Gee (1888) first described Celiac disease in “On the Coelic Affection”– Gluten sensitive entropathy– Nontropical sprue

• Aretaeus from Cappadocia (now Turkey) described similar malabsorption disorder in second century AD

Celiac disease “There is a kind of chronic indigestion

which is met with in persons of all ages, yet is especially apt to affect

children between one and five years old .

Signs of the disease are yielded by the fæces; being loose, not formed, but not watery; more bulky than the food taken would seem to account for; pale in colour, as if devoid of bile; yeasty, frothy, an appearance probably due to fermentation; stinking, stench often very great, the food having undergone putrefaction rather than concoction".

What is celiac disease ?

• Chronic inflammatory disease primary affecting small intestine

• Results from inflammatory response initiated by dietary gluten

• Inflammation leads to damage and atrophy of intestinal villae

Clinical featuresConsequence of intestinal inflammation & atrophy• Common clinical symptoms

– Abdominal pain– Diarrhea / vomiting nonspecific– Failure to thrive/malnutrition

• Comorbid conditions– Immunologic abnormalities

• Selective IgA deficiency

– Autoimmune endocrine disorders• Type 1 diabetes

– Dermatologic disorders

How common is it ?

World Wide Prevalence

Celiac Disease can present at ANY age to ANY specialty

Farrell RJ & Kelly CP: New Engl J Med 2002; 336: 180 - 188

Cause of celiac disease

• Willem K Diche recognized association between consumption of bread & relapsing diarrhoea

• WW 2: unconventional, non-cereal foods– Fruits, potatoes, banana, milk or meat

• After WW 2, symptoms reappeared

cereals

Deamidated Gliadin

Role of tTG in Celiac Disease

Endomycial antibodies

HLA & Celiac DiseaseUseful for ruling out celiac disease

Development of celiac disease

• Environmental component– Exposure to cereal grain proteins

• Wheat, barley, rye [gluten]

• Genetic component– Family members of individuals– HLA DQ 2 or HLA DQ 8

Auto Immune Reaction

Dermatitis Herpetiformis(Duhring’s disease)

Dermatitis Herpetiformis(Duhring’s disease)

• Chronic blistering skin condition• No virus involved• Autoantibodies present, gluten intolerance• Affects both male & females, 15 to 40 yrs of age• Intensively itchy, chronic papulo-vesicular rash• EMA positive (IFA): Ig A isotype• eTG (epidermal Transglumase) positive IgG / IgA• HLA DQ 2• Improvement when put on Gluten free diet

Ciliac Disease Histopathology

Small bowel mucosa in celiac disease showing subtotal villus atrophy.

Normal small bowel mucosa

Diagnosis

• Presumptive diagnosis– Positive serology– Intestinal biopsy with villous atrophy

• Definitive diagnosis– Resolution of clinical symptoms after initiation of

gluten free diet• Generally accompanied by conversion to negative

serology & reconstitution of villi

Laboratory Diagnosis of Celiac DiseaseMilestones

• Before 1960: based on clinical suspicion & biopsy

• 1982: Anti gliadin; Sensitivity: 70%; Specificity 70%

• 1985: Endomysial IFA; Sen: 70 – 90%; Specificity 100%

• 1997: Anti tTG by ELISA; Sen & Spec: 90 – 95%

• 2005: Anti deamidated Gliadin: Sen: 85%, Spec 90%

Serologic tests for celiac disease2014

• Tissue transglutaminase antibodies– IgA and IgG isotypes [ELISA]

• Deamidated gliadin antibodies– IgA and IgG isotypes [ELISA]

• Endomysial antobodies– IgA isotype only by IFA

Other investigations

• HLA DQ typing

• Small intestinal biopsy

• Total IgA

Test for selective IgA deficiency

Normal Total IgA

CD unlikely

HLA DQ2 & DQ8

Negative

S.I BiopsyPositive

Deamidated Gliadin IgA & IgGEMA IgA

+/+, +/-,-/+

CD unlikely

-/-

1.

IgA detectable but below RR

HLA DQ 2 & DQ 8

2.

Undetectable Total Ig A

• Selective IgA deficiency• Test for tTG • Test for Deamidated Gliadin

– Both for IgG isotype only

• If positive advice small intestinal biopsy

3.

Summary

• Total IgA– Identify individuals with selective IgA deficiency

• Anti TTG & Anti deamidated gliadin antibodies • IgA & IgG isotypes• Anti EMA IgA isotype by IFA

• Identify individuals with suspected celiac disease• Confirm with small intestine biopsy

– Specific antibodies may be absent if on gluten free diet

• HLA DQ 2 & HLA DQ 8– Negative results virtually excludes diagnosis of CD

Additional tests that need to be carried out

• CBC• TSH• LFT• Vitamins: D, A, E, K, Folate, B12• Calcium, Phosphate, Zinc• PTH• Iron studies• Bone Mineral Density Scan

Who should be tested ?Rubio Tapia R et al: Am J Gastro 2013: 108: 656 – 76

American Gastroenterology Society Recommendations

• Consider testing in symptomatic patients at high risk of– Autoimmune Hepatitis– Premature onset

osteoprosis– Primary Biliary cirrhosis– Unexplained increase in

liver transaminases– Unexplained iron

deficiency anemia

• Consider testing for CD when following are present:– Autoimmune Thyroid

disease– Cerebellar Ataxia– 1st & 2nd degree relatives – IBS– Peripheral neuropathies– Selective IgA deficiency– Type 1 diabetes– Turner & Down syndrome

Who should be tested ?ESPGHAN Guidelines for Celiac Disease 2012

European Society for pediatric gastroenterology, hepatology and nutrition • Group 1

– Children & adolescents with otherwise unexplained symptoms & signs of

• Chronic or intermittent diarrhea• Failure to thrive / Weight loss/

Stunted growth• Delayed puberty / Amenorrhea• Iron deficiency anemia• Nausea or vomiting• Abdominal pain, cramping or

distention• Chronic fatigue• Recurrent aphthous ulcer

• Group 2– Asymptomatic children &

adolescent with • Type 1 diabetes• Down syndrome• Autoimmune thyroid

disease• Turner syndrome• Selective IgA deficiency• Autoimmune liver disease• First degree relatives of

Celiac disease patients

A simple scoring system ESPGHAN Guidelines for Celiac Disease 2012

European Society for pediatric gastroenterology, hepatology and nutrition

Elements (Need Score of 4 for diagnosis) Score Symptoms: Malabsorption Other CD relevant symptoms or TIDM or 1st degree relative Asymptomatic

210

Serum antibodies EMA positivity and/or high positivity for anti tTG Low positivity for tTG or isolated anti DGP positivity Serology not performed Serology performed but all celiac specific antibodies negtive

210-1

HLA Full HLA DQ 2 or HLA 8 hetrodimer present No HLA performed or half DQ 2 present HLA neither DQ 2 or DQ 8

10-1

Histology Marsh 3b or 3c (subtotal villous atrophy, flat lesion) Marsh 2 or 3a (moderate decreased villous height) plus tTG antibodies Marsh 0 – 1 or no biopsy performed

210

One man’s alloo paratha maybe another man’s poison

CautionESPGHAN Guidelines for Celiac Disease 2012

European Society for pediatric gastroenterology, hepatology and nutrition

• A gluten free diet (GFD) should be introduced only after the completion of the diagnostic process and when a conclusive diagnosis has been made.

• Healthcare professionals should be advised that starting patients on a GFD, when CD has not been excluded or confirmed, may be detrimental.