3. Definition of Food Allergy ?
Definition of Food Allergy
Food allergy has no universally accepted
definition. The NIAID has suggested
that 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”
20. Food allergy & “Intolerance”
Type of Reaction
Cause
Food Involved
Allergy
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
21. Food proteins are recognized as “foreign”
Food specific IgG production and formation of
antigen/antibody complexes
Complexes are deposited in tissues and activate
Complement
Complement and macrophages stimulate
Inflammation
Delayed reaction and may last for days
27. Class 0
Classes 1-2
No allergic reaction against tested food.
No restriction is necessary.
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.
28.
29.
30. Improvement of symptoms (%)
after omitting allergenic food
Study, 2002-2008; evaluated by Mediveritas Institiute for Medical Studies, Munich
30
31.
32.
33. 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
34. 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".
35. 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
36. Clinical features
Consequence 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
40. Celiac Disease can present at ANY age to
ANY specialty
Farrell RJ & Kelly CP: New Engl J Med 2002; 336: 180 - 188
41. 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
48. HLA & Celiac Disease
Useful for ruling out celiac disease
49. 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
55. 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
56. Laboratory Diagnosis of Celiac Disease
Milestones
• 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%
57. Serologic tests for celiac disease
2014
• Tissue transglutaminase antibodies
– IgA and IgG isotypes [ELISA]
• Deamidated gliadin antibodies
– IgA and IgG isotypes [ELISA]
• Endomysial antobodies
– IgA isotype only by IFA
63. 3.
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
64.
65.
66. 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
67. 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
68. 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
69. 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
70. 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
2
1
0
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
2
1
0
-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
1
0
-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
2
1
0
72. Caution
ESPGHAN 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.
