1. Diagnosis and Dietary Management of Food Allergies and Intolerances
Clinical Applications
J.M.Joneja, Ph.D. 2013

2. Tests for Adverse Reactions to Foods
Rationale and Limitations

3. Standard Allergy Tests Skin tests
Scratch or prick
Allergen extract applied to skin surface
of arm or back
Skin is scarified (scratched) or pricked with lancet
Allergen encounters mast cells below skin surface
If allergen-specific IgE is present, allergen plus antibody causes release of mediators (mast cell degranulation), especially histamine
Histamine causes reddening and swelling: “wheal and flare” reaction of the skin test
Size of reaction measured (usually 1+ to 4+)
J.M.Joneja, Ph.D. 2013

4. Standard Allergy Tests Skin tests continued
Intradermal tests
Allergen extract is injected into dermis
Rationale: release of histamine produces wheal and flare
Note: many countries do not approve this type of testing because of increased risk of anaphylaxis as allergen introduced directly into blood stream
Controls for all skin tests:
Negative: medium in which allergen is suspended (usually saline)
Positive: measured amount of histamine

5. Wheal and Flare Reaction
Skin prick tests

6. Value of Skin Tests in Practice
Positive predictive accuracy of skin tests rarely exceeds 50%
Many practitioners rate them lower
Negative skin tests do not rule out the possibility of non-IgE-mediated reactions
Do not rule out non-immune-mediated food intolerances
J.M.Joneja, Ph.D. 2013

7. Value of Skin Tests in Practice
Tests for highly allergenic foods thought to have close to 100% negative predictive accuracy for diagnosis of IgE-mediated reactions
Such foods include:
Egg  Milk
 Fish  Wheat
 Tree nuts  Peanut
J.M.Joneja, Ph.D. 2013

8. Reasons for False Positive Skin Tests
Degranulation of skin mast cells by stimuli that do not degranulate mast cells in the digestive tract
Differences in the form in which the food is applied to the skin compared to that which encounters immune cells in the digestive tract
Raw form in extract may be degraded during cooking
Digestion by gastric acid and digestive enzymes can degrade antigens
Allergen extract contains histamine
J.M.Joneja, Ph.D. 2013

9. False Negative Skin Tests
Children younger than 2-3 years are more likely to have a negative skin test and positive food challenge than adults
Adverse reaction is not mediated by IgE
Commercial allergen may contain no material that the immune system can recognize
Processing of food leads to degradation of allergen (e.g. crushing produces phenols and catabolic enzymes)
J.M.Joneja, Ph.D. 2013

10. Other Skin Tests Prick-to-Prick
Sterile needle is inserted into raw food, and the patient’s skin is pricked with the same needle
Used for suspected contact allergy
e.g. oral allergy syndrome
Especially where allergen is easily
denatured by heat and acid
Crushing plant tissue during preparation of allergen extracts releases phenols that rapidly cause break-down of protein
Prick-to prick test transfers “native” allergen

11. Other Skin Tests Patch Test for Contact Allergies
Involves Type IV (delayed) hypersensitivity reaction, requiring cell-to-cell contact
Examples:
Poison ivy rash
Nickel contact dermatitis
Preservatives, dyes and perfumes in cosmetics
Allergen is placed on the skin, or applied as an impregnated patch, which is kept in place by adhesive bandage for up to 72 hours
Local reddening, swelling, irritation, indicates positive response

12. Other Skin Tests
DIMSOFT (dimethylsulphoxide test) for delayed reaction to food
Food extract is suspended in 90% dimethylsulfoxide
Aids in skin penetration of allergen
Patch held in place hours
Especially useful in skin and gastrointestinal reactions which may not have immediate onset symptoms
Especially useful for milk and cereal grains

13. Risks associated with skin tests
High number of false positive and false negative tests creates risk of diagnostic inaccuracy
All tests must be considered together with:
Clear medical history
Exclusion of non-allergic causes
Confirmation by elimination and challenge of suspect foods
Danger of sensitisation to allergens through the skin:
Initial exposure via the digestive tract most likely to lead to tolerance
Initial exposure via the skin more likely to lead to sensitization and initiation of allergy especially if inflammation exists (e.g. eczema)

14. Standard Allergy Tests Blood Tests
RAST: radioallergosorbent test (e.g. ImmunoCap-RAST; Phadebas-RAST)
FAST; Fluorescence allergosorbent test
ELISA: enzyme-linked immunosorbent assay
Designed to detect and measure levels of allergen-specific antibodies
Used for detection of levels of allergen-specific IgE
May measure total IgE - thought to be indicative of “atopic potential”
Some practitioners measure IgG
(especially IgG4) by ELISA

15. Value of Blood Tests in Practice
Blood tests have about the same sensitivity as skin tests for identification of IgE-mediated sensitisation to food allergens
Anti-food antibodies (especially IgG) are frequently detectable in all humans, usually without any evidence of adverse effect
IgG production likely to be the first stage of development of oral tolerance to a food
Studies suggest that IgG4 indicates protection or recovery from IgE-mediated food allergy

16. Value of Blood Tests in Practice
There is often poor correlation between high level of anti-food IgE and symptoms when the food is eaten
Many people with clinical signs of food allergy show no elevation in IgE
Reasons for failure of blood tests to indicate foods responsible for symptoms are the same as those for skin tests

17. Tests for Intolerance of Food Additives
There are no reliable skin or blood tests to detect food additive intolerance
Skin prick tests for sulphites are sometimes positive
A negative skin test does not rule out sulphite sensitivity
History and oral challenge provocation of symptoms are the only methods for the diagnosis of additive sensitivity at present
Caution: Challenge may occasionally induce anaphylaxis in sulphite-sensitive asthmatics

18. Unorthodox Tests
Many people turn to unorthodox tests when avoidance of foods positive by conventional test methods have been unsuccessful in managing their symptoms
Tests include:
Vega test (electro-dermal)
Biokinesiology (muscle strength)
Analysis of hair, urine, saliva
Radionics
ALCAT (lymphocyte cytotoxicity)
J.M.Joneja, Ph.D. 2013

19. Controversial Tests Electro-Dermal (Vega) Test
Measures change in electrical potential on skin
Circuit linking
Patient holding a metal rod
Vial containing food, or other material being tested
Meter to measure energy level
Technician holding probe held at acupuncture point on patient’s other hand
Disturbance in energy flow to meter indicates reactivity

20. Controversial Tests Biokinesiology
Assumption: muscles become weak when influenced by the allergen to which the patient reacts
Patient holds a vial containing the suspect allergen (food)
Practitioner tests the strength of the patient’s other arm in resisting downward pressure
Weakening of resistance indicates a positive (allergic) reaction

21. Drawbacks of Unreliable Tests
Diagnostic inaccuracy
Therapeutic failure
False diagnosis of allergy
Creation of fictitious disease entities
Failure to recognize and treat genuine disease
Inappropriate and unbalanced diets
J.M.Joneja, Ph.D. 2013

22. Consequences of Mismanagement of Adverse Reactions to Foods
Malnutrition; weight loss, due to extensive elimination diets
Especially critical in young children where nutritional deficiency at a crucial stage in development can cause permanent damage
Food phobia due to fear that “the wrong food” will cause permanent damage, and in extreme cases, death
Frustration and anger with the “medical system” that is perceived as failing them
Disruption of lifestyle, social and family relationships
J.M.Joneja, Ph.D. 2013

23. Elimination and Challenge
Protocols

24. Identification of Allergenic Foods
Removal of the suspect foods from the diet, followed by reintroduction is the only way to:
Identify the culprit food components
Confirm the accuracy of any allergy tests
Long-term adherence to a restricted diet should not be advocated without clear identification of the culprit food components
J.M.Joneja, Ph.D. 2013

25. Food Intolerance: Clinical Diagnosis
Elimination Diet: Avoid Suspect Food
Increase Restrictions
Symptoms Disappear
Symptoms Persist
Reintroduce Foods Sequentially or Double-blind
Symptoms Provoked
No Symptoms
Diagnosis Confirmed
Diagnosis Not Confirmed
J.M.Joneja, Ph.D. 2013

26. Elimination and Challenge
Stage 1: Exposure Diary
Record each day, for a minimum of 5-7 days:
All foods, beverages, medications, and supplements ingested
Composition of compound dishes and drinks, including additives in manufactured foods
Approximate quantities of each
The time of consumption
J.M.Joneja, Ph.D. 2013

27. Exposure Diary (continued)
All symptoms graded on severity:
 1 (mild);  2 (mild-moderate)
 3 (moderate)  4 (severe)
Time of onset
How long they last
Record status on waking in the morning.
Was sleep disturbed during the night, and if so, was it due to specific symptoms?
J.M.Joneja, Ph.D. 2013

28. Elimination Diet Based on:
Detailed medical history
Analysis of Exposure Diary
Any previous allergy tests
Foods suspected by the patient
Formulate diet to exclude all suspect allergens and intolerance triggers
Provide excluded nutrients from alternative sources
Duration: Usually four weeks
J.M.Joneja, Ph.D. 2013

29. Selective Elimination Diets
Certain conditions tend to be associated with specific food components
Suspect food components are those that are probable triggers or mediators of symptoms
Examples:
Eczema: Highly allergenic foods
Migraine: Biogenic amines
Urticaria/angioedema: Histamine
Chronic diarrhea: Carbohydrates; Disaccharides
Asthma: Cyclo-oxygenase inhibitors Sulphites
Latex allergy: Foods with structurally similar antigens to latex
Oral allergy syndrome: Foods with structurally similar antigens to pollens

30. Few Foods Elimination Diet
When it is difficult to determine which foods are suspects a few foods elimination diet is followed
Limited to a very small number of foods and beverages
Limited time: days for an adult
7 days maximum for a child
If all else fails use elemental formulae:
May use extensively hydrolysed formula for a young child

31. Expected Results of Elimination Diet
Symptoms often worsen on days 2-4 of elimination
By day 5-7 symptomatic improvement is experienced
Symptoms disappear after days of exclusion
J.M.Joneja, Ph.D. 2013

32. Challenge Double-blind Placebo-controlled Food Challenge (DBPCFC)
Lyophilized (freeze-dried) food is disguised in gelatin capsules
Identical gelatin capsules contain a placebo (glucose powder)
Neither the patient nor the supervisor knows the identity of the contents of the capsules
Positive test is when the food triggers symptoms and the placebo does not

33. Challenge (continued)
Drawback of DBPCFC
Expensive in time and personnel
Capsule may not provide enough food to elicit a positive reaction
Patient may be allergic to gelatin in capsule
May be other factors involved in eliciting symptoms, e.g. taste and smell

34. Challenge (continued)
Single-blind food challenge (SBFC)
Supervisor knows the identity of the food; patient does not
Food is disguised in a strong-tasting “inert” food tolerated by the patient:
lentil soup
apple sauce
tomato sauce

35. Challenge Phase continued
Open food challenge
Sequential Incremental Dose Challenge (SIDC)
Each food component is introduced separately
Starting with a small quantity and increasing the amount according to a specific schedule
This is usually employed when the symptoms are mild, and the patient has eaten the food in the past without a severe reaction
Any food suspected to cause a severe or anaphylactic reaction should only be challenged in suitably equipped medical facility

36. Open Food Challenge
Each food or food component is introduced individually
The basic elimination diet, or therapeutic diet continues during this phase
If an adverse reaction to the test food occurs at any time during the test STOP.
Wait 48 hours after all symptoms have subsided before testing another food

37. Incremental Dose Challenge
Day 1: Consume test food between meals
Morning: Eat a small quantity of the test food
Wait four hours, monitoring for adverse reaction
If no symptoms:
Afternoon: Eat double the quantity of test food eaten in the morning
Evening: Eat double the quantity of test food eaten in the afternoon
J.M.Joneja, Ph.D. 2013

38. Incremental Dose Challenge (continued)
Day 2:
Do not eat any of the test food
Continue to eat basic elimination diet
Monitor for any adverse reactions during the night and day which may be due to a delayed reaction to the test food
J.M.Joneja, Ph.D. 2013

39. Incremental Dose Challenge (continued)
Day 3:
If no adverse reactions experienced
Proceed to testing a new food, starting Day 1
If the results of Day 1 and/or Day 2 are unclear :
Repeat Day 1, using the same food, the same test protocol, but larger doses of the test food
Day 4:
Monitor for delayed reactions as on Day 2
J.M.Joneja, Ph.D. 2013

40. Sequential Incremental Dose Challenge
Continue testing in the same manner until all excluded foods, beverages, and additives have been tested
For each food component, the first day is the test day, and the second is a monitoring day for delayed reactions

41. Sequence of Testing Milk and Milk Products
Test 1: Casein proteins
Test 2: Annatto, biogenic amines, plus casein
Test 3: Casein plus whey proteins
Test 4: Lactose in addition to casein and whey proteins
Test 5: Modified milk components
Test 6: Whey proteins (lactose-free)
Test 7: Lactose (in whey)
Test 8: Complex milk products (e.g. ice cream)
J.M.Joneja, Ph.D. 2013

42. Sequence of Testing: Wheat
Test 1: Pure cereal grain
Test 2: Wheat Cracker without yeast
Test 3: White Bread
Test 4: Whole Wheat Bread
J.M.Joneja, Ph.D. 2013

43. Maintenance Diet

44. Final Diet
Must exclude all foods and additives to which a positive reaction has been recorded
Must be nutritionally complete, providing all macro and micro-nutrients from non-allergenic sources
There is no benefit from a rotation diet in the management of food allergy
A rotation diet may be beneficial when the condition is due to dose-dependent food intolerance
J.M.Joneja, Ph.D. 2013

45. Important Micronutrients in Common Allergenic Foods
Minerals
Milk
Egg
Peanut
Soy
Fish
Wheat
Rice
Corn
Calcium +
Phosphorus
Iron
Zinc
Magnesium
Selenium
Potassium
Molybdenum
Chromium
Copper
Manganese

46. Vitamins Milk Egg Peanut Soy Fish Wheat Rice Corn A + Biotin
Folacin (folate; folic acid)
B-1 (thiamin)
B-2 (riboflavin)
B-3 (niacin)
B-5 (pantothenic acid)
B-6 (pyridoxine)
B-12 (cobalamin) D
E (alpha-tocopherol) K

47. Current Areas of Research
Promotion of Tolerance to Foods

48. Prevention of Food Allergy in Clinical Practice
Significant change in directives within the past 3 years:
Previously:
Avoidance of allergen to prevent sensitization (allergen-specific IgE)
Current:
Active stimulation of the immature immune system to induce tolerance of the antigens in food
________________
Rautava et al 2005
J.M.Joneja, Ph.D. 2013

49. Diet During Pregnancy and Lactation
There is no convincing evidence that women who avoid highly allergenic foods, or other foods during pregnancy and breast-feeding lower their child’s risk of allergies
Current directive: the atopic mother should strictly avoid her own allergens and replace the foods with nutritionally equivalent substitutes
There are no indications for mother to avoid other foods during pregnancy
A nutritionally complete, well-balanced diet is essential
_______________
Kramer et al 2006
J.M.Joneja, Ph.D. 2013

50. Introduction of Fish
Historically, fish consumption during infancy was considered to be a risk factor for allergy
Recent research indicates otherwise:
Regular fish consumption during the first year of life associated with a reduced risk for allergic disease by age 4 years (n=4089)1
Babies of mothers who frequently consumed fish (2-3 times per week or more) during pregnancy had one third less food sensitivities than those whose mothers did not consume fish during pregnancy2
_____________
1Kull et al 2006
_______________
2Calvani et al 2006
J.M.Joneja, Ph.D. 2013

51. Introduction of Fish
Babies who were fed fish before nine months of age were 24% less likely to develop eczema by age 1 year1
Children less likely to develop allergy to fish if the mother consumes fish two or three times a week during pregnancy2
Regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age four3
____________
Alm et al 2009
_______________
Calvani et al 2006
_____________
Kull et al 2006
J.M.Joneja, Ph.D. 2013

52. Recent Evidence for Early Introduction of Solids
Delaying initial exposure to cereal grains until after 6 months may increase the risk of wheat allergy1
Research suggests that high risk for celiac disease occurs if gluten-containing grains are introduced before 3 months or after 7 months2
_________________
1Poole et al June 2006
______________
2Norris et al 2005

53. Introduction of Peanuts
Study (n=10,786) among primary school age Jewish children in UK and Israel
Prevalence of peanut allergy (PA):
In UK: 1.85%
In Israel: 0.17%
Median monthly consumption of peanut in infants aged 8 – 14 months:
In UK: 0
In Israel: 7.1 g
Difference not due to atopy, genetic background, social class, or peanut allergenicity
Israeli infants consume peanuts in high quantities during the first year of life
______________
Du Toit et al 2008
J.M.Joneja, Ph.D. 2013

54. Development of Tolerance
25% of infants lost all food allergy symptoms after 1 year of age
Most infants will outgrow milk allergy by 3 years of age, but may have become intolerant to other foods in the meantime
Tolerance of specific foods :
After 1 year:
26% decrease in allergy to:
 Milk  Soy  Peanut
 Egg  Wheat
2% decrease in allergy to other foods
________________
Bishop et al 1990
J.M.Joneja, Ph.D. 2013

55. Prognosis Age at which milk was tolerated by milk-allergic children:
Diverse studies report different statistics
Allergy to some foods more often than others persists into adulthood:
 Peanut  Tree nuts
 Shellfish  Fish
28% by 2 years 1
56% by 4 years
78% by 6 years
56% at 1 year 2
77% at 2 years
87% at 3 years
19% by 4 years 3
42% by 8 years
64% by 12 years
79% by 16 years
_______________________________________________________________________
1Bishop et al Host and Halken Skripak et al 2007
J.M.Joneja, Ph.D. 2013

56. Induction of Oral Tolerance
Allergy to a specific food can be induced by oral administration of the offending food (SOTI: specific oral tolerance induction)
Starting with very low dosages
Gradually increasing daily dosage up to the equivalent of the usual daily intake
Followed by daily maintenance dose
__________________
Niggemann et al 2006
J.M.Joneja, Ph.D. 2013

57. Desensitization to Cow’s Milk
18 children with confirmed CMA >4 years of age underwent SOTI
Starting dose 0.05 ml cow’s milk
Increased to 1 ml on first day
Increasing dosage weekly up to a daily dose of ml
Results: 16/18 tolerated ml milk
Length of process median 14 weeks (range weeks)
Tolerance has been maintained for >1 year
_______________
Zapatero et al 2008
J.M.Joneja, Ph.D. 2013

58. Oral Tolerance Induction to Milk, Egg, and Peanut
36% of children with IgE-mediated allergy to cow’s milk and hen’s egg developed permanent tolerance of the foods after a median 21 months specific oral tolerance induction (SOTI)1
4 peanut-allergic children underwent SOTI:
Daily doses of peanut flour starting at 5 mg peanut protein
2-weekly dosage increase up to 800 mg protein
All subjects tolerated at least 10 whole peanuts (2.38 g protein) on post-intervention challenge2
______________
1Staden et al 2007
____________
2Clark et al 2009
J.M.Joneja, Ph.D. 2013

59. Progression of Peanut Allergy
Peanut allergy, like many early food allergies, can be outgrown
In 2001 pediatric allergists in the U.S. reported that about 21.5 per cent of children will eventually outgrow their peanut allergy1
Those with a mild peanut allergy, as determined by the level of peanut-specific IgE in their blood, have a 50% chance of outgrowing the allergy2
Only about 9% of patients are reported to outgrow their allergy to tree nuts3
__________________
1Skolnick et al 2001
2Fleischer et al 2003
3Fleischer et al 2005

60. Maintaining Tolerance of Peanut
When there is no longer any evidence of symptoms developing after a child has consumed peanuts, it is preferable for that child to eat peanuts regularly, rather than avoid them, in order to maintain tolerance to the peanut
Children who outgrow peanut allergy are at risk for recurrence, but the risk has been shown to be significantly higher for those who continue to avoid peanuts after resolution of their symptoms
_________________
Fleischer et al 2004

61. Summary Food Allergy: Immune system response Food Intolerance:
Usually metabolic dysfunction
Diagnostic Laboratory Tests:
Often ambiguous because different physiological mechanisms are involved in triggering symptoms
J.M.Joneja, Ph.D. 2013

62. Summary
Reliable tests for the detection of adverse reactions to foods:
 Elimination and Challenge
Final diet
Must provide complete nutrition while avoiding all of the foods and food components that elicit symptoms on challenge

63. Summary Recognition of development of tolerance
Periodic test and challenge after usually several years of avoidance of allergenic food
Maintenance of tolerance by regular consumption of allergenic food
J.M.Joneja, Ph.D. 2013

64. Invitation to Further Information
Website:
Janice Vickerstaff Joneja Ph.D
The Health Professional’s
Guide to Food Allergies
and Intolerances
Academy of Nutrition and
Dietetics. Chicago 2013