Monitoring IgE-mediated Food Allergies

  • In general, the longer a food allergy persists (i.e. into the late teenage and early adult years) the less likely that the patient's food allergy will resolve
Food
Monitoring
Natural course
Cow's Milk
  • Annual sIgE
  • Offer regular milk challenge when sIgE ≤2
    • When sIgE ≤2, ~50% chance of negative challenge; consider using lower cutoff in children <2 yo
    • If sIgE falls 99% over >1 year, there is 94% chance of negative challenge
  • Consider baked milk challenge when sIgE ≤10-35, with lower threshold for younger children (Wegrzyn)
    • Majority (70-80%) of children with milk allergy tolerate baked foods containing milk (e.g. muffin and waffle made with milk)
    • Low casein specific IgE level is a very favorable prognostic factor for tolerance of baked milk, with casein sIgE >20 unlikely to pass and <0.94 unlikely to fail a baked milk challenge; sIgE <~5 may be optimal decision point (~75% sens/spec)
    • In one study, milk SPT <7 and <12 mm was 100% and 90% predictive of passing a baked milk challenge
  • Peaks during first year of life and remits during childhood, almost always outgrown
  • Prospective studies
    • Resolution in 51% within 2 years and 80% within 3-4 years of diagnosis.
    • Resolution in 53% by median age of 5.25 yo
  • Risk factors for persistence
    • Referral population (vs. primary care)
    • Multiple food allergy, other atopic diseases
    • Higher peak sIgE or larger SPT wheal
    • Sensitization to alpha-1 casein, beta-casein, and kappa-casein regardless of patient age
    • Intolerance of foods containing heated/baked milk
  • CoFAR cow's milk allergy resolution calculator - for patients <15 months old using their initial test SPT and sIgE test values
Hen's Egg
  • Annual sIgE
  • Offer regular egg challenge when egg white sIgE ≤2
    • When sIgE ≤2, ~50% chance of negative challenge; consider using lower cutoff in children <2 yo
    • HealthNuts study of 11-15 mo Australian infants: egg white SPT 4 mm or sIgE 1.7 with 95% PPV for positive raw egg challenge
    • sIgE to ovomucoid >10.8 correlated with a high risk (95% specific) of reacting to boiled or raw egg white, whereas a level <1.2 correlated with a low risk of reaction (95% sensitive) to boiled egg white (even if the patient might react to raw)
    • sIgE to ovomucoid >22.4 was 100% specific for positive OFC to boiled egg white; sIgE to ovomucoid ~7-8 with ~50% probability of positive OFC to boiled egg white
    • In children who developed allergy <4 yo, if sIgE dropped 50, 75, 90, and 99% over 1 year, there was a 52, 65, 78, and 95% chance of negative challenge.
    • Majority (70-80%) of children with egg allergy tolerate extensively heated egg (e.g. muffin and waffle made with eggs)
  • Consider baked egg challenge when egg white sIgE <7-50, with lower threshold for younger children (Wegrzyn)
    • Burks: consider baked egg challenge when ovomucoid sIgE ≤2 kU/L and SPT to egg white <8 mm
    • In one study, negative predictive value was 89, 77, and 71% with egg white sIgE levels <2.5, 5, and 10
    • In one study, 100% passed if egg white SPT <10 mm, 78% if 10-19 mm, 80% if 20-29 mm, and 66% (2 of n=3) if >30 mm
    • In a large retrospective study, 90% passed (NPV 90%) if ovomucoid sIgE <0.35, egg white sIgE <6, and egg white SPT <11 mm; ovomucoid sIgE >3.38, egg white >9.65, and egg white SPT >25 mm >95% specific in predicting positive challenges
    • Egg white SPT <3 mm may identify candidates for home challenge (100% passed)
    • HealthNuts study of 11-15 mo Australian infants: egg white SPT 9-10 mm with 50% PPV, 11 mm with 82% PPV, and sIgE 50 with 88% PPV for positive baked egg challenge
  • Usually resolves within several years of diagnosis (usually during childhood, majority (80%) by adulthood
    • 50% with resolution by 6 yo; persistence associated with more severe index reaction and higher sIgE/SPT levels
    • 4, 26, 48, and 68% with resolution at 4, 8, 12, and 16 yo
    • sIgE >50 associated with persistence
    • Tolerance is gained twice as rapidly to well-cooked egg than uncooked egg (median age resolution 5.6 years vs. 10.3)
  • Resolution tends to occurs in stages starting with tolerance to well-cooked egg (e.g. cake), then lightly cooked egg (e.g. scrambled) followed finally by raw egg

Mt. Sinai Egg Challenge Algorithm (2012)
Sinai baked egg guidelines.png
Peanut
  • Annual sIgE
  • Offer challenge when 4 yo, no reaction in past 1-2 years, and sIgE ≤2 (~60% chance of negative challenge)
    • Low/undetectable sIgE level is best predictor of a negative challenge but 4-28% with negative sIgE have positive challenge
    • If OFC negative, the patient should ingest a serving of peanut weekly
    • In patients with persistent allergy or if sIgE remains unchanged for years, test less frequently
    • Fleischer: I only challenge patients when sIgE <2
    • Burks: challenge if peanut sIgE ≤2 and SPT <8 mm
    • HealthNuts study of 11-15 mo Australian infants: peanut SPT 2-3 mm or sIgE ~2.5 with 50% PPV and SPT 8 mm or sIgE 34 with 95% PPV for positive peanut challenge
    • sIgE/tIgE ratio 0.42%/2.36% associated with OFC pass/fail in a group of children with peanut SPT <8 mm and sIgE <15 kU/L
  • Resolution rate often quoted as 20-25%; in one study 27% with resolution by 12 yo
  • Spontaneous resolution of early-onset peanut allergy occurs predominantly before 6 yo and at a much lower frequency after 10 yo
  • Recurrence of allergy after negative OFC may occur in up to 8% and may be associated with lack of regular intake (at least weekly to monthly) after a negative challenge
Tree nut
  • Annual sIgE
  • Offer challenge when 4 yo, no reaction in past 1-2 years, and sIgE <5 (~60% chance of negative challenge)
    • 58, 63, and 75% of children with negative challenge had sIgE levels <5, <2, and negative
    • sIgE/tIgE ratio 0.29%/1.9% associated with OFC pass/fail in a group of children with tree nut SPT <8 mm and sIgE <15 kU/L
    • Low/undetectable sIgE level is best predictor of a negative challenge but up to 10% with negative sIgE/SPT have positive challenge
    • If negative, the patient should ingest a serving of culprit tree nut weekly
    • In patients with persistent allergy or if sIgE remains unchanged for years, test less frequently
  • ~10% with resolution over time
  • Resolution less likely if reactions to >2 different tree nuts
  • If peanut allergy resolved, more likely to outgrow tree nut allergy. However, resolution of peanut does not mean resolution of tree nuts or seeds.
Sesame
  • Annual sIgE
  • Challenge to sesame if sIgE ≤20, avoidance if >20. If SPT negative, sesame may be introduced into the diet. (Sampson)
  • HealthNuts study of 11-15 mo Australian infants: sesame SPT 2-3 mm or sIgE 10 with 50% PPV, SPT 8 mm with 95% PPV, and sIgE 50 with 86% PPV for positive sesame challenge
  • 20-30% with resolution over time
Wheat
  • Annual sIgE
  • Consider oral challenge to wheat at least every 2 years regardless of sIgE level
    • Based on observation that resolution is likely to occur in a two-year time span in a younger child (though resolution may occur when older)
    • sIgE <20 to <100 have been associated with 50% negative challenge rate depending on study/population.
    • In one survey, 60% with sIgE level <20 kU/L with negative challenge and 50% with <50 kU/L with negative challenge
    • Median sIgE levels associated with resolution 21-25; persistent allergy 62-70 (in 2-8 yo).
  • Usually outgrown by adolescence
    • In general population, 80% resolved by 5 yo
    • In referral population, 29, 56, and 70% with negative challenge at 4, 8, and 14 yo
Soy
  • Annual sIgE
  • Offer challenge to soy when IgE level is low, however this is not well defined
    • Soy sIgE and SPT may be artificially elevated in patients with peanut allergy, which makes these tests even more difficult to interpret
  • In referral population, 25, 45, and 69% with negative challenge by age 4, 6, and 10 years
  • Generally outgrown more quickly than egg or milk allergy
Seafood
  • Annual sIgE
  • Patients who react to fresh tuna and salmon usually tolerate canned versions of these fish. If interested in eating the canned form, additional testing and OFC are suggested.
  • Considered to be persistent in most cases
  • In a US survey, allergy developed in adulthood for 40-60% and 3-4% reported developing tolerance over time
Other foods
  • In general, annual sIgE, with increasing interval if level is unchanging

Above mostly adapted from Robert Wood
sIgE = serum specific IgE to food via Phadia (Thermo Fisher Scientific) ImmunoCAP


Food Allergy Prevalence

fa_prevalence.png


Oral Food Challenge sIgE Cut-offs

~50% Negative Oral Food Challenge
Test
sIgE (ImmunoCap)
----SPT----
----Cow’s milk----
≤2
n/a
Egg
≤2
≤3
Peanut
≤2 with
and ≤5 without history of reaction
≤3

~95% Positive OFC
Test
-----sIgE (ImmunoCap)-----
-----SPT-----
-----Cow’s milk-----
≥15 (≥5 if <1 yo)
≥8
Egg
≥7 (≥2 if <2 yo)
≥7
Peanut
≥14
≥8
Fish
≥20

Walnut
≥18.5

~73-74% Positive OFC
Soy
≥30

Wheat
≥26


Oral Food Challenge Procedure






References