Laboratory investigations - specific IgE testing, including use of recombinant allergens

What it measures

Serum allergen-specific IgE (ImmunoCAP, formerly RAST) - quantifies circulating IgE to a defined allergen
Reported in kUA/L, usually graded 0-6
Detects sensitisation, not clinical allergy - the single most important distinction
- Sensitisation without reaction is common; treating a positive test in an asymptomatic patient causes harm


Whole-extract sIgE	Crude allergen mix. Cheap, cross-reactivity-prone
Component-resolved diagnostics (CRD)	sIgE to individual purified proteins - distinguishes primary sensitisation from cross-reaction
Total IgE	Almost never diagnostically useful alone. Needed only to dose omalizumab and to interpret ABPA

Sensitisation rates far exceed allergy rates: ~40-50% of Australian adults have at least one positive sIgE; symptomatic allergy is a fraction of this

Solid-phase allergen binds patient IgE -> labelled anti-IgE detection -> fluorescence proportional to IgE quantity
Higher sIgE = higher probability of a clinical reaction, not a more severe reaction
Cross-reactivity arises from conserved protein families
- Profilins and PR-10 (Bet v 1 homologues) - pollen-food syndrome, heat-labile, mild
- CCD (cross-reactive carbohydrate determinants) - clinically irrelevant positives across plants and venoms
- Storage proteins (2S albumins, e.g. Ara h 2) - heat-stable, associated with systemic reaction

Always against the clinical history. A positive test with no matching history = sensitisation
Rising titre supports persistence; falling titre supports resolution and prompts challenge
Predictive decision points exist for a few foods only (e.g. egg, milk, peanut in children) - they estimate the probability of a failed challenge, not severity
Component testing
- Ara h 2 positive -> genuine peanut allergy, systemic risk
- Ara h 8 only -> birch cross-reactivity, mild oral symptoms
- Omega-5 gliadin -> wheat-dependent exercise-induced anaphylaxis
- Alpha-gal -> delayed mammalian meat anaphylaxis

Specific IgE for penicillin has low sensitivity (0-25%) but reasonable specificity (83-100%)
- -> a negative result does not exclude penicillin allergy and cannot be used to delabel
- A positive result is meaningful; a negative one is not
- Skin testing and supervised oral challenge remain the reference standard

Screening panels in unselected patients
Chronic urticaria - not IgE-mediated
Food intolerance, IBS, "food sensitivity" - IgG/IgG4 food panels have no validity and should never be ordered
Distinguishing IgE from non-IgE drug reactions

Confirm concordance of test and history before any avoidance advice
Discordant history and testing -> supervised challenge, which outranks both
Communicate the difference between sensitisation and allergy explicitly - unnecessary avoidance causes nutritional harm, anxiety and, in food allergy, loss of tolerance
Repeat titres at intervals in children to time re-challenge

Atopic dermatitis - high total IgE, multiple positives, many clinically irrelevant
Parasitic infection, ABPA, hyper-IgE syndrome - raised total IgE
Pollen-food syndrome, latex-fruit syndrome, alpha-gal

Falling sIgE over years in egg and milk allergy predicts resolution
Persistently high sIgE to peanut, tree nut, fish and shellfish predicts persistence
Titres do not predict the severity of the next reaction - never reassure on the basis of a low number

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