ImmunologyTier 2Medical Sciences concept

Allergen immunotherapy - indications and mechanism

Core concept

Repeated controlled exposure to allergen reprogrammes the response from effector to tolerant
Sequence over time
- Early (hours-days) - mast cell and basophil desensitisation, dec releasability
- Weeks-months - induction of allergen-specific regulatory T cells (IL-10, TGF-beta) and regulatory B cells
- Months-years - class switch away from IgE toward IgG4 "blocking" antibody
  - IgG4 competes for allergen and prevents IgE-facilitated antigen presentation to T cells
- -> Th2 to Th1/Treg shift; dec IL-4, IL-5, IL-13; dec tissue eosinophils and mast cells
Seasonal specific IgE rise is blunted, then IgE falls; IgG4 rise, not IgE fall, is the earliest marker of response
The only treatment that modifies the natural history of allergic disease - benefit persists for years after a completed course, and it reduces new sensitisations and progression of rhinitis to asthma

Routes

	Subcutaneous (SCIT)	Sublingual (SLIT)
Dose	Lower cumulative	Higher cumulative dose required
Setting	Clinic, with 30 min observation and adrenaline available	First dose supervised, then home
Adverse	Local swelling common; systemic reactions ~0.1-0.2% of injections, rare fatalities	Oral itch/swelling in most, mild; systemic reactions rare
Evidence	Aeroallergens, venom	Grass pollen, house dust mite, ragweed - comparable efficacy to SCIT
Venom	SCIT only	Not used

Course length: build-up over weeks-months, then maintenance for 3-5 years; a course shorter than 3 years does not give durable tolerance
Indications
- Insect venom anaphylaxis - the strongest indication
- Allergic rhinoconjunctivitis inadequately controlled by avoidance and pharmacotherapy, or where the patient prefers disease modification
- Mild-moderate allergic asthma with a demonstrated single dominant sensitisation (HDM SLIT reduces exacerbations)
- Requires demonstrated specific IgE (skin prick or serum) that matches the clinical history - sensitisation alone is not an indication
Contraindications / cautions
- Uncontrolled or severe asthma, or FEV1 <70% predicted - the single biggest risk factor for fatal reactions
- Beta-blockers (impair adrenaline response); ACE inhibitors are a relative caution for venom immunotherapy
- Active malignancy, significant autoimmune disease, immunodeficiency or immunosuppression
- Do not initiate in pregnancy (maintenance may continue if already established and tolerated)
- Acute febrile illness; poor adherence or inability to attend
Not indicated for chronic urticaria, atopic dermatitis alone, non-IgE food reactions, or where no allergen-specific IgE is demonstrated

Venom immunotherapy - the numbers

After a systemic sting reaction, risk of a further systemic reaction is ~40-60%
Venom immunotherapy reduces this to <5%, and the protection is durable after a 3-5 year course
Indicated for a systemic (not large local) reaction with confirmed venom-specific IgE
Measure baseline tryptase before starting - mastocytosis or hereditary alpha-tryptasaemia predicts severe reactions, poorer protection, and argues for lifelong maintenance**
Australian relevance: honeybee, European wasp, jack jumper ant (Myrmecia pilosula) - jack jumper venom immunotherapy is available in Tasmania and Victoria

Food immunotherapy - the contrast that the exam draws

Oral immunotherapy achieves DESENSITISATION (protection while dosing continues) but sustained unresponsiveness after stopping is uncommon and unpredictable
- -> daily dosing must continue indefinitely; ~10-20% withdraw for gastrointestinal symptoms or eosinophilic oesophagitis
- -> this is why food OIT is not offered as routinely as venom immunotherapy
Early introduction of peanut and egg in infancy prevents allergy (LEAP, EAT) - primary prevention, not immunotherapy
Omalizumab (anti-IgE) raises the reaction threshold to multiple foods and is used as monotherapy or as an adjunct to OIT

Safety practicalities

Adrenaline and resuscitation available for every injection; 30 minutes observation (60 min if higher risk)
Withhold or reduce the dose during an asthma exacerbation, acute illness, or after a systemic reaction
A missed maintenance interval requires dose reduction on restart - not simply resuming

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