Residency · Residency · Otolaryngology

Immunotherapy in the Otolaryngology Practice

Introduction

Allergen immunotherapy is the only treatment modality that modifies the natural history of allergic disease. Otolaryngologists are among the primary providers of both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in clinical practice. This lecture reviews the mechanisms, indications, protocols, safety considerations, and emerging trends in immunotherapy as applied in the ENT setting.

Mechanism of Action

Immunologic Changes

Shifts the immune response from a Th2-dominant to a Th1/Treg-dominant profile. Induction of regulatory T cells (Tregs) that produce IL-10 and TGF-beta. Decrease in allergen-specific IgE over time (may initially increase). Increase in allergen-specific IgG4 (blocking antibody) — competes with IgE for allergen binding. Reduction in mast cell and basophil reactivity, Decreased eosinophilic infiltration of target tissues. Decreased sensitivity of end-organ (nasal mucosa, bronchi) to allergen challenge.

Clinical Effects

Reduces symptom severity and medication requirements, Prevents new allergen sensitizations. Reduces the risk of asthma development in children with allergic rhinitis. Effects persist for years after discontinuation (disease-modifying).

Indications

Moderate-severe allergic rhinitis inadequately controlled by pharmacotherapy and allergen avoidance. Allergic asthma (mild-moderate) with documented allergen sensitivity. Stinging insect hypersensitivity (venom immunotherapy — typically managed by allergists). Patients seeking to reduce long-term medication dependence. Patients with adverse effects from pharmacotherapy.

Contraindications

Absolute: severe uncontrolled asthma, beta-blocker use (relative), severe immunodeficiency. Relative: pregnancy (do not initiate, but may continue if already on maintenance), age <5 years (for SCIT), significant cardiovascular disease. Poor compliance or inability to remain in office for observation period (SCIT).

Comparison of SCIT and SLIT

Subcutaneous Immunotherapy (SCIT)

Patient Selection and Testing

Confirmed IgE-mediated sensitivity by skin prick testing or serum-specific IgE. Correlation of test results with clinical history is essential — positive tests without clinical relevance should not be treated.

Protocols

Build-up phase: weekly injections with escalating allergen doses over 6-8 months (conventional) or accelerated schedules (cluster, rush). Maintenance phase: injections every 2-4 weeks at the target dose for 3-5 years. Multi-allergen mixes: common in otolaryngology practice; individual vials based on patient sensitization profile.

Administration and Safety

Injections given in the posterior upper arm, subcutaneously. Patient must remain in the office for 30 minutes post-injection for observation. Epinephrine and resuscitation equipment must be immediately available. Dose adjustments for missed appointments, new allergen season, or prior reaction.

Adverse Reactions

Local reactions: erythema, swelling at injection site (common, usually mild). Large local reactions: >25 mm swelling; may require dose adjustment. Systemic reactions: urticaria, angioedema, bronchospasm, hypotension, anaphylaxis. Anaphylaxis rate: approximately 1 per 1 million injections (fatal); 0.1-0.2% per injection (any systemic reaction). Risk factors: uncontrolled asthma, dosing errors, injection during peak pollen season.

Sublingual Immunotherapy (SLIT)

Available Formulations (FDA-Approved)

Grastek (Timothy grass pollen). Ragwitek (short ragweed pollen). Odactra (house dust mite). Off-label compounded multi-allergen SLIT drops are also widely used in otolaryngology.

Protocol

First dose administered in the office with 30-minute observation. Subsequent doses taken daily at home. Tablet placed under the tongue and held for 1-2 minutes; not swallowed immediately. Treatment duration: 3-5 years (pre-seasonal or continuous).

Safety Profile

Local oral reactions (itching, swelling) are common (40-75%) but usually mild and self-limiting. Systemic reactions are extremely rare compared to SCIT. Patients prescribed an epinephrine autoinjector for home use. No fatalities reported with FDA-approved SLIT products.

Advantages and Limitations

Advantages: home administration, excellent safety profile, patient convenience. Limitations: FDA-approved tablets are single-allergen; daily compliance required; may be less effective than SCIT for multi-allergen sensitivity.

Monitoring and Outcomes

Symptom and medication score tracking. Most patients notice improvement within the first year of treatment. Full benefit typically achieved by year 2-3. Recommended treatment duration: 3-5 years for sustained benefit after discontinuation. Annual reassessment of symptom control and need for continuation.

Emerging Therapies

Intralymphatic immunotherapy (ILIT): direct injection into lymph nodes; reduced number of injections; investigational. Epicutaneous immunotherapy: allergen delivery via skin patches. Adjuvant-modified allergens: recombinant allergens and novel adjuvants for improved efficacy and safety. Biologics (omalizumab, dupilumab): not immunotherapy per se, but may be combined with IT to improve safety and efficacy.

Key Clinical Pearls

Immunotherapy is the only disease-modifying treatment for allergic rhinitis — it should be discussed with all moderate-severe patients. Correlation between testing and clinical symptoms is critical; do not treat positive tests without clinical relevance. SCIT requires a 30-minute observation period and immediate access to epinephrine. SLIT offers excellent safety and convenience but currently has limited FDA-approved single-allergen options. Treatment duration of 3-5 years is necessary for long-term sustained benefit after discontinuation. Uncontrolled asthma is the most important risk factor for severe systemic reactions with SCIT.

References

1. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-S55.
2. Wise SK, Lin SY, Toskala E, et al. International consensus statement on allergy and rhinology: allergic rhinitis. Int Forum Allergy Rhinol. 2018;8(2):108-352.
3. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341(7):468-475.
4. Creticos PS. Advances in sublingual immunotherapy for allergic rhinitis and asthma. Immunol Allergy Clin North Am. 2016;36(1):1-19.

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