# 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

| Feature | SCIT | SLIT |
|---------|------|------|
| Route | Subcutaneous injection | Sublingual tablet/drops |
| Administration | Office-based | Home (after first dose in office) |
| Frequency | Weekly (build-up), then q2-4 weeks | Daily |
| Multi-allergen | Yes (standard practice) | Limited (FDA tablets are single-allergen) |
| Systemic reaction risk | Higher (0.1-0.2% per injection) | Extremely rare |
| Observation period | 30 minutes post-injection | First dose only |
| Efficacy | Strong evidence, multi-allergen | Strong for single allergens |
| Duration | 3-5 years | 3-5 years |
| Compliance | Guaranteed (office visits) | Patient-dependent |

## 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.

![Stepwise dose escalation schedule for subcutaneous immunotherapy showing build-up and maintenance phases](/images/scit-dose-schedule.jpg)

## 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.

![Comparison of SCIT and SLIT immunotherapy delivery routes and key differences](/images/scit-vs-slit-comparison.jpg)

## 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.

![Diagram showing the immunologic shift from Th2 to Treg dominance during successful immunotherapy](/images/immunotherapy-mechanism.jpg)

## 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.