Immunotherapy

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Basics of Immunotherapy - Immune Tune-Up

  • Definition: Therapeutic administration of allergens to induce immune tolerance in allergic individuals, modifying the natural course of allergic disease.
  • Goal: Achieve long-term symptom remission, prevent new sensitizations, and improve quality of life.
  • Mechanism of Action:
    • Shifts immune response from Th2 (pro-allergic) to Th1 (protective).
    • Induces regulatory T cells (Tregs) & regulatory B cells (Bregs).
    • ↑ Production of blocking antibodies (IgG4).
    • ↓ Allergen-specific IgE levels over time.
    • ↓ Mast cell, basophil, and eosinophil reactivity.
  • Core Principle: Gradual, controlled exposure to increasing doses of specific allergens.

⭐ Immunotherapy is the only disease-modifying treatment for allergic diseases.

Immunotherapy mechanism: Th2 to Th1 shift

Allergen Immunotherapy (AIT) - Allergy Avengers Assemble

  • Goal: Induce allergen-specific tolerance, modify disease course.

  • Mechanism: ↑Treg, IL-10, IgG4 (blocking Ab); ↓IgE, mast cell reactivity; Th2→Th1 shift.

  • Indications:

    • Allergic rhinitis/conjunctivitis (mod-severe, persistent).
    • Allergic asthma (mild-mod, controlled, allergen confirmed).
    • Venom hypersensitivity (VIT highly effective).
    • Atopic dermatitis (select cases with aeroallergens).
    • Criteria: IgE-mediated allergy, allergen unavoidable, meds/avoidance insufficient.
  • Contraindications:

    • Absolute: Uncontrolled asthma (FEV1 < 70%), active systemic autoimmune disease, malignancy.
    • Relative: Significant CVD, β-blockers/ACE-i (esp. SCIT), poor adherence, pregnancy (initiation).
  • SCIT vs. SLIT:

⭐ Sublingual Immunotherapy (SLIT) generally has a better safety profile than Subcutaneous Immunotherapy (SCIT), especially regarding systemic reactions.

  • Duration: Typically 3-5 years for sustained benefit post-discontinuation.
  • 📌 AIT: Alleviates Immune Troubles!

AIT Practicalities - Dose, Duration, Dangers

  • Dosing & Standardization:
    • Allergen extracts standardized: Bioequivalent Allergy Units (BAU), Allergy Units (AU).
    • Phases: Build-up (weekly/bi-weekly, gradually ↑dose) & Maintenance (monthly, constant highest tolerated dose).
    • Dose adjustments for missed doses, local/systemic reactions, or new allergen vials.
  • Duration for Tolerance:

    ⭐ The standard duration for allergen immunotherapy (SCIT/SLIT) to achieve long-term tolerance is typically 3-5 years.

    • Decision to stop based on sustained clinical benefit and patient/physician assessment.
  • Dangers & Management:
    • Local Reactions: Common (erythema, pruritus, swelling at injection site). Manage with cold compresses, topical corticosteroids, oral antihistamines.
    • Systemic Reactions (SRs): Range from mild (urticaria, rhinitis) to severe anaphylaxis.
      • Risk factors: Uncontrolled asthma, high allergen dose, dosing errors, concurrent illness.
      • 📌 Anaphylaxis: Epinephrine (0.01 mg/kg of 1:1000 solution IM, max 0.3-0.5 mg per dose), O2, IV fluids, antihistamines, corticosteroids. Observe for 4-6 hours.
    • Contraindications (Absolute): Severe uncontrolled asthma, active autoimmune disease. (Relative): Beta-blocker/ACE inhibitor use, significant cardiovascular disease. Grading Systemic Reactions to Allergen Immunotherapy

Special ITx - Venom Victors & Food Frontiers

  • Venom Immunotherapy (VIT):
    • Highly effective for Hymenoptera venom allergy (bees, wasps, ants).
    • Significantly ↓ anaphylaxis risk from future stings.
    • Protocol: Initial build-up, then maintenance every 4-8 weeks for 3-5 years.
    • Indications: Systemic reaction to sting + positive venom IgE or skin test.

    ⭐ Venom immunotherapy (VIT) is nearly 95-98% effective in preventing anaphylaxis from future stings in sensitized individuals.

  • Food Immunotherapy (FIT):
    • Oral (OIT): Aims to desensitize to specific foods (e.g., peanut, milk, egg). Involves ingesting gradually increasing allergen doses. Requires strict medical supervision.
    • Sublingual (SLIT): Alternative to OIT for food allergy; potentially fewer systemic reactions but less established for food allergens compared to aeroallergens or VIT for venom.

High‑Yield Points - ⚡ Biggest Takeaways

  • Allergen Immunotherapy (AIT) aims to induce allergen-specific immune tolerance.
  • Key indications: severe allergic rhinitis, allergic asthma, and insect venom hypersensitivity.
  • Mechanism: Shifts from Th2 to Th1 response, increases Treg cells and IgG4 blocking antibodies.
  • Routes: Subcutaneous (SCIT) and Sublingual (SLIT) are primary methods.
  • Duration: Typically 3-5 years for sustained, disease-modifying effects.
  • SCIT carries a risk of anaphylaxis; requires post-injection observation.
  • AIT can lead to long-term remission of allergic symptoms after completion of therapy.

Practice Questions: Immunotherapy

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Flashcards: Immunotherapy

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