Allergenics

Introduction

Allergenics, also referred to as allergen immunotherapy (AIT) agents, are therapeutic preparations used in the prevention and treatment of allergic diseases such as allergic rhinitis, allergic conjunctivitis, asthma, and venom hypersensitivity. Unlike antihistamines and corticosteroids that only provide symptomatic relief, allergenics modify the underlying immune response by inducing long-term tolerance to specific allergens.

They are formulated from natural allergen extracts (pollens, animal danders, insect venoms, dust mites, and molds) or recombinant allergens, standardized in terms of potency and protein content. Allergenics are delivered via subcutaneous injections (SCIT) or sublingual tablets/drops (SLIT) over several years, resulting in sustained clinical benefit even after therapy is discontinued.

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Mechanism of Action

Allergenics function through immunological reprogramming, gradually shifting the immune system from an allergic (Th2-dominant) to a more tolerant (Th1 and Treg-dominant) state.

Key immunological mechanisms include:

1. Induction of regulatory T cells (Tregs) → secretion of IL-10 and TGF-β, suppressing IgE-mediated responses.

2. Increased allergen-specific IgG4 (“blocking antibody”) → competes with IgE for allergen binding, reducing mast cell and basophil activation.

3. Suppression of mast cells and basophils → reduced histamine and leukotriene release.

4. Immune deviation → shifting immune response away from Th2 cytokines (IL-4, IL-5, IL-13) toward Th1 cytokines (IFN-γ).

This disease-modifying effect differentiates allergenics from antihistamines, leukotriene receptor antagonists, or corticosteroids, which provide only temporary symptom relief.

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Classification of Allergenics

1. Subcutaneous Immunotherapy (SCIT) – “allergy shots” administered in a clinic.

   • Allergen extracts are injected at gradually increasing doses, followed by maintenance injections.

   • Common allergens: pollens (grass, ragweed, birch), dust mites, animal dander, molds, insect venoms.

2. Sublingual Immunotherapy (SLIT) – tablets or drops placed under the tongue.

   • Administered daily at home after initial supervision.

   • Approved mainly for pollens and dust mites.

3. Venom Immunotherapy (VIT) – specialized immunotherapy with bee or wasp venom extracts.

   • Indicated for patients with life-threatening anaphylaxis after insect stings.

4. Experimental/Next-generation formulations

   • Recombinant allergens

   • Hypoallergenic derivatives

   • Allergoids (chemically modified extracts with reduced allergenicity but preserved immunogenicity)

   • Peptide-based vaccines

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Therapeutic Uses

• Allergic rhinitis (hay fever) – especially when symptoms are severe, prolonged, or unresponsive to antihistamines and nasal corticosteroids.

• Allergic asthma – for patients with IgE-mediated asthma triggered by specific allergens.

• Conjunctivitis associated with allergic rhinitis.

• Venom hypersensitivity – to prevent life-threatening systemic reactions.

• Food allergies – under research, with peanut and milk oral immunotherapy showing promise.

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Allergenics: Generic Preparations and Typical Doses

1. Grass Pollen Allergen Extracts (Subcutaneous or Sublingual)

• Generics: Timothy grass, Rye grass, Orchard grass, Bermuda grass extracts.

• Dosing (SLIT tablet, e.g., timothy grass 2800 BAU):

  • One tablet daily, starting at least 12 weeks before pollen season and continuing throughout.

• Dosing (SCIT):

  • Build-up phase: injections weekly or biweekly with escalating doses.

  • Maintenance: every 2–4 weeks for 3–5 years.

2. Ragweed Pollen Extract (Ambrosia artemisiifolia)

• Indication: Ragweed-induced allergic rhinitis.

• SLIT dose: 12 Amb a 1-U (standardized allergen unit) tablet once daily before and during pollen season.

3. Tree Pollen Extracts (Birch, Alder, Hazel)

• Indication: Seasonal allergic rhinitis.

• SCIT dosing: Escalating microgram protein doses injected weekly, then monthly maintenance.

4. Dust Mite Allergen Extracts (Dermatophagoides pteronyssinus, D. farinae)

• SLIT tablet dose: 12 SQ-HDM (standardized quality house dust mite units) once daily.

• SCIT dosing: Initial buildup from 0.1 mL of 10 SQ-U to 1 mL of 100,000 SQ-U monthly.

5. Cat and Dog Dander Extracts

• Indication: Allergic rhinitis/asthma triggered by animal exposure.

• SCIT dosing: Escalating microgram doses injected weekly, then monthly for 3–5 years.

6. Mold Allergen Extracts (Alternaria, Cladosporium, Aspergillus)

• SCIT dosing: Gradual titration from low μg doses to standardized maintenance (varies by manufacturer).

7. Venom Extracts (Honeybee, Yellow Jacket, Hornet, Wasp, Fire Ant)

• Indication: Systemic anaphylaxis from insect stings.

• SCIT dosing:

  • Build-up phase: Weekly injections starting at 0.1–1 μg.

  • Maintenance: 100 μg venom per injection every 4–8 weeks.

• Duration: At least 3–5 years (sometimes lifelong in high-risk patients).

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Contraindications

• Severe or uncontrolled asthma (risk of fatal reaction).

• Active autoimmune disease or malignancy (theoretical risk of immune modulation).

• Current use of beta-blockers (interferes with epinephrine treatment of anaphylaxis).

• Pregnancy (initiation of therapy contraindicated, but continuation may be considered if already stable).

• History of severe systemic or anaphylactic reaction to immunotherapy.

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Adverse Effects

Local Reactions

• SCIT: Redness, swelling, and itching at injection site.

• SLIT: Oral pruritus, throat irritation, mild swelling of lips/tongue.

Systemic Reactions

• Rhinoconjunctivitis exacerbation

• Urticaria

• Asthma flare-up

• Angioedema

Severe Reactions

• Anaphylaxis: rare but life-threatening, especially with SCIT → mandates administration in a medical setting with epinephrine available.

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Precautions

• First-dose supervision: Initial SLIT or SCIT dose must be given under medical observation.

• Asthma control: Patients should have stable asthma before starting therapy.

• Carrying epinephrine: Patients at risk of systemic reactions should be prescribed an auto-injector (e.g., epinephrine 0.3 mg).

• Adherence: Daily dosing (SLIT) or regular clinic visits (SCIT) are essential for effectiveness.

• Treatment duration: Typically 3–5 years for sustained tolerance.

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Drug Interactions

1. Beta-blockers (propranolol, atenolol, metoprolol)

   • Contraindicated due to impaired response to epinephrine in case of anaphylaxis.

2. ACE inhibitors (lisinopril, enalapril, ramipril)

   • May increase severity of anaphylaxis and interfere with epinephrine response.

3. Immunosuppressants (methotrexate, cyclosporine, corticosteroids)

   • May alter immune modulation and reduce efficacy.

4. Concomitant allergen exposure (e.g., high pollen season with dose escalation)

   • Increases risk of systemic reactions → requires dose adjustment.

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Clinical Considerations

• SCIT vs SLIT:

  • SCIT is more effective but requires clinic visits and has higher risk of systemic reactions.

  • SLIT is safer and more convenient, but adherence is critical.

• Pediatric use:

  • SLIT is generally safe and effective in children ≥5 years.

  • SCIT can be used in children but requires careful monitoring.

• Long-term efficacy:

  • Clinical benefits may persist for years after discontinuation.

  • Reduces risk of new sensitizations and progression from rhinitis to asthma.

• Patient selection:

  • Best candidates are those with IgE-mediated allergic disease confirmed by skin testing or specific IgE measurement.

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Emerging Developments

• Recombinant allergen vaccines: Engineered proteins with defined composition, reducing variability of natural extracts.

• Peptide-based immunotherapy: Short allergenic peptides to induce tolerance without IgE cross-linking, lowering risk of anaphylaxis.

• Epicutaneous immunotherapy (EPIT): Allergen patches applied to the skin (under study for peanut allergy).

• DNA-based vaccines: Investigational approaches aiming for long-lasting tolerance