What is the cause of large skin erythema and wheal after allergen immunotherapy (AIT) injection maintenance dose?

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Last updated: March 24, 2025View editorial policy

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From the Guidelines

A large skin erythema and wheal after an allergen immunotherapy maintenance dose is likely caused by a local allergic reaction to the injected allergen, which triggers mast cell degranulation and histamine release at the injection site, causing inflammation and swelling 1. This reaction is fairly common, with a frequency ranging from 26% to 86% of injections, and is not always predictive of subsequent systemic reactions 1. However, patients with a greater frequency of large local reactions might be at an increased risk for future systemic reactions 1.

Key Considerations

  • The size of the reaction should be documented and reported to the allergist before the next scheduled dose, as they may need to adjust the maintenance dose 1.
  • Local reactions can be managed with oral antihistamines, such as cetirizine 10mg or diphenhydramine 25-50mg, and topical corticosteroids like hydrocortisone 1% cream 1.
  • If the reaction is accompanied by systemic symptoms like difficulty breathing, throat tightness, or dizziness, epinephrine (if prescribed) should be used and emergency care should be sought immediately 1.

Management

  • Apply a cold compress to the affected area to reduce symptoms.
  • Administer an oral antihistamine to reduce symptoms.
  • For severe reactions, apply topical corticosteroids to the site 2-3 times daily for 1-2 days.
  • Notify the allergist before the next scheduled dose to determine if the maintenance dose needs to be adjusted.

Prevention of Systemic Reactions

  • While local reactions are common and usually not dangerous, large reactions (>5cm) may indicate the need for dose adjustment to prevent potential systemic reactions in the future 1.
  • The allergist should review the course of immunotherapy to determine whether the risk/benefit assessment justifies continuation of immunotherapy 1.
  • If there are recurrent systemic reactions at the maintenance dose, one management consideration would be to decrease the maintenance dose provided the dose is still high enough to benefit the patient 1.

From the Research

Causes of Large Skin Erythema and Wheal after Allergen Immunotherapy (AIT) Injection Maintenance Dose

  • The cause of large skin erythema and wheal after AIT injection maintenance dose can be attributed to an allergic reaction, specifically anaphylaxis, which is a known risk factor associated with immunotherapy 2.
  • The reaction may be due to the release of histamine and other chemical mediators from mast cells or basophils, which can cause increased blood flow, permeability, and swelling in the affected area 3.
  • Another possible cause is an injection site reaction, which is a local phenomenon characterized by swelling, erythema, pruritus, and pain around the site of injection 4.
  • The use of biological agents, including allergen immunotherapy, can also cause injection site reactions, which are not necessarily correlated with drug efficacy or development of antidrug antibodies 4.
  • Additionally, the late phase of the immediate wheal and flare skin reaction, which occurs 6-12 hours after challenge, can also contribute to the development of large skin erythema and wheal 3.

Risk Factors

  • Errors in dosage, failure to reduce the dosage after a longer than scheduled interval, administration of the wrong extract, and concurrent use of beta-adrenergic blocking agents are some of the risk factors associated with severe reactions to immunotherapy, including anaphylaxis 2.
  • The type of allergen used in immunotherapy can also play a role in the development of large skin erythema and wheal, with some allergens being more likely to cause reactions than others 5, 6.

Management

  • Clinicians performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis, which is a life-threatening allergic reaction 6.
  • Patients experiencing large skin erythema and wheal after AIT injection maintenance dose should be monitored closely and treated promptly to prevent the reaction from worsening 2, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fatalities following allergen immunotherapy.

Clinical reviews in allergy & immunology, 2004

Research

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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