What are Indications for Allergen-specific Immunotherapy?

Patient Presentation
A 14-year-old female came to clinic with increasing seasonal allergic rhinitis symptoms during the fall. She had increased her cetirizine to 60 mg day and nasal fluticasone to 2 puffs twice a day but still had significant symptoms. Her parents reported that she had snoring without apnea, was always mouth-breathing and had a de-nasal voice. Her running coaches had talked with her twice over the running season as they noticed that she was noticeably pale, and had more problems breathing over the course of her daily workouts. The main reason she came in was that she felt she could not breath at the end of her cross country races because she was “full of snot” and couldn’t catch her breath. “Maybe I can really run if I can breath,” she commented. The past medical history showed mild intermittent asthma with albuterol use averaging 1x/year, seasonal allergic rhinitis usually from March to November that had been resistant to fexofenadine and montelukast in the past. She also had some mild xerosis that had never needed steroid creams. She also had a history of moderate nasal stuffiness when in contact with cats. The family history was positive for mild seasonal allergic rhinitis in some family members. The review of systems was otherwise negative.

The pertinent physical exam showed a healthy female with normal vital signs and weight that was 25% and height that was 50%. She had allergic shiners and cobblestoning of her palpebral conjunctiva. Her nose showed significant edema and a bluish color. With pinching one nare at a time, where was no air movement in either nare. She also had cobblestoning of her posterior pharynx. Her lungs were clear. She had mild dry skin. The rest of her examination was negative.

The diagnosis of persistent seasonal allergic rhinitis that was not effectively treated by medications was made. She was referred to an allergist and skin testing found her to be allergic to several grass pollens, Alternaria alternata mold and cat dander. She was restarted on fexofenadine and montelukast daily and began allergen-specific immunotherapy. At her next appointment she was feeling better but it was also during the winter when she usually improved.

Allergen-specific immunotherapy (AIT) is a disease modifying treatment for allergic disease. Sometimes referred to as desensitization, the premise is to expose the patient to small but regular amounts of a specific antigen thereby building tolerance within the patient to the allergen. AIT is often underused because of safety concerns and lack of appropriately trained health care providers and facilities to safely carry out AIT treatment. There are 4 main AIT treatments options currently:

  • SCIT – subcutaneous immunotherapy
    • Allergen is injected into the subcutaneous skin
    • “Shots are effective in treating reactions to many allergens, including trees, grass, weeds, mold, house dust, dander, and insect stings.”
    • SCIT is safe when used for selected individuals and given by trained health care providers in a setting that has immediate access to treatment for anaphylaxis and resuscitation.
    • Reactions are infrequent and usually localized with erythema or hives. Rarely anaphylaxis can occur.
    • Patients with concomitant asthma have an increased risk of severe bronchospasm. Patients should also not exercise for 2 hours before or after injection.
  • SLIT – sublingual immunotherapy
    • Allergen drops or tablets are placed and held under the tongue for several minutes and then swallowed. Used for food allergies such as peanut allergy.
    • Ragweed and pollen tablets and drops used in other countries. In the US tablets for grass, ragweed and house dust mite are available.
    • Reactions are more common at the beginning of treatment with problems such as oropharyngeal pruritis and angioedema occurring
  • OIT – oral immunotherapy
    • Allergen in tablet/capsule or other measured allergy (i.e. peanut powder) is swallowed. Commonly OIT is used for milk, eggs and peanuts allergy.
  • EPIT – epicutaneous immunotherapy
    • Allergen patches are placed on the upper body and changed daily. Used for peanut allergy and has modest effects while being used but not of sustained benefit

In general, single antigens are more effective than mixtures of antigens for SCIT but may be necessary. Both SCIT and SLIT have been found to have benefit for some years after stopping therapy. Both SCIT and SLIT are safe to use. SLIT appears to have a better safety profile but there are no head to head comparisons of efficacy. “The ultimate goal of AIT safety is to completely prevent fatal reactions, but one must consider that with such treatment amounts of the causative allergen much larger than those associated to natural exposure and administered, the potential risk is unlikely to be completely eliminated.”

Food allergies affect ~4% of children and 1% of adults in the U.S. Most common allergens in the U.S. are milk, eggs, peanuts, tree nuts, soy, wheat, fish and shellfish. Milk and eggs are commonly outgrown by school age but peanut allergy is usually life-long. The LEAP study (Learning Early About Peanut Allergy – http://www.leapstudy.co.uk) found a decrease in peanut allergy at 60 months of age with early introduction of peanut foods to infants. A review can be found here along with recommendations for introduction of peanut allergy to infants.

Patients must have confirmed skin or in vitro testing for specific antigens before any type of AIT is initiated.

Patients and families should have reasonable expectations for AIT:

  • Treatment will not be curative and symptoms may only be reduced – typically 30-40% symptom reduction for allergic rhinitis
  • Effectiveness often continues after completed treatment but it depends on the allergen and the patient
  • Families need to commit to treatment that is usually for 3 years or longer, and consider medical cost, transportation, time in the clinic and other arrangements that are necessary such as absences from school, how treatment over vacations will occur etc.
    Economic analyses find AIT to be cost effective but the amounts depend on the type of AIT and the analysis.

  • Symptom improvement may not be seen for several months

Contraindications to AIT include:

  • Absolute
    • Uncontrolled or unstable asthma
    • No initiation in patients receiving beta-blockers as these can make anaphylaxis difficult to treatment
  • Relative
    • Autoimmune disorders
    • Chronic disorders that impair tolerance to bronchospasm or hypotension
    • Immunodeficiency and immunosuppressive agent use
    • Malignancy

Indications for allergy testing and allergy referral can be reviewed here.

Learning Point
Immunotherapy indications include:

  • IgE medicated seasonal pollen induced rhinitis where patients have not responded to optimal pharmacological management especially those with moderate to severe intermittent symptoms or persistent symptoms
  • Systemic reactions to hymenoptera venom
  • Animal danger or house dust mite allergy where patients have not responded to rigorous allergen avoidance and pharmacological management

Questions for Further Discussion
1. What conditions are recommended for SLIT therapy administration?
2. How do these conditions differ from SCIT therapy administration?
3. When should skin testing versus in vivo allergy testing be used?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Allergy and Hayfever.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Frati F, Ridolo E, Fuiano N, et.al. Safety of sublingual immunotherapy in children. Expert Opin Drug Saf. 2014 Jul;13(7):947-53.

Walker SM, Durham SR, Till SJ, et.al.; British Society for Allergy and Clinical Immunology. Immunotherapy for allergic rhinitis. Clin Exp Allergy. 2011 Sep;41(9):1177-200.

Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et.al. International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016 Feb;137(2):358-68.

Meltzer EO. Hot Topics in Primary Care: Sublingual Immunotherapy: A Guide for Primary Care. J Fam Pract. 2017 Apr;66(4 Suppl):S58-S63.

Pajno GB, Bernardini R, Peroni D, et.al.; Allergen-specific Immunotherapy panel of the Italian Society of Pediatric Allergy and Immunology (SIAIP). Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report. Ital J Pediatr. 2017 Jan 23;43(1):13.

Berings M, Karaaslan C, Altunbulakli C, Gevaert P, Akdis M, Bachert C, Akdis CA. Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance. J Allergy Clin Immunol. 2017 Nov;140(5):1250-1267.

Jones SM, Burks AW. Food Allergy. N Engl J Med. 2017 Sep 21;377(12):1168-1176.

Allergy Shot Overview. American College of Allergy, Asthma, and Immunology.
Available from the Internet at http://acaai.org/allergies/treatment/allergy-shots-immunotherapy (cited 1/12/18).

Allergy Immunotherapy. American College of Allergy, Asthma, and Immunology.
Available from the Internet at http://acaai.org/allergies/allergy-treatment/allergy-immunotherapy (cited 1/12/18).

Allergy Tablets (Sublingual Immunotherapy). American College of Allergy, Asthma, and Immunology.
Available from the Internet at http://acaai.org/allergies/allergy-treatment/sublingual-immunotherapy-slit/allergy-tablets-sublingual-immunotherapy (cited 1/12/18).

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa