Allergen immunotherapy: Difference between revisions

Allergen immunotherapy
Allergen immunotherapy
	An Alutard SQ injection kit
Other names	Desensitization, hypo-sensitization
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Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for environmental allergies (such as insect bites) and asthma.^[1]^[2] Immunotherapy involves exposing people to larger and larger amounts of allergens in an attempt to change the immune system's response.^[1]

Meta-analyses have found that injections of allergens under the skin are effective in the treatment of allergic rhinitis in children^[3]^[4] and in asthma.^[2] The benefits may last for years after treatment is stopped.^[5] It is generally safe and effective for allergic rhinitis, allergic conjunctivitis, allergic forms of asthma, and stinging insects.^[6] The evidence also supports the use of sublingual immunotherapy against rhinitis and asthma, but it is less strong.^[5] In this form the allergen is given under the tongue and people often prefer it to injections.^[5] Immunotherapy is not recommended as a stand-alone treatment for asthma.^[5]

Side effects during sublingual immunotherapy treatment are usually local and mild and can often be eliminated by adjusting the dosage.^[7] Anaphylaxis during sublingual immunotherapy treatment has occurred on rare occasions.^[7]

Potential side effects related to subcutaneous immunotherapy treatment for asthma and allergic rhinoconjunctivitis include mild or moderate skin or respiratory reactions.^[8] Severe side effects such as anaphylaxis during subcutaneous immunotherapy treatment are relatively uncommon.^[8]

Discovered by Leonard Noon and John Freeman in 1911, allergen immunotherapy is the only medicine known to tackle not only the symptoms but also the causes of respiratory allergies.^[9] A detailed diagnosis is necessary to identify the allergens involved.^[10]

Types

Subcutaneous

Subcutaneous immunotherapy (SCIT), also known as allergy shots, is the historical route of administration and consists of injections of allergen extract, which must be performed by a medical professional. Subcutaneous immunotherapy protocols generally involve weekly injections during a build-up phase, followed by a monthly maintenance phase that consists of injections for a period of 3–5 years.^[11] The build-up phase involves the patient being administered injections which contain increasing amounts of allergens about one to two times per week. The length of the build-up phase is dependent upon how often injections are administered, but normally ranges from three to six months. After the effective dose is reached, the maintenance phase is implemented, which varies depending upon an individual's response to the build-up phase.^[12]

When accounting for a person's age, type of allergen, and severity of allergy, there is a high probability that subcutaneous allergen immunotherapy may provide greater clinical and immunological responses than sublingual allergen immunotherapy.^[13] Compared to sublingual allergen immunotherapy, there are no significant differences observed in quality of life.^[13]

It is possible, but rare (1/2.5 million), that people undergoing subcutaneous allergen immunotherapy may experience a fatal anaphylactic event.^[14] Subcutaneous allergen immunotherapy adverse events vary significantly depending on different allergenic extracts and the application of different allergen immunotherapy schedules.^[14]

Allergen immunotherapy schedules include the "cluster" approach, which involves administering several doses sequentially in a single day; a "conventional" approach, which involves incrementally increasing the dose over approximately 15 weeks; and the "rush" approach, which involves administering incremental doses at intervals of 15–60 minutes over 1–3 days.^[14]

It is challenging to perform an adequate risk assessment on the use of subcutaneous allergen immunotherapy compared to other forms of allergen immunotherapy administration due to the variability of immunotherapy schedules and further research is required.^[14]

Sublingual

Sublingual immunotherapy involves putting drops or a tablet of allergen extracts under the tongue, which are then absorbed through the lining of the mouth. Sublingual immunotherapy has been demonstrated to be effective against rhinoconjunctivitis and asthma symptoms.^[15] This effectiveness, however, varies depending on the type of allergen.^[15] The strongest evidence for the efficacy of sublingual immunotherapy comes from studies that used grass allergens or mite allergens to alleviate allergic rhinitis symptoms; the evidence shows modest improvement.^[16]

Sublingual immunotherapy is used to treat allergic rhinitis, often from seasonal allergies, and is typically given in several doses over a 12-week period.^[17] It works best when given 12 weeks before the start of the pollen season.^[17] The first dose is given by a physician to monitor for any rare reactions or anaphylaxis.^[17] Subsequent doses can be taken at home^[17] which makes this a convenient alternative to subcutaneous immunotherapy.

While a number of side effects have been associated with sublingual immunotherapy, serious adverse effects are very rare (about 1.4/100,000 doses), and there has not been a reported fatality.^[15] There have been a small number of reports of anaphylaxis.^[15] The majority of side effects are 'local' and usually resolve within a few days.^[15] They include swelling of the mouth, tongue or lip, throat irritation, nausea, abdominal pain, vomiting, diarrhea, heartburn, and uvular edema.^[15] It is not yet clear if there are any risk factors that might increase a person's susceptibility to these adverse effects.^[15] Sublingual immunotherapy appears to be better tolerated than subcutaneous immunotherapy and causes fewer side effects.^[15] The safety of sublingual immunotherapy has not been studied extensively in people with chronic immunodeficiency or autoimmune disorders.^[15]

Oral

Oral immunotherapy (OIT) involves feeding an allergic individual increasing amounts of a food allergen in order to raise the threshold which triggers a reaction.^[18] Long-term, many study participants still experienced mild allergic reactions or needed to regularly consume the allergen to maintain desensitivity.^[19] Additionally, oral immunotherapy is known to have an increased risk in the probability of needing epinephrine in patients who take it.^[20] Currently, the U.S. Food and Drug Administration has not approved any oral immunotherapy agents for asthma.^[21] In January 2020, the FDA approved Palforzia for mitigating "allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts."^[22]^[23] It is the first drug approved for peanut allergies. It will not allow allergic people able to eat normal amounts of peanuts, but helps prevent allergies due to accidental eating.^[24]

Transdermal

Transdermal immunotherapy (TDIT) involves skin-induced suppression via epicutaneous (EC) application of an antigen in order to raise the threshold which triggers a reaction.^[25]

Mechanism of action

In desensitization immunotherapy the aim is to induce or restore tolerance to the allergen by reducing its tendency to induce IgE production. People are desensitized through the administration of escalating doses of allergen that gradually decreases the IgE-dominated response. The objective of immunotherapy is to direct the immune response away from humoral immunity and toward cellular immunity, thereby encouraging the body to produce fewer IgE antibodies and more CD4+ T regulatory cells that secrete IL-10 and TGF-βべーた, which skews the response away from IgE production.^[26]

Oral immunotherapy also creates an increase in allergen-specific IgG4 antibodies and a decrease in allergen-specific IgE antibodies, as well as diminished mast cells and basophils, two cell types that are large contributors to allergic reaction.^[27]^[28]

Protocol

Reactivity is tested using oral food challenges or with skin prick tests. Phases 1 & 2 of sublingual immunotherapy are conducted in a supervised clinical setting. However, phase 3 can be done at home.^[27]

History

In the late 19th century and early 20th century, allergic conditions were increasingly attracting both medical attention (as an emerging public health problem) and scientific interest (aided by progress in biochemical techniques and the development of molecular and pathogenic theories). However, the many and varied treatment approaches were very unscientific.^{[citation needed]}

The British physicians Noon and Freeman were the first researchers to test pollen allergen immunotherapy in humans. Noon and Freeman, researchers at the Department of Therapeutic Inoculation at St. Mary's Hospital in London, published their findings in The Lancet in 1911.^[29]^[30]^{[non-primary source needed]}^{[failed verification]} Building on the observations of his predecessors Bostock, Blackley and Dunbar, Noon noted that people with hay fever "sometimes become cured" and that this was possibly because they "have had the good fortune to develop an active immunity against the toxin." He hypothesized that by injecting people with hay fever with small amounts of a pollen "toxin", a state of immunity could be achieved.^[31]

Allergen immunotherapy was part of mainstream medical practice for hay fever treatment in the 1930s.^{[citation needed]}

Society and culture

Sublingual immunotherapy drops are currently commercialized and used in most European and South American countries, and in Australia and Asian countries. In most European countries, national regulations allow marketing of allergen products as "named patient preparations" (NPPs). In the United States, drop formulations have not yet received FDA approval, though off-label prescription is becoming common.^[32] In 2014, the FDA approved a once-daily sublingual tablet containing allergen extracts for the treatment of "hay fever" (allergic rhinitis with or without conjunctivitis).^[33]

Recognition by international agencies

The use of subcutaneous immunotherapy for treatment of environmental-based allergies and asthma is well supported by the majority of national and international allergy groups such as the World Allergy Organization, Canadian Society of Allergy and Immunology, European Academy of Allergy and Clinical Immunology, and the American Academy of Allergy, Asthma and Immunology.^[34] The use of sublingual immunotherapy is supported by few allergy agencies in order to allow for more investigation to occur on its practical use.^[34] Oral immunotherapy is generally not recommended, however the EAACI recommends that this treatment only be administered at specialized centres with expert professionals.^[34]

Subcutaneous immunotherapy is both approved and regulated by the American Food and Drug Administration (FDA) and the European Medicinal Agency (EMEA).^[35] The FDA currently allows individual allergists to create the formula for each dosage, whereas the EMEA requires treatment extracts to be prepared at manufacturing sites.^[35] The FDA has approved sublingual therapy through the use of tablets, but has not approved specific formulation.^[35] The EMEA has also approved sublingual therapy through both tablets and solution, and this administration now accounts for 45% of immunotherapy treatments.^[35]

The FDA advisory board has supported the use of AR101, an oral immunotherapy, for patients with peanut allergies in 2019.^[20]

Science communication

Allergen immunotherapy is viewed as a beneficial way to curb allergies in the perspective of the media. It is seen where it can be covered by insurance and offer a more permanent solution than antihistamines or nasal steroids that treat symptoms, not the body's reaction.^[36] Communication about allergen immunotherapy is not described very often in the news media; it is usually only communicated by the science community. The scientific community describes allergen immunotherapy as a scientific solution that helps not only patients with allergies but also positively impacts the quality of life of them and others around them. As temperatures increase due to changing climates, pollen levels also increase.^[37] Allergies are becoming a more common problem among the public, which is why the science community advocates for allergen immunotherapy. Subcutaneous allergen immunotherapy, according to the scientific community, is an effective solution to allergies due to numerous positive studies.^[38]

Research

Oral immunotherapy

As of 2015^[update], oral immunotherapy's balance of risk to benefit for food allergies was not well studied.^[1] As of 2011^[update], OIT was under investigation as a treatment for a variety of common food allergies including peanuts, milk, and eggs. Studies involving OIT have shown desensitization towards the allergen. However, there are still questions about longevity of tolerance after the study has ended.^[39]^[27] However, almost every study has excluded people with severe allergen-induced anaphylaxis.^[28]

One approach being studied is in altering the protein structure of the allergen to decrease immune response but still induce tolerance. Extensive heating of some foods can change the conformation of epitopes recognized by IgE antibodies. In fact, studies show that regular consumption of heated food allergens can speed up allergy resolution. In one study, subjects allergic to milk were 16x more likely to develop complete milk tolerance compared to complete milk avoidance. Another approach regarding changes in protein is to change specific amino acids in the protein to decrease recognition of the allergen by allergen-specific antibodies.^[28]

Another approach to improving oral immunotherapy is to change the immune environment to prevent T_H2 cells from responding to the allergens during treatment. For example, drugs that inhibit IgE-mediated signaling pathways can be used in addition to OIT to reduce immune response. In 1 trial, the monoclonal antibody omalizumab was combined with high-dose milk oral immunotherapy and saw positive results. Several other trials are also currently being done combining omalizumab with OIT for a variety of food allergens. FAHF-2, a Chinese herbal mixture, has shown positive effects on the immune system and has been shown to protect mice from peanut-induced anaphylaxis. FAHF-2 was also well tolerated in a phase I study. While it is possible that omalizumab, FAHF-2 or other immunomodulatory agents alone might be able to treat dangerous allergies, combining these with OIT may be more effective and synergistic, warranting further investigation.^[28]

In addition, various adjuvants (nanoparticles) is a field of development that can be used for OIT. With the potential to modulate antigen release, it may one day be possible to take a pill containing nanoparticles that will modulate dosing, requiring fewer office visits.^[28]

Studies have also been done to determine the efficacy of OIT for multiple allergens simultaneously. One study concluded that multi-OIT would be possible and relatively, though larger studies would be necessary.^[40]

References

^ ^a ^b ^c "Allergen Immunotherapy". April 22, 2015. Archived from the original on 9 September 2016. Retrieved 15 June 2015.
^ ^a ^b Abramson MJ, Puy RM, Weiner JM (August 2010). "Injection allergen immunotherapy for asthma". The Cochrane Database of Systematic Reviews (8): CD001186. doi:10.1002/14651858.CD001186.pub2. PMID 20687065.
^ Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, et al. (August 2006). "Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials". Annals of Allergy, Asthma & Immunology. 97 (2): 141–8. doi:10.1016/S1081-1206(10)60004-X. PMID 16937742.
^ Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S (January 2007). "Allergen injection immunotherapy for seasonal allergic rhinitis". The Cochrane Database of Systematic Reviews. 2007 (1): CD001936. doi:10.1002/14651858.CD001936.pub2. PMC 7017974. PMID 17253469.
^ ^a ^b ^c ^d Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. (December 2009). "Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009". Allergy. 64 (Suppl 91): 1–59. doi:10.1111/j.1398-9995.2009.02309.x. PMC 3488881. PMID 20041860. S2CID 10420738.
^ Rank MA, Li JT (September 2007). "Allergen immunotherapy". Mayo Clinic Proceedings. 82 (9): 1119–23. doi:10.4065/82.9.1119. PMID 17803880.
^ ^a ^b "Sublingual Immunotherapy (SLIT)". ACAAI Public Website. 2015-01-05. Retrieved 2018-11-05.
^ ^a ^b Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, et al. (March 2014). "Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review". The Laryngoscope. 124 (3): 616–27. doi:10.1002/lary.24295. PMID 23832632. S2CID 8796632.
^ Durham S (2010). "One hundred years of allergen immunotherapy: Time to ring the changes". J Allergy Clin Immunol. 127 (1): 3–7. doi:10.1016/j.jaci.2010.11.032. PMID 21211638.
^ Sastre J (2013). "Molecular diagnosis and immunotherapy". Current Opinion in Allergy and Clinical Immunology. 13 (6): 646–650. doi:10.1097/ACI.0b013e328364f4c6. ISSN 1528-4050. PMID 24071714. S2CID 43357832.
^ van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, et al. (February 2000). "Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology". Allergy. 55 (2): 116–34. doi:10.1034/j.1398-9995.2000.00526.x. PMID 10726726. S2CID 39942935.
^ "Allergy Shots (Immunotherapy) | AAAAI." The American Academy of Allergy, Asthma & Immunology, 2019,
^ ^a ^b Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C (May 2013). "Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison". The Journal of Allergy and Clinical Immunology. 131 (5): 1361–6. doi:10.1016/j.jaci.2013.02.013. PMID 23557834.
^ ^a ^b ^c ^d Caminati M, Dama AR, Djuric I, Montagni M, Schiappoli M, Ridolo E, et al. (February 2015). "Incidence and risk factors for subcutaneous immunotherapy anaphylaxis: the optimization of safety". Expert Review of Clinical Immunology. 11 (2): 233–45. doi:10.1586/1744666X.2015.988143. PMID 25484197. S2CID 32045539.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, et al. (March 2014). "Sublingual immunotherapy: World Allergy Organization position paper 2013 update". The World Allergy Organization Journal. 7 (1): 6. doi:10.1186/1939-4551-7-6. PMC 3983904. PMID 24679069.
^ Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G (September 2010). "Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis". The Journal of Allergy and Clinical Immunology. 126 (3): 558–66. doi:10.1016/j.jaci.2010.06.013. PMID 20674964.
^ ^a ^b ^c ^d Pepper AN, Calderón MA, Casale TB (January 2017). "Sublingual Immunotherapy for the Polyallergic Patient". The Journal of Allergy and Clinical Immunology: In Practice. 5 (1): 41–45. doi:10.1016/j.jaip.2016.06.019. ISSN 2213-2198. PMID 27452888.
^ "The Current State of Oral Immunotherapy". American Academy of Allergy, Asthma, & Immunology. American Academy of Allergy, Asthma & Immunology. 4 February 2020. Retrieved 1 October 2023.
^ Feuille E, Nowak-Wegrzyn A (June 30, 2016). "Oral Immunotherapy for Food Allergies". Annals of Nutrition & Metabolism. 68: 18–31. doi:10.1159/000445391. JSTOR 48508034. PMID 27355816. S2CID 21655226.
^ ^a ^b Couzin-Frankel J (September 13, 2019). "First peanut allergy treatment gains backing from FDA advisory panel". Science. doi:10.1126/science.aaz5008.
^ U.S. Department of Health and Human Services. National Institutes of Health - National Heart Lung and Blood Institute (December 2020). "Can Immunotherapy Help with the Treatment of Allergic Asthma?" (PDF). Retrieved November 18, 2022.
^ "FDA approves first drug for treatment of peanut allergy for children". US Food and Drug Administration (Press release). 31 January 2020. Retrieved 31 January 2020. This article incorporates text from this source, which is in the public domain.
^ "Palforzia Approval Letter". U.S. Food and Drug Administration (FDA). 31 January 2020. Retrieved 13 February 2020.
^ "The FDA has approved the first drug to treat peanut allergies". Science News. 2020-02-04. Retrieved 2020-02-13.
^ Szczepanik M, Majewska-Szczepanik M (2016). "Transdermal immunotherapy: Past, present and future". Pharmacological Reports. 68 (4). US National Library of Medicine National Institutes of Health: 773–81. doi:10.1016/j.pharep.2016.04.004. PMID 27236747. S2CID 9714708.
^ Janeway's Immunobiology, 8th Edition, Chapter 14
^ ^a ^b ^c Le UH, Burks AW (2014). "Oral and sublingual immunotherapy for food allergy". The World Allergy Organization Journal. 7 (1): 35. doi:10.1186/1939-4551-7-35. PMC 4325942. PMID 25709745.
^ ^a ^b ^c ^d ^e Moran TP, Vickery BP, Burks AW (December 2013). "Oral and sublingual immunotherapy for food allergy: current progress and future directions". Current Opinion in Immunology. 25 (6): 781–7. doi:10.1016/j.coi.2013.07.011. PMC 3935613. PMID 23972904.
^ Noon L, Cantab BC (1911). "Prophylactic inoculation against hay fever". Lancet. 177 (4580): 1572–3. doi:10.1016/s0140-6736(00)78276-6.
^ Freeman J, Noon L (1911). "Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine". Lancet. 2 (4594): 814–7. doi:10.1016/s0140-6736(01)40417-x.
^ Bostock J. "Case of a periodical affection of the eyes and chest. Med Chir Trans. 1819;10:161.
^ Shute N (27 March 2013). "Allergy Drops Under the Tongue May be Fine Alternative to Shots". NPR. Retrieved 22 July 2013.
^ "Approval Letter - ORALAIR". FDA. Retrieved 20 June 2017.
^ ^a ^b ^c Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. (September 2015). "International consensus on allergy immunotherapy". The Journal of Allergy and Clinical Immunology. 136 (3): 556–68. doi:10.1016/j.jaci.2015.04.047. PMID 26162571.
^ ^a ^b ^c ^d Cox L, Jacobsen L (December 2009). "Comparison of allergen immunotherapy practice patterns in the United States and Europe". Annals of Allergy, Asthma & Immunology. 103 (6): 451–59, quiz 459–61, 495. doi:10.1016/S1081-1206(10)60259-1. PMID 20084837.
^ "With a litter of tactics, scientists work to tame cat allergies". Science News. 2020-02-13. Retrieved 2020-11-15.
^ Barnes CS, Alexis NE, Bernstein JA, Cohn JR, Demain JG, Horner E, et al. (March 15, 2013). "Climate Change and Our Environment: The Effect on Respiratory and Allergic Disease". The Journal of Allergy and Clinical Immunology in Practice. 1 (2): 137–141. doi:10.1016/j.jaip.2012.07.002. ISSN 2213-2198. PMC 3654689. PMID 23687635.
^ Larsen JN, Broge L, Jacobi H (2016-01-01). "Allergy immunotherapy: the future of allergy treatment". Drug Discovery Today. 21 (1): 26–37. doi:10.1016/j.drudis.2015.07.010. ISSN 1359-6446. PMID 26327511.
^ Land MH, Kim EH, Burks AW (May 2011). "Oral desensitization for food hypersensitivity". Immunology and Allergy Clinics of North America. 31 (2): 367–76, xi. doi:10.1016/j.iac.2011.02.008. PMC 3111958. PMID 21530825.
^ Bégin P, Winterroth LC, Dominguez T, Wilson SP, Bacal L, Mehrotra A, et al. (January 2014). "Safety and feasibility of oral immunotherapy to multiple allergens for food allergy". Allergy, Asthma, and Clinical Immunology. 10 (1): 1. doi:10.1186/1710-1492-10-1. PMC 3913318. PMID 24428859.

External links

"American Academy of Allergy, Asthma, and Immunology" information and articles of interest.
"American College of Allergy, Asthma, and Immunology" information and articles of interest.
"American Board of Allergy and Immunology" American Board of Allergy and Immunology

[NIH2015Imm-1] "Allergen Immunotherapy". April 22, 2015. Archived from the original on 9 September 2016. Retrieved 15 June 2015.

[Abra2010-2] Abramson MJ, Puy RM, Weiner JM (August 2010). "Injection allergen immunotherapy for asthma". The Cochrane Database of Systematic Reviews (8): CD001186. doi:10.1002/14651858.CD001186.pub2. PMID 20687065.

[Penagos06-3] Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, et al. (August 2006). "Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials". Annals of Allergy, Asthma & Immunology. 97 (2): 141–8. doi:10.1016/S1081-1206(10)60004-X. PMID 16937742.

[4] Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S (January 2007). "Allergen injection immunotherapy for seasonal allergic rhinitis". The Cochrane Database of Systematic Reviews. 2007 (1): CD001936. doi:10.1002/14651858.CD001936.pub2. PMC 7017974. PMID 17253469.

[Canonica09-5] Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. (December 2009). "Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009". Allergy. 64 (Suppl 91): 1–59. doi:10.1111/j.1398-9995.2009.02309.x. PMC 3488881. PMID 20041860. S2CID 10420738.

[6] Rank MA, Li JT (September 2007). "Allergen immunotherapy". Mayo Clinic Proceedings. 82 (9): 1119–23. doi:10.4065/82.9.1119. PMID 17803880.

[:0-7] "Sublingual Immunotherapy (SLIT)". ACAAI Public Website. 2015-01-05. Retrieved 2018-11-05.

[:1-8] Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, et al. (March 2014). "Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review". The Laryngoscope. 124 (3): 616–27. doi:10.1002/lary.24295. PMID 23832632. S2CID 8796632.

[9] Durham S (2010). "One hundred years of allergen immunotherapy: Time to ring the changes". J Allergy Clin Immunol. 127 (1): 3–7. doi:10.1016/j.jaci.2010.11.032. PMID 21211638.

[10] Sastre J (2013). "Molecular diagnosis and immunotherapy". Current Opinion in Allergy and Clinical Immunology. 13 (6): 646–650. doi:10.1097/ACI.0b013e328364f4c6. ISSN 1528-4050. PMID 24071714. S2CID 43357832.

[11] van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, et al. (February 2000). "Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology". Allergy. 55 (2): 116–34. doi:10.1034/j.1398-9995.2000.00526.x. PMID 10726726. S2CID 39942935.

[12] "Allergy Shots (Immunotherapy) | AAAAI." The American Academy of Allergy, Asthma & Immunology, 2019,

[Dretzke-13] Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C (May 2013). "Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison". The Journal of Allergy and Clinical Immunology. 131 (5): 1361–6. doi:10.1016/j.jaci.2013.02.013. PMID 23557834.

[Caminati-14] Caminati M, Dama AR, Djuric I, Montagni M, Schiappoli M, Ridolo E, et al. (February 2015). "Incidence and risk factors for subcutaneous immunotherapy anaphylaxis: the optimization of safety". Expert Review of Clinical Immunology. 11 (2): 233–45. doi:10.1586/1744666X.2015.988143. PMID 25484197. S2CID 32045539.

[Canonica-15] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, et al. (March 2014). "Sublingual immunotherapy: World Allergy Organization position paper 2013 update". The World Allergy Organization Journal. 7 (1): 6. doi:10.1186/1939-4551-7-6. PMC 3983904. PMID 24679069.

[16] Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G (September 2010). "Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis". The Journal of Allergy and Clinical Immunology. 126 (3): 558–66. doi:10.1016/j.jaci.2010.06.013. PMID 20674964.

[:4-17] Pepper AN, Calderón MA, Casale TB (January 2017). "Sublingual Immunotherapy for the Polyallergic Patient". The Journal of Allergy and Clinical Immunology: In Practice. 5 (1): 41–45. doi:10.1016/j.jaip.2016.06.019. ISSN 2213-2198. PMID 27452888.

[oral-18] "The Current State of Oral Immunotherapy". American Academy of Allergy, Asthma, & Immunology. American Academy of Allergy, Asthma & Immunology. 4 February 2020. Retrieved 1 October 2023.

[:36-19] Feuille E, Nowak-Wegrzyn A (June 30, 2016). "Oral Immunotherapy for Food Allergies". Annals of Nutrition & Metabolism. 68: 18–31. doi:10.1159/000445391. JSTOR 48508034. PMID 27355816. S2CID 21655226.

[:5-20] Couzin-Frankel J (September 13, 2019). "First peanut allergy treatment gains backing from FDA advisory panel". Science. doi:10.1126/science.aaz5008.

[21] U.S. Department of Health and Human Services. National Institutes of Health - National Heart Lung and Blood Institute (December 2020). "Can Immunotherapy Help with the Treatment of Allergic Asthma?" (PDF). Retrieved November 18, 2022.

[FDA_PR-22] "FDA approves first drug for treatment of peanut allergy for children". US Food and Drug Administration (Press release). 31 January 2020. Retrieved 31 January 2020. This article incorporates text from this source, which is in the public domain.

[:6-23] "Palforzia Approval Letter". U.S. Food and Drug Administration (FDA). 31 January 2020. Retrieved 13 February 2020.

[24] "The FDA has approved the first drug to treat peanut allergies". Science News. 2020-02-04. Retrieved 2020-02-13.

[transdermal-25] Szczepanik M, Majewska-Szczepanik M (2016). "Transdermal immunotherapy: Past, present and future". Pharmacological Reports. 68 (4). US National Library of Medicine National Institutes of Health: 773–81. doi:10.1016/j.pharep.2016.04.004. PMID 27236747. S2CID 9714708.

[26] Janeway's Immunobiology, 8th Edition, Chapter 14

[review-27] Le UH, Burks AW (2014). "Oral and sublingual immunotherapy for food allergy". The World Allergy Organization Journal. 7 (1): 35. doi:10.1186/1939-4551-7-35. PMC 4325942. PMID 25709745.

[review_2-28] Moran TP, Vickery BP, Burks AW (December 2013). "Oral and sublingual immunotherapy for food allergy: current progress and future directions". Current Opinion in Immunology. 25 (6): 781–7. doi:10.1016/j.coi.2013.07.011. PMC 3935613. PMID 23972904.

[29] Noon L, Cantab BC (1911). "Prophylactic inoculation against hay fever". Lancet. 177 (4580): 1572–3. doi:10.1016/s0140-6736(00)78276-6.

[30] Freeman J, Noon L (1911). "Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine". Lancet. 2 (4594): 814–7. doi:10.1016/s0140-6736(01)40417-x.

[31] Bostock J. "Case of a periodical affection of the eyes and chest. Med Chir Trans. 1819;10:161.

[32] Shute N (27 March 2013). "Allergy Drops Under the Tongue May be Fine Alternative to Shots". NPR. Retrieved 22 July 2013.

[FDA2014-33] "Approval Letter - ORALAIR". FDA. Retrieved 20 June 2017.

[:2-34] Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. (September 2015). "International consensus on allergy immunotherapy". The Journal of Allergy and Clinical Immunology. 136 (3): 556–68. doi:10.1016/j.jaci.2015.04.047. PMID 26162571.

[:3-35] Cox L, Jacobsen L (December 2009). "Comparison of allergen immunotherapy practice patterns in the United States and Europe". Annals of Allergy, Asthma & Immunology. 103 (6): 451–59, quiz 459–61, 495. doi:10.1016/S1081-1206(10)60259-1. PMID 20084837.

[36] "With a litter of tactics, scientists work to tame cat allergies". Science News. 2020-02-13. Retrieved 2020-11-15.

[37] Barnes CS, Alexis NE, Bernstein JA, Cohn JR, Demain JG, Horner E, et al. (March 15, 2013). "Climate Change and Our Environment: The Effect on Respiratory and Allergic Disease". The Journal of Allergy and Clinical Immunology in Practice. 1 (2): 137–141. doi:10.1016/j.jaip.2012.07.002. ISSN 2213-2198. PMC 3654689. PMID 23687635.

[38] Larsen JN, Broge L, Jacobi H (2016-01-01). "Allergy immunotherapy: the future of allergy treatment". Drug Discovery Today. 21 (1): 26–37. doi:10.1016/j.drudis.2015.07.010. ISSN 1359-6446. PMID 26327511.

[Oral-39] Land MH, Kim EH, Burks AW (May 2011). "Oral desensitization for food hypersensitivity". Immunology and Allergy Clinics of North America. 31 (2): 367–76, xi. doi:10.1016/j.iac.2011.02.008. PMC 3111958. PMID 21530825.

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@@ Line 1: / Line 1: @@
 {{short description|Medical treatment for environmental allergies}}
+{{cs1 config |name-list-style=vanc |display-authors=6}}
 {{Infobox interventions
 |Name        = Allergen immunotherapy
@@ Line 15: / Line 16: @@
 }}
-'''Allergen immunotherapy''', also known as '''desensitization''' or '''hypo-sensitization''', is a medical treatment for environmental [[Allergy|allergies]], such as insect bites, and [[asthma]].<ref name=NIH2015Imm/><ref name=Abra2010/> Immunotherapy involves exposing people to larger and larger amounts of [[allergen]] in an attempt to change the immune system's response.<ref name=NIH2015Imm>{{cite web|title=Allergen Immunotherapy|url=http://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergen-immunotherapy.aspx|access-date=15 June 2015|date=April 22, 2015|archive-url=https://web.archive.org/web/20160909195614/http://www.niaid.nih.gov/topics/allergicDiseases/Pages/allergen-immunotherapy.aspx|archive-date=9 September 2016}}</ref>
+'''Allergen immunotherapy''', also known as '''desensitization''' or '''hypo-sensitization''', is a medical treatment for environmental [[Allergy|allergies]] (such as insect bites) and [[asthma]].<ref name=NIH2015Imm/><ref name=Abra2010/> Immunotherapy involves exposing people to larger and larger amounts of [[allergen|allergens]] in an attempt to change the immune system's response.<ref name=NIH2015Imm>{{cite web|title=Allergen Immunotherapy|url=http://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergen-immunotherapy.aspx|access-date=15 June 2015|date=April 22, 2015|archive-url=https://web.archive.org/web/20160909195614/http://www.niaid.nih.gov/topics/allergicDiseases/Pages/allergen-immunotherapy.aspx|archive-date=9 September 2016}}</ref>
 <!-- Medical uses -->
-[[Meta-analyses]] have found that injections of allergens under the skin are effective in the treatment in allergic rhinitis in children<ref name="Penagos06">{{cite journal | vauthors = Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, Canonica GW | title = Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials | journal = Annals of Allergy, Asthma & Immunology | volume = 97 | issue = 2 | pages = 141–8 | date = August 2006 | pmid = 16937742 | doi = 10.1016/S1081-1206(10)60004-X }}</ref><ref>{{cite journal | vauthors = Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S | title = Allergen injection immunotherapy for seasonal allergic rhinitis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD001936 | date = January 2007 | pmid = 17253469 | doi = 10.1002/14651858.CD001936.pub2 | pmc = 7017974 }}</ref> and in asthma.<ref name=Abra2010>{{cite journal | vauthors = Abramson MJ, Puy RM, Weiner JM | title = Injection allergen immunotherapy for asthma | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD001186 | date = August 2010 | pmid = 20687065 | doi = 10.1002/14651858.CD001186.pub2 }}</ref> The benefits may last for years after treatment is stopped.<ref name=Canonica09/> It is generally safe and effective for [[allergic rhinitis]], [[allergic conjunctivitis]], allergic forms of asthma, and stinging insects.<ref>{{cite journal | vauthors = Rank MA, Li JT | title = Allergen immunotherapy | journal = Mayo Clinic Proceedings | volume = 82 | issue = 9 | pages = 1119–23 | date = September 2007 | pmid = 17803880 | doi = 10.4065/82.9.1119 | doi-access = free }}</ref> The evidence also supports the use of [[sublingual immunotherapy]] against rhinitis and asthma, but it is less strong.<ref name=Canonica09>{{cite journal | vauthors = Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, Potter PC, Bousquet PJ, Cox LS, Durham SR, Nelson HS, Passalacqua G, Ryan DP, Brozek JL, Compalati E, Dahl R, Delgado L, van Wijk RG, Gower RG, Ledford DK, Filho NR, Valovirta EJ, Yusuf OM, Zuberbier T, Akhanda W, Almarales RC, Ansotegui I, Bonifazi F, Ceuppens J, Chivato T, Dimova D, Dumitrascu D, Fontana L, Katelaris CH, Kaulsay R, Kuna P, Larenas-Linnemann D, Manoussakis M, Nekam K, Nunes C, O'Hehir R, Olaguibel JM, Onder NB, Park JW, Priftanji A, Puy R, Sarmiento L, Scadding G, Schmid-Grendelmeier P, Seberova E, Sepiashvili R, Solé D, Togias A, Tomino C, Toskala E, Van Beever H, Vieths S | display-authors = 6 | title = Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009 | journal = Allergy | volume = 64 Suppl 91 | pages = 1–59 | date = December 2009 | pmid = 20041860 | doi = 10.1111/j.1398-9995.2009.02309.x | s2cid = 10420738 | pmc = 3488881 }}</ref> In this form the allergen is given under the tongue and people often prefer it to injections.<ref name=Canonica09/> Immunotherapy is not recommended as a stand-alone treatment for asthma.<ref name=Canonica09/>
+[[Meta-analyses]] have found that injections of allergens under the skin are effective in the treatment of allergic rhinitis in children<ref name="Penagos06">{{cite journal | vauthors = Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, Canonica GW | title = Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials | journal = Annals of Allergy, Asthma & Immunology | volume = 97 | issue = 2 | pages = 141–8 | date = August 2006 | pmid = 16937742 | doi = 10.1016/S1081-1206(10)60004-X }}</ref><ref>{{cite journal | vauthors = Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S | title = Allergen injection immunotherapy for seasonal allergic rhinitis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD001936 | date = January 2007 | volume = 2007 | pmid = 17253469 | doi = 10.1002/14651858.CD001936.pub2 | pmc = 7017974 }}</ref> and in asthma.<ref name=Abra2010>{{cite journal | vauthors = Abramson MJ, Puy RM, Weiner JM | title = Injection allergen immunotherapy for asthma | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD001186 | date = August 2010 | pmid = 20687065 | doi = 10.1002/14651858.CD001186.pub2 }}</ref> The benefits may last for years after treatment is stopped.<ref name=Canonica09/> It is generally safe and effective for [[allergic rhinitis]], [[allergic conjunctivitis]], allergic forms of asthma, and stinging insects.<ref>{{cite journal | vauthors = Rank MA, Li JT | title = Allergen immunotherapy | journal = Mayo Clinic Proceedings | volume = 82 | issue = 9 | pages = 1119–23 | date = September 2007 | pmid = 17803880 | doi = 10.4065/82.9.1119 | doi-access = free }}</ref> The evidence also supports the use of [[sublingual immunotherapy]] against rhinitis and asthma, but it is less strong.<ref name=Canonica09>{{cite journal | vauthors = Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, Potter PC, Bousquet PJ, Cox LS, Durham SR, Nelson HS, Passalacqua G, Ryan DP, Brozek JL, Compalati E, Dahl R, Delgado L, van Wijk RG, Gower RG, Ledford DK, Filho NR, Valovirta EJ, Yusuf OM, Zuberbier T, Akhanda W, Almarales RC, Ansotegui I, Bonifazi F, Ceuppens J, Chivato T, Dimova D, Dumitrascu D, Fontana L, Katelaris CH, Kaulsay R, Kuna P, Larenas-Linnemann D, Manoussakis M, Nekam K, Nunes C, O'Hehir R, Olaguibel JM, Onder NB, Park JW, Priftanji A, Puy R, Sarmiento L, Scadding G, Schmid-Grendelmeier P, Seberova E, Sepiashvili R, Solé D, Togias A, Tomino C, Toskala E, Van Beever H, Vieths S | title = Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009 | journal = Allergy | volume = 64 | pages = 1–59 | date = December 2009 | issue = Suppl 91 | pmid = 20041860 | doi = 10.1111/j.1398-9995.2009.02309.x | s2cid = 10420738 | pmc = 3488881 }}</ref> In this form the allergen is given under the tongue and people often prefer it to injections.<ref name=Canonica09/> Immunotherapy is not recommended as a stand-alone treatment for asthma.<ref name=Canonica09/>
 <!-- Side effects -->
-[[Side effect]]s during sublingual immunotherapy treatment are usually local and mild and can often be eliminated by adjusting the dosage.<ref name=":0">{{Cite news|url=https://acaai.org/allergies/allergy-treatment/allergy-immunotherapy/sublingual-immunotherapy-slit|title=Sublingual Immunotherapy (SLIT)|date=2015-01-05|work=ACAAI Public Website|access-date=2018-11-05|language=en}}</ref> [[Anaphylaxis]] during sublingual immunotherapy treatment has occurred on rare occasions.<ref name=":0" />
+[[Side effect]]s during sublingual immunotherapy treatment are usually local and mild and can often be eliminated by adjusting the dosage.<ref name=":0">{{cite news|url=https://acaai.org/allergies/allergy-treatment/allergy-immunotherapy/sublingual-immunotherapy-slit|title=Sublingual Immunotherapy (SLIT)|date=2015-01-05|work=ACAAI Public Website|access-date=2018-11-05|language=en}}</ref> [[Anaphylaxis]] during sublingual immunotherapy treatment has occurred on rare occasions.<ref name=":0" />
-Potential side effects related to subcutaneous immunotherapy treatment for asthma and allergic [[rhinoconjunctivitis]] include mild or moderate skin or respiratory reactions.<ref name=":1">{{cite journal | vauthors = Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, Lin SY | title = Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review | journal = The Laryngoscope | volume = 124 | issue = 3 | pages = 616–27 | date = March 2014 | pmid = 23832632 | doi = 10.1002/lary.24295 | s2cid = 8796632 }}</ref> Severe side effects such as anaphylaxis during subcutaneous immunotherapy treatment is relatively uncommon.<ref name=":1" /><!-- History -->
+Potential side effects related to subcutaneous immunotherapy treatment for asthma and allergic [[rhinoconjunctivitis]] include mild or moderate skin or respiratory reactions.<ref name=":1">{{cite journal | vauthors = Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, Lin SY | title = Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review | journal = The Laryngoscope | volume = 124 | issue = 3 | pages = 616–27 | date = March 2014 | pmid = 23832632 | doi = 10.1002/lary.24295 | s2cid = 8796632 }}</ref> Severe side effects such as anaphylaxis during subcutaneous immunotherapy treatment are relatively uncommon.<ref name=":1" /><!-- History -->
-Discovered by Leonard Noon and John Freeman in 1911, allergen immunotherapy is the only medicine known to tackle not only the symptoms but also the causes of respiratory allergies.<ref>{{Cite journal|last=Durham|first=Stephen|date=2010|title=One hundred years of allergen immunotherapy: Time to ring the changes|url=https://www.jacionline.org/article/S0091-6749(10)01853-1/pdf|journal=J Allergy Clin Immunol|volume=127|issue=1|pages=3–7|doi=10.1016/j.jaci.2010.11.032|pmid=21211638}}</ref> A detailed diagnosis is necessary to identify the allergens involved.<ref>{{Cite journal|last=Sastre|first=Joaquín|date=2013|title=Molecular diagnosis and immunotherapy|journal=Current Opinion in Allergy and Clinical Immunology|language=en|volume=13|issue=6|pages=646–650|doi=10.1097/ACI.0b013e328364f4c6|pmid=24071714|issn=1528-4050}}</ref>
+Discovered by Leonard Noon and John Freeman in 1911, allergen immunotherapy is the only medicine known to tackle not only the symptoms but also the causes of respiratory allergies.<ref>{{cite journal|last=Durham|first=Stephen|date=2010|title=One hundred years of allergen immunotherapy: Time to ring the changes|url=https://www.jacionline.org/article/S0091-6749(10)01853-1/pdf|journal=J Allergy Clin Immunol|volume=127|issue=1|pages=3–7|doi=10.1016/j.jaci.2010.11.032|pmid=21211638|doi-access=free}}</ref> A detailed diagnosis is necessary to identify the allergens involved.<ref>{{cite journal|last=Sastre|first=Joaquín|date=2013|title=Molecular diagnosis and immunotherapy|journal=Current Opinion in Allergy and Clinical Immunology|language=en|volume=13|issue=6|pages=646–650|doi=10.1097/ACI.0b013e328364f4c6|pmid=24071714|s2cid=43357832 |issn=1528-4050}}</ref>
 ==Types==
 ===Subcutaneous ===
-Subcutaneous immunotherapy (SCIT), also known as allergy shots, is the historical route of administration and consists of injections of allergen extract, which must be performed by a medical professional. Subcutaneous immunotherapy protocols generally involve weekly injections during a build-up phase, followed by monthly a maintenance phase that consists of injections for a period of 3–5 years.<ref>{{cite journal | vauthors = van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, Fokkens WJ, Howarth PH, Lund V, Malling HJ, Mygind N, Passali D, Scadding GK, Wang DY | title = Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology | journal = Allergy | volume = 55 | issue = 2 | pages = 116–34 | date = February 2000 | pmid = 10726726 | doi = 10.1034/j.1398-9995.2000.00526.x | s2cid = 39942935 }}</ref> The build-up phase involves the patient being administered injections which contain increasing amounts of allergens about one to two times per week. The length of the build-up phase is dependent upon how often injections are administered, but normally ranges from three to six months. After the effective dose is reached, the maintenance phase is implemented, which varies depending upon an individual’s response to the build-up phase.<ref>“Allergy Shots (Immunotherapy) | AAAAI.” The American Academy of Allergy, Asthma & Immunology, 2019,</ref>
+Subcutaneous immunotherapy (SCIT), also known as allergy shots, is the historical route of administration and consists of injections of allergen extract, which must be performed by a medical professional. Subcutaneous immunotherapy protocols generally involve weekly injections during a build-up phase, followed by a monthly maintenance phase that consists of injections for a period of 3–5 years.<ref>{{cite journal | vauthors = van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, Fokkens WJ, Howarth PH, Lund V, Malling HJ, Mygind N, Passali D, Scadding GK, Wang DY | title = Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology | journal = Allergy | volume = 55 | issue = 2 | pages = 116–34 | date = February 2000 | pmid = 10726726 | doi = 10.1034/j.1398-9995.2000.00526.x | s2cid = 39942935 }}</ref> The build-up phase involves the patient being administered injections which contain increasing amounts of allergens about one to two times per week. The length of the build-up phase is dependent upon how often injections are administered, but normally ranges from three to six months. After the effective dose is reached, the maintenance phase is implemented, which varies depending upon an individual's response to the build-up phase.<ref>"Allergy Shots (Immunotherapy) | AAAAI." The American Academy of Allergy, Asthma & Immunology, 2019,</ref>
-When accounting for a person’s age, type of allergen, and severity of allergy, there is a high probability that subcutaneous allergen immunotherapy may provide greater clinical and immunological responses than sublingual allergen immunotherapy.<ref name="Dretzke">{{cite journal | vauthors = Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C | title = Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison | journal = The Journal of Allergy and Clinical Immunology | volume = 131 | issue = 5 | pages = 1361–6 | date = May 2013 | pmid = 23557834 | doi = 10.1016/j.jaci.2013.02.013 }}</ref> Compared to sublingual allergen immunotherapy, there are no significant differences observed in quality of life.<ref name="Dretzke" />
+When accounting for a person's age, type of allergen, and severity of allergy, there is a high probability that subcutaneous allergen immunotherapy may provide greater clinical and immunological responses than sublingual allergen immunotherapy.<ref name="Dretzke">{{cite journal | vauthors = Dretzke J, Meadows A, Novielli N, Huissoon A, Fry-Smith A, Meads C | title = Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison | journal = The Journal of Allergy and Clinical Immunology | volume = 131 | issue = 5 | pages = 1361–6 | date = May 2013 | pmid = 23557834 | doi = 10.1016/j.jaci.2013.02.013 }}</ref> Compared to sublingual allergen immunotherapy, there are no significant differences observed in quality of life.<ref name="Dretzke" />
 It is possible, but rare (1/2.5 million), that people undergoing subcutaneous allergen immunotherapy may experience a fatal [[Anaphylaxis|anaphylactic]] event.<ref name="Caminati">{{cite journal | vauthors = Caminati M, Dama AR, Djuric I, Montagni M, Schiappoli M, Ridolo E, Senna G, Canonica GW | title = Incidence and risk factors for subcutaneous immunotherapy anaphylaxis: the optimization of safety | journal = Expert Review of Clinical Immunology | volume = 11 | issue = 2 | pages = 233–45 | date = February 2015 | pmid = 25484197 | doi = 10.1586/1744666X.2015.988143 | s2cid = 32045539 }}</ref> Subcutaneous allergen immunotherapy adverse events vary significantly depending on different allergenic extracts and the application of different allergen immunotherapy schedules.<ref name="Caminati" />
-Allergen immunotherapy schedules include the "cluster" approach, which involves administering several doses sequentially in a single day; a "conventional" approach, which involves incrementally increasing the dose over approximately 15 weeks; and the "rush" approach, which involves administering incremental doses at intervals of 15–60 minutes over 1–3 days).<ref name="Caminati" />
+Allergen immunotherapy schedules include the "cluster" approach, which involves administering several doses sequentially in a single day; a "conventional" approach, which involves incrementally increasing the dose over approximately 15 weeks; and the "rush" approach, which involves administering incremental doses at intervals of 15–60 minutes over 1–3 days.<ref name="Caminati" />
 It is challenging to perform an adequate risk assessment on the use of subcutaneous allergen immunotherapy compared to other forms of allergen immunotherapy administration due to the variability of immunotherapy schedules and further research is required.<ref name="Caminati" />
 ===Sublingual===
-[[Sublingual administration|Sublingual]] immunotherapy involves putting drops or a tablet of allergen extracts under the tongue, which are then absorbed through the [[Oral mucosa|lining of the mouth]]. Sublingual immunotherapy has been demonstrated to be effective against [[Rhinitis|rhinoconjuctivitis]] and asthma symptoms.<ref name="Canonica">{{cite journal | vauthors = Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, Bousquet J, Calderón M, Compalati E, Durham SR, van Wijk RG, Larenas-Linnemann D, Nelson H, Passalacqua G, Pfaar O, Rosário N, Ryan D, Rosenwasser L, Schmid-Grendelmeier P, Senna G, Valovirta E, Van Bever H, Vichyanond P, Wahn U, Yusuf O | title = Sublingual immunotherapy: World Allergy Organization position paper 2013 update | journal = The World Allergy Organization Journal | volume = 7 | issue = 1 | pages = 6 | date = March 2014 | pmid = 24679069 | pmc = 3983904 | doi = 10.1186/1939-4551-7-6 }}</ref> This effectiveness, however, varies depending on the type of allergen.<ref name="Canonica" /> The strongest evidence for the efficacy of sublingual immunotherapy comes from studies that used grass allergens or mite allergens to alleviate allergic rhinitis symptoms; the evidence shows modest improvement.<ref>{{cite journal | vauthors = Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G | title = Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis | journal = The Journal of Allergy and Clinical Immunology | volume = 126 | issue = 3 | pages = 558–66 | date = September 2010 | pmid = 20674964 | doi = 10.1016/j.jaci.2010.06.013 }}</ref>
+[[Sublingual administration|Sublingual]] immunotherapy involves putting drops or a tablet of allergen extracts under the tongue, which are then absorbed through the [[Oral mucosa|lining of the mouth]]. Sublingual immunotherapy has been demonstrated to be effective against [[Rhinitis|rhinoconjunctivitis]] and asthma symptoms.<ref name="Canonica">{{cite journal | vauthors = Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, Bousquet J, Calderón M, Compalati E, Durham SR, van Wijk RG, Larenas-Linnemann D, Nelson H, Passalacqua G, Pfaar O, Rosário N, Ryan D, Rosenwasser L, Schmid-Grendelmeier P, Senna G, Valovirta E, Van Bever H, Vichyanond P, Wahn U, Yusuf O | title = Sublingual immunotherapy: World Allergy Organization position paper 2013 update | journal = The World Allergy Organization Journal | volume = 7 | issue = 1 | pages = 6 | date = March 2014 | pmid = 24679069 | pmc = 3983904 | doi = 10.1186/1939-4551-7-6 | doi-access = free }}</ref> This effectiveness, however, varies depending on the type of allergen.<ref name="Canonica" /> The strongest evidence for the efficacy of sublingual immunotherapy comes from studies that used grass allergens or mite allergens to alleviate allergic rhinitis symptoms; the evidence shows modest improvement.<ref>{{cite journal | vauthors = Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G | title = Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis | journal = The Journal of Allergy and Clinical Immunology | volume = 126 | issue = 3 | pages = 558–66 | date = September 2010 | pmid = 20674964 | doi = 10.1016/j.jaci.2010.06.013 }}</ref>
-Sublingual immunotherapy is used to treat allergic rhinitis, often from seasonal allergies, and is typically given in several doses over a 12 week period.<ref name=":4">{{Cite journal|last1=Pepper|first1=Amber N.|last2=Calderón|first2=Moisés A.|last3=Casale|first3=Thomas B.|date=January 2017|title=Sublingual Immunotherapy for the Polyallergic Patient|journal=The Journal of Allergy and Clinical Immunology: In Practice|volume=5|issue=1|pages=41–45|doi=10.1016/j.jaip.2016.06.019|pmid=27452888|issn=2213-2198}}</ref> It works best when given 12 weeks before the start of the pollen season.<ref name=":4" /> The first dose is given by a physician to monitor for any rare reactions or anaphylaxis.<ref name=":4" /> Subsequent doses can be taken at home<ref name=":4" /> which makes this a convenient alternative to subcutaneous immunotherapy.
+Sublingual immunotherapy is used to treat allergic rhinitis, often from seasonal allergies, and is typically given in several doses over a 12-week period.<ref name=":4">{{cite journal|last1=Pepper|first1=Amber N.|last2=Calderón|first2=Moisés A.|last3=Casale|first3=Thomas B.|date=January 2017|title=Sublingual Immunotherapy for the Polyallergic Patient|journal=The Journal of Allergy and Clinical Immunology: In Practice|volume=5|issue=1|pages=41–45|doi=10.1016/j.jaip.2016.06.019|pmid=27452888|issn=2213-2198}}</ref> It works best when given 12 weeks before the start of the pollen season.<ref name=":4" /> The first dose is given by a physician to monitor for any rare reactions or anaphylaxis.<ref name=":4" /> Subsequent doses can be taken at home<ref name=":4" /> which makes this a convenient alternative to subcutaneous immunotherapy.
-While a number of side effects have been associated with sublingual immunotherapy, serious adverse effects are very rare (about 1.4/100000 doses), and there has not been a reported fatality.<ref name="Canonica" /> There have been a small number of reports of anaphylaxis.<ref name="Canonica" /> The majority of side effects are ‘local’ and usually resolve within a few days.<ref name="Canonica" /> They include swelling of the mouth, tongue or lip, throat irritation, nausea, abdominal pain, vomiting, diarrhea, [[heartburn]], and [[Palatine uvula|uvular]] [[edema]].<ref name="Canonica" /> It is not yet clear if there are any risk factors that might increase a person's susceptibility to these adverse effects.<ref name="Canonica" /> Sublingual immunotherapy appears to be better tolerated than subcutaneous immunotherapy and causes fewer side effects.<ref name="Canonica" /> The safety of sublingual immunotherapy has not been studied extensively in people with chronic [[immunodeficiency]] or [[Autoimmunity|autoimmune]] disorders.<ref name="Canonica" />
+While a number of side effects have been associated with sublingual immunotherapy, serious adverse effects are very rare (about 1.4/100,000 doses), and there has not been a reported fatality.<ref name="Canonica" /> There have been a small number of reports of anaphylaxis.<ref name="Canonica" /> The majority of side effects are 'local' and usually resolve within a few days.<ref name="Canonica" /> They include swelling of the mouth, tongue or lip, throat irritation, nausea, abdominal pain, vomiting, diarrhea, [[heartburn]], and [[Palatine uvula|uvular]] [[edema]].<ref name="Canonica" /> It is not yet clear if there are any risk factors that might increase a person's susceptibility to these adverse effects.<ref name="Canonica" /> Sublingual immunotherapy appears to be better tolerated than subcutaneous immunotherapy and causes fewer side effects.<ref name="Canonica" /> The safety of sublingual immunotherapy has not been studied extensively in people with chronic [[immunodeficiency]] or [[Autoimmunity|autoimmune]] disorders.<ref name="Canonica" />
 ===Oral===
-Oral immunotherapy (OIT) involves feeding an allergic individual increasing amounts of a food allergen in order to raise the threshold which triggers a reaction.<ref name="oral">{{cite web |title=The Current State of Oral Immunotherapy (OIT) for the Treatment of Food Allergy |url=https://www.aaaai.org/conditions-and-treatments/library/allergy-library/oit |publisher=American Academy of Allergy, Asthma & Immunology |access-date=29 September 2019}}</ref> Oral immunotherapy, however, is known to have an increased risk in the probability of needing [[Epinephrine (medication)|epinephrine]] in patients who take it.<ref name=":5">{{Cite journal|last=Couzin-Frankel|first=Jennifer|date=September 13, 2019|title=First peanut allergy treatment gains backing from FDA advisory panel|url=https://www.sciencemag.org/news/2019/09/first-peanut-allergy-treatment-gains-backing-fda-advisory-panel|journal=Science |doi=10.1126/science.aaz5008|doi-access=free}}</ref>
+Oral immunotherapy (OIT) involves feeding an allergic individual increasing amounts of a food allergen in order to raise the threshold which triggers a reaction.<ref name="oral">{{cite web |title=The Current State of Oral Immunotherapy |url=https://www.aaaai.org/tools-for-the-public/conditions-library/allergies/the-current-state-of-oral-immunotherapy |access-date=1 October 2023 |website=American Academy of Allergy, Asthma, & Immunology |publisher=American Academy of Allergy, Asthma & Immunology |publication-date=4 February 2020}}</ref> Long-term, many study participants still experienced mild allergic reactions or needed to regularly consume the allergen to maintain desensitivity.<ref name =":36">{{cite journal|last1=Feuille|first1=Elizabeth|last2=Nowak-Wegrzyn|first2=Anna|date=June 30, 2016|title=Oral Immunotherapy for Food Allergies|journal=Annals of Nutrition & Metabolism|volume=68 |pages=18–31 |doi=10.1159/000445391|jstor=48508034 |pmid=27355816 |s2cid=21655226 |doi-access=free}}</ref> Additionally, oral immunotherapy is known to have an increased risk in the probability of needing [[Epinephrine (medication)|epinephrine]] in patients who take it.<ref name=":5">{{cite journal|last=Couzin-Frankel|first=Jennifer|date=September 13, 2019|title=First peanut allergy treatment gains backing from FDA advisory panel|url=https://www.science.org/content/article/first-peanut-allergy-treatment-gains-backing-fda-advisory-panel|journal=Science |doi=10.1126/science.aaz5008|doi-access=free}}</ref> Currently, the U.S. Food and Drug Administration has not approved any oral immunotherapy agents for asthma.<ref>{{cite web |last=U.S. Department of Health and Human Services. National Institutes of Health - National Heart Lung and Blood Institute |date=December 2020 |title=Can Immunotherapy Help with the Treatment of Allergic Asthma? |url=https://www.nhlbi.nih.gov/sites/default/files/publications/Immunotherapy-Allergic-Asthma.pdf |access-date=November 18, 2022}}</ref> In January 2020, the FDA approved [[Peanut allergen powder|Palforzia]] for mitigating "allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts."<ref name="FDA PR" /><ref name=":6">{{cite web|url=https://www.fda.gov/media/134857/download|title=Palforzia Approval Letter|date=31 January 2020|website=U.S. [[Food and Drug Administration]] (FDA) |access-date=13 February 2020}}</ref> It is the first drug approved for peanut allergies. It will not allow allergic people able to eat normal amounts of peanuts, but helps prevent allergies due to accidental eating.<ref>{{cite web|url=https://www.sciencenews.org/article/fda-first-drug-peanut-allergies|title=The FDA has approved the first drug to treat peanut allergies|date=2020-02-04|website=Science News|access-date=2020-02-13}}</ref>
 ===Transdermal===
 Transdermal immunotherapy (TDIT) involves skin-induced suppression via epicutaneous (EC) application of an antigen in order to raise the threshold which triggers a reaction.<ref name="transdermal">{{cite journal |title=Transdermal immunotherapy: Past, present and future. |publisher=US National Library of Medicine National Institutes of Health
- |pmid=27236747 |year=2016 |last1=Szczepanik |first1=M. |last2=Majewska-Szczepanik |first2=M. |journal=Pharmacological Reports |volume=68 |issue=4 |pages=773–81 |doi=10.1016/j.pharep.2016.04.004 }}</ref>
+ |pmid=27236747 |year=2016 |last1=Szczepanik |first1=M. |last2=Majewska-Szczepanik |first2=M. |journal=Pharmacological Reports |volume=68 |issue=4 |pages=773–81 |doi=10.1016/j.pharep.2016.04.004 |s2cid=9714708
+ }}</ref>
 ==Mechanism of action==
@@ Line 60: / Line 62: @@
 ==Protocol==
-Reactivity is tested using oral food challenges or with skin prick tests. Phases 1 & 2 of sublingual immunotherapy are conducted in a supervised clinical setting. However, phase 3 can be done at home.<ref name="review">{{cite journal | vauthors = Le UH, Burks AW | title = Oral and sublingual immunotherapy for food allergy | journal = The World Allergy Organization Journal | volume = 7 | issue = 1 | pages = 35 | date = 2014 | pmid = 25709745 | pmc = 4325942 | doi = 10.1186/1939-4551-7-35 }}</ref>
+Reactivity is tested using oral food challenges or with skin prick tests. Phases 1 & 2 of sublingual immunotherapy are conducted in a supervised clinical setting. However, phase 3 can be done at home.<ref name="review">{{cite journal | vauthors = Le UH, Burks AW | title = Oral and sublingual immunotherapy for food allergy | journal = The World Allergy Organization Journal | volume = 7 | issue = 1 | pages = 35 | date = 2014 | pmid = 25709745 | pmc = 4325942 | doi = 10.1186/1939-4551-7-35 | doi-access = free }}</ref>
 ==History==
 In the late 19th century and early 20th century, allergic conditions were increasingly attracting both medical attention (as an emerging public health problem) and scientific interest (aided by progress in biochemical techniques and the development of molecular and pathogenic theories). However, the many and varied treatment approaches were very unscientific.{{Citation needed|date=October 2020}}
-The British physicians Noon and Freeman were the first researchers to test pollen allergen immunotherapy in humans. Noon and Freeman, researchers at the Department of Therapeutic Inoculation at St. Mary’s Hospital in London, published their findings in ''The Lancet'' in 1911.<ref>{{cite journal |vauthors=Noon L, Cantab BC | title = Prophylactic inoculation against hay fever | doi = 10.1016/s0140-6736(00)78276-6| journal = Lancet | volume = 177 | year = 1911 | issue = 4580| pages = 1572–3 | url = https://zenodo.org/record/1428534 }}</ref><ref>{{cite journal |vauthors=Freeman J, Noon L | year = 1911 | title = Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine | doi = 10.1016/s0140-6736(01)40417-x | journal = Lancet | volume = 2 | issue = 4594| pages = 814–7 | url = https://zenodo.org/record/1428546 }}</ref>{{primary-inline|date=November 2018}}{{failed verification|date=November 2018}} Building on the observations of his predecessors Bostock, Blackley and Dunbar, Noon noted that people with hay fever “sometimes become cured” and that this was possibly because they “have had the good fortune to develop an active immunity against the toxin.” He hypothesized that by injecting people with hay fever with small amounts of a pollen “toxin”, a state of immunity could be achieved.<ref>Bostock J. "Case of a periodical affection of the eyes and chest. ''Med Chir Trans.'' 1819;10:161.</ref>
+The British physicians Noon and Freeman were the first researchers to test pollen allergen immunotherapy in humans. Noon and Freeman, researchers at the Department of Therapeutic Inoculation at St. Mary's Hospital in London, published their findings in ''The Lancet'' in 1911.<ref>{{cite journal |vauthors=Noon L, Cantab BC | title = Prophylactic inoculation against hay fever | doi = 10.1016/s0140-6736(00)78276-6| journal = Lancet | volume = 177 | year = 1911 | issue = 4580| pages = 1572–3 | url = https://zenodo.org/record/1428534 }}</ref><ref>{{cite journal |vauthors=Freeman J, Noon L | year = 1911 | title = Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine | doi = 10.1016/s0140-6736(01)40417-x | journal = Lancet | volume = 2 | issue = 4594| pages = 814–7 | url = https://zenodo.org/record/1428546 }}</ref>{{primary-inline|date=November 2018}}{{failed verification|date=November 2018}} Building on the observations of his predecessors Bostock, Blackley and Dunbar, Noon noted that people with hay fever "sometimes become cured" and that this was possibly because they "have had the good fortune to develop an active immunity against the toxin." He hypothesized that by injecting people with hay fever with small amounts of a pollen "toxin", a state of immunity could be achieved.<ref>Bostock J. "Case of a periodical affection of the eyes and chest. ''Med Chir Trans.'' 1819;10:161.</ref>
-Allergen immunotherapy was part of mainstream medical practice for [[hay fever]] treatment in the 1930s.
+Allergen immunotherapy was part of mainstream medical practice for [[hay fever]] treatment in the 1930s.{{cn|date=February 2023}}
 ==Society and culture==
-Sublingual immunotherapy drops are currently commercialized and used in most European and South American countries, and in Australia and Asian countries. In most European countries, national regulations allow marketing of allergen products as "named patient preparations" (NPPs). In the United States, drop formulations have not yet received FDA approval, though off-label prescription is becoming common.<ref>{{cite web|last=Shute|first=Nancy|title=Allergy Drops Under the Tongue May be Fine Alternative to Shots|url=https://www.npr.org/blogs/health/2013/03/26/175348886/allergy-drops-under-the-tongue-may-be-fine-alternative-to-shots|work=NPR|access-date=22 July 2013}}</ref> In 2014, the FDA approved a once-daily sublingual tablet containing allergen extracts for the treatment of "hay fever" (allergic rhinitis with or without conjunctivitis).<ref name=FDA2014>{{cite web|title=Approval Letter - ORALAIR
+Sublingual immunotherapy drops are currently commercialized and used in most European and South American countries, and in Australia and Asian countries. In most European countries, national regulations allow marketing of allergen products as "named patient preparations" (NPPs). In the United States, drop formulations have not yet received FDA approval, though off-label prescription is becoming common.<ref>{{cite news|last=Shute|first=Nancy|title=Allergy Drops Under the Tongue May be Fine Alternative to Shots|url=https://www.npr.org/blogs/health/2013/03/26/175348886/allergy-drops-under-the-tongue-may-be-fine-alternative-to-shots|work=NPR|date=27 March 2013|access-date=22 July 2013}}</ref> In 2014, the FDA approved a once-daily sublingual tablet containing allergen extracts for the treatment of "hay fever" (allergic rhinitis with or without conjunctivitis).<ref name=FDA2014>{{cite web|title=Approval Letter - ORALAIR
 |url=https://www.fda.gov/BiologicsBloodVaccines/Allergenics/ucm421205.htm|work=FDA|access-date=20 June 2017}}</ref>
@@ Line 80: / Line 82: @@
 The FDA advisory board has supported the use of AR101, an oral immunotherapy, for patients with peanut allergies in 2019.<ref name=":5" />
+=== Science communication ===
-===Cost===
+Allergen immunotherapy is viewed as a beneficial way to curb allergies in the perspective of the media. It is seen where it can be covered by insurance and offer a more permanent solution than [[antihistamine]]s or [[Corticosteroid|nasal steroids]] that treat symptoms, not the body's reaction.<ref>{{cite web|date=2020-02-13|title=With a litter of tactics, scientists work to tame cat allergies|url=https://www.sciencenews.org/article/scientists-work-tame-cat-allergies-crispr-vaccine-food-therapy|access-date=2020-11-15|website=Science News|language=en-US}}</ref> Communication about allergen immunotherapy is not described very often in the news media; it is usually only communicated by the science community. The scientific community describes allergen immunotherapy as a scientific solution that helps not only patients with allergies but also positively impacts the quality of life of them and others around them. As temperatures increase due to changing climates, pollen levels also increase.<ref>{{cite journal|last1=Barnes|first1=Charles S.|last2=Alexis|first2=Neil E.|last3=Bernstein|first3=Jonathan A.|last4=Cohn|first4=John R.|last5=Demain|first5=Jeffrey G.|last6=Horner|first6=Elliott|last7=Levetin|first7=Estelle|last8=Nel|first8=Andre|last9=Phipatanakul|first9=Wanda|date=March 15, 2013|title=Climate Change and Our Environment: The Effect on Respiratory and Allergic Disease|journal=The Journal of Allergy and Clinical Immunology in Practice|volume=1|issue=2|pages=137–141|doi=10.1016/j.jaip.2012.07.002|issn=2213-2198|pmc=3654689|pmid=23687635}}</ref> Allergies are becoming a more common problem among the public, which is why the science community advocates for allergen immunotherapy. Subcutaneous allergen immunotherapy, according to the scientific community, is an effective solution to allergies due to numerous positive studies.<ref>{{cite journal|date=2016-01-01|title=Allergy immunotherapy: the future of allergy treatment|journal=Drug Discovery Today|language=en|volume=21|issue=1|pages=26–37|doi=10.1016/j.drudis.2015.07.010|issn=1359-6446|doi-access=free|last1=Larsen|first1=Jørgen Nedergaard|last2=Broge|first2=Louise|last3=Jacobi|first3=Henrik|pmid=26327511}}</ref>
-The cost for allergen immunotherapy varies by country and administration route. There is no clear and holistic transparency across therapy forms.
-=== Science Communication ===
-Allergen Immunotherapy is viewed as a beneficial way to curb allergies in the perspective of the media. It is seen where it can be covered by insurance and offer a more permanent solution than [[antihistamine]]s or [[Corticosteroid|nasal steroids]] that treat symptoms, not the body’s reaction.<ref>{{Cite web|date=2020-02-13|title=With a litter of tactics, scientists work to tame cat allergies|url=https://www.sciencenews.org/article/scientists-work-tame-cat-allergies-crispr-vaccine-food-therapy|access-date=2020-11-15|website=Science News|language=en-US}}</ref> Communication about allergen immunotherapy is not described very often in the news media, it is usually only communicated by the science community. The scientific community describes allergen immunotherapy as a scientific solution that helps not only patients with allergies but also positively impacts the quality of life of them and others around them. As temperatures increase due to changing climates, pollen levels also increase.<ref>{{Cite journal|last1=Barnes|first1=Charles S.|last2=Alexis|first2=Neil E.|last3=Bernstein|first3=Jonathan A.|last4=Cohn|first4=John R.|last5=Demain|first5=Jeffrey G.|last6=Horner|first6=Elliott|last7=Levetin|first7=Estelle|last8=Nel|first8=Andre|last9=Phipatanakul|first9=Wanda|date=March 15, 2013|title=Climate Change and Our Environment: The Effect on Respiratory and Allergic Disease|journal=The Journal of Allergy and Clinical Immunology in Practice|volume=1|issue=2|pages=137–141|doi=10.1016/j.jaip.2012.07.002|issn=2213-2198|pmc=3654689|pmid=23687635}}</ref> Allergies are becoming a more common problem among the public, which is why the science community advocates for allergen immunotherapy. Subcutaneous allergen immunotherapy, according to the scientific community, is an effective solution to allergies due to numerous positive studies.<ref>{{Cite journal|date=2016-01-01|title=Allergy immunotherapy: the future of allergy treatment|url=https://www.sciencedirect.com/science/article/pii/S1359644615002810|journal=Drug Discovery Today|language=en|volume=21|issue=1|pages=26–37|doi=10.1016/j.drudis.2015.07.010|issn=1359-6446|doi-access=free|last1=Larsen|first1=Jørgen Nedergaard|last2=Broge|first2=Louise|last3=Jacobi|first3=Henrik|pmid=26327511}}</ref>
 ==Research==
@@ Line 94: / Line 93: @@
 Another approach to improving oral immunotherapy is to change the immune environment to prevent T<sub>H</sub>2 cells from responding to the allergens during treatment. For example, drugs that inhibit IgE-mediated signaling pathways can be used in addition to OIT to reduce immune response. In 1 trial, the [[monoclonal antibody]] [[omalizumab]] was combined with high-dose milk oral immunotherapy and saw positive results. Several other trials are also currently being done combining omalizumab with OIT for a variety of food allergens. FAHF-2, a Chinese herbal mixture, has shown positive effects on the immune system and has been shown to protect mice from peanut-induced anaphylaxis. FAHF-2 was also well tolerated in a phase I study. While it is possible that omalizumab, FAHF-2 or other immunomodulatory agents alone might be able to treat dangerous allergies, combining these with OIT may be more effective and synergistic, warranting further investigation.<ref name="review 2" />
-In addition, [[nanoparticles]] is a field of development that can be used for OIT. With the potential to modulate [[antigen]] release, it may one day be possible to take a pill containing nanoparticles that will modulate dosing, requiring fewer office visits.<ref name="review 2"/>
+In addition, various adjuvants ([[nanoparticles]]) is a field of development that can be used for OIT. With the potential to modulate [[antigen]] release, it may one day be possible to take a pill containing nanoparticles that will modulate dosing, requiring fewer office visits.<ref name="review 2"/>
-Studies have also been done to determine the efficacy of OIT for multiple allergens simultaneously. One study concluded that multi-OIT would be possible and relatively, though larger studies would be necessary.<ref>{{cite journal | vauthors = Bégin P, Winterroth LC, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, Trela A, Hoyte E, O'Riordan G, Seki S, Blakemore A, Woch M, Hamilton RG, Nadeau KC | title = Safety and feasibility of oral immunotherapy to multiple allergens for food allergy | journal = Allergy, Asthma, and Clinical Immunology | volume = 10 | issue = 1 | pages = 1 | date = January 2014 | pmid = 24428859 | pmc = 3913318 | doi = 10.1186/1710-1492-10-1 }}</ref>
+Studies have also been done to determine the efficacy of OIT for multiple allergens simultaneously. One study concluded that multi-OIT would be possible and relatively, though larger studies would be necessary.<ref>{{cite journal |vauthors=Bégin P, Winterroth LC, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, Trela A, Hoyte E, O'Riordan G, Seki S, Blakemore A, Woch M, Hamilton RG, Nadeau KC |title=Safety and feasibility of oral immunotherapy to multiple allergens for food allergy |journal=Allergy, Asthma, and Clinical Immunology |volume=10 |issue=1 |pages=1 |date=January 2014 |pmid=24428859 |pmc=3913318 |doi=10.1186/1710-1492-10-1 |doi-access=free }}</ref>
 == References ==
-{{reflist|30em}}
+{{reflist|refs=
+<ref name="FDA PR">{{cite press release | title=FDA approves first drug for treatment of peanut allergy for children | website=US Food and Drug Administration |date=31 January 2020 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treatment-peanut-allergy-children |access-date=31 January 2020}} {{PD-notice}}</ref>
+}}
 == External links ==
@@ Line 105: / Line 108: @@
 * [http://www.acaai.org "American College of Allergy, Asthma, and Immunology"] information and articles of interest.
 * [http://www.abai.org "American Board of Allergy and Immunology"] American Board of Allergy and Immunology
-* [http://www.asthmahelpline.com/allergy-shots.htm "Allergy shots, allergy immunotherapy"] FAQs on Allergy Immunotherapy.
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