Allergen immunotherapy (also termed desensitization) is a medical treatment aiming at patients suffering from allergies that are insufficiently controlled by symptomatic treatments.
Allergen immunotherapy rehabilitates the immune system. This involves administering increasing doses of allergens to accustom the body to substances that are generally harmless (pollen, house dust mites) and thereby induce specific long-term tolerance. Allergen immunotherapy can be administered under the tongue (sublingually with drops or tablets) or by injections under the skin (subcutaneous). Discovered by Leonard Noon and John Freeman in 1911, allergen immunotherapy represents the only causative treatment for respiratory allergies. It is the only medicine known to tackle not only the symptoms but also the causes of respiratory allergies. A detailed diagnosis is necessary to identify the allergens involved. The medicine must be prescribed and initiated by an allergy specialist.
Sub-lingual immunotherapy is used by physicians in many countries: it involves putting drops or a tablet of allergen extracts under the tongue to swallow the extract. It allows the body to become tolerant of the allergen by absorbing the allergen through the stomach lining. The treatment is usually taken at home. Sublingual immunotherapy is 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, it has not yet received FDA approval, though off-label prescription is becoming common. Today, sublingual immunotherapy can count on more than 60 controlled clinical trials, proving its efficacy and safety profile and leading to its recognition as a viable route by the international guidelines.
Subcutaneous immunotherapy is the historical route of administration and consists of allergen extract injections. Subcutaneous immunotherapy can only be performed with a medical observation. Subcutaneous immunotherapy protocols generally involve weekly injections during a build-up phase, followed by monthly maintenance injections for a period of 3–5 years. Although efficacy of subcutaneous immunotherapy has been demonstrated by several studies, subcutaneous immunotherapy entails the risk of systemic anaphylactic reactions. Hence the necessity for subcutaneous immunotherapy to be performed by clinicians trained in allergy.
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.
The British physicians Noon and Freeman were the first researchers to test pollen allergen immunotherapy in a patient cohort. Noon and Freeman, researchers at the Department of Therapeutic Inoculation at St. Mary’s Hospital in London, published their findings in The Lancet in 1915. Building on the observations of his predecessors Bostock, Blackley and Dunbar, Noon noted that hay fever patients “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 hay fever patients with small amounts of a pollen “toxin”, a state of immunity could be achieved.
After the groundbreaking work by Noon and Freeman in the UK and by Cooke and colleagues in the US, allergen immunotherapy was part of mainstream medical practice for hay fever treatment in the 1930s.
Later, sublingual formulations are found to be effective in symptom reduction in allergic rhinitis. Sublingual immunotherapy is also found to have a better safety profile than subcutaneous immunotherapy since the local side effects caused by sublingual immunotherapy contrasted with the possible systemic events that can occur with the subcutaneous immunotherapy.
Recognition by international guidelines
As the clinical evidence accumulated, the use of sublingual immunotherapy became incorporated into major international guidelines. In a position paper published by a scientific society (by WHO in 1981 then by the ARIA consensus in 2002), sublingual immunotherapy’s established efficacy and a favourable safety profile were quoted.
In 2001, scientific guidelines confirmed and extended the indication of sublingual immunotherapy also to children. The guidelines acknowledge that sublingual immunotherapy is safer than subcutaneous immunotherapy.
World Allergy Organisation Position Paper in 2009 on sublingual immunotherapy emphasized the benefits of licensing allergen immunotherapy as a therapeutic class.
By following the advice of the experts in reconsidering the role of allergen immunotherapy, the European Medicines Agency has issued in 2009 new recommendations concerning the clinical development, production and quality of immunotherapy products with a view to register allergen immunotherapy as pharmaceutical specialties.
Mechanism of therapeutic action
In desensitization immunotherapy the aim is to restore tolerance to the allergen by reducing its tendency to induce IgE production. Patients are desensitized by injection with escalating doses of allergen, starting with tiny amounts, an injection schedule that gradually decreases the IgE-dominated response. The mechanisms underlying desensitization therapy are complex, but the key to success seems to be the induction of regulatory T cells secreting IL-10 and/or TGF-beta, which skew the response away from IgE production.
Sublingual immunotherapy involves, putting drops or a tablet of allergen extract under the tongue and then swallowing the extract. Besides its efficacy, sublingual immunotherapy is known to have a better safety profile than subcutaneous immunotherapy and one of the significant benefits of sublingual immunotherapy is also that the patient can take the treatment at home. It is thus also considered a patient-friendlier formulation than subcutaneous immunotherapy, while ensuring the same efficacy.
Today allergen immunotherapy is available in tablet form (for grass pollens).
citation needed] and provides such a favorable benefit/risk ratio. Allergen immunotherapy has therefore acquired a level of evidence equivalent to that of “conventional” drugs, both in terms of documentation of its pharmaceutical quality and the rigor of its production, and its terms of demonstration of its clinical efficacy and safety for patients.[
Prescribed by an allergy specialist, injections of allergens are administered in a medically controlled environment and followed by an observation period of 30 minutes. These pain-free injections are given in order to subcutaneously (under the skin) administer the allergen on the arm between the elbow and shoulder.
Allergen injections are started at very low doses. The dose is gradually increased on a regular (and usually weekly) basis, until a "maintenance" dose is reached. Once the maintenance dose is reached, the injections are administered less often (every two to four weeks), still on a regular basis. After 3 years or 3 seasons (if seasonal allergy) of successful completion of immunotherapy, long-term protection can be expected.
- Van Overtvelt L. et al. Immune mechanisms of allergen-specific sublingual immunotherapy. Revue française d’allergologie et d’immunologie clinique. 2006; 46: 713–720.
- Olivier CE, Lima RPS, Argentão DGP, Silva MDd, Santos RAPG, Pensuti M, et al. Multi-allergen Sublingual/Swallow Immunotherapy Improves the Quality of Life of Polysensitized Children and Adults with Allergic Rhinitis. The Open Allergy Journal 2013; 4:148. doi: 10.4172/2155-6121.1000148. LINK
- Shute, Nancy. "Allergy Drops Under the Tongue May be Fine Alternative to Shots". NPR. Retrieved 22 July 2013.
- J. David et al. History of Immunotherapy: The First 100 Years. Immunol Allergy Clin N Am 31 (2011) 149–157.
- Bousquet J. et al. EAACI Position Paper. Allergy 2000: 55: 116±134
- Straley, DR (January–February 2013). "Office IgE-mediated environmental allergy evaluation and treatment.". Osteopathic Family Physician 5 (1): 9–16. doi:10.1016/j.osfp.2012.08.003.
- Noon L, Cantab BC. Prophylactic inoculation against hay fever. Lancet. 1911:1572-3.
- Freeman J, Noon L. Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine. Lancet. 1911;2:814-7.
- Bostock J. Case of a periodical affection of the eyes and chest. Med Chir Trans. 1819;10:161.
- Janeway's Immunobiology, 8th Edition, Chapter 14
- Khinchi MS, Poulsen LK, Carat F, Andre C, Hansen AB, Malling HJ. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo controlled, double-blind, double-dummy study. Allergy. 2004;59(1):45-53.
- "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
- "Allergy shots, allergy immunotherapy" FAQs on Allergy Immunotherapy.