Allergen immunotherapy

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ALK Alutard SQ immunotherapy injection kit

Allergen immunotherapy (also termed desensitization or hypo-sensitization) 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 (grass, pollen, house dust mite fecal proteins) and thereby induce specific long-term tolerance.[1] Allergen immunotherapy can be administered under the tongue (with drops or tablets) or by injections under the skin (subcutaneous). 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. A detailed diagnosis is necessary to identify the allergens involved. The medicine must be prescribed and initiated by a physician with experience of treating allergy patients.

Most studies in the last 20 years state that immunotherapy is a relatively safe and effective treatment for asthma and allergic rhinitis. It is currently being studied as a possible treatment for eczema and food allergies in children. Side effects during treatment are usually local and mild and can usually be eliminated by adjusting the dosage. Anaphylaxis has occurred on rare occasions and this is why treatment should only be administered by an allergist.[2]

Sublingual immunotherapy[edit]

Sublingual 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.[3] It allows the body to become tolerant of the allergen by absorbing the allergen through the stomach lining. Today, sublingual immunotherapy can count on more than 60 controlled clinical trials, proving its efficacy and safety profile. Though the efficacy is less than superlative. In 2013, the Journal of the American Medical Association said the drops are moderately effective in reducing asthma symptoms, with 8 out of 13 studies reporting more than 40 percent improvement in symptoms. The evidence was stronger in studies with children.

Sublingual immunotherapy drops[edit]

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, drops have not yet received FDA approval, though off-label prescription is becoming common.[4]

Sublingual immunotherapy tablets[edit]

Sublingual immunotherapy tablets are currently commercialized and approved for use in most European countries, Canada, and the USA.

Subcutaneous immunotherapy[edit]

Subcutaneous immunotherapy is the historical route of administration and consists of allergen extract injections which 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.[5] Although efficacy of subcutaneous immunotherapy has been demonstrated by several studies, it entails the risk of systemic anaphylactic reactions.[6] Hence the necessity for it to be performed by clinicians trained in allergy.

Mechanism of therapeutic action[edit]

In desensitization immunotherapy the aim is to restore tolerance to the allergen by reducing its tendency to induce IgE production. Patients are desensitized through the administration of escalating doses of allergen, starting with tiny amounts, an administration schedule 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 less IgE antibodies and more Th1 regulatory T cells, which secrete IL-10 and/or TGF-beta, which skew the response away from IgE production.[7]


Sublingual immunotherapy drops[edit]

Sublingual immunotherapy drops involves putting drops 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.

Sublingual immunotherapy tablets[edit]

Sublingual immunotherapy tablets contain allergen extract and are placed under the tongue until they dissolve. As with drops, tablets have a better safety profile than subcutaneous immunotherapy and patients can take the treatment at home. Along with drops therefore, tablets are considered a patient-friendlier formulation than subcutaneous immunotherapy, while ensuring the same efficacy.

Subcutaneous immunotherapy[edit]

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.


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 1911.[8][9] 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.[10]

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 were 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[edit]

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 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.

See also[edit]


  1. ^ Van Overtvelt L. et al. Immune mechanisms of allergen-specific sublingual immunotherapy. Revue française d’allergologie et d’immunologie clinique. 2006; 46: 713–720.
  2. ^ "Sublingual Immunotherapy (SLIT) – Overview: What is SLIT?", American College of Allergy, Asthma & Immunology 
  3. ^ 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
  4. ^ Shute, Nancy. "Allergy Drops Under the Tongue May be Fine Alternative to Shots". NPR. Retrieved 22 July 2013. 
  5. ^ Bousquet J. et al. EAACI Position Paper. Allergy 2000: 55: 116±134
  6. ^ 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. 
  7. ^ Janeway's Immunobiology, 8th Edition, Chapter 14
  8. ^ Noon L, Cantab BC. Prophylactic inoculation against hay fever. Lancet. 1911:1572-3.
  9. ^ Freeman J, Noon L. Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine. Lancet. 1911;2:814-7.
  10. ^ Bostock J. Case of a periodical affection of the eyes and chest. Med Chir Trans. 1819;10:161.

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