Desensitization

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Under immunotherapy , also allergy vaccination called, refers to a form of therapy can be treated with over-reaction of the immune system. It is also specific immunotherapy . Specific immunotherapy (SIT), called because it is similar to active immunization . At the present time, desensitization is the only causal therapy for allergies that treats the cause of the allergy, the overreaction of the immune system. It is a long-term therapy. Repeated administration of an allergen in an extremely low dose, which does not yet lead to an allergic reaction, should lead to habituation to the allergen in order to end the excessive reaction of the immune system to the allergen in the long term. In the case of insect venom allergies , desensitization therapy is often life-saving and therefore strongly recommended.

The outdated but colloquial term desensitization is misleading because the patient remains sensitized to the allergen, but the immune system does not react or only occurs when the allergen is very exposed. The success of the therapy can be recognized by the reduction in the symptoms; in the best case, these no longer occur.

application

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Desensitization is an antigen-specific therapy for IgE- mediated type I allergies. It is carried out for allergic complaints such as seasonal allergic rhinitis (so-called hay fever ) and for mild and moderate allergic asthma to grass pollen (rye pollen), birch pollen (hazel pollen, alder pollen), mugwort pollen, house dust mites , as well as possibly animal allergens and molds . In the case of insect venom allergies to bee venom or wasp venom, desensitization therapy is often life-saving and therefore strongly recommended.

There are different forms of therapy:

  • Subcutaneous immunotherapy (SCIT) - the allergens are injected subcutaneously under the skinby a specialist doctor ( allergist ) as thedose increases. The allergens are either in an aqueous solution (especially in the case of insect venom allergens) or are bound to a depot carrier (mostly aluminum hydroxide , also L-tyrosine , calcium phosphate ). The dose is increased at the beginning and the therapy is continued at regular intervals (4–6 weeks) after the maintenance dose has been reached, so that the immune system can get used to the allergen and the formation of antibodies can be regulated.
  • Sublingual immunotherapy (SLIT) - the allergens are administered via drops or orodispersible tablets that aredripped or placedunder the tongue ( sublingual ), from where they are absorbed through the oral mucosa. In contrast to SCIT, the allergens must be taken daily. Similar to subcutaneous therapy, the duration of treatment is three years. Initially, the allergen dose is increased to the maintenance dose within a few days. After taking it for the first time under medical supervision, it can be carried out independently at home. Visits to the doctor are therefore required somewhat less often than with therapy with syringes. The advantage is that it is easy to take at home.
  • Oral immunotherapy , mainly for food allergies , has beentriedin small studies for allergies to milk , peanut and chicken eggs .
  • Further therapy methods are being researched or have not caught on in Germany (e.g. nasal desensitization).
  • The application in veterinary medicine (including cats, dogs, horses) is possible and is based on the same therapeutic approaches.
  • The short-term immunotherapy ( rush immunotherapy ) is currently used mainly for pollen allergies and is based on high-purity use and high doses of allergen extracts, which allow rapid desensitization treatment. This saves time during treatment.

Mechanism of action

Allergies are mediated via class E (IgE) immunoglobulins . It is assumed that IgE is in principle more suitable for the defense against parasites. IgE binds to the high-affinity IgE receptor, which is found on mast cells , among other things . The allergen can then bind to the mast cells via the receptor-antibody complex and activate them through receptor cross-linking. This leads to the release of histamine and other cytokines and of proinflammatory substances .

By slowly increasing the dose and repeated exposure to the allergen, it is hoped to achieve a so-called isotype switch in the antibody-producing B cells . IgE is an isotype ; the switch should lead to the IgG. Most of the antibodies detectable in blood belong to the IgG class; if it binds its epitope , a cell-mediated activity of the immune system is induced, as is usual for the defense against bacteria (e.g. elimination by phagocytosis , see macrophages ).

In this way, the allergens are recognized and cleared away on the one hand before they can bind IgE and lead to allergic complaints; and on the other hand, fewer IgE antibodies are produced in favor of the corresponding IgG antibodies.

With natural exposure, the allergy sufferer ingests the allergen in irregular and comparably low doses. The effect of desensitization is due to the constant effect of high doses on the immune system. It learns that the allergen is "harmless". In the increase phase, the allergen is dosed until the (individual) maximum dose is reached. This dose is then continued to be administered daily (SLIT) or monthly (SCIT).

In the case of short-term immunotherapy, an accelerated dose can be increased in one day. Highly pure, high-dose depigmented allergoids are used here.

Numerous studies on the clinical effectiveness of allergic rhinoconjunctivitis ( allergic runny nose with involvement of the eyes) show a 45% reduction in symptoms and drug consumption . The majority of the studies were carried out in adults, whereby it can be assumed that the chances of success in children are higher rather than lower. So far, however, despite extensive studies and in some cases long observation periods, there is no evidence that sublingual therapy is clearly effective in childhood. This particularly affects the house dust mite SLIT. Here the conventional SCIT used to date is clearly superior (and also considerably cheaper) to SLIT by injecting an appropriate allergen solution under the skin. Therefore, the German guideline does not currently recommend SLIT in children in general.

Risks

Redness after allergen injection

The desensitization should only be carried out by allergists or doctors experienced in the therapy, since the administration of the allergy-causing substance generally involves a treatment risk and undesirable reactions can occur, since the effect is achieved by exposing the patient to the allergy-causing substance.

Subcutaneous desensitization (SCIT) With subcutaneous desensitization, a local reaction is possible, which manifests itself in a (severe) swelling of the further injection region and the formation of wheals over a few days . Both reactions, however, are less dangerous and can be weakened by giving anti-inflammatory substances or antihistamines. Other side effects may be an allergic reaction to the allergen in its respective form, e.g. B. breathlessness, asthma attacks, sneezing attacks, severe itching.

The dangerous allergic shock is rare . If the dosage is incorrect, the injection technique is inadequate or - rarely - for no apparent reason, there is a risk of allergic shock. In order to be able to counter this danger, the outpatient desensitization takes place in such a way that the patient remains under medical supervision for at least 30 minutes after the injection of the allergen. In the event of an allergic shock, a specially trained doctor can then initiate protective countermeasures.

Sublingual desensitization (SLIT) With sublingual desensitization via drops or tablets, dangerous systemic complications should occur even less frequently. With one of the newer preparations, for example, systemic reactions have only been observed when the first tablet was taken. However, local side effects are common (1–10%) to very common (a little over 10% of users), especially in the first days of treatment: The lips or mucous membranes in the mouth may itch, burn or swell. , Throat and throat area. Since there are not infrequently the smallest wounds or cracks in the mouth and on the lips, the allergens , if they come into contact with them, can lead to temporary wheals or to a slight swelling of the lip. Asthma attacks can occur in asthma sufferers.

Course and duration of therapy

The approach in therapy is decided depending on the allergen to which the body is overreacting and the allergen extract used, which is used therapeutically. The allergen dose is slowly increased at the beginning until the maintenance dose is finally reached. The total duration of therapy is usually given as 3 (to 5) years. Lifelong therapy is recommended for insect venom allergies. The therapy is divided into an increase phase , in order to slowly get the immune system used to the high allergen doses, and a subsequent maintenance phase , the actual therapy time. The situation is different with short-term immunotherapy with depigmented allergoids. Here you start with the maximum dose, whereby a faster onset of action is achieved.

In the case of subcutaneous injection therapy, this is injected at regular intervals over a period of 2-4 years. How quickly the saturation takes place depends on the type of allergen extract. The syringe therapy can be carried out either as preseasonal (short-term) or perennial desensitization. In the preseasonal form, there is a rehabilitation treatment after the allergy season. Once the maintenance dose has been reached, it is then administered at intervals until the start of the new allergy season. Therapy is then interrupted during the allergy season and resumed when it is over. In the perennial therapy, there is no break, but the allergen extract is supplied over the entire season.

If the therapy is carried out with drops or tablets, the allergen enters the body by means of drops or orodispersible tablets that are dripped or placed under the tongue, or by means of a tablet that is swallowed. Whether the therapy should be carried out perennial or pre- / co-seasonal depends on the allergen extracts and the respective approval. Here too, increasing doses are used at the beginning of the treatment. The first dose is taken in the doctor's office. The tablet is held under the tongue for about two minutes and then swallowed. It is recommended to take the tablet in the morning on an empty stomach. Studies have shown that, with sublingual desensitization, the additional intake of antisymptomatic drugs could be roughly halved in the first season. In the case of drop preparations, the flexibility of the dose is valued, whereas in tablet therapy the full dose is always applied, with the risk of side effects.

Growth phase

  • In the case of aqueous preparations (insect venom only), a large number of injections (2–3 times per week, up to 16 weeks) up to the maximum dose are necessary, since the allergens are administered in their original, native form.
  • With depot preparations, the allergens are bound to a depot carrier ( L-tyrosine , aluminum hydroxide , calcium phosphate ). This enables the allergen to be released evenly over a longer period of time. On the one hand, a distinction is made between native preparations, which are administered with weekly injections within 5 to 15 weeks. On the other hand, allergoids, ie chemically modified allergens, are used. The effect of glutaraldehyde or formaldehyde changes the protein structures of the allergens in such a way that the allergy-triggering components are not recognized by the immune system and the increase phase is shortened to 3–7 weeks.
  • With cluster or ultra-rush therapies, several injections are given in one day in order to shorten the increase phase even further. This form has become particularly well established in the inpatient setting of insect venom allergy sufferers. The hospital stay can be shortened from 7 days to 2-3 days.
  • With SLIT, the doses are increased daily. Some forms of treatment (e.g. tablets) do not require an increase phase and start straight away with the full dose.

Maintenance phase

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  • In the case of injectable therapies with mites and animal epithelia, a therapy cycle of 4 to 6 (8) weeks is generally observed. The therapy is carried out continuously for 3 (to 5) years.
  • For pollen allergy sufferers, the therapy is often interrupted during the pollen season. One then speaks of preseasonal or short-term therapy. After the pollen count, the therapy is started all over again. Here, allergoids have the advantage that a longer therapy phase is possible due to the shorter increase phase.
  • A new approach is to shorten the total therapy to 4 injections by adding an adjuvant . Bacterial components ( MPL ) or DNA components ( CpG fragments ) also stimulate the immune system in a targeted manner.
  • With SLIT, the allergen is still taken daily in the maintenance phase, as no depot is created.

Alternatives

If it is not possible to carry out a desensitization (e.g. due to an individual, intolerable increased risk of allergic shock), the following options essentially remain:

  • Symptom-suppressing treatment with antihistamines , which can be taken permanently by the patient in times of high allergen exposure.
  • Treatment with cortisone (glucocorticosteroids) is the most effective pharmacotherapy currently available. Nasal obstruction (especially in house dust mite allergy) can be influenced better in therapy with corticosteroids than with antihistamines. First of all, the topical corticoids (cortisone) should be mentioned; they only act on the nasal or bronchial mucosa. Systemic effects of topical corticosteroids, ie effects affecting the whole body, are extremely rare. Older topical corticoids such as budesonide and flunisolide already show a high level of safety, whereby the very old topical corticoids should be avoided, especially in children, such as B. Beclometasone . New topical corticosteroids such as fluticasone and mometasone are more effective with a simultaneous lower bioavailability (the whole body, especially the adrenal cortex).
  • Systemically acting glucocorticoids ( cortisone derivatives ) are sometimes useful at the beginning of therapy, whereby oral administration is preferable to the depot injection with cortisone in the muscle (intramuscular) because of the better dose control. In addition, the continuous release from the depot disrupts the physiological daily rhythm of the cortisone level. Furthermore, the intramuscular syringe offers the risk of muscle wasting ( atrophy ). Both systemic treatment methods show a clear side effect profile, especially with longer treatment. For example, water retention in the body or the so-called "moon face" are non-local side effects. For this reason, treatment with a systemic glucocorticoid is limited and must be monitored particularly closely, while topical nasal as well as bronchial treatment with corticosteroids has few side effects and is safe.
  • Moving to a region that has a different flora and thus a different pollen spectrum or even a completely different climate is certainly only rarely possible (depending on the allergy, e.g. place of residence above 1200 m, southern, dry areas).
  • If you can avoid the allergen at all: Change of living conditions with the aim of avoiding the allergen if possible.

literature

  • Janeway, Travers: Immunobiology in Health and Disease. 6th edition. Garland Science, 2005.
  • Vera Mahler, Robert E. Esch, Jörg Kleine-Tebbe, William J. Lavery, Greg Plunkett: Understanding differences in allergen immunotherapy products and practices in North America and Europe . In: Journal of Allergy and Clinical Immunology . tape 143 , no. 3 , March 1, 2019, p. 813–828 , doi : 10.1016 / j.jaci.2019.01.024 ( elsevier.com [accessed March 5, 2019]).
  • A. Nowak-Węgrzyn, HA Sampson: Future therapies for food allergies. In: The Journal of allergy and clinical immunology. Volume 127, Number 3, March 2011, pp. 558-573, ISSN  1097-6825 . doi: 10.1016 / j.jaci.2010.12.1098 . PMID 21277625 . PMC 3066474 (free full text).
  • Johannes Ring : Applied Allergology . 3., rework. Edition. Urban and Vogel, Munich 2007, ISBN 3-89935-128-2 .

Web links

Wiktionary: Desensitization  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ Antje Hüter-Becker : Investigations in Physiotherapy , p. 157.
  2. ↑ Erika Jensen-Jarolim: Aluminum in Allergies and Allergen immunotherapy . In: The World Allergy Organization Journal . tape 8 , no. 1 , February 28, 2015, doi : 10.1186 / s40413-015-0060-5 , PMID 25780491 , PMC 4348159 (free full text).
  3. ^ A. Wesley Burks et al .: Oral immunotherapy for treatment of egg allergy in children . In: The New England Journal of Medicine . tape 367 , no. 3 , July 19, 2012, p. 233-243 , doi : 10.1056 / NEJMoa1200435 , PMID 22808958 , PMC 3424505 (free full text).
  4. ↑ Stacie M. Jones et al .: Clinical Efficacy and Immune Regulation With Peanut Oral Immunotherapy . In: The Journal of allergy and clinical immunology . tape 124 , no. 2 , August 2009, p. 292-300 , doi : 10.1016 / j.jaci.2009.05.022 , PMID 19577283 , PMC 2725434 (free full text).
  5. ^ Corinne A. Keet et al .: The safety and efficacy of sublingual and oral immunotherapy for milk allergy . In: The Journal of allergy and clinical immunology . tape 129 , no. 2 , February 2012, p. 448–455 , doi : 10.1016 / j.jaci.2011.10.023 , PMID 22130425 , PMC 3437605 (free full text).
  6. ↑ (Allergen) specific immunotherapy for IgE mediated allergic diseases. In: AWMF. October 10, 2014, accessed April 1, 2020 .
  7. ↑ Trend towards higher dosage and faster titration. Allergo J 2007, 16, 1-2.
  8. ↑ "Safety instructions for the treatment of children and adolescents with GRAZAX", ALK-Abelló Allergie-Service GmbH.
  9. ↑ Differences in immunotherapies against allergies between the USA and Europe. In: Press release 5/2019. Paul Ehrlich Institute, March 5, 2019, accessed March 5, 2019 .