Editors

ErkkaValovirta

Allergen Immunotherapy

Essentials

Allergen immunotherapy (also known as desensitization or hypo-sensitization) can be carried out either by giving subcutaneous injections or by sublingual immunotherapy, depending on the product and according to the marketing authorisation, from 5 years of age onwards, if the patient has an IgE-mediated allergic disease that impairs his/her quality of life.
It is recommended to start allergen immunotherapy at an early stage of an IgE-mediated allergic disease.
The physician and the nurse should actively discuss with the patient about allergen immunotherapy, since a large share of patients receiving such therapy have taken the issue up themselves.
The most common allergens used in the therapy include birch and timothy grass. More rarely used allergens include cat, dog, wasp, bee and house dust mite.
For sublingual immunotherapy, timothy grass, house dust mite and birch are the first more widely available allergen tablets.
The effect of allergen immunotherapy is good in allergic rhinitis and in allergy to Hymenoptera venoms both in adults and in children.
Allergen immunotherapy is also used in allergic asthma as a part of anti-inflammatory treatment with good effect both in adults and in children.

General

Allergen immunotherapy is the causal treatment of IgE-mediated
- allergic rhinitis and conjunctivitis
- allergic asthma and
- allergy to wasp and bee venoms (i.e. Hymenoptera).
During allergen immunotherapy the allergic inflammatory reaction diminishes.
In allergy to Hymenoptera venoms, allergen immunotherapy suppresses any life-threatening reactions in 80% of patients and alleviates the severity of reactions in the rest 20%.
The treatment is usually continued for 3 years, in Hymenoptera allergy for 5 years.
The treatment has an effect in 80-90% of the patients. The effect lasts several years after the treatment has been stopped; in children with grass allergy it has been shown to last for 12 years.
The treatment is started by a physician with expertise in the investigation and treatment of allergic diseases.
Sublingual immunotherapy may be started even in primary care, in student health care services or in occupational health care, provided that the physician has adequate expertise.

Preconditions

General preconditions to be met before starting allergen immunotherapy
- The patient has confirmed IgE-mediated allergy (allergic rhinoconjuctivitis) that causes symptoms.
- There are no contraindications to the treatment.
- The patient wishes to have the treatment.
- Trained personnel are available to give and follow up the treatment according to current clinical guidelines.
The treatment can already be started at an early stage of the disease.
- The risk of children allergic to pollen of birch or timothy grass to develop asthma may diminish when allergen immunotherapy is started sufficiently early.
Good patient guidance includes all information about the duration, expected efficacy and cost of the treatment as well as about the restrictions and possible adverse effects caused by it. This improves compliance.

Indications

The efficacy of each product in allergy to pollen, animals and house dust mite is presented below in the chapter Allergen immunotherapy products here. In allergy to Hymenoptera venoms allergen immunotherapy is the only effective causative treatment. Asthma in itself is hardly ever treated solely with allergen immunotherapy.
Allergy to Hymenoptera venoms
Allergic rhinitis and conjuctivitis caused by
- pollens
- house dust mite
- animals/pets when indirect contact causes symptoms or when it is not possible to avoid direct contact (work, guide dogs)
Asthma caused by
- pollens
- house dust mite
- animals/pets
Occupational allergies
- animals

Contraindications

Asthma with poor control (FEV1 below 80%, z score <-1.65)
Active immunological or malignant disease
Severe heart and respiratory illnesses
Continuous oral glucocorticoid medication (over 10 mg of prednisolone or corresponding other glucocorticoid per day)
Beta-blocker medication (also as eye drops because in a severe reaction the effect of adrenaline is reduced)
Age under 5 years
Pregnancy and breastfeeding
Contraindications to injectable and sublingual allergen immunotherapy, as well as to immunotherapy for hymenoptera allergy are listed below, see table T1.

Contraindications to allergen immunotherapy. Source: Finnish Current Care Guideline Siedätyshoito [Allergen immunotherapy], Duodecim, 2019 http://www.kaypahoito.fi/en/ccs00046.

Illness, medication or other aspect to be considered	Subcutaneous immunotherapy	Sublingual immunotherapy	Hymenoptera immunotherapy
Asthma (with poor control)	A	A²⁾	A
Malignant tumour	A	A	R
Pregnancy (starting therapy)	A	A	A
Pregnancy (maintenance therapy)	R	R	R
Diseases of the respiratory and circulatory system	R	R	N
Beta blockers¹⁾	R	R	N
ACE inhibitors	N	N	R
Active immunological disease, such as
autoimmune disease	A	A	A
HIV	R	R	R
AIDS	A	A	A
immunosuppressive medication	R	R	R
immune deficiencies	R	R	R
Chronic inflammatory disease in the oral cavity	N	A	N

A = absolute contraindication
R = relative contraindication
N = not a contraindication
¹⁾ the efficacy of adrenaline may be decreased in the treament of anaphylaxis
²⁾ does not apply to house dust mite desensitization

Subcutaneous immunotherapy

Practical aspects

The treatment is administered around the year by giving subcutaneous injections of aluminium hydroxide-bound depot allergen extracts.
During the updosing phase, which lasts 7 or 15 weeks, the injection dose is increased every 1-2 weeks. After the updosing phase the treatment can be given in a health care centre in cooperation with the centre where it was first started in accordance with the local practices and agreements.
In the maintenance phase the injections are usually given every 6 (4-10) weeks.
The maintenance dose is individual (the largest dose the patient can tolerate), but no more than recommended by the manufacturer of the allergen extract (the side-effects increase, but the effect does not).
The next dosage is dictated by the possible reaction from the previous injection and the symptoms the patient has at that time.
It is recommended to complete the updosing phase before the start of the pollen season.
The treatment duration is 3 years for inhaled allergens and 5 years for hymenoptera venoms.

Precautions

A qualified nurse should give the injections and a physician should always be present at the centre.
The patient is interviewed about possible reactions after the previous visit before giving the injection.
The patient should be observed for at least 30 minutes after the injection.
Patients below 15 years of age must be accompanied.
Intensive physical exercise and alcohol must be avoided after the injection.

Treatment-related reactions

Various injection reactions are a natural part of the treatment: local redness and swelling.
The dosage of the extract is estimated every time on the basis of the swelling reaction (a lump which can be felt and measured with the finger, not a possible prick lump on the skin!).
Generalized reactions (urticaria, asthma, fatigue, generalized allergic reaction) might occur.
The patient is given medication for the reactions:
- antihistamine
- glucocorticoid cream
- a bronchodilator
- possibly self-injected adrenaline (training equipment should be used to initially teach the patient and to regularly check the patient's skills in proper use of the injector!).

Sublingual immunotherapy

Sublingual immunotherapy is effective and safe for allergic rhinitis and asthma caused by grass pollen, house dust mite, or birch.
The indications for sublingual immunotherapy are the same as for subcutaneous immunotherapy, and the contraindications are listed in table T1.
The first dose is administered at the nurse's office with a physician present.
The patient should be observed for at least 30 minutes after taking the tablet.
The tablet is placed under the tongue with dry, clean fingers immediately after taking the tablet from its package, and it is allowed to dissolve in the mouth.
Swallowing should be avoided for 1 minute after taking the tablet and eating or drinking should be avoided for 5 minutes.
After surgery of the mouth or dental procedures, the treatment is paused for 7 days. In children, a 1-day pause is warranted after shedding of a primary tooth (milk tooth).
If a patient with asthma has a respiratory infection, the treatment is paused for 7 days.
If the treatment is paused for 30 days or more, the patient should be instructed to contact the unit that started the therapy so that it can be restarted.

Allergen immunotherapy products

According to the recommendation by the WAO (World Allergy Organization), the evidence on the efficacy and safety of the different therapies is indicated below per product. The products and their names may vary accross countries.
Timothy grass sublingual tabletGrazax^®
- The treatment is effective, safe and well-tolerated in allergic rhinitis, both in adults 1 2 3 and children 4 5.
- The treament may reduce asthma symptoms and the need for asthma medication in adults 6 7, and it apparently reduces the development of asthma symptoms and use of asthma medication in children with allergic rhinitis 8.
- For adults and children from 5 years of age
House dust mite sublingual tabletAcarizax^®
- The treatment is effective, safe and well-tolerated in allergic rhinitis in adults 9 10 11 12 13 and, apparently, also in children 14 15.
- Sublingual immunotherapy for asthma associated with house dust mite allergy apparently reduces the development of asthma symptoms in adults and adolescents 16 11 18 7.
- Sublingual immunotherapy may reduce the need for asthma medication in adults and adolescents 20.
- For adults (allergic rhinitis and asthma) and children from 12 years of age (allergic rhinitis)
Birch pollen sublingual tabletItulazax^®
- The treament is well-tolerated and reduces nasal and eye symptoms in adults with birch allergy 21 22 23 24.
- For adults
Timothy grass subcutaneous immunotherapyAlutard SQ timotei^®
- The treatment reduces symptoms and it is well-tolerated in allergic rhinitis in adult patients 25 26.
- For adults and children from 5 years of age
Birch subcutaneous immunotherapy Alutard SQ birch^®
- The treatment reduces symptoms and it is well-tolerated in allergic rhinitis in adult patients 27 28 26.
- For adults and children from 5 years of age
House dust mite subcutanous immunotherapyAlutard SQ house dust mite^®
- The treatment is apparently effective and well-tolerated in allergic rhinitis in adults 30 31 32.
- The treament may reduce the need for asthma medication in adults 33, children and adolescents 34.
- For adults and children from 5 years of age
Cat subcutaneous immunotherapyAlutard SQ cat^®
- Research evidence is scarce concerning the effectiveness of the treatment in allergic rhinitis and asthma.
- For adults and children from 5 years of age.
Dog subcutanous immunotherapyAlutard SQ dog^®
- Research evidence is scarce concerning the effectiveness of the treatment in allergic rhinitis and asthma.
- For adults and children from 5 years of age.

Organization of treatment

Find out about the availability and organization of locally available allergen immunotherapy.

Follow-up

The doctor who first started the treatment should evaluate the efficacy annually.
This evaluation is based on the allergic symptoms and the use of other medication.
So-called VAS evaluation (visual analogue scale) is a method for evaluating efficacy. The patient may give his estimate of the effect yearly by using the VAS. The evaluation is based on changes in symptoms and use of medication during the treatment.

References

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