The only compelling argument in favour of establishing a specific diagnosis in allergic disease is that when the offending allergen is identified, a specific treatment can be instituted.
Only two specific treatments are available to the allergic patient – allergen avoidance and allergen-specific immunotherapy (SIT). Medication although useful, will only suppress symptoms but do little to modify the long-term disease process. When one considers the expense of long term allergy medication, immunotherapy must be viewed as a cost-effective treatment option.
A very old and controversial practice
Few medical treatments have been shrouded in as much controversy as the practice of allergen-specific immunotherapy or desensitisation. The use of allergen-specific subcutaneous injection immunotherapy spans 90 years. The procedure was pioneered by Dr. Noon at St Mary’s Hospital, London in 1911. Noon and Freeman successfully treated Hayfever sufferers by injecting them with pollen extracts. Immunotherapy has been enthusiastically adopted as the treatment of choice for allergic rhinitis and asthma in North America and Europe. In Canada, the procedure has never become as popular but is used as a treatment option in grass pollen allergic rhinitis and for bee or wasp sting anaphylaxis. For stinging insects it is not an option but a necessary treatment. The practice of immunotherapy slowed in Canada as researchers and doctors became excited about the many new medicines and decreased teaching about SIT, but now are rediscovering the treatment as the only alternative that will change the abnormal immune response back to normal. Problems arise mainly as a result of inappropriate and injudicious use of the procedure in treating uncontrolled asthma. Critics would therefore say that immunotherapy is a potentially life-threatening treatment for rather harmless, although inconvenient diseases. Immunotherapy does however definitely has a place in selected patient groups. The risk of adverse reactions is greatly reduced by careful patient selection and adoption of “good clinical practices” in immunotherapy.
How does immunotherapy work at a cellular level?
The exact immuno-modulatory mechanism by which immunotherapy switches off allergies is uncertain. It was hypothesised that specific “IgE blocking” antibodies were produced, as during successful immunotherapy an initial increase in specific IgE was followed by an IgE fall and compensatory rise in IgG (a blocking antibody). Researchers then postulated that specific IgG4 antibodies where induced towards the offending allergen. An associated reduction in mucosal mast cell numbers and a decrease in antigen-induced eosinophil migration to the site of inflammation are noted during immunotherapy. The latest “hot” hypothesis is that immunotherapy modulates the T-helper cells, causing switching from predominantly TH2 (IgE inducing) to predominantly TH1 (IgG inducing) subsets and as a result of this, allergen-specific IgE falls with successful immunotherapy.
Who will benefit from allergen immunotherapy?
Allergen immunotherapy should only be considered to treat type I IgE-mediated allergy that has been confirmed either by allergen skin prick testing or radio-allergosorbent testing. Another equally important consideration is whether the patient is likely to be compliant and adhere to this regular treatment regime for at least three years. The ideal candidate is an allergic person who is unable to avoid the offending allergen in daily life and in whom drug therapy has failed to control the allergy or in whom drug side-effects have become intolerable or in someone who whats a defonative approach to their condition. The patient must be carefully evaluated to determine whether the severity of the disease justifies this kind of treatment by balancing the relative benefits, risks, cost and inconvenience of immunotherapy versus drug therapy.
Most allergy sufferers in the Canada will benefit from this excellent treatment!
Immunotherapy has been most successfully used in the Canada to treat ragweed and grass pollen, House dust mite, Cat and tree (Birch) Pollen allergic rhino-conjunctivitis (hayfever) as well as Wasp and Bee sting anaphylaxis.
The fewer allergens used in immunotherapy, the better the result. Vaccine mixtures tend to be unstable and should not contain multiple mixtures of unrelated allergens. People with a single specific inhalant allergy derive most benefit from immunotherapy. However, if indicated, two inhalant allergens can be administered at the same time, at different injection sites. For House-dust mite allergy we use the standardised Dermatophagoides pteronyssinus and farinae mite vaccines. Grass pollen allergy is treated using a 6 Grass Mix pollen extract.
Wasp and Bee venom immunotherapy is highly effective, and should only be considered in every patient experiencing significant systemic symptoms after a sting and especially for those people living in a remote part of the country who if stung, have no access to emergency medical care. After successful wasp and bee venom immunotherapy, the patient will usually tolerates 100ug/ml pure venom, which is equivalent to two stings.
Immunotherapy should usually only be considered to treat animal dander allergy such as that to cats and dogs, when these animals cannot be avoided in the case of veterinarians and animal handlers.
Who should not receive immunotherapy?
The procedure is generally and arbitrarily not used in those under 5 years of age. It should not be used in patients with coronary heart disease. Some hesitate to use it in hyperthyroidism and auto-immune disease or malignancy. B-blocker and angiotensin converting enzyme inhibitor medication should be stopped before commencing the procedure as they interfere with the action of epinephrine/adrenaline if used to treat anaphylaxis. The patient should also not be wheezing at the commencement of therapy. Relative contra-indications are; pregnancy, chronic uncontrolled asthma, and for food allergy. It has been shown that immunotherapy may modify the natural history of asthma and may even prevent asthma in allergen sensitized children.
Immunotherapy – the procedure.
The injections should be given in the presence of a doctor and resuscitation equipment must always be available with epinephrine/adrenaline 1:1000, ready for injection. At each visit, the patient should be assessed for any intercurrent febrile illnesses, sudden increased exposure to the allergen or any delayed adverse reaction to the last injection. If there has been a problem, the next dose may need to be modified or omitted. The manufacturers dose schedule for each extract should be regarded as a guideline, and frequently will have to be modified in the light of events occurring during the course of treatment. The injection of allergen extract is given subcutaneously into the outer portion of the upper arm once a week. A one millilitre finely calibrated syringe is used and is first draw back so as to prevent intravenous injection. Dosage starts at a dilute solution and usually increases to a maintenance dose of allergen that induces desensitization.
The injection dose is doubled weekly until a state of tolerance to the allergen is achieved, usually at 15 weeks. Pollen immunotherapy should be commenced pre-seasonally to so as to reach the maintenance dose before the pollen season starts. Thereafter maintenance injections are given at about 4 weekly intervals for a period of 3 years to complete the immune modulating process. If an injection is missed the next dose may need to be proportionally reduced. The patient should be observed for about one half hour after each injection to ensure an adverse reaction does not occur. All forms of sport, exercise, alcohol and hot baths should be avoided for 6 – 8 hours afterwards as the increased blood circulation could precipitate an anaphylactic reaction. Contact with the relevant allergens immediately after the injection should be avoided as this may also trigger an adverse reaction. Changing from one vaccine manufacturer to another should be done with extreme caution and we usually recommend a temporary reduction in dosage over the transition period.
More about the allergen extracts.
Only allergen vaccines that have been standardised and fulfil reference IUIS/WHO guidelines should be used. The vials should be labelled declaring their potency in relevant units and should contain no non-allergenic material. Specific vaccine content may be tailored to the results of the required dose shown to be effective and the patients skin or RAST tests. In the case of bee venom immunotherapy, the vaccine should preferably contain the venom and not the whole-body extract. The vaccines must be stored in a refrigerator at a temperature between 2degC and 8degC and need to be discarded after their expiration date. They need to be gently mixed, not shaken, but not warmed before use. Allergen mixtures of too many unrelated allergens are not efficacious as they degrade easily and therefore should not be used.
Adverse reactions to immunotherapy
Most adverse reactions to immunotherapy are attributed to errors in dosage and timing. Special care should therefore be taken to ensure that the patient receives the correct dose at the correct time. Adverse reactions are most likely to occur during the initial induction phase of immunotherapy. Non-specific reactions such as excessive tiredness and headache are quite often reported but of no clinical significance. However, dizziness, itching and repeated clearing of the throat often precedes a systemic reaction. The routine use of “pre-med” antihistamines before immunotherapy should be discouraged as they will suppress an immediate adverse reaction but the patient may then go on to have a delayed systemic reaction later on (at home!).
If a small local reaction (less than 5cm diameter of swelling) occurs, continue the schedule as normal. If a larger area of swelling (greater than 5cm) occurs, then treat with an oral anti-histamine and maintain the same dose at the next injection. A mild systemic reaction is indicated by intense itching, erythema, rhinitis, localized angioedema and is treated by antihistamines and possibly a stepwise reduction of the next dose. A more severe systemic reaction includes; laryngeal oedema and respiratory distress and is promptly treated with intra-muscular epinephrine/adrenaline 1:1000 0,5ml solution. The adrenaline injection may need to be repeated after 5 minutes if no improvement occurs. Oxygen and intravenous fluids may need to be administered with intravenous hydrocortisone 200mg and antihistamines in the case of generalised anaphylaxis. A tourniquet can be applied to the limb above the site of allergen injection and a further injection of adrenaline given to the allergen injection site will delay further absorption of allergen. If these severe reactions occur, a decision may need to be made to abandon the immunotherapy program.
Outcome & benefits of successful immunotherapy.
The success of immunotherapy is dependent on the patient receiving regular injections of the highest tolerated dose of the biologically standardised vaccine for at least 3 years. Only limited knowledge exists about the optimal duration of immunotherapy and the duration of the therapeutic response achieved. Pollen allergic patients seem to derive benefit for at least 6 years after completion of the full course of immunotherapy. In House dust mite allergy the duration of clinical response may be shorter and immunotherapy may need to be re-commenced at a later stage. Between 7 and 17% of bee-venom allergic people will relapse 1-2 years after completion of successful immunotherapy and venom immunotherapy may need to be continued indefinately. Because of this small risk of relapse, it may be advisable for patients to carry emergency antihistamines or epinephrine/adrenaline after completing their immunotherapy.
Successful immunotherapy will reduce the severity of an allergic disorder, improve the quality of life of allergy sufferer and diminish the risk and cost of pharmacotherapy. The ideal end point to signify successful immunotherapy is a negative skin prick test or a fall in allergen specific IgE to negligible levels. However, only a minority of patients will achieve this end point despite the procedure producing a good clinical and symptomatic response. Immunotherapy is a popular adjunct to anti-allergy pharmacotherapy and is often used to augment asthma treatment.
The future
Allergy Canada Ltd is constantly keeping abreast of developments in the field of allergy vaccine and will make these available to you through your allergist.
