Hyposensitization

Hyposensitization (or allergy desensitization) is a form of immunotherapy where the patient is gradually vaccinated against progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG ("the blocking antibody") production, as opposed to the excessive IgE production seen in hypersensitivity type I cases.

Disambiguation
Immunotherapy or desensitization therapy for allergies must not be confused with homeopathic treatments. Immunotherapy administered through cutaneous injections or sublingually has substantial empirical support. Numerous research articles and several meta-analytic studies support its clinical effectiveness. Conversely, homeopathy (or Enzyme Potentiated Desensitization or low-dose immunotherapy or Rinkel immunotherapy) is not generally endorsed by the medical profession as it lacks substantial empirical support.

The term immunotherapy may refer not only to desensitization for allergies but also to a number of other immunomodulatory techniques that aim to alter the response of the immune system in order to alleviate or cure autoimmune disease, cancer, and so forth.

Clinical Experience and Research
Immunology is a relatively young science that originated in the 19th century. Grass pollens were identified for the first time as the likely trigger of seasonal hay fever in the 1870s. Skin allergy testing became an accepted assessment technique around 1910. IgE was identified in the 1960s. The first scholarly report of immunotherapy for allergy appeared in 1911 in the medical journal "Lancet" but research lagged behind clinical practice. Whereas clinical lore in medicine generally supports the effectiveness of immunotherapy, sufficient research evidence on the effectiveness and mechanism of immunotherapy began to accumulate in the last 15 years of the 20th century. Currently, researchers are developing new ways to extract and even genetically engineer allergen extracts in order to improve the effectiveness and reduce the potential side effects of immunotherapy. Recent animal and human studies using fragments of DNA or human antibodies attached to allergens offer the prospect of stimulating a potent anti-allergic immune response without the risk of adverse allergic reactions. These vaccines are currently being trialed in humans, after having shown promising results in animal studies. Such methods offer the possibility of developing preventative allergy "vaccines" that might prevent the onset of anaphylaxis if administered to children at high risk. From time to time, studies describing more convenient and less frequent treatments have been described, but these are not currently commercially available.

Benefits from Immunotherapy
Current pharmacotherapies do not prevent allergic reaction. Immunotherapy injections (also known as desensitization or allergy shots) can reduce symptom severity, reduce medication use, improve quality of life, and even reduce the risk of developing new allergies in the future. Desensitization (immunotherapy) is the only way of "teaching" the immune system to tolerate allergic triggers. It is effective in most people with hay fever and often helps those with asthma. Immunotherapy is also an essential part of managing people with dangerous allergic reactions (anaphylaxis) to bee and wasp stings. Medicines may help you to live with allergies but will not cure these problems. Furthermore, it is not always possible to avoid allergic triggers, such as grass pollens. About 3 in 4 patients with hay fever experience significant improvement with immunotherapy. Sometimes symptoms are reduced rather than abolished. In that case one may need medication as well. In stinging insect allergy (bee, wasp), the protection against further dangerous allergic reactions to stinging insects is variously quoted at between 80 and 95 %. Recent studies in children suggest that if immunotherapy is commenced soon after allergies first develop, it may actually reduce the risk of developing allergic reactions to other allergens, and even reduce the risk of later developing asthma.

Mechanism of Therapeutic Action
The current thinking is that in allergic reaction the body responds to innocuous substances from the environment as if they were invading parasites. The body begins to produce specific immunoglobulin of the E class, Immunoglobulin E (IgE). The goal of immunotherapy is to alter this response, much like a vaccine alters the response to an infectious agent. It appears that allergy shots work by increasing the amount of a different class of immunoglobulins, called IgG. When IgG circulate in the blood plasma and tissue fluids in large amounts, they bind to allergens and reduce the ability of IgE to detect the presence of the allergens. The body begins to treat the allergen more like a bacterium or a virus (effectively destroying it) instead of as a parasite. Thus, the inflammation, secretions, and tissue alterations that take place in untreated allergic disease decrease with immunotherapy. The relative increase of the IgG to IgE ratio leads to better or complete tolerance of the allergen. By giving small but increasing amounts of allergen at regular intervals, tolerance increases. The end result is that the person becomes "immune" to the allergens, so that they can tolerate them with fewer or no symptoms. This process is also known as specific immunotherapy, because one is trying to turn off one or more specific allergic responses. Thus, the solution that is being injected has been tailored by the allergist to contain one or more kinds of allergens according to the person's allergy profile. The higher the dose tolerated without significant side-effects, the more likely is treatment successful.

Indications for Immunotherapy
Immunotherapy is indicated for patients with dangerous allergic reactions (anaphylaxis) to stinging insects like bees, wasps, and the imported South American Fire Ant. It may also be indicated for patients with hay fever or asthma in whom it is difficult or impossible to successfully avoid the cause; Medication does not work; Medication causes side-effects; An alternative to medication is needed. Immunotherapy is occasionally recommended for the treatment of atopic eczema. It is not currently recommended for the treatment of food allergy, or for insect or tick bites, because it doesn't appear to work. There are commercial extracts available for the imported South American Fire Ant which was identified for the first time in Australia during 2002. Unfortunately, there are no commercially available vaccines yet for the Australian Jumper Ant, although research in this area is under way.

Age Considerations
Immunotherapy injections work in both children and adults. They are generally safe to give to pregnant women. Some doctors recommend stopping treatment during pregnancy. This is not because immunotherapy could cause malformations in the developing baby, but because of the concern that, in the case of a rare adverse reaction to the treatment, the fetus may suffer from oxygen deprivation. When dangerous allergic reactions to insect stings occur, immunotherapy may be advised regardless of age. In older patients, immunotherapy may not be recommended as they may have a reduced capacity to cope with side-effects. When treating non-life threatening allergies like hay fever, young children may be difficult to convince of the benefits. Nevertheless, research suggests that immunotherapy is especially effective when started early in life, soon after the development of allergies. The evidence is particularly strong that, in children, immunotherapy prevents future sensitization (the development of new allergies).

Procedure
Small hypodermic syringes are used to inject commercial allergen extracts. Injections are normally given into the loose tissue over the back of the upper arm, half way between the shoulder and elbow. Injections are given under the skin ("subcutaneous"). This is the least painful place to inject allergen, as there are few nerve endings in the skin. When given correctly, the injections should be slightly uncomfortable. They are not normally painful and are usually well tolerated by adults and teenagers. Some doctors may advise you to take an antihistamine a few hours before each injection to reduce the likelihood of local discomfort and other side-effects.

Allergy 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. This usually means four to six months of weekly injections to reach the maintenance dose. Once the maintenance dose is reached, the injections are administered less often (every two to four weeks), still on a regular basis. Maintenance injections are normally given once per month for a few years. Generally, the longer the treatment and the higher the dose, the greater the therapeutic benefit.

Some allergy specialists use a form of treatment called pre-seasonal immunotherapy. Injections are given approximately once per week during winter, stopping just before the spring hay fever season begins. This is repeated each year for 3 - 5 years, and increasing improvement is seen year after year. In the United States, this form of treatment is controversial and usually not employed by allergists who are certified by the American Board of Allergy and Immunology.

After successful completion of immunotherapy, long-term protection can be expected for a period of 3-5 years or more. Therapy can be repeated should symptoms begin to return or if the individual becomes exposed to new allergens that were not included in the previous treatment regiment. This form of treatment is covered by the vast majority of insurance companies in the United States, because allergy vaccine injections have been proven to be significantly more effective than placebo injections.

In some countries, particularly in Europe, there is a strong tradition of undertaking immunotherapy using oral vaccines or sublingual drops. While there has been some interesting research in this area in recent years, the effectiveness of this form of treatment is difficult to compare with standard injected immunotherapy. Double-blind, placebo-controlled studies in Europe using high-dose sublingual immunotherapy have shown benefit. However, this form of treatment is not approved or licensed in the United States. Some forward thinking practitioners in the United States, particularly ENT physicians, offer sublingual immunotherapy as another immunotherapy option.

Side Effects and Adverse Reactions
Itchiness, swelling, and redness at the site of injection are expected. Systemic reactions such as hives or anaphylaxis occur rarely and need to be treated immediately. If such reactions occur, the allergy specialist will adjust the dosage to a safe level. Patients are advised or required to wait in the clinic for 20-30 minutes so that they can be treated immediately in the case that they develop a severe systemic reaction. The risk of a systemic reaction is reduced if the patient avoids exercising or overheating for a few hours before and after the procedure. Some heart and blood pressure medications such as beta-blockers are contraindicated as well.

The physician should be consulted if the patient notices a worsening of allergy symptoms or if he or she is suffering from a cold or has been undergoing a different kind of vaccination procedure. Immunotherapy does not increase the risk of contracting a cold.