Hyposensitization

Hyposensitization (or allergy desensitization) is a form of immunotherapy in which the patient is vaccinated with progressively larger doses of an allergen to which they have been diagnosed as being sensitive. Hyposensitization can either reduce the severity of symptoms or eliminate hypersensitivity altogether.

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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 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 immunomodulator techniques that aim to alter the response of the immune system in order to alleviate or cure autoimmune disease, cancer, and so forth. These include Enzyme Potentiated Desensitization (EPD) and its variant, Ultra Low Dose Enzyme Activated Immunotherapy (LDA), which have replaced "escalating dose" treatments in the U.K. but not in the U.S.

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.^[1]

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 (Antihistamines) do not prevent allergic reaction, but instead block the action of histamine in the body, reducing allergic symptoms. Immunotherapy injections (also known as desensitization or allergy shots), in contrast, literally train the immune system to tolerate allergic triggers, by means of gradual exposure to increasing amounts of the offending allergen. Immunotherapy is most effective for pollen, dust, and animal dander allergies, and may help those with asthma.^[2]

About 3 in 4 patients with hay fever experience significant improvement with immunotherapy. Sometimes symptoms are reduced rather than abolished. In that case immunotherapy may allow the patient to reduce the quantity of medication required for symptom relief.

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.

Immunotherapy is also an essential part of managing dangerous allergic reactions (anaphylaxis) to bee and wasp stings. In these cases, the protection against further dangerous allergic reactions to stinging insects is variously quoted at between 80 and 95%.

Mechanism of Therapeutic Action

It is currently thought that a person becomes 'sensitized' to a specific allergen prior to development of fully developed allergic disease. The immune system of these individuals, for reasons not fully understood, misinterprets a usually innocuous substance as a disease agent, and begins producing a type of antibody against it, called immunoglobulin E (IgE). This is called the 'primary antibody response.' The IgE produced during this response binds to basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. When the person again encounters the allergen, these basophils and mast cells that have bound to IgE release histamine, prostaglandins, and leukotrienes, which causes inflammation of the surrounding tissues, resulting in allergic symptoms.

However, allergic reactions require a sufficient quantity of allergen to be present to occur. Even the most allergic individual can tolerate minuscule amounts of an allergen without experiencing symptoms. Immunotherapy commences with the injection of a tiny amount of offending allergen, and gradually increases the dose until the individual's immune system is essentially 'retrained' to tolerate exposure without producing an allergic response. This process is also known as specific immunotherapy. The serum injected is compounded specifically for the individual, based on his or her unique allergy profile, and treats for specific allergens. Thus, if a person allergic to grass pollen and cat dander is treated with serum containing only grass pollen, the allergy to cat dander will remain.

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 is not indicated for food allergies, because it has not been proven effective in these cases, possibly because of the different immunoglobulin mechanism involved in food allergy.

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.

Immunotherapy may also be appropriate for patients with other allergies for which it is effective, in whom it is difficult or impossible to successfully avoid the cause, or for whom medication has proven ineffective or causative of undesirable side effects.

Considerations

Immunotherapy injections work in both children and adults. They are generally safe to give to pregnant women, although some doctors recommend stopping treatment during pregnancy. This is not because immunotherapy itself is dangerous to 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.

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 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.

See also

Sublingual immunotherapy