Another, more routinely used approach that aims to permanently eliminate the allergic response is allergen desensitization. This form of immunotherapy aims to restore the patient’s ability to tolerate exposure to the allergen. Patients are desensitized by injection with escalating doses of allergen, starting with tiny amounts. The mechanism by which desensitization occurs is not definitively established, but for most successfully desensitized patients, the procedure results in a change in the antibody response from one that is IgE predominant to one dominated by an IgG subclass. Successful desensitization appears to depend on the induction of Treg cells secreting IL-10 and/or TGF-β, which skew the response away from IgE production (see Section 14-4). For example, beekeepers exposed to repeated stings (paralleling the therapeutic desensitization process) are often naturally protected from severe allergic reactions such as anaphylaxis through a mechanism that involves IL-10-secreting T cells. Similarly, specific allergen immunotherapy for sensitivity to insect venom and airborne allergens induces the increased production of IL-10 and in some cases TGF-β, as well as the production of IgG isotypes, particularly IgG4, an isotype selectively promoted by IL-10. Recent evidence shows that desensitization is also associated with a reduction in the numbers of inflammatory cells at the site of the allergic reaction. A potential complication of the desensitization approach is that in spite of starting with extremely small doses of allergen, some patients can experience an IgE-mediated allergic response, sometimes including bronchospasms. Thus, many physicians feel that allergen immunotherapy is contraindicated in patients with severe asthma. For patients who experience resolution of their allergy symptoms during allergen immunotherapy, weekly or every other week injections are continued for 3 years, and then the therapy is discontinued. In approximately half of patients treated in this fashion, symptoms do not recur following cessation of the injections. These patients experience durable ability to tolerate the allergen without symptoms. Recent studies suggest that administration of immunotherapy via the sublingual route is equally or more effective than administration by subcutaneous injection, offering the possibility of less expensive and perhaps more effective immunotherapy in the future.
When a patient is allergic to a drug that is essential for treatment of a disease (such as an antibiotic, insulin, or a chemotherapeutic agent), it is often possible to achieve a state of temporary acute desensitization by treating the individual with progressively increasing doses of the drug, starting at a very low dose that causes no allergic symptoms and increasing the dose every half hour until the therapeutic dose is reached. It is common for individuals undergoing drug desensitization to manifest mild to moderate allergic symptoms (itching, urticaria, mild wheezing) at some time during the procedure. If this occurs, the physician reduces the dose to the previous tolerated dose and then advances the dose again. This procedure is thought to lead to subclinical activation of mast cells and basophils that have been sensitized with IgE against the drug, inducing them to gradually release their intracellular mediators at a rate that does not cause severe symptoms; eventually all of the cell-bound IgE is consumed by this process, leaving insufficient IgE available to cause an allergic reaction when subsequent therapeutic doses are administered. In order to maintain the desensitized state, the patient must receive daily therapeutic doses of the drug. If treatment is interrupted, then newly formed mast cells and basophils can be charged with newly secreted drug-specific IgE and can accumulate at levels sufficient to yield a new anaphylactic reaction.