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Allergen immunotherapy practice parameter update.

In 1911 Leonard Noon proposed a theory that patients suffering from hay fever were overly sensitive to toxins from grass pollen. As a trial treatment, he began inoculating patients with increasing strengths of grass pollen vaccines. By clinical observation standards, this treatment was found to be successful. By the 1920s it was found that vaccines could be given for other allergens. Perennial allergen therapy required perennial treatment, unlike the original pre-season treatment for pollens. It was empirically appreciated that immunotherapy was effective but not scientifically proven until the early 1960s. Since then, the immunologic evidence continues to encourage broadened use of immunotherapy for inhalant sensitivities. As the employment of this immune modulation has advanced, guidelines have been adopted to promote the most appropriate, consistently safe, and efficacious methods of application. This summary article is intended as a guide for Kentucky Physicians to the current state of the art for immunotherapy vaccinations in the treatment of allergic disorders, as set forth in Allergy, Asthma, and Immunology Practice Parameters published in January 2003.

Algorithms↗

Effect of hyposensitization on atopic dermatitis in dogs.

In a double-blind study, 51 dogs with clinically defined atopic dermatitis were injected with either alum-precipitated allergen solutions or a placebo. Comparing the treatment results of both groups on the basis of scores for clinical signs, a significant difference in clinical improvement was established in favor of the allergen-treated dogs (P less than 0.01). The proportional changes of scores for clinical signs in the allergen-treated group ranged between +27.3% and -100% (median, -61.5%) and in the placebo group between +36.4% and -100% (median, 0.0%) with respect to the initial scores. Immediate skin test reactivity disappeared only in the dogs with a good clinical response. Of 27 dogs treated with an allergen solution, 16 (59.3%) had an improvement of 51% or more. In the placebo group, 5 of 24 dogs (20.8%) reacted this way. There was total remission of the clinical signs in 9 and 4 dogs, respectively. In the dogs in which, after 9 months of hyposensitization, any improvement was observed, the chance for final improvement of more than 51% was calculated as 84%. Discriminant analysis revealed that evaluation of the effect of immunotherapy can be restricted to the 9-month follow-up examination.

Adjuvants, Immunologic↗

[Situation and trends of hyposensitisation treatment (author's transl)].

Since the introduction of the hyposensitization treatment by Noon and Freeman in 1911, an essential change of the hyposensibilisation technique, despite numerous recently published results, has not been able to be demonstrated up to now. In most cases, treatment is still done with and allergen mixture consisting of a variety of unknown compounds with changing composition according to own experiences concerning initial and final dosis of the allergen or the application intervals. The linkage of the allergens to chemical substances, the modification into so-called allergoids as well as the investigation of the hyposensitisation success, such as determination of blocking antibodies, the course of the titre of specific antibodies by the RAST technique, the histamin liberation from leucocytes of allergic persons after antigen contact and the lymphocyte stimulation by allergens are starting points for developing a scientific base to the hyposensitisation treatment and for introducing new results mainly from experiments on animals into the clinical practice. Standardisation of allergens, optimisation of the dosis and the application intervals as well as the further decrease of the allergenicity and the optimal choice of the adjuvants have to be regarded as the problems to be solved in the next future. On the other hand, the use of allergen determinants linked to non-immune carriers or the induction of a tolerance by another way seem to be not yet a subject with clinical relevance during the next years.

Adjuvants, Immunologic↗

Antigen-specific densensitization in a rabbit model of acute hypersensitivity pneumonitis.

Rabbits that had been prepared to develop acute alveolitis after aerosol challenge with simple protein antigens did not develop chronic alveolitis but rather gradually recovered despite continued challenge. Immunologic accompaniments of waning disease were compared in this model to those associated with intravenous injections of antigen causing "desensitization." We also studied the effects of aerosol challenge prior to systemic immunization, antigen specificity, and the duration of desensitization by aerosolized and intravenous antigen. We found that repeated aerosol or intravenous challenges produced antigen-specific desensitization in this model, and the effect lasted several weeks. Prior exposure to aerosolized antigen was not protective. Neither aerosol nor intravenous desensitization maneuvers abrogated antigen-specific lymphocyte blastogenesis, although an early transient fall did occur. Humoral responses were boosted. These findings suggest that chronic alveolitis is prevented in this model by specific desensitization, without the induction of true tolerance or of nonspecific anergy. Such immunoregulation may result from development of antigen-specific blockade or blocking factors (e.g., lymphokines), antigen-antibody complexes, or suppressor cells affecting specific effector cells. Evaluation of these mechanisms may have implications for diagnosis and prognosis in human hypersensitivity pneumonitis.

Acute Disease↗