Allergen immunotherapy: what can and cannot be mixed?

Allergen immunotherapy is performed with allergenic products derived from a wide variety of sources in differing formulations, dilutions, and expressed potencies. The use of standardized allergen products is leading to more uniform potency designations with these products, but only a few products have been standardized. Increased information regarding allergen crossreactivity and the stability of allergens is becoming available, but the scientific knowledge is still incomplete. Despite these problems and the lack of a standardized approach to immunotherapy, a growing body of knowledge is becoming available to move toward uniform formulation practices. The selection, total number, and proportions of allergen components that are included in therapeutic mixtures are critical aspects of formulating allergen immunotherapy. From a practical perspective, it is tempting to include all relevant allergens into a single vial in equal proportions. This approach can eliminate the need for multiple injections and potentially reduce cost and time. However, this potential gain can be at the expense of clinical efficacy. Based on current evidence for effective doses for allergen immunotherapy, the total number of allergenic extracts that theoretically can be added to a therapeutic mixture is between 7 and 15, depending on the potency of stock allergen extracts used and the volume administered to the patient. The incremental additions of allergenic extracts could reduce the final concentrations of the individual components in the mixture and thus reduce their clinical effect. The preparation of allergen immunotherapy vaccines with an increasing number of extracts creates a potential for interactive effects that can change their allergenic and immunogenic properties. Of particular importance is the contribution of proteolytic enzymes in some fungal and whole-body insect allergenic extracts. For these reasons, guidelines are needed to reduce the number of extracts to include in allergen immunotherapy mixtures.