Proposition for a New Classification of Hypersensitivity Reactions – an Expanded Nomenclature

Diseases associated with hypersensitivity reactions (HRs) are extremely common and can affect the quality of life of millions of people, sometimes with life-threatening severity. In order to diagnose, treat, cure, or potentially prevent these diseases, clinicians and scientists need a better understanding of the entire immune process, from its initiation through the central mechanism to the effector phase. A new classification is needed, primarily because earlier classifications defined HRs almost exclusively by their effector mechanisms. However, outstanding achievements in immunological science over the past decades have revealed the critical, decision-making roles of initiation and central mechanisms in shaping the well-known effector phases. In addition, a crucially important group of HRs consists of small-molecule drug-induced reactions, which include both immunological and non-immunological pharmacological processes; therefore, the incorporation of these entities represents a key aspect of the revised classification. This review article provides a historical overview of the evolution of the main HR classifications, and proposes a new, expanded classification that (a) considers the initiation, central, and effector phases of HRs as interconnected, equally important processes; (b) highlights the role of peripheral barrier tissues in the breakdown of tolerance, thereby contributing to the development of HRs, and (c) distinguishes between classic and non-classic HRs (e.g., pharmacological interaction with immune receptors [p-i] reactions and pseudoallergies). Adoption of this new classification may expand the possibilities for developing preventive and causal therapies and help physicians appropriately interpret and thus effectively treat the heterogeneous phenotypes of hypersensitivity diseases.