Histamine-Mediated Syndrome (HMS): Beyond Allergy and Therapeutic Potential of Immunoglobulin/Histamine Complex (IHC)

Histamine, present in almost all tissues, exerts diverse biologic actions through four receptors expressed across multiple organs and cell types. Histamine concentrations are elevated in various conditions. A wide spectrum of clinical manifestations where histamine levels increase has been described. When plasma histamine concentrations are increased, multiple symptoms may occur via histamine receptor-mediated signaling. These clinical situations are defined as histamine-mediated syndrome (HMS). Recent reports describe the use of an immunoglobulin/histamine complex (IHC) to treat conditions beyond classical allergic diseases, such as allergic rhinitis (AR) and chronic urticaria (CU). Baseline plasma histamine levels in AR and CU can be higher than expected. This suggests histamine-driven comorbid manifestations in tissues and organs expressing histamine receptors. Accordingly, HMS may be more common in routine practice than is generally appreciated. IHC may represent a rational therapeutic option for HMS. In this review, we define HMS and integrate the available evidence to propose a systematic clinical framework.