To establish a unified clinical concept for histamine-driven pathologies beyond classical allergy, this review introduces the term Histamine-Mediated Syndrome (HMS), defined as the spectrum of multi-organ symptoms arising from elevated plasma histamine levels via receptor-mediated signaling through H1–H4 receptors expressed across diverse tissues and cell types. The authors highlight that baseline plasma histamine concentrations in conditions such as allergic rhinitis (AR) and chronic urticaria (CU) are frequently higher than conventionally recognized, thereby driving comorbid manifestations in histamine receptor-expressing organs beyond the primary allergic focus. Emerging clinical evidence is integrated to support the use of an immunoglobulin/histamine complex (IHC) as a rational therapeutic strategy for HMS, extending its applicability well beyond its established indications in AR and CU. By synthesizing available mechanistic and clinical data, the review proposes a systematic clinical framework for recognizing and managing HMS, suggesting that this syndrome may be substantially underdiagnosed in routine practice. These findings position IHC as a promising candidate for the broader treatment of histamine-driven disorders across multiple organ systems. 

Kim, H.S., Noh, G. Histamine-Mediated Syndrome (HMS): Beyond Allergy and Therapeutic Potential of Immunoglobulin/Histamine Complex (IHC). International Journal of Molecular Sciences. 2026 May 17; 27: 4494. doi:10.3390/ijms27104494.