JMIR Publications

ABSTRACT

Aquagenic pruritus (AP) is a rare itch disorder with few effective treatments, and recent case evidence suggests that oral β-alanine may reduce symptoms. The purpose of this letter is to propose a biologically plausible mechanism through which β-alanine may alleviate primary AP. We reviewed case reports describing β-alanine use in AP and integrated these clinical observations with experimental data on mas-related G-protein coupled receptor D (MrgprD)-expressing sensory neurons and their role in mast-cell regulation. Prophylactic β-alanine markedly improved water-induced pruritus in two patients with primary AP, and preclinical data indicate that MrgprD-neuronal glutamate release suppresses mast-cell hyperresponsiveness, suggesting a potential pathway for the observed antipruritic effect. This hypothesis is based on two clinical cases and mechanistic insights derived from mouse models. β-alanine may act through a nonhistaminergic neuroimmune circuit and represents a promising therapeutic candidate for further investigation in AP.