New concepts of hive formation in cholinergic urticaria

Abstract

Patients with cholinergic urticaria (CU) show a number of small, short-lasting hives when their body core temperature increases, usually during sweating following exercise or bathing. The precise mechanism(s) of hive formation in CU has been unclear except for the involvement of acetylcholine. We recently reported that most CU patients show immediate-type skin responses to their own sweat, whereas the rest of CU patients have positive autologous serum skin tests (ASSTs). The former group produced satellite wheals following acetylcholine injection, whereas the latter group produced hives in conjunction with hair follicles. We propose two subtypes of CU: 1) a sweat-hypersensitivity type with strong hypersensitivity to autologous sweat, nonfollicular hives, development of satellite wheals, and lack of positive ASST; and 2) a follicular type with follicular hives and positive ASST, but no hypersensitivity to autologous sweat or satellite wheals. We discuss the mechanisms of hive formation in these subtypes.

Cholinergic urticaria: pathogenesis‐based categorization and its treatment options

“…Consequently, excess acetylcholine stimulates sensory nerve terminals to produce pain and acts on the muscarinic CHRM3 on mast cells in the vicinity of sweat glands to cause weals. In accord with this hypothesis, an intradermal test with cholinergic agents was typically positive in this type of CU 1 . However, we experienced a case of CU patients with AGH which showed the absence of CHRM3 expression even on mast cells, 11 suggesting that some molecules other than acetylcholine may involve the development of CU.…”

“…The sweat glands receive sympathetic innervations but express muscarinic acetylcholine receptors, which are normally expressed on parasympathetic nervous systems; therefore, acetylcholine is considered to be a central signal mediator for the secretion of sweat. Previous reports have demonstrated that subcutaneous injection of cholinergic agents induce sweating and the development of numerous pin‐point hives in patients with CU, and that the symptoms of CU are inhibited by prior atropinization of the skin 1 . In addition, recent studies have shown that not only sweat glands but also mast cells express muscarinic cholinergic receptor 3 (CHRM3), which is a responsible cholinergic receptor for sweating 2 .…”

Clinical Characteristics of Cholinergic Urticaria in Korea

“…It is known that follicular and non-follicular forms have different pathogenic mechanisms8. It is hypothesized that hypersensitivity to autologous serum and sweat may be involved in the wheal formation of the former and the latter type, respectively8.…”

Epidemiology of Non-hereditary Angioedema

“…Although the symptoms of FDEIA and cholinergic urticaria occur after exercise, FDEIA is clearly distinguishable fi'om cholinergic urticaria, which appears as pinpoint-sized wheals with surrounding erythema that occur after sweating (5,6). Patients with FDEIA usually have immunoglobulin E (IgE) antibodies and positive skin prick tests (SPTs) against the causative food allergens.…”