Release of prostaglandin D2 and histamine in a case of localized heat urticaria, and effect of treatments

Abstract

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.

The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions

“…Although PGD2 potentiates the increase in vascular permeability due to histamine in rat skin (Flower et al, 1976) there is no evidence for the potentiation of the wheal (Barnes & Heavey, 1986) erythema, or increased blood flow (Maurice et al, 1987) due to histamine injection in human skin. The relative proportions of histamine and PGD2 found in this study are similar to the ratio in blood draining whealed skin in immediate cold and heat urticaria (Heavey et al, 1986a;Koro et al, 1986) and we conclude that PGD2 has at best a minor role in immediate allergic reactions in skin.…”

“…PGD2 and PGE2 were analysed by radioimmunoassay (RIA) as their methyloximate derivatives by methods similar to those previously described Koro et al, 1986). Briefly, each 0.2ml sample was mixed with 0.2ml of methyloximating reagent (methoxyamine hydrochloride 0.12mM, sodium acetate 1.OM and ethanol 10% v/v, pH 5.6-5.8) and incubated either at 60°C for 30 min or at room temperature overnight.…”

“…were first extracted on C18 SepPak cartridges as previously described (Koro et al, 1986 In the in vivo antigen challenge experiments the abraded sites were washed twice for a total time of 10min to remove most of the prostaglandins generated in response to the abrasion. Although care was taken to prepare uniform abrasions there was variation in the release of prostaglandins from the three sites on each subject.…”

“…PGD2 is released from passively sensitized guinea-pig skin challenged with antigen in vitro (Kozuka et al, 1987) and further evidence suggesting that mast cells in human skin generate PGD2 has come from studies on subjects with urticaria. Venous blood draining thermally challenged skin contained substantially increased concentrations of PGD2 in both cold (Heavey et al, 1986a) and heat (Koro et al, 1986) urticaria. The time course of release was similar to that of histamine suggesting the mast cell as the common source.…”

Prostaglandin D2 release from human skin mast cells in response to ionophore A23187

“…Lung mast cells generate prostaglandin D2 (PGD2) in vitro following calcium ionophore A23 187-and IgE-dependent activation (Holgate et al, 1984). Evidence ofPGD2 generation by human skin derives from experiments in vivo in which local provocation of cold or heat urticaria and anaphylaxis is accompanied by a rise in venous plasma histamine or PGD2 concentrations (Heavey et al, 1986;Koro et al, 1986;Barr et al, 1986). The precise function of released PGD2 in the skin is not known, although recent studies have shown it to be a weak vasodilator in the human cutaneous vasculature (Beasley et al, 1987) and it is also a weak chemokinetic agent in human leukocytes (Goetzl et al, 1976) causing neutrophil accumulation when injected 'Author for correspondence at: Clinical Pharmacology, CF104, Centre Block, Southampton General Hospital, Southampton S09 4XY. intradermally (Soter et al, 1983).…”