Considerable evidence has been presented by Lewis1 to support the conclusion that a diffusible substance is responsible for the development of the urticarial lesion which comprises "the triple response" of local vasodilatation, flare and eventually local edema. This material, which is called the H substance, is liberated by injured cells and closely resembles histamine in its action. It apparently causes the local vasodilatation and wheal by direct action on the capillary wall and the flare by the chemical stimulation of the sensory ending of the skin, bringing about widespread arteriolar and venous dilatation through the mechanism of the axon reflex. Support of this theory has been offered by others.2 However, the evidence that histamine is the urticariogenic substance is indirect. It has never been isolated from a wheal, and not all investigators agree that it plays any part in the development of the wheal.
CURTIS AC, OWENS BB. BETA DIMETHYLAMINOETHYL BENZHYDRYL ETHER HYDROCHLORIDE (BENADRYL) IN TREATMENT OF URTICARIA. Arch Derm Syphilol. 1945;52(4):239–242. doi:10.1001/archderm.1945.01510280023003
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