A fourth view is that the initial injection of a foreign protein by the fly (i.e., with the first bite) sensitizes the body to that protein. Its subsequent injection at any point in the skin gives rise to a local expression of systematic sensitization. Such local sensitization reactions have been described by Arthus and Breton, by Hamburger and Pollack and by Cowie. The description of such a lesion given by the first named authors, in the rabbit, however, does not suggest, histopathologically at least, a strong resemblance to that of the black-fly. Such an explanation of many insect urticariæ deserves further investigation, however, and may align them under cutaneous expressions of anaphylaxis to a foreign protein injected by the insect. Depending on the chemical nature of the protein injected, a specific chemotactic reaction like eosinophilia may or may not occur. Viewed in this light the development of immunity to insect bites assumes a place in the larger problem of anaphylaxis.
Summary
In order to bring the results of the foregoing studies together, the author appends the following résumé of the clinical data presented in the first paper.
The black-fly, Simulium venustum, inflicts a painless bite, with ecchymosis and hæmorrhage at the site of puncture. A papulo-vesicular lesion upon an urticarial base slowly develops, the full course of the lesion occupying several days to several weeks. Marked differences in individual reaction occur, but the typical course involves four stages. These are, in chronological order, the papular stage, the vesicular or pseudovesicular, the mature vesico-papular or weeping papular stage and the stage of involution terminating in a scar. The papule develops in from 3 to 24 hours. The early pseudovesicle develops in 24 to 48 hours. The mature vesico-papular lesion develops by the third to fifth day and may last from a few days to three weeks. Involution is marked by cessation of oozing, subsidence of the papule and scar-like changes at the site of the lesion. The symptoms accompanying this cycle consist of severe localized or diffused pruritus, with some heat and burning in the earlier stages if the œdema is marked. The pruritus appears with the pseudovesicular stage and exhibits extraordinary persistence and a marked tendency to periodic spontaneous exacerbation. The flies tend to group their bites and confluence of the developing lesions in such cases may result in extensive œdema with the formation of oozing and crusted plaques. A special tendency on the part of the flies to attack the skin about the cheeks, eyes and the neck along the hair line and behind the ears, is noted. In these sites inflammation and œdema may be extreme.
A distinctive satellite adenopathy of the cervical glands develops in the majority of susceptible persons within 48 hours after being bitten in the typical sites. This adenopathy is marked, discrete and painful, the glands often exquisitely tender on pressure. It subsides without suppuration.
Immunity may be developed to all except the earliest manifestations, by repeated exposures. Such an immunity in natives of an infested locality is usually highly developed. There are also apparently seasonal variations in the virulence of the fly and variations in the reaction of the same individual to different bites.
Constitutional effects were not observed but have been reported.