Unreliability of local reactions to serum as tests for general sensitivity.

Abstract

The problem of sensitivity tests for serum can be stated to be as follows: Is it possible, by observing local reaction which follows an intradermal or subcutaneous injection of a small amount of serum, to determine beforehand whether or not a patient will develop anaphylactic shock, and/or severe serum sickness, when given a full therapeutic or prophylactic dose? To be of practical value, local reaction should show within at least one hour of test dose, otherwise doctor would have to postpone main dose far too long. We have long maintained that local reactions are unreliable guides of general sensitivity (Laurent and Parish, 1952). A recent paper, however, entitled An Analysis of Tetanus Prophylaxis in 3,455 Cases by Binns (1961), though it is a useful collection of data, contains some statements and conclusions in opposition to our views, and they should not be permitted to pass unchallenged. The author claims, on basis of 9 months' experience at Leeds Public Dispensary, that local reaction which follows a subcutaneous injection of 0 1 ml. serum is important and that due cognizance should be taken of it. He has found a relationship between local reaction and general reaction, and he implies?though he does not say so?that tests for a local reaction could be of value in detecting presence of general serum-sensitivity. According to Binns's own figures, 73 patients had a local reaction within an hour, and of these only three developed either anaphylactic shock or serious serum sickness; presumably other seventy had average or mild serum sickness or had none at all. Local reaction appeared within 4 days in 133 patients, and of these eight developed anaphylactic shock or serious serum sickness; presumably other 125 had average or mild serum sickness or had none at all. It follows, therefore, that when tests are read after one hour, a positive result signifies hypersensitivity in only 4 per cent.; when read after 4 days, it signifies hypersensitivity in only 6 per cent. Binns remarks that the timing of local reaction seemed to make little difference to risk of developing a general reaction subsequently. Our comment on this statement is that time is necessarily at crux of problem. How can late appear ance of a local reaction (say after 24 hours or more) be helpful as a guide to procedure in administering main dose of serum? Between 5th and 12th day after injec tion of tetanus antitoxin, he has observed a sharp increase in incidence of local reactions followed immediately by a sharp decrease; there was a similar and almost simultaneous fluctuation in incidence of general reactions. He remarks on this close correlation and notes short intervals, in hours, between local and general reactions; it is not clear whether or not he grasps significance of observation. These local reactions were obviously part of serum sickness which normally starts between 5th and 12th day. Pain, swelling, redness, and often urticaria, at site of injection of serum, before, at same time as, or after appearance of a serum rash, are of course extremely common, and have been known ever since sero therapy began. These local reactions at site of injection are often sole manifestation of serum disease in mild cases; they are not evidence of a pre-existent sensitivity., A lack of correlation between positive intradermal tests and general serum sensitivity has been experience of one of us (L. J. M. L.) in course of titration of streptococcal antitoxin on scarlet fever patients. A little over fifty patients, with strongly positive intradermal reactions (mean diameter 20 mm. or more) to a serum dilution of 1 in 10, had to be given full doses of antitoxin a few hours later; none developed any serious general reaction. Ill