HYPERSUSCEPTIBILITY IN MAN 237 



found that only 75 per cent, of these reacted positively, whereas experi- 

 ence has shown that at least 90 per cent, of such individuals are 

 immune to reinfection. He also pointed out that the immune state 

 following an attack is of much greater duration than is indicated by the 

 typhoidin test. Furthermore, those who have survived typhoid fever or 

 have been vaccinated with bacillus typhosus react positively to para- 

 typhoidin, but it is known that these individuals are not immune to 

 paratyphoid fever. Kolmer and his associates have found no con- 

 stant parallelism between the presence of positive cutaneous tests 

 and those circulating antibodies, whose presence is indicative of im- 

 munity. " The positive anaphylactic skin reaction is, therefore, evidence 

 of infection or sensitization to a particular protein without bearing any 

 direct relation to resistance to infection or reinfection." 



Drug Idiosyncrasies. It is well known in connection with certain 

 drugs, such as morphin, that prolonged use makes it necessary to in- 

 crease the dose in order to obtain physiological effects. This increase in 

 resistance to morphin is specific, but in the case of chronic alcoholism 

 the individual's resistance to somewhat related substances, such as 

 chloroform and ether, is also increased. Experiment fails to show that 

 this resistance is a state of immunity, and no immune reactions 

 in the ordinary sense of the term have been demonstrated. The use 

 of certain drugs, such as iodof orm, iodides, bromides, coal-tar products 

 and quinine, sometimes gives evidence on the part of the patient of 

 a special susceptibility or idosyncrasy in the form of cutaneous erup- 

 tions and more or less severe general symptoms. Both Bruck and 

 Klausner expressed the view that this is an evidence of hypersuscepti- 

 bility similar to or identical with anaphylaxis. Inasmuch as anaphylaxis 

 is a phenomenon concerning proteins, Bruck offered the hypothesis 

 that the drugs enter into combination with the body proteins, so that 

 a new drug-protein complex of specific character is formed 1 . This pro- 

 tein complex may act as a sensitizer, and upon subsequent injection of 

 the drug there occurs a combination with blood proteins to produce 

 a similar complex which reacts with the sensitizer to produce symptoms. 

 Bruck and Klausner claimed to be able to sensitize guinea-pigs passively 

 with the blood of susceptible patients, so that the animals reacted with 

 the symptoms of anaphylaxis. The autopsies on these animals failed 

 to show the characteristic findings of anaphylactic shock. Cole studied 

 patients sensitive to iodides and to copaiba but failed to obtain results 

 justifying the conclusion that the phenomenon should be included among 

 anaphylactic manifestations. Specific cutaneous reactions to such drugs 

 as quinine and aspirin have been described, and it is maintained that 

 small doses by mouth may desensitize, but no widespread confirmation 

 has been recorded. None of the drugs studied is without some essential 

 toxicity and the idiosyncrasies in some instances, according to Sollmann, 

 " are doubtless due to differences in the strength or constituents of 

 drugs." He further states in regard to increased susceptibility that it 

 " may be due to very rapid absorption, or slow elimination ; to the 



