226 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



Another characteristic of the individual who shows these idiosyncrasies 

 is that his tissues are likely to react to more than one substance, and 

 .as a rule about one-half of the patients show what has been termed mul- 

 tiple sensitizatio'n. The variety of material which calls forth these reac- 

 tions and are known to produce the symptoms in many of these hyper- 

 sensitive individuals, is very great and is not confined to the proteins 

 or those substances producing antibodies when injected into animals. Not 

 only are reactions obtained to the extracts of many pollens of plants, such 

 as ragweed and timothy in the hay fever patients, extracts of hair and 

 the epidermis of both domestic and wild animals and fowls in the asthmat- 

 ics, preparations of blood serum from these same animals or extracts of 

 their meat, or of fish, vegetables, nuts and various fruits, as well as prep- 

 arations of egg albumen, of milk and of cereals, which are often responsible 

 for the eczemas, especially in children ; but symptoms may also be produced 

 and skin reactions obtained from the use of a variety of crystalloids and 

 of drugs and chemicals. Since these latter substances contain no protein, 

 as far as one can determine, it is difficult to explain their action upon 

 the same hypothesis as that used to elucidate the anaphylactic reaction 

 in animals. Of the crystalloids, White has described cutaneous reactions 

 to lactose in eczematous children. The metals and drugs which have been 

 reported as producing symptoms and which are responsible for the idio- 

 syncrasies cover a wide field and include the true metals (mercury and 

 arsenic) ; the halogens (iodin) ; the alkaloids (quinin) ; the methane 

 derivatives (iodoform) ; cold tar products such as antipyrin, benzol deriva- 

 tives and others. 



Attempts have been made to correlate these reactions from drugs 

 with those produced by protein substances, by assuming that the drug or 

 metal united with the protein of the individual to form a new protein sub- 

 stance and evidence has been brought forward by Friedberger and Ito(a), 

 to show that guinea-pigs may be sensitized to a mixture of iodin and 

 guinea-pig serum or to a mixture of salvarsan and a guinea-pig serum. 

 It is perhaps possible to conceive that in the drug and metal idiosyncrasies, 

 such a combination does take place between the blood serum of the in- 

 dividual and the drug or metal, and that thus a new protein is formed. 

 So far, however, there is no evidence in human beings which would con- 

 firm this hypothesis. It is true that some of these drug idiosyncrasies 

 do develop only after repeated use of the substances. This has been the 

 case with salvarsan and arsphenamin idiosyncrasy, that developing after 

 the repeated use of atoxyl and that recently described by Gerden which 

 develops in dye workers and is caused by the inhalation of p-phenyldiamin 

 or ursol. In the latter instance, the dye is used for coloring fur and one 

 might be suspicious that the sensitization had been produced towards the 

 epidermal dust of the animal skins rather than towards the dye. Though 

 perhaps gradual sensitization after repeated use is common in drug idio- 



