ADMINISTRATION OF SALVARSAN AND NEOSALVARSAN 869 



days. The most common are urticarial and scarlatinoid and morbilli- 

 form erythemas, and in rare cases purpura. In some instances an itching 

 of the skin or pruritus without accompanying eruption has been noted. 

 Most of these eruptions are ephemeral and disappear in a day or two. 

 Later and more persistent eruptions have been observed to occur from 

 six to ten days after the administration of the drug. These late erup- 

 tions are more common after intramuscular injection. Some instances 

 of universal exfoliating dermatitis have been reported, persisting for 

 weeks, with fever and debility, and sometimes leading to a fatal termi- 

 nation. 



(c) The Late Symptoms. Delayed reactions may come on after 

 twenty-four hours, in which event they usually consist of vomiting, 

 fever, and diarrhea, similar to the intermediate reactions. More rarely 

 serious and even fatal reactions may develop about three days after the 

 administration of the drug. In these cases the phenomena are either 

 referable to the brain or the liver. In the severe cases there may be 

 headache, vomiting, muscular twitchings, epileptiform convulsions, di- 

 lation of the pupils, absent reflexes, coma, and death. These symptoms 

 are usually the expression of edema of the 'brain or of encephalitis hem- 

 orrhagica. Meirowsky and Kretzmer, 1 in their splendid monograph on 

 the salvarsan therapy of syphilis, present a critical analysis of the fatal- 

 ities following the use of salvarsan. Of 109 fatal terminations recorded in 

 literature, 41 per cent, occurred in the secondary period and 27 per cent, 

 in late nerve syphilis. Three-fifths of the fatalities during the secondary 

 stage resulted from encephalitis. Forty-five per cent, of these occurred 

 in cases in which the dose exceeded 0.5 gm. Grouping all of the cases 

 of single and multiple injections, 66 per cent, of the cases received 

 doses over 0.5 gm. The size of the dose is, therefore, a most important 

 factor in the causation of encephalitis. The danger decreases in pro- 

 portion to the duration of the interval between the injections. 



Another rare syndrome following the administration of salvarsan is 

 characterized by severe jaundice accompanied, as a rule, by fever. This 

 may appear in from three days to several weeks after treatment. Such 

 accidents are much more frequent after intramuscular than after intra- 

 venous injections. Most cases of postsalvarsan jaundice pursue a 

 favorable course, but there are exceptional cases which terminate fatally 

 with the symptoms and autopsy findings of acute yellow atrophy of 

 the liver. 



The Causes of Reaction. At the outset it should be clearly stated 



1 Prakt. Ergeb. auf dem debist der Haut und Geschlechtk, Wiesbaden, 1914. 



