SERUM REACTIONS 313 



vagus nerve which correlates with increased permeability of the 

 tissues but not with the classical anaphylactic sensitization. 



That the existence of an incubation period is not in itself proof 

 of the antigen-antibody mechanism of serum sickness is suggested 

 by the fact that periods varying from hours to days elapse be- 

 tween the injection of various drugs, tuberculin and toxic sub- 

 stances and the appearance of symptoms. In drug allergy there 

 is frequently an incubation period of 6 or more days and symptoms 

 that in part at least may resemble serum sickness. As in serum 

 sickness tlic incubation ])eriod is shortened by subsequent injections 

 of tlie exciting agent. In the tuberculin type of skin reactions and 

 in positive Schick tests there is an incubation period, so to speak, 

 of 24 to 48 hours or longer. All efforts to show that drug allerg}^ 

 and allergy due to infection are mediated by an antigen-antibody 

 mechanism have failed. In the case of the positive Schick test it is 

 the absence of antibodies that permits the toxin to act upon the 

 tissues. To explain the short incubation period occasionally ob- 

 served in serum sickness Zinsser, Enders and Fothergill suggest 

 the possibility of intrauterine or intestinal sensitization but offer 

 no statistical data to support such a correlation. 



Since the incubation period for serum sickness is frequently seven 

 to ten days and since horse serum contains antigenic proteins one 

 might exi)ect that frequently the correlation would be noted be- 

 tween the appearance of antibodies and the development of symp- 

 toms. This could easily be a coincidence. It is not likely that the 

 union of antigen and antibody in the blood stream would cause 

 symptoms as this phenomenon is offered as an explanation for the 

 failure of symptoms to occur in sensitized animals. It has been 

 called "masked anaphylaxis." Dean (1931) has suggested that 

 perhaps tlie reason that antigen and antibody, at times, coexist in 

 the blood without the formation of a precipitate is the ab- 

 sence of optimal ratios of concentrations of each. Furthermore 

 the symptoms in serum disease are not those of anaphylaxis. Con- 

 trast the fever of serum disease with the subnormal temperature 

 of anaphylaxis, the absence of pulmonary symptoms in serum 

 disease and their presence in human anaphylaxis. In the rabbit, 

 note that in serum disease there Ls an elevation of temperature, 

 swelling and hyperemia of the ear but no cardiac symptoms while 



