230 THE PRINCIPLES OF IMMUNOLOGY 



of injection in from a few minutes to an hour or two and show edema, 

 erythema or urticaria. There may also be a general immediate reaction 

 which appears in from twelve to twenty-four hours and in addition to 

 the usual symptoms and signs of serum disease may be accompanied 

 by severe asthmatic form of dyspnea, cardio-vascular disturbances with 

 cyanosis, collapse, chills, nausea and vomiting and renal disturbances 

 including complete suppression for several hours. If the second injection 

 is given when hypersusceptibility is not marked, as for example after 

 a small primary dose, or several years after a primary dose, the accel- 

 erated reaction is not likely to be immediate but appears in from two 

 or three to five or six days. Under these circumstances the reaction 

 may appear as an ordinary case of serum disease or may be more severe. 



Anaphylactic Shock in Man. There is little doubt that the accel- 

 erated reactions of serum disease bear in some way a relation to ana- 

 phylactic shock. During the period of .hypersusceptibility in man the 

 subcutaneous administration of serum rarely if ever produces death, 

 in spite of the fact that the clinical symptoms may be extremely severe. 

 On the other hand, intravenous injections have been reported to produce 

 death following symptoms closely resembling those of anaphylactic 

 shock in animals. Reports of accidents of this sort led to the funda- 

 mental investigations of Rosenau and Anderson, which have been 

 described. Injections of serum into the spinal canal have been followed 

 by fatalities, but an analysis by Auer of the reported cases leads him 

 to believe that for the most part these deaths were due to other causes 

 than anaphylaxis. Miller and Root, in analysis of death following 

 subcutaneous administration of horse serum, find that death in some 

 instances was probably caused by status thymo-lymphaticus and that in 

 other cases the cause of death had not been demonstrated to be ana- 

 phylactic. The clinical and pathological picture of fatalities has in most 

 instances not been clearly described. Nevertheless, Boughton has 

 recently reported a case in which a man, the subject of bronchial 

 asthma when near horses, died upon being given intravenously one 

 minim of normal horse serum. Autopsy showed enormous distention 

 of the lungs with congestion of other viscera and numerous small hemor- 

 rhages. This apparently is an instance of true anaphylactic shock in 

 man, and it cannot be doubted that such accidents occur. Caution 

 must be exercised, however, in attributing death to anaphylaxis because 

 of the numerous other conditions which may lead to sudden death, 

 particularly in the course of acute infectious diseases. 



Natural Hypersusceptibility. The recent scientific investigations 

 of hay fever and its various modifications, as well as asthma, eczema, 

 other diseases of the skin, angio-neurotic edema and certain gastro- 

 intestinal disturbances, have shown that a considerable number of these 

 cases are hypersusceptible to proteins of various origins. The skin 

 reactions, to be described subsequently, and the effect of specific treat- 

 ment both demonstrate the etiological influence of the special proteins. 

 The evidence presented from large clinics devoted to the study of these 

 conditions leaves no doubt concerning the fact that many of these cases 



