THE " SERUM-DISEASE 



to be quite different in nature, and in many cases were dependent 

 on the " status lymphaticus," or " thymicus," a condition in 

 which a slight disturbance of any kind may cause sudden 

 death. 



In general terms, the severity and frequency of the serum 

 disease are proportionate to the amount of serum given the larger 

 the dose, the greater the likelihood of its development and the more 

 severe the disease. There are, however, some exceptions : 

 (i) Certain samples of serum appear more potent in this respect 

 than others. The purified diphtheria antitoxin prepared by 

 Gibson (which consists of a solution of globulin) appears to 

 reduce the occurrence of the disease to a minimum. (2) The 

 serum disease is more likely to occur when a second injection is 

 given at an interval of three or four weeks or longer after the 

 first. 



Under ordinary circumstances the disease manifests itself after 

 an interval of eight to twelve clays, or sometimes longer, after the 

 injections. This period is insignificant, since it approximates 

 closely to the period of maximum development of most of the 

 antibodies after an injection of an antigen. Hence it was 

 suggested (by Hamburger and others) that the symptoms might 

 be due to the development of a precipitin, which, by combining 

 with the unaltered horse serum still present in the patient's blood, 

 might cause the production of small precipitates in the circula- 

 tion. These, being deposited in the minute capillaries of the 

 skin, joints, etc., might act as emboli, and cause the characteristic 

 symptoms. Now the blood of a patient who has been treated 

 with serum is frequently found to contain precipitin after a week 

 or ten days, so that the possibility of this explanation is obvious. 

 The phenomenon of the accelerated reaction also appears to lend 

 it support. A patient who has been injected with horse serum 

 may be presumed to have precipitin persisting in his system for 

 some unknown but possibly lengthy period afterward, and on the 

 injection of more horse serum (its antigen) might cause a precipi- 

 tate which would lead to an immediate or accelerated development 

 of the serum disease. It is found in practice that this immediate 

 reaction does occur, but is comparatively rare. In ninety cases 

 where a second injection was given the disease was developed 

 within six hours in nine ; in thirty-nine others it was produced 

 within a period varying from nineteen hours to five days (Goodall). 

 The " immediate effect " described by Goodall differs somewhat 



