HYPERSUSCEPTIBILITY IN MAN 229 



injection, and in our experience have been most frequent after ten to 

 eleven days. The most noticeable and most common symptom is a skin 

 eruption which is usually urticarial but may be a patchy or diffuse 

 erythema, a scarlatiniform or a multiform eruption. Edema may 

 appear in the lips, eyelids, face or other parts of the body and rarely 

 may effect the larynx. According to Longcope, " in one instance a 

 transient hemiplegia was supposed to be caused by local edema of the 

 meninges." We have seen one case in which a broncho-pneumonia, 

 following a prophylactic injection of serum appeared to be the sequence 

 of an edema of the bronchi. There is often lymph-node enlargement, 

 which may precede the eruption and may be accompanied by enlarge- 

 ment of the spleen. There is likely to be a moderate fever, headache, 

 malaise and occasionally nausea and vomiting. Multiple joint pains, 

 increased by motion, but without tenderness, redness or swelling, are 

 common in severe cases. Albuminuria appears in 5 to 9 per cent, 

 of the cases, and Longcope has found that there is likely to be salt 

 and water retention with little or no disturbance of nitrogenous elim- 

 ination. There may be a primary leucocytosis, followed by a leuco- 

 penia, which latter shows an absolute increase of lymphocytes. The 

 condition usually lasts twenty-four, forty-eight or seventy-two hours 

 and occasionally is prolonged to twenty days or more. Relapses may 

 occur, more particularly after the use of large amounts of serum. 



Several factors enter into the occurrence, severity and duration of 

 the disease, the larger doses giving more frequent occurrence, greater 

 severity and longer duration. There are certainly individual differences 

 in the resistance of patients and probably individual differences in 

 specimens of serum. Sera from different species exhibit differences 

 in toxicity for man, that of the ox, according to Kraus, being less likely 

 to produce serum disease than that of the horse. The globulin pre- 

 cipitation or so-called concentration of horse serum in the preparation 

 of antitoxins reduces the toxic manifestations in man. 



The Accelerated Reaction. Frequently repeated injections of serum 

 at properly spaced intervals may lead to a state of resistance or im- 

 munity, but this is practically never permanent. Following a primary 

 injection or series of injections, there usually develops a state of hyper- 

 susceptibility. This condition does not precede the appearance of the 

 delayed reaction and does not precede the tenth day after injection, 

 even if the delayed reaction fails to appear. Repeated doses of serum at 

 short intervals delay the appearance of hypersusceptibility. The height 

 of sensitiveness is reached in from two to three months, after which it 

 slowly subsides but probably never entirely disappears. We have 

 observed accelerated reactions nine and fourteen years after primary 

 injection. The hypersusceptibility exhibits itself only on injection of 

 the protein and is specific for the species from which it originated. 

 Following the second injection of the protein or serum there is occa- 

 sionally no acceleration of reaction, but if accelerated it may be mod- 

 erately or markedly so, the last producing the so-called immediate 

 reactions. These immediate reactions may be local, appear about the site 



