toms either develop after a few hours, the "immediate reaction," or after a few days, the "accelerated reaction." As the time interval between the injections increases the "immediate reaction" no longer appears, but the "accelerated reaction" still occurs and has even been noted when the second injection followed seven years after the first. The symptoms which characterized the "accelerated" reaction are similar to those already described, with this difference that they occur suddenly, and disappear swiftly within approximately a day. The "immediate" reaction is somewhat different and characterized by a local edema at the site of injection which slowly increases and reaches its maximum within about twenty-four hours, and disappears within two to five days. Associated with this local reaction there is high fever, and the skin shows crops of transitory eruptions of varying character. In a small proportion of all cases the immediate reaction shows a grave picture, there is nausea and vomiting, and at times even collapse.
The similarity between serum disease and anaphylaxis was early noted by v. Pirquet and Schick. The specific local edema, for example, is exactly analogous to Arthus's phenomenon in rabbits; the non-fatal collapse cases also are similar to the results which Arthus obtained in rabbits where he noted a strong drop in blood pressure.
There is another class of severe reactions, fortunately rare, which occur suddenly when a patient is injected for the first time with serum. The symptoms bear a striking analogy to those observable in lethal anaphylaxis in guinea-pigs and rabbits. Some individuals show a marked respiratory distress of an asthmatic type with cyanosis, similar to guinea-pigs, and others again show symptoms where the respiratory involvement is not so pronounced, but where cardiac weakness predominates. These cases often end in death. Examination of the history of such individuals often shows that they were subject to asthma, or possessed a peculiar idiosyncrasy to the odor of horses which brought on the symptoms of hayfever and asthma. Cases of this kind are probably examples of anaphylaxis in spite of the apparent absence of any sensitizing injection, for this state of sensitization could easily be attributed to inheritance or to a gradual sensitization via the lungs or the stomach. It is well-known, for example, that a sensitized guinea-pig will transmit this property to her offspring, and we may assume that this also plays some role in human cases; moreover Rosenau and Anderson have shown that sensitization may be accomplished in guinea-pigs by feeding raw horsemeat, and more recently Rosenau and Amoss reported that they were able to sensitize guinea-pigs for human serum by injecting the infinitesimal amount of organic material found in the expired breath of human beings. These experimental facts render it quite probable that all these cases where the first injection of horse serum produced alarming symptoms or even death, were sensitized in
