Repeating the serum injection within ten days after the first injec tion does not produce symptoms which differ from those following the first injection. But if reinjection takes place in intervals of twelve days to four months, we very frequently see the symptoms of "immediate reaction." Contrary to the first injection the symptoms of the disease appear within the first twenty-four hours, not infrequently a few minutes after reinjection.
The most prominent symptom is the sudden eruption of a general urticaria, with marked (rdema of the face and rise of temperature. In several cases there developed with the eruption of urticaria symptoms of collapse (general cyanosis, dyspno2a, small pulse). These grave symp toms remind one of the fatal termination in guinea-pigs which invariably follows the intravenous reinjection of horse scrum. Fortunately these symptoms of collapse occur only exceptionally in man. Theoretically it is not at all improbable that an intravenous reinjection could result in death. The fatal cases, however, described in literat ure at the beginning of serum therapy, do not belong here, because they were cases of first injection.
A more frequent symptom and often the only one following reinjec tion is a local reaction at the site of reinjection. The subcutaneous tis sues become greatly swollen, sometimes within a few hours, the skin is reddened and there is present a faint erythema and tenderness on pres sure.
As rapidly as the general and local symptoms appear, so as a rule do they subside.
This, however, is not always the end of the disease, for often, espe cially after large doses, there is after four to six days a second general eruption of urticaria accompanied by a rise of temperature, which may recur for a number of days.
After a period of over four months from the first injection, the "im mediate reaction" is not seen, only the second part of the symptoms. As the period of incubation seems to be but half of that of the first injection (which is from S to 12 days), this form of serum disease has been called "accelerated reaction." The disposition to accelerated reac tion seems to be present for years.
Immediate and accelerated reaction only exceptionally follow the first injection, but occurring almost invariably with reinjection, we may almost with certainty conclude that the individual has at one time been injected with horse serum.
We cannot discuss here the theoretical questions as to the cause of the period of incubation and serum disease; we may briefly mention that we believe the cause of serum symptoms to be antibodies.
It is our opinion the action of antibodies on the heterogeneous serum results in a substance which has a disease-producing effect on the organism. After the first injection these antibodies are developed in eight to ten days, the normal period for the development, of serum disease; they remain in the body for several months and if a reinjection takes place during this time, the injected horse serum and the antibodies, which are present, produce the substance \•hich the immediate reaction.
After the antibodies have disappeared, the organism is capable of developing antibodies more rapidly after a renewed injection; and although the serum disease does not manifest itself immediately, it appears earlier than after the first injection and thus we speak of an "accelerated reaction."
The antibodies of "vital reaction" are not identical with the pre cipitins which arc formed in the human organism following the injec tion of heterogeneous serum. The laws, however, governing the develop ment of both kinds of antibodies are similar.
The importance of serum disease to the physician should not be overestimated. Fear of serum disease should not prevent one from employing serum in diphtheria. Only when using large doses we should consider whether the disease is so grave as to make even an intense serum reaction of secondary importance. For this reason we employ Moser's scarlet-fever serum, for example, which must be given in doses of 100 to 200 c.c., only in eases with a doubtful prognosis.
A word of warning is in place against the careless injection of serum, especially against superfluous prophylactic injections, as this tends to produce a hypersensitiveness, which is observed when after the develop ment of the disease a therapeutic injection becomes necessary. There is some danger connected with intravenous injection of serum, especially with reinjection, which can prove fatal. The intravenous serum therapy, recently quite strongly advocated (employing serum free from carbolic acid), should therefore be considered only in very severe cases of diph theria and only in cases to be injected for the first time. It is possible, perhaps, to reduce the hypersensitiveness of those to be reinjected by giving a small dose of scrum subcutaneously previous to the intravenous injection. Experiments on animals give encouraging results in this respect.
Serum disease could be avoided if the serum could be given by mouth, or by the rectum, but this prophylaxis would be valueless because, thus employed, the antitoxin would not get into the general circulation.
Various experiments to remove the toxic properties from the horse serum and still retain the antitoxic property, have not proved successful. It is advisable, however, to let the serum settle after withdrawing the blood from the artery of the horse.
The statements of Neter, that the internal administration of calcium salts would prevent serum disease, should be received cautiously as a mere reduction in percentage of cases does not prove much, as serum disease in diphtheria is not of frequent occurrence.
We employ the following symptomatic treatment : In the presence of tenderness and swelling at the place of injection, applications of liquor Burrowii, warm baths for the extremities. Itching associated with urticaria is relieved by application of a one per cent. alcoholic solution of salicylic acid or menthol. If the temperature is high, cold packs are applied. The use of salicylic acid preparations is followed by a prompt fall of the temperature with perspiration, but the result is only tempo rary. Salicylic acid preparations have no effect on the joint pains, where we advise warm, moist applications.