A PRELIMINARY REPORT ON THE EMPLOYMENT OF NEOSALVARSAN IN SYPHILIS.

UDO J. WILE, A. B., M. D.

PROFESSOR OF DERMATOLOGY AND SYPHILOLOGY IN THE UNIVERSITY OF MICHIGAN. ANN ARBOR, MICHIGAN.

THE almost universal success which has attended the use of salvarsan in the treatment of syphilis, both as a symptomatic and in some cases as a probable curative remedy, is almost without parallel in the annals of therapeutics.

It is but natural, however, that the application of so potent a remedy should be attended by occasional risk and infrequent untoward consequence. Even after two years, the remedy is admittedly still in the experimental stage, and as such must be subjected to the closest scrutiny.

Of equal importance as the beneficial results in a clincal survey of the new therapy, are the instances illustrating accident, toxicity, and difficulties of administration. An extensive literature, covering these three factors has sprung up. In some hands the drug has proved more or less toxic; deaths from one cause or another are reported, and in the hands of those without laboratory and hospital facilities, the remedy heretofore has been difficult of administration.

Of greatest import is the subject of toxicity. The effects reported as untoward, reflect upon all the systems, with a possible predilection for the gastrointestinal system. The various clinical symptoms of toxicity are sufficiently well known to be passed over briefly. Giddiness, headache, nausea, and profuse diarrhea, are fairly frequent; severe

chill, erythematous and scarlatiniform rashes, neuritis, pigmentation and keratosis, while more rare are nevertheless reported sufficiently often to merit attention.

Since the use of freshly distilled water has been insisted upon, it must be admitted that the initial toxic effects, especially those of the gastrointestinal system have been largely eliminated.

With regard to the difficulty of administration, particular objection has been made to the relative insolubility of the drug, and the necessity of converting its solution from acid to alkaline in reaction by the use of sodium hydrate.

Early recognizing these few disadvantages, Professor Ehrlich and his colleagues sought an improvement in the molecular composition of the drug which should obviate the disadvantages of the older preparation. Their efforts have resulted in the production of a later arsenic derivative which is more readily soluble, capable of more rapid succession of administration, isotonic, and neutral in its original solution with water. This product Ehrlich has called neosalvarsan.

Neosalvarsan (dioxydiamidoarsenobenzolmonomethylenesulfoxylate of sodium) like the older preparation is a yellowish powder dispensed in exhausted ampulles. Its dosage varies somewhat from the original salvarsan; thus

.9 gram of neosalvarsan-0.6 old salvarsan.

.75 gram of neosalvarsan-0.5 old salvarsan.

.6 gram of neosalvarsan-0.4 old salvarsan, et cetera.

Or in other words one gram of the old salvarsan is equivalent to one and one-half grams of the neosalvarsan.

The new drug may be administered intramuscularly or intravenously. The method of preparation is extremely simple: the drug is readily soluble in cold water and in this solution is neutral. In the ratio of twenty cubic centimeteres of water to each decigram of the preparation, the solution is isotonic. The solution is made with water at room temperature and injected at this temperature. It is expressly stated that the solution must under no circumstances be heated.

The advantages of this over the older method is manifest; the solution requires practically no agitation, it is made up in one step and within a few moments is ready for use. Furthermore the bulk of the injected material is decreased by more than one-half.

Through the courtesy of Professor Ehrlich I have had the opportunity of testing the new remedy and comparing its action with that of salvarsan. In the line of this investigation the endeavor has been simply to compare the toxicity of the new drug with the older preparation and also to compare their relative efficiency upon the manifestations of the disease.

During the past five months I have administered neosalvarsan sixty-four times to twenty-six different patients. The cases treated allow of the following grouping:

Primary syphilis,.....2 cases.

Secondary syphilis,...8 cases with florid manifestations
8 cases in the latent stage.

Tertiary syphilis,.....5 cases with tertiary manifestations.
2 cases in the latent stage.

Lymphosarcoma,.....I case (thought to be luetic despite
negative Wassermann reaction).

Only two of these cases showed any marked reaction. They were both cases of florid secondary syphilis in young men. Both were given four doses of neosalvarsan at forty-eight-hour intervals. In each case, after the fourth injection there occurred within a few hours, sudden chill, fever, ranging from 102° to 104° Fahrenheit, slight diarrhea, and within a few days there appeared a generalized morbiliform eruption which rapidly became confluent and scarlatiniform. This rash gradually involuted with slight desquamation, and within a week the patients were entirely well and seemed none the worse for the violent reaction. In each case during the febrile period a slight albuminuria with few casts occurred. These two cases are typical examples of sensitization of the organism to repeated doses of the drug. Similar reactions were noticed also with the older preparation and indeed are thought to be more frequent with it. The European authorities are inclined to regard this reaction as something in the nature of an anaphylactic phenomenon.

In a few other cases in the florid secondary stage, a slight fever lasting a few hours was noticed. This reaction is regularly encountered both with the new and older preparation where spirochetæ are present in large numbers. In all the remaining cases the injections were tolerated without the slightest symptom of any untoward effect. About eighty per cent of the patients belonged to the laboring classes; they received their injections in the late afternoon and were without exception able to resume their usual tasks the following morning.

Of considerable importance in comparing the relative toxicity of new and old salvarsan were those cases in which both preparations had been used. Of these there were four patients who had had more than usually severe reactions with old salvarsan. In all four, the injections had resulted in violent chill, nausea, headache, vomiting, diarrhea and incapacity for several days. Subsequent injections of neosalvarsan in these patients were tolerated without the slightest indication of reactive symptoms.

As to the effect of the new drug upon the lesions of syphilis as compared to that of the old, a fair comparison can only be made by considering the effect of the single dose of each. It is quite patent that four doses each repeated within forty-eight hours would be productive of more rapid involution of symptoms than the same four doses spread over a period of four weeks, an interval of a week being conceded as the shortest time in which repeated doses of old salvarsan may with safety be administered.

From my observation of a few cases in which but a single dose