VALUE AND PROPER USE 01 Arsenic in Skin Diseases By George h. robe, m. d., BALTIMORE, MD. Reprint from the Virginia Medical Monthly, January, 1888. VALUE AND PROPER USE OF ARSENIC IN SKIN DISEASES.* GEORGE H. ROHE, M. D., Baltimore, Md. The uncertainty of therapeutics is well illustrated by the contradictory opinions hold by practical men upon the util- ity of arsenic as a remedy in skin diseases. While some claim arsenic as a specific, lauding it in the most varied af- fections as the remedy par excellence, others discard it almost altogether. We do not have to go far to find the causes of this disa- greement. In the first place, the study of the physiologi- cal action of drugs is still limited to a small number of prac- titioners; and secondly, the diagnosis of diseases of the skin is not a highly developed branch of medical art. Hence it is easy to see why agreement on this point is so difficult. Most of the therapeutic knowledge at our command is de- rived from practical experience, and as the conditions under which the observations are made are not accurately defined, the results are incomplete, and must, in the nature of the case, often be discrepant. The internal use of arsenic in skin diseases dates from the beginning of the present century, when Girdlestone recom- mended it highly in lepra and psoriasis, or what we should call now, psoriasis and scaly eczema. Willan, in the first American edition of his book, published in Philadelphia in 1809, also refers to its use in "lepra alphoides"-(our present psoriasis). *Read before the Medical Society of Virginia, Oct. 20, 1887. 2 The careful clinical observations of the older physicians, and the more recent researches in pharmacology, indicate that the nutrition of the skin is powerfully affected by ar- senic. In experimenting upon frogs, Drs. Ringer and Mur- rell discovered that if the animals were poisoned with ar- senic, the epidermal layer of the skin could be readily stripped off after a few hours. This shows that it causes some profound alteration of nutrition of this organ. On examining sections of the skin of frogs which had been so poisoned, Miss Emily Nunn, working under the direction of Professor Michael Foster, found that the columnar layer of the rete was more or less separated from the cutis, the epi- dermis being attached only by a few protoplasmic processes. In corroboration of this result of experiment, Piffard re- lates a case, in which a patient affected with psoriasis had taken, by mistake, a teaspoonful of Fowler's solution, with the effect of completely removing the eruption within a few days. Under my own observation, several years ago, a young man attempted suicide with arsenic. The poison caused acute gastritis, and a complete exfoliation of the epi- dermis. Afterward he also had a nervous affection, with symptoms resembling those of acute anterior poliomyelitis. These toxic manifestations of the drug are merely the ex- aggerated evidences of its physiological action. They show that arsenic modifies especially the nutrition of tissues de- 'rived from the epiblastic layer of the embryo-the skin and nervous system. If we boar this in mind, it will not be dif- ficult to determine the classes of cutaneous diseases in which the drug will probably be useful. One other physiological effect of arsenic is hyperemia of the skin. This renders it an appropriate remedy in most cases of acute inflammation. Hence, in such diseases as acute eczema, the administration of arsenic usually intensi- fies the affection. Some writers on arsenic claim that its beneficial effects are entirely due to its tonic or restorative action upon the blood. Comparison with such remedies as iron and manga- nese shows, however, that its hematinic action does not ac- count for its specific or selective effects upon the skin. 3 The diseases in which arsenic, when properly employed, may be expected to prove useful are the following: Chronic eczema, especially its papular and scaly forms. In the pustular form of eczema, which so often occurs upon the face and scalp of children of a strumous habit, it is also of use, but must be combined with iron and cod-liver oil in order to produce its best effect. In these cases some local antiseptic application should also be used. In papular eczema, I frequently depend almost altogether upon the arsenic for a cure, the local application being merely such as will relieve the intense itching. I recall a case of this sort in a German boy of ten years of age. He had a universal papular eczema, which caused great suffering from the intense itching. Nearly the entire surface of the body was covered with a small papular erup- tion, which had existed since his second year. From the distribution of the eruption, its persistence for years, and the intense pruritus, I was at first inclined to venture a di- agnosis of prurigo, and afterward learned that such had been the diagnosis of one of the most distinguished derma- tologists of Berlin. However, after keeping the patient un- der observation in the City Hospital for a few weeks, I was satisfied that the case was a severe papular eczema. After a few small doses of calomel, I began the adminis- tration of arsenic in the form of Fowler's solution, com- mencing with thrfee drops thrice daily. Every third day the daily dose was increased by one drop. No effect was apparent until the dose of six drops was reached, when red- ness and irritation of the conjunctivae came on, followed by a pretty rapid disappearance of the eruption. No other in- ternal treatment was used. Locally, a lotion of bicarbonate of sodium (1:16) was employed to allay the itching. Another case was that of a negro boy, 20 years of age, suffering from a chronic scaly eczema, covering almost the entire trunk and thighs. There was much infiltration and deep fissures about the joints, causing great pain on motion. The itching was severe. Fowler's solution was ordered in four-drop doses, to be gradually increased, as in the former case. For three weeks no effect was manifested, and the Resident Physician of the Hospital asked permission to change the treatment. He was directed to persevere, how- ever, and in a week longer the effects of the remedy were apparent. In the course of a month the patient left the 4 Hospital, entirely recovered. External treatment was com- bined with the arsenical medication, but it could only have been of minor influence in this case. I could easily quote dozens of cases of eczema where the effects of this remedy were equally striking. In pemphigus, a disease against which we were formerly entirely helpless, arsenic acts as a specific. This effect was first noticed by Hutchinson. In all the cases that have come under my observation I have used arsenic, and always with the happiest effect. I may be pardoned for referring here to a case which has recently been under my care. The patient was a female of 60 years of age, who suffered from an intensely itching' bullous eruption of the vulva, perineum, upper portion of the thighs, and buttocks. The constant maceration and scratching brought about an in- flammatory condition of the parts, which for a long time obscured the diagnosis. Under the most various medica- tion, both internal and external, the disease which had been diagnosticated as eczema rubrum, constantly became worse. When I was consulted, the vulva, inner surface of the thighs and buttocks were excoriated, exquisitely sensitive to the touch or to the mildest applications, and studded with blisters varying from a pea to a lima bean in size. These blisters re- curred in crops, several of them appearing every two or three days. The remainder of the body was free from eruption, with the exception of a solitary bleb on the back of the right wrist. After the diagnosis was corrected, arsenious acid, in doses of ^3 grain, afterward increased to grain, was given every two hours during the day, and a weak lead and opium lo- tion applied externally. In two weeks the formation of blisters had diminished in rapidity, the sensitiveness had almost disappeared, and the extent of surface affected had been reduced to one-third. In two months the patient was well enough to go driving, the first time she had gone out of doors for eight months. In this case arsenic had been given before I was consulted, but no good effect had been obtained from the remedy, on account of the smallness of the dose. In arsenic, we possess a sovereign remedy in that charac- teristic epidermal hyperplasia, psoriasis. Dermatologists always use local remedies in this disease, as a matter of course, in combination with the internal medication; and I have frequently secured the temporary disappearance of the 5 eruption with local applications alone. But the disappear- ance is always more rapid if arsenic is given at the same time. Drs. Taylor, Piffard, Keyes and Sturgis, of New York, give arsenic for its tonic effect in syphilis, and claim good results from it. I have no experience with it in this disease, but believe it to be useful in certain cases. In acne, arsenic is of limited utility, most cases of the pus- tular form being rendered worse by it; but in cases of what I have been accustomed to call menstrual acne in young women, it often acts like magic. Several of my patients keep a small vial of grain tablet triturates on hand, and take the remedy during the menstrual period. They claim almost absolute immunity from what was formerly one or two weeks' disfigurement in every month. Lichenruber is a comparatively rare disease in this coun- try, but in the few cases I have seen, arsenic has maintained the reputation bestowed upon it by the elder Hebra. In his admirable "Practical Observations on the Vene- real Disease, and the Use of Mercury," Dr. Abraham Colles says: " It will be readily conceded that the efficiency of any remedy in the treatment of disease must, in a great measure, depend on the accurate knowledge which the practitioner possesses as. to the most judicious mode of administering it." I suppose every practical physician will agree with this. If half the time and labor expended in seeking out new drugs were devoted to the careful study of those already in our hands, I feel sure the results would be fully as good as those, now obtained. Much valuable knowledge has been recently added by the labors of devoted students of pharmacology, especially in Great Britain and Germany. In this country, also, the work of such experimenters as Wood, Smith and Ott de- serves the heartiest recognition and encouragement. It would seem more profitable, however, if some of the older druffs, whose good effects in certain morbid conditions, clinicians have long since proven, wore submitted to the rigid tests of the experimentalists, instead of newly-intro- duced substances, of which we often do not even know the 6 derivation. How little do we really know of the mode of action of mercury, iron, or iodine; and until the researches of Binz, how vague and indefinite were our views of the ac- tion of quinine and alcohol. Pharmacology should there- fore not be looked upon as a mere "fancy study," but as a valuable adjunct to practical therapeutics, and studied side by side with clinical medicine. Basing my practice upon the results of experimental in- vestigation and the clinical observation of my predecessors and co-workers in practical medicine, I have followed a plan in the administration of arsenic which has, in the class of cases before mentioned, yielded, almost uniformly, the best results. I now use, in appropriate cases, but two prepara- tions of this drug-arsenious acid in substance, and the so- lution of arsenite of potassium (Fowler's solution). For a time I gave a solution of arsenious acid in dilute hydrochloric acid, but have discontinued it because its administration is so fre- quently followed by an eruption of abscesses or pustules. 1 am not quite prepared to assert that the abscesses were the result of the administration of this preparation, but as they were so uniformly the sequel of its use, and did not follow the employment of other arsenical preparations, I discon- tinued the use of the former combination. Dr. Fothergill has pointed out that in certain cases o anemia, iron fails to have any good effect until a course of saline laxatives has been administered. According to my observation, arsenic likewise often fails in producing any beneficial action until certain preliminary, or what might be termed preparatory, treatment is instituted. To children I generally give, for three or four days, small doses (TV grain) of calomel every three hours. After this brief mer- curial course, the administration of arsenic (Fowler's solu- tion) is begun in two or three drop doses thrice daily, ac- cording to age, increasing the dose by one drop per day on every third day, until the physiological or therapeutical ef- fects of the drug become manifest. When this point is reached, the dose is decreased one drop, and held at that dose until the effects sought are obtained. In adults, I also frequently begin the treatment with the 7 mercurial, but rarelv continue it longer than two davs, after which I give the following saline combination for ten days. The diuretic-I am tempted to say depurative-action of this prescription seems to prepare the system to derive the fullest benefit from the arsenical course. The formula is: B . Potassii acetat oj Ext. taraxaci fl f§j Aquee, qs. ft f^ij M. S.-Teaspoonful in a tumblerful of water three times a day, a half hour after meals. The patient is now prepared to benefit from the arsenic. Whether arsenious acid or Fowler's solution be given, the dose must be strictly regulated. I usually fix an hour at which the medicine is to be taken, if the patient is confined to the house. Thus, instead of saying, take one dose every two or three hours, as the case may be, I direct the dose to be taken at 8, 10, 12, 2, 4, 6 and 8 o'clock. Such specific directions are more likely to be closely followed than when .any discretion is allowed the patient. When ordering arsenious acid in substance, 1 generally ■direct the tablet triturates, first introduced by Dr. R. M. Fuller, of New York, and now made by most manufactur- ing druggists. They are made in tablets containing from nV to nH grain. I rarely use a larger tablet than grain, more frequently grain. If a larger dose is desired, it is easy to give two or three tablets. By ordering the smaller tablets, it is much easier also to increase the dose gradually. These tablets may be taken like pills, or dissolved in water. I have never known them to cause irritation of the stomach when the dose was properly adjusted. It is perhaps better to give the dose, especially if at all large, after taking food. I frequently precede the dose, in the intervals between meals, by a glass of milk. In this way I have given a pa- tient one-fourth of a grain of arsenious acid daily for two months without producing any unfavorable effect upon the system. If, instead of the arsenious acid, I give Fowler's solution, I order it in sherry wine, or cinnamon water. For chil- dren, equal parts of simple syrup and cinnamon water 8 makes an elegant vehicle, in which the remedy is readily taken. If given simply diluted with water, the flavor of lavender in the Fowler's solution soon palls upon the taste, and in many cases produces nausea. This preparation is likewise begun in small doses (3-4 drops), and increased gradually until the desired (or toxic) effects are obtained. Regarding the danger of poisoning by medicinal doses of arsenic, I desire to say a few words. The smallest toxic dose, as pointed out long ago by Mr. Hunt, is fifty times as large as the average medicinal dose. Hence, the proba- bility of fatal or dangerous poisoning from arsenic admin- istered in medicinal doses is extremely remote. Further, cumulative effocts need not be feared. The drug is rapidly eliminated from the system; and.if the excretory functions are dropcrly performed, no accumulation of the poison in the body can take place. Its harmlessness, when its effects are watched, is attested by the absence of cases of fatal poi- soning from the remedial use of the mineral. In what I have here said, I have desired to put upon record my conviction that arsenic, properly used, is one of our most valuable means of combatting certain skin dis- eases, most prominent of which are papular eczema, psoria- sis, lichen ruber and pemphigus; that when intelligently used, this time-honored remedy is non-toxic and harmless, and that it is rapidly eliminated from the system, and hence cannot produce what are termed "cumulative" poi- sonous effects. I would not be understood, however, that I omit appropriate local treatment in any case. Both for pal- liative and curative effects, I regard local medication in skin diseases generally as the main indication. But in some affections of the integument, notably those just men- tioned, the main reliance must be placed upon the internal treatment. In these, the local applications can only be looked upon as adjuvants. G11 A. Calvert Street, Baltimore.