With the occasion of research currently under way at the Dermatological Clinic of Geneva on l-ascorbic acid (vitamin C) (1), we studied its action on a certain number of allergic states of the skin.
These tests, the first results of which we report here, showed that ascorbic acid (2) has extremely active desensitizing properties, and make it possible to foresee the exceptional role that this drug has to play in the therapeutic dermatology.
(1) See the thesis of Mr. Piesocki, Research clinical on the reduction in the toxicity of arsenobenzenes by addition of Redoxon (in press).
(2) The preparation employed is Redoxon (Roche).
Mrs. B... Eugénie, 43 years, housewife.
Hospitalized with the Dermatological Clinic for varicose eczema of both legs.
Personal antecedents: nothing in particular. Tuberculosis among relatives and descendants.
The Wassermann [Test], performed by established procedure, was found strongly positive with this patient, without one being able to discover the origin of her syphilis.
Combined treatment: Salvarsan and Bismuth.
| May 23. | 1st | inj. Néo-Mesarca.. | 0,15 | 1st | inj. Oléo-Bi. | 1 cc. | |
| May 25. | 2nd | " " | 0,30 | 2nd | " " | 1 cc. | |
| May 27. | 3rd | " " | 1 cc. | ||||
| May 28. | 3rd | " " | 0,45 |
From the start of treatment, the patient had complained about headaches.
29 May. The headaches are more violent, temperature increases to 38°2-38°5. Treatment is suspended temporarily.
31 May. Appearance over entire body of an eruption of small, very pruriginous erythemato-papulous elements, with a tendency to join in places into large plaques; the eruption has all the charactersistics of a salvarsanic erythema.
The patient receives as an experiment an intravenous injection of 5 centigrams ascorbic acid, dissolved in 10 cubic centimeters of water.
The following day, the lesions are no longer elevated, but form wide plaques of scarlatiniform erythema. This erythema disappears almost completely during the afternoon.
The patient receives a second intravenous injection of ascorbic acid, 5 centigrams. The temperature, which was 38°6 on 31 May, 38°3 on June 1st, fell on 2 June. The eruption disappears completely.
6 June. Attempt at resumption of the treatment. The patient receives an injection of 30 centigrams Néo-Mesarca dissolved in an ascorbic acid solution (5 cgr. of ascorbic acid, 10 cc. distilled water).
Shortly after the injection, appearance on the arms, the belly and the thighs of an eruption of nonpruriginous ortiées [stinging? fr. ortie = nettle] papules, which persists a few hours, then disappears, to be replaced with a diffuse redness of the face upon injection of the sclerotic, and buzzing of the ears until the evening.
[In] the evening, the eruption disappeared.
The patient complains about a great tiredness about the arms and legs and painful articulation.
7 June. The patient feels completely well. Ascorbic acid injection, 5 centigrams.
13 June. New attempt to resume treatment. Injection of 15 centigrams Néo-Mesarca dissolved in an ascorbic acid solution at 1/100th [1%] (ascorbic acid 0.10, distilled water, 10 cc.). This injection is tolerated perfectly.
18 June. Injection of 30 centigrams Néo-Mesarca dissolved in the same ascorbic acid solution, tolerated very well.
21 June. Injection of 30 centigrams Néo-Mesarca in the same ascorbic acid solution, tolerated very well.
At this time. the patient leaves the Clinic and finishes on an outpatient basis an ascorbine-salvarsanic cure of a total of 4.50 g, without incident (injections of 30 cgr. of dissolved Néo-Mesarca each time in 10 cc. ascorbic acid solution at 1/100th [1%]).
Mrs. F... Berthe, 34 years, housewife.
Syphilis ignored until the beginning of April 1935. At that time, ictus; coma for two days, then regained consciousness with reduction of strength of the right hand.
The consulted doctor finds Bordet-Wassermann positive and puts the patient under salvarsanic treatment.
From 22 April to 27 May, she receives 5.10 gr. of Néo-Mesarca (maximum amount by injection, 0.60).
The initial injection causes pruritis initially localised to the arm, then generally.
The last injection (0.60 on May 27) is followed by a generalized erythema.
June 11, the patient is admitted to the Dermatological Clinic.
She presents a salvarsanic erythrodermy [with] generalized oozing exfoliation, and many lesions of secondary pyodermitis, especially of the arms. Face, arm, lower limbs are affected by a very strong œdema, making impossible any treatment by intravenous injections, [necessitating] administration of ascorbic acid in the form of tablets, at a rate of 3 tablets of 5 centigrams per day as of June 12.
Moreover, following established procedures at the Dermatological Clinic, a daily bath of potassium permanganate (2 gr. for a bath).
14 June. Reduction of œdema and redness.
15 June. Marked improvement. Increase amount of ascorbic acid to 5 tablets per day.
17 June. Almost complete disappearance of œdema, the skin of the face no longer scaly.
23 June. The œdema disappeared; exfoliation of the trunk ceased. Persistence of a slightly squamous state of the skin of hands and feet.
7 July - Cure of the erythrodermy.
Persistence of a feeling of pruritis in the legs; no lesions other than those from scratching, which yield in a few days to boric-water compress.
M.W... Louis, 39 years, cook in a briquetterie.
Antecedents: nothing in particular.
In January 1935, the patient manifests ideas of grandeur. At the same time, he complains about exaggerated tiredness after work, and about a tremor of the left hand, for which he consults a doctor.
The Bordet-Wassermann performed on this occasion appears positive, and the patient, who claims to be entirely unaware of his syphilis in spite of many possibilities of contamination, is put in salvarsanic treatment: 7 intravenous injections of Néo-Mesarca (amounts I, II, III, IV and 3 amounts V) are well tolerated.
7 May. Last injection.
14 May. Initial appearance of erythrodermy on the arms, which spreads quickly over the entire body.
22 May. Redness and œdema take hold in the face.
25 May. The patient is admitted to the Dermatological Clinic with a salvarsanic erythrodermy [with] generalized oozing exfoliation. Temperature 38°3, positive Wassermann. Reading 10.
External treatment by permanganate baths, without result, over 10 days.
5 June. The patient receives initial intravenous injection of ascorbic acid (acid ascorbic 5 cgr., distilled water 10 cc.).
6 June. The erythema seems to have decreased; second ascorbic acid injection of 5 centigrams.
7 May. Reduced manifestation of erythema and œdema of the face.
The state of the veins of this patient makes the injections impossible. Consequently, ascorbic acid is administered by mouth, at a rate of 2 tablets of 5 centigrams per day.
Very quickly, the general and cutaneous states improve. The fever falls at the end of eight days. Redness and œdema disappear. Aappetite returns. The patient puts on weight (53.6 kg on June 4; 54.6 kg on June 18; 56.9 kg on June 25).
25 June. The exfoliation, which was generalized and abundant, is finished.
Only some cutaneous abscesses persist, remnants of the secondary pyodermitis that this patient presented during the treatment, and which do not seem to be influenced by the ascorbic acid. They yield slowly to injections of an auto-vaccine (staphylococcus aureus).
Mr. F... Albert, 50 years, merchant.
Chancre and roseola at 24 years (1909). Treaty by Ricord XXX pills , then by some boxes of Polak pills.
No other treatment. No manifestation of infection until spring of 1935 (26 years of latent syphilis).
May 13. The patient admitted to the Dermatological Polyclinic for a red-brick tumefaction dating back about fifteen days, localised on the end of the nose and the median partition. Its edges are very clearly delimited, without inflammatory reaction in the vicinity. No subjective symptom. The lesion presents the typical aspect of a tuberous syphilitic.
Very positive Bordet-Wassermann. Reading: 60
Combined treatment.
1st July. Last injection of Néo-Mesarca, dose V; 20th injection of 1 cc. Oleo-Bi.
3 July. Beginning on the four limbs of an erythema of the urticarien type. Starch baths.
8 July. Generalization of the erythema, particularly marked on the thighs, the buttocks and the arms, which are strongly œdemous. With the arms and ears, beginning of exfoliation.
The eruption is of the classic type of salvarsanic erythrodermy.
The patient receives on an out-patient basis a first intravenous injection of ascorbic acid (0.10 in distilled water 10 cc.).
9 July. Light reduction in the œdema of the limbs. Second intravenous injection of ascorbic acid, 10 centigrams.
12 July. The œdema of the limbs further decreased, but the patient presents a very marked œdema of the face.
Fifth ascorbic injection of acid (0,10).
14 July. Oozing lesions of the ears, the forearms and the internal face of the thighs; hospitalization of the patient, who receives a daily potassium permanganate bath (2 gr. per bath) and a daily intravenous injection of 10 centigrams ascorbic acid (20 cgr. by injection as of July 16).
18 July. Great improvement. The œdema and the seepage gradually disappeared. The erythema decreased.
Exfoliation is still abundant.
22 July . Exfoliation persists, but the erythema is in the process of disappearing. One notes nothing more but a light redness of the face and the internal face of the thighs, on the level of the initial plaques. The patient rises and feels so much better that he asks to leave the hospital.
24 July. Cure of the face.
Persistence of a light redness in the thighs. Exfoliation is still marked with the thighs and the arms.
25 July. Exfoliation is finished on the trunk and the limbs, except at the ends, where a slightly squamous state of the skin persists.
Miss M..., 21 years, typist.
Treated as of September 1932 for a fibro-caseous tuberculosis of the para-hiliar area, right-hand side.
From 29 November, 1932 to 5 July, 1933, 1st course chrysalbine:
22 injections of 5 centigrams tolerated well, followed by good clinical improvement.
From 16March, 1934 to 11 June, 1934, 2nd course chrysalbine:
10 injections of 5 centigrams, tolerated well.
From 23 October, 1934 to 11 June, 1935, 3rd course chrysalbine:
5 centigrams distributed evenly into14 injections.
With the five last, the chrysalbine was prophylactically dissolved in one ampoule of calcium (Sandoz).
11 June, 1935. The patient notices upon the external face of her left arm a small round lesion, pruriginous, which she self-treats by applications of tincture of iodine and Antipyol, without result.
24 June. Beginning of a discrete eruption, especially marked on the left arm. The attending doctor gave an intravenous injection of calcium gluconate (Sandoz) and refers the patient to us.
25 June. We note on the left arm and forearm, which are slightly œdemous, an eruption of small erythematous elements, slightly elevated, merging in places and slightly pruriginous.
The erythema also exists on the arm right, the trunk and the thighs of the patient, but more discrete.
Expectancy. Starch baths.
28 June. The œdema of the left upper limb strongly increased and spread to the back of the hand. Appearance of a light œdema to the right arm; increase in the eruption which is generalized, except on the face.
The fore-and-aft erythrodermy is no longer in doubt. We give to the patient a first intravenous injection of ascorbic acid (acid ascorbic, 0,10; distilled water, 10 cc.).
29 June. Increase in the erythema which is no longer raised, but which merges into a cyanotic sheet on the entire left upper limb.
The remainder of the eruption is also more marked than the day before, the œdema increased.
Second injection of ascorbic acid, 0,10.
1st July. Third ascorbic injection of acid, 0,10.
2 July. Œdema unchanged, but light reduction in the erythema. Beginning of a very fine exfoliation, almost furfuraceous, on the left arm.
(daily starch Baths, starched water compress. From July 2, daily injections of ascorbic acid, 0,10).
5 July. The eruption almost completely disappeared; the œdema of the arms decreased. On the other hand, the face of the patient is very strongly oedématié, but without redness (no albumin).
Squamous state of the left arm without change.
7 July. The erythema disappeared.
Light reduction in the œdema of the face and the arms.
10 July. Disappearance of the œdema of the face. Reduction in the œdema of the limbs.
12 July. The right arm and the left hand completely unswollen.
Only the left arm, which is no longer scaly, is still very slightly œdematious, and retains a colour slightly darker than the remainder of the skin.
16 July. Positive trace of œdema. The skin of the left arm still has a slightly rough consistency, and has a light brownish pigmentation.
By comparing the preceding observations with those of other patients, by rereading the observations of other authors (Wood, Golay and Silvestre, Gougerot, Milian, Tzanck, etc), one is struck by the rapidity of recovery obtained, and of the benign nature of the course of the disease under the influence of ascorbic acid.
Until now, the mortal end result of an erythrodermy was not exceptional, and the words of Dekeyser to the last Congress of Dermatologists and Syphiligraphists of the French Language (Lyon, July 1934) suffice to say what one could expect from his treatment:
“For exfoliant erythrodermy we are unequipped. Apart from the desensitizing injections of hyposulfite of soda at 200/0, recommended by Ravaut, we do not have any means of acting on the organism. And even those seem illusory in the majority of the cases (1).”
(1) Vth Congress of Derm. and Syph. of the French Language, vol. I, p. 347.
Further research [and] more observations will make it possible to establish a precise posology of ascorbic acid, and will show if it is better to administer it by mouth or intravenously.
Already, however, a certain number of results remain certain.
We showed that ascorbic acid has exceptional desensitizing properties, and that this drug is able, in the amounts we employed, to profoundly modify the clinical evolution of erythrodermy, and to entirely transform the prognosis.
In completing this work, we bid our director, Mr. Professor Du Bois, to allow expression of our deep gratitude for the benevolent interest which he expressed for this research prepared in his service, and for the authorization given to use, for this purpose, the facilities of the Dermatological Clinic.
From Annals of Dermatology and Syphiligraphy — 7th Series, Volume 6, Number 9, September, 1935.
Salvarsan: arsephenamine, Ehrlich/Hata formulation 606. Arsenic
compound developed in 1909.
Néo-Mesarca: presumably a trade name for neoarsephenamine,
Ehrlich/Hata formulation 914; a later derivative of Salvarsan.
Oléo-Bi: presumably an injectible bismuth preparation.
Ricord XXX pills: probable reference to French venereologist Phillipe
Ricord (b. 1799);
Ricord pills: [?] possibly an oral preparation of argentum chloratum ammoniacale
(silver ammonium chloride)
Polak pills: [?] possible reference to John Osborn Polak, 1870-1931, professor of Obstetrics & Gynecology.
Furfuraceous: thin scaling or flaking of dead epidermis
Chrysalbine: sodium aurothiosulfate. Formerly used to fix photographic negatives. Proposed in 1924 by Prof. Holger Christian Mollgaard (Copenhagen, 1885-1973) to be used to treat tuberculosis under trade name Sanocrysine. Marketed as Thiocrysine by Usines du Rhône (Lyon), and as Chrysalbine by Maison Poulenc Freres (Paris), becoming Crisalbine when the two companies merged into Societe parisienne d'expansion chimique (Specia). Use gradually abandoned after 1945.
Antipyol: [?] probably identical or similar to Antipeol, a trade name of a zinc oxide ointment.
Erythema: generally, a redness of the skin produced by congestion of the capillaries, esp. inflammation.
Œdema = oedema = edema: swelling of tissue.
Pruritis: itching.
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