Lassar's Paste Research Articles

Eponyms that honor Jewish dermatologists: A celebration and a remembrance, Part one: Jewish physicians who practiced before 1933.

This multipart feature celebrates the Jewish contribution to dermatology over the past 200 years, as reflected by medical eponyms that honor the names of Jewish physicians. Many of these physicians practiced in Germany and Austria after the emancipation of Jews in Europe. Part one discusses 17 physicians who practiced medicine before the Nazi takeover of Germany during 1933. Examples of such eponyms from this period include the Auspitz phenomenon, Henoch-Schonlein purpura, Kaposi's sarcoma, Koebner phenomenon, Koplik spots, Lassar paste, ital Neisseria gonorrhoeae, and Unna boot. One of these physicians, Paul Ehrlich (1854-1915), became the first Jew to be awarded the Noble Prize in Medicine or Physiology, an honor he received in 1908 and shared with his fellow Jew, Ilya Ilyich Mechnikov (1845-1916). Parts two and three of this project will present the names of 30 more Jewish physicians honored by medical eponyms and who practiced medicine during the Holocaust era and its aftermath, including those physicians who perished at the hands of the Nazis.

Remembering the Pioneers of Topical Agents.

While everyone remembers seeing a traveling salesman pushing “Dr Smith’s Wonder Pills” or something similar in a Class B Western movie, many have forgotten that several serious dermatologic preparations carry the name of a colleague of the past. These former mainstays of dermatologic therapy are disappearing because proof of efficacy is lacking, a declining interest in compounding them, and the inclusion of ingredients no longer deemed suitable for topical use. We recall a few examples that, a generation ago, were prescribed daily by almost every dermatologist. Burowsolution is an aluminumacetate solutionwith astringent and antibacterial properties thatwasprimarily usedwithwetdressings.Karl AugustBurow (1809-1874)was anophthalmologist inKonigsberg, East Prussia. Castellani paint is a carbol fuchsin solution that is an effective antifungal and antimicrobial agent. It discolors the skin so badly that colorless formsweredeveloped.AldoCastellani (1877-1971wasan Italianphysicianwith abroad rangeof interests, especially in tropicalmedicine.He was an enthusiastic Italian royalist and also supporter of BenitoMussolini as well as a peripatetic physician who practiced around the world, including NewOrleans, Louisiana. Lassar paste is a zinc oxide paste, still in use to treat diaper dermatitis. It was also one of the early vehicles used for anthralin in treating psoriasis.OscarLassar (1849-1907)wasa flamboyantpractitioner inBerlin, Germany, who had a flourishing private clinic, had an earlymoulage collection,andwasa leader indevelopingpublicbaths.Hemayhavebeen the first dermatologist to die in an automobile accident. Schamberg lotion is an inexpensive antipruritic formulation of zinc oxide with menthol and phenol. Because of the latter ingredient, it fell into disrepute. Jay Schamberg (1870-1934) established the Dermatological Research Laboratories at the University of Pennsylvania, which was theonlyAmericansupplierofaneo-arsphenamineduringWorldWar I. He plowed the considerable profits back into further research, helping establish Pennsylvania as a leading dermatologic center. The Unna boot is a gauze bandage impregnated with calamine and zinc oxide paste used to treat stasis dermatitis and leg ulcers. Paul Gerson Unna (1850-1929) was a pioneer histopathologist whoworked out ofhisown institute, theDermatologicum, inHamburg,Germany.Hewas also an innovative therapist who trained a number of prominent dermatologists. Whitfield ointment is an inexpensive antifungal agent still in use. It contains 3% salicylic acid and 6%benzoic acid in a lanolin base. Arthur Whitfield (1868-1947) was a pioneer British dermatologist who started the program at King’s College, authored a widely used small textbook, and was a founder of the British Association of Dermatology. Even as their compounds gradually fall victim tomodernization,we should be thankful to these individuals for their highly personal contributions to the dermatologic treatment armamentarium.

STABILITY OF A NOVEL DITHRANOL OINTMENT FORMULATION, CONTAINING ASCORBYL PALMITATE AS AN ANTI-OXIDANT

An emulsifying ointment-based dithranol formulation is described which was, with the addition of 0.1% w/w ascorbyl palmitate, stable for 52 weeks at room temperature. This is in contrast to the more conventionally used dithranol in Lassar's paste, which is stable for only 4 weeks at room temperature. An emulsifying ointment-based paste was additionally more convenient to use since it was easier to apply and remove.

The irritancy of anthralin is inhibited by repeat applications of a subirritant concentration.

Anthralin is a safe, effective treatment for psoriasis, but its efficacy is hampered by the side-effects of irritation and staining of the uninvolved skin. To avoid burning, it is customary to start at low concentrations and increase every 48-72 h until the therapeutically effective concentration is reached, which takes time and appears to prolong treatment. We felt that if the minimal erythema concentration (MEC) of anthralin could be determined initially in an individual, this ought to be near or at the final achievable therapeutic concentration. Hence, by analogy with ultraviolet therapy, treatment could start just below this concentration and thus avoid delay. A series of concentrations of anthralin in Lassar's paste was applied to the back for 3 h, and erythemal responses assessed at 24 and 48 h. MECs (0.015-0.03%) were far below those usually reached during normal therapy. To test the possibility that the skin was adapting to anthralin, we pretreated areas of skin with a subirritant concentration of anthralin (0.007%) for 3 h on 2 consecutive days prior to application of the full dose series. On the pretreated areas, the MEC increased fourfold from 0. 015% to 0.06% (P < 0.01); the concentration of anthralin required to produce the mid-point on the dose-response curve increased from 0. 06% to 0.25% (P = 0.01), demonstrating a clear adaptive response. One pretreatment produced a 52% reduction in erythema compared with control challenge, and maximal 61% inhibition was seen after three applications. Pretreatment with a subirritant concentration of a control irritant, croton oil, had no effect on the response to anthralin and vice versa. Pretreatment of skin with danthron, the non-irritant oxidation product of anthralin, had no effect, suggesting that the attenuation effect is specific to native anthralin. To see whether the attenuation might be due to modulation of xenobiotic metabolizing enzymes, skin was pretreated with inducers and inhibitors of the cytochrome P450 and NADPH-dependent quinone reductase (NDQR) enzyme systems. However, no effect was seen. In conclusion, we have shown that the irritant response to anthralin is attenuated by repeated applications of a subirritant concentration of anthralin; this is not a non-specific response to all irritants, but a specific property of native anthralin, and the enzymes P450 and NDQR are apparently not responsible for this effect.

The development and clinical efficacy of a dithranol-impregnated hydrogel in the treatment of psoriasis.

Dithranol was incorporated into a hydrogel to develop a slow-release occlusive dithranol therapy for psoriasis. A method of loading the hydrogel with dithranol was developed. Stability of dithranol in the hydrogel was assessed by HPLC assay. Release of dithranol from the hydrogel into an aqueous medium was assessed in vitro. Pilot studies confirmed a comparable irritancy of the resulting dithranol/ hydrogel (DHG) to that of proprietary dithranol preparations. The effect of duration of application was studied in two patients and the rate of dithranol release assessed in vivo. Release from the hydrogel was complete in 14 h. Finally in a clinical study in eight patients comparing the application of DHG with hydrogel alone and conventional dithranol in Lassar's paste, the results of DHG were comparable to conventional treatment and significantly better than hydrogel alone.

Water-miscible dithranol cream in the treatment of psoriasis

Dithranol was prepared in water-miscible O/W cream formulations at 1, 2 and 4% concentrations. These creams were stable after up to 15 months storage at room temperature. When used for short-contact (10 to 20 minutes) therapy in 29 psoriasis patients, the results with 4% cream were similar to the published results with 1% dithranol in Lassar's paste or in petrolatum. Irritation was minimal. Electron microscopic studies before and after treatment revealed no ultrastructural alterations, in particular no damage to the mitochondria.

Anthralin-Corticosteroid Combination Therapy in the Treatment of Chronic Plaque Psoriasis

A prospective randomized trial of anthralin in Lassar's paste compared with anthralin in 0.0125% clobetasol propionate in the treatment of chronic plaque psoriasis was undertaken. The psoriatic skin of patients treated with the corticosteroid-anthralin combination cleared significantly more quickly than those treated with anthralin alone, with a mean time to clearance of 14.9 days compared with 18.5 days, and with lower concentrations of anthralin. No significant difference was found in the rate of relapse of the two treatment groups, with relapse occurring in over 80% of patients within one year. Anthralin in 0.0125% clobetasol propionate was found to be an effective agent in the treatment of chronic plaque psoriasis, and one that was cosmetically acceptable to patients and nursing staff. An important disadvantage, however, was the development of a staphylococcal folliculitis in four of the 35 patients in which it was used. Because of this, anthralin in Lassar's paste remains our standard inpatient therapy, although the ease of use and cosmetic acceptability of anthralin in clobetasol propionate make it a useful remedy for outpatient use.

Anthralin-corticosteroid combination therapy in the treatment of chronic plaque psoriasis

† A prospective randomized trial of anthralin in Lassar's paste compared with anthralin in 0.0125% clobetasol propionate in the treatment of chronic plaque psoriasis was undertaken. The psoriatic skin of patients treated with the corticosteroid-anthralin combination cleared significantly more quickly than those treated with anthralin alone, with a mean time to clearance of 14.9 days compared with 18.5 days, and with lower concentrations of anthralin. No significant difference was found in the rate of relapse of the two treatment groups, with relapse occurring in over 80% of patients within one year. Anthralin in 0.0125% clobetasol propionate was found to be an effective agent in the treatment of chronic plaque psoriasis, and one that was cosmetically acceptable to patients and nursing staff. An important disadvantage, however, was the development of a staphylococcal folliculitis in four of the 35 patients in which it was used. Because of this, anthralin in Lassar's paste remains our standard inpatient therapy, although the ease of use and cosmetic acceptability of anthralin in clobetasol propionate make it a useful remedy for outpatient use. (<i>Arch Dermatol</i>1988;124:548-550)

Anthralin stability in various vehicles

The stability of anthralin in white soft paraffin, Lassar's paste, and Unguentum Merck was assessed using a sensitive assay for degradation products, over a 1-year period. The stability was found to vary with concentration, weaker preparations being less stable. Significant degradation was observed in Unguentum Merck, and this increased when salicylic acid was present. Preparations with Unguentum Merck could be stabilized with ascorbic or oxalic acid. Salicylic acid stabilized anthralin in Lassar's paste but had a negligible effect in white soft paraffin. Preparations with white soft paraffin were relatively stable.

The stability of dithranol in various bases

With the advent of short‐contact dithranol therapy, a variety of bases such as white soft paraffin, yellow soft paraffin, Lassar's paste and Unguentum Merck® have been used. Yellow soft paraffin is the recommended base for dithranol ointment B.P. Salicylic acid is usually added as an anti‐oxidant to prevent degradation to therapeutically inactive compounds. In this study, a variety of dithranol formulations have been regularly assayed over a 1 ‐year period. Using high‐performance liquid chromatography, which is the only reliable means of assessing dithranol degradation, shelf‐lives were evaluated. The stability was found to vary with concentration; weaker preparations being less stable. Dithranol was found to be unstable in yellow soft paraffin and Unguentum Merck®, although ascorbic and oxalic acid could be added to the latter to increase stability. Salicylic acid produced a destabilizing effect on dithranol in Unguentum Merck® and yellow soft paraffin a stabilizing effect in Lassar's paste, but little effect in white soft paraffin. Dithranol is relatively stable in white soft paraffin which is the preferred base for short‐contact therapy. The inclusion of salicylic acid in this preparation is questionable because it has a negligible effect as an anti‐oxidant, is irritant to the skin and percutaneous absorption can be significant.

Dithranol in a cream base in the treatment of psoriasis.

Summary In this study, twenty patients with mild or moderately severe psoriasis were divided into two groups. In one group the combination of PUVA therapy and dithranol cream was compared with PUVA therapy alone. In the other group dithranol 0.2% in Lassar's paste was compared with dithranol cream. On an overall assessment, patients improved after treatment for a period of four weeks. In the group comparing dithranol cream with 0.2% dithranol in Lassar's paste, seven of the eight patients preferred dithranol cream. Both preparations caused staining of the skin and clothes but irritation of the normal skin was more prevalent in those areas treated with dithranol 0.2% in Lassar's paste. The dithranol cream formulation (Di-Cream) was shown to be a stable, effective formulation that was more acceptable to patients than dithranol in Lassar's paste.

A note on the use of lassar's paste in the “Weeping eczema” of infancy

A note on the use of lassar's paste in the “Weeping eczema” of infancy

A Case of Radio-dermatitis

A patient who had been operated on in May, 1928, for carcinoma of the breast with axillary and supraclavicular metastasis, had been given two courses of post-operative prophylactic roentgen therapy, with an interval of four months between the courses. On her return in January, 1929, several small local recurrent growths were present and the supraclavicular nodes were still enlarged. A slight tanning of the skin was still visible, but it was deemed wise to give another treatment in spite of the fact that a sharp reaction might be expected. In each course of treatment the following technic was employed: To the chest areas, K.V. 140, filter 4 mm. aluminum; to the supraclavicular and axillary areas, K.V. 195, filter 0.53 mm. copper plus 1 mm. aluminum. The skin received on each field 600 r-units. The patient experienced a moderate systemic reaction, and two weeks later a sharp skin reaction, for which her attending physician prescribed unguentine butesin picrate. Quickly the skin reaction became very angry. I saw the patient at this time and continued the use of the ointment, since it is said to be useful for burns. The local condition became progressively worse for two days—there was great pain and burning, the redness increased, and the tissues were markedly edematous, even beyond the fields which had been irradiated. I feared that the entire irradiated area might be destroyed. I was certain that such a severe reaction should not have resulted from the irradiation alone, therefore the ointment was discontinued and, at the advice of a consultant dermatologist, we substituted Lassar's paste (original) with ichthyol (5 per cent). There was a disseminated dermatitis venenata which involved the entire body but was particularly severe within and just bordering the irradiated field. Calamine lotion with phenol (1 per cent) and menthol (0.5 per cent) was employed for this, and gave considerable relief. At the time when the dermatitis appeared, small ulcerations were also present on the buccal mucosa. They were very painful and were thought to be some form of “angina,” but they may also have been a reaction to the ointment similar to that manifested by the skin. The stomatitis was treated successfully with methylene blue (2 per cent). After the use of the Lassar's paste the local condition began to improve immediately and within 48 hours the edema had subsided, the epidermis had begun to regenerate, and the patient was comfortable and recovering. Of course, it is impossible to state what will be the ultimate outcome, but at this time (May, 1929) the skin is apparently healthy except for a moderate tanning. It is interesting to note that the local recurrences disappeared completely and that the supraclavicular nodes are scarcely palpable. This is a case in which radiation dermatitis was intensified by the use of unguentine butesin picrate.