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Objective To evaluate the safety and efficacy of botulinum toxin type A (BTX-A) (BOTOX) over 16 months in the treatment of bilateral primary axillary hyperhidrosis. Design A 16-month study with initial double-blind randomization to 50 U of BTX-A or placebo per axilla. After 4 months, participants could receive up to 3 further treatments with open-label BTX-A over 12 months. Setting Fourteen dermatology or neurology clinics in Germany, Belgium, and the United Kingdom. Participants Of 207 individuals aged between 17 and 74 years who had persistent bilateral primary axillary hyperhidrosis that interfered with daily activities, 174 (84%) completed the study. The baseline gravimetric assessment was a spontaneous sweat production of 50 mg or greater in each axilla prior to initial treatment. Main Outcome Measures At week 4 after each treatment, the response rate of subjects who had at least a 50% reduction from baseline in axillary sweating, as measured by gravimetric assessment, was evaluated. Adverse events were spontaneously reported throughout the study, together with quality-of-life parameters and assessment of neutralizing antibodies to BTX-A. Results Over the 16-month period, 356 BTX-A treatments were given to 207 subjects. After placebo treatment, the response rate at week 4 was 34.7%. After the first, second, and third treatment with BTX-A, response rates at week 4 were 96.1%, 91.1%, and 83.3%, respectively. For subjects receiving more than 1 treatment, the mean duration between BTX-A treatments was approximately 7 months; however, 28% of subjects completed the study after only 1 BTX-A treatment. Subjects' satisfaction after treatments was consistently high, their quality of life improved, and there was a reduction in the impact of the disease on their lives. The safety profile of BTX-A after repeated treatments was excellent and no confirmed positive results for neutralizing antibodies to BTX-A occurred. Conclusion Repeated intradermal injections of BTX-A over 16 months for treatment of primary axillary hyperhidrosis is safe and efficacious.

To determine the efficacy and safety of 0.1% tazarotene cream for the treatment of photodamage.A 24-week multicenter, double-blind, randomized, vehicle-controlled intervention study followed by a 28-week open-label extension.Ambulatory patients in private and institutional practice.Of 563 patients with facial photodamage, 91% and 86% completed the double-blind and open-label phases, respectively. In the double-blind phase, 20 of 283 tazarotene-treated patients and 1 of 280 vehicle-treated patients discontinued treatment owing to adverse events.Once-daily application of 0.1% tazarotene cream or nonmedicated vehicle cream to the face for 24 weeks. Then, all continuing patients received treatment with 0.1% tazarotene cream for another 28 weeks.Primarily, fine wrinkling and mottled hyperpigmentation. Also, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, telangiectasia, actinic keratoses, overall integrated assessment of photodamage, global response to treatment, patients' overall assessment of photodamage, and plasma levels of tazarotenic acid.Compared with the vehicle, at week 24 tazarotene resulted in a significantly greater incidence of patients achieving treatment success (or=50% global improvement) and at least a 1-grade improvement in fine wrinkling, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, and the overall integrated assessment of photodamage (P.01). Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52. Plasma tazarotenic acid concentrations did not exceed 0.71 ng/mL.Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.

Objective To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. Design Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. Setting University hospitals and clinical research centers. Patients Three hundred forty-nine subjects with facial photodamage. Intervention Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. Results Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. Conclusions Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

This pilot study represents the first application of sustained-release local chemotherapy with fluorouracil and epinephrine in an injectable gel for the treatment of psoriatic plaques. The objectives were to assess the feasibility, safety, and efficacy of three dose volumes of fluorouracil and epinephrine in an injectable gel, which was administered intralesionally as a single dose, and to determine qualitative effects in plaque appearance in given affected areas. This gel contains fluorouracil (30 mg/mL) and epinephrine (0.1 mg/mL) in an aqueous system, using purified bovine collagen as a biocompatible, biodegradable carrier matrix. The primary mechanism of action of fluorouracil as an antimetabolite is thought to be inhibition of DNA synthesis by competitive inhibition of thymidylate synthetase. 1 The collagen matrix of the gel formulation provides sustained drug release and thereby increases the exposure of diseased tissue to high drug concentrations for extended periods. The therapeutic effect is amplified by inclusion of

To determine safety and efficacy of monotherapy with etanercept.Randomized, double-blind, placebo-controlled, multicenter study.Outpatient, ambulatory; private practice and university dermatology research centers.Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug.Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study.Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures.After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups.Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques.Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study.Medical center outpatient dermatology services.One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms.Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B).Treatment success and plaque elevation, scaling, and erythema vs time.The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P.05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily.The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.

Pityriasis rubra pilaris (PRP) has been classified into five subtypes by Griffiths. 1 Type I, classic adult PRP , is the most common subtype, representing over 50% of cases. Systemic retinoids (etretinate and isotretinoin) and antimetabolites (methotrexate and azathioprine) are effective treatments of PRP. 2 The use of cyclosporine for treatment of PRP was first discussed in 1989. 3 We present a case of successful treatment of adult-onset PRP with lose-dose cyclosporine. Complete clearance of PRP was achieved with no recurrence for over 2 years. Report of a Case. A 60-year-old white woman was evaluated by her primary dermatologist for a 1-month history of a pruritic facial rash. A preliminary diagnosis of facial dermatitis led to treatment with oral prednisone (80 mg/ d). However, the facial rash worsened, and the palms soon appeared yellowish and thickened. Within 2 months of onset, a widespread eruption of pruritic erythematous plaques appeared over much

The effects of 28 different antiproliferative agents applied topically to normal and hyperproliferative hairless mouse skin were studied. Epidermal cell hyperproliferation was induced by an essential fatty acid-deficient diet or by irradiation with short-wavelength ultraviolet (UV) energy. Epidermal DNA synthesis was measured by hydroxyapatite column chromatography. We compared the effects of these drugs used on normal and hyperproliferative hairless mouse skin with clinical responses in patients with psoriasis treated using the same topical preparations. For most of the drugs tested, the normal and essential fatty acid-deficient mouse model effects showed a good correlation with clinical responses seen in treated patients with psoriasis. The short-wavelength UV energy-treated mouse model effects showed a poorer clinical correlation, perhaps partially caused by wide variations in DNA synthetic rates encountered in the epidermis in this model.

Two patients with lichen aureus are described. The clinical and histologic features of our patients were compared with previously reported cases of lichen aureus in an effort to classify this entity properly among the pigmented purpuric dermatoses. We regard lichen aureus as a distinct entity. Although this disorder has been described principally in adult patients it began at the age of 14 years in one of our patients.

Precipitation of generalized pustular psoriasis was manifested in a patient with previously stable psoriasis vulgaris following lithium carbonate therapy for manic-depressive psychosis. Methotrexate toxicity was observed during the acute stage of the illness, and photochemotherapy was the successful treatment. Further pustulation occurred when lithium carbonate therapy was reintroduced.

We have investigated the clinical responses of 21 patients with severe psoriasis to therapy with etretin, a metabolite of etretinate. In a preliminary double-blind dose-finding study, the optimum dose of etretin was determined to be 50 mg/d (mean, 0.66 mg/kg/d). In an open study, patients receiving etretin therapy were followed up for a minimum of six months. An excellent or good response (greater than 50% clearance) was obtained in 18 of 21 patients. The incidence of mucocutaneous side effects from etretin therapy was similar to that previously reported with etretinate therapy. As a group, patients who received etretin therapy for six or more months showed no significant aberrations from normal levels of serum lipids or serum liver enzymes. However, five patients had mild elevation of liver enzymes or blood lipids, which were corrected by dose reduction. Etretin showed equivalent efficacy to that previously reported with etretinate in severe recalcitrant plaque psoriasis vulgaris. Taken with the reportedly more rapid clearance of etretin from the body, there may be clinical advantages of the use of etretin over the use of etretinate.

The clinical response to isotretinoin (13-cis-retinoic acid) in 11 patients with generalized pustular psoriasis was evaluated. Control of pustulation and systemic symptoms was achieved in ten cases, but additional therapy was required to produce complete clearing of all psoriatic lesions. Also, the efficacy of isotretinoin and etretinate in the treatment of chronic plaque psoriasis was compared in 29 patients. Isotretinoin was found to be less effective than etretinate in the treatment of chronic plaque psoriasis.

The effects of 28 different antiproliferative agents applied topically to normal and hyperproliferative hairless mouse skin were studied. Epidermal cell hyperproliferation was induced by an essential fatty acid-deficient diet or by irradiation with short-wavelength ultraviolet (UV) energy. Epidermal DNA synthesis was measured by hydroxyapatite column chromatography. We compared the effects of these drugs used on normal and hyperproliferative hairless mouse skin with clinical responses in patients with psoriasis treated using the same topical preparations. For most of the drugs tested, the normal and essential fatty acid-deficient mouse model effects showed a good correlation with clinical responses seen in treated patients with psoriasis. The short-wavelength UV energy-treated mouse model effects showed a poorer clinical correlation, perhaps partially caused by wide variations in DNA synthetic rates encountered in the epidermis in this model.

Essential fatty acid deficiency (EFAD) results in epidermal hyperproliferation with acanthosis and hyperkeratosis. The EFAD hairless mouse has been used to study the percutaneous absorption of a 0.1% solution of 4-(14)C-hydrocortisone. In vitro absorption was increased significantly through EFAD compared with normal hairless mouse skin. This is further evidence for a defective skin barrier function in epidermal hyperproliferation.

An elderly man with Hodgkin's disease who was receiving multiple drug chemotherapy became septic and a wide spread bullous eruption developed. Intraepidermal cleavage on skin biopsy supported a diagnosis of the staphylococcal scalded skin syndrome (SSSS) type of toxic epidermal necrolysis. Blood cultures confirmed a staphylococcal septicemia. Occurrence of this syndrome in an adult is unusual. A review of the literature on SSSS indicates an increased mortality when adults are compared with children with this syndrome.

To the Editor.— Etretinate has been shown to be effective in severe types of psoriasis. 1 Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in both normolipidemic and hyperlipidemic subjects. 2 The effects of fish oil on serum lipids in 11 psoriatic patients with drug-induced hyperlipidemia from etretinate (aromatic retinoid) therapy were investigated (Table). These patients received 3 g of omega-3 fatty acids (1.8 g of eicosapentaenoic acid, EPA 20:5w3; 1.2 g of docosahexaenoic acid, DHA 22:6w3; Pharmavite, Los Angeles) and continued to consume their normal diet for four weeks. The fish oil supplementation led to a significant decrease in mean plasma triglyceride concentration from 3.31 ± 1.64 mmol/L (293 ± 145 mg/dL) (SD) to 2.32 ± 1.14 mmol/L (206 ± 101 mg/ dL) (-30%, P

Etretinate is a synthetic retinoid that has been shown to be effective for several types of psoriasis in numerous studies, including severe recalcitrant plaque psoriasis and erythrodermic and generalized pustular psoriasis. 1-10 The drug has recently been approved by the Food and Drug administration for these types of psoriasis. We would like to discuss the appropriate use of this drug in severe forms of psoriasis, and to comment on some of the contents of the editorial "Etretinate and Psoriasis" that was authored by Warwick L. Morison, MD, and published in the July 1987 issue of theArchives. 11 We feel that the attempts to educate the dermatologist in the selection of patients and use of this agent have been appropriate. It would have been remiss for this agent to have been made available for prescription without a carefully organized educational endeavor to ensure the correct use of this drug. See

The clinical response to isotretinoin (13-cis-retinoic acid) in 11 patients with generalized pustular psoriasis was evaluated. Control of pustulation and systemic symptoms was achieved in ten cases, but additional therapy was required to produce complete clearing of all psoriatic lesions. Also, the efficacy of isotretinoin and etretinate in the treatment of chronic plaque psoriasis was compared in 29 patients. Isotretinoin was found to be less effective than etretinate in the treatment of chronic plaque psoriasis.

Nine patients with stages 2 or 3 mycosis fungoides (MF) and one with Sezary's syndrome were treated with oral methoxsalen and long-wave ultraviolet light. Previous therapy had either failed or achieved only partial control. Satisfactory clinical control was achieved in all but one case. Histological improvement was seen in all cases, but complete clearance of lymphoid infiltrate was noted mainly in epidermal and papillary dermal infiltrates. Lower dermal infiltrate remained largely unchanged. The case of Sezary's syndrome was inadequately controlled with systemic prednisone and cyclophosphamide, but addition of photochemotherapy improved the erythema and pruritus. This shows that photochemotherapy may have a place in MF treatment both alone and perhaps in conjunction with other treatments. An early relapse occurred on stopping photochemotherapy in four cases, but one patient has had three months' full remission.

In this second volume, Dr Fleichmajer has assembled a group of experts in several important aspects of basic and clinical investigative dermatology. This book is comprised of 13 chapters covering a wide range of topics, from skin lipid biochemistry to photoimmunology. Particularly interesting and important topics include the possible roles of stratum corneum lipids, immunology of skin cancer, and important information on the newly evolving research into immune responses to UV radiation. Also included are valuable chapters on regulatory mechanisms of collagen in scleroderma skin and clinical and immunologic subsets of lupus erythematosus. Finally, two recent therapeutic agents available for dermatology practice, ketaconazole and acyclovir, are reviewed in detail. All the chapters are well written, well illustrated, and contain appropriately comprehensive reference lists. The topics covered have obviously been carefully chosen to reflect important areas of current interest and research activity in clinical and investigative dermatology. I enjoyed reading this

• Two patients with lichen aureus are described. The clinical and histologic features of our patients were compared with previously reported cases of lichen aureus in an effort to classify this entity properly among the pigmented purpuric dermatoses. We regard lichen aureus as a distinct entity. Although this disorder has been described principally in adult patients, it began at the age of 14 years in one of our patients. ( Arch Dermatol 116:1183-1184, 1980)

A perilesional pale ring of skin that was seen during ultraviolet (UV) treatment of psoriatics was described by Woronoff in 1926.1Recent studies into the pathogenesis of Woronoff's ring (WR) phenomenon were conducted by Penneys et al2during coaltar and UV-light treatment of psoriatics. A phenomenon similar to the Woronoff's rings (WR) was observed by us in a patient who was undergoing Psoralen and UVA (PUVA) therapy for psoriasis and this study was conducted to determine the frequency of WR in PUVA-treated psoriatics. Patients and Methods Twenty patients with psoriasis vulgaris were examined before and during PUVA treatment. The regimen followed that of Parrish et al in 1974.3Patients took methoxsalen capsules orally (0.6 mg/kg of body weight) two hours before treatment with long wavelength UV light irradiation. The lamps used were of two types—one with 48 and the other with 36 vertical lamp tubes. Each contained

• We have investigated the clinical responses of 21 patients with severe psoriasis to therapy with etretin, a metabolite of etretinate. In a preliminary double-blind dose-finding study, the optimum dose of etretin was determined to be 50 mg/d (mean, 0.66 mg/kg/d). In an open study, patients receiving etretin therapy were followed up for a minimum of six months. An excellent or good response (>50% clearance) was obtained in 18 of 21 patients. The incidence of mucocutaneous side effects from etretin therapy was similar to that previously reported with etretinate therapy. As a group, patients who received etretin therapy for six or more months showed no significant aberrations from normal levels of serum lipids or serum liver enzymes. However, five patients had mild elevation of liver enzymes or blood lipids, which were corrected by dose reduction. Etretin showed equivalent efficacy to that previously reported with etretinate in severe recalcitrant plaque psoriasis vulgaris. Taken with the reportedly more rapid clearance of etretin from the body, there may be clinical advantages of the use of etretin over the use of etretinate. (Arch Dermatol1987;123:55-58)

In Reply.— I appreciated the correction of the error in our report by Drs Steger and Hollander. They are correct in saying that the title translation should have read "cignolin." In fact, the reference to the report by Galewsky1contained the wordcignolinin the bibliography of our report.2 Their further historical information on anthralin is interesting and informative.

An elderly man with Hodgkin's disease who was receiving multiple drug chemotherapy became septic and a wide spread bullous eruption developed. Intraepidermal cleavage on skin biopsy supported a diagnosis of the staphylococcal scalded skin syndrome (SSSS) type of toxic epidermal necrolysis. Blood cultures confirmed a staphylococcal septicemia. Occurrence of this syndrome in an adult is unusual. A review of the literature on SSSS indicates an increased mortality when adults are compared with children with this syndrome.

• We have previously described the clinical and dermatopathologic features of a psoriasiform dermatosis in a rhesus monkey ( Macaca mulatta ). This animal has been studied further in attempts to characterize its skin disease. Epidermal cell DNA synthesis was measured following the intradermal injection of tritiated thymidine. Epidermal cell labeling indexes in the involved and uninvolved skin of the affected monkey and in the skin of a normal monkey were compared. The labeling indexes in the involved skin were significantly increased as compared with uninvolved skin; they were also significantly higher than in normal skin. Epidermal polyamine assays showed increased epidermal putrescine in involved skin together with increased spermidine and an increased spermidine-spermine ratio compared with uninvolved and normal skin sites. ( Arch Dermatol 1982; 118:993-996)

The association of cutaneous and mucosal pigmentation with gastrointestinal polyposis has been well-described as the Peutz-Jeghers syndrome. A case is described of a patient who has evidence of gastrointestinal polyposis, diffuse and circumscribed macular hyperpigmentation, a nasal polyp, and the additional features of buccal mucosal pigmented papillomas.

Acrodermatitis continua (Hallopeau's acrodermatitis) is a rare and distinctive variant of pustular

• Precipitation of generalized pustular psoriasis was manifested in a patient with previously stable psoriasis vulgaris following lithium carbonate therapy for manic-depressive psychosis. Methotrexate toxicity was observed during the acute stage of the illness, and photochemotherapy was the successful treatment. Further pustulation occurred when lithium carbonate therapy was reintroduced. (Arch Dermatol114:1788-1789, 1978)

• Essential fatty acid deficiency (EFAD) results in epidermal hyperproliferation with acanthosis and hyperkeratosis. The EFAD hairless mouse has been used to study the percutaneous absorption of a 0.1% solution of 4- 14 C-hydrocortisone. In vitro absorption was increased significantly through EFAD compared with normal hairless mouse skin. This is further evidence for a defective skin barrier function in epidermal hyperproliferation. ( Arch Dermatol 114:1029-1030, 1978)

In Reply.— We wish to thank Dr Warin and Professor Greaves for their interest in our report of perilesional pale rings (similar to WR) in some psoriatic patients treated with PUVA. The underlying mechanism of the perilesional rings of pallor in PUVA-treated psoriatic patients must obviously remain speculative at this time as the relevant studies have not been performed. We think this point was made in our report. It may well be that delayed erythema from any ultraviolet light (UVL) wavelength range is not mediated by PGEs. It has been shown, for example, that topical indomethacin (a PG synthetase inhibitor) will only suppress early UVB- (290 to 320 nm) induced erythema and has little effect on the persistent erythema after 24 to 48 hours. 1 The reason for the delayed or persistent post-UVL erythema is therefore not known at present. There may be several mechanisms for perilesional pale rings following PUVA

• Coal tar therapy has been used for many years in the treatment of scaling skin diseases, including psoriasis and eczema. Previous studies of the potential effectiveness of tar have utilized phototoxic erythema assays with long-wave ultraviolet light (UV-A). However, in clinical use, coal tar is rarely used with UV-A, particularly for scalp disease. Therefore, we investigated a nonphototoxic approach to evaluate different coal tar products. Coal tar was found to suppress epidermal cell DNA synthesis in the hairless mouse model, and this is the basis for the assay presented. Using the epidermal cell DNA synthesis suppression assay, we observed that crude coal tar and a new extract of crude coal tar were equally effective and that a concentration gradient effect was achieved. In addition, four commercial coal tar shampoos assayed varied greatly in their ability to suppress epidermal cell DNA synthesis. One shampoo was washed after ten minutes and no significant alteration of suppressive effect was seen. ( Arch Dermatol 1982;118:487-489)

Ornithine decarboxylase (ODC) level and the levels of its biosynthetic product, putrescine, are elevated in various proliferative cell systems. Furthermore, numerous studies have indicated that the polyamine biosynthetic enzymes ODC and S-adenosylmethionine decarboxylase (SAMD) are implicated in neoplastic growth. 1-3 In adult mouse epidermis, very high levels of induction of ODC may be obtained by application of certain phorbol esters, 4,5 and more recently it has been shown that irradiation of adult hairless mouse skin with ultraviolet energy (UVL) in the sunburn range will also induce similar high levels of ODC. 6,7 A smaller increase of epidermal ODC activity was found in the epidermis of patients suffering from psoriasis by Russell et al. 8 Elevation of epidermal ODC level has also been found in the skin of rats subjected to hair plucking and in rats that were fed high-protein diets. 9 The purpose of this review, therefore, is to discuss