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Background: Radial head arthroplasty (RHA) is commonly used for the treatment of comminuted radial head fractures. Indications as well as implant types continue to evolve. RHA has had good outcomes with midterm longevity. The literature is limited to small case series with varying implant types, and larger studies are needed to determine the optimal implant type and radial head diameter., Methods: A retrospective analysis of RHA cases performed by 75 surgeons at 14 medical centers in an integrated health care system between 2006 and 2017 was completed. Patient demographics, comorbidities, implant type and head diameter, and indications for revision were recorded. Patients' in-person clinical visit data were recorded. Patients were also contacted via telephone at a minimum of 2 years to obtain abbreviated Disabilities of the Arm, Shoulder, and Hand questionnaire and Oxford scores. Implant survivorship was also captured within our integrated system., Results: 405 cases met our inclusion criteria. Mean age was 51.5 ± 15.5 years (range 16-88 years) and more common in females (62%). Chart review and telephone follow-up was performed at a mean of 68.9 ± 31.5 months (range 24-146 months). Our study found that revision rate was positively correlated with increasing radial head diameter. A 26-mm head had 7.7 odds of revision compared to a size 18-mm head (95% confidence interval 1.2-150.1). More than 95% of revision cases were performed within the first 36 months of the index procedure. Obese patients had a significantly lower mean postoperative Oxford score (35.5) compared to controls (38.3) (P = .02). There was a significantly higher overall reoperation rate for terrible triad (18.4%) vs. isolated injuries (10.4%) (P = .04). There was no difference between Acumed Anatomic and Evolve radial head implants in overall reoperation, implant revision, postoperative range of motion, or patient-reported outcomes., Conclusions: Risk of revision is directly correlated with implanted radial head diameter. There were no differences in outcomes and complications between the 2 main implants used. Individuals who did not undergo a revision by 3 years' time tend to retain the implant. Terrible triad injuries had a higher all-cause reoperation rate than isolated radial head fractures, but no difference in the rate of RHA revision. These data reinforce the practice of downsizing radial head implant diameter., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Ulnar collateral ligament reconstruction (UCLR) has allowed the return of overhead athletes to throwing sports. We describe a new double suspensory (DS) technique using a single tunnel in the ulna and humerus, achieving fixation with adjustable loop buttons., Methods: Inclusion criteria included skeletally mature baseball players with clinical and magnetic resonance imaging diagnosis of UCL insufficiency who failed a trial of structured nonoperative treatment. A total of 36 baseball players underwent DS UCLR, between 2011 and 2017, by 1 surgeon with minimum 2-year follow-up. The graft was fixated with an adjustable button loop on the humeral side and a tension slide technique with a button on the ulnar side. Pre- and postoperative Kerlan-Jobe Orthopaedic Clinic and Single Assessment Numerical Evaluation and postoperative Conway scores were obtained., Results: The mean age was 19.8 ± 4.6 years (range, 14-35 years). All were male. Mean years played before surgery was 14.3 ± 4.6 years (range, 8-28 years). There were 32 (89%) pitchers and 4 (11%) position players. There were 13 (36%) high school, 20 (55%) college, 2 (6%) minor league, and 1 (3%) adult league athletes. The mean follow-up was 55.3 ± 23.7 months (range, 26-97 months). There was significant improvement in Kerlan-Jobe Orthopaedic Clinic (33.2 ± 19.9 to 89.7 ± 15.1, P < .0001) and Single Assessment Numerical Evaluation (20.7 ± 16.7 to 93.6 ± 11.9, P < .0001) scores. Using Conway scoring, 25 (69%) had excellent, 5 (14%) good, 3 (8%) fair, and 3 (8%) poor scores. Mean return to play was 9 ± 1.5 months (range, 6-16 months). Only 1 (3%) athlete required a revision surgery and ultimately returned to play and 1 (3%) hardware removal. None developed ulnar nerve symptoms., Conclusion: DS fixation for UCLR in baseball players can lead to excellent clinical results and early return to play., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Different formulations of botulinum toxin type A can behave differently. There has been little clinical research directly comparing formulations., Objective: We sought to compare the efficacy and tolerability of two botulinum toxin type A formulations-BoNTA1 and BoNTA2-in the treatment of moderate and severe glabellar lines., Methods: Sixty-two patients with moderate or severe glabellar lines at maximum contraction were randomly assigned to receive 20 U of BoNTA1 or 50 U of BoNTA2 (20% in the procerus muscle, 80% in the corrugator muscles)., Results: The incidence of 1-grade improvement or greater in glabellar line severity at maximum contraction was as follows: 77% (BoNTA1) versus 59% (BoNTA2) at week 12, 53% versus 28% at week 16. The estimated incidence of relapse was 23% (BoNTA1) versus 40% (BoNTA2) at week 16. Both formulations were similarly well tolerated., Limitations: Few male and non-Caucasian subjects were studied., Conclusion: BoNTA(1) offered more prolonged efficacy than BoNTA2 in the treatment of glabellar lines at the dose ratio of 2.5:1 (BoNTA2:BoNTA1) used in this study.

Background: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis., Objective: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed., Methods: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10., Results: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%)., Conclusion: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.

Background: Hyaluronic acid (HA) fillers have been proposed as alternatives to other temporary skin fillers, such as bovine collagen, for treating facial skin lines and for providing lip augmentation. Several types of commercial HA fillers are now available in many countries. They include Restylane, which is produced by microbiologic engineering techniques, and Hylaform, which is HA extract derived from rooster combs. They have been approved for use in several countries, but not currently in the United States. There are no recommendations to perform pretreatment skin testing by the manufacturers., Objective: Our purpose is to describe and comment on our experiences with Hylaform and Restylane fillers. Observation of any side effects and skin testing results were documented., Methods: Between September 1996 and September 2000, 709 patients were treated with Hylaform and Restylane and were followed up clinically for at least 1 year. Three of these patients (0.42%) developed delayed skin reactions. Three other patients were referred for evaluation of their skin reactions from other practitioners. Five of these 6 patients agreed to skin testing of their forearms., Results: In the 5 patients tested, challenge intradermal skin testing was positive in 4 patients; the reactions started approximately 8 weeks after injection., Conclusions: There was a slight incidence of delayed inflammatory skin reactions to two HA fillers. Both of these reactions occurred after the first and repeat injections. Challenge skin testing was positive in 4 of 5 tested patients.

Background: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously., Objective: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane)., Methods: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy., Results: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin., Conclusion: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Background: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food., Objective: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent., Methods: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks., Results: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables., Conclusion: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Background: The addition of oral retinoids to phototherapy may accelerate and enhance antipsoriatic efficacy, but can result in systemic adverse events and additional laboratory monitoring costs., Objective: Our purpose was to determine whether the topical addition of tazarotene to UVB phototherapy improves efficacy without problems related to photosensitivity., Methods: Bilateral target plaques were randomized to receive two of the following, one on each plaque once daily for 14 days: tazarotene 0.1% gel, vehicle gel, or no treatment. Thereafter, the same treatments were continued 3 times per week, plus UVB phototherapy 3 times per week, for an additional 67 days., Results: Tazarotene plus UVB phototherapy achieved faster and significantly greater reductions in plaque elevation and scaling throughout treatment and achieved at least 50% improvement from the pretreatment baseline with a significantly lower median cumulative UVB exposure than vehicle gel plus UVB light or UVB phototherapy alone. No case of unusual photosensitivity was noted in the tazarotene plus UVB treatment group., Conclusion: The addition of tazarotene to UVB phototherapy improves and accelerates efficacy and maintains acceptable safety and tolerability.

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Background: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone., Objective: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition., Methods: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences., Results: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials., Conclusion: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

Background: Data suggest that androgenetic alopecia is a process dependent on dihydrotestosterone (DHT) and type 2 5alpha-reductase. Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with androgenetic alopecia., Objective: We attempted to determine the effect of finasteride on scalp skin and serum androgens., Methods: Men with androgenetic alopecia (N = 249) underwent scalp biopsies before and after receiving 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride or placebo for 42 days., Results: Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively., Conclusion: In this study, doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels. These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg.

Background: Therapy with aromatic retinoids for psoriasis is associated with abnormal liver function test findings and toxic hepatitis (in 1.5% of patients)., Objective: Our purpose was to determine the safety of acitretin with respect to liver function, on the basis of biopsy., Methods: We treated 128 adults (with chronic, stable psoriasis) with oral acitretin (25-75 mg/day) for four 6-month intervals in a prospective, open-label, 2-year multicenter study. Liver biopsies were performed before and after study completion (2 years)., Results: Eighty-three available pairs of pretreatment and posttreatment liver biopsies demonstrated no change in 49 patients (59%), improvement in 20 (24%), and worsening in 14 (17%). Of these 14 patients with decrements in biopsy status, most changes were mild. There was no correlation between liver function test abnormalities or cumulative acitretin dose and changes in liver biopsy status., Conclusion: Acitretin therapy elicited no biopsy-proven hepatotoxicity in this prospective 2-year study. These findings suggest that periodic liver biopsy may not be necessary with acitretin treatment.

Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections., Objective: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes., Methods: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure., Results: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration., Conclusion: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Background: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed., Objective: The purpose of this study was to determine plasma and toenail concentrations of fluconazole., Methods: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued., Results: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects., Conclusion: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Background: A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed., Objective: Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis., Methods: Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial., Results: Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy., Conclusion: Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.

Background: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis., Objective: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods., Methods: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment., Results: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation., Conclusion: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Background: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated., Objective: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis., Methods: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases., Results: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group., Conclusion: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Background: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases., Objective: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial., Methods: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure., Results: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle., Conclusion: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Background: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known., Objective: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects., Methods: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function., Results: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension., Conclusion: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.

Background: Botulinum A exotoxin (BTX) has been used successfully to treat a variety of hyperkinetic movement disorders. BTX is also capable of reducing hyperkinetic facial lines including prominent glabellar frown lines., Objective: The purposes of this study were to (1) confirm the efficacy of BTX in a double-blind, placebo-controlled investigation; (2) evaluate the use of an electromyogram attached to the injection needle to confirm intramuscular corrugator placement of the BTX; and (3) determine the optimum direction injection technique., Methods: Length and depth of glabellar frown lines were measured before treatment and 4 and 12 weeks after injection of 10 units of BTX or saline solution., Results: Patients treated with BTX had a highly significant reduction in depth and length of glabellar frown lines compared with control subjects., Conclusion: BTX appears to be effective and safe for reduction of glabellar frown lines.

Background: The biologically active form of vitamin D3, calcitriol, is effective in the treatment of psoriasis but can alter calcium metabolism. Calcipotriene is an analog of calcitriol that has low calcemic activity and aids in clearing psoriasis., Objective: The purpose of this study was to determine the safety of topical therapy with calcipotriene particularly in relation to calcium and bone metabolism., Methods: In a double-blind, randomized, parallel, vehicle-controlled trial, 78 adults with plaque psoriasis were treated twice daily with topical calcipotriene ointment (50 microgram/gm, maximum usage, 120 gm per week) or vehicle for 8 weeks. After a screening visit, patients were admitted to the hospital at weeks 0 (baseline), 1,2,4, and 8. Blood and urine chemistry analysis included parathyroid hormone, serum calcium, bone-specific alkaline phosphatase, urinary hydroxyproline, and 24 hour urinary calcium excretion. Bone densitometry measures were performed at baseline and week 8., Results: No incidences of calcipotriene treatment-related hypercalcemia, calcium mobilization from bone, or clinically significant changes in bone density wer noted during this study., Conclusion: Topical application of up to 120 gm per week of calcipotriene ointment for 8 weeks is safe and effective for plaque psoriasis. There were no adverse effects on calcium and bone metabolism during this 8 week study.

Background: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy., Objective: We assessed the safety of long-term therapy with etretinate for psoriasis., Methods: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation to the frequency of these events in control populations., Results: Our data do not provide evidence for an increased risk of cardiovascular disease, cancer, diabetes, or inflammatory bowel disease in association with long-term etretinate use. Although some patients reported that joint problems improved with the use of etretinate, a greater number associated the use of etretinate with joint problems., Conclusion: With proper patient selection and monitoring, long-term etretinate therapy (up to 4 years) does not appear to be accompanied by a substantial increased risk of major adverse effects.

Background: The nevus of Ota is a benign dermal melanocytic lesion that has previously proved difficult to treat. Recently, the Q-switched ruby laser has been reported to be successful in treating benign pigmented lesions and tattoos., Objective: Our study evaluates the treatment of 16 patients with nevus of Ota with the Q-switched ruby laser (694 nm)., Methods: Sixteen patients with nevus of Ota were treated with the Q-switched ruby laser with a pulse width of 28 nsec and energy fluences ranging from 7.5 to 10 J/cm2. Response to treatment was assessed by an independent investigator with photographs., Results: The average number of treatments was 3.8 per patient. After two treatments, 44% of patients showed a 50% or greater improvement. After three treatments, 85% of patients showed a 50% or greater improvement; after four treatments, 100% of patients showed 50% or greater improvement. No patients had permanent textural changes or scarring., Conclusion: High-energy fluences of the Q-switched ruby laser lead to significant improvement without scarring of nevus of Ota after a few treatments.

Background: Basal cell carcinomas (BCCs) are usually treated with ablative procedures. A nonsurgical treatment alternative would be of value in selected patients., Objective: We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003, 5-Fluorouracil Therapeutic Implant, for treatment of BCCs., Methods: Two doses of intralesional MPI 5003 (0.25 and 0.5 ml) were compared in a double-blind study of 20 patients with biopsy-proven BCC. One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination. Before excision the cosmetic appearance of the test site was graded., Results: Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60% of 10 tumors treated with the lower dose (0.25 ml). Cosmetic assessments before excision were typically good to excellent. No systemic side effects occurred., Conclusion: Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC.

Background: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence., Objective: Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes., Methods: Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy., Results: Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle., Conclusion: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.

The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle-controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self-assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations.

Rapid clearing of psoriasis in a psoriasis treatment center setting has been obtained with a combination of short-contact coal tar, phototherapy from high-pressure metal halide lamps (consisting of UVA and UVB), and short-contact high-potency anthralin therapy. These intensive 1 1/2- to 2-hour treatment sessions done three or four times weekly were as efficacious as reported responses to PUVA therapy or conventional psoriasis day care therapy. The treatment schedule allows minimal time away from work, decreased hours per week in contact with crude coal tar, shortened UV treatment times, decreased cost, and a low risk of side effects. It is suggested that the use of UVA and UVB combined with anthralin (UVABA) is effective for many patients with moderate to severe psoriasis.

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.

We report a retrospective review of 18 patients with pityriasis rubra pilaris treated with isotretinoin or etretinate, or both. Of patients treated with only isotretinoin, 60% have achieved sustained resolution. Of four patients treated with etretinate, three have cleared completely and the other patient has shown substantial improvement. Our data suggest that etretinate may be superior to isotretinoin in the treatment of adult-onset pityriasis rubra pilaris.

Recent studies have questioned the therapeutic value of coal tar versus ultraviolet (UV) radiation and their relative necessity in phototherapy for psoriasis. In this investigation, different aspects of tar phototherapy have been studied in single-blind bilateral paired comparison studies. The effects of 1% crude coal tar were compared with those of petrolatum in conjunction with erythemogenic and suberythemogenic doses of ultraviolet light (UVB) using a FS72 sunlamp tubed cabinet. Crude coal tar was clinically superior to petrolatum with suberythemogenic ultraviolet. With the erythemogenic UVB, petrolatum was equal in efficacy to crude coal tar. Suberythemogenic UVB was also used adjunctively to compare the effects of a 5% concentration of a tar extract in an oil base to 5% crude coal tar in petrolatum or the oil base without tar. The tar extract in oil plus suberythemogenic UVB produced significantly more rapid improvement than the oil base plus UVB. The direct bilateral comparison of equal concentrations of tar extract in oil base versus crude coal tar in petrolatum in a suberythemogenic UV photo regimen revealed no statistical differences between treatments. In a study comparing tar extract in oil and the oil base without ultraviolet radiation, the tar extract in oil side responded more rapidly. This demonstrates a direct effect of tar alone in therapy. We have also studied the effects of erythemogenic and suberythemogenic UVB with and without tar extract in oil in the hairless mouse epidermal deoxyribonucleic acid (DNA) synthesis suppression assay. It was found that erythemogenic dosages of UVB produced near maximal inhibition of DNA synthesis with or without coal tars. Suberythemogenic dosages of UVB produced submaximal suppression of DNA synthesis that was enhanced by adjunctive coal tar but not by vehicle, findings which are consistent with the above clinical results. These studies suggest that coal tars combined with suberythemogenic UVB therapy is a practical alternative (to more aggressive UVB therapy without coal tar) which reduces the UVB exposure to the patient.

Vitamin A is important for epithelial cell proliferation and differentiation and therefore has been used as a therapy for a variety of skin diseases. Synthetic vitamin A derivatives, called retinoids, have been used to treat a number of clinical skin conditions, including cystic acne and various forms of ichthyosis, Darier's disease, and psoriasis. Because of the toxicity of existing retinoids, newer vitamin A derivatives have been synthesized and must be evaluated in preclinical assays. Retinoids have profoundly differing biologic properties that can be evaluated selectively by studying their efficacy in different in vivo animal assays. This review will discuss some of the assays that may be useful predictors of retinoid efficacy.

The release and permeation of 1% Westragel and 1% Westrastick and three commercial 1% anthralin products were investigated in vitro with the use of a Franz diffusion cell unit. An inert Teflon membrane with a mesh opening of 74 mu was used for measuring the rate of release. Involved psoriatic and uninvolved human skin collected from the same subjects were used for the permeation study. The permeation of danthron and dianthrone, the major degradation products of anthralin, was also studied with the use of microemulsion gels of 1% danthron and 1% dianthrone, which were prepared in the same way as 1% Westragel. The penetrating anthralin, danthron, and dianthrone were stabilized by a modified receptor fluid, and sample solutions were analyzed by a high-power liquid chromatography method. Involved psoriatic skin was found to be much more permeable to anthralin than was uninvolved psoriatic skin. The slow permeation rate of anthralin, danthron, and dianthrone through normal skin and uninvolved skin indicates that the stratum corneum is the rate-limiting barrier. In involved psoriatic skin, the release rate of anthralin from the topical product becomes the rate-determining step. Large individual variations were found in the permeation of anthralin through involved psoriatic skin, suggesting that the permeation rate of anthralin also may depend on the disease state of psoriatic patients. The anthralin molecule, possessing both hydrophilic and lipophilic centers, diffused significantly faster than did danthron and dianthrone. Westragel, 1%, showed the highest diffusion rate as well as the highest driving force when compared to other commercial 1% anthralin products. This suggests that 1% Westragel may be an optimal design, especially for short-contact anthralin therapy.

Comparison in ultraviolet (UV) dosimetry is reported for three different phototherapy machines. Two of the machines used UV-emitting fluorescent tubes in a standard upright cabinet formation. One of these machines was equipped with predominantly UVB-emitting fluorescent tubes and the other with predominantly UVA-emitting tubes. The third machine consisted of a series of vertically mounted high-pressure mercury halide lamps equipped with two different filters for selection of wavelengths between 295 and 400 nm or 320 and 400 nm. The horizontal UV output of the mercury halide and UVB fluorescent units was reduced between the UV-emitting areas, and it is advised that patients rotate when using these units. It was determined that the vertical uniformity and intensity of UV emission was superior in the mercury halide unit compared with the fluorescent tubed units.

The use of 8-methoxypsoralen water soaks plus ultraviolet A was evaluated retrospectively in 11 patients with moderate to severe palmoplantar psoriasis that had been resistant to previous topical therapies. Patients received twice- or thrice-weekly 30-minute hand and/or foot soaks in 8-methoxypsoralen, 2.5 mg/L, followed by UVA irradiation. The condition of one patient cleared completely, and seven showed good improvement. The range of treatments required for maximal improvement was 14 to 43 with a mean of 28. The range of maximum UVA dosage per treatment was 3.5 to 17.5 joules/cm2, and the range of cumulative UVA required for maximal improvement was 45 to 388 joules/cm2 with a mean of 165 joules/cm2. The mean serum level of 8-methoxypsoralen 60 minutes after completion of hand and foot soaks was 2.5 +/- 0.5 ng/ml compared with 95.75 +/- 10.43 ng/ml after oral 8-methoxypsoralen, 0.5 mg/kg. In our experience this treatment has been a safe and relatively effective form of therapy for resistant palmoplantar psoriasis.

Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.

Phototherapy using sunburn spectrum ultraviolet radiation (UVB) is now a frequently utilized treatment for psoriasis that is extensive or has not responded to topical preparations. Four university centers performed a prospective randomized clinical trial to compare remission times of patients with psoriasis who continued UVB phototherapy after initial clearing with this therapy and patients whose UVB phototherapy was discontinued within 3 weeks of clearing. As assessed by life table methods, the time to flare after initial clearing for patients on UVB maintenance therapy was significantly longer than for patients who discontinued UVB within 3 weeks after initial clearing. Our data suggest that continuing UVB phototherapy after initial clearing contributes to the duration of disease control and is justified for many patients.

Anthralin is an effective topical drug for psoriasis therapy. Recent studies have suggested that anthralin may be effective in high concentrations for short periods of skin contact. The purpose of these studies was to compare psoriasis improvement rates in patients treated with 0.3% anthralin ointment for 10 minutes' skin contact daily with patients treated with a topical steroid, difluorosone diacetate. A further study conducted was a bilateral paired comparison between conventional strength (0.1%-0.5%) anthralin ointment overnight with high concentration anthralin (0.5%-3%) for short contact periods of 10 minutes daily. The results showed good responses in all treatment groups. Short-contact anthralin is confirmed as a practical means of outpatient therapy for psoriasis.

The efficacy of a sunscreen containing an investigational drug, butyl methoxydibenzoylmethane in combination with padimate O against the erythemogenic effect of ultraviolet A (UVA) radiation was evaluated in two double-blind studies involving subjects sensitized with topical 8-methoxypsoralen. UVA radiation was supplied from either a filtered solar simulator (indoors) or filtered sunlight (outdoors). Five formulations were tested: 3% butyl methoxydibenzoylmethane and 7% padimate O, 7% padimate O, 5% octyl salicylate, and 3% oxybenzone, 3% butyl methoxydibenzoylmethane alone, 7% padimate O alone, and vehicle. Sunscreen protection against the erythemogenic effect of UVA radiation was expressed as phototoxic protection factors. The phototoxic protection factor for each sunscreen was derived from a ratio of the minimal phototoxic dose of UVA radiation that produced delayed erythema on sunscreen-protected and unprotected skin. The combination of 3% butyl methoxydibenzoylmethane and 7% padimate O provided significantly greater protection than the other sunscreen formulations, and for each sunscreen the phototoxic protection factors determined indoors and outdoors were comparable.

Two alternate oral formulations of 8-methoxypsoralen, one liquid and the other crystalline, were evaluated in a double-blind trial for their comparative efficacy in combination with ultraviolet A (UVA) light in the treatment of severe psoriasis. With the liquid formulation a greater proportion of patients achieved a good clinical result within the 20 treatment sessions than patients receiving the crystalline formulation. This difference is even more striking using a more rigorous criterion of clearance. Among all patients who achieved clearance, no significant differences were seen in either the number of treatments required or in the total UVA energy employed between the two groups. The preceding clinical results are discussed in light of published pharmacokinetic data.

Three cases of the simultaneous occurrence of lichen planus (LP) and systemic lupus erythematosus (SLE) are presented. Each patient had clinical, histologic, and immunopathologic LP. Additionally, each patient had clinical SLE that fulfilled the American Rheumatism Association criteria for the diagnosis of SLE. The clinical manifestations of SLE were predominantly cutaneous. The three patients had positive lupus band test and high titers of antinuclear antibodies. One patient had vitiligo in addition to SLE and LP. LP and SLE have common clinical, histologic, and immunopathologic features. It is possible that a common agent (or agents) may cause either disease or the overlap syndrome, depending on the immunogenetic predisposition of the patient.

Previous studies of the polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) in psoriatic skin have revealed several abnormalities, including significantly elevated ODC activity. Retinoids have also been shown to modulate polyamine biosynthesis and inhibit ODC activity after different stimuli in various cell and tissue systems. The effect of etretinate has been studied on ODC activity in involved and uninvolved psoriasis skin. Increased ODC activity was found in pretreatment samples from both involved and uninvolved psoriatic skin compared with normal volunteers. Etretinate treatment significantly reduced ODC activity in both involved and uninvolved skin in psoriatics to a similar level of activity before any improvement in clinical appearance was noted. Inhibition of epidermal ODC activity in psoriasis may represent one mechanism of retinoid action on the abnormal skin psoriasis.

The efficacy of a new hydrocolloid dressing occlusion, alone or with 0.1% triamcinolone cream, was compared with triamcinolone acetonide alone or under plastic film occlusion in the treatment of localized plaque-type psoriasis. Thirty-eight patients were randomly assigned to one of four bilateral, paired-comparison treatment groups. Patients underwent 3 weeks of treatment, after which they were followed up for an additional week. After 3 weeks hydrocolloid occlusion with triamcinolone acetonide yielded a significantly better response than the cream alone or the hydrocolloid dressing alone, but the new dressing was comparable to a plastic film occlusive dressing of triamcinolone acetonide. After discontinuation of treatment, however, the sites that had been treated with hydrocolloid-occluded triamcinolone acetonide retained the better results. Topical steroids under hydrocolloid occlusive dressing may be a useful alternative to steroids alone for treatment of localized recalcitrant psoriasis.

Although retinoid derivatives are an effective treatment for severe psoriasis, they result in systemic toxicity, including hyperlipidemia. In an attempt to reverse this retinoid-related hyperlipidemia in patients with psoriasis, a prospective 4-week pilot study of fish oil supplementation was carried out in 25 patients with psoriasis vulgaris receiving etretinate (Ro-10-9359) or acitretin (Ro 10-1670). Daily fish oil supplements containing 3 gm of omega-3 fatty acids (1.8 gm of eicosapentaenoic acid 20:5 omega 3, and 1.2 gm of docosahexaenoic acid 22:6 omega 3) were found to be effective in reducing hypertriglyceridemia, with a significant mean reduction from 215.6 +/- 92.5 to 156.9 +/- 58.5 mg/dl (-27%) when compared with controls (203.6 +/- 46.9 to 204.1 +/- 54.3 mg/dl). High-density lipoprotein cholesterol levels increased from 41.4 +/- 10.5 to 46.1 +/- 10.8 mg/dl (+11%), and the ratio of total cholesterol to high-density lipoprotein cholesterol decreased from 6.6 +/- 1.9 to 5.9 +/- 1.7 (-11%). It is concluded that fish oil supplementation may prove a valuable adjunct to ameliorate the lipid changes secondary to retinoids.

A direct clinical comparison has been made of the efficacy of oral 8-methoxypsoralen with bath-water delivery of 8-methoxypsoralen during psoralen ultraviolet A (PUVA) phototherapy for a group of forty patients with stable plaque-type psoriasis vulgaris. The 8-methoxypsoralen concentration was 3.7 mg/liter in the bath water. The efficacy of these treatments was assessed by their ability to improve or clear the psoriasis. The skin of eight of the twenty patients with oral psoralen cleared, and another eight showed good improvement. Of the twenty patients who received 8-methoxypsoralen in bath water, eight patients had clearing of the skin, whereas nine patients had good improvement during the initial 8-week treatment period. Administration of 8-methoxypsoralen in bath water required much lower ultraviolet A irradiance to achieve maximum improvement. There were no systemic side effects in the patients treated by bath-water delivery; however, some patients did develop phototoxic erythema. Minimal phototoxic doses were also studied in patients and in volunteers using both routes of psoralen delivery. The minimal phototoxic dose threshold after psoralen bath delivery gradually declined over five treatments from 5.3 +/- 0.6 joules/cm2 to 2.8 +/- 0.3 joules/cm2, suggesting an accumulation of psoralen in the skin with this method of drug delivery. Bath-water delivery of 8-methoxypsoralen was therefore found to be as effective as oral administration of 8-methoxypsoralen and yet required smaller amounts of ultraviolet A radiation and yielded fewer side effects. It would thus seem to be confirmed as a useful alternative means of 8-methoxypsoralen administration in PUVA therapy.

Retinoids are potent therapuetic agents that have been found to be effective in a variety of skin diseases. They are of benefit in various forms of severe psoriasis. With severe plaque psoriasis, they are used most effectively in combination with other forms of therapy, such as phototherapy. With generalized pustular psoriasis, they are effective monotherapy and are frequently helpful for the control of exfoliative psoriasis. A variety of new retinoid analogs have been studied in clinical investigations. This article discusses important aspects of the use of etretinate, isotretinoin, acitretin, and arotinoid ethyl ester in the treatment of severe forms of psoriasis.

A prospective study was carried out over 12 months involving twenty patients with psoriasis vulgaris who were treated with all-trans-aromatic derivative of vitamin A, etretinate. Etretinate was found to be an effective therapy for this skin disorder. Arthritis accompanying psoriasis vulgaris in four of seven of our patients was greatly improved by retinoid therapy. Side effects were found to be dose-related and included mucocutaneous abnormalities as well as abnormalities of blood lipids and liver function tests. Maintenance therapy appears to be required in nearly all patients, with relapse occurring within approximately 8 weeks. Polyamine biosynthesis has been determined previously to be accelerated in patients with psoriasis vulgaris. Polyamines (putrescine [Pu], spermidine [Sp], and spermine [Sm] were measured in skin samples of six patients with stable plaque-stage psoriasis before treatment and at 4 weeks during treatment. Pu, Sp, Sm levels, as well as the Sp/Sm ratio, fell. Epidermal DNA synthesis is increased in involved and noninvolved psoriatic skin; it was measured before and during treatment (at 4 weeks) in this study and found not to fall significantly during this period of time. Polyamine levels therefore decreased prior to any significant expected decrease in epidermal DNA synthesis measured in both involved and uninvolved skin.