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Background: Patients with psoriasis have elevated risk of coronary artery disease., Objective: Do patients with severe psoriasis have larger epicardial adipose tissue volumes (EAT-V) that are associated with cardiovascular risk?, Methods: For this cross-sectional study, we recruited dermatology patients with severe psoriasis and control patients without psoriasis or rheumatologic disease themselves or in a first-degree relative. Participants aged 34 to 55 years without known coronary artery disease or diabetes mellitus underwent computed tomography (CT); EAT-V was obtained from noncontrast CT heart images., Results: Twenty-five patients with psoriasis (14 men, 11 women) and 16 controls (5 men, 11 women) participated. Groups had no statistical difference in age, body mass index, various cardiovascular risk factors (except high-sensitivity C-reactive protein in men), CT-determined coronary artery calcium scores or plaque, or family history of premature cardiovascular disease. Mean EAT-V was greater in the psoriasis group compared to controls (P = .04). There was no statistically significant difference among women; however, male patients with psoriasis had significantly higher EAT-V than controls (P = .03), even when corrected for elevated high-sensitivity C-reactive protein (P = .05)., Limitations: A single-center convenience sample may not be representative., Conclusion: Males with psoriasis without known coronary disease or diabetes had greater EAT-V than controls. EAT-V may be an early identifier of those at increased risk for cardiovascular events., Competing Interests: Conflict of interest Drs Ellis, Elder, and Gudjonsson have served as consultants to various manufacturers of pharmaceuticals for psoriasis. Drs Neville, Sayyouh, Nair, Kazerooni, Rubenfire, and Agarwal and Author Ma have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Background: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B., Objectives: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD., Methods: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks., Results: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity., Limitations: Further confirmatory phase-III studies are required., Conclusion: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

In the last few years, there has been progress in identifying some of the risk genes for psoriasis. This has resulted in a major impetus toward drug development as many of the same pathways and processes identified in psoriasis have been shown to have major roles in other chronic inflammatory diseases, suggesting that psoriasis can be used as a treatment model for many other diseases. This has resulted in a shift in research toward a select number of biological processes and has been accompanied by a surge in drug development with over 20 systemic agents currently in clinical testing for psoriasis, many of which target the pathways identified through genetic and basic research. Although it is too early to tell for many of these agents how effective and safe they will be, and where they will fit into treatment algorithms, it is evident that our range of options in treating this often perplexing disease will greatly increase in the future., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Use of e-mail among patients and physicians is limited by reservations over issues such as medicolegal aspects, reimbursement, and time-management., Objective: Our purpose was to identify the content of patient-related e-mails in an academic dermatology practice and determine whether clinical questions could be answered by e-mail., Methods: The first 100 e-mails received each year that related to patients from January 1, 2000 to June 1, 2005 (plus any messages received in e-mail threads started in the original 100) were studied (N = 614). E-mails were sent by patients, potential patients, or physicians in reference to a patient. E-mails were divided into 8 categories on the basis of content. E-mails were subdivided as relating to new (patients who had never been seen in-person) or established patients. All clinical questions were categorized as to whether they were answered by e-mail. The average number of e-mails received per e-mail thread was tallied., Results: E-mails were distributed as follows: clinical question from a physician (20%), clinical question from a patient (17%), appointment request (18%), request for referral to another physician (7%), prescription refill (3%), research inquiry (2%), thank-you correspondence (31%), other (17%). Percentages do not equal 100 because some e-mails contained more than one subject. Clinical questions were more likely to be answered when posed by physicians (100%) than patients (70%; P = .001), and when from established (79%) versus new patients (60%; P = .02). There were fewer e-mails per thread for queries from physicians (1.6 messages received) versus patients (2.2; P < .001) and for established (1.6) versus new patients (2.2; P < .001)., Limitations: This study was limited to the experience of one dermatologist in an academic setting., Conclusion: E-mail broadens communication between patients and their dermatologist. E-mail may facilitate consultation with other physicians and management of patients with chronic disease. "Thank-you" responses engage a substantial amount of e-mail resources.

Although not completely understood, there is clearly a genetic component in the development of psoriasis. Twin studies show a 67% concordance for monozygotic twins versus 18% for dizygotic twins. This lack of complete concordance in monozygotic twins suggests multifactorial inheritance and interaction between genetic predisposition and the environment. At present, 8 different psoriasis susceptibility loci have been identified in genome-wide linkage scans, including locations on 15 different chromosomes. Genetic connections have been made between psoriasis and other diseases, including atopic dermatitis, rheumatoid arthritis, and Crohn's disease. A variety of approaches are available for the treatment of psoriasis, ranging from topical agents for milder forms of the disease to phototherapy and systemic agents for severe psoriasis. Despite the importance of systemic therapies and recent advances represented by biologic agents, topical treatments will probably remain the mainstay of psoriasis therapy for most patients. The advent of new, cosmetically attractive vehicles may enhance compliance, add to the use of topical agents, and potentially improve patient outcomes.

Background: Over-the-counter (OTC) topical corticosteroids, such as hydrocortisone cream (HC), are commonly used for the treatment of minor dermatological conditions. The safety and efficacy of such products are well documented, but details on patterns of use and self-treatment with HC in the OTC environment remain scarce., Objective: We sought to determine compliance with label directions of OTC HCs by examining self-reported patterns of OTC HC use in adults and children., Methods: A random digit-dialed telephone survey was conducted with 2000 US adults. Following identification of users of OTC HC in the last 6 months, respondents were asked questions about the conditions being treated with OTC HC and the frequency and duration of use in both adults and children., Results: Of adults completing the survey, 20% (n = 396) had used OTC HC. In 83% of cases, the conditions treated were consistent with the OTC label. Use was limited; HC was applied < or =4 times daily in 98% of adult users and lasted < or =7 days in 92%. Patterns of pediatric use were similar and almost always consistent with the labeling. Of households with children, 25% (n = 168) had used OTC HC to treat pediatric dermatological conditions. Of child users, 93% were 2 years of age or older, treatment was limited (97% applied HC < or =4 times daily and 94% of treatments lasted < or =7 days), and the conditions treated were appropriate in 86% of cases., Limitations: This telephone survey relied on respondents' recall and self-reporting. Our data on pediatric use of OTC HC are skewed toward treatment of younger children., Conclusion: The data suggest that OTC HC products are used for self-treatment in a limited and appropriate fashion that is likely to be safe in both adults and children.

Background: Reliable assessment of severity in psoriasis is essential to document treatment responses in clinical research. The reliability of current clinical outcome measures is uncertain., Objective: To quantify the relative variation in commonly used outcome measures (the Psoriasis Area and Severity Index [PASI] and one version of the Psoriasis Global Assessment [PGA]), and a newer measure, the Lattice System Physician's Global Assessment (LS-PGA)., Methods: Physicians who were experienced (53%; 9/17) or inexperienced (47%; 8/17) in using PASI and PGA evaluated 35 patients with psoriasis in random order twice with each rating system. We assessed the variation in scoring psoriasis severity within (intrarater) and among (interrater) physicians., Results: PASI, PGA, and LS-PGA were highly correlated (r > 0.8 for all comparisons) and had high overall reliability (Cronbach's alpha > 0.9 for each). PGA and LS-PGA had lower intrarater variation than PASI. LS-PGA had a 55% higher concordance coefficient between the two evaluations than did PGA. Interrater variation was lower for PGA and LS-PGA than for PASI both before and after correction for measurement error. Experience was beneficial in reducing variation in PASI scores but was not required with PGA or LS-PGA., Conclusion: The LS-PGA, which is standardized, does not require experience, and provides discrete word-based scores with intrinsic meaning, is a reliable measure of therapeutic effect in psoriasis, and would allow comparisons across different clinical trials.

Background: Few cost-effectiveness analyses have been conducted on topical therapies for atopic dermatitis., Objective: We sought to compare cost-effectiveness of high-potency topical corticosteroids (HPTCs) and tacrolimus ointment for the treatment of moderate to severe atopic dermatitis for patients who are not responsive to or not well controlled with mid-potency topical corticosteroids., Methods: A Markov model represented the cyclic nature of atopic dermatitis. Clinical outcomes were derived from published literature. "Efficacy" was defined as disease-controlled days on which patients experienced a greater than 75% improvement in their disease. Resource use and changes in management were on the basis of opinions of a physician panel; secondary treatment was an oral antibiotic with topical corticosteroids. Sensitivity analyses were conducted for all variables., Results: The model was sensitive to duration of continuous treatment with HPTCs. HPTCs, when limited to 2-week treatment cycles, were associated with the highest total costs ($1682 per year) and the least efficacy (185 disease-controlled days). HPTCs in 4-week treatment intervals and tacrolimus ointment were similar in total costs and efficacy ($1317 vs $1323 for 194 vs 190 disease-controlled days, respectively). Although primary drug costs were higher for patients treated with tacrolimus ointment, patients treated with regimens of HPTCs incurred higher secondary drug costs., Conclusion: In the base case analyses, tacrolimus ointment was more cost-effective than HPTCs administered in 2-week treatment cycles, and similar in cost-effectiveness to 4-week cycles of HPTCs.

Background: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable., Objective: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis., Methods: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course., Results: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses., Conclusion: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.

Sulfasalazine is used as a therapy for various autoimmune conditions, including psoriasis; its effectiveness is presumed to be the result of its immunomodulatory effects. We have treated patients with severe alopecia areata with sulfasalazine as part of our dermatology practice and have noticed cosmetically acceptable regrowth in 23% of patients in whom a response could be determined. In view of its good safety profile, sulfasalazine may be considered for systemic treatment of severe alopecia areata.

Background: Atopic dermatitis/eczema (AD/E) is a common disease. Few studies have attempted to quantify the cost to third-party payers., Objective: Our purpose was to identify the annual cost of medical services and prescription drugs for the treatment of AD/E to private insurance and Medicaid payers in the United States., Methods: We used a retrospective study design employing claims data from 1997 and 1998 from a private insurer and a state Medicaid program to analyze costs incurred. Beneficiaries were considered to have AD/E if they had at least one claim in 1997 with a primary or secondary listing of 1 of 3 diagnosis codes: 691.8, other atopic dermatitis and related conditions; 692.9, contact dermatitis and other eczema when no cause is specified; or 373.3, noninfectious dermatoses of eyelid. Patients who did not meet the diagnosis criteria served as a control group in each payer for comparisons of expenditures with the AD/E group., Results: Disease prevalence was 2.4% (private insurer) to 2.6% (Medicaid) of all eligible beneficiaries, and 3.5% to 4.1% of patients submitted at least one health care claim during the study period. Medicaid-insured patients used outpatient hospital visits and hospitalizations at a greater rate than did privately insured patients; neither used emergency departments extensively. The third-party payer cost of illness for AD/E ranged from $0.9 billion to $3.8 billion when projected across the total number of persons younger than 65 years insured by private insurers and Medicaid in the United States. More than one fourth of all health care costs for patients with AD/E may be attributed to AD/E and co-morbid conditions., Conclusions: Annual costs of AD/E are similar to those of other diseases such as emphysema, psoriasis, and epilepsy. Patients incur significant costs associated with AD/E and co-morbid conditions.

Background: Because health care resources are limited, therapeutic regimens should be assessed for their relative costs and effectiveness., Objective: We assessed cost-effectiveness for treating psoriasis using two strategies: one consisted principally of methotrexate and the other was principally a rotational schedule of modified cyclosporine (Neoral) with methotrexate., Methods: We performed a cost-effectiveness analysis using a computerized decision analytic model of simulated patients with moderate to severe psoriasis. Patients were randomly assigned to receive treatment with one of the two strategies. Direct costs included acquisition of medications, laboratory and physician fees, and costs of treating side effects. Because of uncertainty regarding rates of clearing of psoriasis, the relative efficacy of methotrexate and cyclosporine was varied over a wide range in a sensitivity analysis., Results: In the base case over a 10-year treatment period, the methotrexate strategy cost $33,000 and provided approximately 2 years clear of psoriasis compared with $38,000 and approximately 4 years clear of psoriasis for the rotational strategy. When the relative effectiveness of cyclosporine to methotrexate in clearing psoriasis varied from approximately 1 to 20, the rotational strategy cost from $4100 to $2700 per incremental clear year., Conclusion: In selecting therapies for psoriasis patients, both costs and effectiveness should be considered. In this simulation, patients could obtain additional periods clear of psoriasis at an incremental cost by using cyclosporine in rotation with methotrexate. If even a small utility gain accompanies the complete clearing of psoriasis, such a strategy may be a worthwhile investment of resources comparable to other healthcare interventions.

Cost-effectiveness studies are rising in importance as means for justifying expenditures on health interventions and as guides for making treatment and resource allocation decisions. However, the term "cost-effective" often is used erroneously, attributed to therapies that have not been subjected to rigorous cost analysis or comparison to an appropriate alternative. Health economic studies include cost-of-illness, cost-minimization, cost-effectiveness, cost-utility, and cost-benefit analyses. Each of these types of analyses differs in what it measures and under what circumstances its use is appropriate. This article describes the different types of economic studies, using examples to highlight their key features, and provides a summary of the key components of an economic analysis including perspective, cost and outcomes measurement, time horizon, cost-discounting, and sensitivity analysis.

Isotretinoin (13-cis-retinoic acid) is a retinoid that has been used over the past 2 decades to treat a wide variety of dermatologic conditions, some with great success. Although it is beneficial in many skin conditions, the side effects and toxicities of oral retinoids require careful monitoring by experienced physicians. The clinical applications of oral retinoids continue to expand both within and beyond the field of dermatology.

Background: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis., Objective: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined., Methods: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months., Results: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes., Conclusion: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections., Objective: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes., Methods: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis., Results: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively., Conclusion: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Background: Tacrolimus is a potent immunosuppressant used in organ transplant recipients; an ointment formulation is being developed as a therapeutic agent for atopic dermatitis., Objective: Our purpose was to define the pharmacokinetics and evaluate tacrolimus 0.3% ointment as therapy for moderate to severe atopic dermatitis., Methods: Thirty-nine patients, 5 to 75 years of age, received 14 applications over 8 days. Serial blood samples were collected on days 1 and 8, with predose samples collected on days 2 through 7. Overall response and signs/symptoms were rated daily on days 1 through 11. Incidence of adverse events and laboratory profile were determined., Results: Mean area under the curve (0.9 to 42.5 ng x hr/ml) was highly variable and appeared to be related to size of application area. No systemic accumulation of tacrolimus was observed. Comparison to historical intravenous data indicates that absolute bioavailability of topical tacrolimus was less than 0.5%. Ninety-five percent of patients showed at least good improvement. All adverse events were transient. Burning was the most common application site adverse event and vasodilatation ("flushing/warmth") was the most common nonapplication site adverse event. No drug-related changes in laboratory profile were observed., Conclusion: The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.

Background: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process., Objective: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies., Methods: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted., Results: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel., Conclusion: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Background: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris., Objective: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris., Methods: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus., Results: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed., Conclusion: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

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 psychosocial aspects of the treatment of photodamaged skin have received little attention., Objective: We prospectively examined the psychosocial correlates of the treatment of mildly to severely photodamaged skin., Design: Sixty subjects (age, 53.3 +/- 1.3 years [mean +/- standard error]; 35 receiving retinoic acid and 25 the inactive vehicle) completed a battery of psychosocial ratings before starting therapy and after 24 weeks of therapy with retinoic acid or vehicle., Results: Before therapy, the subjects had pathologically high obsessive-compulsiveness scores (measured by the Brief Symptom Inventory [BSI]). From before to after therapy, the retinoic acid group reported decreased obsessive-compulsiveness (BSI) (p = 0.01), and decreased phobic anxiety (BSI) (p = 0.04), whereas the vehicle group reported an increase (p < 0.05) in both these symptom dimensions., Conclusion: High obsessive-compulsiveness (BSI), which is associated with excessive perfectionism and need for control, probably predisposed the subjects to seek treatment of their wrinkles. In the retinoic acid group but not the vehicle group there was an improvement in obsessive-compulsiveness and decreased anxiety in previously anxiety-provoking situations.

Background: Hyperpigmented lesions are a predominant component of photoaging in Chinese and Japanese persons. Topical 0.1% tretinoin cream improves the hyperpigmentation associated with photoaging in Caucasian persons., Objective: Our purpose was to assess the efficacy of 0.1% tretinoin cream treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients., Methods: Forty-five photoaged patients (23 Chinese, 22 Japanese) completed a double-blind, randomized study in which 21 applied 0.1% tretinoin cream and 24 applied vehicle cream once daily to face and/or hands for 40 weeks. Patients' hyperpigmented lesions were evaluated clinically and by colorimetry throughout the study and by histologic analysis of skin biopsy specimens taken before therapy and at the end of treatment., Results: At the end of treatment, hyperpigmented lesions of the face and hands were lighter or much lighter in 90% of patients receiving tretinoin compared with 33% receiving vehicle (p < 0.0001). Colorimetry demonstrated significant lightening of lesions after tretinoin compared with vehicle (p < 0.05). Histologic analysis of hyperpigmented lesions demonstrated a statistically significant 41% decrease in epidermal pigmentation with tretinoin therapy as compared with a 37% increase in the vehicle group (p = 0.0004). No patient withdrew for adverse effects., Conclusion: By clinical, colorimetric, and histologic evaluation, 0.1% tretinoin cream significantly lightens the hyperpigmentation of photoaging in Chinese and Japanese patients.

Background: Substance P, an undecapeptide neurotransmitter, has been implicated in the pathophysiology of psoriasis and pruritus., Objective: Safety and efficacy of topical capsaicin, a potent substance P depletor, were evaluated in patients with pruritic psoriasis., Methods: Patients applied capsaicin 0.025% cream (n = 98) or vehicle (n = 99) four times a day for 6 weeks in this double-blind study. Efficacy was based on a physician's global evaluation and a combined psoriasis severity score including scaling, thickness, erythema, and pruritus., Results: Capsaicin-treated patients demonstrated significantly greater improvement in global evaluation (p = 0.024 after 4 weeks and p = 0.030 after 6 weeks) and in pruritus relief (p = 0.002 and p = 0.060, respectively), as well as a significantly greater reduction in combined psoriasis severity scores (p = 0.030 and p = 0.036, respectively). The most frequently reported side effect in both treatment groups was a transient burning sensation at application sites., Conclusion: Topically applied capsaicin effectively treats pruritic psoriasis, a finding that supports a role for substance P in this disorder.

Background: Alcohol has been reported to be a risk factor in psoriasis mainly based on the observation that there is a higher prevalence of alcohol abuse in persons with psoriasis, especially in men., Objective: We prospectively examined the relation between pretreatment average daily ethanol consumption and treatment outcome in inpatients with moderate to severe psoriasis., Methods: The severity of psoriasis of 94 inpatients (48 men and 46 women) was assessed before and after treatment. Ethanol use was determined by obtaining the patients' reports of their average daily consumption of alcoholic beverages during the 6 months before admission., Results: The average daily ethanol intake of more than 80 gm before treatment was more frequently associated with less treatment-induced improvement (less than 10%) (p = 0.02) in the percentage of the total body surface area affected by psoriasis in men but not in women., Conclusion: Ethanol abuse may have an adverse effect on treatment outcome in men with psoriasis.

Background: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis., Objective: Our purpose was to determine in a randomized, placebo-controlled, double-blind multicenter study the effects of recombinant human interferon gamma therapy in patients with atopic dermatitis., Methods: Patients received 50 micrograms/m2 rIFN-gamma (n = 40) or placebo (n = 43) by daily subcutaneous injection for 12 weeks. Seventy-eight patients completed the treatment course; two patients receiving rIFN-gamma (one because of constitutional side effects) and three receiving placebo discontinued treatment before completion. Physician and patient overall response evaluations, clinical severity scores, body surface area involvement, and laboratory parameters were monitored throughout the trial., Results: Patients in both treatment groups were similar except that the rIFN-gamma group was older and had a longer disease duration. Forty-five percent of rIFN-gamma-treated patients and 21% of placebo-treated patients achieved greater than 50% improvement in physicians' overall response evaluations (p = 0.016). As estimated by patients, responses also showed significant improvement in the rIFN-gamma group compared with the placebo group (53% vs 21%, p = 0.002). Significant reductions in erythema (p = 0.035) and in excoriations or erosions (p = 0.045) occurred in rIFN-gamma-treated patients. Other atopic symptoms such as conjunctivitis (p < 0.002) were also reduced in the rIFN-gamma group. Occasional headaches, myalgias, or chills occurred in 30% to 60% of rIFN-gamma-treated patients but were effectively prevented by pretreatment acetaminophen and by dosing at bedtime. Grade II granulocytopenia occurred in five rIFN-gamma patients but normalized with continued treatment. Reduction to alternate-day dosing was necessary for six patients in the rIFN-gamma group and two in the placebo group. Seven had mild elevations of hepatic transaminase levels that did not affect therapy. The mean eosinophil count was significantly reduced (p = 0.003), whereas a nonsignificant increase in serum IgE levels occurred in the active treatment group., Conclusion: This study demonstrated that rIFN-gamma given by daily subcutaneous injection over a 12-week period was safe, well accepted, and effective in reducing inflammation, clinical symptoms, and eosinophilia in severe atopic dermatitis.

Background: Cutaneous T-cell lymphomas (CTCLs) rarely arise before 30 years of age; therefore the characteristics of these lymphomas are largely unknown., Objective: Our purpose was to assess the clinical and pathologic aspects of CTCL in young persons., Methods: We identified nine patients who had epidermotropic CTCL by 30 years of age and analyzed their lymphoma phenotypes and genotypes., Results: The diagnosis of CTCL was made an average of 6 years after the reported onset of the lesion. Histologic examination revealed the mycosis fungoides (MF) form of CTCL, and none of the patients underwent conversion to nonepidermotropic or large-cell variants of CTCL. The immunophenotypes were typical of MF-type CTCL; seven of eight lymphomas tested were predominantly CD4+ although in only three were abnormal CD4/CD8 ratios present. All four cases tested were CD7- (Leu-9-), and seven of eight specimens tested exhibited deficient Leu-8 expression. The loss of one or more pan-T-cell markers was found in four of eight patients tested. Clonal beta-chain T-cell receptor gene rearrangements occurred in skin samples from four of eight tested cases., Conclusion: A persistent eruption, even in youths and young adults, should be thoroughly evaluated for possible CTCL.

We describe a 48-year-old woman who had worsening psoriasis, photosensitive reticular erythematous mucinosis (REM), and acne rosacea. The psoriasis was unresponsive to etretinate, and the REM was unsuccessfully treated with hydroxychloroquine. Cyclosporine (6 mg/kg/day) successfully cleared the psoriasis in 8 weeks but did not improve the REM and acne rosacea. Possible causes for the lack of response of the REM to cyclosporine are discussed.

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.

Three patients with chronic urticaria, two of whom also had angioedema, were treated with oral cyclosporine, 6 mg/kg per day. In each patient, complete resolution of symptoms occurred within the first week of therapy; however, all patients eventually had to stop therapy as a result of side effects. On stopping therapy, all side effects resolved and the urticaria and angioedema recurred. Although cyclosporine therapy is not an appropriate treatment of urticaria, the results of this preliminary study suggest that cyclosporine and related drugs should be investigated in the treatment of mast cell-mediated diseases.

Treatment of chronic urticaria presents a challenge to both practitioner and patient. Traditional H1 antagonists with good efficacy but substantial side effects are being supplanted in many cases by nonsedating H1 antagonists such as terfenadine and astemizole. Antidepressant medications and combinations of H1 and H2 antagonists offer improved results for selected patients. Further development and investigation of mast cell stabilizers and inhibitors of urticaria mediators other than histamine hold promise. A better understanding of the underlying pathogenesis remains the greatest hope of formulating rational and effective therapy.

The efficacy and safety of clobetasol propionate 0.05% scalp application was evaluated in 378 patients with moderate to severe scalp psoriasis in a double-blind vehicle-controlled parallel group study. After 2 weeks of twice-daily applications, 81% receiving active drug versus 22% receiving vehicle had clearing of 50% or greater. Complete clearing was seen in 26% with active drug and 1% with vehicle. Local side effects were primarily burning or stinging in 11% and 10% of patients treated on an active or a vehicle regimen, respectively. The morning cortisol levels of 168 patients were checked at baseline and again after 2 weeks of drug therapy. Subnormal morning plasma cortisol values were seen in 5% of the patients receiving active drug and in 5% receiving vehicle; 13% of those taking active drug versus 5% taking vehicle had a 50% or greater decrease in morning cortisol at the 2-week visit compared with baseline values. Clobetasol propionate 0.05% scalp application appears to be a safe and an effective treatment for scalp psoriasis.

Cyclosporine has been used in the experimental treatment of multiple inflammatory diseases of presumed autoimmune origin, including insulin-dependent diabetes mellitus, uveitis, rheumatoid arthritis, inflammatory bowel diseases, Graves' disease, and myasthenia gravis. In dermatology, the drug has been used successfully as primary therapy for psoriasis and psoriatic arthritis, alopecia areata, pyoderma gangrenosum, Behçet's disease, atopic dermatitis, and lichen planus. At a dose of 3 to 5 mg/kg per day, cyclosporine is well tolerated by most patients. However, because of concerns about its potential short- and long-term side effects, patients who use this drug require close monitoring. This review discusses appropriate clinical and laboratory evaluations, common and unusual side effects and their management, drugs that might alter the pharmacokinetics of cyclosporine metabolism, and criteria for dosage adjustments.

Topical cyclosporine may be effective in the treatment of various oral mucosal disorders. In three open trials and in one double-blind study, a topical formulation of this drug produced significant improvement in oral lichen planus. Cyclosporine blood levels were generally low in these studies and no abnormalities of laboratory values resulted during use. Of six patients with oral bullous diseases treated with topical cyclosporine, four showed a decrease in erythema, partial healing of ulcerations, and a reduction in pain. Three patients relapsed shortly after cyclosporine was discontinued. Four of eight patients with persistent aphthous stomatitis remained virtually free of ulcers during 8 weeks of topical cyclosporine therapy. These results indicate that topical cyclosporine is beneficial as a therapy for oral lichen planus and possibly other mucosal diseases.

Several prospective studies have documented the effectiveness of oral cyclosporine in the treatment of psoriasis. Despite this, the use of cyclosporine has been limited because of concern about the possibility of drug-induced renal dysfunction. We review the effects of cyclosporine on renal function.

Three patients, one of whom has been previously reported, had erythematous papules and nodules of the face and upper part of the chest during cyclosporine therapy for inflammatory skin diseases. Histologic examination and DNA analysis (performed in two cases) revealed benign dermal lymphocytic infiltrates. In two cases proliferation of only T cells occurred. In the third case, both T and B cell populations were expanded and there was vacuolar degeneration of the basal layer of the epidermis and IgG, IgM, and C3 deposition along the dermoepidermal junction. These findings may be the result of cyclosporine-induced immune dysregulation. The lesions resolved in all patients after therapy was stopped.

We performed a 22-month trial of topical tretinoin (retinoic acid) in the treatment of photoaging. Thirty patients participated in a 4-month, randomized, blinded, vehicle-controlled study that has been reported previously; 21 patients continued tretinoin therapy on an open-label basis, participating in the study for a total of 10 months, and 16 patients continued for 22 months. During the open-label study, the statistically significant improvement that had occurred in fine and coarse wrinkling and skin texture during our original study was sustained, despite reductions in dose or frequency of application of tretinoin. The number of discrete lentigines decreased by 71% compared with the number before therapy. Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded.

Cyclosporine inhibits the activation of helper T cells that may be pathogenic in alopecia areata. Therefore we treated six patients with alopecia areata (five men, one woman) with oral cyclosporine, 6 mg/kg/day for 12 weeks. Three patients had alopecia universalis, one had alopecia totalis, and two had patchy alopecia areata of the scalp. Hair regrowth in the scalp of all patients occurred within the second and fourth weeks of therapy, followed by hair regrowth of the face and chest (in the male patients), pubic area, extremities, and axillae. Overall, the site of best response was the scalp. Cosmetically acceptable terminal hair regrowth on the scalp occurred in three of six patients. Significant hair loss, however, occurred in all patients within 3 months of discontinuation of cyclosporine treatment. Clinical response correlated with changes in immune cell infiltration of the hair follicles. The number of leukocytes per hair follicle was quantified in transverse scalp biopsy sections stained with a panel of monoclonal antibodies. The degree of terminal hair regrowth correlated significantly with decreases in follicular epithelial human lymphocyte antigen-DR and intercellular adhesion molecule-1 expression, T cells, helper/inducer (CD4) T cells, suppressor/cytotoxic (CD8) T cells and Langerhans cells (CD1+DR+) from the hair follicles during cyclosporine therapy. A significant decrease in the CD4/CD8 ratio occurred early in the course of treatment and was maintained throughout the therapy. This decrease suggests that cyclosporine not only cleared immune cells from the hair follicles but also altered the balance of regulatory lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

In a double-blind, vehicle-controlled study, all of six psoriatic plaques treated with intralesional cyclosporine administered three times weekly for 4 weeks showed complete clearing or incomplete but significant clearing in comparison with vehicle-treated plaques (p less than 0.01). Epidermal thickness decreased from 0.42 +/- 0.07 to 0.27 +/- 0.08 mm at 4 weeks (p less than 0.03). Biopsy specimens obtained on day 5, before any clinical improvement, revealed a significant reduction of epidermal DR+CD1- antigen-presenting cells, epidermal and dermal monocytes, and keratinocyte intercellular adhesion molecule-1 expression. By day 5 the stratum corneum reverted to normal in the plaques receiving cyclosporine. Pain at the injection site was the major side effect. Steady-state blood cyclosporine levels ranged from 20 to 30 ng/ml during the first 12 hours after injection and became undetectable at 48 hours. These data suggest that cyclosporine improves the skin of patients with psoriasis by a local mechanism of action.

Two patients with severe chronic lichen planus were successfully treated with oral cyclosporine (6 mg/kg/day). A response was noted within 4 weeks, and complete clearing was achieved after 8 weeks of treatment. No significant adverse effect was noted. The patients have remained in remission 3 and 10 months after therapy, respectively. Clinical improvement was accompanied by significant reduction in the T cell infiltrate in the skin. Abnormal expression of keratinocyte intercellular adhesion molecule-1 (ICAM-1), which was present before therapy, became undetectable after 1 week of cyclosporine therapy, before any significant clinical and histologic change.

5-Bromodeoxyuridine (BUDR), a halopyrimidine thymidine analogue, is incorporated into the DNA of dividing cells and causes photoradiosensitization. Twenty-five patients with malignant astrocytomas were treated with continuous intracarotid BUDR radiosensitization and radiotherapy for 8 1/2 weeks. Unique dose-limiting mucocutaneous complications were encountered. Ipsilateral facial dermatitis with epilation of eyebrows and eyelashes, ocular irritation, and bilateral nail dystrophy developed in all patients. Less common reactions included oral ulceration in six patients, body exanthem on the trunk in five, and atypical erythema multiforme major in one.

A prospective evaluation of the efficacy and safety of oral ibuprofen and tetracycline hydrochloride was conducted for 8 weeks in patients with moderately severe acne. Sixty-eight patients were randomly assigned in a double-blind fashion to one of four regimens: (1) one 600 mg ibuprofen tablet plus one 250 mg tetracycline capsule four times daily; (2) one 600 mg ibuprofen tablet plus one placebo capsule four times daily; (3) one 250 mg tetracycline capsule plus one placebo tablet four times daily; and (4) one placebo tablet and one placebo capsule four times daily. Sixty patients completed the 8-week study. The mean percent improvement in the groups treated with ibuprofen and tetracycline (56% +/- 5 SE), ibuprofen alone (26% +/- 13 SE), or tetracycline alone (26% +/- 9 SE) was statistically significant. However, only the combination of ibuprofen and tetracycline therapy had an effect statistically better than the placebo response (16+ +/- 11 SE). Adverse effects were transient and were similar in all four groups.

Urticaria is one of the more common skin conditions seen by physicians. Physical agents are an important cause of urticaria, with pressure or shearing forces being the most common. Dermographism is due to a combination of pressure and shearing forces and is present in a large number of healthy individuals. The purpose of this article is to provide a review of dermographism and its clinical variants.

Using a Boyden chamber technic, we measured the directed chemotaxis of polymorphonuclear leukocytes obtained from control subjects or psoriasis patients when the leukocytes were placed in sera obtained from control subjects or psoriasis patients. The samples from patients were obtained before therapy and after 2 and 4 weeks of etretinate administration. Compared with control sera, the sera from seven untreated psoriasis patients significantly enhanced the chemotaxis of polymorphonuclear leukocytes from control subjects toward a chemotaxin (p less than 0.05). After 4 weeks of etretinate therapy, the chemotaxis-stimulating ability of the sera from psoriasis patients was no longer significantly greater than that of the control sera. This decline in the chemotaxis-stimulating activity of our patients' sera preceded significant clearing of their psoriasis. The levels of circulating etretinate in the blood of our patients could not account for the reduction. Etretinate therapy had no apparent direct effect on the chemotactic activity of polymorphonuclear leukocytes from the psoriasis patients but may act in part by reducing the inflammatory effects of psoriatic sera.

We present an unusual case of nodular late syphilis in a 52-year-old black man who had grouped, violaceous, pruritic papulonodules. Overlapping features of both secondary and teritary stages of the disease were present. The clinical presentation and histopathology are discussed.