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Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]1.5, FDR.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH1.3, FDR.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r.6; P .05).This study was limited by a small sample size and predominantly female FFA patients.Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition.

Background Although hidradenitis suppurativa (HS) shares some transcriptomic and cellular infiltrate features with psoriasis, their skin proteome remains unknown. Objective To define and compare inflammatory protein biomarkers of HS and psoriasis skin. Methods We assessed 92 inflammatory biomarkers in HS (n = 13), psoriasis (n = 11), and control skin (n = 11) using Olink high-throughput proteomics. We also correlated HS skin and blood biomarkers using proteomics and RNA sequencing. Results We identified 57 differentially expressed proteins (DEPs) in lesional psoriasis and 64 DEPs in lesional HS skin, compared to healthy controls. Both HS and psoriasis lesional skin demonstrated a significant upregulation of T helper 1 and T helper 17 proteins. Healthy-appearing perilesional HS skin had 63 DEPs compared to healthy controls. Nonlesional HS and psoriasis skin had 24 and 7 DEPs, respectively, compared to healthy controls. Tumor necrosis factor and 8 other proteins were significantly correlated with clinical severity in perilesional HS skin (2 cm from a nodule). Limitations Inclusion of only moderate-to-severe patients and the cohort size. Conclusion HS has a greater inflammatory profile and is more diffusely distributed compared with psoriasis. Proteins correlated with disease severity are potential disease mediators. Perilesional skin is comparably inflamed to lesional skin, suggesting the need to treat beyond skin nodules.

BACKGROUND: Psoriasis is associated with increased cardiovascular risk that is not captured by traditional proinflammatory biomarkers. OBJECTIVE: To investigate the relationship between Psoriasis Area and Severity Index, circulating proinflammatory biomarkers, and vascular health in psoriasis. METHODS: In patients with psoriasis and in age and sex-matched controls, 273 proteins were analyzed with the Proseek Multiplex Cardiovascular disease reagents kit and Inflammatory reagents kit (Olink Bioscience), whereas vascular endothelial inflammation and health were measured via direct transcriptomic analysis of brachial vein endothelial cells. RESULTS: In psoriasis, chemokine ligand 20 (CCL20), interleukin (IL) 6, and IL-17A were the top 3 circulating proinflammatory cytokines. Vascular endothelial inflammation correlated with CCL20 (r = 0.55; P

BACKGROUND: The Hidradenitis Suppurativa Clinical Response (HiSCR) is the gold standard primary outcome measure for Hidradenitis Suppurativa (HS) clinical trials, however it does not assess the presence of draining tunnels, a common finding in advanced disease. It is unclear what the effect of the presence or absence of draining tunnels has upon the efficacy of adalimumab therapy in moderate and advanced disease. OBJECTIVES: We evaluated the efficacy of adalimumab versus placebo using the International Hidradenitis Suppurativa Severity Score System (IHS4). Additionally, we assessed the impact of draining tunnels upon therapeutic response as measured by both the HiSCR and change in nodule counts. METHODS: Re-analysis was conducted using the IHS4 and PIONEER 1 and 2 Individual Patient Data. Both binary outcomes (achieving HISCR and achieving change in IHS4 severity category) and continuous outcomes (nodule counts and IHS4 score) were calculated using R version 3.5.3. Regression modeling was undertaken to assess the impact of draining tunnels and other variables. P

Background Interleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease. Objectives To evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an anti–interleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis. Methods This multicenter, double-blind, placebo-controlled dose escalation phase 1 study randomized 44 patients 4:1 to treatment with subcutaneous M1095 (30, 60, 120, or 240 mg) or placebo biweekly for 6 weeks, in 4 ascending dose cohorts. Results The most frequent treatment-emergent adverse events with M1095 were pruritus (n = 4) and headache (n = 3); 2 patients withdrew owing to adverse events (injection site reaction and elevated liver enzyme levels). The terminal half-life of M1095 was 11 to 12 days. The area under the curve/maximum concentration was dose proportional. Of 10 M1095-treated patients positive for antidrug antibodies, 5 showed treatment-emergent antidrug antibody responses. There was no effect on M1095 exposure. Marked decreases in psoriasis inflammatory markers were observed with M1095. By day 85, 100% and 56% of patients receiving M1095, 240 mg, achieved psoriasis area and severity index 90 and 100, respectively. Improvements in static Physician's Global Assessment and affected body surface area were also seen. Limitations Interpretation of efficacy data is limited by the small sample size. Conclusion Multiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.

Plaque psoriasis is a common, chronic, systemic, immune-mediated inflammatory disease. The Janus kinase-signal transducer and activator of transcription pathway plays a major role in intracellular cytokine signaling in inflammatory processes involved in psoriasis. Although Janus kinase (JAK) 1-3 inhibitors have demonstrated efficacy in patients with moderate-to-severe psoriasis, safety concerns persist and no JAK inhibitor has received regulatory approval to treat psoriasis. Thus, an opportunity exists for novel oral therapies that are safe and efficacious in psoriasis. Tyrosine kinase 2 (TYK2) is a member of the JAK family of kinases and regulates signaling and functional responses downstream of the interleukin 12, interleukin 23, and type I interferon receptors. Deucravacitinib, which is an oral, selective inhibitor that binds to the regulatory domain of TYK2, and brepocitinib (PF-06700841) and PF-06826647, which are topical and oral TYK2 inhibitors, respectively, that bind to the active (adenosine triphosphate-binding) site in the catalytic domain, are in development for psoriasis. Selective, allosteric inhibition of TYK2 signaling may reduce the potential for toxicities associated with pan-JAK inhibitors. This article reviews Janus kinase-signal transducer and activator of transcription and TYK2 signaling and the efficacy and safety of JAK inhibitors in psoriasis to date, focusing specifically on TYK2 inhibitors.

Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate,.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.Our analysis was limited to 350 proteins.This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.

Background Hidradenitis suppurativa is an autoinflammatory disorder of keratinization, with dysregulation of T helper type 17 cytokines. Brodalumab is a monoclonal antibody that targets the interleukin (IL) 17 receptor A receptor. Objectives To assess the safety and tolerability and clinical response at weeks 12 and 24 of brodalumab in moderate to severe HS. Ten participants with no history of inflammatory bowel disease were administered brodalumab 210 mg/1.5 mL subcutaneously at weeks 0, 1, and 2 and every 2 weeks thereafter until week 24. Participants were assessed for adverse events (grade 2/3 adverse events) and clinical response (Hidradenitis Suppurativa Clinical Response [HiSCR], Sartorius, International Hidradenitis Suppurativa Severity Scoring System [IHS4]), including ultrasonography and skin biopsies. Results All 10 participants completed the study. No grade 2/3 adverse events associated with the use of brodalumab were reported. All patients (100%) achieved HiSCR, and 80% achieved IHS4 category change at week 12. HiSCR achievement occurred as early as week 2, likely due to the unique blockade of IL-17A, IL-17C, and IL-17F by brodalumab. Significant improvements were seen in pain, itch, quality of life, and depression. Conclusions Brodalumab was well tolerated in this HS cohort, with no serious adverse events and improvement in clinical outcomes. Alterations in dose frequency may be required in those with advanced disease, which requires further exploration.

Moderate-to-severe atopic dermatitis (AD) is increasingly recognized as a systemic disease, largely due to proteomic blood studies. There are growing efforts to develop AD biomarkers using minimal tissues.To characterize the AD skin proteomic signature and its relationship with the blood proteome and genomic skin profile in the same individuals.We evaluated lesional and nonlesional biopsy samples and blood from 20 individuals with moderate-to-severe AD and 28 healthy individuals using Olink Proteomics (Uppsala, Sweden), using 10 μg/10 μL for skin and blood and RNA sequencing of the skin.The AD skin proteome demonstrated significant upregulation in lesional and even in nonlesional skin compared with controls in inflammatory markers (matrix metalloproteinase 12; T-helper cell [Th]2/interleukin [IL]-1 receptor-like 1[IL1RL1]/IL-33R, IL-13, chemokine [C-C motif] ligand [CCL] 17; Th1/C-X-C motif chemokine 10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (E-selectin, matrix metalloproteinases, platelet growth factor, myeloperoxidase, fatty acid binding protein 4, and vascular endothelial growth factor A; false discovery rate,0.05). Skin proteins demonstrated much higher and significant upregulations (vs controls) compared with blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r = 0.410, P .001), with commonly upregulated inflammatory and cardiovascular risk-associated products, suggesting protein translation in skin.Our analysis was limited to 354 proteins.The AD skin proteome shows an inflammatory and cardiovascular signature even in nonlesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.

Background The effectiveness of psoriasis therapies in real-world settings remains relatively unknown. Objective We sought to compare the effectiveness of less commonly used systemic therapies and commonly used combination therapies for psoriasis. Methods This was a multicenter cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared with 168 patients receiving methotrexate evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. Results In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval [CI] 1.18-3.41), infliximab (relative response rate 1.93; 95% CI 1.26-2.98), adalimumab and methotrexate (relative response rate 3.04; 95% CI 2.12-4.36), etanercept and methotrexate (relative response rate 2.22; 95% CI 1.25-3.94), and infliximab and methotrexate (relative response rate 1.72; 95% CI 1.10-2.70) were more likely to have clear or almost clear skin compared with patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life. Limitations Single time point assessment may result in overestimation of effectiveness. Conclusions The efficacy of therapies in clinical trials may overestimate their effectiveness as used in clinical practice. Although physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes.

Background The impact of palmoplantar psoriasis on health-related quality of life (QoL) is largely unknown. Objective We sought to compare clinical characteristics and patient-reported outcomes between patients with palmoplantar psoriasis and moderate to severe plaque psoriasis. Methods We conducted a cross-sectional study of patients with plaque psoriasis (N = 1153) and palmoplantar psoriasis (N = 66) currently receiving systemic or light treatment for psoriasis. Results Patients with palmoplantar psoriasis were more likely to report Dermatology Life Quality Index scores that correspond to at least a moderate impact on QoL (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.20-3.61); problems with mobility (OR 1.98; 95% CI 1.10-3.58), self-care (OR 3.12; 95% CI 1.24-7.86), and usual activities (OR 2.47; 95% CI 1.44-4.22) on the European Quality of Life-5 Dimensions questionnaire; and heavy topical prescription use of at least twice daily in the preceding week (OR 2.81; 95% CI 1.63-4.85) than those with plaque psoriasis. Limitations Our assessment tools may not account for all dimensions of health-related QoL affected by palmoplantar disease, and these results may not be generalizable to patients with milder forms of psoriasis. Conclusion Patients with palmoplantar psoriasis experience greater health-related QoL impairment and are more likely to report heavy use of topical prescriptions than those with moderate to severe plaque psoriasis.

A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis. Many consider this endpoint to be too stringent as it places potentially useful therapies at risk of failing to demonstrate efficacy. We hypothesized that a 50% reduction in the PASI score (PASI 50) represents a meaningful change in a person's life and thus is a better primary endpoint. To test this hypothesis, we analyzed PASI scores, quality of life (QoL) data, and desired re-treatment scores from a number of clinical trials in addition to studying individual elements that make up the PASI. This analysis shows (1). the PASI score is not linearly reflective of psoriasis severity (eg, a reduction in area of 95% without a change in redness, scaliness, and induration translates to only a 66% reduction in PASI); conversely, a drop in erythema, scale, and induration from an average of 3 to 1 would not lead to a 75% reduction in PASI; (2). treatment with methotrexate, an effective psoriasis therapy, more frequently reaches PASI 50 than PASI 75 as evidenced by a recent open trial in which 63% of patients achieved PASI 50 versus 26% achieving PASI 75; (3). improvement in QoL exists at PASI 50, using the Dermatology Quality of Life Index, as documented in several recently completed large clinical trials; (4). patients achieving PASI 75 frequently defer therapy until they are well below PASI 50; a clinical trial where retreatment was patient initiated showed patients did not re-treat until their PASI dropped to an average of 20% improvement from baseline; and (5). effective, meaningful therapies are consistently differentiated from placebo at PASI 50 as evidenced by histologic and photographic parameters of clinical trials of alefacept, efalizumab, and etanercept. We conclude that PASI 50 equates to a clinically meaningful improvement in psoriasis and represents a discerning primary endpoint.

The Psoriasis Area and Severity Index (PASI) is considered the gold standard assessment tool for psoriasis severity, but PASI is limited by its complexity and insensitivity in people with mild psoriasis.We sought to evaluate the product of a Physician Global Assessment (PGA) and Body Surface Area (BSA) (PGAxBSA) as an alternative to PASI.Psoriasis severity was evaluated at 6-month intervals in participants of the Utah Psoriasis Initiative registry. Correlation coefficients were used to compare PGAxBSA with PASI and the Simplified PASI (SPASI).Between August 2008 and November 2010, 435 assessments were completed in 226 participants. The median PASI score was 3.2 (interquartile range 1.8-5.4) and the median BSA was 3.0% (interquartile range 1.0%-5.0%). PGAxBSA had higher correlations with PASI than SPASI (0.87 vs 0.76, P .001). PGAxBSA also had higher correlations with a Global Patient Assessment of psoriasis severity (0.65) than both PASI (0.59, P .001) and SPASI (0.51, P .001).The use of PGAxBSA for measuring severe psoriasis and response to therapy is unclear, because most participants had mild to moderate psoriasis and data were not collected at predefined intervals in relation to therapy initiation. Interrater reliability was not assessed.PGAxBSA is a simple and sensitive instrument for measuring psoriasis severity.

Despite widespread dissatisfaction and low treatment persistence in moderate to severe psoriasis, patients' reasons behind treatment discontinuation remain poorly understood.We sought to characterize patient-reported reasons for discontinuing commonly used treatments for moderate to severe psoriasis in real-world clinical practice.A total of 1095 patients with moderate to severe plaque psoriasis from 10 dermatology practices who received systemic treatments completed a structured interview. Eleven reasons for treatment discontinuation were assessed for all past treatments.A total of 2231 past treatments were reported. Median treatment duration varied by treatment, ranging from 6.0 to 20.5 months (P.001). The frequency of each cited discontinuation reasons differed by treatment (all P.01). Patients who received etanercept (odds ratio [OR] 5.19; 95% confidence interval [CI] 3.23-8.33) and adalimumab (OR 2.10; 95% CI 1.20-3.67) were more likely to cite a loss of efficacy than those who received methotrexate. Patients who received etanercept (OR 0.34; 95% CI 0.23-0.49), adalimumab (OR 0.48; 95% CI 0.30-0.75), and ultraviolet B phototherapy (OR 0.21; 95% CI 0.14-0.31) were less likely to cite side effects than those who received methotrexate, whereas those who received acitretin (OR 1.56; 95% CI 1.08-2.25) were more likely to do so. Patients who underwent ultraviolet B phototherapy were more likely to cite an inability to afford treatment (OR 7.03; 95% CI 3.14-15.72).The study is limited by its reliance on patient recall.Different patterns of treatment discontinuation reasons are important to consider when developing public policy and evidence-based treatment approaches to improve successful long-term psoriasis control.

Objective We sought to determine what clinical features of psoriasis predict sleep interference. Methods Data were obtained from 420 respondents to the 2005 National Psoriasis Foundation telephone and e-mail surveys. Logistic regression was used to determine whether disease severity, body mass index, age of onset, psoriatic arthritis, income, ethnicity, sex, current therapy, and quality-of-life measures predicted reported sleep interference within the last month. Results Psoriatic arthritis was the most significant predictor of sleep disturbance (odds ratio=3.26). Itch, pain of lesions, and impact on emotional well-being were also significant predictors (odds ratio 1.26, 1.22, and 1.18, respectively). Body surface area covered with psoriasis, body mass index, and therapy were not significant predictors of sleep interference. Limitations All data were self-reported and not physician-assessed. Conclusions History of psoriatic arthritis, presence of itch and pain of psoriatic lesions, and impact of psoriasis on overall emotional well-being predict sleep interference.

Activated memory T cells, expressing CD2, are key components in the pathogenesis of psoriasis. Alefacept binds to CD2, blocks co-stimulatory signaling, and selectively induces apoptosis of pathogenic T cells. Our objective is to present safety and efficacy results which lead to the new drug application (NDA) of alefacept for the treatment of psoriasis. We reviewed the key phase II and III trials in over 1300 patients and found that during treatment and follow-up of patients receiving 12 weekly intramuscular or intravenous injections of alefacept, about 1/3 will achieve a reduction in psoriasis area and severity index (PASI) ofor =75% and nearly 2/3 a reduction in PASI ofor =50%. Patients who achieved aor =75% reduction from baseline PASI during or after a single course maintained aor =50% reduction in PASI for a median duration of7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved aor =75% andor =50% reduction in PASI, respectively and duration of effect was prolonged. Adverse events in the placebo and active treatment arms did not differ. We conclude that alefacept significantly improves psoriasis and produces durable clinical improvement with a very favorable safety profile.

Background: Tazarotene in a gel formulation is widely used in the treatment of psoriasis. Objective: To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis. Methods: A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period. Results: Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation. Conclusion: Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream. (J Am Acad Dermatol 2003;48:760-7.)

Psoriasis vulgaris is the most prevalent T-cell-mediated inflammatory disease in humans. The pathogenesis of psoriasis is linked to activation of several types of leukocytes that control cellular immunity and to a T-cell-dependent inflammatory process in skin that accelerates the growth of epidermal and vascular cells in psoriasis lesions. Critical steps in immunologic activation include Langerhans cell maturation (activation), T-cell activation, differentiation and expansion of type 1 T cells, selective trafficking of activated T cells to skin, and induction of an inflammatory cytokine and chemokine cascade in skin lesions. In turn, each of these steps offers an opportunity for intervention with engineered biologic therapeutics. (J Am Acad Dermatol 2002;46:1-23.) Learning objective: By reading this article, the participant will be able to understand molecules involved in regulating immune responses and the ways in which rationally designed biologic agents may be used to intercept pathologic immune activation.

The above-referenced article has been voluntarily withdrawn by the authors in order to present more updated data in a subsequent manuscript. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Background There is little evidence to guide the establishment of treatment goals for moderate to severe psoriasis in the clinical setting. Objective We sought to compare Dermatology Life Quality Index scores and prescription topical medication use between patients with clear versus almost clear skin. Methods This was a multicenter cross-sectional study of 97 patients with clear skin and 441 patients with almost clear skin receiving current systemic therapy or phototherapy for a primary indication of plaque psoriasis evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. Results In adjusted analyses, patients with clear versus almost clear skin were more likely to report no impact of psoriasis on quality of life (relative risk 1.60; 95% confidence interval 1.37-1.86). Patients with clear versus almost clear skin were also more likely to report no prescription topical medication use in the preceding week (relative risk 2.08; 95% confidence interval 1.73-2.49). Limitations Cross-sectional design prohibits longitudinal assessment of outcomes. Conclusions Clinically important differences in quality of life and prescription topical medication use exist between patients with clear versus almost clear skin. Collectively, our results indicate that achievement of clear skin may be an important clinical distinction among patients with moderate to severe psoriasis.

Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis.This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks.The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur.Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.

Background: A variety of systemically administered drugs are used to treat psoriasis, including methotrexate, cyclosporine, acitretin, and hydroxyurea. Unfortunately, some wpatients are unresponsive to these agents. For others, side effects and cumulative toxicity prevent continued use. Objective: Our purpose is to report the results of thioguanine (6-thioguanine) treatment of 21 patients with refractory psoriasis. Methods: We conducted a retrospective review of the treatment courses of 21 patients with psoriasis who were treated with thioguanine. Daily dosing and pulse dosing were both used, from 20 mg two times a week to 120 mg daily. All patients had been treated with other systemic therapies, and the majority (86%) had been treated with methotrexate. Results: Patient outcome (response to treatment relative to baseline) was classified into 3 groups: those with more than 90% improvement, those with between 50% and 90% improvement, and those with less than 50% improvement. Outcome data were based on the patient's subjective rating of disease severity before the start of thioguanine therapy and during the entire treatment course. Of the 18 patients able to be evaluated, 14 of 18 (78%) had dramatic improvement (>90%); 3 of 18 (17%) had lesser improvement (50%-90%); and only 1 of 18 had less than 50% improvement. The mean duration of treatment was 15.5 months. The primary side effect was myelosuppression, mild in 9 of 18 (white blood cell counts ranging from 1600-3700/μL; platelet counts ranging from 90,000-122,000/μL, and hematocrit values ranging from 24%-31%), and severe in 1 of 18 (white blood cell count of 1300/μL, platelet count of 17,000/μL, and hematocrit of 20%). Conclusion: Thioguanine appears to be an effective treatment for patients with severe recalcitrant psoriasis. Myelosuppression is a significant, but easily monitored side effect that can now be more accurately predicted by determining thiopurine methyltransferase levels before starting thioguanine. Further prospective studies are needed to establish criteria, which will maximize efficacy of this drug in the treatment of psoriasis and minimize toxicity. (J Am Acad Dermatol 2001;44:67-72.)

Narrow-band UVB (NB-UVB) is a new phototherapy option for psoriasis. Action spectrum studies previously done with different UVB wavelengths suggest that suberythemogenic doses of NB-UVB could be highly effective in treating psoriasis vulgaris. Even so, no comparative studies with suberythemogenic doses of NB versus conventional UVB have been performed previously.Our purpose was to compare conventional broad-band UVB (BB-UVB) with NB-UVB at suberythemogenic doses for the treatment of psoriasis vulgaris.Eleven patients were treated using a split-body approach for 6 weeks on a three-times-a-week basis. Outcomes were evaluated by means of Psoriasis Severity Index scores and quantitative histologic measures.We were able to induce clinical clearing in 81.8% of patients after NB-UVB, but in only 9.1% of patients after BB-UVB (P.01). Biopsy specimens obtained at the end of treatment revealed that keratin 16 staining was absent in 75% of patients on the NB side compared with none on the BB side, suggesting a reversal of regenerative epidermal hyperplasia by NB-UVB.NB-UVB is superior to UVB-BB in reversing psoriasis at suberythemogenic doses when given three times per week. This schedule was well tolerated by all patients.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy. (J Am Acad Dermatol 1998;39:464-75.)

Background: Flurandrenolide tape has recently been listed as a group I topical cortico-steroid. There are no studies that compare this product to group I ointments in the treatment of steroid-responsive dermatoses. Objective: Our purpose was to determine the relative efficacy of flurandrenolide (4 mg/cm 2 ) tape versus 0.05% diflorasone diacetate ointment in plaque psoriasis. Methods: Thirty patients participated in an investigator-blinded, randomized, bilateral paired-comparison study of flurandrenolide tape applied to lesions of one side of the body once daily for up to 16 hours versus diflorasone diacetate ointment applied contralaterally twice daily. Lesions were assessed at baseline, then reevaluated at 2 and 4 weeks. Results: Flurandrenolide tape–treated plaques showed consistently greater clearing in terms of erythema, scaling, induration, and treatment success for all plaques, as well as the subset of knee and elbow plaques, when compared with the lesions receiving diflorasone diacetate ointment. Conclusion: The efficacy of flurandrenolide tape in the treatment of psoriatic plaques surpasses that of diflorasone diacetate ointment. (J Am Acad Dermatol 1998;38:186-90.)

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.Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods.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.Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients withor = 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.Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Background Multiple systemic treatments are available for moderate to severe psoriasis, but dermatologists' perceptions of these treatments are unknown. Physician perceptions can influence prescribing patterns and patient outcomes, and may help to explain variations in clinical practice. Objective We sought to describe the variation in dermatologist's beliefs about the safety and effectiveness of psoriasis treatments and evaluate how these relate to dermatologist characteristics and treatment preferences. Methods We conducted a cross-sectional mail survey of a random sample of 500 National Psoriasis Foundation (NPF) members and 500 American Academy of Dermatology (AAD) members who treat psoriasis. Results Of 989 clinicians who could be contacted, 246 NPF members and 141 AAD members returned the survey (39% response rate). Respondents perceived infliximab, ustekinumab, cyclosporine, and adalimumab to have the highest likelihood of skin clearance in 3 months (67%-75%). Etanercept, adalimumab, ultraviolet B, and ustekinumab had the lowest perceived likelihood of side effects requiring treatment discontinuation (9%-11%). Up to 49% of respondents "didn't know" the effectiveness or likelihood of side effects; calculated coefficients of variation were higher for perceived likelihood of side effects than perceived effectiveness. There were few significant associations between safety and effectiveness perceptions and respondent characteristics, and treatment preferences were not consistently predictive of perceptions. Limitations Only dermatologists with interest in treating psoriasis were surveyed and general perceptions were elicited via survey format. Perceptions may differ between survey respondents and nonrespondents. Conclusions Psoriasis providers demonstrate wide variation in their perception of the effectiveness and especially safety of systemic treatments.

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.

We describe 5 patients with severe pompholyx who did not respond to conventional therapy or who had debilitating side effects from corticosteroids. Low-dose methotrexate was added to their treatment regimens and led to significant improvement or clearing with a favorable side-effect profile. In all 5 patients the need for oral corticosteroid therapy was substantially decreased or eliminated, thus decreasing potential corticosteroid-induced morbidity. In this uncontrolled series of patients with recalcitrant palmoplantar pompholyx, methotrexate was an effective treatment and acted as a steroid-sparing agent.

Clinical trials for systemic psoriasis therapy typically enroll healthy patients and exclude patients with cardiovascular disease, latent tuberculosis, liver disease, histories of malignancies, viral infections, children, and pregnant or breast-feeding women. Physicians often require guidance for optimum management of severe psoriasis in patients that have a combination of underlying disease states. To provide treatment recommendations for complex psoriasis scenarios, a consensus panel comprising 15 experts in psoriatic disease convened to review and discuss available evidence-based data and to arrive at a consensus for treatment options of difficult cases. An application of the Delphi Method was used to select case scenarios, provide medical treatment options, present the case study with existing medical evidence, and anonymously vote on treatment options. The top 10 treatment options were ranked and statistically analyzed to compare the differences between treatments. The final rankings and analysis provide guidance for practical, safe, and efficacious treatment options in a number of complex psoriasis scenarios.

There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population.

Background Biologics are widely used in the treatment of psoriasis and psoriatic arthritis. Objective Our aim was to arrive at a consensus on the kind of monitoring and the vaccinations that should be performed before and during biologic therapy. Methods Medical literature and data presented at meetings were reviewed and a consensus conference was held by members of the Medical Board of the National Psoriasis Foundation. Results Consensus was established on monitoring and vaccination practices that included discussion and recognition of variations in those practices. History, physical examination, chemistry screen with liver function tests, complete blood cell count, and platelet count and tuberculosis testing are widely obtained at baseline and with variable frequencies thereafter. Patients treated with efalizumab have platelet counts checked more often; liver function tests are repeated more frequently in patients treated with infliximab; patients taking tumor necrosis factor blockers undergo tuberculosis testing more often; and patients treated with alefacept have CD4 counts checked approximately every 2 weeks. Avoidance of live vaccines during biologic therapy and administration of essential vaccines before biologic therapy were discussed, although vaccination is performed only to a variable degree. There was no consistency in the measurement of antinuclear antibodies among the experts. Limitations There are few evidence-based studies on monitoring practices for patients with psoriasis taking biologic therapies. Conclusions In patients taking biologic therapies for psoriasis, monitoring of blood chemistries, blood counts, CD4 counts, antinuclear antibodies, tuberculin skin tests, history, and physical examination may be warranted depending on the particular therapy and the particular patient. Vaccination practices are also addressed.

Background Etanercept is a tumor necrosis factor-α binding fusion protein that demonstrates efficacy in the treatment of psoriasis, which is accompanied by decreased plaque infiltration of T cells and myeloid dendritic cells. We hypothesized that etanercept decreases inflammatory cell infiltration by inducing apoptosis. Objective We sought to investigate the effect of etanercept on circulating and plaque leukocyte apoptosis in psoriasis. Methods Blood and plaque specimens were obtained from 10 patients with psoriasis treated with etanercept (25 mg subcutaneously twice weekly) for 24 weeks. Apoptosis was determined in tissue samples using immunohistochemistry and flow cytometry. Results Etanercept selectively induced apoptosis in dermal dendritic cells in plaques of responding patients at 1 month, before most of the clinical and histologic response was achieved. No apoptosis was detected in plaque or circulating T cells or in circulating monocytes. Limitations Addition of multiple time points earlier than 1 month would be valuable to establish the time point of maximum induction in cell apoptosis. Conclusion Etanercept selectively induces apoptosis of pathogenic dermal dendritic cells in responding patients early in the course of treatment.

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 Etanercept provides rapid, significant improvement in psoriatic symptoms and disease. Objective The effectiveness of continued etanercept treatment beyond 24 weeks in patients who initially did not achieve at least a 50% improvement from baseline in the Psoriasis Area and Severity Index (PASI 50) was assessed. Methods Patients with moderate to severe plaque psoriasis received 50 mg open-label, subcutaneous etanercept per week after completing blinded therapy with placebo or 1 of 3 doses of etanercept. The PASI was measured. Results Irrespective of prior dosing regimens, 43% of 157 patients who did not attain PASI 50 responses at week 24 achieved PASI 50 responses at week 36; 55% achieved PASI 50 responses at week 60. Etanercept was safe and well tolerated. Limitations Interpretation of these results is limited by the open-label design of the analysis. Conclusion More than half of patients who initially had an inadequate response to treatment achieved satisfactory responses with continued etanercept therapy. The safety profile of etanercept in these patients and in patients who had more immediate responses was similar.

Background Previous studies indicate that tazarotene is efficacious in reducing signs of photodamage. Objective We sought to confirm the efficacy and tolerability of tazarotene 0.1% cream in the treatment of facial photodamage. Methods A total of 568 patients with at least moderate fine wrinkling or mottled hyperpigmentation applied tazarotene 0.1% cream or vehicle cream to their face once daily for 24 weeks. Results Tazarotene cream was significantly more effective than vehicle in reducing fine wrinkles, mottled hyperpigmentation, lentigines, irregular depigmentation, apparent pore size, elastosis, tactile roughness, and an overall integrated assessment of photodamage. Significance was achieved as early as week 2 for some parameters and had not plateaued by week 24. The majority of patients reported improvements in their photodamage as early as week 4. Adverse events were predominantly mild or moderate signs or symptoms of skin irritation. Conclusion Once-daily tazarotene 0.1% cream is effective in ameliorating multiple signs of facial photodamage.

In this randomized, double-blind, phase III trial, patients with psoriasis received etanercept for 24 weeks or placebo for 12 weeks followed by etanercept for 12 weeks. At week 12, improvement in Dermatology Life Quality Index was 47% to 61% with etanercept compared with 11% with placebo (P.0001). Etanercept rapidly and substantially improved patients' health-related quality of life.