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11. Acne, Psoriasis, and Disorders of Keratinization

Psoriasis patients find online support communities helpful. Idriss SZ, Kvedar JC, Watson AJ. The role of online support communities. Benefits of expanded social networks to patients with psoriasis. Arch Dermatol 2009;145(1):46–51. doi:10.1001/archdermatol.2008.529 Objective: To determine the demographics, usage patterns, attitudes, and experiences of online psoriasis support site users. Background and support: An online survey was executed in 260 subjects recruited from five online psoriasis support groups. An exploratory analysis was performed to determine demographic and disease characteristics of online support site users. Perceived benefits were also documented. Results: Mean age of respondents was 40.1 (11.5) years (range, 18–75 years), most (75.7%) were white, female (60.4%), and college educated (84.3%). Key factors associated with use of online support sites included availability of resources (95.3%), convenience (94.0%), access to good advice (91.0%), and lack of embarrassment when dealing with personal issues (90.8%). The most common activities were posting messages (65.0%) and searching for information (63.1%). Nearly half of all respondents perceived improvement in quality of life (49.5%) and psoriasis severity (41.0%) since joining the site. Intensity of participation in online support activities was associated with improved quality of life (p=.002), but not with improvement in psoriasis severity. Conclusion: The present data demonstrate that psoriasis virtual communities offer users both a valuable educational resource and a source of psychological and social support. Such benefits could be further enhanced by physician engagement within these communities. Reprint requests to Ms. Idriss, Center for Connected Health, Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA. Outcome measures in acne need assessment and agreement on which are optimal. Barratt H, Hamilton F, Car J, et al. Outcome measures in acne vulgaris. Systematic review. Br J Dermatol 2009;160(1):132–136. doi:10.1111/j.1365-2133.2008.08819.x

Objective: To review the literature about investigator-assessed outcome measures used in clinical trials for acne vulgaris; and evaluate the measurement properties of these tools. Background and methods: Clinical trials require valid and reliable outcome measures to facilitate the interpretation and communication of results, and secondary use of data for systematic reviews. There are numerous tools available to assess the severity of acne vulgaris in clinical trials, and extensive debate about the merits of these. A systematic literature review was conducted of articles outlining and evaluating investigator-assessed outcome measures for acne. Results: Thirty-one papers met criteria for inclusion in the literature review, including nine papers proposing a novel means of assessing acne, and five evaluating existing outcome measures. Variable attempts had been made to evaluate these tools. Conclusion: The array of evaluation tools used in acne trials prohibits good secondary analysis of trial data, and complicates the interpretation of study results, potentially compromising clinical care. Existing outcome measures need to be assessed further and agreement reached about which should be used more widely. Other innovative methods of assessing acne should also be explored. Reprint requests to Dr. Barratt, Department of Primary Care and Social Medicine, Imperial College London, London W6 8RP, UK. Biological therapies have been helpful in the treatment of severe psoriasis in the UK. Warren RB, Brown BC, Lavery D, et al. Biologic therapies for psoriasis. Practical experience in a U.K. tertiary referral centre. Br J Dermatol 2009;160(1):162–169. doi:10.1111/j.1365-2133.2008.08865.x Objective: To evaluate efalizumab, etanercept, and infliximab in a U.K. cohort of patients with psoriasis and examine the approach to processes involved in the initiation of biological therapies in the era of National Institute for Health and Clinical Excellence guidance. Background and methods: Large-scale clinical trials provide clear evidence of the efficacy and short-term toxicity of biological therapies for psoriasis. There are few reports, however, of the practical use of these therapies outside of the trial setting and none from a U.K. cohort of patients with psoriasis. Study patients had a mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21·8 and 21·7, respectively, outside of the clinical trial setting.

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Results At 3 months of treatment the efficacy of efalizumab (n= 28), etanercept (n=70), and infliximab (n=20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35%, and 85%, respectively. All three biologicals used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biological therapy in 30% of cases. Streamlined approaches to screening and funding significantly (p≤.05) hastened the initiation of biological therapies. Conclusion: In a cohort of U.K. patients with severe psoriasis, biological therapies have proved to be a significant step forward in expanding the therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs. Reprint requests to Dr. Warren, Dermatological Sciences, Salford Royal Hospital, University of Manchester, Manchester M6 8HD, UK. Calcipotriol + betamethasone dipropionate is better than either agent alone in scalp psoriasis. van de Kerkhof PCM, Hoffmann V,. Anstey A, et al. A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis. A randomized, double-blind, controlled trial. Br J Dermatol 2009;160(1):170–176. doi:10.1111/j.1365-2133.2008.08927.x Objective: To compare a new, once-daily, two-compound scalp formulation (Xamiol®; LEO Pharma A/S) containing calcipotriol 50μg/g plus betamethasone 0·5 mg/g (as dipropionate), with the active ingredients as single compounds in the same vehicle. Background and methods: There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. In this 8-week, multicenter, double-blind, parallel-group study, randomized adult patients with scalp psoriasis involving >10% of the scalp to the two-compound scalp formulation (n=568), betamethasone dipropionate 0.5 mg/g (n=563), or calcipotriol 50μg/g (n=286). The primary efficacy measure was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ according to investigators’ assessments at week 8. Results: The proportion of patients with ‘absence of disease’ or ‘very mild disease’ at week 8 was significantly higher in the twocompound group (68.4%) than the betamethasone dipropionate (61.0%, p=.0079) or calcipotriol (43.4%, p<.0001) groups. The proportion of patients rating their scalp psoriasis as ‘clear’ or ‘almost clear’ was significantly higher for the two-compound scalp formulation (69.6%) than for betamethasone dipropionate (59.9%, p=.0006) or calcipotriol (44.7%, p<.0001). The incidence of lesional/perilesional adverse events was lower in the twocompound and betamethasone dipropionate groups than the calcipotriol group. Conclusion: The two-compound scalp formulation was well tolerated and more effective for scalp psoriasis than either of its individual components in the same vehicle.

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Reprint requests to Dr. De Kerkhof, Department of Dermatology, University Hospital Nijmegen, Centrum St Radboud, Postbus 9101, 6525 GL Nijmegen, The Netherlands. Ultraviolet B improves etanercept response in psoriatic lesions. Wolf P, Hofer A, Legat FJ, et al. Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept. Br J Dermatol 2009;160(1):186–189. doi:10.1111/j.1365-2133.2008.08926.x Objective: To determine whether treatment with 311-nm ultraviolet (UV) B can improve therapeutic response in patients treated with etanercept. Background and methods. Some patients with plaque-type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful. Four women and one man (mean age, 57 years; range. 48–66 years) with moderate to severe plaque-type psoriasis who had received standard treatment with etanercept 50 mg twice weekly for 6 weeks without Psoriasis Area and Severity Index (PASI) reduction of 75% or greater (of initial mean PASI, 16.0; range, 15.4–20.4) were enrolled. Starting at 6 weeks, 311-nm UVB treatment was given to a randomly selected body half (left or right, excluding the head) for another 6 weeks, while all patients continued receiving etanercept. Patients were monitored by halfbody PASI at weekly intervals. Results: During the 6-week irradiation regimen, 311-nm UVB significantly bolstered the therapeutic response in the patients on etanercept treatment. After 6 weeks of 311-nm UVB, the patients had a mean PASI on their UV-irradiated body halves of 1.6 (range, 0.6–3.3) vs 4.7 (range, 1.4–8.6) on nonirradiated body halves (p=.0192), compared with 10.7 (range, 6–16.4) and 10.5 (range, 5.2–16.4) at start of 311-nm UVB treatment. Overall mean PASI reduction from baseline (that is, at etanercept start) was 89% vs 68%, respectively (p=.0009 and .0088). Conclusion: Treatment with 311-nm UVB significantly accelerates and improves the clearance of psoriatic lesions in patients responding slowly to etanercept monotherapy. Reprint requests to Dr. Wolf, Research Unit for Photodermatology and †Department of Dermatology, Medical University of Graz, A-8036 Graz, Austria. Interleukin-20 is a possible new target in psoriasis treatment. Stenderup K, Rosada C, Worsaae A, et al. Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model. Br J Dermatol 2009;160;2:284–296. doi:10.1111/j.1365-2133.2008.08890.x Objective: To investigate the effects both of blocking interleukin 20 (IL-20) signaling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin. Background and methods: IL-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interest-

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ingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the etiology of psoriasis is unknown. The human skin xenograft transplantation model was employed, in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immunodeficient mice. Transplanted mice were treated with antiIL-20 antibodies or recombinant human IL-20. Results: Blocking IL-20 signaling with anti-IL-20 antibodies induced psoriasis resolution and inhibited psoriasis induction. Continuous IL-20 infusion, together with injection of additional nonactivated leukocytes, promoted induction of psoriasis in nonlesional skin from patients with psoriasis. Conclusion: IL-20 appears to play a critical role in the induction and maintenance of psoriasis. IL-20 is suggested as a new possible specific target in psoriasis treatment. Reprint requests to Dr. Stenderup, Department of Dermatology, Aarhus University Hospital, DK-8000 Aarhus, Denmark. Protein levels of three interleukin-17 are augmented in psoriatic skin lesions. Johansen C, Usher PA, Kjellerup RB, et al. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol 2009;160(2):319–324. doi:10.1111/j.1365-2133.2008.08902.x Objective: To characterize the expression of interleukin-17 (IL-17) isoforms and receptors in lesional and nonlesional psoriatic skin. Background and methods: Th17 cells are a lineage of proinflammatory T helper cells producing IL-17. The importance of Th17 cells in inflammation and autoimmunity has now been recognized. The IL-17 cytokine family consists of six isoforms (IL-17A–IL-17F) whereas five members of the IL-17 receptor (IL17R) family have been identified (IL-17RA–IL-17RE). Keratome and punch biopsies taken from patients with psoriasis were examined by enzyme-linked immunosorbent assay and quantitative reverse transcription–polymerase chain reaction in order to measure the IL-17 isoforms and receptors. Results: Significantly increased mRNA expression of IL-17A, IL-17C, and IL-17F was demonstrated in psoriatic skin. In contrast, mRNA expression of IL-17B and IL-17D was significantly decreased in lesional compared with nonlesional skin, while IL-17E mRNA was undetectable. Increased mRNA expression of IL-17A, IL-17C, and IL-17F was paralleled by increased protein accumulation of these cytokines in psoriatic skin. Analysis of IL-17R mRNA expression revealed significantly impaired mRNA expression of IL-17RB, IL-17RC, IL-17RD, and IL-17RE in lesional psoriatic skin, whereas mRNA expression of IL-17RA was similar in lesional and nonlesional psoriatic skin. Conclusion: The present study has characterized the mRNA profile of the IL-17 isoforms and receptors in psoriatic skin lesions. Furthermore, augmented protein levels of IL-17A, IL17C, and IL-17F was demonstrated for the first time in psoriatic skin lesions, indicating a possible role for IL-17C in addition to IL-17A and IL-17F in the pathogenesis of psoriasis.

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Reprint requests to Dr. Johansen, Department of Dermatology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Neither psoriasin nor psoriasin-specific autoantibodies are biomarkers of psoriasis. Anderson KS, Wong J, Polyak K, et al. Detection of psoriasin/ S100A7 in the sera of patients with psoriasis. Br J Dermatol 2009;160(2):325–332. doi:10.1111/j.1365-2133.2008.08904.x Objective: To determine whether patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. Background and methods: Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titers using recombinant purified psoriasin and overlapping peptides. Results: Strong and specific expression of psoriasin in psoriatic epidermis was confirmed by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean, 213 ng/mL) than in controls (mean, 331 ng/mL, not significant) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean, 0.347 vs 0.255 units, not significant). Epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. Conclusion: Though psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasinspecific autoantibodies appear to be promising serum biomarkers for clinical psoriasis. Reprint requests to Dr. Anderson, Cancer Vaccine Center and †Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. Corticotropin-releasing hormone expression is abundant in acne-involved skin. Ganceviciene R, Graziane V, Rimmel S, et al. Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. Br J Dermatol 2009;160(2):345–352.† and C.C. Zouboulis†§. doi:10.1111/j.1365-2133.2008.08959.x Objective: To detect expression changes of corticotropin-releasing hormone (CRH)/CRH binding protein (CRHBP)/CRH receptors (CRHRs) in acne-involved skin, especially in the sebaceous glands.

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Background and methods: The sebaceous gland exhibits an independent peripheral endocrine function and expresses receptors for neuropeptides. Previous reports have confirmed the presence of a complete corticotropin-releasing hormone (CRH) system in human sebocytes in vitro. The capability of hypothalamic CRH to induce lipid synthesis, induce steroidogenesis, and interact with testosterone and growth hormone implicates a possibility of its involvement in the clinical development of acne. Expression of CRH/CRHBP/CRHRs was analyzed by immunohistochemistry in biopsies from facial skin of 33 patients with acne, noninvolved thigh skin of the same patients and normal skin of eight agematched healthy volunteers. Results: Very strong positive reaction for CRH was observed in acne-involved skin in all types of sebaceous gland cells, irrespective of their differentiation stage, whereas in noninvolved and normal skin sebaceous glands exhibited a weaker CRH staining depending upon the differentiation stage of sebocytes. The strongest reaction for CRHBP in acne-involved sebaceous glands was in differentiating sebocytes. CRHR-1 and CRHR-2 exhibited the strongest expression in sweat glands and sebaceous glands, respectively. Conclusion: Expression of the complete CRH system is abundant in acne-involved skin, especially in the sebaceous glands, possibly activating pathways which affect immune and inflammatory processes leading to the development and stress-induced exacerbation of acne. Reprint requests to Dr. Zouboulis, Department of Dermatology and Immunology, Dessau Medical Center, Auenweg 38, 06847 Dessau, Germany. Etanercept 50 mg twice weekly is cost effective in severe psoriasis in the UK. Lloyd A, Reeves P, Conway P, et al. Economic evaluation of etanercept in the management of chronic plaque psoriasis. Br J Dermatol 2009;160(2):380–386. doi:10.1111/j.1365-2133.2008.08863.x Objective: To assess the cost-effectiveness of etanercept 50 mg twice weekly (biw) for chronic plaque psoriasis, and explore characteristics of patients who benefited most from 50 mg dosing. Background and methods: The National Institute for Health and Clinical Excellence has recommended that etanercept 25 mg biw be used in adults with severe plaque psoriasis. However, its economic model did not consider the alternative licensed regimen of etanercept 50 mg biw. An economic model was constructed to estimate the incremental cost per quality-adjusted life year (QALY) gained. The model considered patients with chronic plaque psoriasis who had both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) of 10 or higher who were unable to take standard systemic therapies. Quality of life gain was estimated from the DLQI responses of patients enrolled in three clinical studies. The model considered expenditure on drugs, monitoring visits, adverse events and inpatient stays. Costs were estimated from the perspective of the UK National Health Service over a time period of 10 years. Results: The incremental cost per QALY for etanercept 50 mg biw compared with no systemic therapy was found to be £6217

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(£5396–7486). The cost-effectiveness of 50 mg dosing was more attractive in patients with baseline PASI ≥20 (£5163) or baseline DLQI ≥20 (£4599). Conclusion: The present model found the licensed dose regimen of etanercept 50 mg biw to be cost effective in the UK. This regimen was particularly appropriate for patients with severe disease or poor quality of life at baseline. Reprint requests to Dr. Garth Baxter, Wyeth Pharmaceuticals Ltd, Taplow, Berkshire SL6 0PH, UK. Four genetic polymorphisms relevant to methotrexate metabolism do not predict response to the drug. Warren RB, Smith RL, Campalani E, et al. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. Br J Dermatol 2009;160(2):438–441. doi:0.1111/j.1365-2133.2008.08898.x Objective: To determine whether single nucleotide polymorphisms (SNPs) across four genes are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gammaglutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis. Background and methods: The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug. DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r2 >.8) for the four genes with a minor allele frequency of >5% were selected from HAPMAP phase 2 data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom®). Results: There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated. Conclusion: Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis. Reprint requests to Dr. Warren, Dermatological Sciences, Salford Royal Hospital, University of Manchester, Manchester M6 8HD, UK. Pulsed dye laser is effective in a subgroup, and PDL + UVB confers no added benefit. De Leeuw J, Van Lingen RG, Both H, et al. A comparative study on the efficacy of treatment with 585 nm pulsed dye laser and ultraviolet B-TL01 in plaque type psoriasis. Dermatol Surg 2009;35(1):80–91. doi:10.1111/j.1524-4725.2008.34386.x

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Objective: To compare pulsed dye laser (PDL) with ultraviolet-B light therapy (UVB) and look for synergism of both therapies in patients with plaque type psoriasis. Background and methods: Narrow-band UVB and PDL affect psoriasis but via different pathways. In each eligible individual, four similar target plaques were selected, and halves of these plaques were treated using PDL, UVB, or a combination of PDL and UVB or were not treated. Results were recorded single-blind using the Physician’s Global Assessment score at study enrolment and Week 13. Nonparametric, paired statistical tests were used to test for differences within and between therapies. Results were also analyzed after dichotomization of the changes in the Physician’s Global Assessment score into responsive and nonresponsive to treatment. Results: Significant improvement of psoriasis lesions was noted at Week 13 (p<.001) with each therapy. No significant differences were noted between the therapies. Synergism of PDL and UVB was not observed. Conclusion: PDL is safe for plaque type psoriasis, but its efficacy is limited to a subgroup of patients. Combining PDL with UVB confers no additional benefit.

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Sequential applicatieons of topical tacrolimus+steroids may limit adverse steroid effects. Kubota Y, Yoneda K, Nakai K, et al. Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis. An open-label pilot study. J Am Acad Dermatol 2009;60(2):212–217. doi:10.1016/j.jaad.2008.09.034

Objective: To summarize studies regarding therapy of intertriginous psoriasis. Background and methods: Involvement of areas of the skin fold is common in patients with psoriasis though the exact incidence is unknown. A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Reports in the literature were reviewed regarding psoriasis affecting the skin-fold areas and its therapy. Results: The recommended short-term (2–4 weeks) therapy for inverse psoriasis is low- to mid-potency topical steroids. For longterm therapy, topical calcipotriene (calcipotriol) or one of the immunomodulating agents, pimecrolimus or tacrolimus, is favored. Conclusion: Low- to mid-potency topical steroids are recommended as first-line, short-term treatment. It is recommended that use be of limited duration (less than 2-4 weeks) or that the lowest effective strength be used intermittently for long-term care to minimize risk. Calcipotriene (calcipotriol), pimecrolimus, and tacrolimus, while not as highly efficacious as topical steroids, are associated with fewer long-term risks and are therefore recommended for long-term therapy.

Objective: To determine whether a regimen of sequential application of topical corticosteroids and topical tacrolimus is effective for pediatric atopic dermatitis. A second goal was to assess the impact of this treatment regimen on quality of life (QOL) and the response shift on QOL changes. Background and methods: The efficacy of combination therapy with topical corticosteroids and tacrolimus in the treatment of atopic dermatitis remains to be established. The study regimen consisted of three phases. In the induction phase, patients were treated for a 2-week period with application of 0.03% tacrolimus ointment in the morning and a strong- or weak-potency corticosteroid ointment in the evening. In the transitional phase, they were treated for an additional 2 weeks with 0.03% tacrolimus ointment twice daily on weekdays and concurrent tacrolimus and a topical corticosteroid ointment on weekend days. In the maintenance phase, corticosteroid ointment was discontinued and 0.03% tacrolimus ointment was applied twice daily for an additional 2 weeks. Daily application of tacrolimus ointment was then discontinued and replaced by an emollient with 0.03% tacrolimus ointment only when necessary for an additional 6 weeks. Eczema Area and Severity Index score, Investigators’ Global Assessment, severity of pruritus and sleep disturbance scores, and QOL evaluation were measured. After 12 weeks, patients completed a retrospective version of the pretreatment QOL evaluation for analysis of response shift bias. Results: Eczema Area and Severity Index scores decreased by the sixth week, and continued improvement was observed during an additional 6-week period. Both the pruritus and sleep disturbance scores decreased throughout the study. Of patients, 90% showed marked clinical improvement at week 6 and 96% at week 12. On the Children’s Dermatology Life Quality Index and the Infant’s Dermatology QOL Index survey, mean QOL scores improved after completion of therapy at week 12. The mean difference between pretest and the retrospective pretest scores indicated the presence of a response shift bias. Conclusion: A fixed sequential regimen of application of tacrolimus ointment with tapering of topical corticosteroids may limit long-term use and adverse effects of topical corticosteroids, while maintaining clinical control of pediatric atopic dermatitis and improving QOL. The finding of a response shift bias suggests that parents/guardians underestimate the seriousness of skin disease and its impact on QOL.

Reprint requests to Dr. Abby S. Van Voorhees, Hospital of the University of Pennsylvania, 2 Rhoads 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.

Reprint requests to Dr. Kubota, Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Mikicho, Kita-gun, Kagawa, Japan 761-0793.

Reprint requests to Dr. de Leeuw, Department of Dermatology & Venereology, Erasmus Medical College, University Medical Center, PO. Box 2040, 3000 CA Rotterdam, The Netherlands. Low- to mild-potency topical steroids are recommended first-line for intertriginous psoriasis. Kalb RE, Bagel J, Korman NJ, et al. Treatment of intertriginous psoriasis. From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2009;60(1):120–124. doi:10.1016/j.jaad.2008.06.041

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A psoriatic skin model is effective for studying abnormal cell growth and interactions. Jean J, Lapointe M, Soucy J, et al. Development of an in vitro psoriatic skin model by tissue engineering. J Dermatol Sci 2009;53(1):19–25. doi:10.1016/j.jdermsci.2008.07.009 Objective: To develop and characterize a novel in vitro psoriatic human skin model produced by tissue engineering. Background and methods: Psoriasis is a chronic skin disease characterized by a thickening and disorganization of the skin’s protective barrier. The self-assembly method, a tissue engineering approach based on the capacity of mesenchymal cells, such as fibroblasts, to create their own extracellular matrix in vitro, was used to create substitutes. Manipulatable sheets of fibroblasts were superimposed creating a new dermis on which keratinocytes are seeded, leading to a complete bilayered skin substitute. Characterization of psoriatic substitutes was performed by macroscopic, histological, and immunohistochemical analyses and contrasted to those constructed from healthy cells. Results: Macroscopically, psoriatic substitutes were more white and thicker than healthy substitutes. Histological analysis of psoriatic substitutes stained with Masson’s trichrome revealed characteristic thickening of the epidermal layer seen in psoriatic skin in vivo. Immunohistochemical analysis of psoriatic substitutes showed, among other things, overexpression of involucrin and underexpression of filaggrin and loricrin. Conclusion: Macroscopic, histological, and immunohistochemical characteristics of psoriasis are partially retained in substitutes, providing a good model to investigate mechanisms of abnormal keratinocyte growth and cell–cell interactions. Reprint requests to Dr. Jean, Laboratoire d’Organogénèse Expérimentale (LOEX), Hôpital du Saint-Sacrement du CHA, 1050 Chemin Sainte-Foy, Québec, Canada G1S 4 L8. Anti-cyclic citrullinated peptide positive patients have a subtype of psoriatic arthritis. Shibata S, Tada Y, Komine M, et al. Anti-cyclic citrullinated peptide antibodies and IL-23p19 in psoriatic arthritis. J Dermatol Sci 2009;53(1): 34–39. doi:10.1016/j.jdermsci.2008.06.008 Objective: To determine the prevalence of cyclic citrullinated peptide antibodies (anti-CCP) in patients with psoriatic arthritis (PsA) and characterize these anti-CCP-positive patients of PsA. Background and methods: Anti-CCP are reported to be found in 5–13% of patients with PsA. However, whether anti-CCP-positive PsA patients and rheumatoid arthritis (RA) patients have a similar pathophysiological background remains uncertain. Serum levels of the anti-CCP antibodies were measured in patients with PsA (n= 16), psoriasis (n=15), RA (n=9), and healthy controls (n=11). Serum levels of rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), cartilage oligomeric matrix protein (COMP), interleukin (IL)-23p19 and IL-12p40 were also measured in all samples. Results: Two of the 16 PsA patients (13%) were positive for antiCCP antibodies with high titers of RF. However, serum IL-23p19

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levels were two orders of magnitude higher in anti-CCP-positive PsA patients than those in RA patients and anti-CCP-negative PsA patients. No significant elevation of serum levels of MMP-3, COMP and IL-12p40 was found in these patients. Conclusion: Thirteen percent of PsA patients were positive for antiCCP. These patients do not fulfill American College of Rheumatology (ACR) classification criteria for RA so far. Furthermore, they showed typical clinical features of PsA rather than RA. Though antiCCP-positive PsA patients may be at risk of developing RA, these patients should be classified, for the moment, into a independent subtype of PsA, a different entity from RA. Reprint requests to Dr. Shibata, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-8655, Japan.

ESSENCES Psoriasis: an opportunity to identify cardiovascular risk. Federman DG, Shelling M, Prodanovich S, Gunderson CG, Kirsner RS. Br J Dermatol 2009;160:1–7. doi:10.1111/j.1365-2133.2008.08874.x Psoriasis is highly prevalent and is associated with skin-associated complaints as well as arthritis, depression and a lower quality of life. This article reviews the association between psoriasis, atherosclerosis and inflammation, as well as some treatable cardiovascular risk factors that may prove beneficial in reducing a patient's cardiovascular risk. It has been demonstrated that not only do patients with psoriasis have an increased prevalence of cardiovascular risk factors, but an increased risk of myocardial infarction, and for those with severe disease, increased mortality. Dermatologists and other health professionals need to be cognizant of this association and ensure that cardiovascular risk factors are evaluated and treated appropriately in those patients with psoriasis. Tuberculosis and tumour necrosis factor-α inhibitor therapy: a report of three cases in patients with psoriasis. Comprehensive screening and therapeutic guidelines for clinicians. Perlmutter A, Mittal A, Menter A. Br J Dermatol 2009;160:8–15. doi:10.1111/j.1365-2133.2008.08891.x Tumor necrosis factor (TNF)-α inhibitors, long used in rheumatology and gastroenterology, have made a significant impact on the therapy of psoriasis and psoriatic arthritis. This article reports three cases of tuberculosis induced by TNF-α inhibitors despite a rigorous screening policy TNF-α is an important cytokine in normal physiological processes such as the immune response to granulomatous infection. Inhibition of this process by TNF-α inhibitors has been reported to increase the susceptibility of patients to granulomatous infections such as Mycobacterium tuberculosis. Despite the numerous reported cases in the literature and appropriate warnings

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on the labels for the three currently approved TNF-α inhibitors, current guidelines do not address case-specific issues across the full spectrum of tuberculosis. The probability of developing active tuberculosis has been reported to be as much as seven times higher when recommendations are not followed. Tuberculosis-specific guidelines are suggested based on a review of the literature. Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families. Kainu K, Kivinen K, Zucchelli M, Suomela S, Kere J, et al. Exper Dermatol 2009;18:109–115. doi:10.1111/j.1600-0625.2008.00769.x A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. This study analyzed association to three candidate gene clusters of the region, the S100, small proline-rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. The authors genotyped 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analyzed association with psoriasis using transmission disequilibrium test. A five-SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, Abello MV, Novitskaya I, et al. J Invest Dermatol 2009;129:79–88. doi:10.1038/jid.2008.194 Myeloid dermal dendritic cells (DCs) accumulate in chronically inflamed tissues such as psoriasis. The importance of these cells for psoriasis pathogenesis is suggested by comparative T-cell and

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DC-cell counts, where DCs outnumber T cells. The authors previously identified CD11c+ -blood dendritic cell antigen (BDCA)-1+ cells as the main resident dermal DC population found in normal skin. In this study, they show that psoriatic lesional skin has two populations of dermal DCs: (1) CD11c+BDCA-1+ cells, which are phenotypically similar to those contained in normal skin and (2) CD11c+BDCA-1− cells, which are phenotypically immature and produce inflammatory cytokines. Although BDCA-1+ DCs are not increased in number in psoriatic lesional skin compared with normal skin, BDCA-1− DCs are increased 30-fold. For functional studies, FACS-sorted psoriatic dermal single-cell suspensions were sorted to isolate these two cutaneous DC populations, and then cultured as stimulators in an allogeneic mixed leukocyte reaction. Both BDCA-1+ and BDCA1− myeloid dermal DC populations induced T-cell proliferation, and polarized T cells to become T helper 1 (Th1) and T helper 17 (Th17) cells. Genetic variants of the IL-23R pathway: Association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. Hüffmeier U, Lascorz J, Böhm B, Lohmann J, Wendler J. et al. J Invest Dermatol 2009;129:355–358. doi:10.1038/jid.2008.233 Variants in two genes of the IL-23 receptor (R) pathway have been shown to be associated with psoriasis vulgaris (PV). This study assessed whether the risk conferred by these variants differs between psoriatic skin and joint disease. Four variants of the IL12B and IL23R genes were analyzed in 1,114 PV patients, 748 patients with psoriatic arthritis (PA) and 937 healthy controls before and after stratification for the major psoriasis risk allele at psoriasis susceptibility locus 1 (PSORS1). For both PA and PV, the strongest association was detected with two IL12B singlenucleotide polymorphisms and the corresponding haplotype as reflected by minimal P-values of 10−7 and highest odds ratios of 1.50 (1.28–1.75) for rs6887695 in PA patients and 1.50 (1.27– 1.76) for rs3212227 in the PV cohort, respectively. For IL23R, only rs11209026 showed an association. While confirming recent reports on variants of the IL-23R pathway as susceptibility factors for PV, this study is the first to extend analysis of both genes to PA. However, the results indicate that these variants are not specific risk factors for arthritis, but relevant for susceptibility to psoriasis in general.