Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases. / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study.

BACKGROUND: Ixekizumab (anti-IL17A) is effective as treatment for moderate-to-severe plaque psoriasis, but real-life data on effectiveness and safety are currently very limited. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab in a cohort of real-life plaque psoriasis patients. METHODS: Retrospective chart review of 100 patients with moderate-to-severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres. RESULTS: According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%-50.0% at week 12-16; 88.3%-58.4% at week 24 and 82.9%-58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12-16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio-naive group showed significantly higher PASI 75 response rate at week 12-16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty-six (26%) patients experienced adverse events (AEs) during the follow-up period, being most of them of mild-to-moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow-up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months. CONCLUSION: The present study illustrates the initial experience with ixekizumab in real-world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.

The Spanish Psoriasis Patients' Association According to Its Members: Cross-Sectional Descriptive Study of Members' Opinions of the Association's Functions. / Función y respaldo a la asociación de pacientes con psoriasis en España según sus miembros: estudio descriptivo transversal.

INTRODUCTION: Patient associations form part of health care systems, but little is known about how their members' view the functionality of these associations and whether they endorse their goals and activities. OBJECTIVE: To study how the members of the leading Spanish association of patients with psoriasis and their relatives view the group's functioning. MATERIAL AND METHODS: Survey study using a self-administered questionnaire answered by members of the association (total membership, 26 349 persons). The credibility of the association and respondents' confidence in and satisfaction with it were studied and compared with their attitudes toward other agents in the health care system. A Rasch model was used to analyze respondents' ranking of functions. Analysis of variance was used to study between-group differences. RESULTS: A total of 746 members participated (response rate 2.83%). The association's credibility was rated in second place, after that of specialists who treat psoriasis. Support for the association functions was good (7.53 on a scale of 0 to 10). The function the members rated highest was the raising of societal awareness of psoriasis and its problems. Rated lowest were functions related to personal services for members. Educational level was the only participant factor associated with significant differences in evaluations (P<.05). CONCLUSIONS: The psoriasis association contributes by disseminating information about the disease and patient care, and it serves to represent patients. Health professionals and institutions should take the association into account in their efforts to deal with the disease and in designing effective policies.

Expert Recommendations on Treating Psoriasis in Special Circumstances (Part II). / Recomendaciones de expertos para el tratamiento de la psoriasis en situaciones especiales (II).

BACKGROUND: There is insufficient information on how best to treat moderate to severe psoriasis in difficult clinical circumstances. MATERIAL AND METHODS: We considered 5 areas where there is conflicting or insufficient evidence: pediatric psoriasis, risk of infection in patients being treated with biologics, psoriasis in difficult locations, biologic drug survival, and impact of disease on quality of life. Following discussion of the issues by an expert panel of dermatologists specialized in the management of psoriasis, participants answered a questionnaire survey according to the Delphi method. RESULTS: Consensus was reached on 66 (70.9%) of the 93 items analyzed; the experts agreed with 49 statements and disagreed with 17. It was agreed that body mass index, metabolic comorbidities, and quality of life should be monitored in children with psoriasis. The experts also agreed that the most appropriate systemic treatment for this age group was methotrexate, while the most appropriate biologic treatment was etanercept. Although it was recognized that the available evidence was inconsistent and difficult to extrapolate, the panel agreed that biologic drug survival could be increased by flexible, individualized dosing regimens, continuous treatment, and combination therapies. Finally, consensus was reached on using the Dermatology Quality of Life Index to assess treatment effectiveness and aid decision-making in clinical practice. CONCLUSIONS: The structured opinion of experts guides decision-making regarding aspects of clinical practice for which there is incomplete or conflicting information.

Methotrexate in Moderate to Severe Psoriasis: Review of the Literature and Expert Recommendations.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Estimation of the prevalence of latent tuberculosis infection in patients with moderate to severe plaque psoriasis in Spain: The Latent study.

BACKGROUND AND OBJECTIVE: Anti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. MATERIAL AND METHOD: Non-interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-γ release assay (IGRA) based on enzyme-linked immunosorbent assay (QuantiFERON(®) TB Gold In-Tube) in the 2 years preceding the study. RESULTS: Data for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (κ=0.516; P<.001). CONCLUSIONS: The prevalence of LTBI in this study was similar to previous estimates for Spain.

Multidisciplinary psoriasis and psoriatic arthritis unit: report of 4 years' experience.

INTRODUCTION AND OBJECTIVES: Up to 30% of patients with psoriasis develop joint disease, the course of which can be improved by early diagnosis and treatment. The aim of this study was to describe our experience with a new multidisciplinary psoriasis and psoriatic arthritis unit over a period of 4 years (2009-2012). MATERIAL AND METHODS: Implementation of a PSOriasis Rheumatology and Dermatology unit (PSORD) to provide patient care and physician training. In the first phase of the project, referral criteria for the unit were defined and several meetings were organized to train and prepare the specialists involved in the program. In the second phase, a schedule was drawn up for monthly patient visits with the PSORD team. Starting in 2011, training was offered to dermatologists and rheumatologists from other hospitals interested in implementing a similar model. RESULTS: A total of 259 visits (71% first visits, 8% no-shows) were scheduled during the period analyzed, with a median of 8 visits (range, 2-14 visits) per session. Sixty-three percent of the patients were referred from the rheumatology department. Diagnosis and treatment were modified in 32% and 47% of cases, respectively. Three training courses were held with 15 physicians from 6 hospitals, 3 of which created similar units. CONCLUSIONS: The PSORD model improved the management of difficult-to-diagnose and/or uncontrolled disease, the early diagnosis and treatment of psoriatic arthritis, and collaboration between dermatologists and rheumatologists. Finally, the model lends itself to being exported to other settings.

Lipopolysaccharide-binding protein is increased in patients with psoriasis with metabolic syndrome, and correlates with C-reactive protein.

Lipopolysaccharide-binding protein (LBP) is a reliable indicator of serum lipopolysaccharide (LPS) concentration. Raised levels of circulating LPS can trigger an increase in chronic pro-inflammatory cytokines, which may mediate the development of insulin resistance and obesity. Psoriasis is a chronic inflammatory skin disease that has been associated with metabolic syndrome. We aimed to study the expression of LBP in patients with psoriasis treated with narrowband ultraviolet B phototherapy, and controls matched by age, gender and body mass index (BMI). We did not find any differences in serum LBP concentration between patients and controls, and serum LBP did not correlate with the Psoriasis Area and Severity Index. However, patients with psoriasis and metabolic syndrome had higher serum concentration of LBP than controls. Furthermore, correlation with BMI and apolipoprotein B was present in controls, but not in patients with psoriasis. Serum LBP level did not change significantly after treatment with phototherapy.

Adherence and patient satisfaction with topical treatment in psoriasis, and the use, and organoleptic properties of such treatments: a Delphi study with an expert panel and members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

BACKGROUND: Topical therapy is key to the successful management of psoriasis, and patient adherence to treatment contributes to its effectiveness in the long-term. OBJECTIVES: To establish consensus on adherence to topical treatment in psoriasis, draw up recommendations on how adherence could be improved, and evaluate the properties of the main vehicles used. METHOD: We designed a questionnaire on adherence to topical treatments in psoriasis and another on the properties of the main vehicles used; the 2 questionnaires were evaluated using the Delphi method by a panel of experts and members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology, respectively. RESULTS: Consensus was reached on the following statements: a) treatment adherence increases the effectiveness of topical treatments in psoriasis; b) to improve adherence, it is necessary to improve communication between patients and health care staff, provide written instructions, and simplify treatment with easy-to-use, pleasant products that are preferably applied only once a day; c) treatment satisfaction increases adherence and tends to improve the health-related quality of life of the patient. Ointment was rated the worst vehicle, while foams and solutions were rated the best. Creams and lipophilic gels were considered to be better than ointment in several respects. CONCLUSION: To improve adherence to topical regimens in psoriasis and the effectiveness of such therapy, we need to give patients more information, simplify treatment regimens, and prescribe easy-to-use products that will ensure satisfaction.

Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis.

Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

Biologic therapy is a well-established strategy for managing moderate and severe psoriasis. Nevertheless, the high cost of such therapy, the relatively short span of clinical experience with biologics, and the abundance of literature now available on these agents have made evidence-based and consensus-based clinical guidelines necessary. The ideal goal of psoriasis treatment is to achieve complete or nearly complete clearing of lesions and to maintain it over time. Failing that ideal, the goal would be to reduce involvement to localized lesions that can be controlled with topical therapy. Although current evidence allows us to directly or indirectly compare the efficacy or risk of primary or secondary failure of available biologics based on objective outcomes, clinical trial findings cannot be directly translated to routine practice. As a result, the prescribing physician must tailor the treatment regimen to the individual patient. This update of the clinical practice guidelines issued by the Spanish Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis incorporates information from the most recent publications on this topic.

Effect of narrowband ultraviolet B therapy on inflammatory markers and body fat composition in moderate to severe psoriasis.

BACKGROUND: Previous studies have shown increased prevalence of metabolic syndrome in patients with psoriasis. OBJECTIVES: To characterize the anthropometric and metabolic profile of Spanish patients with moderate to severe psoriasis compared with controls without psoriasis matched for gender, age and body mass index (BMI), and to evaluate the impact of narrowband ultraviolet B (NB-UVB) therapy on patient profiles. METHODS: Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine, vitamins D, B(6) and B(12) and folic acid of 50 patients with psoriasis and 50 matched controls were recorded then evaluated after NB-UVB in patients with psoriasis and correlated with clinical outcome. RESULTS: Despite very similar BMIs, 54% of patients met International Diabetes Foundation criteria for metabolic syndrome compared with 42% of controls (P = 0·01); body fat was 29·9% in patients and 28·0% in controls (P = 0·037), correlating with waist circumference; while patient atherogenic profiles were less favourable, with higher apolipoprotein B and low density lipoprotein cholesterol than controls, and both patients and controls showed insufficient vitamin D serum levels (< 20 ng mL(-1)). Mean improvement of Psoriasis Area and Severity Index (PASI) after NB-UVB was 78·2%. Ferritin, B(12) and C-reactive protein decreased significantly after NB-UVB therapy. Vitamin D levels reached adequate levels after phototherapy; however, no relationship with PASI improvement was observed. CONCLUSIONS: We characterized inflammatory and atherogenic profiles of Spanish patients with psoriasis compared with matched controls. After NB-UVB therapy we demonstrated improvement in psoriasis and some systemic inflammation markers, which were not mediated by enhancement of vitamin D synthesis.

[Guide to buying a camera for dermatological photography]. / Guía para la compra de una cámara fotográfica para Dermatología.

Choosing a camera for use in the dermatology office is difficult, particularly in the case of a digital camera because the market is constantly evolving. This article explains the features that should be taken into account, including camera type, sensor, lens and macro capability, aperture priority mode, screen, viewfinder, operating speed, flash, battery, memory card, and image format. The most recent advances in the field of digital photography relevant to the dermatologist are discussed.

Unmet needs in patients with moderate-to-severe plaque psoriasis treated with methotrexate in real world practice: FirST study.

BACKGROUND: Methotrexate (MTX) is frequently used in the treatment of moderate-to-severe psoriasis, however, there is limited data on health-related quality-of-life (HRQoL), psoriasis clinical outcomes and hepatic fibrosis in MTX-treated patients in routine clinical practice. OBJECTIVES: To investigate the impact of moderate-to-severe psoriasis in MTX-treated patients in Spain regarding to HRQoL, psoriasis clinical data and risk of hepatic fibrosis. METHODS: Observational, non-interventional, cross-sectional, retrospective, multicentre study, performed in Spain in moderate-to-severe plaque psoriasis patients treated with MTX > 16 weeks prior to inclusion. RESULTS: Despite ongoing treatment, 17.1% of 457 evaluable patients reported moderate-to-extreme impact on HRQoL (DLQI > 5); 21.4% BSA > 5 and 35.2% moderate-to-severe pruritus (VAS ≥ 4). Persistent severe psoriasis (PASI ≥ 10 and/or DLQI ≥ 10) was observed in 10.7%. Hepatic steatosis was identified in 64.1% of patients (HSI ≥ 36) and 37.2% of the patients were at-risk of advanced fibrosis which was associated to the MTX treatment duration. CONCLUSIONS: The study identified unmet needs in moderate-to-severe plaque psoriasis patients treated with MTX, revealing a significant proportion of sub-optimally controlled patients in terms of HRQoL and different domains of the disease. This study also found patients at-risk of advanced fibrosis, with evidence suggesting a correlation between longer exposures to MTX and higher risk of advanced fibrosis.

[Portfolios: a tool for the training and assessment of residents in dermatology, part 1]. / El portafolio como herramienta de formación y evaluación de los residentes de Dermatología (I).

The medical resident's portfolio is a collection of materials that show reflective learning in the context of clinical practice. A portfolio contains documents (such as case histories and questionnaires the resident has used), images, and video recordings that reveal that an individual has acquired the competencies needed for professional practice. A portfolio is an assessment tool that simultaneously supports learning and gives evidence for certifying competence. It encourages independent continuing professional development that is incremental and centered on answering questions about what one has learned, how it might be applied, what still needs to be learned, and what must be done to reach one's goal. Answering such questions provides evidence of competencies that have been acquired and what is still lacking, allowing the trainee to develop a plan for personal improvement and evaluate subsequent achievements. The first step in creating a portfolio is to list required skills and abilities, along with the actions that will allow the resident to acquire them during each year of residency training. The ultimate goal is to define the resident's professional competence. We describe a model on which to base a training and assessment portfolio for residents in dermatology.

[Treatment of acne in daily clinical practice: an opinion poll among Spanish dermatologists]. / Tratamiento del acné en la práctica clínica habitual: encuesta de opinión entre los dermatólogos españoles.

BACKGROUND AND OBJECTIVES: the aim of this study was to determine the approaches used to treat acne in clinical practice by Spanish dermatologists. A secondary objective of the study was to compare the practices of Spanish dermatologists with the Acne Global Alliance treatment algorithm and develop a Spanish treatment algorithm for acne. PATIENTS AND METHODS: a multicenter, cross-sectional survey was undertaken among 872 Spanish dermatologists. The study comprised 4 randomly distributed questionnaires. The first 3 contained the following case descriptions: severe acne associated with masculinization (case 1), mild comedonal acne (case 2), and moderate papulopustular acne (case 3). The fourth questionnaire contained 5 photographs of different types of acne and an algorithm containing various treatment options, from which dermatologists were asked to choose the most appropriate. RESULTS: for case 1, 55% of dermatologists chose oral antiandrogens/contraceptive drugs plus topical retinoids or topical benzoyl peroxide/antibiotics. In case 2, 62% chose topical retinoids and, in case 3, 68% chose systemic antibiotics plus benzoyl peroxide. Combination therapy was considered the treatment of choice in all types of acne, with topical retinoids as the initial treatment option for mild and moderate forms and the preferred option for maintenance therapy. CONCLUSIONS: in general, Spanish dermatologists treat acne in accordance with the Acne Global Alliance treatment algorithm. The varying opinions reported in response to open questions, however, confirm the need to unify criteria for the treatment of acne.

[Portfolios: a tool for the training and assessment of residents in dermatology, part 2]. / El portafolio como herramienta de formación y evaluación de los residentes de dermatología (II).

A portfolio is a collection of material documenting reflection about practice. It contains documents (eg, case histories and questionnaires the resident has used), images, and video recordings that reveal that an individual has acquired the competencies needed for professional practice. This assessment tool simultaneously supports learning and provides evidence for certifying competence. The adoption of portfolio use by a dermatology department requires the support of both the training supervisor and the chief of department. The learning objectives defined by the National Board for Medical-Surgical Dermatology and Venereology must be taken into consideration so that ways to assess each objective can be included; this approach supports holistic ongoing education as well as the certification of competencies the resident finally achieves. Use of portfolios in medical residency training can improve on current assessment methods, which we believe lack precision. We propose that portfolios gradually begin to replace the resident's training log. We are currently developing an online software application that will facilitate the use of portfolios.