[Translated article] Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS: An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS: A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION: Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.

[Translated article] Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP). / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists. / Aproximación a la epidemiología, manejo de la enfermedad y retos actuales en la gestión de la psoriasis pustulosa generalizada en España a través de un cuestionario dirigido a dermatólogos.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS: An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS: A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION: Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Definition of minimal disease activity in psoriasis.

OBJECTIVE: To generate an operational definition to adequately reflect the construct 'Minimal Disease Activity (MDA)' in psoriasis. METHODS: A systematic review of domains included in clinical trials of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as 'No MDA/MDA/Unclassifiable'. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC). RESULTS: The following domains were included: itching, scaling, erythema and visibility by 0-10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%). CONCLUSION: This study provides, for the very first time, the construct of 'Minimal Disease Activity' in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.

Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Update on Topical Treatments for Psoriasis: The Role of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam. / Actualización del tratamiento tópico en psoriasis: aportación de la combinación de calcipotriol y dipropionato de betametasona en espuma.

Topical agents are the first-line treatment for mild and moderate psoriasis, but factors such as frequency of administration, organoleptic properties, and the limited short term results can reduce treatment adherence and effectiveness. Innovations in topical treatments are linked not only to the discovery of new molecules, but also to the reformulation of existing active ingredients based on improvements to administration, organoleptic properties, bioavailability, and ease of use. Calcipotriol and betamethasone dipropionate aerosol foam is a new formulation in which the active ingredients are dissolved in a mixture of volatile propellants that evaporate quickly, leaving a supersaturated solution of calcipotriol and betamethasone dipropionate that enhances penetration into the epidermis. In this article, we take a look at the new calcipotriol and betamethasone dipropionate aerosol formulation and briefly review the main evidence supporting the use of topical treatments for psoriasis.

Consensus Statement on the Psychological Needs of Patients With Chronic Inflammatory Skin Diseases. / Documento de consenso sobre las necesidades psicológicas de los pacientes con enfermedades inflamatorias crónicas dermatológicas.

OBJECTIVE: To establish recommendations to determine, identify, and manage the psychological and emotional needs of patients with chronic inflammatory skin diseases in clinical practice. METHODS: A guided discussion was held at meeting of a nominal group of expert dermatologists and psychologists on the psychological and emotional needs of patients with chronic inflammatory skin diseases, how to manage these cases, and which referral criteria to employ. Based on the results of the discussion, and with the aid of a patient focus group and a review of the literature, a master document was drawn up with recommendations for discussion. A Delphi survey was circulated among a larger group of dermatologists and psychologists to assess the level of agreement with the recommendations. RESULTS: Ten recommendations were established and can be summarized as follows: explore the psychological sphere of the patients with open questions at the time of diagnosis and during the course of the disease; provide patients with clear explanations that address their concerns and inform them of the existence of patient associations; investigate symptoms of anxiety and depression and, if confirmed by means of a Hospital Anxiety and Depression score (HADS) of 11 or greater, consider referral to a mental-health specialist; and, during visits, create a climate of trust, empathize with patients, agree goals and treatment options with them, and motivate them to adhere to those treatments. CONCLUSIONS: These recommendations may help health care professionals address psychological and emotional aspects of their patients in daily clinical practice.

Lymph Node Dissection in Patients With Melanoma and Sentinel Lymph Node Metastasis: An Updated, Evidence-Based Decision Algorithm. / Disección ganglionar en el paciente con melanoma y metástasis en el ganglio centinela: propuesta de decisión basada en la evidencia actual.

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with low-risk sentinel node metastasis (sentinel node tumor load ≤1mm).

Redefining the therapeutic objective in psoriatic patients candidates for biological therapy.

The advances in psoriasis management currently allow achieving a good control of the disease. In particular, with the latest developed molecules, available evidence suggests that it is possible to pose an ambitious therapeutic goal, such as a Dermatology Life Quality Index 0/1, a Physician Global Assessment 0/1, or a Psoriasis Area and Severity Index 90/100 response. However, patients often fail to achieve the complete clearance of their cutaneous lesions or the improvement of disease factors that impair their quality of life. To optimize the treatment of psoriasis, it is not enough to define precisely the therapeutic objective, but also to adapt the therapeutic strategy to make the necessary modifications in case of not achieving it at the time point (at the end of the induction phase, or every 3-6 months) to be agreed with the patient (the so-called treat-to-target approach). In the present report, based on the Delphi methodology, 11 dermatologists from the Spanish Psoriasis Group addressed key issues that could be involved in the achievement and maintenance of the therapeutic goals of patients with moderate to severe psoriasis. The document provides 27 consensus statements intended to support clinical decision-making by healthcare professionals for patients who might be candidates to receive biologic therapy.

IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm.

BACKGROUND: Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice. OBJECTIVE: The study aimed to investigate AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm). MATERIALS AND METHODS: Multicentre, prospective, cohort study of patients with moderate-to-severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies. RESULTS: A total of 4218 courses of treatment were given to 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient-years (PY) (95% CI: 12.14-13.93), 9.34 events/100 PY (95% CI: 8.44-10.33) for biologics and 19.67 (95% CI: 17.9-21.6) events/100 PY for classics (P < 0.001). Of 810 discontinuation-related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100 PY (95% CI: 41.91-57.72)] and infliximab [26.52/100 PY (95% CI: 20.98-33.51). Ustekinumab presented the lowest IR (2.6/100 PY (95% CI: 1.83-3.69). LIMITATIONS: Observational study with potential selection bias. CONCLUSION: Biologic therapies are associated with a lower rate of discontinuation-related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence.