Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. / Consenso sobre las actuaciones a seguir durante la edad fértil, el embarazo, el posparto y la lactancia en pacientes con psoriasis.

OBJECTIVE: To develop evidence- and experience-based recommendations for the management of psoriasis during preconception, pregnancy, postpartum, and breastfeeding. METHODS: The nominal group technique and the Delphi method were used. Fifteen experts (12 dermatologists, 2 of whom were appointed coordinators; 1 rheumatologist; and 2 gynecologists) were selected to form an expert panel. Following a systematic review of the literature on fertility, pregnancy, postpartum, and breastfeeding in women with psoriasis, the coordinators drew up a series of preliminary recommendations for discussion by the panel at a nominal group meeting. The experts defined the scope, sections, and intended users of the statement and prepared a final list of recommendations. Consensus was obtained using a Delphi process in which an additional 51 dermatologists rated their level of agreement with each recommendation on a scale of 1 (total disagreement) to 10 (total agreement). Consensus was defined by a score of 7 or higher assigned by at least 70% of participants. Level of evidence and strength of recommendation were reported using the Oxford Center for Evidence-Based Medicine categories. The final statement was approved by the expert panel. RESULTS: The resulting consensus statement includes 23 recommendations on preconception (fertility and contraception), pregnancy (planning, pharmacological management, and follow-up), and breastfeeding (management and follow-up). Consensus was achieved for all recommendations generated except one. CONCLUSIONS: These recommendations for the better management of psoriasis in women of childbearing age could improve outcomes and prognosis.

Body dysmorphic disorder in patients with acne: a multicentre study.

BACKGROUND AND OBJECTIVE: Body dysmorphic disorder (BDD) is a mental disorder that is difficult to diagnose, causes a lot of suffering and is more prevalent in dermatology patients than in the general population. Our objective was to screen for possible cases of BDD in patients with acne and to determine the prevalence according to DSM-IV and DSM-5 criteria, as well as to analyse the relationship between dermatological and sociodemographic variables. METHODS: A total of 245 patients diagnosed with acne in 11 dermatological centres in Spain were included in the study by members of the Aragon Psychodermatology Research Group and Spanish Research Group of Psychiatric Dermatology. We used the Body Dysmorphic Disorder Questionnaire (BDDQ) as a screening tool. RESULTS: In our sample, we obtained a prevalence for BDD of 10.6% (95% CI: 7.6-13.6%). The prevalence was the same with DSM-IV or DSM-5 criteria. Possible cases of BDD were predominantly women (P = 0.021), and 56% had non-inflammatory lesions vs. 30% of negative patients (P = 0.002). Positive patients as possible cases of BDD spent more than two hours on average a day worrying about their appearance. Most people only worried about one part of their body (86%), and in 95% of the cases, the part of their body that worried them was the face. The three most frequent compulsive behaviours in patients who screened positive for BDD were mirror checking (90.7%), camouflaging (79.1%) and using make-up (72.1%). CONCLUSIONS: As a consequence of the high prevalence of possible cases of BDD in patients with acne observed in our study, there is a need for dermatologists to screen for BDD so that they can be referred to a mental health unit to confirm the diagnosis and be offered treatment to reduce the progression of psychosocial deterioration and the development of comorbid disorders.

Early Detection of Emotional and Behavioral Disorders in Dermatology. / Detección precoz de la enfermedad psicoemocional en dermatología.

Many skin diseases are associated with mental disorders. When the psychological symptoms are mild, as is often the case in dermatology, it can be difficult to distinguish between normality and the manifestations of a mental disorder. To facilitate the distinction we review the concept of mental disorder in the present article. It is also important to have instruments that can facilitate early detection of psychological disease, i.e. when the symptoms are still mild. Short, simple, self-administered questionnaires have been developed to help dermatologists and other health professionals identify the presence of a mental disorder with a high degree of certainty. In this article, we focus on the questionnaires most often used to detect the 2 most common mental disorders: anxiety and depression. Finally, we describe the circumstances in which it is advisable to refer a dermatological patient to a psychiatrist, who can diagnose and treat the mental disorder in accordance with standard protocols.

Core Content for Undergraduate Medical Education in Spain: Recommendations of the Instructors' Group of the Spanish Academy of Dermatology and Venereology (AEDV).

BACKGROUND: Skin problems are among the most frequent reasons for seeking medical attention in primary care. In recent years, as a result of the process of adapting medical curricula to the requirements of the European Higher Education Area, the amount of time students spend learning the concepts of dermatology has been reduced in many universities. MATERIAL AND METHODS: In order to reach a consensus on core content for undergraduate education in dermatology, we sent a survey to the 57 members of the instructors' group of the Spanish Academy of Dermatology and Venereology (AEDV), asking their opinions on what objectives should be set for a dermatology course in Spain. A total of 131 previously selected objectives were listed. We then applied the Delphi method to achieve consensus on which ones the respondents considered important or very important (score≥4 on a Likert scale). RESULTS: Nineteen responses (33%) were received. On the second round of the Delphi process, 68 objectives achieved average scores of at least 4. The respondents emphasized that graduates should understand the structure and functions of the skin and know about bacterial, viral, and fungal skin infections, the most common sexually transmitted diseases (STDs), and the 4 main inflammatory dermatoses. Students should also learn about common complaints, such as itching and bald patches; the management of dermatologic emergencies; purpura and erythema nodosum as signs of internal disease; and the prevention of STDs and skin cancer. During clinical clerkships students should acquire the communication skills they will need to interview patients, write up a patient's medical history, and refer the patient to a specialist. CONCLUSIONS: The AEDV's group of instructors have defined their recommendations on the core content that medical faculties should adopt for the undergraduate subject of dermatology in Spain.

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.

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting.

BACKGROUND: Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. OBJECTIVE: To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. METHODS: This was a retrospective, multicentre study. Twenty-five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. RESULTS: In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow-up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow-up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow-up. CONCLUSIONS: Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk-benefit ratio is justified.

[Clinical characteristics and disease course in patients treated with efalizumab following suspension of marketing authorization by the European medicines agency: a multicenter observational study]. / Perfil clínico y curso evolutivo de los pacientes tratados con efalizumab tras la suspensión de su autorización por la EMEA. Estudio observacional y multicéntrico.

BACKGROUND AND OBJECTIVES: The withdrawal of marketing authorization for efalizumab by the European Medicines Agency in February, 2009 provided a unique opportunity to assess the course of disease in patients who were not subject to the selection criteria and biases that were common in the pivotal trials. The aim of this study was to evaluate the course of psoriasis following forced suspension of efalizumab in a group of patients treated in normal clinical practice. As secondary objectives, we sought to assess the relationships between clinical characteristics, treatment response, and disease course during efalizumab treatment and 12 and 24 weeks after suspension. PATIENTS AND METHODS: Information on the epidemiological profile and disease course during treatment and following suspension of the drug was collected from a group of patients treated with efalizumab. Statistical analyses were performed to identify predictive factors. RESULTS: One hundred forty-seven patients from 12 Spanish hospitals were included in the study. During treatment, 4% of patients were diagnosed with generalized inflammatory flares. Most patients could be classified as having a good (55%) or moderate (18%) response to treatment. Rebound following withdrawal of efalizumab was observed in 30% of patients. The likelihood of rebound was independent of clinical characteristics, treatment response, or therapeutic approach used by the dermatologist following suspension. CONCLUSIONS: There was a high frequency of rebound following suspension of efalizumab, exceeding the rate reported in pivotal trials. This is particularly noteworthy given the large proportion of patients with a good response to treatment and therefore believed to have a better prognosis. Other significant findings were the higher frequency of positive treatment response than observed in previous studies (possibly influenced by the mean treatment duration) and the high frequency of generalized inflammatory flares.

[Guidelines on the use of methotrexate in psoriasis]. / Metotrexato: guía de uso en psoriasis.

Psoriasis, a chronic multifactorial inflammatory disease that develops in genetically predisposed individuals, affects approximately 1.5% of the Spanish population. This disease has a negative impact on patients' quality of life, and long-term therapy is often required to control the symptoms. In addition to the classical systemic treatments (methotrexate, acitretin, cyclosporine, and ultraviolet light), the group of drugs known as biologics (etanercept, infliximab, adalimumab, and ustekinumab) provides the dermatologist with an expanded therapeutic armamentarium, thereby improving the likelihood of controlling psoriasis in patients with severe and/or extensive disease. Methotrexate, a classic antipsoriatic drug, is still very useful either as single-drug therapy or in combination with other systemic drugs, particularly as a rescue therapy or combined with biologics. This article aims to establish the role of methotrexate in the treatment of psoriasis. We considered it of interest to develop guidelines for using methotrexate in the management of psoriasis with a view to ensuring the safe and proper use of this drug in the management of psoriasis. This document was developed by consensus among members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

[Adverse reactions during biological therapy for psoriasis: results of a survey of the Spanish Psoriasis Group]. / Efectos adversos observados durante la terapia biológica en la psoriasis. Resultados de una encuesta al Grupo Español de Psoriasis.

BACKGROUND: Biologic therapies have been a major breakthrough in the treatment of psoriasis because they are more selective and have a better short-term and medium-term safety profile. There are reliable data to support both the efficacy and the safety of these drugs. However, it is always useful to report the clinical experience of dermatologists who are experts in the use of biologic agents to treat psoriasis, particularly with regard to their safety. MATERIAL AND METHODS: We present the results of a survey administered to the members of Spanish Psoriasis Group and based on a series of questions referring to the clinical safety of these agents. A total of 988 patients treated with efalizumab, infliximab, etanercept, and adalimumab were reported by 15 members of the group. RESULTS: There was a particularly high proportion of reactions (34%) to infliximab infusions. Blood test abnormalities were detected in 13.25% of patients and infections in 12.24%, with one case of pulmonary tuberculosis. Attention is drawn to the adverse effects profile of efalizumab: de novo arthritis in 5.8% and rebound in 20.9% of patients. CONCLUSION: The safety data provided by our study should be taken into account in view of the large number of patients recruited by dermatologists experienced in the use of this type of therapy.

Guidelines on the Use of Methotrexate in Psoriasis. / Metotrexato: guía de uso en psoriasis.

Psoriasis, a chronic multifactorial inflammatory disease that develops in genetically predisposed individuals, affects approximately 1.5% of the Spanish population. This disease has a negative impact on patients' quality of life, and long-term therapy is often required to control the symptoms. In addition to the classical systemic treatments (methotrexate, acitretin, cyclosporine, and ultraviolet light), the group of drugs known as biologics (etanercept, infliximab, adalimumab, and ustekinumab) provides the dermatologist with an expanded therapeutic armamentarium, thereby improving the likelihood of controlling psoriasis in patients with severe and/or extensive disease. Methotrexate, a classic antipsoriatic drug, is still very useful either as single-drug therapy or in combination with other systemic drugs, particularly as a rescue therapy or combined with biologics. This article aims to establish the role of methotrexate in the treatment of psoriasis. We considered it of interest to develop guidelines for using methotrexate in the management of psoriasis with a view to ensuring the safe and proper use of this drug in the management of psoriasis. This document was developed by consensus among members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.

[Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents]. / Directrices españolas basadas en la evidencia para el tratamiento de la psoriasis moderada a grave con agentes biológicos.

Psoriasis vulgaris is an inflammatory skin disease that is generally chronic and that affects between 1 % and 2 % of the population in industrialized Western countries. It is associated with a marked decline in quality of life. A wide range of treatments are currently available, although surveys conducted before the advent of biologic agents reflected a strong degree of dissatisfaction with the treatments then available. Extensive scientific evidence has been gathered on the safety of biologic agents, and this has led to a review of the role of systemic treatment in general and has allowed new therapeutic goals and strategies to be contemplated in patients with moderate-to-severe psoriasis. In this new situation, there is a need for Spanish guidelines on the treatment of moderate-to-severe psoriasis with biologic agents, drafted by consensus among specialists and ratified by the Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology (AEDV). These guidelines should be evidence-based with regard to the pharmacologic characteristics, mechanism of action, administration route and regimen, efficacy, contraindications, adverse effects, and cost estimates of biologic agents approved for the treatment of moderate-to severe psoriasis in Spain.

An unusual case of congenital linear eccrine spiradenoma.

Eccrine spiradenoma (ES) is a benign uncommon tumor of skin adnexa with a characteristic clinical and histopathological presentation. Typically, it presents as a painful, slow growing and solitary nodule on the head or upper trunk in adult patients. We report a child with linear ES which presented with asymptomatic papulonodular lesions in a blaschkoid distribution on the face. Cases reported in the literature of multiple spiradenomas are very rare and multiple linear lesions are even rarer. To date, 21 cases of linear/multiple ES have been reported. Of these, eight were in children or adolescents. We report an additional case of this rare clinical presentation and review the literature.

Randomized, double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight exposure in the treatment of adult nonsegmental vitiligo.

BACKGROUND: Vitiligo is a common skin disease which is difficult to treat. Approximately half of patients acquire the disease before the age of 20 years. This disease has a high stigmatizing impact but no ideal, aetiology-oriented, effective therapy has been found to date. Tacalcitol and other vitamin D analogues have been shown to have stimulating activity both on immunomodulatory mediators and on melanocytes in lesional skin. OBJECTIVE: To investigate the efficacy and safety of tacalcitol ointment plus sunlight exposure in the treatment of nonsegmental vitiligo. METHODS: A single-centre, randomized, double-blind, vehicle-controlled study including 80 patients with nonsegmental vitiligo was carried out in a specialized outpatient dermatology clinic within a tertiary care, university-affiliated hospital in Spain. Efficacy was assessed by quantification of the lesional repigmentation area at the end of the study compared with the baseline. Tacalcitol (n = 40) or matching placebo ointment (n = 40) was applied once a day at night. Daily exposure to sunlight for 30 min was performed. Treatment was continued for 4 months. The response of the lesions was clinically verified every 2 weeks by a blinded medical investigator. All adverse effects were recorded. RESULTS: Eighty adult patients with nonsegmental vitiligo were recruited. Over 16 weeks, 64 patients completed the study requirements. There was no significant difference in the repigmentation response at the 16-week time point between the vehicle + sunlight exposure and the tacalcitol + sunlight exposure groups. No reduction in the size of the lesions > 25% was observed in the tacalcitol-treated patients. No serious adverse effects were observed. CONCLUSION: The combination of tacalcitol with heliotherapy has no additional advantages compared with heliotherapy alone.