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.

Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry.

BACKGROUND: There are few data on the prevalence of obesity in the general psoriasis population and on the real impact of obesity on the management of psoriasis patients in the clinical setting. OBJECTIVES: To evaluate the prevalence of overweight and obesity in patients with moderate-to-severe psoriasis compared to the general population and to assess the relationship between Body Mass Index (BMI) and the risk of discontinuing treatment. METHODS: Patients registered on Biobadaderm, a prospective registry, were grouped according the different categories of BMI and compared to the general Spanish population. Drug survival was analysed considering only drug withdrawal due to lack of effectiveness, remission and adverse events. RESULTS: A total of 1162 moderate-to-severe psoriasis patients on systemic conventional or biological treatment were recruited. The prevalence of obesity was found to be significantly higher in psoriasis patients than in the general Spanish population (P < 0.001). In multivariate analysis a 5-unit increase in BMI, similar to a change in BMI category from normal weight to overweight and from overweight to obesity, was associated with a 12% increased risk of discontinuing therapy due to lack of effectiveness (HR 1.12, 95% CI: 1.01-1.24) and with a 17% increased risk of having an adverse event (HR 1.17, 95% CI: 1.02-1.36), both independently of the drug used. CONCLUSIONS: Patients with moderate-to-severe psoriasis had a higher prevalence of obesity than the general population. Increased BMI was associated with an increased risk of treatment discontinuation due to lack of effectiveness and a higher risk of adverse events.

Acitretina: guía de uso en psoriasis / Guidelines for the Use of Acitretin in Psoriasis

La fototerapia y los tratamientos sistémicos clásicos (metotrexato, acitetrina, ciclosporina), junto con las denominadas terapias biológicas (etanercept, infliximab, adalimumab, ustekinumab), permiten al dermatólogo disponer de un arsenal terapéutico amplio que aumenta las posibilidades de control de pacientes con psoriasis grave y/o extensa. La acitretina sigue siendo de gran utilidad tanto en monoterapia como combinada con otros fármacos sistémicos (clásicos o «biológicos»), o en terapia secuencial. Se distingue por no ser inmunosupresor directo y mantener respuestas a muy largo plazo, lo que le confiere un papel relevante en el tratamiento de la psoriasis, que no siempre ha sido reconocido en las diversas guías terapéuticas de esta enfermedad. Se presenta una guía de uso de acitretina consensuada por los miembros del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología, en la que se exponen de forma detallada aspectos de la farmacología del fármaco, sus indicaciones y contraindicaciones, su eficacia antipsoriásica, los efectos adversos asociados al fármaco, las acciones a tener en cuenta para aumentar la seguridad de su uso, y se propone diversas estrategias terapéuticas de aplicación en la práctica clínica habitual. El objetivo global es facilitar los criterios de indicación y manejo de la acitretina en pacientes con psoriasis (AU)

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 (AU)

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.

Latent tuberculosis infection and active tuberculosis in patients with psoriasis: a study on the incidence of tuberculosis and the prevalence of latent tuberculosis disease in patients with moderate-severe psoriasis in Spain. BIOBADADERM registry.

INTRODUCTION: The incidence of tuberculosis (TB) or the prevalence of latent tuberculosis infection (LTBI) in psoriasis patients has not been described in the Spanish population. We carried out a study with the objectives: (i) To describe the incidence of TB in patients with psoriasis on systemic treatment in the Spanish population; (ii) To determine the prevalence of LTBI in patients who are candidates for biological treatment; and (iii) To investigate the level of compliance with current recommendations for LTBI and TB screening. METHODS: Data were obtained from BIOBADADERM (Spanish registry for systemic biological and non-biological treatments in psoriasis). An analysis was performed of the exposed cohort to determine the prevalence of LTBI and to describe compliance with the screening guidelines. RESULTS: A total of 1425 patients were registered in BIOBADADERM. They included 793 (56%) patients exposed to biological treatment and 632 (44%) treated with conventional systemic drug. Overall follow-up was 3720 person-years. Of the 793, 20.5% (163) were diagnosed with LTBI before starting biological treatment. The rate of active TB for the exposed cohort was 145 cases × 100,000 patient-years (95% CI 54-389). No case of TB was found in the control group. Screening for LTBI was performed in 83% of the exposed sample. CONCLUSION: Patients with psoriasis who are exposed to biological treatment appear to be at greater risk for tuberculosis. In Spain, up to 20% of patients with psoriasis who are candidates for biological therapy have LTBI. There continues to be a significant percentage of errors in compliance with clinical guidelines.

Atrofia blanca con buena respuesta a estanozolol y ácido acetilsalicílico / Atrophic blanche with good response to stanozol. Case report and literature review

La atrofia blanca es un proceso ulcerativo de los miembros inferiores que, en su evolución, da lugar a lesiones atróficas, rodeadas de pigmentación hemosiderótica y telangiectasias, La mayoría de los casos se asocian a insuficiencia venosa crónica, aunque en otras ocasiones se han relacionado con enfermedades sistémícas. Considerada anteriormente como un cuadro de origen vasculltico, actualmente se describe como una vasculopatía trombogénica, en la que se han descrito numerosos tratamientos para corregir las alteraciones de la microcirculación existentes en estos pacientes (AU)

Atrophie blanche is a lower leg ulcerative condition, which develops atrophic lesions, with hemosiderotic changes and telangiectasia. Most cases are associated with chronic venous insufficiency, although underlying systemic diseases have also been described. Although the process was previously considered to be of vasculitic origin, currently it is described as a thrombogenic vasculopathy, with a wide range of therapies aimed at correcting impaired microcirculation in these patients (AU)

Self-association of pyridine-2,6-dicarboxylic acid in aqueous solution as determined from ultraviolet hypochromic and hyperchromic effects.

The self-association of pyridine-2,6-dicarboxylic acid (dipicolinic acid), was studied in aqueous solution at the pH values of 0.2, 3.5, 6.9 and 13.0, by ultraviolet spectroscopy. The variation in molar absorptivity with the concentration of this compound was measured for the band in the mid-ultraviolet region. Deviations from Beer-Lambert law with increasing concentration were found at the pH values of 0.2, 3.5 and 6.9. Hypochromic effects were detected at pH 0.2 and 6.9, while a hyperchromic effect was observed at pH 3.5. These results were interpreted in terms of self-association leading to the formation of dimers. From the fitting of the experimental curves of hypochromic or hyperchromic effects, self-association constants were calculated. The occurrence of hypochromic and hyperchromic effects was analyzed in terms of vertical and horizontal interactions, respectively, to elucidate the nature of the self-association processes, stacking or hydrogen bonding, relevant to each of the protolytic species of dipicolinic acid in aqueous solution.

The self-organization of adenosine 5'-triphosphate and adenosine 5'-diphosphate in aqueous solution as determined from ultraviolet hypochromic effects.

The self-association of adenosine 5'-triphosphate (ATP) and of adenosine 5'-diphosphate (ADP) was studied in aqueous solution at different pH values, over the concentration range from 5 x 10(-6) to 5 x 10(-2) M, by ultraviolet spectroscopy. Measures of the molar absorptivity of the ultraviolet bands of these compounds with increasing concentration have shown two hypochromic effects, at concentrations below 10(-3) and above 10(-3) M, respectively. These results can be interpreted in terms of self-association processes involving the formation of dimers and of polymers. From the fitting of the experimental curves of hypochromic effects, self-association constants for dimerization and polymerization were calculated. The results obtained are discussed in relation to the values reported in the literature and indicate the influence of the concentration range not only on the numerical value but also on the order of magnitude of the association constants. Comparison of ATP with ADP shows that the length of the phosphate chain may be a relevant feature in the nature of the self-organization processes in these adenine nucleotides in aqueous solution.

A study by ultraviolet spectroscopy on self-association of purine, 6-methylpurine, benzimidazole, and imidazo [1,2-a]pyridine in aqueous solution.

The self-association of four heteroaromatic compounds with fused five- and six-membered rings: purine, 6-methylpurine, benzimidazole, and imidazo[1,2-a]pyridine, was studied in aqueous solution at different pH values, by ultraviolet spectroscopy. The variation in molar absorptivity with the concentration of these compounds was measured for the band systems in the mid-ultraviolet region. Hypochromic deviations from the Beer-Lambert law with increasing concentration were found for all compounds. These results were interpreted in terms of self-association processes involving the formation of dimers and, in certain cases, also the formation of polymers. From the fitting of the experimental curves of hypochromic effects, self-association constants for dimerization and polymerization were calculated. The results obtained are discussed in relation to the self-association properties of the building blocks of each compound, studied by us in previous works. The relevance of the position of the nitrogen atoms at the five- and six-membered rings was analyzed to elucidate the nature of the self-association processes, in particular the tendency to polymerization. The values of the calculated self-association constants are discussed in relation to the intermolecular interaction energies of these compounds in aqueous solution.

Changes in external trehalase activity during human serum-induced dimorphic transition in Candida albicans.

Yeast-like cells (blastoconidia) of Candida albicans growing exponentially on a glucose-containing medium (YPD) exhibited low external trehalase activity and stored a negligible amount of intracellular trehalose. The addition of human serum at 37 degrees C to exponential cultures promoted a high degree of germ-tube formation with no significant changes in trehalase activity or trehalose content. In contrast, stationary cells accumulated a large amount of trehalose, while external trehalase remained at a low and practically constant level. However, resting cultures were unable to enter the dimorphic program, except when they were supplemented with fresh YPD and serum together. Only under these conditions was trehalase activated and trehalose hydrolyzed. Specific inhibition of external trehalase by validoxylamine A caused a certain delay in, and a lower level of, germ-tube formation, but did not totally block the dimorphic conversion. These results suggest that external trehalase is not involved in the serum-induced morphological transition in C. albicans.

Trehalose hydrolysis is not required for human serum-induced dimorphic transition in Candida albicans: evidence from a tps1/tps1 mutant deficient in trehalose synthesis.

Exponential yeast-like cells of a Candida albicans wild-type strain exhibited strong capacity for germ tube formation in a glucose-containing medium (YPD) after induction with human serum at 37 degrees C, whereas the isogenic double disruptant tps1/tps1 mutant, which is deficient in trehalose synthesis, failed to produce germ tubes. In a medium without glucose (YP), the morphological transition fraction was roughly equivalent in both strains. Substitution of glucose by galactose or glycerol increased the number of wild-type proliferating cells able to enter the dimorphic program with no noticeable change in their trehalose content, while stationary cells, which accumulate a large amount of trehalose, did not form germ tubes. When fresh medium was added, a high proportion of these resting cells recovered their ability to carry out dimorphic transition. The tps1/tps1 mutant followed the same pattern of hyphae formation, despite the fact that it was unable to accumulate trehalose either during dimorphism induction or after several stress challenges. Furthermore, trehalose-6-phosphate synthase activity was barely detectable in the mutant. These results strongly suggest that serum-induced dimorphic transition does not require trehalose mobilization; they also support the idea that TPS1 is the only activity involved in trehalose biosynthesis in C. albicans.

Carcinoma hepatocelular fibrolaminar: presentación clinica con hipertiroidismo paraneoplasico; a proposito de un caso / Fibrolamellar hepatocellular carcinoma: clinical report with paraneoplastic hyperthyroidism; apropos of a case

Se comunica un caso de carcinoma hepatocelular variedad fibrominar, asociado a fenómenos paraneoplásicos, en una mujer de 17 años. La presentación clínica fue con hipertiroidismo y cursó con metástasis pulmonares y en tejido muscular de región glútea. Se revisa la literatura científica, encontrándose sólo un caso relatado con similar cuadro endócrino

Carcinoma hepatocelular fibrolaminar: presentación clinica con hipertiroidismo paraneoplasico; a proposito de un caso / Fibrolamellar hepatocellular carcinoma: clinical report with paraneoplastic hyperthyroidism; apropos of a case

Se comunica un caso de carcinoma hepatocelular variedad fibrominar, asociado a fenómenos paraneoplásicos, en una mujer de 17 años. La presentación clínica fue con hipertiroidismo y cursó con metástasis pulmonares y en tejido muscular de región glútea. Se revisa la literatura científica, encontrándose sólo un caso relatado con similar cuadro endócrino (AU)

[Fibrolamellar hepatocellular carcinoma: a clinical report with paraneoplastic hyperthyroidism (apropos of a case)]. / Carcinoma hepatocelular fibrolaminar: presentación clínica con hipertiroidismo paraneoplásico (a propósito de un caso).

The case of a 17 years old female patient with fibrolamellar hepatocarcinoma and several paraneoplastic signs is reported. The clinical picture was hyperthyroidism like; subsequently metastasis lesions in lungs and muscular tissue (gluteal region) developed. Hyperthyroidism as clinical picture has been reported only once before us for the available literature reveals.

Carcinoma hepatocelular fibrolaminar: presentación clínica con hipertiroidismo paraneoplásico (a propósito de un caso). / [Fibrolamellar hepatocellular carcinoma: a clinical report with paraneoplastic hyperthyroidism (apropos of a case)]

The case of a 17 years old female patient with fibrolamellar hepatocarcinoma and several paraneoplastic signs is reported. The clinical picture was hyperthyroidism like; subsequently metastasis lesions in lungs and muscular tissue (gluteal region) developed. Hyperthyroidism as clinical picture has been reported only once before us for the available literature reveals.