Predictors for liver fibrosis in non-alcoholic patients with psoriatic diseases: A multicenter cross sectional-study.

Psoriasis has been related to metabolic dysfunction-associated fatty liver disease and, liver fibrosis. This study aimed to evaluate the prevalence of liver fibrosis in psoriasis and identify predictors for fibrosis. This is a cross-sectional study conducted from December 2012 to June 2016 assessing psoriasis and psoriatic arthritis patients attended at four centers in Mexico City. Data regarding history of the skin disease, previous and current medication, and previously diagnosed liver disease was collected. Liver fibrosis was assessed with four different non-invasive methods (FIB4, APRI, NAFLD score and elastography). We compared data based on the presence of fibrosis. Adjusted-logistic regression models were performed to estimate OR and 95% CI. A total of 160 patients were included. The prevalence of significant fibrosis using elastography was 25% (n = 40), and 7.5% (n = 12) for advanced fibrosis. Patients with fibrosis had higher prevalence of obesity (60% vs 30.8%, P = 0.04), type 2 diabetes (40% vs 27.5%, P = 0.003), gamma-glutamyl transpeptidase levels (70.8±84.4 vs. 40.1±39.2, P = 0.002), and lower platelets (210.7±58.9 vs. 242.8±49.7, P = 0.0009). Multivariate analysis showed that body mass index (OR1.11, 95%CI 1.02-1.21), type 2 diabetes (OR 3.44, 95%CI 1.2-9.88), and gamma-glutamyl transpeptidase (OR 1.01, 95%CI1-1.02) were associated with the presence of fibrosis. The use of methotrexate was not associated. Patients with psoriasis are at higher risk of fibrosis. Metabolic dysfunction, rather than solely the use of hepatotoxic drugs, likely plays a major role; it may be beneficial to consider elastography regardless of the treatment used. Metabolic factors should be assessed, and lifestyle modification should be encouraged.

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Expert recommendations for biological treatment in patients with psoriasis.

In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.

En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.

Recomendaciones de expertos para el tratamiento biológico en pacientes con psoriasis / Expert recommendations for biological treatment in patients with psoriasis

Resumen En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.

Abstract In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.

Association of Pathogenic Th17 Cells with the Disease Severity and Its Potential Implication for Biological Treatment Selection in Psoriasis Patients.

Psoriasis is an inflammatory autoimmune disease characterized by cutaneous lesions in plaques. It has been proposed that the immune response has a key role in the disease progression. Particularly, the Th17 cells through IL-17 can contribute to maintain the inflammatory process. The pathogenic Th17 phenotype has been described in human diseases and associated with high severity in inflammatory experimental models. However, it is not clear if the pathogenic phenotype could be present in the skin and peripheral blood as well as its possible association to severity in psoriasis. In the lesional skin, we found high infiltration of Th17 cells and the pathogenic phenotype, finding a correlation between the frequency of Th17 cells and the Psoriasis Area and Severity Index (PASI) score. In peripheral blood, we observed a pool of Th17 lymphocytes with potential to acquire pathogenic features. Interestingly, the percentage of pathogenic Th17 cells (CD4+ RORγt+ IFN-γ +) correlates with disease severity. Moreover, we distinguished three groups of patients based on their IL-17/IFN-γ production by Th17 lymphocytes, which seems to be related with a dynamic or stable potential to express these cytokines. Remarkably, we evaluated the cytokine production by Th17 cells as an immunological marker for the adequate selection of biologic therapy. We found that patients analyzed by this immunological approach and treated with antibodies against IL-17 and TNFα showed great improvement depicted by reduction in PASI and Dermatology Life Quality Index (DLQI) score as well as the percentage of Body Surface Area (BSA). Altogether, our results highlight the importance of the assessment of the pathogenic phenotype in Th17 cells as an immune personalized analysis with the potential to support the therapy choice in the clinical practice.

Biosimilar medicines for psoriasis. Positioning of the Mexican Academy of Dermatology.

The development and marketing of biosimilars opens a new scenario in the treatment of many pathologies, including psoriasis. This article reflects the position of the Mexican Academy of Dermatology (AMD) on the use of biosimilar medicines for the treatment of psoriasis in Mexico. In summary, the AMD estates that there is sufficient evidence to accept comparability of pharmacokinetics and pharmacodynamics of some biosimilar medicines to adalimumab, infliximab and etanercept; this evidence does not sufficiently support interchangeability or indication extrapolation. It is essential to establish a close pharmacovigilance not only to guarantee compliance with the Cofepris rules in Mexico, but also to facilitate the effective monitoring of the adverse effects of biosimilar medicines. Although the goal of biotechnological drugs is to achieve substantial savings for patients and public institutions, no economic criteria should prevail over rigorous scientific criteria that guarantee maximum therapeutic efficacy and optimum safety for patients.

El desarrollo y comercialización de biocomparables abre un nuevo escenario en el tratamiento de muchas patologías, entre ellas la psoriasis. El presente artículo recoge la postura de la Academia Mexicana de Dermatología (AMD) respecto al uso de medicamentos biocomparables para el tratamiento de la psoriasis en México. En resumen, la AMD establece que existe suficiente evidencia para aceptar la comparabilidad farmacocinética y farmacodinámica entre algunos medicamentos biocomparables al adalimumab, el infliximab y el etanercept; esta evidencia no sustenta suficientemente su intercambiabilidad ni la extrapolación de indicaciones; es fundamental establecer una farmacovigilancia estrecha no solo para garantizar el cumplimiento de las reglas de la Comisión Federal para la Protección contra Riesgos Sanitarios en México, sino para facilitar un seguimiento efectivo de los efectos adversos de los medicamentos biocomparables. Si bien la meta de los medicamentos biotecnológicos es lograr un ahorro sustancial para los pacientes y las instituciones públicas, los criterios económicos no deben anteponerse a criterios científicos rigurosos que garanticen la máxima eficacia terapéutica y la óptima seguridad para los pacientes.

[Diagnostic approach of erythroderma in the adult]. / Abordaje diagnóstico de la eritrodermia en el adulto.

Erythroderma consists on erythema and scaling that covers more than 90% of the cutaneous surface. It has multiple causes and for the most common we can use the acronym PALM (psoriasis, atopic dermatitis, lymphoproliferative disease and medication). It is important to diagnose the cause in order to get a prognosis and a targeted treatment. In 30% of the cases the cause is not evident and the patient requires periodic assessment to rule out evolution to a lymphoproliferative disease. In many cases, erythroderma is a chronic disease but it can also be a life-threatening dermatologic urgency that requires hospitalization.

La eritrodermia se caracteriza por eritema y escama en más del 90% de la superficie cutánea. Tiene muchas causas y es un reto para el dermatólogo identificarlas. Las más comunes se engloban en el acrónimo derivado de sus siglas en inglés PALM (psoriasis, dermatitis atópica, proceso linfoproliferativo y medicamentos). La importancia del diagnóstico certero es el tratamiento dirigido y el pronóstico. En los casos idiopáticos que llegan a ser de hasta el 30%, el paciente requiere de valoraciones periódicas por probable evolución a un proceso linfoproliferativo. Aunque en muchas ocasiones la eritrodermia es un cuadro crónico, también puede presentarse como una urgencia dermatológica que pone en riesgo la vida del paciente y requiere hospitalización.

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials.

INTRODUCTION: There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients. METHODS: Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup. RESULTS: Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator's Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52. CONCLUSIONS: Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients. FUNDING: Novartis Pharmaceutical Corporation.

A Human Lin- CD123+ CD127low Population Endowed with ILC Features and Migratory Capabilities Contributes to Immunopathological Hallmarks of Psoriasis.

Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127- ILC populations and an early ILC precursor (EILP) CD127low. ILC development has predominately been investigated in mouse models. However, in humans, different transcription factors have been described for ILC identification. NFIL3 (nuclear factor, IL-3 regulated) is crucial for ILC development in response to IL-7. CD123 (IL-3Rα) is usually used to exclude basophils during ILC identification, however, it is unknown if in response to IL-3, NFIL3 could be relevant to induce ILC features in Lin- CD123+ populations in addition, is also unknown whether peripheral blood (PB) population with ILC features may have skin-homing potential to participate in skin inflammatory chronic diseases. Here, we report a Lin- CD123+ CD127low CD7+ CLA+ population that share some phenotypic properties with basophils, but expresses several transcription factors for ILC commitment such as inhibitor of DNA binding 2 (Id2), NFIL3, promyelocytic leukemia zinc finger (PLZF), thymocyte selection-associated high-mobility group box protein (TOX), and T cell factor-1 (TCF-1). In addition, this population expresses different ILC markers: CD132, CD90, CD161, α4 integrin, c-Kit, CRTH2, AhR, and IL-23R. IL-3 prevents apoptosis and increases their NFIL3, TOX, and PLZF expression. In PB, the CD123+ CD127low population is predominantly a conspicuous population that expresses T-bet and RORγt. The Lin- CD123+ CD127low population in PB has a limited Th type cytokine expression and highly expresses IL-8. The Lin- CD123+ CD127low population expresses skin-homing receptors (cutaneous lymphocyte antigen and CXCR4) and transmigrates through endothelial cells in response to SDF-1. An equivalent Lin- CD123low population was identified in control skin, which shows a broader phenotypic diversity and cytokine production, including IL-22 and IL-17. Remarkably, the CD123low population in the lesion and non-lesion skin of psoriasis patients expresses IL-17 and IL-22. Our findings suggest the identification of an alternative Lin- CD123+ CD127low population with ILC features endowed with migratory capabilities that might contribute to immunopathological hallmarks of psoriasis.

[Mexican treatment goals for plaque psoriasis]. / Metas mexicanas de tratamiento de psoriasis en placas.

Psoriasis is a chronic inflammatory disease with a worldwide prevalence between 6 and 39% in moderate to severe forms. In European countries like Germany and England was identified that only one third of patients with moderate to severe forms will receive systemic management, this fact motivated to integrate into Europe an international consensus on treatment goals with the aim of providing support to the dermatologist by algorithms that serve as a therapeutic guide that allows you to gain control short and long term effects of this disease. The European group met to develop the definitions of severity of psoriasis, treatment goals for moderate to severe disease, and optimization options and / or therapeutic transition than a paper published in 2011 was obtained. In Mexico a working group of experts on biological therapy (GTEB), made up of 10 members and an extended group of 150 dermatologists' voters in the country for the purpose of issuing Mexico's position on the proposals of the European group was formed. In this document the findings of the Working Group of Experts on Biological Therapy in Mexico are listed.

La psoriasis es una enfermedad crónica inflamatoria, con una prevalencia mundial entre 6 y 39% en las formas moderadas a severas. En países europeos como Alemania e Inglaterra se identificó que solo la tercera parte de los pacientes que padecen formas moderadas a severas reciben manejo sistémico; este hecho motivó la integración en Europa de un consenso internacional sobre metas de tratamiento con el objetivo de brindar apoyo al dermatólogo con algoritmos que sirvan como guía terapéutica para lograr el control a corto y largo plazo de esta enfermedad. El grupo europeo se reunió para elaborar las definiciones de severidad de la psoriasis, las metas de tratamiento en la enfermedad moderada a severa, entre otros temas, de lo que se obtuvo un documento publicado en el 2011. En México se conformó un grupo de trabajo de expertos en terapia biológica (GTEB), formado por 10 integrantes y un grupo extendido de 150 dermatólogos votantes del país, con la finalidad de emitir la posición de México sobre las propuestas del grupo europeo. En el presente documento se enumeran las conclusiones del grupo de trabajo de expertos en terapia biológica en México.

[Antihistamines for the treatment of urticaria in Mexico]. / Antihistamínicos en el tratamiento de la urticaria en México.

There are four types of histamine receptors. Allergic symptoms, especially those in rhinoconjunctivitis and urticaria, are mainly caused by activation of histamine receptor 1 (H1). Consequently, oral H1-antihistamines form and integral part of the treatment of these diseases. Antihistamines are inverse agonists that stabilize the non-active configuration of the histamine receptor. First generation H1-antihistamines cause a variety of adverse effects via several mechanisms: sedation (accumulation in the central nervous system), dry mouth, urinary retention, weight gain (low selectivity: stimulation of serotonin/muscarinic/alpha-adrenergic receptors) and drug interactions (substrate of CYP450-3A4). Generally second generation H1-antihistamines have a better safety profile. New guidelines on allergic rhinitis and urticaria recommend second generation H1-antihistamines as first line drugs, with -if necessary- four-times updosing to obtain control in urticaria. The enhanced efficacy of quadruple doses in urticaria, while maintaining a good safety profile, has been shown for bilastine, desloratadine and levocetirizine (rupatadine). For ebastine and fexofenadine only the safety of quadruple doses has been shown till now. Extreme precaution should be taken with astemizol and terfenadine that never should be up-dosed, as high serum concentrations can cause potentially fatal ventricular tachycardia. First generation antihistamines are not recommended as first line treatment and updosing is not safe.

Existen cuatro tipos de receptores histaminérgicos. Los síntomas de alergia, especialmente rinoconjuntivitis alérgica y urticaria, son principalmente causados por activación del receptor H1; por ende, los antihistamínicos H1 orales (anti-H1) forman parte integral del tratamiento de estas enfermedades. Los antihistamínicos son agonistas inversos, porque estabilizan la forma inactiva del receptor. Los antihistamínicos H1 de primera generación producen efectos adversos por varios mecanismos: sedación (fijación a receptores H1 cerebrales), boca seca, retención urinaria, aumento de peso (baja selectividad: estimulación de los receptores de serotonina, muscarina y alfa-adrenérgicos) e interacciones medicamentosas (con sustrato de citocromo P450-3A4). Los antihistamínicos H1 de segunda generación son generalmente más seguros. Las nuevas guías de tratamiento de la rinitis alérgica y urticaria recomiendan como manejo de primera intención a los antihistamínicos H1 de segunda generación. En urticaria se recomienda hasta cuadruplicar su dosis en caso necesario. El aumento de la eficacia en el control de la urticaria con cuádruple dosis, sin que se afecte la seguridad, se ha documentado para bilastina, desloratadina y levocetirizina (rupatadina). Respecto de ebastina y fexofenadina, hasta ahora, sólo se comprobó la seguridad de cuádruple dosis. Una rigurosa excepción son astemizol y terfenadina, que a concentraciones séricas elevadas pueden causar taquicardia ventricular. No se recomiendan los antihistamínicos H1 de primera generación y aumentar su dosis no es seguro.

[Mexican guidelines on the diagnosis and treatment of urticaria]. / Guía Mexicana para el Diagnóstico y el Tratamiento de la Urticaria.

BACKGROUND: Urticaria is a disease that a fifth of the population shallsuffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups -both specialists and primary health care workers-, necessary in Mexico. MATERIAL AND METHOD: Internationally recognized tools for guidelinedevelopment were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline development) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. RESULTS: By a formal process of discussion and voting during several working-sessions, experts and first level healthcare physicians determined the wording of the final guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as first line treatment is emphasized. CONCLUSION: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, first line health care physicians and specialists.

Antecedentes: la urticaria es una enfermedad que padece una quinta parte de la población en algún momento de su vida. Las guías internacionales recientes han propuesto unos cambios de fondo en su diagnóstico y tratamiento, por lo que había la necesidad de crear una guía nacional y multidisciplinaria, con base amplia en los gremios de especialistas y médicos de primer contacto en México. Material y método: un grupo interdisciplinario de expertos clínicos y algunos expertos en metodología determinó los objetivos y alcances de la Guía de Práctica Clínica Basada en Evidencia con el instrumento SCOPE. Se decidió llevar a cabo la adaptación y transculturización de guías internacionales para el diagnóstico y tratamiento de urticaria. Con el instrumento AGREE-II se seleccionaron las tres guías de alta calidad, como guías base (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) para formular y contestar la preguntas clínicas clave, en el contexto cultural y económico mexicano, según el método de desarrollo de recomendaciones GRADE. Resultados: mediante un proceso formal de discusión y votación durante varias juntas de expertos, se terminó la redacción de la forma final de la guía, con especial cuidado de lograr un ajuste a las realidades, valores y preferencias de los pacientes de México. Se hace hincapié en la administración de antihistamínicos vía oral de segunda generación, como tratamiento de primera elección. Conclusión: este documento es una Guía de Práctica Clínica Basada en Evidencia para el diagnóstico y tratamiento de urticaria aguda y crónica, basada en tres guías internacionales de alta calidad. Se desarrolló por un grupo multidisciplinario. Los cuadros y algoritmos hacen a la guía amigable para su uso por médicos de primer contacto y por especialistas.

Necrotic carpal tunnel syndrome in a child.

Median nerve entrapment at the wrist level causes carpal tunnel syndrome (CTS). Although frequent in adults, CTS is a rare entity in children. Bouvier described an exceptional necrotic variant in 1979 in which skin, nail, and bone lesions are typical. We report the case of a 10-year-old child with necrotic CTS secondary to trauma. To our knowledge, this is the first case reported in a child.