Losartan ameliorates renal fibrosis by inhibiting tumor necrosis factor signal pathway / Losartán mejora la fibrosis renal al inhibir la vía de señalización del factor de necrosis tumoral

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-β1 (TGF-β1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway.(AU)

El Losartán es ampliamente utilizado en el tratamiento de la enfermedad renal crónica (CKD) y ha logrado buenos resultados clínicos, pero su mecanismo exacto aún no está claro. Utilizamos la técnica de secuenciación de alto rendimiento (HTS) para detectar posibles dianas de losartán para el tratamiento de la CKD. Según los resultados de HTS, encontramos un enriquecimiento de la vía de señalización del factor de necrosis tumoral (TNF). Así, realizamos experimentos in vivo e in vitro para verificar esto. Encontramos que, tanto en ratas con obstrucción ureteral unilateral (uuo) como en células epiteliales tubulares renales proximal humanas (HK-2) tratadas con factor de crecimiento transformador β1 (TGF-β1), se activó la vía de señalización del TNF. El losartán inhibe significativamente la expresión de las vías de señalización del TNF y genes relacionados con la fibrosis, como COL-1, α-SMA y vicentin. Estos datos sugieren que el losartán puede mejorar la fibrosis renal regulando la vía del TNF.(AU)

Antagonistas del factor de necrosis tumoral (TNF) en la enfermedad inflamatoria intestinal pediátrica: Una revisión sistemática / Tumour necrosis factor (TNF) antagonist therapy for paediatric inflammatory bowel disease: A systematic review

La enfermedad inflamatoria intestinal incluye 2 enfermedades crónicas inflamatorias, la colitis ulcerosa y la enfermedad de Crohn. Su carga de enfermedad está aumentando en el mundo. Se han publicado algunas revisiones que evalúan el uso pediátrico de los antagonistas del factor de necrosis tumoral (TNF), aunque incluyen mayoritariamente estudios observacionales y no consideran las evaluaciones económicas. En esta revisión sistemática se evalúa la evidencia disponible en cuanto a eficacia, seguridad y coste-efectividad de los antagonistas del TNF en el tratamiento de la enfermedad inflamatoria intestinal pediátrica. Se realizaron búsquedas en PubMed/MEDLINE, Embase y Cochrane Central (hasta mayo de 2022). Se incluyeron 9 ensayos clínicos aleatorizados y 4 evaluaciones económicas que estudiaran alguno de los fármacos anti-TNF (infliximab, adalimumab, golimumab, certolizumab) frente a diferentes alternativas. En los estudios que evaluaron la eficacia del tratamiento anti-TNF en enfermedad de Crohn, la mayoría valoraron la pauta de mantenimiento en pacientes que previamente habían respondido a la inducción (respuesta=28-63%, y remisión clínica=17-83% dependiendo de la dosis, fármaco y seguimiento). En colitis ulcerosa, el tratamiento de mantenimiento con anti-TNF presentó tasas de remisión clínica entre 17-44%. Nueve estudios mostraron información sobre acontecimientos adversos. No se encontraron ensayos clínicos que compararan diferentes fármacos anti-TNF. Los resultados de esta revisión indican que el tratamiento de mantenimiento con fármacos anti-TNF (como infliximab y adalimumab) en la enfermedad inflamatoria intestinal pediátrica es probablemente eficaz y seguro. Sin embargo, las evaluaciones económicas incluidas presentaron resultados contradictorios sobre las razones coste-efectividad (AU)

Inflammatory bowel disease includes two chronic inflammatory diseases, ulcerative colitis and Crohn's disease. The burden of disease is increasing worldwide. A few reviews evaluating the paediatric use of tumour necrosis factor (TNF) antagonists have been published, although these mostly include observational studies and do not consider economic evaluations. This systematic review evaluated the available evidence regarding the efficacy, safety, and cost-effectiveness of TNF antagonist therapy for paediatric inflammatory bowel disease. We searched PubMed/MEDLINE, Embase, and Cochrane Central (up to May 2022). Nine randomized clinical trials and four economic evaluations that examined any anti-TNF drugs (e.g., infliximab, adalimumab, golimumab, and certolizumab) against different alternatives were included. In studies evaluating the efficacy of anti-TNF drugs in Crohn's disease, most assessed the efficacy of maintenance regimen in patients who had previously responded to induction (response=28%–63%, and clinical remission=17%–83% depending on dose, drug, and follow-up). In ulcerative colitis, maintenance treatment with anti-TNF drugs reported clinical remission rates between 17% and 44%. Nine studies reported information on adverse events. No clinical trials comparing different anti-TNF drugs were found. The findings from this review suggest that maintenance treatment with anti-TNF drugs (such as infliximab and adalimumab) in paediatric inflammatory bowel disease is probably effective and safe. However, the economic evaluations reported contradictory results of the cost-effectiveness ratios (AU)

Prevalence of aphthous stomatitis in patients with inflammatory bowel disease after the treatment with monoclonal antibodies: a systematic review and meta-analysis

Background: Currently, the most frequently employed therapies in the treatment of inflammatory bowel diseases (IBD), i.e., Crohn's Disease (CD), Ulcerative Colitis (UC) or unclassified IBD (IBD-U) are monoclonal anti-TNFs and anti-integrin therapies, such as vedolizumab (VDZ). Forty-seven per cent of these patients present extra-intestinal manifestations, the second most prevalent being aphthous stomatitis (AS). The present study aims to investigate which of the two therapies is associated with a lower prevalence of AS after treatment. Material and methods: An electronic search of the MEDLINE (via PubMed), Web of Science, SCOPUS, LILACS and OpenGrey databases was carried out. The criteria used were those described by the PRISMA Statement. The search was not temporarily restricted and was updated to January 2022. The quality assessment was analyzed using the JBI Prevalence Critical Appraisal Tool. Results: After searching, 7 studies were included that met the established criteria. Of these, 6 analysed the prevalence of AS in CD patients and 4 in UC. A total of 1,744 patients were analysed (CD=1,477 patients; 84.69%; UC=267; 15.31%). The greatest reduction in AS prevalence was observed after anti-TNF therapy. The effect of these therapies on the prevalence of AS in patients with IBD-U could not be determined. Conclusions: Both biologic therapies achieve a reduction in the prevalence of AS in IBD patients (CD and UC). However, the best results were obtained in patients treated with anti-TNFs, possibly because VDZ is often used in patients who do not respond adequately to previous treatment with anti-TNFs and because of its intestinal specificity. (AU)

Intensificación de Ustekinumab en enfermedad de Crohn: Revisión sistemática / Ustekinumab intensification in Crohn’s disease: a systematic review

Introducción: Ustekinumab surge como una alternativa terapéutica en enfermedad de Crohn en pacientes con fracaso a anti-TNF. Sin embargo, en muchas ocasiones, es habitual tener que reducir/acortar sus tiempos de admi-nistración para evitar el fracaso terapéutico. El objetivo de esta revisión sistemática es evaluar la efectividad de la intensificación de ustekinumab mediante el acortamiento de su intervalo terapéutico. Método: Se realizó una revisión sistemática de la literatura basada en las directrices de la declaración PRISMA. Se consultaron las bases de datos Medline, Embase y Web of Science, incluyéndose estudios con adultos diagnostica-dos de enfermedad de Crohn moderada o grave a los que se le hubiera realizado como intervención un cambio de posología del fármaco ustekinumab mediante acortamiento de intervalo a cada 4 semanas. Resultados: Se incluyeron 5 artículos, siendo uno de ellos una revisión sistemática. A los 6 meses se muestran tasas de remisión clínica en torno al 45%, una reducción media de 3 puntos en el índice de Harvey Bradshaw sobre el nivel basal, así como una normalización de niveles de PCR en un 21% de los pacientes. Conclusiones: Los resultados apoyan el uso del acortamiento de intervalo de ustekinumab como una opción te-rapéutica efectiva y útil para pacientes con pérdida de respuesta a la pauta habitual. Sin embargo, se recomienda realizar nuevos estudios de diseño experimental que aumenten el nivel de evidencia existente. (AU)

Introduction: Ustekinumab emerges as a therapeutic alternative in Crohn’s disease in patients with anti-TNF fail-ure. However, on many occasions, it is common to have to reduce/shorten their administration times to avoid thera-peutic failure. The objective of this systematic review is to evaluate the effectiveness of ustekinumab intensification by shortening its therapeutic interval. Method: A systematic review of the literature based on the guidelines of the PRISMA statement was performed. The Medline, Embase and Web of Science databases were consulted, including studies with adults diagnosed with moderate or severe Crohn’s disease who had undergone a change in ustekinumab dosage as an intervention by shortening the interval to every 4 weeks. Results: Five articles were included, one of them being a systematic review. At 6 months, clinical remission rates of around 45% are shown, an average reduction of 3 points in the Harvey Bradshaw index over baseline, as well as a normalization of CRP levels in 21% of patients. Conclusions: The results support the use of ustekinumab interval shortening as an effective and useful therapeutic option for patients with loss of response to the usual regimen. However, it is recommended to carry out new studies of experimental design that increase the level of existing evidence. (AU)

Survey of immunopharmacological effects of botulinum toxin in cell signaling of bronchial smooth muscle cells in allergic asthma

Background Asthma is a lung disease that has influenced more than 350 million people worldwide. Airway smooth muscle (ASM) spasm leads to airway hyperresponsiveness (AHR) and bronchial obstruction, which are clinical manifestations of an asthma attack. Botulinum toxin (BTX) is a bacteria toxin that acts as muscle relaxant and may have therapeutic effects on AHR and asthma.Objective In this study, the effect of BTX on AHR and related gene expressions was evaluated.Material and Methods An asthma mice model was developed which was treated with BTX in two ways: intranasally (IN) and via nebulization (N) (0.01, 0.1, and 1 U/mL and 10 U/mL, respectively) on days 25, 27 and 29. AHR was evaluated on days 24, 26, 28, and 30, and gene expressions were evaluated for TrkA, TrkB, M1–M5, α7nAChR, TNF-α, and extracellular signal-regulated kinase 2 (ERK2) proteins. For histopathology of the lungs, perivascular and peribronchial inflammation, production of mucus, and goblet cell hyperplasia were studied.Results On day 24, treatment with BTX (for all doses) had no significant effect on AHR, but on days 26 and 28, AHR was decreased and this continued up to day 30 for all treated groups. Treatment with BTX had no significant effect on the gene expressions of TrkA, TrkB, M1–M5, α7nAChR, TNF-α, and ERK2 proteins, perivascular inflammation, peribronchial inflammation, hyperplasia of the goblet cell and production of mucus. Besides, mice administered with 10 mg/mL BTX perished. The BTX therapy controlled asthma attacks by decreasing AHR and relaxation of ASMs.Conclusion However, BTX had no significant effect on airway inflammation and production of mucus. While using BTX, it is necessary to prescribe safe doses in order to prevent adverse reactions (AU)

Medication adherence and persistence of psoriatic arthritis patients treated with biological therapy in a specialty pharmacy in Brazil: a prospective observational study

Pharmaceutical services in Brazil provide access, supply, and rational use of drugs for all population and an effort has been made to improve the quality of these services. Biological drugs are high-cost drugs supplied in Brazil that can inhibit disease progression and improve the quality of life of psoriatic arthritis (PsA) patients. However, some patients did not achieve therapeutic goals. Objective: To evaluate the medication adherence and persistence of PsA patients treated with tumor necrosis factor inhibitors (anti-TNF) drugs and their associated factors. Methods: A prospective observational study was performed at a single-specialty pharmacy in Belo Horizonte, Brazil. Medication adherence, persistence, and clinical outcomes were evaluated at 12 months of follow-up. Medication persistence was historically compared to overall PsA patients treated in Brazil. Associated factors were identified through log-binomial regression. Results: One hundred ninety-seven PsA patients were included in the study, of whom 147 (74.6%) and 142 (72.1%) had medication adherence and persistence, respectively. Patients treated with infliximab presented the highest adherence (90.5%) and persistence rate (95.2%) in comparison to patients treated with other drugs, except for adalimumab versus infliximab for adherence outcome. All clinical measures significantly improved in patients with medication adherence and persistence. Medication persistence was higher for patients attended by specialty pharmacy than other PsA patients in Brazil. The associated factors to higher medication adherence were lower disease activity by BASDAI, being non-white race, and intravenous drug use. The associated factors to higher medication persistence were lower disease activity by Bath Ankylosing Spondylitis Activity Index (BASDAI), intravenous drug use, non-use of corticoids and non-steroidal anti-inflammatory drugs, and comorbidity (AU)

Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies / Infecciones fúngicas como consecuencia de tratamientos con anticuerpos monoclonales y otras terapias inmunomoduladoras

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease

El factor de necrosis tumoral (TNF) es una citocina proinflamatoria involucrada en una amplia gama de procesos fisiológicos importantes y desarrolla un papel en la patogenia de algunas enfermedades. Los antagonistas del TNF (infliximab, adalimumab, etanercept) son efectivos en el tratamiento de afecciones inflamatorias. Los agentes biológicos antilinfocitarios (rituximab, alemtuzumab), los antagonistas de la integrina (natalizumab, etrolizumab y vedolizumab), de la interleucina 17A (secukinumab, ixekizumab) o los antagonistas de la IL-2 (daclizumab, basiliximab) se usan ampliamente después del trasplante y en trastornos gastroenterológicos, reumatológicos, dermatológicos, neurológicos y hematológicos. Dado el papel relevante de estos elementos de defensa del huésped contra agentes bacterianos, virales y fúngicos, el riesgo de infección durante el tratamiento con estos antagonistas genera preocupación. Las infecciones por hongos, tanto oportunistas como endémicos, se han asociado con estas terapias biológicas, pero la relación causal no está clara, especialmente entre los pacientes con un control deficiente de su enfermedad subyacente o que están recibiendo terapia con esteroides. Los pacientes en tratamiento con estos medicamentos deben ser examinados para detectar infecciones micóticas endémicas latentes. La profilaxis con cotrimoxazol podría ser útil para prevenir la infección por Pneumocystis jirovecii en pacientes mayores de 65 años que estén tomando antagonistas de TNF, agentes biológicos antilinfocitarios, o tengan linfopenia y estén en tratamiento concomitante con esteroides. Al igual que con otros fármacos inmunosupresores, deben suspenderse los antagonistas de TNF y los anticuerpos antilinfocitarios en pacientes con enfermedad infecciosa activa hasta su control

Supervivencia a largo plazo de los fármacos biológicos anti-TNF subcutáneos administrados durante los años 2008-2012 en una cohorte de pacientes con artritis reumatoide / Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients

Objetivo: Comparar la supervivencia de los anti-TNF subcutáneos utilizados durante el periodo 2008-2012 según práctica clínica. Material y métodos: Estudio observacional retrospectivo de todos los pacientes diagnosticados de AR que habían iniciado tratamiento con un anti-TNF subcutáneo y mantenido durante al menos 6 meses. Los datos fueron analizados mediante SPSS V17,0. Resultados: Cuarenta y nueve pacientes con AR iniciaron tratamiento con anti-TNF subcutáneo (32 con etanercept y 17 con adalimumab). La media de edad fue de 45,94 años (75,5% mujeres). La media de duración de la enfermedad previa al inicio del anti-TNF fue de 2,67 años. La media de edad al inicio del tratamiento fue de 51,84 años, índice de actividad de la enfermedad en 28 articulaciones medio de 4,93. La supervivencia media del tratamiento anti-TNF fue de 8,40 años, mostrando una mayor supervivencia etanercept. La principal razón de discontinuación fue por fallo secundario (90,9%). Conclusión: En la práctica clínica habitual, la supervivencia a largo plazo de los tratamientos anti-TNF subcutáneos fue elevada e independiente de que tuvieran o no tratamiento inmunosupresor concomitante

Objective:To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. Material and methods:Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. Results:Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). Conclusions:In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy

Efectividad y seguridad en nuestro entorno de adalimumab como tratamiento anti-TNF de primera linea en niños con enfermedad de Crohn / A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease

Introducción y objetivos: Adalimumab (ADA), anticuerpo anti-TNF-α monoclonal recombinante de origen humano, generalmente se emplea como tratamiento de segunda línea en niños con enfermedad de Crohn (EC) que no han respondido o han perdido respuesta a infliximab (IFX). En las series publicadas más del 70% de los pacientes habían sido tratados inicialmente con IFX. Los datos sobre la eficacia a corto y a largo plazo de ADA en pacientes naïve a anti-TNF son muy limitados. El objetivo del presente estudio es describir nuestra experiencia con ADA como tratamiento anti-TNF de primera línea en niños con EC. Material y método: Estudio multicéntrico, retrospectivo que incluye pacientes con EC tratados con ADA como anti-TNF de primera línea. Resultados: Se incluyeron 62 pacientes (34 varones) con una edad media de 13,0 ± 2,4años, un tiempo de evolución de la enfermedad de 7,3 meses (RIQ 2,7-21) y un wPCDAI de 35 puntos (RIQ 24,3-47,5). En el momento de comenzar ADA, 58 pacientes (93,5%) estaban recibiendo tratamiento inmunomodulador. A las 12 semanas de tratamiento el 80,6% (50/62) habían alcanzado la remisión clínica, así como el 95% (57/60) a las 52 semanas. Ocho pacientes (13%) presentaron efectos adversos. Se constató un incremento significativo de los z-scores de talla, velocidad de crecimiento e índice de masa corporal (IMC) a las 52 semanas de tratamiento, en especial en aquellos con retraso de crecimiento. Conclusiones: El tratamiento con ADA favorece una remisión clínica prolongada en pacientes naïve a anti-TNF. El tratamiento con ADA mejora la velocidad de crecimiento en niños con EC y retraso de crecimiento al inicio del tratamiento (AU)

Background and objectives: Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term effectiveness of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients. Material and methods: This is a multicentre retrospective study including anti-TNF naïve paediatric CD patients treated with ADA as first-line anti-TNF. Results: Sixty-two patients (34 males), with a mean age of 13.0 ± 2.4years and a disease duration of 7.3 (IQR 2.7-21) months were included. Median wPCDAI was 35 (IQR 24.3-47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline. Clinical remission at week 12 was achieved in 50 out of 62 (80.6%) and in 57 out of 60 (95.0%) at week 52. Eight patients (13%) reported adverse events. Mean height, growth rate and BMI z-scores improved significantly between baseline and week 52, especially in patients with growth failure. Conclusions: ADA treatment leads to lasting clinical remission in anti-TNF naïve paediatric patients with CD. ADA significantly improved growth rate in children with CD who had growth delay at baseline (AU)

Evolution over thirty years of the profile of inpatients with reactive arthritis in a tertiary rheumatology unit / Evolución durante 30 años del perfil de pacientes hospitalizados con artritis reactiva en una unidad de reumatología de tercer nivel

Reactive arthritis (ReA) is sterile arthritis occurring after extra articular bacterial infection. The aim of this study was to analyze, over 30 years, clinical, biological and imaging characteristics as well as therapeutic management of new cases of ReA, comparing two periods. Methods. retrospective monocentric study, data of all the patients followed in our unit between January 1st 1984 and April 2014 with the diagnosis or ReA were analyzed (clinical and biological features, management and outcome), and compared between two periods: from January 1984 to December 1993, and from January 2004 to December 2013. Results. Sixty two patients fulfilling international diagnosis criteria were analyzed. There was no significant difference between the two periods in number of new cases, clinical presentation, biological data or outcome. Changes in therapeutic management were obvious with occurrence of anti TNF in the recent period. Conclusion. Reactive arthritis is still a current rheumatologic problem in a developed country, with a need of early and tailored rheumatologic management (AU)

Las artritis reactivas (ARe) son artritis estériles que se manifiestan después de una infección bacteriana extraarticular. El objetivo de este estudio es analizar, durante 30 años, las características clínicas, biológicas e imagenológicas, así como la gestión del tratamiento de la ARe, mediante la comparación de 2 periodos. Métodos. Estudio retrospectivo monocéntrico. Se analizaron los datos de todos los pacientes diagnosticados con ARe en nuestra unidad entre el 1 de enero de 1984 y abril de 2014 (rasgos clínicos y biológicos, gestión y resultados) y se compararon con 2 periodos: de enero de 1984 a diciembre de 1993, y de enero de 2004 a diciembre de 2013. Resultados. Se analizaron los datos de 62 pacientes que cumplieron los criterios de diagnóstico internacionales. No existió una diferencia significativa entre los 2 periodos en la cantidad de casos, presentación clínica, datos biológicos o resultados. Los cambios de la gestión del tratamiento fueron evidentes, con la aparición de anti-TNF en el periodo reciente. Conclusión. La artritis reactiva continúa siendo un problema reumatológico actual en los países desarrollados, con una necesidad de tratamiento reumatológico temprano y personalizado (AU)

Panarteritis nudosa con patrón de respuesta inflamatoria sistémica: respuesta a anti-TNF / Polyarteritis Nodosa with a Systemic Inflammatory Response Pattern: Effectiveness of anti-TNF

No disponible

Pioderma gangrenoso: terapias clásicas y emergentes / Pyoderma gangrenosum: Classic and emerging therapies

El pioderma gangrenoso es una dermatosis ulceronecrótica que representa un desafío importante para el clínico no solo porque puede simular otras dermatosis, sino porque en general no responde a los tratamientos habituales. Durante el último año han surgido nuevos estudios acerca de la eficacia real de los tratamientos convencionales, tales como la ciclosporina y los glucocorticoides sistémicos. Estos estudios han demostrado que los tratamientos clásicos son comparables pero insuficientes como monoterapia. Han surgido nuevos tratamientos, como los agentes ahorradores de glucocorticoides, los inhibidores del factor de necrosis tumoral y la cirugía. Esta revisión es una puesta al día de la evidencia actual para el tratamiento del pioderma gangrenoso (AU)

Pyoderma gangrenosum is an ulceronecrotising dermatosis that represents a challenge for any clinician, not only for its ability to mimic other dermatoses but also for its lack of response to treatment. During the past year, there have been new studies about the efficacy of standard therapies, such as cyclosporine and systemic corticosteroids. These studies showed that classic treatment was comparable, but they are insufficient as monotherapy. That being said, new emerging therapies are becoming important, as the use of corticosteroid-sparing agents, tumour necrosis factor inhibitors or even surgery. This review updates the current evidence for the treatment of pyoderma gangrenosum (AU)

Psoriasis e hígado graso no alcohólico / Psoriasis and Nonalcoholic Fatty Liver Disease

El hígado graso no alcohólico es la principal causa de enfermedad hepática en nuestro medio. Los pacientes con psoriasis presentan mayor prevalencia y gravedad y peor pronóstico de esta hepatopatía. El vínculo patogénico entre ambas es el estado de inflamación crónica y la resistencia periférica a la insulina, habitual en las comorbilidades asociadas a la psoriasis. Por este motivo, en la evaluación de los pacientes con psoriasis, en particular si existen componentes del síndrome metabólico y se requiere tratamiento sistémico, se recomienda descartar esta posibilidad. La coexistencia de psoriasis e hígado graso no alcohólico, con probable sinergia entre ambos, condiciona las medidas generales que deben recomendarse en estos pacientes y también la estrategia terapéutica, por la potencial hepatotoxicidad de algunos de ellos. En este sentido, algunos de los fármacos convencionales habituales como acitretino, metotrexato o ciclosporina presentan potenciales efectos hepatotóxicos cuya repercusión en cada paciente debe evaluarse de forma individualizada. Los fármacos anti-TNF podrían tener efectos beneficiosos fundamentados en el buen control del proceso inflamatorio y de una mejoría de la resistencia periférica a la insulina. Sin embargo, se han descrito casos de hepatotoxicidad en algunos pacientes. No existe evidencia de efectos beneficiosos o perjudiciales de los fármacos anti p40 o anti IL-17 (AU)

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects (AU)

Nuevos tratamientos en psoriasis / New treatments in psoriasis

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Meningitis por Moraxella catarrhalis durante tratamiento con certolizumab / Moraxella catarrhalis meningitis during certolizumab pegol treatment

No disponible

Fármacos anti-TNF, anticuerpos antinucleares y autoinmunidad en pacientes con psoriasis / Tumor Necrosis Factor Inhibitors, Antinuclear Antibodies, and Autoimmunity in Patients With Psoriasis

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Inducción de anticuerpos y enfermedades autoinmunes en pacientes con psoriasis tratados con fármacos anti-TNFalfa / Induction of Autoantibodies and Autoimmune Diseases in Patients with Psoriasis Receiving Tumor Necrosis Factor Inhibitors

Introducción: Se ha descrito la inducción de anticuerpos antinucleares (ANA) y el desarrollo de enfermedades autoinmunes tras el tratamiento con fármacos anti-TNFα, aunque existe controversia sobre su significado. Objetivos: Determinar la aparición de enfermedades autoinmunes y de autoanticuerpos en pacientes psoriásicos tratados con fármacos anti-TNFα subcutáneos (adalimumab y etanercept). Relacionar su desarrollo con la efectividad del tratamiento, posibles efectos adversos y con el orden de administración del fármaco anti-TNFα. Evaluar los factores predictores de aparición de ANA y de enfermedades autoinmunes. Métodos: Estudio retrospectivo sobre una cohorte de 121 pacientes seguidos en un período de 11 años. Se determinaron los ANA (si fueran positivos), también se investigaron los anticuerpos anti-ADN de doble cadena y los anticuerpos extraíbles del núcleo basales a los 3, 6, 12 meses (admitiendo en el estudio a aquellos pacientes con una determinación basal y otra durante el primer año) y posteriormente cada año. En cada consulta se calculó el Psoriasis area and severity index y se recogieron los posibles efectos adversos. Resultados: Durante el tratamiento de la psoriasis moderada-grave con adalimumab y etanercept se produce un aumento significativo en la positivización de los ANA, no acompañada del desarrollo de enfermedades autoinmunes. No se observa correlación con la efectividad del tratamiento, el orden cronológico de utilización de los fármacos anti-TNFα ni, aparentemente, con la aparición de efectos adversos. No se demuestran factores predictores del desarrollo de ANA excepto el índice de masa corporal. Conclusión: Recomendamos la determinación de ANA y el despistaje de enfermedades autoinumnes previos al tratamiento con fármacos anti-TNFα, pero no una determinación seriada y rutinaria durante el seguimiento, excepto en aquellos casos en los que existan signos o síntomas de sospecha de enfermedad autoinmune (AU)

Background: The induction of antinuclear antibodies (ANA) and the onset of autoimmune diseases have been reported after treatment with tumor necrosis factor (TNF) inhibitors, though controversy persists. Objectives: To determine the frequency of onset of autoimmune diseases and of the appearance of autoantibodies in psoriasis patients administered TNF inhibitors (adalimumab and etanercept) subcutaneously and to correlate this with the effectiveness of treatment, adverse effects, and the order of use of TNF inhibitors. We also tried to identify any factors that might predict the appearance of ANA and autimmune diseases. Methods: We performed a retrospective study of a cohort of 121 patients monitored over an 11-year period. ANA were measured at baseline and at 3, 6, and 12 months; positive results were followed up by study of antibodies to double-stranded DNA. Extractable nuclear antigen (ENA) antibodies were also studied at baseline and at 3, 6, and 12 months. Patients with a baseline assay of ANA and ENA at least one more assay during the first year were included in the study, and these antibodies were measured annually thereafter. Psoriasis area severity index was calculated and adverse effects were recorded at each visit. Results: A significant increase in ANA positivity was observed during treatment of moderate-to-severe psoriasis with adalimumab and etanercept, but this was not associated with the onset of autoimmune diseases. No correlation was observed with treatment efficacy, the order of use of TNF inhibitors, or the appearance of adverse effects. No predictive factors for the appearance of ANA were identified, except for the body mass index. Conclusions: We recommend ANA measurement and screening for autoimmune diseases prior to treatment with TNF inhibitors, but not routine serial measurements of ANA during follow-up except in patients with signs or symptoms suggestive of autoimmune disease (AU)

Pustulosis palmoplantar por adalimumab en un paciente con enfermedad de Crohn / Palmoplantar pustulosis by adalimumab in a patient with Crohn disease

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Radionecrosis versus progresión de la enfermedad en metástasis cerebrales: valor del 18F-DOPA PET/TC/RM / Radionecrosis versus disease progression in brain metastasis. Value of 18F-DOPA PET/CT/MRI

La utilización del 18F-DOPA PET/TC junto a la superposición con imágenes de resonancia magnética y el empleo de métodos de análisis visual y semicuantitativo permitió diferenciar entre las alteraciones posradiocirugía vs. sospecha de progresión de la enfermedad en un paciente con metástasis cerebrales de melanoma, permitiendo tomar una conducta quirúrgica correcta precozmente (AU)

The use of 18F-DOPA PET/CT with magnetic resonance imaging fusion and the use of visual methods and quantitative analysis helps to differentiate between changes post-radiosurgery vs. suspicion of disease progression in a patient with brain metastases from melanoma, thus facilitating taking early surgical action (AU)

Risk factors for tuberculosis in inflammatory bowel disease: anti-tumor necrosis factor and hospitalization

Aims: To determine risk factors for active tuberculosis in patients with inflammatory bowel diseases. Methods: Retrospective, case-control study at 4 referral hospitals in Spain. Cases developed tuberculosis after a diagnosis of inflammatory bowel disease. Controls were inflammatory bowel disease patients who did not develop tuberculosis. For each case, we randomly selected 3 controls matched for sex, age (within 5 years) and time of inflammatory bowel disease diagnosis (within 3 years). Inflammatory bowel disease characteristics, candidate risk factors for tuberculosis and information about the tuberculosis episode were recorded. Multivariate analysis and a Chi-squared automatic interaction detector were used. Results: Thirty-four cases and 102 controls were included. Nine of the 34 cases developed active tuberculosis between 1989 and 1999, and 25 became ill between 2000 and 2012. Multivariate regression showed an association between active tuberculosis and anti-TNF (tumor necrosis factor) therapy in the previous 12 months (OR 7.45; 95% CI, 2.39-23.12; p = 0.001); hospitalization in the previous 6 months (OR 4.38; 95% CI, 1.18-16.20; p = 0.027); and albumin levels (OR 0.88; 95% CI, 0.81-0.95; p = 0.001). The median time between the start of biologic therapy and the onset of active tuberculosis was 13 (interquartile range, 1-58) months. Tuberculosis developed after a year of anti-TNF therapy in 53%, and late reactivation occurred in at least 3 of 8 patients. Conclusions: The main risks factors for developing tuberculosis were anti-TNF therapy and hospitalization. Over half the cases related to anti-TNF treatment occurred after a year (AU)

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