Evaluación del papel de la calprotectina plasmática como marcador de inflamación en las uveítis no infecciosas

La uveítis está considerada una afección grave que causa entre el 5 y el 20% de los casos de ceguera legal y hasta un 10% de las alteraciones visuales asociadas con discapacidad laboral. Además, la uveítis no infecciosa, que es la forma más prevalente de uveítis en nuestro medio, se ha ha asociado a altos costes económicos, relacionados tanto con su diagnóstico como con su tratamiento. Hasta la fecha, no se han validado biomarcadores de inflamación ocular. La evaluación de la actividad de las uveítis se basa en general en sistemas de gradación semicuantitativos subjetivos. Los niveles de calprotectina circulante están elevados en diferentes enfermedades inflamatorias, habiéndose propuesto como indicadores sensibles de actividad en pacientes con uveítis. Objetivo principal: Comparar los niveles de calprotectina plasmática en pacientes con uveítis no infecciosa activa con los de controles sin uveítis. Objetivos secundarios: Evaluar la correlación entre los niveles de calprotectina plasmática y el grado de celularidad en cámara anterior en pacientes con uveitis anterior. Evaluar los cambios en los niveles de calprotectina plasmática en pacientes con uveítis entre el inicio del brote de uveítis y su resolución. Se llevó a cabo un estudio observacional, transversal y prospectivo. Se reclutaron pacientes con uveítis no infecciosa activa y controles sin uveítis. Se programó un seguimiento de 3 meses para el grupo de pacientes. Se determinó la concentración de calprotectina plasmática y se realizaron exploraciones oftalmológicas en pacientes y controles. Se recogieron y se analizaron las variables independientes que pudiesen influenciar los niveles de calprotectina. Para llevar a cabo el análisis estadístico se utilizaron los programas R (versión 3.6.0) y SPSS (versión 11). En el estudio transversal se incuyeron 74 pacientes y 40 controles, y en el estudio prospectivo, 36 pacientes. Los niveles de calprotectina plasmática de los pacientes con uveítis fueron superiores a los de los controles. Está diferencia se observó tanto en las uveítis activas como en las inactivas. La concentración de calprotectina se vio influenciada por la edad de los pacientes y por la localización anatómica de las uveítis, siendo más elevada en los pacientes más jóvenes, y en aquellos con uveítis anterior y posterior. En los pacientes con enfermedad sistémica asociada a la uveítis, los valores de calprotectina fueron superiores en aquellos que presentaban actividad sistémica. No se encontró correlación entre los niveles de calprotectina y el grado de celularidad en cámara anterior. La concentración de caprotectina no se vio influenciada por el uso de corticosteroides, tópicos o sistémicos, en el momento de la determinación analítica. En el estudio prospectivo, no se encontraron diferencias significativas entre los niveles de calprotectina de la fase de uveítis activa y tras su resolución. Las concentraciones de calprotectina plasmática difieren entre pacientes con uveítis y controles sanos y están influenciadas por la edad, la localización anatómica de la uveítis y la presencia de enfermedad inflamatoria sistémica activa. Teniendo en cuenta la muestra del estudio, la concentración de calprotectina plasmática no resultó ser un buen marcador de actividad clínica.Uveitis is considered a serious disease that causes 5 to 20% of legal blindness cases and up to 10% of visual disturbances associated with laboral disability. Non-infectious uveitis, which is the most predominant form of uveitis in our environment, has been associated with high costs, both with its diagnosis and its treatment. Up until now, no biomarkers have been validated to assess ocular inflammation and the evaluation of disease activity depends basicaly on semiquantitative subjective grading systems. Circulating calprotectin levels are increased in different inflammatory conditions and they have been proposed to be sensitive indicators of disease activity in patients with uveitis. Main objective: To compare levels of plasma calprotectin in patients with active noninfectious uveitis with those of nonuveitic controls. Secondary objectives: To evaluate the correlation between levels of plasma calprotectin and anterior chamber cell grade in anterior uveitis and evaluate the changes of plasma calprotectin levels in uveitic patients between flare beginning and its resolution. This is an observational both cross-sectional and prospective study. Patients with active noninfectious uveitis were recruited as well as nonuveitic controls. A 3 month follow-up was conducted for uveitis patients. Plasma calprotectin was determined and an ophthalmological examination was performed for both patients and controls. Independent variables possibly influencing levels of plasma calprotectin were recorded and analyzed. R software (version 3.6.0) and SPSS software (version 11) were used to perform the statistical analysis. 74 patients and 40 controls were included in the cross-sectional study, and 36 patients in the prospective study. Plasma calprotectin levels were higher in uveitis patients compared to those of controls. This difference was observed for active uveitis as well as for inactive uveitis. Calprotectin levels were influenced by age and anatomical location of uveitis, being higher in younger patients and patients with anterior and posterior uveitis. Among patients with systemic inflammatory disease associated to uveitis, calprotectin levels were higher in those who showed systemic activity of the disease. We found no influence of corticosteroid use, topical or systemic, on calprotectin levels. No correlation between calprotectin and anterior chamber inflammation degree was found. No significant differences in calprotectin levels between active and inactive uveitis were found. Plasma calprotectin levels in uveitis patients are different from those of nonuveitic controls and are influenced by age, anatomical location of the uveitis and systemic inflammatory disease activity. Considering this study sample, plasma calprotectin concentration didn’t prove to be a good marker of clinical activity.MedicinaCiencias de la Salu

Síndrome de DRESS inducido por sulfasalazina

El síndrome de DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), es una reacción severa inducida por fármacos que puede llegar a ser potencialmente mortal. Se han descrito mas de 50 fármacos asociados, incluyendo las sulfamidas, aunque es más frecuente su aparición por anticonvulsivantes. Presentamos el caso de un varón de 34 años de raza negra que recibió tratamiento con sulfasalazina durante 21 días por una clínica de poliartritis. Requirió ingreso hospitalario por presentar fiebre, malestar general, rash cutáneo y alteraciones hematológicas y orgánicas. Tras 48 horas de terapia con corticoides se evidenció una respuesta con recuperación del estado general, parámetros analíticos y resolución de lesiones cutáneas.El síndrome DRESS sigue teniendo una alta tasa de mortalidad por lo que una alta sospecha del mismo debe ser tenida en cuenta en aquellos pacientes que reciben estos fármacos

Identifying social cognition subgroups in euthymic patients with bipolar disorder: a cluster analytical approach

Background: Bipolar Disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in patients with BD, and further explore the potential impact of distinct variables on SC. Methods: Hierarchical cluster analysis was conducted using three SC domains (Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)). The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical and neurocognitive variables. A logistic regression model was used to estimate the effect of SC associated risk factors. Results: A two-cluster solution was identified with an adjusted performance group (N=48, 67.6%) and a low performance group (N=23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR=0.920; 95%CI=0.863-0.981), male gender (OR=5.661; 95%CI=1.473–21.762) and longer illness duration (OR=1.085; 95%CI=1.006–1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. Conclusions: Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender and lower estimated IQ were associated with low SC performance.

Long-term outcome predictors after functional remediation in patients with bipolar disorder

Background: Improving functioning in patients with bipolar disorder (BD) is a main objective in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. Methods: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale (FAST). Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in previous scientific literature. Results: The regression model revealed that only two independent variables significantly contributed to the model (F(6, 53): 4.003; p=0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. Conclusions: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis Due to Behçet's Disease: National Multicenter Study of 177 Cases

Objective: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). Methods: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. Results: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). Conclusion: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up

Anti-IL-6 Receptor Tocilizumab in Refractory Graves? Orbitopathy: National Multicenter Observational Study of 48 Patients

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the e cacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age standard deviation 51 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 0.25 vs. 0.9 0.16; p = 0.0001), CAS (4.64 1.5 vs. 1.05 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 4.1 vs. 16.73 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 2.1 months, low disease activity (CAS 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or ine cacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis

Introduction Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. Methods A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. Results Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate–high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild–moderate. Conclusions The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.We would like to acknowledge the support of Abbvie: this study was conducted with an unrestricted grant from Abbvie. The Spanish Society of Rheumatology is the sponser and funder of this study and the journal's Rapid Service Fee, and has participated in the study design; in the analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all study data and had final responsibility for the decision to submit the manuscript for publication

Isquemia de miembros inferiores en paciente con esclerosis sistémica

Se presenta el caso de una mujer de 38 años diagnosticada de esclerosis sistémica que desarrolló una isquemia aguda de miembro inferior derecho. La asociación de bosentan al tratamiento con heparina de bajo peso molecular e iloprost endovenoso permitió mantener la estabilidad clínica de la paciente, impidiendo el desarrollo de nuevas lesiones isquémicas