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1.
J Clin Rheumatol ; 29(3): 132-138, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728382

RESUMEN

BACKGROUND: Evaluating the efficacy and refractoriness to treatment and determining factors associated with adverse outcomes in uveitis associated with spondylarthritis (SpA) are complicated by the lack of validated outcome measures. OBJECTIVES: The aims of this study were to develop an outcome score SpA-U in patients with uveitis associated with SpA and to determine factors associated with adverse outcomes in patients with uveitis under systemic treatment. METHODS: The outcome score SpA-U was defined by best-corrected visual acuity, anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their SEs are displayed together with linear regression coefficients with 95% confidence intervals. For continuous factors, averages and SDs are reported in addition to linear regression coefficients with 95% confidence interval. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. RESULTS: One hundred ninety-seven uveitis outbreaks were included. Sixty-two uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history ( ß = 0.34), axial and peripheral involvement ( ß = 0.43), Ankylosing Spondylitis Disease Activity Score >2.1 ( ß = 0.45), positive HLA-B27 ( ß = 0.29), female sex ( ß = 0.19), patients with C-reactive protein elevation ( ß = 0.002), and bilateral ocular involvement ( ß = 0.32). At the same time, shorter disease evolution ( ß = -0.02) was associated with less severe uveitis activity. CONCLUSION: We have determined factors associated with adverse outcomes in patients with uveitis associated with SpA by developing an outcome score SpA-U that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.


Asunto(s)
Espondiloartritis , Espondilitis Anquilosante , Uveítis , Humanos , Femenino , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico , Espondiloartritis/epidemiología , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Espondilitis Anquilosante/complicaciones , Inflamación , Antígeno HLA-B27
2.
Clin Exp Rheumatol ; 40(1): 142-149, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33666160

RESUMEN

OBJECTIVES: Rapid control of intraocular inflammation in non-infectious uveitis (NIU) is mandatory to avoid irreversible structural and functional damage. In this study, we assessed the efficacy and safety of intravenous methylprednisolone (IVMP) pulses in the treatment of NIU. METHODS: A retrospective case series of 112 patients who received IVMP for the treatment of NIU, either isolated or associated with different underlying diseases, was studied. Intraocular inflammation (anterior chamber cells and vitritis) was the primary outcome measure. Secondary outcome measures were macular thickness and best corrected visual acuity (BCVA). Patients were assessed at baseline visit, and at days 2-5, 7, 15 and 30 after initiation of IVMP pulse therapy. RESULTS: A total of 112 patients (mean age 42±14.5 yrs) were assessed. An underlying immune-mediated disease was diagnosed in 73 patients. Inflammatory ocular patterns were panuveitis (n=68), posterior uveitis (n=30), anterior uveitis (AU) (n=12), and intermediate uveitis (n=2). Additionally, patients presented cystoid macular oedema (CME) (n=50), retinal vasculitis (n=37), and exudative retinal detachment (n=31). Therapies used before IVMP included intraocular glucocorticoids (n=4), high-dose oral systemic glucocorticoids (n=77), and conventional (n=107) or biologic (n=40) immunosuppressive drugs. IVMP dose ranged from 80 to 1,000 mg/day for 3-5 consecutive days. Improvement was observed in AU, vitritis, BCVA, CME, and retinal vasculitis. At first month evaluation, total remission was achieved in 19 patients. Side effects of IVMP were respiratory infections (n=3), uncontrolled hyperglycaemia (n=1), herpes zoster (n=1), and oral candidiasis (n=1). CONCLUSIONS: IVMP pulse therapy was effective and safe, and achieved rapid control of NIU.


Asunto(s)
Metilprednisolona , Uveítis , Adulto , Glucocorticoides/efectos adversos , Humanos , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Agudeza Visual
3.
Clin Exp Rheumatol ; 39 Suppl 132(5): 37-42, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33886457

RESUMEN

OBJECTIVES: Anti-IL6R tocilizumab (TCZ) therapy has proved to be useful in the treatment of refractory ocular and/or neurological involvement of Behçet's disease (BD). However, TCZ efficacy in other BD manifestations remains unclear. In this study we aimed to assess the efficacy of TCZ in the different clinical phenotypes of BD. METHODS: This is a multicentre study of BD patients treated with TCZ, due to refractivity to standard systemic treatment. RESULTS: We studied 16 patients (10 men/6 women); mean age 36.5±18.2 years. The main clinical manifestations at TCZ onset were ocular, oral and/or genital ulcers, arthritis, folliculitis and/or neurological involvement. Before TCZ, they had received several conventional and/or biological immunosuppressants, such as methotrexate, cyclosporine, adalimumab or infliximab. TCZ was used in monotherapy or combined with conventional immunosuppressive drugs. The main indications for TCZ prescription were refractory uveitis (n=14) and refractory neurobehçet (n=2). After a median [IQR] follow-up of 20 [9-45] months using TCZ, neurological and ocular domains improved in most cases with complete remission in most patients with uveitis. Articular and peripheral venous manifestations also experienced a favourable evolution. However, oral/genital ulcers, skin lesions and intestinal manifestations followed a torpid course. CONCLUSIONS: TCZ is effective in BD with major clinical involvement. However, it does not seem to be effective in oral/genital ulcers or skin lesions.


Asunto(s)
Síndrome de Behçet , Uveítis , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Uveítis/etiología , Adulto Joven
4.
Clin Exp Rheumatol ; 39(1): 105-114, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33124565

RESUMEN

OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.


Asunto(s)
Mujeres Embarazadas , Uveítis , Adulto , Terapia Biológica , Certolizumab Pegol/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Lactante , Recién Nacido , Embarazo , Resultado del Tratamiento , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico
5.
Hum Mol Genet ; 27(24): 4333-4343, 2018 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-30215709

RESUMEN

Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed 'MHC-I (major histocompatibility complex class I)-opathy' family. Genetic studies have pinpointed the endoplasmic reticulum aminopeptidase (ERAP1) and (ERAP2) genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression. We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC-I-opathies. We show that the risk ERAP1 haplotype conferred significantly altered expression of ERAP1 isoforms in transcriptomic data (n = 360), resulting in lowered protein expression and distinct enzymatic activity. Both the association for rs10044354 (meta-analysis: odds ratio (OR) [95% CI]=2.07[1.58-2.71], P = 1.24 × 10(-7)) and rs2287987 (OR[95% CI]: =2.01[1.51-2.67], P = 1.41 × 10(-6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either variant alone [meta-analysis: P=3.9 × 10(-9)]. Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n = 3353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly.


Asunto(s)
Aminopeptidasas/genética , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Menor/genética , Uveítis/genética , Femenino , Estudios de Asociación Genética , Genotipo , Antígenos HLA-A/genética , Antígenos HLA-A/inmunología , Haplotipos/genética , Humanos , Masculino , Sitios Menores de Histocompatibilidad/genética , Polimorfismo de Nucleótido Simple/genética , Uveítis/inmunología , Uveítis/patología
6.
Ophthalmology ; 127(6): 814-825, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31952883

RESUMEN

PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.


Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Uveítis/tratamiento farmacológico , Adalimumab/efectos adversos , Adulto , Antiinflamatorios/efectos adversos , Terapia Biológica , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , España , Uveítis/diagnóstico , Uveítis/fisiopatología , Privación de Tratamiento , Adulto Joven
7.
Rheumatology (Oxford) ; 57(5): 856-864, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29471416

RESUMEN

Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome de Behçet/complicaciones , Receptores de Interleucina-6/antagonistas & inhibidores , Uveítis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Uveítis/diagnóstico , Uveítis/etiología , Adulto Joven
8.
Ophthalmology ; 125(9): 1444-1451, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29602570

RESUMEN

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.


Asunto(s)
Adalimumab/administración & dosificación , Síndrome de Behçet/complicaciones , Uveítis/tratamiento farmacológico , Agudeza Visual , Adulto , Antiinflamatorios/administración & dosificación , Síndrome de Behçet/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Inmunosupresores/uso terapéutico , Masculino , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Uveítis/diagnóstico , Uveítis/etiología
9.
Clin Exp Rheumatol ; 36(4): 652-657, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29303704

RESUMEN

OBJECTIVES: To assess the efficacy of golimumab (GLM), a fully humanised anti-TNF-α monoclonal antibody, in refractory juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: This was a multicentre study of JIA-associated uveitis refractory to standard synthetic immunosuppressive drugs and in most cases to other anti-TNF-α agents. Results were expressed as mean±standard deviation or as median (range or interquartile range). The Wilcoxon signed-rank test was used to compare continuous variables. A literature review of the efficacy of GLM in uveitis related to JIA was also conducted. RESULTS: We studied 7 patients (5 females; mean age 21.7±7.5 years; 13 affected eyes). Uveitis was bilateral in 6. Cystoid macular oedema (CME) occurred in 3 patients (5 eyes). Besides corticosteroids and synthetic immunosuppressive drugs, patients had received before GLM a median of 2 biologic agents (range 0-3) including adalimumab (n=6), etanercept (n=2), infliximab (n=3) and abatacept (n=2). GLM dose was 50 mg/sc every 4 weeks. After 6 months of therapy the number of anterior chamber cells decreased from 1 [0.25-1.5] to 0 [0-0.5] (p=0.02) and optical coherence tomography (in patients with CME) from 313.6±77.05 to 261.4±75.1 µm (p=0.03). The best-corrected visual acuity increased from 0.5 to 0.62 (p=0.018). Complete remission of uveitis was achieved in 4 of 7 patients after 16.8±11.4 months of follow-up. However, 2 of the seven patients had to be switched to tocilizumab due to inefficacy. Local erythema at the injection site was observed in 2. CONCLUSIONS: GLM may be considered in the management of refractory JIA-related uveitis.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Artritis Juvenil/complicaciones , Uveítis/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Tomografía de Coherencia Óptica , Uveítis/fisiopatología , Agudeza Visual
10.
J Med Genet ; 54(1): 38-46, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27609017

RESUMEN

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.


Asunto(s)
Uveítis/genética , Alelos , Estudios de Casos y Controles , Femenino , Sitios Genéticos/genética , Antígenos HLA/genética , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Población Blanca/genética
11.
Rheumatol Int ; 37(4): 647-656, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27815703

RESUMEN

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases.


Asunto(s)
Inflamación/diagnóstico , Uveítis/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
12.
Int Ophthalmol ; 37(5): 1235-1238, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27761762

RESUMEN

PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Occasionally, triggering causes are identified, such as neoplasms, and they are termed sarcoid-like reactions, which may appear in any sarcoidotic target tissue. Choroidal metastases appear as part of widespread metastatic disease or as the first suggestion of neoplastic disease. They can also be a part of the differential diagnosis of a spectrum of inflammatory eye diseases. We present a case in which a lung carcinoma, pulmonary and eye sarcoid-like reactions, and choroidal metastasis take place in the same patient. CASE REPORT: A 60-year-old male with a past history of pulmonary sarcoidosis and associated anterior uveitis was diagnosed with a lung carcinoma with no regional lymph nodes extension, so that the resection surgery was performed without additional systemic treatment. At the same time, he complained of visual acuity loss and pain in his right eye. An intense ocular inflammatory reaction and a choroidal mass compatible with metastasis were identified. A vitrectomy with an accompanied histological exam of the lesion was deemed inconclusive. Ocular symptoms progressively worsened showing mass growth, and as a result, an enucleation was performed and the histological study subsequently revealed metastasis from his lung carcinoma. CONCLUSION: Sarcoid-like reactions may be due to incipient malignancies. Any diagnosis of sarcoidosis requires ruling out other diseases that can produce secondary sarcoid-like reactions. In addition, any choroidal mass suggestive of metastasis requires exclusion of metastatic disease even in the absence of clinical signs indicating tumor extension.


Asunto(s)
Coroides/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Sarcoidosis Pulmonar/complicaciones , Uveítis Anterior/etiología , Biopsia con Aguja Fina , Broncoscopía , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Sarcoidosis Pulmonar/diagnóstico , Ultrasonografía , Uveítis Anterior/diagnóstico , Uveítis Anterior/cirugía , Vitrectomía
13.
Hum Mol Genet ; 23(22): 6081-7, 2014 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-24957906

RESUMEN

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.


Asunto(s)
Aminopeptidasas/genética , Coriorretinitis/genética , Estudio de Asociación del Genoma Completo , Alelos , Aminopeptidasas/metabolismo , Retinocoroidopatía en Perdigonada , Estudios de Casos y Controles , Coriorretinitis/metabolismo , Femenino , Antígenos HLA-A/genética , Haplotipos , Humanos , Masculino , Población Blanca/genética
14.
Ophthalmology ; 123(8): 1632-1636, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27084561

RESUMEN

PURPOSE: To describe and analyze the prevalence of spondyloarthritis (SpA) in patients with anterior uveitis (AU). DESIGN: Multicentric, observational, prospective study. PARTICIPANTS: Consecutive patients with AU who were human leukocyte antigen (HLA)-B27 positive or HLA-B27 negative with more than 1 episode of AU separated by at least 3 months were selected. Patients with a previous diagnosis of SpA were excluded. METHODS: Included patients were evaluated by an ophthalmologist and a rheumatologist following a predefined visit schedule. MAIN OUTCOME MEASURES: Sociodemographic and clinical variables including the diagnosis of SpA according to Assessment of SpondyloArthritis International Society (ASAS) criteria and an exhaustive ophthalmological examination (best-corrected visual acuity, intraocular pressure, biomicroscopic examination of the anterior and posterior segment of the eye, cataract evaluation, optical coherence tomography evaluating both the 1-mm central retina thickness and the optic nerve head and retinal nerve fiber layer, and visual field in a dark room with 1 eye patched) were collected. Baseline descriptive, bivariate, and concordance analyses were performed. RESULTS: We included 798 patients, mostly men (59%) with a mean age of 45 years; 60% were AU HLA-B27 positive, and 40% had recurrent negative AU HLA-B27. A total of 50.2% and 17.5% of patients presented axial and peripheral SpA according to ASAS criteria, respectively. Patients with AU who were HLA-B27 positive were more frequently diagnosed with axial (69.8% vs. 27.3%, P < 0.0001) and peripheral SpA (21.9% vs. 11.1%, P < 0.0001) than patients with recurrent negative AU HLA-B27. In general, we did not detect important differences between groups in the ophthalmologic variables. CONCLUSIONS: A large percentage of patients with clinically significant AU have an undiagnosed SpA. This percentage is even higher if the HLA-B27 haplotype is positive.


Asunto(s)
Espondiloartritis/epidemiología , Uveítis Anterior/epidemiología , Adulto , Femenino , Antígeno HLA-B27/inmunología , Humanos , Estudios Interdisciplinarios , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Prevalencia , Estudios Prospectivos , Retina/patología , Células Ganglionares de la Retina/patología , España/epidemiología , Espondiloartritis/diagnóstico , Espondiloartritis/inmunología , Tomografía de Coherencia Óptica , Uveítis Anterior/diagnóstico , Uveítis Anterior/inmunología , Agudeza Visual/fisiología , Campos Visuales/fisiología
15.
Ophthalmology ; 123(12): 2618-2625, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27692527

RESUMEN

PURPOSE: To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. DESIGN: Prospective observational study. PARTICIPANTS: Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. METHODS: All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. MAIN OUTCOME MEASURES: Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing. RESULTS: Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014). CONCLUSIONS: Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors.


Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Anticuerpos Antiidiotipos/sangre , Uveítis/sangre , Uveítis/tratamiento farmacológico , Adalimumab/inmunología , Adolescente , Adulto , Anciano , Antiinflamatorios/inmunología , Antiinflamatorios/farmacocinética , Formación de Anticuerpos/inmunología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Resultado del Tratamiento , Agudeza Visual
16.
Clin Exp Rheumatol ; 34(6 Suppl 102): S34-S40, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27054359

RESUMEN

OBJECTIVES: To assess the efficacy of other biologic therapies, different from infliximab (IFX) and adalimumab (ADA), in patients with Behçet's disease uveitis (BU). METHODS: Multicenter study of 124 patients with BU refractory to at least one standard immunosuppressive agent that required IFX or ADA therapy. Patients who had to be switched to another biologic agent due to inefficacy or intolerance to IFX or ADA or patient's decision were assessed. The main outcome measures were the degree of anterior and posterior chamber inflammation and macular thickness. RESULTS: Seven (5.6%) of 124 cases (4 women/3 men; mean age, 43 (range 28- 67) years; 12 affected eyes) were studied. Five of them had been initially treated with ADA and 2 with IFX. The other biologic agents used were golimumab (n=4), tocilizumab (n=2) and rituximab (n=1). The ocular pattern was panuveitis (n=4) or posterior uveitis (n=3). Uveitis was bilateral in 5 patients (71.4%). At baseline, anterior chamber and vitreous inflammation were present in 6 (50%) and 7 (58.3%) of the eyes. All the patients (12 eyes) had macular thickening (OCT>250µm) and 4 of them (7 eyes), cystoid macular edema (OCT>300 µm). Besides reduction anterior chamber and vitreous inflammation, we observed a reduction of OCT values, from 330.4±58.5 µm at the onset of the biological agent to 273±50 µm at month 12 (p=0.06). Six patients achieved a complete remission of uveitis. CONCLUSIONS: The vast majority of patients with BU refractory to standard immunosuppressive drugs are successfully controlled with ADA and/or IFX. Other biologic agents appear to be also useful.


Asunto(s)
Adalimumab/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Sustitución de Medicamentos , Inmunosupresores/uso terapéutico , Infliximab/uso terapéutico , Uveítis/tratamiento farmacológico , Adalimumab/efectos adversos , Adulto , Anciano , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/inmunología , Productos Biológicos/efectos adversos , Resistencia a Medicamentos , Femenino , Humanos , Inmunosupresores/efectos adversos , Infliximab/efectos adversos , Masculino , Persona de Mediana Edad , Inducción de Remisión , España , Factores de Tiempo , Resultado del Tratamiento , Uveítis/diagnóstico , Uveítis/inmunología
17.
Retina ; 36(9): 1778-85, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27183031

RESUMEN

PURPOSE: To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. METHODS: We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. RESULTS: We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 µm (115) at baseline and 266.3 µm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. CONCLUSION: In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients.


Asunto(s)
Dexametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Edema Macular/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Adulto , Anciano , Dexametasona/efectos adversos , Implantes de Medicamentos , Femenino , Glucocorticoides/efectos adversos , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico por imagen , Edema Macular/microbiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Uveítis/diagnóstico por imagen , Uveítis/microbiología
19.
Rheumatology (Oxford) ; 53(12): 2223-31, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24996907

RESUMEN

OBJECTIVE: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). METHODS: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 µm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 µm) that improved from 420 µm (s.d. 119.5) at baseline to 271 µm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Uveítis/tratamiento farmacológico , Adalimumab , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Síndrome de Behçet/complicaciones , Productos Biológicos/efectos adversos , Productos Biológicos/uso terapéutico , Niño , Esquema de Medicación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Resultado del Tratamiento , Uveítis/etiología , Adulto Joven
20.
Mediators Inflamm ; 2014: 717598, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24976689

RESUMEN

OBJECTIVE: To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. METHODS: Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. RESULTS: Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20-38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 µ, P = 0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. CONCLUSIONS: GLM is a new and promising therapeutic option for patients with severe and refractory uveitis.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Uveítis/tratamiento farmacológico , Adulto , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
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