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1.
Clin Exp Rheumatol ; 40(1): 142-149, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33666160

RESUMO

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.


Assuntos
Metilprednisolona , Uveíte , Adulto , Glucocorticoides/efeitos adversos , Humanos , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Acuidade Visual
2.
Clin Exp Rheumatol ; 32(6): 864-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25288110

RESUMO

OBJECTIVES: The aim of this paper is to assess the clinical response to golimumab (GLM) in patients with non-infectious uveitis from a single centre that had previously been treated with other anti-TNF-α drugs. METHODS: A retrospective chart review was carried out of patients with immune-mediated uveitis refractory to standard synthetic immunosuppressive drugs who were treated with GLM at Hospital Universitario Marqués de Valdecilla, Santander (Spain). Patients were included in this study if they had previously been treated with other anti-TNF-α drugs. A literature review of patients with immune-mediated uveitis undergoing GLM therapy was conducted. RESULTS: Three patients (2 men and 1 woman) were included in this study. Two of them were refractory to other anti-TNF-α drugs. The median age of patients was 26 years (range 20-42). Uveitis was bilateral in two patients. The underlying diseases were uveitis associated with HLA-B27 and psoriasis in one case and sarcoidosis in the other two cases. Improvement of the main ocular parameters following GLM therapy was achieved in all cases. After a median follow-up of 3 (range 1-9) months using GLM therapy, none of the patients had experienced new relapses of uveitis. None of them had side effects during treatment with this drug. A literature review disclosed that our observations were in keeping with other reports that showed good response to GLM in 13 of 16 patients with immune-mediated uveitis refractory to other biologic agents. CONCLUSIONS: Although the follow-up was too short in our series, GLM could be an effective and safe therapy for the management of patients with uveitis previously treated with other anti-TNF-α drugs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adulto , Resistência a Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Espanha , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/imunologia , Adulto Jovem
3.
Clin Exp Rheumatol ; 32(4 Suppl 84): S54-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25005576

RESUMO

OBJECTIVES: To evaluate the clinical response to Tocilizumab (TCZ) in three patients with non-infectious uveitis refractory to anti-TNF-α drugs. METHODS: Assessment of TCZ-treated patients with immune-mediated uveitis from two Spanish medical referral centers. Uveitis had been refractory to previous standard synthetic immunosuppressive drugs and at least one TNF-α inhibitor. A literature review of patients with immune-mediated uveitis treated with TCZ therapy was also conducted. RESULTS: 3 women (5 eyes) with uveitis refractory to conventional immunosuppressive therapy and at least one anti-TNF-α drug were treated with TCZ. The mean age of the patients was 48.6±16.1 (range 37-67) years. In two cases uveitis was bilateral and in the other unilateral. The underlying diseases were rheumatoid arthritis in one case and Behçet's disease in the other two cases. After a mean follow-up of 7.3±5.7 (range 1-12) months using TCZ therapy, all patients experienced ocular improvement. Also, in 3 eyes inactive intraocular inflammation was achieved. None of the patients had side effects during the period of treatment with this drug. A literature review disclosed that our observations are in keeping with other reports that showed good response to TCZ in 11 of 12 patients with immune-mediated uveitis refractory to other biologic agents. CONCLUSIONS: TCZ appears to be an effective and safe therapy for the management of patients with uveitis refractory to other biologic drugs.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Idoso , Resistência a Medicamentos , Feminino , Humanos , Resultado do Tratamento , Uveíte/patologia
4.
BMC Med Genet ; 14: 52, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23676143

RESUMO

BACKGROUND: Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. METHODS: A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. RESULTS: A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. CONCLUSION: Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.


Assuntos
Predisposição Genética para Doença , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade beta de Receptor de Interleucina-2/genética , Interleucina-2/genética , Interleucinas/genética , Polimorfismo Genético , Uveíte/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único
5.
Mol Vis ; 19: 638-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23559857

RESUMO

OBJECTIVE: Endogenous uveitis is a major cause of visual loss mediated by the immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell receptor (TCR) signaling. Two independent functional missense single nucleotide polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been associated with different autoimmune disorders. We aimed to analyze for the first time the influence of these PTPN22 genetic variants on endogenous non-anterior uveitis susceptibility. METHODS: We performed a case-control study of 217 patients with endogenous non-anterior uveitis and 718 healthy controls from a Spanish population. The PTPN22 polymorphisms (rs33996649 and rs2476601) were genotyped using TaqMan allelic discrimination assays. The allele, genotype, carriers, and allelic combination frequencies were compared between cases and controls with χ(2) analysis or Fisher's exact test. RESULTS: Our results showed no influence of the studied SNPs in the global susceptibility analysis (rs33996649: allelic P- value=0.92, odds ratio=0.97, 95% confidence interval=0.54-1.75; rs2476601: allelic P- value=0.86, odds ratio=1.04, 95% confidence interval=0.68-1.59). Similarly, the allelic combination analysis did not provide additional information. CONCLUSIONS: Our results suggest that the studied polymorphisms of the PTPN22 gene do not play an important role in the pathophysiology of endogenous non-anterior uveitis.


Assuntos
Substituição de Aminoácidos/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Uveíte Anterior/enzimologia , Uveíte Anterior/genética , Alelos , Estudos de Casos e Controles , Demografia , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Espanha
6.
PLoS One ; 8(10): e76777, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24116155

RESUMO

OBJECTIVE: Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS: A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION: Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.


Assuntos
Predisposição Genética para Doença/genética , Fatores Reguladores de Interferon/genética , Edema Macular/genética , Polimorfismo de Nucleotídeo Único , Uveíte Anterior/complicações , Adulto , Alelos , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Edema Macular/complicações , Masculino , Pessoa de Meia-Idade , Fenótipo
7.
PLoS One ; 8(11): e72892, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24312163

RESUMO

OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS: No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION: Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.


Assuntos
Autoimunidade/genética , Polimorfismo Genético , Receptores de Interleucina/genética , Fator de Transcrição STAT4/genética , Uveíte/genética , Uveíte/imunologia , Adulto , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Uveíte/diagnóstico
8.
Scand J Infect Dis ; 39(3): 225-30, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17366052

RESUMO

The evolution of the incidence and the epidemiology of ocular candidiasis in our hospital during the past 12 y, as well as the factors associated with poor functional outcome were analysed. A retrospective study of all cases of ocular candidiasis admitted to a university hospital between 1993 and 2004 was performed. Epidemiological, clinical and final outcome data were recorded. 37 episodes of ocular candidiasis in 36 patients were studied. 28 (75%) episodes occurred between 1993 and 1998 (13.09 episodes/100,000 admissions/y), and all of these patients were intravenous drug users. In contrast, only 9 episodes of ocular candidiasis were recorded between 1999 and 2004 (4.42 episodes/100,000 admissions/y; p<.0001) and 3 (33%) patients were not drug users (p<0.01). 19 (57%) cases had final visual acuity <0.1. Treatment with conventional amphotericin B instead of other newer antifungal drugs was associated with poor visual prognosis in the univariate (p = 0.03) and multivariate (p = 0.03) analysis. In conclusion, the incidence of ocular candidiasis has decreased significantly in recent y and the epidemiology has changed. Currently, one-third of patients are immunocompromised non-drug users. Therapy with conventional amphotericin B instead of newer antifungal drugs appears to be associated with a poorer functional outcome.


Assuntos
Candidíase/epidemiologia , Infecções Oculares Fúngicas/epidemiologia , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/fisiopatologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/fisiopatologia , Feminino , Fluconazol/uso terapêutico , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/microbiologia , Resultado do Tratamento , Acuidade Visual
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