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1.
Artigo em Inglês | MEDLINE | ID: mdl-38710493

RESUMO

INTRODUCTION: Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging. OBJECTIVES: To evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis. METHODS: Retrospective chart review of non-infectious PGU occurring in children before the age of 16 years recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023. RESULTS: We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with juvenile idiopathic arthritis, and one with Vogt-Koyanagi-Harada disease. Median age at diagnosis was 9.8 years (range 7.2-12.5). The sex-ratio M/F was 0.52. The most common features of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%) particularly in cases of panuveitis. The most commonly used treatments were systemic corticosteroids (72%) and methotrexate (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years. CONCLUSION: We report the largest cohort of PGU. PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.

2.
Orbit ; : 1-10, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913546

RESUMO

Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.

3.
J Clin Microbiol ; 61(12): e0088523, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38038483

RESUMO

Diagnosis of herpes simplex keratitis (HSK) is mostly based on clinical findings, yet biological confirmation supports management of challenging cases. This study evaluated the place of real-time quantitative PCR (RT-qPCR) on tear samplings in the management of HSK. Clinical records of patients who underwent tear sampling tested by RT-qPCR for herpes simplex virus type 1 for an acute episode of corneal inflammation or defect between January 2013 and December 2021 were retrospectively reviewed, and results were compared to clinical diagnosis (i.e., HSK or not) based on biomicroscopic findings and medical history. Of 465 tested tear samples from 364 patients, a clinical diagnosis of active (ongoing) HSK was recorded in 240 cases, among which 76 were RT-qPCR positive (global sensitivity of 31.6%, specificity of 99.5%). Sensitivity of RT-qPCR was higher in epithelial (97.4%) and stromal keratitis with ulceration (48.7%), compared to other types of HSK (23.5% in keratouveitis, 13.6% in endotheliitis, 11.1% in postherpetic neurotrophic keratopathy, and 8.1% in stromal keratitis without ulceration). The highest viral loads were detected from epithelial and stromal keratitis with ulceration, while in HSK with no epithelial involvement, the viral load detected was 196-fold lower, on average. The proportion of clinically characterized HSK patients with negative tear samples was higher in patients receiving antiviral treatment (P < 0.0001). RT-qPCR, performed on tear samples, can help in confirming diagnosis in case of presumed HSK, including clinical forms with no obvious epithelial involvement. The sensitivity of tear sampling is much higher whenever epithelial keratitis is present.


Assuntos
Herpesvirus Humano 1 , Ceratite Herpética , Lacerações , Humanos , Estudos Retrospectivos , Ceratite Herpética/diagnóstico , Herpesvirus Humano 1/genética , Reação em Cadeia da Polimerase em Tempo Real , Lágrimas
4.
BMC Ophthalmol ; 23(1): 474, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990307

RESUMO

BACKGROUND: Pediatric Behçet's disease (PBD) is rarer than BD and can be a challenging diagnosis as clinical picture may be incomplete. As in adult patients, sight-threatening ocular manifestations may lead to diagnosis. In this study, we aimed to report a series of cases of PBD with ocular manifestations and provide a review of the literature. METHODS: Retrospective case series of PBD patients with ocular manifestations. Demographic, ophthalmological and systemic data at presentation and during follow-up were collected and analyzed. RESULTS: Four patients, aged 13.0 ± 2.9 years (9-16) were included. Posterior uveitis with retinal vasculitis, papillitis and macular edema was present in all patients, with associated anterior uveitis in 2 cases. Other features included occlusive vasculitis (2/4) and necrotizing retinitis (2/4). All patients were improved by systemic treatments except one patient with severe bilateral optic neuropathy. Ocular manifestations were the presenting symptoms in 3/4 cases. CONCLUSION: Ocular manifestations and systemic associations of PBD are comparable to those encountered in adult patients. The lack of complains in pediatric patients may lead to a longer diagnosis delay, especially in unilateral uveitis. Aggressive and long-term treatment is mandatory to prevent vision loss and recurrences.


Assuntos
Síndrome de Behçet , Uveíte , Adulto , Criança , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Estudos Retrospectivos , Uveíte/diagnóstico , Transtornos da Visão , Visão Ocular , Adolescente
5.
BMC Ophthalmol ; 23(1): 318, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452284

RESUMO

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.


Assuntos
Glaucoma , Descolamento Retiniano , Perfurações Retinianas , Retinosquise , Humanos , Retinosquise/diagnóstico , Estudos Retrospectivos , Descolamento Retiniano/cirurgia , Glaucoma/cirurgia , Perfurações Retinianas/cirurgia , Tomografia de Coerência Óptica , Vitrectomia/métodos , Imagem Multimodal
6.
Doc Ophthalmol ; 144(2): 147-152, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34978660

RESUMO

PURPOSE: To report a case of typical delayed-onset hypoxic cortical blindness that occurred few days after resuscitation from drowning in a young male. METHODS: Neurological and ophthalmological examination were performed including optical coherence tomography (OCT), Goldmann perimetry, pattern electroretinogram (pERG), pattern and flash visual evoked potentials (pVEP and fVEP) and brain magnetic resonance imaging (MRI). RESULTS: At presentation, at day 12 post-hypoxic incident, best corrected visual acuity (BCVA) was reduced to hand motion OU with an abolished optokinetic nystagmus, a normal fundus and no relative afferent pupillary defect. Macular and peripapillary OCT were normal. Goldmann perimetry revealed bilateral centrocecal scotoma. pERG was normal while pVEPs were undetectable and fVEPs were abnormal with delayed, decreased and disorganized responses, without interhemispheric asymmetry. Brain MRI disclosed a bilateral cortical-subcortical occipital hypersignal with laminar necrosis and thus confirmed the diagnosis of delayed-onset hypoxic cortical blindness. Visual rehabilitation, including visual stimulation in the scotomatous areas, was associated with a dramatic and rapid visual improvement with a BCVA of 20/32 OU, an ability to read after 2 weeks (day 30 post-hypoxic incident), and a reduction in the size of the scotoma. CONCLUSION: Delayed-onset hypoxic cortical blindness is a rare presentation of cortical blindness that develops few days after a cerebral hypoxic stress. While initial presentation can be catastrophic, visual improvement may be spectacular and enhanced with visual rehabilitation.


Assuntos
Cegueira Cortical , Eletrorretinografia , Cegueira/diagnóstico , Cegueira/etiologia , Cegueira Cortical/diagnóstico , Cegueira Cortical/etiologia , Eletrorretinografia/métodos , Potenciais Evocados Visuais , Humanos , Masculino , Escotoma/diagnóstico , Escotoma/etiologia , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico
7.
Int J Mol Sci ; 23(5)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35269576

RESUMO

Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Lubrificantes Oftálmicos/uso terapêutico , Composição de Medicamentos , Humanos , Lubrificantes Oftálmicos/química , Lubrificantes Oftálmicos/farmacologia , Viscosidade
8.
Rheumatology (Oxford) ; 60(11): 5413-5418, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33528012

RESUMO

OBJECTIVES: Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled RA. Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms. METHODS: Four patients (six eyes), 47-62 years of age, were included. At the onset of PUK, the median duration of RA was 13 years [interquartile range (IQR) 3-13] and the median treatment with TCZ was 9 months (IQR 3-14). Two patients had active disease [28-joint DAS (DAS28) >3.2] and the disease was controlled in two patients (DAS28 ≤3.2). RESULTS: TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in two patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye. CONCLUSION: PUK may occur in patients with long-standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy and paradoxical reactions of biologics.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/complicações , Úlcera da Córnea/etiologia , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
J Virol ; 93(24)2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31554680

RESUMO

Ocular herpes simplex keratitis (HSK) is a consequence of viral reactivations from trigeminal ganglia (TG) and occurs almost exclusively in the same eye in humans. In our murine oro-ocular (OO) model, herpes simplex virus 1 (HSV-1) inoculation in one side of the lip propagates virus to infect the ipsilateral TG. Replication here allows infection of the brainstem and infection of the contralateral TG. Interestingly, HSK was observed in our OO model only from the eye ipsilateral to the site of lip infection. Thus, unilateral restriction of HSV-1 may be due to differential kinetics of virus arrival in the ipsilateral versus contralateral TG. We inoculated mice with HSV-1 reporter viruses and then superinfected them to monitor changes in acute- and latent-phase gene expression in TG after superinfection compared to the control (single inoculation). Delaying superinfection by 4 days after initial right lip inoculation elicited failed superinfecting-virus gene expression and eliminated clinical signs of disease. Initial inoculation with thymidine kinase-deficient HSV-1 (TKdel) completely abolished reactivation of wild-type (WT) superinfecting virus from TG during the latent stage. In light of these seemingly failed infections, viral genome was detected in both TG. Our data demonstrate that inoculation of HSV-1 in the lip propagates virus to both TG, but with delay in reaching the TG contralateral to the side of lip infection. This delay is responsible for restricting viral replication to the ipsilateral TG, which abrogates ocular disease and viral reactivations from the contralateral side. These observations may help to understand why HSK is observed unilaterally in humans, and they provide insight into vaccine strategies to protect against HSK.IMPORTANCE Herpetic keratitis (HK) is the leading cause of blindness by an infectious agent in the developed world. This disease can occur after reactivation of herpes simplex virus 1 in the trigeminal ganglia, leading to dissemination of virus to, and infection of, the cornea. A clinical paradox is evidenced by the bilateral presence of latent viral genomes in both trigeminal ganglia, while for any given patient the disease is unilateral with recurrences in a single eye. Our study links the kinetics of early infection to unilateral disease phenomenon and demonstrates protection against viral reactivation when kinetics are exploited. Our results have direct implications in the understanding of human disease pathogenesis and immunotherapeutic strategies for the treatment of HK and viral reactivations.


Assuntos
Herpesvirus Humano 1/fisiologia , Ceratite Herpética/virologia , Lábio/virologia , Latência Viral/fisiologia , Replicação Viral/fisiologia , Animais , Córnea/virologia , Feminino , Regulação Viral da Expressão Gênica , Genes Virais/genética , Herpesvirus Humano 1/genética , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , MicroRNAs/metabolismo , Gânglio Trigeminal/virologia , Latência Viral/genética
10.
PLoS Pathog ; 14(9): e1007313, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30235352

RESUMO

Herpes simplex virus 1 (HSV-1) latency establishment is tightly controlled by promyelocytic leukemia (PML) nuclear bodies (NBs) (or ND10), although their exact contribution is still elusive. A hallmark of HSV-1 latency is the interaction between latent viral genomes and PML NBs, leading to the formation of viral DNA-containing PML NBs (vDCP NBs), and the complete silencing of HSV-1. Using a replication-defective HSV-1-infected human primary fibroblast model reproducing the formation of vDCP NBs, combined with an immuno-FISH approach developed to detect latent/quiescent HSV-1, we show that vDCP NBs contain both histone H3.3 and its chaperone complexes, i.e., DAXX/ATRX and HIRA complex (HIRA, UBN1, CABIN1, and ASF1a). HIRA also co-localizes with vDCP NBs present in trigeminal ganglia (TG) neurons from HSV-1-infected wild type mice. ChIP and Re-ChIP show that vDCP NBs-associated latent/quiescent viral genomes are chromatinized almost exclusively with H3.3 modified on its lysine (K) 9 by trimethylation, consistent with an interaction of the H3.3 chaperones with multiple viral loci and with the transcriptional silencing of HSV-1. Only simultaneous inactivation of both H3.3 chaperone complexes has a significant impact on the deposition of H3.3 on viral genomes, suggesting a compensation mechanism. In contrast, the sole depletion of PML significantly impacts the chromatinization of the latent/quiescent viral genomes with H3.3 without any overall replacement with H3.1. vDCP NBs-associated HSV-1 genomes are not definitively silenced since the destabilization of vDCP NBs by ICP0, which is essential for HSV-1 reactivation in vivo, allows the recovery of a transcriptional lytic program and the replication of viral genomes. Consequently, the present study demonstrates a specific chromatin regulation of vDCP NBs-associated latent/quiescent HSV-1 through an H3.3-dependent HSV-1 chromatinization involving the two H3.3 chaperones DAXX/ATRX and HIRA complexes. Additionally, the study reveals that PML NBs are major actors in latent/quiescent HSV-1 H3.3 chromatinization through a PML NB/histone H3.3/H3.3 chaperone axis.


Assuntos
Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Proteína da Leucemia Promielocítica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Estruturas do Núcleo Celular/metabolismo , Estruturas do Núcleo Celular/virologia , Células Cultivadas , Proteínas Correpressoras , DNA Viral/genética , DNA Viral/metabolismo , Feminino , Genoma Viral , Herpesvirus Humano 1/patogenicidade , Chaperonas de Histonas/metabolismo , Histonas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Chaperonas Moleculares , Proteínas Nucleares/metabolismo , Proteína da Leucemia Promielocítica/deficiência , Proteína da Leucemia Promielocítica/genética , Fatores de Transcrição/metabolismo , Latência Viral/genética , Latência Viral/fisiologia , Proteína Nuclear Ligada ao X/metabolismo
11.
BMC Ophthalmol ; 20(1): 81, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126990

RESUMO

BACKGROUND: Cataract surgery in diabetics is more technically challenging due to a number of factors including poor intraoperative pupil dilation and a higher risk of vision threatening complications. This study evaluates the safety and efficacy of an intracameral combination of 2 mydriatics and 1 anesthetic (ICMA, Mydrane) for cataract surgery in patients with well-controlled type-2 diabetes. METHODS: Post-hoc subgroup analysis of a phase 3 randomized study, comparing ICMA to a conventional topical regimen. Data were collected from 68 centers in Europe and Algeria. Only well-controlled type-2 diabetics, free of pre-proliferative retinopathy, were included. The results for non-diabetics are also reported. The primary efficacy variable was successful capsulorhexis without additional mydriatic treatment. Postoperative safety included adverse events, endothelial cell density and vision. RESULTS: Among 591 randomized patients, 57 (9.6%) had controlled type 2 diabetes [24 (42.1%) in the ICMA Group and 33 (57.9%) in the Topical Group; intention-to-treat (ITT) set]. Among diabetics, capsulorhexis was successfully performed without additional mydriatics in 24 (96.0%; modified-ITT set) patients in the ICMA Group and 26 (89.7%) in the Topical Group. These proportions were similar in non-diabetics. No diabetic patient [1 (0.5%) non-diabetics] in the ICMA Group had a significant decrease in pupil size (≥3 mm) intraoperatively compared to 4 (16.0%; modified-ITT set) diabetics [16 (7.3%) non-diabetics] in the Topical group. Ocular AE among diabetics occurred in 2 (8.0%; Safety set) patients in the ICMA Group and 5 (16.7%) in the Topical Group. Endothelial cell density at 1 month postoperatively was similar between groups in diabetics (P = 0.627) and non-diabetics (P = 0.368). CONCLUSIONS: ICMA is effective and can be safely used in patients with well-controlled diabetes, with potential advantages compared to a topical regimen including reduced systemic risk, better corneal integrity and reduced risk of ocular complications. TRIAL REGISTRATION: The trial was registered at (reference # NCT02101359) on April 2, 2014.


Assuntos
Catarata/complicações , Diabetes Mellitus Tipo 2/complicações , Implante de Lente Intraocular/métodos , Lidocaína/administração & dosagem , Midriáticos/administração & dosagem , Facoemulsificação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Câmara Anterior , Quimioterapia Combinada , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Resultado do Tratamento
12.
Virologie (Montrouge) ; 24(5): 295-306, 2020 Oct 01.
Artigo em Francês | MEDLINE | ID: mdl-33111703

RESUMO

Ocular manifestations of herpes simplex virus are mostly caused by herpes simplex (HSV-1), and are the second most frequent clinical manifestation of HSV-1 after cold sore. Corneal involvement, known as herpetic keratitis is by far the most frequent: in France, it affects 90,000 people with nearly 20,000 attacks each year. Herpes keratitis is considered to be the leading cause of infectious blindness in industrialized countries. In addition to its visual consequences, this recurrent disease may severely impact the quality of life. This review will first focus on current pathophysiological concepts and epidemiological data, then detail clinical forms and their treatment and finish with new therapeutic challenges and developing therapeutic strategies.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Ceratite Herpética , França , Herpes Simples/diagnóstico , Humanos , Ceratite Herpética/diagnóstico , Qualidade de Vida
13.
PLoS Pathog ; 12(9): e1005834, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27618691

RESUMO

Herpes simplex virus 1 (HSV-1) establishes latency in trigeminal ganglia (TG) sensory neurons of infected individuals. The commitment of infected neurons toward the viral lytic or latent transcriptional program is likely to depend on both viral and cellular factors, and to differ among individual neurons. In this study, we used a mouse model of HSV-1 infection to investigate the relationship between viral genomes and the nuclear environment in terms of the establishment of latency. During acute infection, viral genomes show two major patterns: replication compartments or multiple spots distributed in the nucleoplasm (namely "multiple-acute"). Viral genomes in the "multiple-acute" pattern are systematically associated with the promyelocytic leukemia (PML) protein in structures designated viral DNA-containing PML nuclear bodies (vDCP-NBs). To investigate the viral and cellular features that favor the acquisition of the latency-associated viral genome patterns, we infected mouse primary TG neurons from wild type (wt) mice or knock-out mice for type 1 interferon (IFN) receptor with wt or a mutant HSV-1, which is unable to replicate due to the synthesis of a non-functional ICP4, the major virus transactivator. We found that the inability of the virus to initiate the lytic program combined to its inability to synthesize a functional ICP0, are the two viral features leading to the formation of vDCP-NBs. The formation of the "multiple-latency" pattern is favored by the type 1 IFN signaling pathway in the context of neurons infected by a virus able to replicate through the expression of a functional ICP4 but unable to express functional VP16 and ICP0. Analyses of TGs harvested from HSV-1 latently infected humans showed that viral genomes and PML occupy similar nuclear areas in infected neurons, eventually forming vDCP-NB-like structures. Overall our study designates PML protein and PML-NBs to be major cellular components involved in the control of HSV-1 latency, probably during the entire life of an individual.


Assuntos
Genoma Viral/genética , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Proteína da Leucemia Promielocítica/metabolismo , Latência Viral/genética , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Herpesvirus Humano 1/fisiologia , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Mutação , Proteína da Leucemia Promielocítica/genética , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Transdução de Sinais , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Gânglio Trigeminal/virologia
14.
Ann Rheum Dis ; 76(1): 9-16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27789466

RESUMO

OBJECTIVES: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS. METHODS: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgement. We then validated the performance of the classification criteria in a separate cohort of patients. RESULTS: The final classification criteria are based on the weighted sum of five items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 min and an unstimulated salivary flow rate of ≤0.1 mL/min, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, that is, 96% (95% CI92% to 98%) and 95% (95% CI 92% to 97%), respectively. CONCLUSION: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well suited as criteria for enrolment in clinical trials.


Assuntos
Seleção de Pacientes , Glândulas Salivares/patologia , Sialadenite/patologia , Síndrome de Sjogren/classificação , Síndrome de Sjogren/diagnóstico , Autoanticorpos/sangue , Autoantígenos/imunologia , Biópsia , Ensaios Clínicos como Assunto , Consenso , Humanos , Guias de Prática Clínica como Assunto , RNA Citoplasmático Pequeno/imunologia , Ribonucleoproteínas/imunologia , Saliva/metabolismo , Sensibilidade e Especificidade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/patologia
15.
J Pediatr ; 186: 131-137.e1, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28457525

RESUMO

OBJECTIVE: To evaluate treatment, ocular complications and outcomes of children with pediatric uveitis not associated with juvenile idiopathic arthritis. STUDY DESIGN: This was a retrospective chart review of pediatric uveitis in children under 16 years of age, recruited from the pediatric rheumatology department at Bicêtre Hospital from 2005 to 2015. Patients with juvenile idiopathic arthritis-associated and infectious uveitis were excluded. We used the Standardization of Uveitis Nomenclature Working Group to classify uveitis, disease activity, and treatment end points. RESULTS: We enrolled 56 patients and 102 affected eyes. The mean age at diagnosis was 10 ± 3.5 years (range 3-15), and the mean follow-up 4.2 ± 3.3 years (1-15). The main diagnoses were idiopathic (55%), Behçet disease (15%), and sarcoidosis (5%). The main localization was panuveitis in 44 of 102 eyes (43%). Corticosteroid sparing treatment was needed in 62 of 102 eyes (60%). Second-line therapies included methotrexate and azathioprine, and the third-line therapy was a biologic agent, mainly infliximab, in 33 of 102 eyes (32%). Infliximab achieved uveitis inactivity in 14 of 18 eyes (80%), in all etiologies. Severe complications were present in 68 of 102 eyes (67%). The most common were synechiae 33% of eyes, cataract (20%), and macular edema (25%). Of these, 37% were present at diagnosis. Remission was achieved in 22 of 102 eyes (21%). CONCLUSIONS: Conventional therapies were insufficient to treat many of the cases of posterior or panuveitis. This study underlines the need for earlier and more aggressive treatment and antitumor necrosis factor-α therapy was rapidly efficient in most cases of refractory uveitis.


Assuntos
Uveíte/etiologia , Uveíte/terapia , Adolescente , Fatores Etários , Artrite Juvenil , Criança , Pré-Escolar , Tomada de Decisão Clínica , Feminino , Humanos , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/diagnóstico
16.
Ophthalmology ; 124(2): 160-169, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27863844

RESUMO

PURPOSE: To evaluate the quality of life (QoL) in patients with quiescent herpes simplex keratitis compared with control patients without ocular herpes. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty-three patients with a unilateral and relapsing herpes simplex keratitis (HSK group) that was quiescent during evaluation (no acute episode in the past 3 months) and 66 patients with no history of HSK (control group). Both groups were age and gender matched. METHODS: Three previously validated QoL questionnaires were used in this study: the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), Glaucoma Quality of Life 17 (Glau-QoL17) questionnaire, and Ocular Surface Disease Quality of Life (OSD-QoL) questionnaire. Each questionnaire covered various aspects of the disease. MAIN OUTCOME MEASURES: The outcomes of the 3 questionnaires were compared between groups. For the HSK group, the results were correlated to the clinical findings and the history of herpetic disease. RESULTS: The mean total questionnaire scores of the 3 QoL questionnaires were significantly lower in the HSK group compared with controls (NEI VFQ-25: 70.5±3.8 vs. 91.1±0.8, P < 0.0001; Glau-QoL17: 68.2±3.1 vs. 87.9±1.0, P < 0.0001; and OSD-QoL: 65.4±2.9 vs. 93.1±0.6, P < 0.0001, respectively). In the HSK group, the level of visual acuity (VA) in the affected eye had the greatest impact on QoL, inducing lower QoL results related to "general vision," "distance activities," "dependency," "peripheral vision," "self-image," "daily living," and "driving" dimensions. Decreased VA in the unaffected eye also negatively affected "self-image" and "driving" results. Patients with frequent HSK relapses had lower QoL related to "ocular pain" and "acknowledgement." CONCLUSIONS: Even during a quiescent phase of the disease, unilateral and relapsing HSK significantly impairs the QoL of patients to a similar level as most sight-threatening diseases. The decrease of VA has the greatest overall effect, but other factors also significantly affect QoL, such as the frequency of relapses.


Assuntos
Ceratite Herpética/psicologia , Qualidade de Vida , Transtornos da Visão/psicologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Ceratite Herpética/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Perfil de Impacto da Doença , Inquéritos e Questionários , Estados Unidos , Transtornos da Visão/virologia , Acuidade Visual
19.
J Virol ; 87(12): 7102-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23596303

RESUMO

Efficient intracellular transport of the capsid of alphaherpesviruses, such as herpes simplex virus 1 (HSV-1), is known to be dependent upon the microtubule (MT) network. Typically, the MT network radiates from an MT-organizing center (MTOC), which is, in most cases, the centrosome. During herpesvirus egress, it has been assumed that capsids travel first from the nucleus to the centrosome and then from the centrosome to the site of envelopment. Here we report that the centrosome is no longer a primary MTOC in HSV-1-infected cells, but it retains this function in cells infected by another alphaherpesvirus, pseudorabies virus (PrV). As a result, MTs formed at late times after infection with PrV grow from a major, centralized MTOC, while those formed after HSV-1 infection arise from dispersed locations in the cytoplasm, indicating the presence of alternative and minor MTOCs. Thus, loss of the principal MT nucleating center in cells following HSV-1 infection raises questions about the mechanism of HSV-1 capsid egress. It is possible that, rather than passing via the centrosome, capsids may travel directly to the site of envelopment after exiting the nucleus. We suggest that, in HSV-1-infected cells, the disruption of centrosomal functions triggers reorganization of the MT network to favor noncentrosomal MTs and promote efficient viral spread.


Assuntos
Centrossomo/metabolismo , Centrossomo/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Suídeo 1/patogenicidade , Animais , Capsídeo/metabolismo , Linhagem Celular , Chlorocebus aethiops , Fibroblastos/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Herpesvirus Suídeo 1/fisiologia , Humanos , Microtúbulos/metabolismo , Microtúbulos/virologia , Pseudorraiva/virologia , Células Vero
20.
J Virol ; 87(20): 11008-18, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23903849

RESUMO

During infection by herpes simplex virus 1 (HSV-1), the viral capsid is transported around the cytoplasm along the microtubule (MT) network. Although molecular motors have been implicated in this process, the composition of the molecular machinery required for efficient directional transport is unknown. We previously showed that dystonin (BPAG1) is recruited to HSV-1 capsids by the capsid-bound tegument protein pUL37 to promote efficient cytoplasmic transport of capsids during egress. Dystonin is a cytoskeleton cross-linker which localizes at MT plus ends and has roles in retrograde and anterograde transport in neurons. In this study, we investigated the role of dystonin during the entry stages of HSV-1 infection. Because of the way in which the MT network is organized, capsids are required to change their direction of motion along the MTs as they travel from the point of entry to the nucleus, where replication takes place. Thus, capsids first travel to the centrosome (the principal microtubule organizing center) by minus-end-directed transport and then switch polarity and travel to the nucleus by plus-end-directed transport. We observed that transport of capsids toward the centrosome was slowed, but not blocked, by dystonin depletion. However, transport of capsids away from the centrosome was significantly impaired, causing them to accumulate in the vicinity of the centrosome and reducing the numbers reaching the nucleus. We conclude that, during entry of HSV-1, dystonin has a specific role in plus-ended transport of capsids from the centrosome to the nucleus.


Assuntos
Capsídeo/metabolismo , Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Herpesvirus Humano 1/fisiologia , Interações Hospedeiro-Patógeno , Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Internalização do Vírus , Animais , Linhagem Celular , Distonina , Humanos
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