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A 17-year-old girl recently diagnosed with systemic lupus erythematosus (SLE) presented to the Emergency Room with acute onset of psychosis. A variety of potential etiologies, including those related to SLE, to the treatment of her SLE, or to another psychiatric condition, are discussed. In addition, the work-up and management decisions for this patient are reviewed in detail.
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Glucocorticoides/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Prednisolona/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Psicoses Induzidas por Substâncias/diagnósticoRESUMO
The erythrocyte sedimentation rate (ESR) has become a ubiquitously used technique in medicine as a marker of systemic illness. The test involves placing anticoagulated whole blood into an upright test tube and monitoring the rate at which red blood cells (RBC) fall over time. Negative charges keep RBC from sticking together. If this charge is neutralised, RBC stack into chains, or rouleaux, and fall more rapidly. ESR can be measured with a variety of tests: Westergren and modified Westergren; Wintrobe; micro-ESR. The Westergren is the most commonly used method of performing the ESR. Technical factors, such as temperature, time from specimen collection, tube orientation and vibration, can affect the results. RBC size, shape and concentration impact the ESR. Plasma characteristics are also important determinants of the ESR. Other factors that can change ESR include age, sex, race, medications and disease states, such as obesity, hypofibrinogenaemia and congestive heart failure. Other acute-phase reactants besides the ESR include C-reactive protein, fibrinogen, complement, ferritin, plasma viscosity, serum amyloid A and albumin. When clinical suspicion for infection or inflammation is low, a normal ESR can reassure that there is no active disease. The slow rise (48â h) and fall of the ESR relative to other acute-phase reactants may make it superior for monitoring inflammation in more chronic conditions. In conjunction with physical findings and other laboratory values, the ESR value can be used to screen for disease or disease complications, aid in disease diagnosis or assess disease activity or response to therapy.
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Sedimentação Sanguínea , Inflamação/sangue , Criança , HumanosRESUMO
BACKGROUND: Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30-45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae. Little is known about the rate at which providers evaluate TMJ involvement in their clinical practice. METHODS: Data were obtained from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Data fields related to assessment for TMJ arthritis were added in 2019. Patients were included in the study if they had a diagnosis of JIA and had data recorded between January 2020 and August 2021. Standard descriptive statistics were used to describe demographic and clinical features. RESULTS: A total of 17,761 visits were reviewed for a total of 7473 patients with JIA. A total of 52.7% of patients had maximal mouth opening (MMO) recorded as finger breadths or total incisal distance (TID). Only 8% had TID measured. A total of 5.0% had MRI with contrast performed. A total of 939 patients had a diagnosis of TMJ arthritis. Of these, 28.5% had an MRI documented, 83% had an MMO documented, and 40% had TID measured. Few patient-level characteristics were statistically related to having MMO assessed. MRI was more likely to be obtained in older and in female patients. MMO was recorded at a given visit > 80% of the time at 17 sites, and it was recorded < 1% of the time at 8 sites. MRIs were infrequently performed at all sites, with 27 sites having no MRIs obtained and only 7 sites having an MRI obtained at > 10% of visits. CONCLUSIONS: MMO is not consistently measured in patients with JIA, and it is rarely measured quantitatively. Similarly, TMJ MRIs are rarely obtained in patients with JIA. Site of care is more associated with TMJ assessments than patient-level characteristics. These data suggest that provider education is needed to improve the assessment of the TMJ in patients with JIA to enable earlier recognition and prevent long-term complications.
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Artrite Juvenil , Reumatologia , Transtornos da Articulação Temporomandibular , Criança , Humanos , Feminino , Idoso , Artrite Juvenil/diagnóstico , Artrite Juvenil/diagnóstico por imagem , Estudos Retrospectivos , Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/etiologia , Imageamento por Ressonância Magnética/métodosRESUMO
Here we report the use of denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), as monotherapy for multicentric carpotarsal osteolysis syndrome (MCTO) in an 11.5-year-old male with a heterozygous missense mutation in MAFB (c.206C>T; p.Ser69Leu). We treated the subject with 0.5 mg/kg denosumab every 60-90 days for 47 months and monitored bone and mineral metabolism, kidney function, joint range of motion (ROM), and bone and joint morphology. Serum markers of bone turnover reduced rapidly, bone density increased, and renal function remained normal. Nevertheless, MCTO-related osteolysis and joint immobility progressed during denosumab treatment. Symptomatic hypercalcemia and protracted hypercalciuria occurred during weaning and after discontinuation of denosumab and required treatment with zoledronate. When expressed in vitro, the c.206C>T; p.Ser69Leu variant had increased protein stability and produced greater transactivation of a luciferase reporter under the control of the PTH gene promoter than did wild-type MafB. Based on our experience and that of others, denosumab does not appear to be efficacious for MCTO and carries a high risk of rebound hypercalcemia and/or hypercalciuria after drug discontinuation. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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OBJECTIVE: The present study was undertaken to evaluate high-quality care delivery in the context of provider goal-setting activities and a multidisciplinary care model using an electronic health record (EHR)-enabled pediatric lupus registry. We then determined associations between care quality and prednisone use among youth with systemic lupus erythematosus (SLE). METHODS: We implemented standardized EHR documentation tools to autopopulate a SLE registry. We compared pediatric Lupus Care Index (pLCI) performance (range 0.0-1.0; 1.0 representing perfect metric adherence) and timely follow-up 1) before versus during provider goal-setting activities and population management, and 2) in a multidisciplinary lupus nephritis versus rheumatology clinic. We estimated associations between pLCI and subsequent prednisone use adjusted for time, current medication, disease activity, clinical features, and social determinants of health. RESULTS: We analyzed 830 visits by 110 patients (median 7 visits per patient [interquartile range 4-10]) over 3.5 years. The provider-directed activity was associated with improved pLCI performance (adjusted ß 0.05 [95% confidence interval (95% CI) 0.01, 0.09]; mean 0.74 versus 0.69). Patients with nephritis in multidisciplinary clinic had higher pLCI scores (adjusted ß 0.06 [95% CI 0.02, 0.10]) and likelihood of timely follow-up than those in rheumatology (adjusted relative risk [RR] 1.27 [95% CI 1.02, 1.57]). A pLCI score of ≥0.50 was associated with 0.72-fold lower adjusted risk of subsequent prednisone use (95% CI 0.53, 0.93). Minoritized race, public insurance, and living in areas with greater social vulnerability were not associated with reduced care quality or follow-up, but public insurance was associated with higher risk of prednisone use. CONCLUSION: Greater attention to quality metrics is associated with better outcomes in childhood SLE. Multidisciplinary care models with population management may additionally facilitate equitable care delivery.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Adolescente , Humanos , Criança , Prednisona/uso terapêutico , Objetivos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Atenção à SaúdeRESUMO
Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA.
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Artrite Juvenil , Deformidades Dentofaciais , Transtornos da Articulação Temporomandibular , Criança , Humanos , Artrite Juvenil/complicações , Artrite Juvenil/terapia , Artrite Juvenil/diagnóstico , Consenso , Qualidade de Vida , Transtornos da Articulação Temporomandibular/etiologia , Transtornos da Articulação Temporomandibular/terapiaRESUMO
OBJECTIVE: To determine whether there is a temporal association between arthritis and uveitis activity among children with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS: Uveitis and arthritis data from patients with JIA-U age ≤21 years were collected from July 2013 to December 2019 at a tertiary care center. Arthritis activity was assessed at each rheumatology visit, and the primary outcome was the presence of active uveitis at ophthalmologic examination within 45 days of the rheumatology visit. Repeated-measures logistic regression was used to evaluate the temporal association between any uveitis activity within 45 days of arthritis activity. Models were adjusted for demographic-, disease-, and treatment-related factors. RESULTS: A total of 98 patients were included: 81 (83%) female, 67 (69%) antinuclear antibody positive, 59 (60%) oligoarticular, and 13 (13%) enthesitis-related arthritis (ERA) subtypes. There were 1,229 rheumatology visits, with a median of 13 visits per patient (interquartile range 7-18). Concordance between arthritis and uveitis activity was observed 73% of the time (694 of 947). There was an independent temporal association between uveitis and arthritis activity (odds ratio 2.47 [95% confidence interval 1.72-3.54]; P < 0.01), adjusted for demographic and disease characteristics. Use of combination biologic and nonbiologic disease-modifying antirheumatic drugs, female sex, HLA-B27 positivity, and ERA and polyarticular (rheumatoid factor negative) subtypes were associated with decreased odds of active uveitis at any time point. CONCLUSION: In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity. These novel results suggest that an arthritis flare should prompt an expedited referral to the ophthalmologist.
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Artrite Juvenil/etiologia , Progressão da Doença , Uveíte/complicações , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
Patients with juvenile idiopathic arthritis (JIA) often have involvement of the temporomandibular joint (TMJ) during their disease course. Active arthritis of the TMJ remains difficult to assess. Clinical signs and symptoms alone are unreliable, and active TMJ arthritis needs confirmation by gadolinium-enhanced MRI. In recent years, changes in treatment approach have occurred. This article discusses the latest evidence on diagnosis and treatment of JIA-associated TMJ arthritis.
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Artrite Juvenil , Transtornos da Articulação Temporomandibular , Artrite Juvenil/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/etiologia , Transtornos da Articulação Temporomandibular/terapiaRESUMO
BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome combines acute inflammatory nephritis (AIN) and uveitis. Uveitis in TINU often requires systemic immunomodulatory therapy (IMT), including steroid-sparing agents. Although common for other noninfectious uveitides, the use of tumor necrosis factor-α inhibitors (TNFi) in TINU has seldom been described. METHODS: This retrospective case series included patients <18 years of age with TINU followed at our tertiary care pediatric hospital. Disease characteristics at time of diagnosis and subsequent ophthalmological and rheumatologic evaluations were extracted from the record. AIN was defined as the presence of abnormal renal function and urinalysis or renal biopsy findings consistent with TINU. Uveitis grading, site of inflammation, inactivity, and flare were defined according to Standardization of Uveitis Nomenclature. RESULTS: A total of 10 patients (median age, 12.3 years; 6 females) were included. AIN preceded uveitis onset in 6 patients. Uveitis was bilateral at onset in 7 patients. Uveitis inactivity was achieved with systemic corticosteroids (CS) in 2 and with mycophenolate mofetil (MMF) in 3 patients. Because of persistent ocular inflammation, despite CS and IMT, 4 patients were treated with TNFi. All rapidly achieved uveitis quiescence and maintained prolonged inactivity under combined treatment with TNFi and MMF. CONCLUSIONS: Most patients in our study cohort required a steroid-sparing immunomodulator to achieve and maintain uveitis control. In the 50% of the cohort in whom conventional IMTs were inadequate, TNFi were able to maintain quiescence. TNF inhibition might be a useful treatment in IMT-refractory uveitis in TINU patients.
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Nefrite Intersticial , Uveíte , Criança , Feminino , Humanos , Imunomodulação , Nefrite Intersticial/tratamento farmacológico , Estudos Retrospectivos , Fator de Necrose Tumoral alfa , Uveíte/tratamento farmacológicoRESUMO
BACKGROUND: Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA. This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients. FINDINGS: This is a cross sectional/retrospective study involving patients with JSpA followed in a tertiary referral hospital. Two hundred twenty-three patients were enrolled in the study. The prevalent diagnosis was enthesitis-related arthritis (ERA) (62%) followed by juvenile psoriatic arthritis (PsA), undifferentiated arthritis (UA), and the arthropathies associated with inflammatory bowel disease (IBD-A) (18, 14, 6%, respectively). Uveitis was reported in twenty-four patients (11%) of the JSpA cohort (JSpA-U). ERA patients had the highest uveitis prevalence (ERA-U) (13%) with similar prevalences in UA, PsA and in IBD-A (7% each). The prevalence of HLA-B27 positivity was similar amongst the entire JSpA-U cohort (N = 22, 45%) and those with ERA-U (N = 8, 44%). The overall prevalence of symptomatic uveitis was 79%. Neither the likelihood of uveitis, nor of symptomatic uveitis, varied by HLA-B27 status either in the entire cohort nor in those with ERA. CONCLUSIONS: About one-tenth of patients developed uveitis, the majority of which was symptomatic. Fewer than half of the patients with uveitis were HLA-B27 positive. HLA-B27 status was not statistically associated with either the development of uveitis or symptomaticity of uveitis.
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Artrite Juvenil/epidemiologia , Espondiloartropatias/epidemiologia , Uveíte/epidemiologia , Adolescente , Artrite Juvenil/imunologia , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/imunologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Antígeno HLA-B27/imunologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Masculino , Prevalência , Estudos Retrospectivos , Espondiloartropatias/imunologia , Uveíte/imunologiaRESUMO
PURPOSE: To describe the prevalence of symptoms with noninfectious uveitis (NIU) in a pediatric cohort and to assess the association between the presence of symptoms with first episode of uveitis (first-U) compared to symptoms at uveitis recurrence. METHODS: The medical records of patients with NIU treated at a tertiary referral hospital from March 2008 to November 2107 were reviewed retrospectively. Symptomaticity (eye pain, eye redness, photosensitivity) was captured at initial uveitis activation and subsequent episodes. Univariate logistic regression modeling was used to identify clinical features associated with symptomatic first-U. Ordinal regression identified patient characteristics associated with symptomatic recurrence. RESULTS: A total of 118 cases were reviewed; of these, 92 were followed for at least 6 months and had at least 1 reactivation. Juvenile idiopathic arthritis-related uveitis (JIAU) was the most common diagnosis (67/118 [57%]), followed by idiopathic uveitis (33%). In the majority, uveitis was restricted to the anterior chamber (82%). Of the 118 cases, 58 patients (49%) had symptomatic first-U, 34% JIA versus 69% non-JIA. Non-JIAU, age ≥7 years, and negative antinuclear antibody (ANA) test were significantly associated with symptomatic first-U; spondyloarthritis was not. With recurrence, half had symptoms: 41% JIA versus 66% non-JIA. Of those who had symptomatic first-U, 35% were asymptomatic at recurrence. Those with JIA had 50% or less odds of symptomaticity at reactivation. Complications did not vary based on having had symptoms at first-U. CONCLUSIONS: Non-JIA diagnosis, older age, and ANA-negativity were associated with symptomatic first-U in our study cohort, but no patient characteristics were significantly associated with symptomatic recurrence. Clinical patterns may change during disease course, with uveitis switching from symptomatic to asymptomatic, which has implications for uveitis monitoring recommendations.
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Câmara Anterior/diagnóstico por imagem , Artrite Juvenil/complicações , Uveíte/diagnóstico , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Recidiva , Estudos Retrospectivos , Estados Unidos/epidemiologia , Uveíte/epidemiologia , Uveíte/etiologia , Adulto JovemRESUMO
OBJECTIVE: Systemic immunosuppressive treatment of pediatric chronic anterior uveitis (CAU), both juvenile idiopathic arthritis-associated and idiopathic anterior uveitis, varies, making it difficult to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments using comparative effectiveness analysis techniques. METHODS: A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup that performed a literature review on pharmacologic treatments, held teleconferences, and developed a case-based survey administered to the CARRA membership to delineate treatment practices. We held 3 face-to-face consensus meetings using nominal group technique to develop CTPs. RESULTS: The survey identified areas of treatment practice variability. We developed 2 CTPs for the treatment of CAU, case definitions, and monitoring parameters. The first CTP is directed at children who are naive to steroid-sparing medication, and the second at children initiating biologic therapy, with options for methotrexate, adalimumab, and infliximab. We defined a core data set and outcome measures, with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted to accept the CTPs with a >95% approval (n = 233). CONCLUSION: Using consensus methodology, 2 standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options.
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Antirreumáticos/uso terapêutico , Artrite Juvenil/complicações , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Criança , Protocolos Clínicos , Técnica Delphi , Humanos , Uveíte Anterior/etiologiaRESUMO
Anterior uveitis (AU), inflammation of the iris, choroid or ciliary body, can cause significant eye morbidity, including visual loss. In the pediatric age group, the most common underlying diagnosis for AU is juvenile idiopathic associated uveitis and idiopathic AU, which are the focus of this paper. AU is often resistant to medications such as topical corticosteroids and methotrexate. In the past 15 years, biologic agents (biologics) have transformed treatment. In this review, we discuss those in widespread use and those with more theoretical applications for anterior uveitis. Tumor necrosis factor alpha inhibitors (anti-TNFα) have been available the longest and are used widely to treat pediatric uveitis. The effects of anti-TNFα in children are described mostly in small retrospective case series. Together, the literature suggests that the majority of children treated with anti-TNFα achieve decreased uveitis activity and reduced corticosteroid burden. However, many will have disease flares even on treatment. Only a few small studies directly compare outcomes between alternate anti-TNFα (infliximab and adalimumab). The use of different uveitis grading systems, inclusion criteria, and outcome measures makes cross-study comparisons difficult. Whether the achievement and maintenance of inactive disease occurs more frequently with certain anti-TNFα remains controversial. Newer biologics that modulate the immune system differently (e.g., interfere with Th17 activation through IL-17a and IL-6 blockade, limit T lymphocyte costimulation, and deplete B lymphocytes), have shown promise for uveitis. Studies of these agents are small and include mostly adults. Additional biologics are also being explored to treat uveitis. With their advent, we are hopeful that outcomes will ultimately be improved for children with AU. With many biologics available, much work remains to identify the optimal inflammatory pathway to target in AU.
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Produtos Biológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte Anterior/tratamento farmacológico , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Criança , Glucocorticoides/uso terapêutico , Humanos , Infliximab/uso terapêutico , Metotrexato/uso terapêuticoRESUMO
PURPOSE: To evaluate reactivation of pediatric uveitis during/following treatment with tumor necrosis factor alpha inhibition (anti-TNFα). DESIGN: Retrospective cohort study. METHODS: We assessed the incidence of uveitis reactivation in children ≤18 years who had achieved uveitis quiescence under anti-TNFα. Survival analysis was used to calculate reactivation rates while still on (primary outcome), and following discontinuation of (secondary outcome), anti-TNFα. Potential predictive factors were assessed. RESULTS: Among 50 children observed to develop quiescence of uveitis under anti-TNFα, 39 met criteria to be "at risk" of the primary (19 for the secondary) outcome. 60% were female, â¼half had juvenile idiopathic arthritis, and most were treated with infliximab. Overall, the estimated proportion relapsing within 12 months was 27.8% (95% confidence interval [CI]: 15.9%-45.8%); the estimated probability of reactivation was higher following (63.8% [95% CI: 38.9%-87.7%]) vs before (21.6% [95% CI: 10.8%-40.2%]) anti-TNFα discontinuation. Among those who discontinued anti-TNFα, the likelihood of reactivation was higher for those treated with adalimumab vs infliximab (hazard ratio [HR] 13.4, P = .01, 95% CI: 2.2-82.5) and those with older age at uveitis onset (HR 1.3, P = .09, 95% CI: 1.0-1.7). The duration of suppression, on medication, did not significantly affect the likelihood of reactivation when quiescence was maintained for ≥1.5 years. CONCLUSIONS: Approximately 75% of children remaining on anti-TNFα following achievement of uveitis quiescence remain quiescent at 1 year. However, most reactivate following anti-TNFα discontinuation. These results suggest that infliximab more often is followed by remission, off medication, than adalimumab. The data do not suggest that maintenance of suppression for more than 1.5 years decreases the reactivation risk.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/diagnóstico , Adalimumab , Adolescente , Artrite Juvenil/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Infliximab , Masculino , Recidiva , Estudos Retrospectivos , Uveíte/tratamento farmacológicoRESUMO
The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery.
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Artrite/diagnóstico , Artrite/terapia , Betametasona/administração & dosagem , Eletroporação/métodos , Sonicação/métodos , Administração Tópica , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina , Terapia Combinada/métodos , Sinergismo Farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sonicação/instrumentação , Resultado do TratamentoRESUMO
Accumulating evidence indicates that regulatory T cells play a crucial role in preventing autoimmunity. To examine the processes by which regulatory CD4(+) T cells are produced during immune repertoire formation, we have developed transgenic mice that express the influenza virus hemagglutinin (HA) and coexpress major histocompatibility complex class II-restricted T cell receptors (TCRs) with varying affinities for the HA-derived CD4(+) T cell determinant S1. We show that interactions with a single self-peptide can induce thymocytes bearing an autoreactive TCR to undergo selection to become CD4(+) CD25(+) regulatory T cells, and that thymocytes bearing TCRs with low affinity for S1 do not undergo selection into this pathway. We show that CD4(+) thymocytes with identical specificity for the S1 self-peptide can undergo overt deletion versus abundant selection to become CD4(+) CD25(+) regulatory T cells in response to variations in expression of the S1 self-peptide in different lineages of HA transgenic mice. We also show that CD4(+) CD25(+) T cells proliferate in response to their selecting self-peptide in the periphery. Moreover, they do not proliferate in response to lymphopenia in the absence of the selecting self-peptide, reflecting a low level of expression of the high-affinity receptor for IL-7 (CD127) relative to conventional CD4(+) T cells. These studies are determining how specificity for self-peptides directs the thymic selection and peripheral expansion of CD4(+) CD25(+) regulatory T cells. Moreover, the differing responsiveness of CD4(+) CD25(+) regulatory T cells to cytokine- versus self-peptide-mediated signals may direct their accumulation to sites where the self-peptide is expressed.
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Linfócitos T CD4-Positivos/imunologia , Receptores de Interleucina-2/imunologia , Linfócitos T/imunologia , Animais , Autoimunidade , Camundongos , Receptores de Antígenos de Linfócitos T/imunologia , Timo/imunologiaRESUMO
OBJECTIVE: To evaluate the outcome of tumor necrosis factor-α inhibition (anti-TNF) for pediatric uveitis. METHODS: We retrospectively assessed children (age ≤ 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥ 2 consecutive ophthalmological examinations ≥ 28 days apart while taking no oral and ≤ 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. RESULTS: Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%-87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%-76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%-80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%-31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%-43%). CONCLUSION: Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF.