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1.
ACR Open Rheumatol ; 6(4): 172-178, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38196183

RESUMO

OBJECTIVE: Given fibromyalgia (FM) frequently co-occurs with autoimmune disease, this study was initiated to objectively evaluate FM in a multiracial/ethnic cohort of patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE were screened for FM using the 2016 FM classification criteria during an in-person rheumatologist visit. We evaluated hybrid Safety of Estrogens in Lupus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) scores, SLE classification criteria, and Systemic Lupus International Collaborating Clinics damage index. We compared patients with and without FM and if differences were present, compared patients with FM with patients with non-FM related chronic pain. RESULTS: 316 patients with SLE completed the FM questionnaire. 55 (17.4%) met criteria for FM. The racial composition of patients with FM differed from those without FM (P = 0.023), driven by fewer Asian patients having FM. There was no difference in SLE disease duration, SELENA-SLEDAI score, or active serologies. There was more active arthritis in the FM group (16.4%) versus the non-FM group (1.9%) (P < 0.001). The Widespread Pain Index and Symptom Severity Score did not correlate with degree of SLE activity (r = -0.016; 0.107) among patients with FM or non-FM chronic pain (r = 0.009; -0.024). Regarding criteria, patients with FM had less nephritis and more malar rash. Systemic Lupus International Collaborating Clinics damage index did not differ between groups. CONCLUSION: Except for arthritis, patients with SLE with FM are not otherwise clinically or serologically distinguishable from those without FM, and Widespread Pain Index and Symptom Severity Score indices do not correlate with SLEDAI. These observations support the importance of further understanding the underlying biology of FM in SLE.

3.
Arthritis Rheumatol ; 74(2): 284-294, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34347939

RESUMO

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.


Assuntos
Antirreumáticos/uso terapêutico , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , Ad26COVS1/uso terapêutico , Adulto , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Vacina BNT162/uso terapêutico , Vacinas contra COVID-19/imunologia , Estudos de Casos e Controles , Estudos de Coortes , ELISPOT , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Interferon gama/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Prednisona/uso terapêutico , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologia , Exacerbação dos Sintomas
4.
Arthritis Res Ther ; 22(1): 191, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807233

RESUMO

BACKGROUND: Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients. METHODS: Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation. RESULTS: Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient's preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%). CONCLUSIONS: In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.


Assuntos
Antirreumáticos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lúpus Eritematoso Sistêmico , Idoso , Antirreumáticos/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos Retrospectivos , Exacerbação dos Sintomas
5.
Rheumatology (Oxford) ; 51(6): 1086-92, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22308531

RESUMO

OBJECTIVE: The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies. METHODS: A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed. RESULTS: Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology. CONCLUSION: Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage.


Assuntos
Doenças Fetais , Bloqueio Cardíaco , Sistema de Condução Cardíaco , Lúpus Eritematoso Sistêmico/congênito , Anticorpos Antinucleares/metabolismo , Biomarcadores/metabolismo , Calcinose/imunologia , Calcinose/metabolismo , Calcinose/patologia , Feminino , Morte Fetal/imunologia , Morte Fetal/metabolismo , Morte Fetal/patologia , Doenças Fetais/imunologia , Doenças Fetais/mortalidade , Doenças Fetais/patologia , Fibrose/imunologia , Fibrose/metabolismo , Fibrose/patologia , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/mortalidade , Bloqueio Cardíaco/patologia , Sistema de Condução Cardíaco/imunologia , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/patologia , Humanos , Lactente , Recém-Nascido , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/patologia , Miocárdio/imunologia , Miocárdio/metabolismo , Miocárdio/patologia , Gravidez , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
6.
Rheumatology (Oxford) ; 48(5): 513-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19286697

RESUMO

OBJECTIVE: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy. METHODS: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year. RESULTS: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices. CONCLUSION: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.


Assuntos
Antígenos CD/metabolismo , Endotélio Vascular/metabolismo , Córtex Renal/irrigação sanguínea , Nefrite Lúpica/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Biomarcadores/metabolismo , Biópsia , Capilares/metabolismo , Capilares/patologia , Receptor de Proteína C Endotelial , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Córtex Renal/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
7.
J Rheumatol ; 36(1): 89-95, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19040311

RESUMO

OBJECTIVE: Individualized therapy based on genetic background and monitoring of metabolites can optimize drug safety and efficacy. Such an approach is available for azathioprine (AZA), the thiopurine antimetabolite. AZA exerts therapeutic effects when metabolized to the active thiopurine nucleotide, 6-thioguanine (6-TGN). In inflammatory bowel disease (IBD), 6-TGN levels in the target range of 235-400 pmol/8x10(8) red blood cells (RBC) are associated with a high likelihood of response. Our objective was to evaluate whether drug escalation based on metabolite levels improves efficacy and maintains safety in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a 6-month open-label dose-escalation clinical study of patients with active SLE treated with azathioprine dosed by body weight and metabolite levels. The primary endpoint was >or=50% improvement in any one parameter of disease activity, or 50% decrease in glucocorticoid dose. RESULTS: Of 50 patients enrolled in the study, 21 achieved clinical responses, 13 of whom had 6-TGN<235 pmol/8 x10(8) RBC. Ten patients had no clinical response at 6 months, yet achieved either therapeutic IBD 6-TGN levels (>235, n=4) or received maximum AZA dose>or=3.5 mg/kg (n=6). In 19 patients the drug was discontinued prematurely due to side effects or SLE activity. For those patients in whom either liver function test or white blood cell count abnormalities were encountered, metabolites guided attribution to drug or disease activity. CONCLUSION: Clinical responses in SLE can occur at levels of 6-TGN lower than the target range established for IBD. During followup, measurements of AZA metabolites may provide a rational approach to safety.


Assuntos
Azatioprina/farmacocinética , Monitoramento de Medicamentos/métodos , Imunossupressores/farmacocinética , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Farmacogenética , Adulto , Idoso , Azatioprina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Heterozigoto , Humanos , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Metiltransferases/genética , Pessoa de Meia-Idade , Cooperação do Paciente , Fenótipo , Tioguanina/sangue , Adulto Jovem
8.
J Rheumatol ; 36(2): 298-305, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19040310

RESUMO

OBJECTIVE: To evaluate responses to mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) in lupus nephritis in a multiethnic population. METHODS: This was a retrospective study of all patients with systemic lupus erythematosus (SLE) that underwent kidney biopsy at New York University Medical Center. Patients with followup of at least 6 months were included. Clinical response was defined as complete (return to +/- 10% of normal) or partial (improvement of 50% in abnormal renal measurements). RESULTS: Ninety-nine patients were included in the study: 86% females, 86% non-Caucasian, age 34.2 +/- 1.1 years, 62% with proliferative nephritis (PN; ISN/RPS-III and IV), and 32% with membranous nephritis (MN; ISN/RPS-V). Of the 70 patients with PN, 37 were treated with CYC and 33 with MMF. The baseline characteristics of the 2 treatment groups were different in the incidence of ISN/RPS-IV, values of serum creatinine and serum albumin, and type of insurance (p < 0.05). The response rate was greater in the MMF than in the CYC group (70% vs 41%). Responses to MMF were different in Asians (11/11), Caucasians (4/5), African Americans (3/5), and Hispanics (5/11). Responses to CYC had a similar distribution (Asians 6/10, Caucasians 4/5, African Americans 4/9, Hispanics 1/11). In the MN group (N = 23) responses were similar to the PN group (73% MMF and 38% CYC). After adjusting for race, serum creatinine, serum albumin, type of insurance, and class of nephritis, in a logistic regression model, response to MMF was superior to CYC: OR 6.2 (95% CI 1.9-20.2). Hispanics had worse outcome than Caucasians (OR 0.17). Longterm followup suggested no difference in maintenance with MMF or CYC. CONCLUSION: After controlling for the fact that less severe nephritis is preferentially treated with MMF, we found overall that response to MMF was superior to CYC. In this US population, ethnicity was observed to have an influence on response.


Assuntos
Ciclofosfamida/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Ácido Micofenólico/análogos & derivados , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Creatinina/análise , Creatinina/sangue , Feminino , Humanos , Imunossupressores/administração & dosagem , Nefrite Lúpica/sangue , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Grupos Raciais , Estudos Retrospectivos , Albumina Sérica/análise , Adulto Jovem
9.
Arthritis Rheum ; 54(11): 3623-32, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17075807

RESUMO

OBJECTIVE: Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week. RESULTS: Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring 40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment. CONCLUSION: These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare.


Assuntos
Glucocorticoides/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisona/administração & dosagem , Doença Aguda , Adolescente , Adulto , Autoanticorpos/sangue , Criança , Complemento C3a/metabolismo , DNA/imunologia , Método Duplo-Cego , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Placebos , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
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