RESUMO
This study investigated risk factors for osteonecrosis involving multiple joints (MJON) among glucocorticoid-treated patients. The best predictor of MJON was cumulative oral glucocorticoid dose. Risk of MJON was 12-fold higher in patients who had a second risk factor for osteonecrosis. Further research is needed into strategies for prevention of MJON. INTRODUCTION: Osteonecrosis (ON) is a debilitating musculoskeletal condition in which bone cell death can lead to mechanical failure. When multiple joints are affected, pain and disability are compounded. Glucocorticoid treatment is one of the most common predisposing factors for ON. This study investigated risk factors for ON involving multiple joints (MJON) among glucocorticoid-treated patients. METHODS: Fifty-five adults with glucocorticoid-induced ON were prospectively enrolled. MJON was defined as ON in ≥ three joints. Route, dose, duration, and timing of glucocorticoid treatment were assessed. RESULTS: Mean age of enrolled subjects was 44 years, 58% were women. Half had underlying conditions associated with increased ON risk: systemic lupus erythematosus (29%), acute lymphoblastic leukemia (11%), HIV (9%), and alcohol use (4%). Mean daily oral dose of glucocorticoids was 29 mg. Average cumulative oral dose was 30 g over 5 years. The best predictor of MJON was cumulative oral glucocorticoid dose. For each increase of 1,000 mg, risk of MJON increased by 3.2% (95% CI 1.03, 1.67). Glucocorticoid exposure in the first 6 months of therapy, peak dose (oral or IV), and mean daily dose did not independently increase risk of MJON. The risk of MJON was 12-fold in patients who had a second risk factor (95% CI 3.2, 44.4). CONCLUSIONS: Among patients with glucocorticoid-induced ON, cumulative oral dose was the best predictor of multi-joint disease; initial doses of IV and oral glucocorticoids did not independently increase risk. Further research is needed to better define optimal strategies for prevention and treatment of MJON.
Assuntos
Artropatias , Lúpus Eritematoso Sistêmico , Osteonecrose , Adulto , Feminino , Glucocorticoides/efeitos adversos , Humanos , Osteonecrose/induzido quimicamente , Osteonecrose/epidemiologia , Fatores de RiscoRESUMO
Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience. Differences in socio-demographic and clinical characteristics between participants and non-participants were evaluated. Results A total of 204 (86%) of 238 socioeconomically and racially diverse SLE patients completed PROMIS CATs. There were no significant differences between participants and non-participants. Time constraints were cited most frequently as reasons for non-participation. More than 75% of individuals submitted positive comments, including approval of the content and format of questions, and the survey's promotion of self-reflection. A minority of participants cited challenges, most often related to question phrasing (8%) and technical difficulties (6%). Conclusions The administration of PROMIS CATs was feasible and positively received in a diverse cohort of SLE outpatients. Neither socio-demographic nor disease characteristics were significant barriers to successful completion of PROMIS CATs. PROMIS CATs have great potential for efficiently measuring important patient-centered outcomes in routine clinical care of a wide range of SLE patients.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Pacientes Ambulatoriais/psicologia , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Compreensão , Estudos de Viabilidade , Retroalimentação Psicológica , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Rising anti-double-stranded (ds) DNA titers have been shown by some, but not all, studies to be predictive of disease flares in systemic lupus erythematosus (SLE). We hypothesized that a rapid and substantial rise in anti-dsDNA titer (anti-dsDNA surge) would be a good predictor of a clinically important SLE flare. METHODS: A matched case-control study was conducted in an academic rheumatology practice setting. Our primary endpoint was the occurrence of a severe SELENA-SLEDAI (SS) flare within six months of an anti-dsDNA surge, and secondary endpoints were mild/moderate SS flares, as well as BILAG A and B renal flares. Cases were identified as those patients whose disease course included a surge of anti-dsDNA, defined as an increase of anti-dsDNA titer by the Crithidia luciliae immunofluorescence (CLIF) assay from 0 to 3+/4+, or from 1+ to 4+, within a period of less than 12 months. The date of the anti-dsDNA surge was defined as Day 0. Two control SLE patients were identified for each case and were matched for age, sex, race, and visit date closest to case Day 0, but without an anti-dsDNA surge. Logistic regression models were used to detect associations between anti-dsDNA surges and severe SS flares. RESULT: A higher proportion of cases, compared to controls, experienced a severe SS flare within six months of Day 0 (OR 6.3 (95% confidence intervals 2.0-19.9), p = 0.02). Associations with all flares and hospitalizations for flares were also observed. However, an anti-dsDNA surge was not predictive of a renal flare. CONCLUSION: An anti-dsDNA surge predicts the subsequent development of a severe SS flare within six months. Physicians should closely monitor such patients and treat promptly at the first sign of clinical activity.
Assuntos
Anticorpos Antinucleares/sangue , DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Centros Médicos Acadêmicos , Adulto , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Imunofluorescência , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Regulação para Cima , Adulto JovemRESUMO
Osteopontin (OPN) is a multifunctional cytokine involved in long bone remodeling and immune system signaling. Additionally, OPN is critical for interferon-alpha (IFN-alpha) production in murine plasmacytoid dendritic cells. We have previously shown that IFN-alpha is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variants of OPN have been associated with SLE susceptibility, and one study suggests that this association is particular to men. In this study, the 3' UTR SLE-risk variant of OPN (rs9138C) was associated with higher serum OPN and IFN-alpha in men (P=0.0062 and P=0.0087, respectively). In women, the association between rs9138 C and higher serum OPN and IFN-alpha was restricted to younger subjects, and risk allele carriers showed a strong age-related genetic effect of rs9138 genotype on both serum OPN and IFN-alpha (P<0.0001). In African-American subjects, the 5' region single nucleotide polymorphisms, rs11730582 and rs28357094, were associated with anti-RNP antibodies (odds ratio (OR)=2.9, P=0.0038 and OR=3.9, P=0.021, respectively). Thus, we demonstrate two distinct genetic influences of OPN on serum protein traits in SLE patients, which correspond to previously reported SLE-risk variants. This study provides a biologic relevance for OPN variants at the protein level, and suggests an influence of this gene on the IFN-alpha pathway in SLE.
Assuntos
Interferon-alfa/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Osteopontina/sangue , Osteopontina/genética , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto JovemRESUMO
A 34-year-old African-American female diagnosed earlier with idiopathic thrombocytopenic purpura (ITP), lymphadenopathy, splenomegaly, uveitis, and pulmonary nodules, developed a subclavian artery aneurysm, and generalized annular osteosclerotic lesions with disabling arthralgias. Biopsies from bone and lymph node revealed non-caseating granulomas and no evidence of malignancy or infection, confirming the clinical impression of sarcoidosis.
Assuntos
Artralgia/patologia , Osteosclerose/patologia , Sarcoidose/patologia , Vasculite/patologia , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Granuloma/patologia , Humanos , Imageamento por Ressonância Magnética , Trombocitopenia/diagnósticoRESUMO
Production of pathogenic autoantibodies in systemic lupus erythematosus (SLE) requires T cell help, along with ligation of the B cell surface immunoglobulin receptor by antigen. It is likely that macrophages, dendritic cells, and endothelial cells are also activated by interactions with T cells and contribute to lupus pathology. CD40 ligand (CD40L, CD154), a member of the tumor necrosis factor family of cell surface molecules, mediates these contact dependent signals delivered by CD4 + T helper cells to CD40 + target cells. Recent data from SLE patients and murine lupus models have demonstrated prolonged expression of CD40L on lupus T cells and its capacity to mediate excessive B cell activation. This review summarizes the current information regarding transcriptional and post-transcriptional regulation of CD40L expression in normal and SLE T cells. More complete characterization of the mechanisms that regulate the magnitude and duration of CD40L expression should suggest new approaches to modulate this promising therapeutic target.
Assuntos
Ligante de CD40/biossíntese , Lúpus Eritematoso Sistêmico/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD40/imunologia , Ligante de CD40/genética , Ligante de CD40/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
Interferon-alpha (IFN-alpha) was among the first cytokines studied and the earliest to be used in clinical medicine for the treatment of viral infections and malignancies. Although the capacity of IFN-alpha to augment NK cell cytotoxicity against virus-infected target cells or tumor cells is well established, the mechanism has not been fully elucidated. Here we report that IFN-alpha stimulation of PBMC from healthy donors induces Fas (CD95) ligand (FasL) transcription and leads to increased cell surface FasL expression exclusively on the NK cell fraction. Furthermore, IFN-alpha augments the FasL-mediated cytotoxicity of normal PBMC against Fas-sensitive lymphoid tumor cells. In the context of innate immunity, induction of FasL by IFN-alpha can be viewed as an efficient mechanism to potentiate NK cell cytotoxicity in the presence of harmful targets, such as virally infected or transformed cells.
Assuntos
Apoptose/efeitos dos fármacos , Interferon-alfa/farmacologia , Glicoproteínas de Membrana/efeitos dos fármacos , Glicoproteínas de Membrana/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Relação Dose-Resposta Imunológica , Proteína Ligante Fas , Humanos , Células Matadoras Naturais/química , Leucócitos Mononucleares/química , Ligantes , Glicoproteínas de Membrana/genética , RNA Mensageiro/sangueRESUMO
A 22-year-old Caucasian woman with a 6 year history of persistently active, systemic onset juvenile rheumatoid arthritis (JRA) developed symptoms of headache, dry cough, nausea, vomiting, abdominal pain, diarrhea, and dehydration associated with a high fever, elevated liver enzymes, and lymphopenia. Subsequent investigation revealed acute infection with parvovirus B19. Following clinical improvement over 10-14 days solely with supportive care, her underlying disease remained in remission for about 7 months.
Assuntos
Artrite Juvenil/terapia , Terapia Biológica , Infecções por Parvoviridae/fisiopatologia , Parvovirus B19 Humano , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/fisiopatologia , Artrite Juvenil/virologia , Feminino , Humanos , Metotrexato/uso terapêutico , Infecções por Parvoviridae/complicações , Indução de RemissãoRESUMO
OBJECTIVE: To measure soluble CD40 ligand (sCD40L) in sera from patients with systemic lupus erythematosus (SLE) and to study the functional capacity of sCD40L in mediating B cell activation. METHODS: A 2-site enzyme-linked immunosorbent assay (ELISA) was used to measure sCD40L in the sera of 66 SLE patients, 30 disease control patients, and 23 healthy subjects. Induction of B cell activation antigen expression was used to assess the functional capacity of sCD40L in SLE sera. RESULTS: The mean concentration of sCD40L was statistically significantly higher (P < 0.0001) in SLE patients than in disease controls or healthy subjects, and segregation of SLE patients by severe, moderate, or mild extent of disease showed a relationship between disease severity and sCD40L concentration. Western blot analysis demonstrated the presence of the 18-kd band of sCD40L in SLE sera, and the results of a 1-site ELISA protocol suggested that some of the product in SLE sera was present in dimer or trimer form. Functional studies showed that 10 ng/ml of recombinant CD40L, a level present in some SLE sera, induced increased expression of CD95 on B cells. Several SLE sera also induced CD95 or CD86 on Ramos B cells, a result that was inhibited by anti-CD40L monoclonal antibodies. CONCLUSION: The soluble form of CD40L is present in the sera of most patients with SLE and may have the capacity to mediate B cell activation. Aberrant expression of CD40L might be predicted to result in activation of bystander B cells, including those that have encountered self antigens, and to contribute to autoantibody secretion.