ABSTRACT
BACKGROUND: Osteonecrosis is common in systemic lupus erythematosus (SLE) and often disabling. The role of glucocorticoids in its development is well known. OBJECTIVE: To explore other possible risk factors for osteonecrosis in SLE. METHODS: A nested matched case-control study undertaken in the context of a large, longitudinal, multiethnic lupus cohort (LUMINA), currently formed of 571 SLE patients meeting American College of Rheumatology criteria. All those developing symptomatic osteonecrosis after the diagnosis of SLE were considered cases. Two controls matched for age, disease duration, ethnicity, and centre were selected for each case. Cases and controls were compared by univariable analyses using selected variables. Variables with p<0.10 and those thought clinically relevant were entered into conditional logistic regression models including either the average dose or the highest dose of glucocorticoids, with osteonecrosis as the dependent variable. RESULTS: 32 cases were identified and 59 matched controls selected (in five cases only one control could be found). By univariable analyses, both groups were largely comparable for socioeconomic-demographic, clinical, and laboratory variables. Cases were less exposed to hydroxychloroquine (as assessed by the percentage of exposure time) (p = 0.026), used higher doses of glucocorticoids (average and highest doses) (p = 0.011 and 0.001, respectively), and received cytotoxic drugs more often (p = 0.015). In the multivariable analyses only cytotoxic drug use (both models) and the highest dose of glucocorticoids remained associated with the occurrence of osteonecrosis. CONCLUSIONS: Cytotoxic drug use is a risk factor for the development of symptomatic osteonecrosis in SLE patients, along with glucocorticoids. No definite protective factors were identified.
Subject(s)
Ethnicity , Lupus Erythematosus, Systemic/ethnology , Osteonecrosis/etiology , Adult , Black or African American , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Epidemiologic Methods , Female , Glucocorticoids/therapeutic use , Hispanic or Latino , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Male , United States , White PeopleABSTRACT
OBJECTIVE: To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). METHODS: Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. RESULTS: A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. CONCLUSIONS: Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive treatment strategies should be directed to both smoking cessation and control of disease activity in patients with SLE.
Subject(s)
Lupus Erythematosus, Systemic/complications , Thrombosis/etiology , Antibodies, Antiphospholipid/blood , Antirheumatic Agents/therapeutic use , Epidemiologic Methods , Female , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/ethnology , Male , Severity of Illness Index , Smoking/adverse effects , Thrombosis/ethnology , Thrombosis/immunologyABSTRACT
The aim of this study was to assess the synovial fluid (SF) neurotransmitter excitatory amino acid (EAA) levels, including glutamate (Glu) and aspartate (Asp), in the context of SF levels of other amino acids, TNF-alpha and chemokines from patients with active arthropathies. The SF was collected from patients with active rheumatoid arthritis (RA), gout, or osteoarthritis (OA). The SF samples were analysed for levels of neurotransmitters glutamate and aspartate, tumour necrosis factor-alpha (TNF-alpha), Regulated upon Activation Normally T-cell Expressed and Secreted (RANTES), macrophage inhibitory factor-1 alpha (MIP-1alpha) and interleukin 8 (IL-8). SF WBC counts were also determined. Correlations between SF EAA, TNF-alpha and chemokines were determined by the Pearson product-moment correlation. Primary cultures derived from SF from active RA and gout patients were incubated with added l-glutamate, to assess if exposure to Glu could increase TNF-alpha levels. There were significant elevations in SF EAA, SF TNF-alpha and SF RANTES in RA patients compared to gout or OA patients. Significant correlations between SF EAA and SF RANTES, MIP-1alpha and IL-8 levels were seen, and SF EAA and SF TNF-alpha or SF WBC levels approached significance. Addition of exogenous neurotransmitter glutamate significantly increased TNF-alpha levels in primary cell cultures derived from RA and gout patients. The SF neurotransmitter EAA levels significantly correlated to selected SF chemokine levels, in clinically active RA, gout and OA patients, independent of disease. Added Glu resulted in significantly increased TNF-alpha levels in primary synovial cell cultures. These data expand the relationship of SF neurotransmitter EAA levels to SF cytokines and chemokines in patients with clinically active arthritis, and suggest that neurotransmitters Glu and Asp contribute to peripheral inflammatory processes.
Subject(s)
Arthritis/metabolism , Chemokines/analysis , Excitatory Amino Acids/analysis , Synovial Fluid/chemistry , Tumor Necrosis Factor-alpha/analysis , Adult , Aged , Arthritis/immunology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Chemokine CCL3 , Chemokine CCL4 , Chemokine CCL5/analysis , Chromatography, High Pressure Liquid/methods , Female , Gout/immunology , Gout/metabolism , Humans , Interleukin-8/analysis , Macrophage Inflammatory Proteins/analysis , Male , Middle Aged , Osteoarthritis/immunology , Osteoarthritis/metabolismABSTRACT
OBJECTIVES: To compare the baseline clinical manifestations, immunological features, disease activity and damage accrual in systemic lupus erythematosus (SLE) patients from two US Hispanic subgroups. METHODS: A total of 105 Hispanic SLE patients from Texas (a population of Mexican or Central American ancestry) and 81 from the island of Puerto Rico (all Puerto Ricans) participating in a longitudinal study of outcome were examined. The socio-economic/demographic, clinical and immunological variables were obtained at the time of enrollment (T(0)). Disease activity was determined with the Systemic Lupus Activity Measure (SLAM), and disease damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). Disease activity was also determined at the time of diagnosis (T(D)). RESULTS: At T(0) Hispanics from Texas were younger than those from Puerto Rico (33.1 +/- 12.0 vs 37.5 +/- 11.6 yr, P = 0.0125). Both groups were similar with regard to gender distribution (92.4 vs 95.1% females) and disease duration (1.4 +/- 1.4 vs 1.7 +/- 1.3 yr). Hispanics from Texas were more likely to have serositis (60.0 vs 8.6%, P < 0.0001), renal involvement (41.0 vs 13.6%, P < 0.0001), psychosis (5.7 vs 0.0%, P = 0.0365) and thrombocytopenia (21.0 vs 3.7%, P = 0.0006). On the other hand, Hispanics from Puerto Rico were more likely to have photosensitivity (81.5 vs 41.0%, P < 0.0001), malar rash (65.4 vs 45.7%, P = 0.0074) and discoid rash (13.6 vs 2.9%, P = 0.0060). At baseline, the presence of anti-dsDNA antibodies was higher in Hispanics from Texas (69.5% vs 46.9%, P = 0.0018) while anti-Ro antibodies were more frequent in Hispanics from Puerto Rico (24.7 vs 11.4%, P = 0.0175). Mean SLAM scores at T(D) (12.9 +/- 6.4 vs 9.1 +/- 4.6, P < 0.0001) and T(0) (10.9 +/- 6.3 vs 6.6 +/- 3.8, P < 0.0001) were significantly higher in Hispanics from Texas. Similarly, mean SDI scores at T(0) were higher in Hispanics from Texas (0.67 +/- 1.08 vs 0.26 +/- 0.54, P = 0.0026). By stepwise Poisson regression, SDI scores were associated with older age, disease activity and ethnicity (Hispanics from Texas). CONCLUSIONS: Early in SLE, marked differences are observed between Hispanics from Texas and Puerto Rico. Higher disease activity, more major organ involvement, higher frequency of anti-dsDNA antibodies and more damage accrual occur in Hispanic lupus patients from Texas than in those from Puerto Rico.
Subject(s)
Autoantibodies/blood , Hispanic or Latino , Lupus Erythematosus, Systemic/ethnology , Adult , Age Factors , Antibodies, Antinuclear/blood , Female , Humans , Longitudinal Studies , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/therapy , Male , Middle Aged , Puerto Rico , Regression Analysis , Texas , Treatment OutcomeABSTRACT
OBJECTIVE: To examine the predictors of damage in a multiethnic cohort of systemic lupus erythematosus (SLE) patients with a specific focus on damage at baseline. PATIENTS AND METHODS: SLE patients from a multiethnic US (Hispanic, African-American and Caucasian) cohort (LUMINA: Lupus in Minority populations, Nature versus nurture) were included if they had > or =6 months of follow-up in the cohort. Damage was measured with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). The dependent variable was the change in SDI score between study visits. Predictors were from the preceding visit. Variables known to affect damage accrual in SLE were included in the analyses. RESULTS: Three hundred and fifty-two patients (82 Hispanics, 153 African-Americans and 117 Caucasians) representing 1795 patient visits were included. Previous damage was found to be a significant predictor of subsequent damage accrual (P < 0.0001). Other variables predictive of subsequent damage accrual were disease activity (P < 0.0001), older age (P = 0.041) and use of corticosteroids (P = 0.0048). CONCLUSIONS: Once damage occurs in SLE, further damage is expected to occur. This is more likely to be the case if disease activity persists. These data have clinical implications for the management of SLE patients.
Subject(s)
Lupus Erythematosus, Systemic/ethnology , Adult , Black or African American , Cohort Studies , Disease Progression , Female , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Risk Factors , Severity of Illness Index , United States , White PeopleABSTRACT
The aim of this study was to compare and contrast the clinical, immunogenetic and outcome features of two subgroups of Hispanic patients with systemic lupus erythematosus (SLE), one from Northern Spain (Spaniards) and one of from the USA (Hispano-Americans: Hispanics primarily of Mexican ancestry (Amerindian and Spaniard backgrounds). Patients with SLE as per the American College of Rheumatology classification criteria, from two University-affiliated Hospitals (Universidad de Cantabria) and disease of five or less years in duration (n = 28) and with four years of follow up constituted the Spaniard subgroup. Fifty-two patients of Hispano-American ancestry from the LUMINA (Lupus in Minority populations: Nature versus Nurture) cohort constituted the Hispano-American subgroup. Patients were studied using a similar protocol. In short, sociodemographic, clinical, immunological, immunogenetic and psychosocial and behavioral features were obtained at enrollment into the study (baseline visit) and yearly thereafter. The relationship between these variables and disease activity at baseline and over time, as measured by the systemic lupus activity measure (SLAM) and disease damage, as measured by the SLICC (Systemic Lupus International Collaborating Clinics) Damage Index (SDI) were determined. Variables found to be significant at P = 0.10 were then entered into multivariable linear regression models with disease activity at baseline and over time, and damage as the outcome measures. Patients of Hispano-American and Spaniard ethnicity had comparable sociodemographic features except for home density, which was higher among the Hispano-Americans. HLA-DRB1*08 was associated with SLE among the Hispano-Americans but not among the Spaniards. Hispano-American patients had more severe disease as manifested by more frequent clinical manifestations (renal and neurological), higher SLAM scores at baseline and over time and higher SDI scores at the year 4 visit (that despite the fact that Hispano-American patients had overall shorter disease duration than the Spaniard patients). Hispano-American ethnicity, younger age at disease onset and the number of ACR criteria at baseline and over time were consistently associated with disease activity, whereas increased home density and the absence of HLA-DRB1*0301 were significant predictors only over time. Disease damage was associated with disease activity over time, the number of ACR criteria at baseline, increased home density and the presence of HLA-DRB1*08. This is the first longitudinal study of SLE in two different Hispanic subgroups. Hispanics with a strong Amerindian background have a more serious disease than that observed in Spaniards. Genetic and socio-economic differences between these two Hispanic subgroups probably account for these findings.
Subject(s)
Hispanic or Latino/genetics , Lupus Erythematosus, Systemic/ethnology , Adult , Disease Progression , Female , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Multivariate Analysis , Socioeconomic Factors , Spain , TexasABSTRACT
The purpose of this study was to determine the prevalence and correlates of fibromyalgia (FM) in a prospective, multiethnic systemic lupus (SLE) cohort. A total of 266 SLE patients with disease duration of < or = 5 years at study entry were evaluated longitudinally for the presence of FM (per ACR criteria). Sociodemographic factors, behavioral/psychological variables, clinical features, serologic factors (autoantibodies), and self-reported functioning (MOS SF-36) were ascertained in all patients. Subjects were evaluated at study entry and annually thereafter. The prevalence of FM was then calculated, as was the prevalence of FM-like manifestations (widespread pain with at least 6, but fewer than 11/18 tender points). Variables were evaluated for association with FM or FM-like manifestations by univariate and stepwise logistic regression analyses. FM was present in 14 patients (5%; 9/92 Caucasians (C), 4/109 African Americans (AA), 1/65 Hispanics (H)) and FM/FM-like manifestations in 35 (13%; 16 C, 9 AA, 10 H). There was no difference noted between those with and without FM with respect to gender, education level, income below poverty level, disease activity or damage. By stepwise logistic regression analyses, the strongest association with both FM and FM/FM-like manifestations was a self-reported history of anxiety or affective disorder (P = 0.0237, OR = 4.6 and P = 0.0068, OR = 3.4, respectively). Caucasian ethnicity was strongly associated with FM (P = 0.0066, OR = 7.5) and African American ethnicity was negatively associated with FM/FM-like (P = 0.0204, OR = 0.3). Poorer self-reported physical functioning was associated with FM/FM-like (P = 0.0443, OR = 0.96). FM and FM-like manifestations correlate best with the presence of Caucasian ethnicity, concomitant anxiety or affective disorder, and to a lesser extent with poorer self-reported physical functioning. African American ethnicity is negatively associated with the combination of FM and FM-like manifestations. Clinical measures of disease activity, disease damage, specific organ dysfunction, sociodemographic factors and serologic features are not correlated with FM in this early SLE cohort.
Subject(s)
Fibromyalgia/ethnology , Lupus Erythematosus, Systemic/ethnology , Black People , Cohort Studies , Female , Humans , Logistic Models , Longitudinal Studies , Male , Prevalence , White PeopleABSTRACT
Our objective was to identify the role of various disease states and additional risk factors in the development of thrombosis in patients with anticardiolipin antibodies (aCL). We undertook a retrospective chart review of patients with aCL (IgG or IgM titres > 20 GPL or 20 MPL by ELISA). Patients with a thrombotic event were compared to patients without thrombosis for potential risk factors: age, gender, ethnicity, hypertension (HTN), diabetes (DM), hyperlipidaemia, tobacco use and sequential aCL determinations. The role of systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), hepatitis C and renal disease was also analysed. Statistical analysis was performed using the t-test, the chi(2) test and multivariate analysis. Of the 107 patients who had moderately positive aCL (IgM and/or IgG), 53 had a thrombotic event. The patients with thrombosis were significantly older than patients without thrombosis (mean age 46.6 vs. 38.75 years, respectively, P=0.014). No significant differences in gender, race, HTN, DM, hyperlipidaemia, tobacco use or concomitant diseases were identified in the two groups. Thrombosis was more frequent in patients who were seropositive for both IgG and IgM ( P=0.027). Thrombosis was observed in equal frequencies in patients with aCL on both determinations and in patients with aCL on only one of the two determinations. In patients with aCL on two determinations a high-titre IgG aCL was associated with thrombosis. Patients with renal disease and aCL on only one of the two determinations had fewer thrombotic events ( P=0.0046). Mean aCL IgM titres were higher in thrombosis groups containing venous thromboses than in the thrombosis group with arterial thrombosis only. We concluded that risk factors for thrombosis with a single aCL determination include older age and both IgM and IgG aCL. With persistent aCL, high-titre IgG aCL was associated with thrombosis.
Subject(s)
Antibodies, Anticardiolipin/analysis , Thrombosis/etiology , Thrombosis/immunology , Adult , Aging/physiology , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Lupus Erythematosus, Systemic/complications , Male , Middle Aged , Renal Insufficiency/complications , Retrospective Studies , Thrombosis/complicationsABSTRACT
The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.
Subject(s)
Ethnicity , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Nephritis/complications , Lupus Nephritis/epidemiology , Black or African American , Autoantibodies/immunology , Cohort Studies , Female , HLA-D Antigens/immunology , Hispanic or Latino , Humans , Logistic Models , Lupus Nephritis/ethnology , Lupus Nephritis/immunology , Male , Odds Ratio , Risk Factors , Survival Analysis , White PeopleABSTRACT
OBJECTIVE: To examine the relationship between allelic polymorphisms of IgG receptors (FcgammaR) and the development of lupus nephritis in a prospective study, and to determine the distribution of FcgammaR haplotypes (FcgammaRIIA and FcgammaRIIIA genotypes) in lupus patients and disease-free control subjects. METHODS: We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from a prospective study of outcome and 53 disease-free control subjects. Patients were followed up longitudinally for 3 years. FcgammaRIIA and FcgammaRIIIA genotypes were determined using allele-specific polymerase chain reaction. RESULTS: Nephritis was present in 28% of patients at entry into the study and in 69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low-binding alleles (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05-0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131 or FcgammaRIIIaV176). The frequency of individuals homozygous for high-binding alleles at either locus decreased as the burden of disease increased (P < 0.002, by Mann-Whitney test). There was no linkage disequilibrium between FcgammaRIIA and FcgammaRIIIA in Hispanics, yet in the SLE patients, there was a clear overrepresentation of the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype (SLE patients 48% versus controls 30%) and a decrease in the frequency of the high-binding haplotype (4% versus 23%) (P < 0.002). CONCLUSION: We observed an increase in the frequency of low-binding FcgammaR alleles in an SLE population with a high prevalence of renal disease. The apparent selection for the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype in Hispanic patients suggests that low-binding alleles of both FcgammaRIIa and FcgammaRIIIa confer risk for SLE and may act additively in the pathogenesis of disease, whereas the high-binding haplotype FcgammaRIIa-H131;FcgammaRIIIa-V176 is protective, particularly in the homozygous state.
Subject(s)
Antigens, CD/genetics , Hispanic or Latino/genetics , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/genetics , Receptors, IgG/genetics , Alleles , Cohort Studies , Family Health/ethnology , Genotype , Humans , Linkage Disequilibrium/geneticsABSTRACT
OBJECTIVE: To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. METHODS: H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. RESULTS: Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). CONCLUSIONS: Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.
Subject(s)
Ethnicity , Fatigue , Lupus Erythematosus, Systemic/physiopathology , Black or African American , Black People , Cohort Studies , Demography , Follow-Up Studies , Hispanic or Latino , Humans , Longitudinal Studies , Lupus Erythematosus, Systemic/classification , Lupus Erythematosus, Systemic/diagnosis , Pain , Social Support , Socioeconomic Factors , Time Factors , United States , White PeopleABSTRACT
OBJECTIVE: To investigate the usefulness of hydroxychloroquine (HCQ) dose-loading to increase the percentage of responders or rate of response in treating rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with early RA (mean duration 1.5 years) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/day and then began a 6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n = 71), 800 mg/day (n = 71), and 1,200 mg/day (n = 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day. RESULTS: All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modifying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.97%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related. CONCLUSION: Dose-loading with HCQ increased the degree of response at 6 weeks in this group of patients with early, predominantly seronegative RA. Adverse GI events were dose related, while adverse ocular events were not.
Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Hydroxychloroquine/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/pathology , Dose-Response Relationship, Drug , Double-Blind Method , Eye Diseases/chemically induced , Female , Gastrointestinal Diseases/chemically induced , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Naproxen/therapeutic use , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To study the relative impact of immunogenetic versus socioeconomic factors on systemic lupus erythematosus (SLE) at disease onset/presentation. METHODS: Medical records regarding SLE onset/ presentation were abstracted on 229 SLE patients who were enrolled in a prospective lupus outcome study. Patients were grouped in equivalent proportions of Caucasians, African Americans, and Hispanics. HLA-DRB1, DQA1, and DQB1 oligotyping, as well as C4 and CR1 allotyping, were carried out by standard methods. In addition to these genetic factors, data on ethnicity, age at SLE onset, monthly income, level of education, and home ownership were entered into stepwise logistic or stepwise multiple linear regression models as independent variables, and each specific clinical feature (neurologic, renal, and cardiovascular disease due to SLE), as well as the total Systemic Lupus Activity Measure (SLAM) score and physician's global assessment of disease activity at disease onset, were entered as dependent variables. RESULTS: HLA-DRB1*0301 (DR3), DRB1*1503 (DR2), and DRB1*08 (DR8) alleles were more frequently found in Caucasians, African Americans, and Hispanics, respectively. Hispanics were more likely to have cardiac and renal disease, as well as a higher physician's global assessment of disease activity. African Americans were more likely to have neurologic disease, renal disease, and a higher SLAM score. Those with less education had a higher SLAM score. Patients with HLA-DRB1*01 had less renal disease and a lower SLAM score. Those with C4A*3 alleles had a higher SLAM score and a higher physician's global assessment of disease activity. CONCLUSION: Both genetic and socioeconomic determinants, as well as other factors associated with Hispanic and African-American ethnicity, affect the presentation of SLE.
Subject(s)
Complement C4/genetics , HLA-DR Antigens/genetics , Lupus Erythematosus, Systemic/immunology , Receptors, Complement 3b/genetics , Adolescent , Adult , Black or African American , Aged , Alleles , Black People/genetics , Ethnicity , Female , HLA-DRB1 Chains , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/genetics , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Socioeconomic Factors , White PeopleABSTRACT
OBJECTIVE: To assess the efficacy of outpatient arthroscopic lavage in rheumatoid arthritis (RA) of the knee. METHODS: 9 patients with RA and active synovitis of at least one knee were selected. All patients were taking disease modifying antirheumatic drugs and nonsteroidal antiinflammatory drugs and had failed intraarticular corticosteroid injection of the knee. Using the 1.9 mm office arthroscope and strict sterile technique the affected knee was lavaged with at least 750 cc of normal saline. At the end of the procedure 40 mg triamcinolone acetonide was injected through the arthroscope. Assessment was done at baseline and 4, 8, and 12 weeks after the lavage using a visual analog scale for pain and 50 foot walk time. RESULTS: 8 of the 9 patients showed marked improvement in their pain and walk time. This effect was maintained at least 12 weeks after the procedure. CONCLUSION: Office arthroscopic lavage treatment is beneficial in a selected group of patients. This procedure is simple and well tolerated without major complications, and may be an option when more conservative therapies have failed.
Subject(s)
Arthritis, Rheumatoid/therapy , Knee Joint/pathology , Therapeutic Irrigation/methods , Activities of Daily Living , Aged , Arthritis, Rheumatoid/etiology , Arthroscopy/adverse effects , Arthroscopy/methods , Female , Humans , Male , Middle Aged , Pain Measurement , Pilot Projects , Therapeutic Irrigation/adverse effects , Treatment Outcome , Triamcinolone Acetonide/administration & dosageABSTRACT
OBJECTIVE: To cross-culturally adapt a brief self-assessment questionnaire to measure outcome among English- or Spanish-speaking patients with arthritis. METHODS: A questionnaire containing the following items was translated to Spanish: the 8 activities of daily living (ADL) question of the Modified Health Assessment Questionnaire; a question about the duration of morning stiffness; and a 10-point pain scale. Equivalence to the original English, test-retest reliability, and construct, criterion, and discriminant validity were determined on a population of patients with 4 clinical centers. RESULTS: English-Spanish equivalence and test-retest reliability of the questionnaire were almost perfect (intra-class correlation coefficients [ri] > or = 0.90 for each). Construct validity, measured by comparing questionnaire scores with an occupational therapist's evaluation, was also near-perfect in both languages (ri = 0.93 for English and 0.89 for Spanish). Both versions of the questionnaire correlated well with the physician-determined Steinbrocker functional class, as well as with the amount of pain, grip strength, and walking velocity. Patients with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and fibromyalgia differed significantly in their pain:ADL ratios, in both languages. CONCLUSIONS: The items of the Spanish questionnaire that we have adapted are equivalent to the original English versions. This questionnaire is suitable for studying Spanish-speaking subjects with arthritis in the US and elsewhere.
Subject(s)
Arthritis/complications , Disability Evaluation , Hispanic or Latino , Surveys and Questionnaires , Translations , Activities of Daily Living , Adult , Aged , Female , Humans , Male , Middle Aged , Pain Measurement , Reproducibility of ResultsSubject(s)
Arthritis, Rheumatoid/immunology , HLA Antigens/immunology , Polymyositis/immunology , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To evaluate dietary therapy in the treatment of hyperlipidemia in patients with systemic lupus erythematosus (SLE). METHODS: Using the National Cholesterol Education Program (NCEP) guidelines, we screened 89 patients with SLE for hyperlipidemia. Step 1 dietary therapy was instituted in 28 patients as recommended by the NCEP. Twenty-six patients failed Step 1 intervention and received Step 2 dietary therapy for an additional 3 months. Twenty-nine control patients with SLE were tested for hyperlipidemia. RESULTS: The 89 patients with SLE (94% women, 77% black) had a mean age of 37.2 years. Fasting values were total cholesterol (TC) 6.22 +/- 0.16 mmol/l (240.9 +/- 6.0 mg/dl), low density lipoprotein cholesterol (LDL-C) 4.08 +/- 0.14 mmol/l, (157.6 +/- 5.3 mg/dl), high density lipoprotein (HDL-C) 1.37 +/- 0.08 mmol/l (53.0 +/- 3.1 mg/dl), and triglyceride (TG) 1.71 +/- 0.12 mmol/l, (151.9 +/- 10.6 mg/dl). The mean dose of prednisone was 14.2 +/- 1.6 mg/day. Prednisone dose correlated with levels of TC (p < 0.01) by linear regression. The 28 patients receiving Step 1 dietary intervention had TC 6.11 +/- 0.19 mmol/l (236.4 +/- 7.3 mg/dl), LDL-C 4.05 +/- 0.19 mmol/l (156.6 +/- 7.5 mg/dl), HDL-C 1.31 +/- 0.08 mmol/l (50.7 +/- 3.0 mg/dl), and TG 1.64 +/- 0.12 mmol/l (145.4 +/- 10.3 mg/dl). The 26 patients receiving Step 2 dietary intervention had TC 5.84 +/- 0.17 mmol/l (226.0 +/- 6.6 mg/dl), LDL-C 3.83 +/- 0.19 mmol/l (148.0 +/- 7.2 mg/dl), HDL-C 1.25 +/- 0.08 mmol/l (48.5 +/- 3.2 mg/dl), and TG 1.66 +/- 0.15 mmol/l (147.1 +/- 13.4 mg/dl). The mean prednisone dose was 14.8 +/- 3.0 mg/day for both study groups. There was no significance between prednisone doses in all groups studied (p = 0.08). After 6 months of dietary therapy, there was a significant decrease in only the TC (p = 0.158). CONCLUSION: TC correlated directly with the prednisone dose. Six months of dietary intervention was required to significantly decrease the TC. Further management of hyperlipidemia will probably require drug intervention.
Subject(s)
Hyperlipidemias/diet therapy , Lupus Erythematosus, Systemic/blood , Adult , Cholesterol/blood , Cohort Studies , Female , Humans , Hyperlipidemias/blood , Hyperlipidemias/epidemiology , Lipids/blood , Lupus Erythematosus, Systemic/drug therapy , Male , Prednisone/therapeutic use , Risk FactorsABSTRACT
OBJECTIVES: To examine the expression of the natural killer (NK) antigen CD56, and T cell receptor delta chain antigen (TCR delta), expressed on the gamma delta T cell subset, in patients with scleroderma, and to correlate levels of expression with clinical characteristics. METHODS: Peripheral blood mononuclear cells (PBMCs) from 15 patients with scleroderma and 11 controls were obtained from heparinised blood on a ficoll/hypaque gradient, stained with monoclonal antibodies, and examined by flow cytometry for expression of CD56 and TCR delta. RESULTS: Overall, the proportion of PBMCs expressing CD56 in the patient group (14.4 (SEM 2.6)%) was not significantly different from controls (8.75 (2.6)%). The greatest levels of expression were found in patients late (more than three years) in their disease course (18.1 (3.3)%) and in patients who did not express anti-Scl-70 antibodies (17.1 (3.5)%). The proportion of gamma delta T cells was significantly lower in the patient group (1.61 (0.52)% v control 2.61 (0.46)%) (p < 0.05). Patients early in their disease or with anti-Scl-70 antibodies accounted for the reduction in gamma delta T cells (0.71 (0.29)% and 0.96 (0.41)% (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: This study emphasis that NK and gamma delta T cell numbers vary depending upon patient characteristics and may help explain prior contradictory reports. Decreased numbers of gamma delta T cells were seen in scleroderma patients, especially those with anti-Scl-70 antibodies and a disease duration of less than three years.
Subject(s)
Killer Cells, Natural/immunology , Nuclear Proteins/immunology , Receptors, Antigen, T-Cell, gamma-delta/analysis , Scleroderma, Systemic/immunology , T-Lymphocyte Subsets/immunology , Adult , Antibodies, Antinuclear/blood , Antigens, CD/blood , Antigens, Differentiation, T-Lymphocyte/blood , CD56 Antigen , DNA Topoisomerases, Type I , Female , Flow Cytometry , Humans , Lymphocyte Count , Male , Middle Aged , Scleroderma, Systemic/blood , Time FactorsABSTRACT
Systemic lupus erythematosus (SLE) frequently involves the pleura with resultant pleural effusion. Previous studies have reported that detection of antinuclear antibodies (ANA) in pleural fluid using animal tissue as substrate was a sensitive and specific method for distinguishing SLE pleural effusions from other etiologies. The HEp-2 ANA, which uses a human cell line as substrate, is now the preferred ANA test; however, to our knowledge, no studies on pleural fluid using this assay have been reported. To determine its sensitivity and specificity, when measured in pleural fluid, HEp-2 ANA levels were determined in pleural effusion samples associated with a variety of different etiologies, including SLE, malignancy, congestive heart failure, pneumonia, tuberculosis, and a miscellaneous group of diseases. Pleural fluid ANA results were positive in 14 of 82 samples. Six of the eight (75 percent) pleural fluid samples collected from patients with SLE were ANA positive, and all but one had high titers (> 1:160) with a homogenous staining pattern. The remaining two patients with SLE with negative pleural fluid ANA had recurrent pulmonary emboli and congestive heart failure, rather than lupus pleuritis. Eight of 74 patients (10.8 percent) without clinical evidence of SLE had a positive pleural fluid ANA, with the majority having a speckled pattern. High titers were noted in three. These results indicate that a negative or low titer ANA and a speckled staining pattern in pleural fluid from a patient suspected of lupus pleuritis suggest an alternative diagnosis. High pleural fluid titers (up to 1:640) were seen occasionally in patients with inflammatory pleural effusions in the absence of SLE.