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Tumor necrosis factor alpha inhibitors (TNFi) are biological drugs used worldwide to treat various autoimmune disorders. Paradoxically, TNF‐α antagonists can also induce autoimmune diseases being systemic vasculitis, systemic lupus erythematosus, and psoriasis, the most common. We present a 22‐year‐old woman with ulcerative colitis (UC) who was started on adalimumab 40 mg subcutaneously every 2 weeks. After two doses of adalimumab, she developed gangrene of all toes and acute kidney injury requiring hemodialysis. Skin biopsy showed thrombi in the small vessels of the dermis. Renal biopsy disclosed diffuse proliferative glomerulonephritis (GN) and acute tubulointerstitial nephritis. Serologic work‐up showed positive IgG anticardiolipin (ACL) antibodies and low C3 levels. Antinuclear, anti‐dsDNA, anti‐Smith, anti‐SSA, anti‐SSB, anti‐RNP, antineutrophil cytoplasmic antibodies, ACL (IgA and IgM), and anti‐β2‐glycoprotein I (IgG, IgM, and IgA) antibodies were not elevated. Lupus anticoagulant test and cryoglobulins were negative. Adalimumab was discontinued, and she was treated with enoxaparin, intravenous (IV) methylprednisolone pulse, IV cyclophosphamide, and plasmapheresis followed by maintenance therapy with warfarin, prednisone, azathioprine, and hydroxychloroquine. She did not have further thrombotic events, and the acute kidney injury completely resolved. ACL IgG antibodies decreased to normal levels, and repeated tests were negative. After 7 years, anticoagulation and immunosuppressive drugs were discontinued. During a follow‐up of 24 months, she remained in complete clinical remission. This report highlights the occurrence of autoimmune disorders induced by TNFi. Thus, careful monitoring of adverse immune reactions to TNFi is highly recommended. [ABSTRACT FROM AUTHOR]

Objective: The long‐term impact of childhood‐onset systemic lupus erythematosus (SLE) on health‐related quality of life (HRQoL) in adult SLE patients in comparison to those with adult‐onset SLE is unknown. We aim to examine and compare HRQoL trajectories in adults with adolescent‐ and adult‐onset SLE. Methods: Patients enrolled in the LUpus in MInorities: NAture versus Nurture cohort were included. Adolescent‐onset SLE were those diagnosed before 24 years of age, and adult‐onset SLE were those diagnosed otherwise. Sociodemographic, clinical, medications, behavioral/psychological, and functioning data were obtained. Longitudinal trajectories of the physical component summary (PCS) and the mental component summary (MCS) Short Form 36 health survey scores were compared between the groups using a linear mixed model accounting for time‐dependent and independent covariates. Results: A total of 470 SLE patients were included (95 with adolescent‐onset SLE and 375 with adult‐onset SLE). The mean ± SD age at diagnosis was 19.7 ± 2.8 years in the adolescent group and 39.3 ± 11.0 years in the adult group. The baseline PCS scores were higher (better physical functioning) in adolescent‐onset SLE than in adult‐onset SLE (38.9 versus 34.3, respectively; P < 0.001); however, the baseline MCS scores were comparable between the groups (41.4 versus 40.5, respectively; P = 0.53). The HRQoL improved equally in both groups with no statistically significant difference within and between the groups (last mean PCS and MCS scores 43.9 and 45.3 in adolescent‐onset SLE; 38.1 and 43 in adult‐onset SLE). Conclusions: Adults with adolescent‐onset SLE exhibited better physical functioning than those in the adult SLE group, despite more severe disease; noteworthy, HRQoL was below the general US population, despite clinically meaningful improvement in HRQoL over time in both groups. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RPC) is an uncommon autoimmune systemic disease characterized by recurrent inflammation of the cartilage tissue. It can occur alone or in association with other autoimmune diseases, vasculitis, or hematologic disorders. However, the association of RPC with dermatomyositis is extremely rare. Herein, we present a case of a 38-year-old man who developed concurrent RPC and clinically amyopathic dermatomyositis (CADM) manifested by auricular chondritis, nasal chondritis, polyarthritis, gottron papules, fingertip papules, skin biopsy consistent with dermatomyositis, and positive antimelanoma differentiation-associated gene 5 (MDA5) antibodies. RPC features resolved with corticosteroids, but CADM manifestations were resistant to corticosteroids, cyclophosphamide, azathioprine, and hydroxychloroquine. Subsequent therapy with rituximab was effective to control CADM manifestations. This case highlights the importance of recognizing CADM as part of the autoimmune diseases linked with RPC and maintaining a high level of awareness to initiate effective therapy to avoid the long-term complications associated with these conditions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between the Systemic Lupus International Collaborating Clinics frailty index (SLICC‐FI) and damage accrual in systemic lupus erythematosus (SLE) patients. Methods: Patients from the multiethnic, multicenter LUpus in MInorities, NAture versus nurture (LUMINA) cohort were included. Damage was ascertained with the SLICC/American College of Rheumatology Damage Index (SDI) at last visit (range 0–51). The first visit in which the SLICC‐FI score could be derived was considered as the baseline (range 0–1). Univariable and multivariable negative binomial regression models were performed to determine the association between the baseline SLICC‐FI score (per 0.05 increase) and the change in the SDI score (difference between last and baseline SDI score), adjusted for sex, age at diagnosis, ethnicity, insurance, prednisone daily dose, and antimalarial and immunosuppressive drug use at baseline. Age and sex were included a priori in the multivariable model; the other variables were included if they reached P < 0.10 in the univariable models. Results: Of the 503 patients included, 454 (90.3%) were female, with a mean ± SD age of 37.1 ± 12.5 years at diagnosis. The mean ± SD baseline SLICC‐FI score was 0.26 ± 0.06. The mean ± SD baseline SDI score was 0.6 ± 1.0, and the mean ± SD change in the SDI score was 1.9 ± 2.2. Higher SLICC‐FI scores at baseline (per 0.05 increase) were associated with greater damage accrual in the multivariable model after adjustment for possible confounders (incidence rate ratio 1.20 [95% confidence interval 1.08–1.33], P = 0.0015). Conclusion: The SLICC‐FI is associated with damage accrual in SLE patients from a multiethnic cohort, supporting the importance of this index in the evaluation of SLE patients, combining several aspects of their disease. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease resulting from the interaction of genetic and environmental factors. In addition, some antiviral vaccines have been associated with the onset of SLE. Few cases of SLE occurring after SARS-CoV-2 mRNA have been reported. Herein, we report the case of a 27-year-old woman with type I diabetes mellitus and family history of SLE who presented with symmetric inflammatory polyarthritis of the proximal interphalangeal joints, metacarpophalangeal joints, wrists, knees, and ankles two weeks after receiving the second dose of the SARS-CoV-2 mRNA-1273 vaccine. Laboratory results revealed positive antinuclear, anti-dsDNA, anti-Ro, and anti-La/SSB antibodies and low C4 levels. She was initially treated with low-dose prednisone and hydroxychloroquine. Hydroxychloroquine was discontinued after she developed an urticarial rash. Subsequently, mycophenolate mofetil was added after she developed proteinuria. This case highlights the importance of considering the diagnosis of SLE in patients who present with inflammatory polyarthritis after COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Transverse myelitis (TM) is a rare complication seen in 1–2% of patients with systemic lupus erythematosus (SLE). Viral infections may cause TM in these patients by causing a dysregulation of their immune system. We report a 30-year-old woman with SLE who had influenza A and a few days later developed urinary retention, bilateral lower extremity paralysis, upper extremity weakness, and optic nerve and macular edema. Magnetic resonance imaging showed C4-T12 hyperintense lesions consistent with TM. She was treated with intravenous methylprednisolone 1 g daily for 3 days and then 6 cycles of monthly intravenous cyclophosphamide. This treatment was followed by oral prednisone. She had a remarkable clinical response. Visual acuity improved to her baseline, and muscle strength almost fully recovered. Clinicians should be aware that viral infections, including influenza, may induce TM. This case highlights the importance of early recognition and prompt treatment with immunosuppressive drugs in such cases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) in terms of earlier SLE classification in comparison to the ACR or the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Methods: Patients from a multiethnic, multicenter cohort, the Lupus in Minorities: Nature versus Nurture cohort, where SLE was defined using the 1982/1997 ACR criteria were included. Demographic, clinical, and immunologic criteria were compared among the 2019 EULAR/ACR and the 1982/1997 ACR and the 2012 SLICC timing categories. Results: The 2019 EULAR/ACR criteria allowed an earlier SLE classification in 13.3% of patients (mean 0.66 years) and 15.3% of patients (mean 0.63 years) compared to the 1982/1997 ACR and the 2012 SLICC criteria, respectively. Patients accruing the 2019 EULAR/ACR criteria later than the 1982/1997 ACR criteria had a lower disease activity, were less likely to have positivity to anti–double‐stranded DNA and anti‐Sm, as well as lupus nephritis classes II or V; they were more likely to have mucocutaneous manifestations, serositis, leukopenia, and antiphospholipid antibodies positivity. These differences were less pronounced when compared to the 2012 SLICC criteria Conclusion: The 2019 EULAR/ACR criteria classified SLE patients earlier than the 2 other criteria sets in real‐life clinical practice scenarios in a relatively small proportion of the patients. However, these criteria could allow earlier classification of a subset of patients with a more severe disease. [ABSTRACT FROM AUTHOR]

Objective: Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. Methods: A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA‐SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. Results: The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. Conclusion: Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the difference in outcomes in patients who achieved or did not achieve the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria. Methods: Patients from the LUpus in MInorities, NAture versus nurture (LUMINA) cohort were included. For these analyses, we compared those patients who achieved the 2019 EULAR/ACR criteria any time during follow‐up to those who did not. The predefined outcomes were the last Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores and survival. Univariable and multivariable negative binomial regression models were performed; adjustment models were based on a forward selection process. Results: In total, 98 of 640 patients never achieved the 2019 EULAR/ACR criteria. There was no difference in mean baseline SDI score among the patients who did not achieve the criteria compared to those who did. Conversely, the mean ± SD SDI score at last visit was lower for those who never achieved the criteria (1.2 ± 1.7 versus 2.0 ± 2.3, P = 0.0004). In the final adjusted model, the SDI score at last visit was 31% lower for those who never achieved the criteria (P = 0.0077). These patients were also more likely to survive, but this was not statistically significant. Conclusion: In our cohort, patients who did not achieve the 2019 EULAR/ACR criteria accrued less damage, suggesting that these criteria could allow us to identify a subset of patients with more severe disease than allowed by previous criteria. [ABSTRACT FROM AUTHOR]

Macrophage-activating syndrome (MAS) is a rare condition characterized by dysfunctional macrophage activation leading to overproduction of cytokines and phagocytosis of erythrocytes, leukocytes, and platelets. MAS is associated with infectious diseases, malignancies, and autoimmune rheumatic disorders. Herein, we present a 22-year-old Hispanic woman with SLE who was hospitalized because of a three-week history of fever, fatigue, polyarthralgia, nausea, and abdominal pain. Initial laboratories showed severe pancytopenia with marked elevation of liver enzymes and ferritin levels. Bone marrow biopsy revealed macrophages with engulfed erythrocytes consistent with MAS. The patient was treated with high-dose corticosteroids, intravenous immunoglobulins, and cyclosporine 3 mg/kg/day. She had a remarkable clinical response to this therapy. She was continued on cyclosporine, and prednisone dose was gradually decreased to 7.5 mg daily without experiencing recurrent disease. She remained in full clinical remission for 12 months. Our case, together with other reports, suggests that combination therapy with corticosteroids, immunoglobulins, and cyclosporine appears to be effective for patients with SLE-associated MAS. Furthermore, cyclosporine seems to be a good drug for maintenance of remission. [ABSTRACT FROM AUTHOR]

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus (SLE). Although infrequent, its mortality is very high. While there are no established therapeutic guidelines, DAH has been traditionally managed with high-dose intravenous (IV) corticosteroids, cyclophosphamide, and plasma exchange. The efficacy of alternative therapies such as rituximab has been described only in a few cases. Herein, we report a 25-year-old Hispanic man who presented with acute-onset SLE manifested by polyarthralgia, nephritis, seizures, pancytopenia, severe hypocomplementemia, and elevated anti-dsDNA antibodies. His disease course was complicated by DAH. His condition was refractory to high-dose intravenous (IV) methylprednisolone pulses, IV cyclophosphamide, and plasmapheresis. Given the lack of clinical response, he was started on IV rituximab 375 mg/m2 weekly for a total of four courses. He rapidly improved after the first two doses. Over the next seven months, he did not present recurrent pulmonary symptoms. Follow-up chest computed tomography did not show residual abnormalities. This case, together with other reports, suggests that rituximab is an effective therapeutic option for DAH in SLE. [ABSTRACT FROM AUTHOR]

Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1×103/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications. [ABSTRACT FROM AUTHOR]

Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI ≤ 24.9 kg/m2 (nonoverweight/obese) and BMI ≥ 25 kg/m2 (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS. [ABSTRACT FROM AUTHOR]

Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2 weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. [ABSTRACT FROM AUTHOR]

Objective. Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis. Methods. We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects. Results. In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10-5, false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58-3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10-4) and European Americans (OR 3.47, P = 0.024). Conclusion. TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the Fcγ receptor IIIa-66L/R/H (FcγRIIIa-66L/R/H) polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by FcγRIIIa-66L/R/H and FcγRIIIa-176F/V, as well as copy number variation (CNV), confer risk of developing systemic lupus erythematosus (SLE) and lupus nephritis. Methods FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry-based human IgG-binding assays. Using Pyrosequencing methodology, FCGR3A single-nucleotide polymorphism and CNV genotypes were determined in a cohort of 1,728 SLE patients and 2,404 healthy controls. Results The FcγRIIIa-66L/R/H (rs10127939) polymorphism influenced ligand binding capacity in the presence of the FcγRIIIa-176V (rs396991) allele. There was a trend toward an association of the low-binding FcγRIIIa-176F allele with lupus nephritis among African Americans ( P = 0.0609) but not among European Americans ( P > 0.10). Nephritis among African American patients with SLE was associated with FcγRIIIa low-binding haplotypes containing the 66L/R/H and 176F variants ( P = 0.03) and with low-binding genotype combinations ( P = 0.002). No association was observed among European American patients with SLE. The distribution of FCGR3A CNV was not significantly different among controls and SLE patients with or without nephritis. Conclusion FcγRIIIa-66L/R/H influences ligand binding. The low-binding haplotypes formed by 66L/R/H and 176F confer enhanced risk of lupus nephritis in African Americans. FCGR3A CNVs are not associated with SLE or lupus nephritis in either African Americans or European Americans. [ABSTRACT FROM AUTHOR]

Objective To examine the prevalence of isolated IgA anti-β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI in a mouse model of thrombosis. Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2GPI-positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI positivity was associated with an increased risk of arterial thrombosis ( P < 0.001), venous thrombosis ( P = 0.015), and all thrombosis ( P < 0.001). The association between isolated IgA anti-β2GPI and arterial thrombosis ( P = 0.0003) and all thrombosis ( P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-β2GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.Methods: SLE patients (per American College of Rheumatology [ACR] criteria) ages ≥16 years with a disease duration of ≤10 years at enrollment and defined ethnicity (African American, Hispanic, or white) from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations, and disease damage (per the Systemic Lupus International Collaborating Clinics/ACR Damage Index) were determined. The association of discoid lupus erythematosus (DLE) with clinical manifestations and disease damage was examined using multivariable logistic regression.Results: A total of 2,228 SLE patients were studied. The mean ± SD age at diagnosis was 34.3 ± 12.8 years and the mean ± SD disease duration was 7.9 ± 6.0 years; 91.8% were women. DLE was observed in 393 patients with SLE (17.6%). In the multivariable analysis, patients with DLE were more likely to be smokers and of African American ethnicity and to have malar rash, photosensitivity, oral ulcers, leukopenia, and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity and to have arthritis, end-stage renal disease, and antinuclear, anti-double-stranded DNA, and antiphospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers.Conclusion: In this cohort of SLE patients, DLE was associated with several clinical features, including serious manifestations such as vasculitis and chronic seizures. [ABSTRACT FROM AUTHOR]

Objective Several confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis in lupus has been established. The aim of this study was to test for gene-gene interactions in a number of known lupus susceptibility loci. Methods Eighteen single-nucleotide polymorphisms tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control subjects of European descent. Epistasis was tested by a 2-step approach using both parametric and nonparametric methods. The false discovery rate (FDR) method was used to correct for multiple testing. Results We detected and confirmed gene-gene interactions between the HLA region and CTLA4, IRF5, and ITGAM and between PDCD1 and IL21 in patients with lupus. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 × 10−5 [FDR ≤0.05], P for multifactor dimensionality reduction = 5.9 × 10−45). Importantly, our data suggest that in patients with lupus, the presence of the HLA lupus risk alleles in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk allele in IRF5 (rs2070197) by 17% and 16%, respectively ( P = 0.0028 and P = 0.0047, respectively). Conclusion We provide evidence for gene-gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction contributing to the complexity of lupus heritability. [ABSTRACT FROM AUTHOR]

The article discusses a study to determine the localization of the genetic effect association of the interleukin (IL)2/IL21 which has previously been reported in lupus and other autoimmune and inflammatory diseases. Conditional analysis and transethnic mapping revealed genetic association between lupus and IL2/IL21 with a genome wide level of significance. Also explored is the IL2/IL21 linkage disequilibrium block being localized to IL21.

The article presents information on a study concerning the genetic relationship between single-nucleotide polymorphisms (SNPs) within systemic lupus erythematosus (SLE) and interleukin-21 receptor (IL21R). It features SLE as a chronic systematic autoimmune disease related to multiple organs. Results of the study suggest that IL21R is a novel susceptibility gene for SLE. It also indicates the importance of IL21R in understanding the origin and development of SLE.

The article focuses on the efficacy of methyl-CpG-binding protein 2 gene (MECP2) polymorphisms as a key transcription regulator in the treatment of systematic lupus erythematosus (SLE). SLE is a chronic autoimmune disease which affect multiple organs including the brain and heart. The MECP2 served as a transcription activator in the majority of genes regulated by MECP2 in the murine hypothalamus. Details on the association of lupus within variants of MECP2 are discussed.

This article discusses a study which examined the prevalence of Klinefelter's syndrome in patients with systemic lupus erythematosus (SLE). The study used fluorescence in situ hybridization (FISH) and karyotyping in transformed B cell lines in the investigating the association between the two disorders. It showed an increase in the frequency of Klinefelter's syndrome in men with SLE.

A letter to the editor is presented in response to an article by Mazlumzadeh et al about the effectiveness and safety of induction therapy with high-dose pulse intravenous methylprednisolone in giant cell arteritis.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway., Methods: We analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively., Results: We found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression., Conclusion: Our results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis., (Copyright © 2012 by the American College of Rheumatology.)

Objective: American Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients., Methods: A total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs)., Results: The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement., Conclusion: In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age., (Copyright © 2012 by the American College of Rheumatology.)

Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development., Methods: Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated., Results: Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10(-5) and P = 4.73 × 10(-5) , respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r(2) = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10(-4) , OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10(-6) , OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model., Conclusion: Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity., (Copyright © 2012 by the American College of Rheumatology.)

Objective: Candidate gene and genome-wide association studies have identified several disease susceptibility loci in lupus patients. These studies have largely been performed in lupus patients who are Asian or of European ancestry. This study was undertaken to examine whether some of these same susceptibility loci increase lupus risk in African American individuals., Methods: Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4, STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region), C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1., Results: We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10⁻⁶, P = 1.9 × 10⁻⁵, P = 5.7 × 10⁻⁵, P = 0.00099, and P = 0.0045, respectively). Further, we confirmed the genetic association between lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and FCGR2A; P = 7.5 × 10⁻¹¹, P = 5.2 × 10⁻⁸, P = 8.7 × 10⁻⁷ , P = 0.0058, and P = 0.0070, respectively), and provided evidence, for the first time, of genome-wide significance for the association between lupus in African American patients and ITGAM and MSH5 (HLA region)., Conclusion: These findings provide evidence of novel genetic susceptibility loci for lupus in African Americans and demonstrate that the majority of lupus susceptibility loci examined confer lupus risk across multiple ethnicities., (Copyright © 2011 by the American College of Rheumatology.)

Objective: T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac., Methods: We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction., Results: A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P=3.8×10(-7)). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P=0.007)., Conclusion: Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians., (Copyright © 2011 by the American College of Rheumatology.)

Objective: The overexpression of interferon (IFN)-inducible genes is a prominent feature of systemic lupus erythematosus (SLE); it serves as a marker for active and more severe disease, and is also observed in other autoimmune and inflammatory conditions. This study was undertaken to investigate the genetic variations responsible for sustained activation of IFN-responsive genes in SLE., Methods: We systematically evaluated association of SLE with a total of 1,754 IFN pathway-related genes, including IFN-inducible genes known to be differentially expressed in SLE patients and their direct regulators. We used a 3-stage study design in which 2 cohorts (total of 939 SLE cases and 3,398 controls) were analyzed independently and jointly for association with SLE, and the results were adjusted for the number of comparisons., Results: A total of 15,166 single-nucleotide polymorphisms (SNPs) passed all quality control filters; 305 of these SNPs demonstrated replicated association with SLE in both cohorts. Nine variants were further genotyped for confirmation in an average of 1,316 independent SLE cases and 3,215 independent controls. Association with SLE was confirmed for several genes, including those for the transmembrane receptor CD44 (CD44 [rs507230]; P = 3.98 × 10⁻¹²), the cytokine pleiotrophin (PTN [rs919581]; P = 5.38 × 10⁻⁴), the heat-shock protein DnaJ (DNAJA1 [rs10971259]; P = 6.31 × 10⁻³), and the nuclear import protein karyopherin α1 (KPNA [rs6810306]; P = 4.91 × 10⁻²)., Conclusion: This study expands the number of candidate genes that have been shown to be associated with SLE and highlights potential of pathway-based approaches for gene discovery. Identification of the causal alleles will help elucidate the molecular mechanisms responsible for activation of the IFN system in SLE., (Copyright © 2011 by the American College of Rheumatology.)

Objective: To examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE)., Methods: SLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm(3) at or before enrollment (baseline). Patients were categorized by the presence and absence of thrombocytopenia. The impact of thrombocytopenia as well as severe thrombocytopenia (platelet count <50,000/mm(3)) on disease activity, damage accrual, and mortality was examined by multivariable analyses., Results: A total of 616 patients were studied; 121 of the patients (20%) had thrombocytopenia, of whom 30 had severe thrombocytopenia. By univariable analyses, those with thrombocytopenia had more pulmonary, neurologic, renal, and hematologic involvement, worse disease activity and damage, and higher mortality rates. By multivariable analyses, thrombocytopenia was associated with higher disease activity over the disease course (P = 0.018), but not with the accrual of damage either at baseline (P = 0.543) or at the last visit (P = 0.086); however, severe thrombocytopenia was associated with damage accrual at the last visit (P = 0.020). When poverty was not included in the models, thrombocytopenia (<100,000/mm(3) or <50,000/mm(3)) was strongly associated with mortality (P < 0.001 for each comparison); however, the level of significance decreased some when poverty was included in the models., Conclusion: Thrombocytopenia early in the course of SLE is indicative of more severe and active disease. Severe thrombocytopenia is an independent predictor of damage accrual at the last visit. Thrombocytopenia is also an independent predictor of mortality, albeit of a lesser magnitude than that predicted by poverty. Patients with thrombocytopenia need close monitoring for possible undesirable outcomes.

Objective: To determine the impact of the patient's sex on the manifestations and outcome of systemic lupus erythematosus (SLE)., Methods: We studied SLE patients who were ages 16 years or older and had a disease duration of < or =5 years at the time of enrollment in the LUpus in MInorities, NAture versus nurture cohort, a multiethnic cohort consisting of Hispanic, African American, and Caucasian patients. Socioeconomic/demographic, clinical, and serologic features, as well as disease activity (by the Systemic Lupus Activity Measure, Revised) and damage accrual (by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were compared between male and female patient groups. Multivariable analyses using male sex and damage accrual as dependent variables were then performed., Results: Sixty-three male SLE patients (10.2%) from all ethnic groups were included. The mean ages of the male and female patients were comparable. Factors that were either more frequent or tended to be more frequent among male SLE patients were Caucasian ethnicity, smoking, alcohol use, lupus anticoagulant (LAC) positivity, and renal involvement, whereas musculoskeletal involvement was less common. American College of Rheumatology criteria accrual time and disease duration were shorter in the male patients; damage was more common and of higher magnitude in this group. LAC positivity, shorter disease duration, and higher early damage scores were independently associated with male SLE. Male sex was a strong predictor of baseline damage, measured as a categorical variable (t-test = 2.357, beta-standardized coefficient 0.113; P = 0.019) or a continuous variable (hazard ratio 3.179 [95% confidence interval 1.999-5.056]; P < 0.001). Male sex was also positively associated with the development of damage over most of the course of the disease., Conclusion: Poorer long-term prognosis among men with SLE appears to be decisively determined by their accelerated development of damage, particularly early in the course of the disease.

Objective: To study the association between deficient mannose-binding lectin (MBL) genotypes and arterial thrombotic events in systemic lupus erythematosus (SLE)., Methods: Patients with SLE of Hispanic, African American, and Caucasian ethnicity from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Arterial thrombotic events (myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene, or tissue loss and/or peripheral arterial thrombosis) that occurred after diagnosis were recorded. Genotyping for MBL gene polymorphisms was performed and their distribution was compared between patients who did and did not have thrombotic events., Results: There were 58 events (21 cardiovascular, 27 cerebrovascular, and 10 peripheral vascular) in 48 patients. Patients who had thrombotic events were older and were more likely to be smokers, to have more severe disease, and to have accrued more damage overall. Also, a larger proportion of these patients had C-reactive protein values in the highest quintile of distribution. No significant difference in arterial thrombotic events was found in patients homozygous for MBL-deficient alleles compared with others. Similar results were seen within ethnic groups. Caucasians who developed potential thrombotic events exhibited a higher frequency of MBL-deficient alleles, but the difference was not statistically significant for all events together or for cardiovascular and cerebrovascular events combined. However, when only the cerebrovascular events were considered, the difference became statistically significant., Conclusion: Age, smoking, and measures of activity and damage were associated with arterial thrombotic events in patients with SLE, but MBL-deficient genotypes were not, with cerebrovascular events in Caucasians being the exception. The relationship between MBL-variant alleles and arterial thrombotic events may exist only within select ethnic groups and event types.

Objective: To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE)., Methods: A nested case-control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age < or = 49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self-reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late-onset lupus, damage accrual, and mortality as dependent variables were then performed., Results: Two hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late-onset lupus was an independent predictor of damage accrual (t-test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98-141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07-37.56) (P < 0.001)., Conclusion: Patients with late-onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early-onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients.

Objective: Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE., Methods: Patients with SLE, ages > or = 16 years with < or = 5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included., Results: Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P = 0.020), shorter disease duration at time 0 (P = 0.017), serum levels of total cholesterol, low-density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P = 0.045) were associated with venous thrombotic events. Survival analyses showed a time-dependent significant association of the primary outcome with smoking (P = 0.008) and a borderline significant association with the presence of LAC (P = 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0., Conclusion: Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over time, and higher mean daily glucocorticoid dose were identified as additional risk factors for the development of this vascular complication. These findings may have implications for the management of patients with SLE.

Objective: To determine the differences in clinical manifestations, disease activity, damage accrual, and medication use in systemic lupus erythematosus (SLE) patients as a function of menopausal status at disease onset., Methods: Women with SLE as per the criteria of the American College of Rheumatology, with disease duration of 6 months, and/or oophorectomy, and/or increased follicle-stimulating hormone values for reproductive-age women, and/or treatment with hormone replacement therapy. Patients were divided into premenopausal and postmenopausal categories. Socioeconomic status, cumulative clinical manifestations, disease activity (at study entry or time 0, last visit, and over time), as measured by the Systemic Lupus Activity Measure, and damage accrual, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (at time 0 and at last visit) were compared between the 2 groups of women. Multivariable models were then examined making adjustments for all possible known confounders. Dependent variables in the models were renal involvement, damage accrual, arterial vascular events, and venous thrombosis., Results: Five hundred eighteen women from the LUMINA cohort were included; 436 (84.2%) were premenopausal and 82 (15.8%) were postmenopausal. Disease onset after menopause was more common among Caucasians. Renal involvement was more common in premenopausal women, whereas vascular arterial events were more frequent in postmenopausal women. All other disease manifestations, as well as disease activity, were comparable between both groups. The presence of damage accrual at time 0 and study end was more frequent in postmenopausal women. Age, rather than menopausal status, independently contributed to damage accrual, renal involvement, and vascular arterial events in these women., Conclusion: A hypoestrogenemic state secondary to menopause appears not to be protective against disease activity and damage accrual. Age rather than menopausal status is a strong independent predictor of damage accrual and of vascular events in women with lupus.

Objective: To determine the baseline (time 0) risk factors associated with the subsequent occurrence of vascular events in a multiethnic US cohort (LUMINA [LUpus in MInorities: NAture versus nurture]) of patients with systemic lupus erythematosus (SLE)., Methods: Five hundred forty-six LUMINA patients were assessed at time 0 for traditional and nontraditional (disease-related) risk factors for vascular events. These were defined as 1) cardiovascular (myocardial infarction and/or definite or classic angina and/or the undergoing of a vascular procedure for myocardial infarction [coronary artery bypass graft]), 2) cerebrovascular (stroke), and 3) peripheral vascular (arterial claudication and/or gangrene or significant tissue loss and/or arterial thrombosis in peripheral arteries). The observation time (followup time in the cohort) was the interval between time 0 and the last visit. The unit of analysis was the patient and not each vascular event. Variables at time 0 and vascular events were examined by univariable and multivariable (logistic and Cox proportional hazards regression) analyses. Age, sex, ethnicity, followup time, and all known risk factors for the occurrence of vascular events were included in the model., Results: Thirty-four patients (6.2%) developed one or more vascular event after time 0. The overall median duration of followup in the cohort was 73.8 months (range 10.8-111.3 months). Vascular events (13 cardiovascular, 18 cerebrovascular, 5 peripheral vascular) occurred in 7 Hispanics from Texas (6.5%), 1 Hispanic from Puerto Rico (1.2%), 15 African Americans (7.5%), and 11 Caucasians (7.1%). The mean total number of traditional risk factors was significantly higher in patients who developed vascular events than in those who did not (7.1 versus 5.6). Independent predictors of vascular events were older age, current smoking status, longer followup time, elevated serum levels of C-reactive protein (CRP), and the presence of any antiphospholipid antibody. The same variables were identified when time-dependent analyses were performed, although azathioprine use was also found to be a contributing factor., Conclusion: Smoking, previously not reported in SLE, emerged as a predictor of vascular events and should be strongly discouraged. Antiphospholipid antibodies and CRP support the role of inflammation and autoimmunity in the development of accelerated atherosclerosis in SLE. Ethnicity was not associated with vascular events in our patients.

Objective: To examine the factors predisposing to initial damage in patients in the LUMINA (lupus in minorities: nature versus nurture) cohort, a multiethnic cohort of patients with systemic lupus erythematosus (SLE) in the US., Methods: One hundred fifty-eight LUMINA patients with no damage at baseline (time 0) according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI) and with disease duration > 6 months were followed up for a median of 24 months (range 5-112 months). Damage was assessed from time 0 to the last visit. Predictors of time to initial damage were examined by univariable and multivariable Cox proportional hazard regression models. Results were reported as hazard ratios (HRs); HR values > or = 1 indicated a shorter time to initial damage, and values < 1 indicated a longer time., Results: Initial damage occurred in 54 patients (34%), of whom 21 were Hispanics from Texas (39%), 2 were Hispanics from Puerto Rico (4%), 21 were African Americans (39%), and 10 were Caucasians (19%). The most frequently observed initially involved SDI domains (and items) were as follows: renal (primarily proteinuria) in Hispanics from Texas and African Americans, integument (primarily scarring alopecia) in Hispanics from Puerto Rico, and ocular (primarily cataracts) in Caucasians. By multivariable analyses, independent predictors of a shorter time to initial damage were Hispanic ethnicity from Texas (HR 2.11, 95% confidence interval [95% CI] 1.15-3.88), greater disease activity according to the Systemic Lupus Activity Measure (HR 1.09, 95% CI 1.04-1.15), the occurrence of thrombotic events in visceral and/or peripheral veins or arteries (HR 7.66, 95% CI 2.13-27.51), and prednisone at a dosage of < 10 mg/day (HR 2.53, 95% CI 1.15-5.55). Prednisone at a dosage of 10-30 mg/day was found to be protective against the occurrence of initial damage (HR 0.46, 95% CI 0.22-0.96)., Conclusion: Given that damage is a predictor of further damage, identifying the factors that may herald the occurrence of initial damage has very practical implications for the management of patients with SLE. These results need to be considered when evaluating therapies for SLE., (Copyright 2004 American College of Rheumatology)