Trajectory of Damage Accrual in Systemic Lupus Erythematosus Based on Ethnicity and Socioeconomic Factors.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is associated with increased healthcare costs and mortality. We compared the trajectory of total and individual damage items of the SDI in African American vs White ethnicities in a large prospective systemic lupus erythematosus (SLE) cohort. We also estimated the association between ethnicity and individual damage items after adjusting for several socioeconomic factors. METHODS: Poisson regression was used to calculate the rate of damage per year for each organ. Cox regression modeling was used to determine the association between time to the individual damage item and ethnicity. RESULTS: We included 2436 patients: 42.9% African American, 57.1% White, and 92% female. There was a linear relationship between time since diagnosis and mean SDI score, with no plateau. Compared to White patients, African American patients had a faster total, renal, pulmonary, and skin damage accrual rate even after adjustment for differences in socioeconomic variables. CONCLUSION: The linear increase in damage in both ethnicities over time is of particular concern. African American patients accrued more damage at a faster rate compared to White patients. For a few organs, higher rates of damage in African American patients was partially explained by socioeconomic differences, whereas for most organs, the difference persisted after adjustment for these factors.

Predictors of Osteonecrosis in Systemic Lupus Erythematosus: A Prospective Cohort Study.

OBJECTIVE: We aimed at determining the predictors of osteonecrosis (ON) in a longitudinal lupus cohort. METHODS: Data were reviewed from the initiation of the cohort in 1987 until October 2019. In total, 2,428 patients were included in the analysis based on 224,295 person-months of follow-up. We used pooled logistic regression to assess the relationship between risk factors and rates of ON events. After identifying a set of variables related to ON incidence, we fit a final multivariable model to identify the most important risk factors for incident ON. RESULTS: In 18,691 person-years of follow-up after cohort entry, 122 incident ON events were observed (rate = 6.5/1,000 person-years). In the multivariable analysis, African American patients were at twice the risk for ON compared to White patients. Male patients and smokers had an increased risk for ON of ~80% and 50% compared to female patients and nonsmokers, respectively. For every 10-year increase in the age at diagnosis, there was a 20% reduced risk for ON. Patients diagnosed after the 1990s had a 50% reduced risk of ON compared to those diagnosed before the 1990s. A highest daily dosage of prednisone of 40 mg or higher, even when administered for a month or less, significantly increased the risk of ON. Use of pulse methylprednisolone or intramuscular triamcinolone was not associated with an increased risk of ON. CONCLUSION: African American patients with systemic lupus erythematosus are at double the risk of experiencing ON compared to White patients. Oral prednisone at 20-39 mg for more than 1 month, or 40 mg daily for even 1 month, at any point in the disease course, remained the most important glucocorticoid predictor of ON.

Cutaneous vasculitis in SLE.

OBJECTIVES: We determined the temporal association between clinical and serological disease manifestations and development of cutaneous small vessel vasculitis in a large prospective multiethnic cohort. METHODS: Patients with SLE diagnosed according to the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria or the revised classification criteria as defined by the American College of Rheumatology (ACR) were enrolled in the Hopkins Lupus Cohort. Cutaneous small vessel vasculitis was determined as a component of the Systemic Lupus Erythematosus Disease Activity Index. SLE-associated cutaneous small vessel vasculitis lesions were reported clinically. They presented as punctate lesions, palpable purpura, tender erythematous plaques or macules with or without necrosis. No histopathological diagnosis was pursued to confirm the diagnosis of vasculitis or to differentiate it from other causes of digital lesions in patients with SLE. Disease manifestations that preceded the first occurrence of cutaneous small vessel vasculitis lesions were analysed using Kaplan-Meier. Cox regression analysis was used to assess the relationship between baseline clinical and immunological manifestations and the development of cutaneous small vessel vasculitis. We adjusted for gender, race and age at SLE diagnosis. RESULTS: A total of 2580 patients were studied: 52.4% were Caucasian and 39.4% were African-American. The mean age of the cohort was 45.5±14.5 years. The mean years of cohort follow-up was 7.9±7.6. Cutaneous small vessel vasculitis was observed in 449 (17.3%). The mean time to cutaneous vasculitis after SLE diagnosis was 4.78 years (95% CI 3.96 to 5.60). At least 159 (35%) patients had recurrences of cutaneous vasculitis lesions. Discoid rash, Raynaud's phenomenon, myositis, anaemia, Coombs' positivity, leucopenia, anti-Smith and anti-RNP (Ribonucleoprotein) were significantly associated with the development of cutaneous vasculitis. The SLICC/ACR Damage Index score was higher in patients with cutaneous vasculitis compared with those without cutaneous vasculitis. CONCLUSIONS: Cutaneous vasculitis is frequent (17.3%) and often recurrent (35%). African-Americans are at higher risk of developing cutaneous small vessel vasculitis than Caucasians. Clinical presentations such as myositis and haematological manifestations are predictors of cutaneous vasculitis development. The presence of cutaneous vasculitis is associated with increased organ damage.

Association of African-American ethnicity and smoking status with total and individual damage index in systemic lupus erythematosus.

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.

Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet's disease.

BACKGROUND AND OBJECTIVES: Behçet's disease (BD) is a multi-system inflammatory disorder that can cause vasculitis. Here we questioned whether Neutrophils in BD cause vasculitis via releasing Neutrophil Extracellular Traps (NETs), a process called NETosis. METHODS: Circulating neutrophils were isolated from a cohort of Middle Eastern BD patients with an active disease and healthy volunteers. The percentage of NETs release was monitored in neutrophils stimulated or not with BD serum, and treated or not with Colchicine, Dexamethasone, Cl-amidine or N-Acetyl Cysteine (NAC). The mRNA expression levels of PAD4 (a key enzyme in NETosis) was also assessed. The effect of NETs on the proliferation and cell death of endothelial cells was investigated using an in vitro co-culture model. The presence of NETs in skin tissues of BD patients was examined using immunolabeling of NETs associated proteins. RESULTS: Circulating Neutrophils from BD patients were more prone to release NETs in vitro and expressed higher levels of PAD4 compared to healthy volunteers. Spontaneous NETs formation in BD neutrophils was inhibited by Colchicine and Dexamethasone, two drugs used to treat BD. NETs formation was also inhibited by Cl-amidine, a specific PAD4 inhibitor, and by NAC, a ROS inhibitor. Interestingly, serum from BD patients stimulated circulating neutrophils from healthy volunteers to release more NETs and increased their mRNA PAD4 expression. Moreover, endothelial cells cultured in the presence of NETs from BD patients showed a decrease in proliferation and an increase in apoptosis and cell death. Finally, NETosis was predominantly identified around affected blood vessels in biopsies of vasculitis from BD patients. CONCLUSION: Our results provide evidence on the implication of NETosis in the pathophysiology of BD especially in inducing vasculitis.

Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease.

First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis.

Requirements of Clinical Journals for Authors' Disclosure of Financial and Non-Financial Conflicts of Interest: A Cross Sectional Study.

IMPORTANCE: It is unclear how medical journals address authors' financial and non-financial conflict of interest (COI). OBJECTIVE: To assess the policies of clinical journals for disclosure of financial and non-financial COI. METHODS: Cross sectional study that included both review of public documents as well as a simulation of a manuscript submission for the National Library of Medicine's "core clinical journals". The study did not involve human subjects. Investigators who abstracted the data, reviewed "instructions for authors" on the journal website and, in order to reflect the actual implementation of the COI disclosure policy, simulated the submission of a manuscript. Two individuals working in duplicate and independently to abstract information using a standardized data abstraction form, resolved disagreements by discussion or with the help of a third person. RESULTS: All but one of 117 core clinical journals had a COI policy. All journals required disclosure of financial COI pertaining to the authors and a minority (35%) asked for financial COI disclosure pertaining to the family members or authors' institution (29%). Over half required the disclosure of at least one form of non-financial COI (57%), out of which only two (3%) specifically referred to intellectual COI. Small minorities of journals (17% and 24% respectively) described a potential impact of disclosed COI and of non-disclosure of COI on the editorial process. CONCLUSION: While financial COI disclosure was well defined by the majority of the journals, many did not have clear policies on disclosure of non-financial COI, disclosure of financial COI of family members and institutions of the authors, and effect of disclosed COI or non-disclosure of COI on editorial policies.