Dongying Chen

Clinical features and independent predictors of pulmonary arterial hypertension in systemic lupus erythematosus

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic lupus erythematosus (SLE). We aim to estimate the putative predictors contributing to early identification of PAH, thus improve appropriate medical intervention and a better prognosis. A retrospective case–control study was conducted. Forty-one SLE patients with PAH and 106 SLE patients without PAH were enrolled. Demographic variables, clinical features, and laboratory data were compared between the two groups. Univariate and multivariate logistic regression models were used to examine the predictors contributing to PAH in SLE. Serositis, Raynaud’s phenomenon, high disease activity, anticardiolipin antibodies, and anti-U1RNP were significantly associated with SLE-PAH. Univariate and multivariate analysis showed that Raynaud’s phenomenon, anticardiolipin antibodies, and anti-U1RNP were independent predictors of PAH in SLE. This study highlighted the clinical pattern of SLE-PAH patients, and underlined the leading predictors of PAH development among patients with SLE. Routine echocardiography is recommended in SLE patients with the independent predictors mentioned above.

Lupus mesenteric vasculitis: Clinical features and associated factors for the recurrence and prognosis of disease

OBJECTIVE To evaluate the clinical characteristics of lupus mesenteric vasculitis (LMV) and identify the potential factors and appropriate treatments that are associated with disease relapse and prognosis in LMV. METHODS A retrospective cohort study was performed among patients admitted to the First Affiliated Hospital of Sun Yet-sen University between 2002 and 2011. Demographic information, clinical symptoms, laboratory findings, imaging characteristics like abdominal CT scan, ultrasonography, medications including corticosteroid, cyclophosphamide, and other immunosuppressive agents, and outcomes were documented. The endpoints of the study were defined as occurrence of severe complications that needed surgical intervention, disease recurrence, or death. RESULTS Out of 3823 systemic lupus erythematosus (SLE) patients, 97 were diagnosed with mesenteric vasculitis with the overall prevalence of 2.5%. Among these 97 LMV patients, 13 died because of serious complications (13/97, 13.4%) and 2 presented intestinal perforation during the induction therapy stage. The logistic regression multivariate analysis indicated that leukopenia [peripheral WBC, odds ratio (OR) = 0.640, 95% confidence interval (CI): 0.456-0.896, P = 0.009], hypoalbuminemia (serum albumin, OR = 0.891, 95% CI: 0.798-0.994, P = 0.039) and elevated serum amylase (OR = 7.719, 95% CI: 1.795-33.185, P = 0.006) were positively associated with the occurrence of serious complications, while intravenous cyclophosphamide (CYC) therapy inhibited the occurrence of serious complications (OR = 0.220, 95% CI: 0.053-0.903, P = 0.036). A total of 79 patients who achieved remission were followed-up for 2-96 months and 18 cases experienced disease relapse (18/79, 22.8%). The statistical analysis adjusted by Cox proportional hazards models indicated that high-dose CYC therapy (≥ 1.0 g/m(2)/month) was a protective factor for disease relapse and led to better outcomes [hazard ratio (HR) = 0.209, 95% CI: 0.049-0.887, P = 0.034], while the severe thickness of the bowel wall (>8mm) was a risk factor (HR = 7.308, 95% CI: 1.740-30.696, P = 0.007). LMV and lupus cystitis occurred concurrently in 22 (22/97, 22.7%) patients, and the symptoms of urinary tract resolved after treatment with corticosteroid and immunosupressants. CONCLUSION LMV is one of the serious complications of SLE with high mortality. The current study demonstrated that leukopenia, hypoalbuminemia, and elevated serum amylase were associated with severe adverse events, while CYC therapy led to better outcomes during remission-induction stage. Severe thickness of the bowel was a risk factor while high-dose CYC therapy was a protective factor for disease relapse in intensification therapy stage. It is necessary to evaluate the urinary tract involvement once LMV is diagnosed due to the frequent coexistence of these 2 diseases.

Clinical Features and Associated Factors of Abdominal Pain in Systemic Lupus Erythematosus

Objective. To evaluate the clinical characteristics of systemic lupus erythematosus (SLE)-induced abdominal pain in a cohort in South China and identify the risk factors for SLE-induced abdominal pain. Methods. This is a retrospective cohort study of SLE patients with complaint of abdominal pain admitted to the first affiliated university hospital of Sun Yat-sen University between 2002 and 2011. Demographic information, clinical features, laboratory findings, SLE Disease Activity Index, and imaging characteristics were documented. Results. Of the 3823 SLE patients reviewed, 213 patients complained of abdominal pain and 132 cases were considered SLE-induced. The most common causes were lupus mesenteric vasculitis (LMV; 73.5%, 97/132) and lupus pancreatitis (LP; 17.4%, 23/132). Other causes included appendicitis, acute gastroenteritis, and peritonitis. Univariate and multivariate logistic regression analysis indicated the European Consensus Lupus Activity Measurement (ECLAM) score was significantly associated with lupus-induced abdominal pain (OR = 1.858, 95% CI: 1.441–2.394, p < 0.001), LMV (OR = 1.713, 95% CI: 1.308-2.244, p < 0.001), and LP (OR = 2.153, 95% CI: 1.282, 3.617, p = 0.004). The serum D-dimer level (OR = 1.004, 95% CI: 1.002-1.005, p < 0.001) was a strongly associated factor for lupus-induced abdominal pain. Moderate and large amounts of ascetic fluid was significantly associated with lupus-induced abdominal pain and LMV. Elevated liver enzymes was a risk factor for LP (OR = 34.605, 95% CI: 3.591-333.472, p = 0.002). Conclusion. LMV and LP were the leading causes of SLE-induced abdominal pain. The serum D-dimer was a strongly associated factor for lupus-induced abdominal pain. ECLAM score was a reliable index in assessment of SLE-associated abdominal pain. Elevated liver enzymes, and moderate or large amounts of ascites, were positively associated with lupus-induced abdominal pain.

Infection in Southern Chinese Patients with Systemic Lupus Erythematosus: Spectrum, Drug Resistance, Outcomes, and Risk Factors

Objective. To investigate the spectrum, antibiotic-resistant pattern, risk factors, and outcomes of infection in patients hospitalized with systemic lupus erythematosus (SLE). Methods. We collected the clinical and microbiological data from hospitalized patients with SLE with infection between June 2005 and June 2015, and then conducted retrospective analyses. Results. Among our sample of 3815 hospitalized patients, 1321 (34.6%) were diagnosed with infection. The majority (78.3%) of infection occurred within 5 years of SLE onset. Bacterial infection was predominant (50.6%), followed by viral infection (36.4%) and fungal infection (12.5%). The lungs (33.7%) and upper respiratory tracts (26.3%) were most commonly affected. Gram-negative bacteria (GNB) were predominant over gram-positive bacteria (178 isolates vs 90 isolates). The most frequently isolated bacteria were Escherichia coli (24.6%), followed by Acinetobacter baumannii (13.4%) and coagulase-negative Staphylococcus (13.4%). Multidrug-resistant (MDR) strains were detected in 26.9% of bacterial isolates. The most common fungus was Candida spp. (99 episodes), followed by Aspergillus (24 episodes) and Cryptococcus neoformans (13 episodes). The overall mortality rate for this cohort was 2.2%; 48 patients died of infection. Factors associated with bacterial and viral infection were higher Systemic Lupus Erythematosus Disease Activity Index, renal involvement, thrombocytopenia, accumulated dose of glucocorticoids (GC), and treatment with cyclophosphamide (CYC). Renal involvement, accumulated dose of GC, and treatment with CYC were associated with fungal infection. Conclusion. Infection was the leading cause of mortality in patients hospitalized with SLE. There were some notable features of infection in Chinese patients including early onset, higher proportion of respiratory tract involvement, predominance of GNB with emergence of MDR isolates, and a variety of pathogens.

Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus

This study aims to investigate the fetal outcomes and associated factors of adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus erythematosus (SLE). Clinical data from 251 SLE patients with 263 pregnancies from 2001 to 2015 were analyzed retrospectively. APOs occurred in 70.0% of pregnancies, in which pregnancy loss occurred in 28.5%; preterm delivery occurred in 21.3%; intrauterine growth retardation occurred in 12.2%; and fetal distress occurred in 8.0%. Over time, the rate of APOs decreased from 82.8% during 2001~2005 to 59.6% during 2011~2015. In multivariate analysis, predictors of APOs included positive antiphospholipid antibodies (OR 8.4, 95% CI 1.7~40.8, P = 0.008), lower complement (OR 3.6, 95% CI 1.3~9.9, P = 0.01), hypoalbuminemia (OR 3.2, 95% CI 1.2~8.3, P = 0.02), and hypertension (OR 14.6, 95% CI 1.5~141.6, P = 0.02). The use of antimalarial medications was associated with lower risk for APOs (OR 0.3, 95% CI 0.1~0.7, P = 0.01). In total, 109 patients underwent fetal umbilical artery Doppler in the third trimester. The The adjusted systole/diastole (S/D) ratio, pulsatility index (PI) and resistance index (RI) of SLE patients with APOs were higher than that of patients without APOs (2.9±0.9 vs. 2.4±0.5, P = 0.001). Lupus pregnancy was still at high risk of APOs in terms of pregnancy loss and preterm delivery. Umbilical artery Doppler was a good monitor method for APOs in the third trimester.

Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.

To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast‐like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme‐linked immunosorbent assay (ELISA) and real‐time polymerase chain reaction (PCR). Migration and invasion in vitro were detected by Boyden chamber assay. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up‐regulated by stimulation with IL‐1β and TNF‐α. Inhibition of PRMT5 by EPZ015666 and siRNA‐mediated knockdown reduced IL‐6 and IL‐8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS, which was mediated by the NF‐κB and AKT pathways. Our data suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA.

Herpes zoster in patients with systemic lupus erythematosus: Clinical features, complications and risk factors

Herpes Zoster (HZ) is reported as the most prevalent viral infection in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate the clinical features, complications, and potential risk factors of HZ in patients with SLE from Southern China. A retrospective study was performed among patients with SLE admitted to the First Affiliated Hospital of Sun Yet-Sen University (Guangzhou, China) between 2009 and 2013. Demographic information, clinical and laboratory data, and medications used were collected and analyzed. A total of 48 instances of HZ from 46 individuals in a cohort of 1,265 SLE patients during the follow-up period were identified, with an overall prevalence of 3.6%. Complications occurred in 23.9% of patients with HZ (11/46). The risk of HZ was highest within 3–6 months following SLE diagnosis and reduced thereafter. The multivariate logistic regression analysis demonstrated that lymphopenia (OR=4.6; 95% CI=1.5–13.8; P=0.006) and treatment with high-dose glucocorticoids (GC; OR=4.3; 95% CI=1.6–11.7; P=0.004) were both significantly associated with occurrence of HZ. Lymphopenia was the only independent risk factor for the occurrence of complicated HZ (OR=15.2; 95% CI=2.7–85.1; P=0.002). There are some notable characteristics of HZ in patients with SLE in Southern China, such as the tendency to manifest in an early stage of SLE, and frequent complications with benign outcomes. The present data supported the role of lymphopenia and high-dose of GC therapy as risk factors for the occurrence of HZ. Lymphopenia was also shown to contribute to complicated HZ.

A Rare Case of Disseminated Tuberculosis of the Bone Marrow in Systemic Lupus Erythematosus: Case Report.

AbstractPatients with systemic lupus erythematosus (SLE) are susceptible to tuberculosis (TB), especially in endemic areas such as China. The variable and nonspecific clinical features of disseminated TB often leads to an erroneous or misdiagnosis. When a patient presents with TB of the bone marrow, the clinical condition is more perplexing and the prognosis is typically poor. Till now, there is no case report after apatinib came in the market.Here, we report a case of TB of the bone marrow accompanied with SLE. The patient exhibited remarkable features, including widespread lesions in the lungs, spinal vertebrae, sacrum, and ilium that were found to be consistent with TB of the bone marrow after histopathological examination.This case highlights the importance of clinical suspicion for TB during the follow-up of SLE patients, especially in endemic areas. An aggressive diagnostic biopsy should be performed in suspected TB patients as early as possible.

Factors Associated with Erosive Arthritis in Rheumatoid Arthritis and Other Connective Tissue Diseases: A Retrospective Study From a Southern Chinese Population.

ObjectiveTo investigate the clinical predictors of erosive arthritis (EA) in patients with rheumatoid arthritis (RA) and other connective tissue diseases. MethodsFour hundred and one consecutive patients with newly diagnosed RA between January 2010 and January 2013 were enrolled in the study. During the study period, 729 consecutive patients with non-RA connective tissue diseases were also included, and a cross-sectional study was performed. Medical records were reviewed. Only those patients with data for 2 years were considered in the analysis (338). ResultsErosive arthritis was noted in 60.4% (204 /338) of patients with RA and occurred early in RA. The multivariate logistic regression analysis indicated that rheumatoid nodules, anemia, and positive anticyclic citrullinated peptide antibody (ACPA) were strongly associated factors for the occurrence of EA in RA patients. Erosive arthritis was also noted in 1.5% of patients with SLE, 5.8% of patients with primary Sjögren syndrome, and 9.1% (3/33) of patients with systemic sclerosis. When compared with patients without EA, high level and prominently higher positive rate of ACPA was found in these patients with EA. On receiver operating characteristic curve analysis, ACPA exhibited a maximum sensitivity with a cutoff value of 1.6 U/mL and 0.6 U/mL for RA and SLE patients, respectively. ConclusionErosive arthritis had a high prevalence in Chinese RA patients and occurred early. Anemia, rheumatoid nodules, and ACPA were associated with EA in RA. Erosive arthritis also could be detected in SLE, primary Sjögren syndrome, and systemic sclerosis. Anticyclic citrullinated peptide antibodies were also associated with EA in these diseases. Intensive monitoring for erosions was recommended for RA patients with a cutoff of ACPA greater than 1.6 U/mL and greater than 0.6 U/mL for SLE patients.

Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study

To investigate the characteristics and associated factors for Mycobacterium tuberculosis (TB) infection in patients with systemic lupus erythematosus (SLE) from Southern China. A retrospective study of 1108 patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2007 to December 2017 was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. A total of 59 (5.3%) lupus patients with active TB were included. Pulmonary TB occurred in 41 (69.5%) patients. Single lobe involvement was showed in 14 (34.1%) patients. Multi-lobar involvement, including miliary TB (36.6%), was presented in 27 (65.8%) patients. Lower lobe involvement accounted for 31 (75.6%) of the cases. Extrapulmonary TB occurred in 18 (30.5%) patients. Nearly one-third (35.6%) of the patients developed disseminated TB. T-SPOT.TB assay was performed in 23 patients and positive in 18 patients (78.3%). Nineteen patients (32.2%) had co-infection with TB and other pathogens, most of which were bacterial-associated (52.6%). Lymphopenia was predominant in TB-infected patients, especially in those with disseminated TB. Multivariate logistic regression analysis found that lymphopenia [odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.03–4.63, P = 0.04] and the accumulated doses of glucocorticoid (GC) (OR = 2.32, 95% CI 1.69–3.20, P < 0.001) were associated with TB. TB infection is a common comorbidity in patients with SLE. Manifestations of pulmonary computed tomography (CT) scan are relatively atypical. Co-infection with TB and other pathogens is not rare. Lymphopenia and the accumulated doses of GC are associated with TB infection in lupus patients.