Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis.

BACKGROUND: Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. METHODS: Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609-54.769; p = 0.013). CONCLUSIONS: Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients' leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients. Methods: Patients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model. Results: There are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts. Conclusions: The CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis.

BACKGROUND: Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients. METHODS: Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM. CONCLUSION: This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.

Development and external validation of a prediction model for venous thromboembolism in systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of venous thromboembolism (VTE). We conducted this study to develop a risk score algorithm for VTE in patients with SLE that provides individualised risk estimates. METHODS: We developed a clinical prediction model of VTE in 4502 patients with SLE based on the Chinese SLE Treatment and Research group cohort (CSTAR) from January 2009 to January 2020 and externally validated in 3780 patients with SLE in CSTAR from January 2020 to January 2022. Baseline data were obtained and VTE events were recorded during the follow-up. The prediction model was developed to predict VTE risk within 6 months in patients with SLE, using multivariate logistic regression and least absolute shrinkage and selection operator. SLE-VTE score and nomogram were established according to the model. RESULTS: A total of 4502 patients included in the development cohort, 135 had VTE events. The final prediction model (SLE-VTE score) included 11 variables: gender, age, body mass index, hyperlipidaemia, hypoalbuminaemia, C reactive protein, anti-ß2GPI antibodies, lupus anticoagulant, renal involvement, nervous system involvement and hydroxychloroquine, with area under the curve of 0.947 and 0.808 in the development (n=4502) and external validation cohort (n=3780), respectively. According to the net benefit and predicted probability thresholds, we recommend annual screening of VTE in high risk (≥1.03%) patients with SLE. CONCLUSION: Various factors are related to the occurrence of VTE in patients with SLE. The proposed SLE-VTE risk score can accurately predict the risk of VTE and help identify patients with SLE with a high risk of VTE who may benefit from thromboprophylaxis.

Identification of Three Different Phenotypes in Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis Patients: Implications for Prediction of Rapidly Progressive Interstitial Lung Disease.

OBJECTIVE: There is substantial heterogeneity among the phenotypes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis (DM), hindering disease assessment and management. This study aimed to identify distinct phenotype groups in patients with anti-MDA5+ DM and to determine the utility of these phenotypes in predicting patient outcomes. METHODS: A total of 265 patients with anti-MDA5+ DM were retrospectively enrolled in the study. An unsupervised hierarchical cluster analysis was performed to characterize the different phenotypes. RESULTS: Patients were stratified into 3 clusters characterized by markedly different features and outcomes. Cluster 1 (n = 108 patients) was characterized by mild risk of rapidly progressive interstitial lung disease (RPILD), with the cumulative incidence of non-RPILD being 85.2%. Cluster 2 (n = 72 patients) was characterized by moderate risk of RPILD, with the cumulative incidence of non-RPILPD being 73.6%. Patients in cluster 3 (n = 85 patients), which was characterized by a high risk of RPILD and a cumulative non-RPILD incidence of 32.9%, were more likely than patients in the other 2 subgroups to have anti-Ro 52 antibodies in conjunction with high titers of anti-MDA5 antibodies. All-cause mortality rates of 60%, 9.7%, and 3.7% were determined for clusters 3, 2, and 1, respectively (P < 0.0001). Decision tree analysis led to the development of a simple algorithm for anti-MDA5+ DM patient classification that included the following 8 variables: age >50 years, disease course of <3 months, myasthenia (proximal muscle weakness), arthritis, C-reactive protein level, creatine kinase level, anti-Ro 52 antibody titer, and anti-MDA5 antibody titer. This algorithm placed patients in the appropriate cluster with 78.5% accuracy in the development cohort and 70.0% accuracy in the external validation cohort. CONCLUSION: Cluster analysis identified 3 distinct clinical patterns and outcomes in our large cohort of anti-MDA5+ DM patients. Classification of DM patients into phenotype subgroups with prognostic values may help physicians improve the efficacy of clinical decision-making.

Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody-Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk.

OBJECTIVE: Interstitial lung disease (ILD) is a common extramuscular complication contributing to significant morbidity and mortality in patients with dermatomyositis (DM) who are positive for antimelanoma differentiation-associated gene 5 antibody (anti-MDA5+). We conducted this study to investigate the association of anti-Ro52 antibodies with clinical characteristics and prognosis in patients with anti-MDA5+ DM. METHODS: We assessed a cohort of 246 patients with anti-MDA5+ DM. To calculate hazard ratios and 95% CIs for rapidly progressive ILD (RP-ILD) and death while controlling for potential confounders, variables selected by univariate Cox regression analysis were included in a multivariate Cox regression model with the stepwise forward-selection method. A 2-tailed analysis with P < 0.05 was considered to be statistically significant. RESULTS: A total of 246 patients with anti-MDA5+ DM were enrolled; 70 patients were male, and the patient group had an average age of 53.1 (12.4) years. Anti-Ro52 was present in 64.2% (158/246) patients. Patients with anti-MDA5+ DM who were positive for anti-Ro52 had a higher rate of RP-ILD (log-rank P < 0.001) and a higher mortality rate (log-rank P = 0.01). For patients with anti-MDA5+ DM who were positive for anti-Ro52, those with a short disease course and high inflammation were at increased risk of RP-ILD and death. The appearance of active rash was an independent protective factor of death. CONCLUSION: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5+ DM, and their coexistence correlated with a higher rate of RP-ILD and mortality. Patients with a short disease course, with increased inflammation, and without rash were more likely to have a poor prognosis.

Time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients: a cohort study of 272 cases in China.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM. METHODS: We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications. RESULTS: There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++∼+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months. CONCLUSION: These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis.

Prognostic factors of systemic lupus erythematosus patients with pulmonary embolism: An 11-year cohort study.

BACKGROUND: Systemic lupus erythematosus (SLE) patients have a higher risk of pulmonary embolism (PE) which is life-threatening, but there has been no research focusing on the prognosis of SLE patients with PE. This study was conducted to explore the prognostic factors of mortality in SLE patients with PE. METHODS: In this observational cohort study, SLE inpatients with PE treated at Peking Union Medical College Hospital between January 2010 and December 2020 were included and age, gender, smoking history, the onset of SLE and PE, organ involvement, SLE disease activity index-2000 (SLEDAI-2K), severity of PE, and treatment regimen were collected. Kaplan-Meier survival curve and univariate and multivariate COX regression analysis were used to explore the prognostic factors of SLE patients with PE. RESULTS: A total of 86 SLE patients with PE were enrolled, with the age of 37.72±15.79 years old and the average lupus duration of 46.5 months. 17 patients (19.77%) died. 1- and 3-year survival rates were 83.40% and 79.40%. Thrombocytopenia (log-rank p = 0.004) and lymphocytopenia (log-rank p = 0.030) were predictors of mortality, and effective anticoagulation (log-rank p = 0.032), hydroxychloroquine (HCQ) (log-rank p = 0.021) were protective factors of mortality in SLE patients with PE. Effective anticoagulation was an independent protective factor of mortality in SLE patients with PE (HR = 0.14, p = 0.006). CONCLUSIONS: Patients with thrombocytopenia and lymphocytopenia are more likely to develop a poor prognosis. Effective anticoagulation and HCQ could improve the prognosis.

Serum Krebs von den Lungen-6 concentrations reflect severity of anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis associated interstitial lung disease.

OBJECTIVES: Rapidly progressive interstitial lung disease (RP-ILD) is a major complication of anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) with a high mortality rate. The aim of the study is to determine whether serum Krebs von den Lungen-6 (KL-6) could be a prognostic biomarker to predict RP-ILD and prognosis in anti-MDA5+DM patients. METHODS: A total of 21 anti-MDA5+DM patients with RP-ILD and 20 anti-MDA5+DM patients without RP-ILD were retrospectively included in this study. Serum KL-6 concentration (pg/mL) was measured using the latex agglutination test. RESULTS: Serum KL-6 level was higher in RP-ILD patients than those in non-RR-ILD patients (1195.61±872.93 vs. 452.6±465.51 pg/mL, p=0.002). The best cut-off value of KL-6 serum level was 500.9 pg/mL using ROC curve (AUC area = 0.7976, p=0.0011). KL-6 >500.9 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR=56.38, 95% CI 5.51-577.504, p=0.001). Serum KL-6 concentrations were significantly higher in dead patients than those in the survivor group (1209.34±840.55 vs. 592.41±667.76, p=0.0033), and higher KL-6 concentration was also an independent risk factor for all-cause death after adjusting confounders (OR = 21.94, 95% CI 3.3-145.73, p=0.001). Anti-MDA5+DM patients with higher KL-6 level displayed a significantly decreased one-year survival rate, as compared with lower KL-6 level (36.36% vs. 89.47%, p=0.0008). CONCLUSIONS: The serum KL-6 levels reflect severity of lung injury and serve as a clinically useful biomarker in detection and monitoring RP-ILD progression in anti-MDA5+DM patients.

Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort.

Objective: Although specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort. Methods: A total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-ß2-glycoprotein I (aß2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits. Results: Of the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aß2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke. Conclusion: Detection of aCL IgA, aß2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice.

Comparison of Different Test Systems for the Detection of Antiphospholipid Antibodies in a Chinese Cohort.

Background: Diagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China. Methods: A total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and aß2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features. Results: CLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or aß2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems. Conclusion: CLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.

Predicting the Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: A Chinese Systemic Lupus Erythematosus Treatment and Research Group Cohort Study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a life-threatening complication of systemic lupus erythematosus (SLE). However, there is no algorithm to identify those at high risk. This study was undertaken to develop a prediction model for PAH in patients with lupus that provides individualized risk estimates. METHODS: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed as having SLE. The diagnosis of PAH was confirmed by right-sided heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were performed for validation. RESULTS: Ninety-two lupus patients (2.54%) developed PAH during a median follow-up of 4.84 years (interquartile range 2.42-8.84). The final prediction model included 5 clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and 3 autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year PAH probability-predictive nomogram was established. The model was internally validated by Harrell's concordance index (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (>4.62%) lupus patients. CONCLUSION: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of PAH in patients with SLE.

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study.

OBJECTIVE: Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. METHODS: SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. RESULTS: We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [p < 0.05], 57.6% [p < 0.05], and 16.5% [p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE (p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group (p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). CONCLUSIONS: ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

Early Initiation of Anticoagulation Improves the Long-Term Prognosis in Patients With Antiphospholipid Syndrome Associated Portal Vein Thrombosis.

Objectives: Portal vein thrombosis (PVT) is a rare and severe clinical phenotype of antiphospholipid syndrome (APS) with a poor prognosis. Anticoagulation therapy is efficient but is associated with potentially severe bleeding episodes, especially for those patients with thrombocytopenia. We conducted this case-control study to explore the clinical features and associated factors of PVT in APS patients, the re-canalization rate of the PVT after anticoagulation and investigate the beneficial effects of early initiation of anticoagulation in patients with APS associated PVT. Methods: We enrolled patients with APS associated PVT as the case group, and age-, and entry-time-matched APS patients without PVT (1:2) as the control group. We explored the associated factors of PVT in APS patients using multivariate logistic regression analysis. The re-canalization rate of the PVT after anticoagulation was analyzed using the survival analysis. Results: A total of 34 patients (8 males and 26 females) with APS-PVT were enrolled, with a median follow-up time of 3 years (1.5, 7 years). Multivariate logistic regression analysis showed that thrombocytopenia (OR 6.4, 95%CI 1.561-26.218, P = 0.01), hypersensitive c-reactive protein >3 mg/L (OR 4.57, 95%CI 1.426-14.666, P = 0.011), anti ß2GPI positive (OR 5, 95%CI 1.816-13.772, P = 0.002) and aPL double-positive (OR 4.08, 95%CI 1.312-12.429, P = 0.013) were independent associated factors for PVT in APS. Survival analysis revealed that effective anticoagulation could increase re-canalization rate significantly (log-rank p = 0.001), with better prognosis (lower mortality rate, log-rank p = 0.045). Conclusions: PVT could be the first presentation of APS with insidious onset and atypical clinical symptoms and easily be misdiagnosed. For patients with APS, double aPLs positive, thrombocytopenia, and inflammation could be the associated factors of PVT. Early diagnosis and anticoagulation treatment can bring thrombus re-canalization thereby significantly improving the prognosis.

Chinese SLE Treatment and Research Group Registry (CSTAR) XIII: prevalence and risk factors for chronic scarring alopecia in patients with systemic lupus erythematosus.

BACKGROUND: Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case-control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients. METHODS: SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements, and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia. RESULTS: We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p < 0.001), high SLICC/ACR-DI (OR 1.409, p < 0.001), and positive anti-Sm (OR 1.374, p = 0.029) were risk factors for scarring alopecia, while renal (OR 0.714, p = 0.028) and cardio-respiratory involvements (OR 0.347, p = 0.044), and immunosuppressant treatment (OR 0.675, p < 0.001) were significantly negative associated with it. CONCLUSIONS: The prevalence of scarring alopecia in SLE patients is 7.80%. Active treatment strategies should be adopted to prevent scarring alopecia occurring.

Tofacitinib as a possible treatment for skin thickening in diffuse cutaneous systemic sclerosis.

OBJECTIVES: To analyse the effectiveness of tofacitinib for the treatment of refractory skin thickening in dcSSc. METHODS: Data from 10 patients with dcSSc treated with tofacitinib (5 mg twice daily) were analysed. A total of 12 dcSSc patients treated with intensive conventional immunosuppressants were selected as the historical comparator group. A clinically relevant response was defined as a decrease in the modified Rodnan skin score (mRSS) of >5 points and ≥25% from baseline. Clinical indicators were compared between the two groups to evaluate the effect of tofacitinib. RESULTS: The mRSS significantly improved the first month after tofacitinib treatment, with a mean change in the mRSS of -3.7 (95% CI -5.52, -1.88; P = 0.001) and greater than the comparators at 6 months [-10.0 (95% CI -14.74, -5.26) vs -4.1 (95% CI -7.49, -0.73), P = 0.026]. Tofacitinib-treated patients had a significantly shorter response time than the comparators (P = 0.015 by log-rank test), with overall response rates of 20% (2/10) vs 0% (0/12) and 60% (6/10) vs 16.7% (2/12) at 1 and 3 months, respectively. CONCLUSION: Our results indicate that tofacitinib may be as effective as or even better than intensive conventional immunosuppressants, with a quicker and higher response rate in refractory dcSSc patients with progressive skin thickness.

Clinical Characteristics of Systemic Lupus Erythematosus with Cirrhosis.

AIM: Cirrhosis is rare in systemic lupus erythematosus (SLE) patients with a poor prognosis. This study is aimed at retrospectively analyzing our single-center experience to explore the characteristics of cirrhosis in SLE patients. METHODS: SLE patients with cirrhosis from 2012 to 2019 were enrolled. SLE diagnosis was rigorously confirmed by a medical record review according to the revised 1997 American College of Rheumatology classification criteria for SLE. The diagnosis of liver cirrhosis was based on a combination of clinical, laboratory, and imaging criteria features. We conducted a case-control study in SLE patients complicated with the cirrhosis group and the age-, sex-, and entry-time-matched noncirrhosis group. RESULTS: A total of 21 patients with SLE cirrhosis were enrolled, 3 males and 18 females. The median age at the time of cirrhosis diagnosis was 47.3 ± 4.0 years, and the mean disease duration of SLE before cirrhosis was 4.7 ± 1.0 years. The most common initial presentation was the involvement of the hematological system in 9 patients and then skin and mucosal involvement in 5 patients, arthritis in 4 patients, and nephritis in 3 patients. Patients with cirrhosis had a significantly higher rate of hematological system involvement (thrombocytopenia and leukopenia) and worse liver function; a higher level of immune globulin G had higher mortality (p < 0.05) than patients without cirrhosis. CONCLUSIONS: Cirrhosis is a rare and severe subtype of SLE with a poor prognosis. Those patients with hematological system involvement and impaired liver function should be paid more attention.

JAK Inhibitors: Prospects in Connective Tissue Diseases.

The dysregulation of the JAK-STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK-STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

Characteristics and risk factors of pulmonary embolism in patients with systemic lupus erythematosus: a case control study.

OBJECTIVES: Pulmonary embolism (PE) is life threatening but evidence assessing risk factors of PE in systemic lupus erythematosus (SLE) is scarce. This study was conducted to explore the characteristics and risk factors of PE in SLE patients. METHODS: Using the Hospital Information System of Peking Union Medical College Hospital, we conducted a case-control study in SLE patients complicated with PE from January 2012 to December 2018 as the case group, and age-, sex-, and entry-time-matched SLE patients without PE at the ratio of 1:3 as the control group. We explored the risk factors of PE in SLE patients using multivariate logistic regression analyses. RESULTS: A total of 90 cases confirmed with PE from 6994 hospitalised SLE patients were identified and 257 matched controls were selected (in 13 cases only two controls could be found). The average annual incidence of PE from 2012 to 2018 among hospitalised SLE patients was 1.29% (95% CI: 1.15% to 1.42%), higher than that among all the hospitalised patients (0.347% and 95% CI: 0.34% to 0.354%). In the case group, the majority were female (74/90; 82.2%), with a mean duration of SLE before PE 3.04±2.16 years, and a high mortality rate of 8.9%. Multivariate analysis revealed that BMI >25 kg/m2 [OR 8.221 (3.125-21.622), p<0.001], duration of SLE course <1.5 years [OR 3.815 (1.824-7.97), p<0.001], hypoalbuminaemia [OR 2.8 (1.226-6.397), p=0.015], hsCRP>3 mg/L [OR 3.744 (1.693-8.276), p=0.001], aPL positive [OR 10.57 (4.389-25.46), p<0.001] and the highest dose of glucocorticoids >0.5 mg/kg/day [OR 15.752 (4.753-52.198), p<0.001] were significant independent risk factors of PE in SLE patients. The use of hydroxychloroquine [OR 0.262 (0.117-0.589), p=0.001] was a protective factor of PE in SLE patients. CONCLUSIONS: This study provides general population-based evidence that SLE patients have an increased risk of PE. Increased vigilance in preventing this serious, but preventable complication, especially within months after SLE diagnosis is recommended.