Chanyuan Wu

Clinical characteristics of immunoglobulin G4–related disease: a prospective study of 118 Chinese patients

OBJECTIVE To characterize the clinical features of IgG4-related disease (IgG4-RD) in China. METHODS A prospective cohort study of IgG4-RD was carried out in Peking Union Medical College Hospital between 2011 and 2013. Patients with newly diagnosed IgG4-RD were enrolled. RESULTS A total of 118 patients with IgG4-RD were enrolled, including 82 males and 36 females, aged 53.1 (s.d. 13.6) years. The most common symptom at onset was lacrimal gland swelling (38/32.2%). A range of organs were involved: 77 patients (65.3%) had lymphadenopathy, 76 (64.4%) had sialadenitis, 60 (50.8%) had dacryoadenitis, 45 (38.1%) had autoimmune pancreatitis, 32 (27.1%) had pulmonary involvement, 31 (26.3%) had periaortitis/retroperitoneal fibrosis, 29 (35.4% of male patients) had prostatitis and 29 (24.6%) had renal involvement. In addition, there were 21 (17.8%) cases of sclerosing cholangitis, 15 (12.7%) of sinusitis and 10 (8.5%) of inflammatory pseudotumour. Uncommon manifestations included mediastinal fibrosis, skin involvement, sclerosing thyroiditis, hypophysitis, orchitis and colitis. Multiple organ involvement was observed in 93 patients, whereas only 4.2% had only a single organ involved. A history of allergy was reported in 73 (61.9%) patients. The serum IgG4 level was elevated in 97.5% and was correlated with the number of organs involved. Most patients were treated with glucocorticoids alone or in combination with immunosuppressive drugs, and the majority usually improved within 3 months. CONCLUSION IgG4-RD is a systemic inflammatory and sclerosing disease. Parotid and lacrimal involvement (formerly called Mikuliczs disease), lymphadenopathy and pancreatitis are the most common manifestations. Patients with IgG4-RD showed favourable responses to treatment with glucocorticoids and immunosuppressive agents.

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China: A Systemic Review of Observational Studies

AbstractSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China.This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China.The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China.We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China.The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators.All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the top 4 causes.The overall survival rates for Chinese patients with SLE resembled previous publications in Asia-Pacific area. But the death causes of SLE in China were of some differences indicating relatively higher proportion of infection and lupus encephalopathy and lower cardiovascular disease. Ethnicity and more aggressive treatment might have contributed to the difference in death composition.

Genetic Association Study of TNFAIP3, IFIH1, IRF5 Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population

Background Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population. Methods A large case–control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform. Results Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20–2.16, Pc = 7.5×10−3; OR: 1.88, 95%CI: 1.30–2.74, Pc = 4.0×10−3, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, Pc = 6.0×10−3; OR: 1.88, 95%CI: 1.28–2.76, Pc = 5.5×10−3,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (Pc = 0.04 and Pc = 0.016; Pc = 0.02 and Pc = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (Pc = 0.026 and Pc = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used. Conclusions This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Dermatomyositis and Polymyositis in the Intensive Care Unit: A Single-Center Retrospective Cohort Study of 102 Patients

Introduction Patients with idiopathic inflammatory myopathies (IIMs) are sometimes complicated with life-threatening conditions requiring intensive care unit (ICU) admission. In the past, owing to the low incidence of IIM, little was known about such patients. Our aim was to investigate the clinical features and outcomes of these patients and identify their risk factors for mortality. Methods A retrospective study was performed of IIM patients admitted over an 8-year period to the medical ICU of a tertiary referral center in China. We collected data regarding demographic features, IIM-related clinical characteristics, reasons for admission, organ dysfunction, and outcomes. Independent predictors of ICU mortality were identified through multivariate logistic regression analysis. Results Of the 102 patients in our cohort, polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM) accounted for 23.5%, 64.7%, and 11.7% respectively. The median duration from the onset of IIM to ICU admission was 4.3 months (interquartile range [IQR], 2.6–9.4 months). Reasons for ICU admission were infection alone (39.2%), acute exacerbation of IIM alone (27.5%), the coexistence of both (27.5%), or other reasons (5.8%). Pneumonia accounted for 97% of the infections; 63.2% of infections with documented pathogens were caused by opportunistic agents. Rapid progressive interstitial lung disease (RP-ILD) was responsible for 87.5% of acute exacerbation of IIM. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score on ICU day 1 was 17 (IQR 14–20). On ICU admission, acute respiratory failure (ARF) was the most common type (80.4%) of organ failure. The mortality rate in the ICU was 79.4%. Factors associated with increased ICU mortality included a diagnosis of DM (including CADM), a high APACHE II score, the presence of ARF, a decreased PaO2/FiO2 ratio, and a low lymphocyte count at the time of ICU admission. Conclusions The outcome of IIM patients admitted to the ICU was extremely poor. A diagnosis of DM/CADM, the presence and severity of ARF, and the lymphocyte counts at ICU admission were shown to be valuable for predicting outcome. Opportunistic infections and rapidly progressive interstitial lung disease warrant concern in treating these patients.

Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37-0.57), 0.96 (95% CI, 0.92-0.97), and 0.90 (95% CI: 0.88-0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77-0.88), 0.86 (95% CI: 0.80-0.91), and 0.87 (95% CI: 0.84-0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (α = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37–0.57), 0.96 (95% CI, 0.92–0.97), and 0.90 (95% CI: 0.88–0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77–0.88), 0.86 (95% CI: 0.80–0.91), and 0.87 (95% CI: 0.84–0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (α = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.

Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis

The presence of anti-MDA5 antibodies in serum represents an important biomarker in the diagnosis and prediction of prognosis for patients with idiopathic inflammatory myopathies (IIMs). Due to conflicting results that have been reported regarding the detection of anti-MDA5 antibodies, the goal of this study was to assess a potential association between the presence of anti-MDA5 antibodies and dermatomyositis/polymyositis (DM/PM), as well as the diagnostic and prognostic values of anti-MDA5 antibodies for DM/PM. For this, a review of literature published prior to October 15, 2016 was conducted. Eight studies with 286 PM patients and 216 healthy controls and nine studies with 628 DM patients and 221 healthy controls were selected according to specific inclusion criteria. The outcomes of these studies revealed that the presence of anti-MDA5 antibodies was associated with DM, especially CADM, and not with PM. Furthermore, the pooled sensitivity, specificity, and area under the curve (AUC) values were 0.62 (95% confidence interval (CI): 0.52–0.70), 1.00 (95% CI: 0.97–1.00), and 0.9381 for CADM patients versus healthy controls when an immunoprecipitation method was used. The presence of anti-MDA5 antibodies was also found to be significantly associated with an increased risk of death in DM (relative risk = 3.32, 95% CI: 1.65–6.67, P = 0.001). These findings suggest that anti-MDA5 antibodies correlate with DM and could be used as a biomarker in the clinical diagnosis of CADM. The presence of anti-MDA5 antibodies was also associated with poor prognosis regarding the overall survival of patients with DM.

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood-Onset Systemic Lupus Erythematosus in China.

Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged < 16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

Hospitalization mortality and associated risk factors in patients with polymyositis and dermatomyositis: A retrospective case-control study

Background Polymyositis and dermatomyositis (PM/DM) are systemic autoimmune diseases with multiple organ involvements that manifest as muscular and cutaneous disorders, interstitial lung disease (ILD) and malignancies. However, information concerning the outcomes and associated factors for PM/DM patients who are hospitalized is limited. Methods We retrospectively reviewed the medical charts of PM/DM patients admitted to a Chinese tertiary referral hospital (Peking Union Medical College Hospital, PUMCH) from 2008 to 2014. The deceased group included 63 patients who had “deceased discharge” status or were confirmed to have died within two weeks of hospital discharge. The demographic data, clinical manifestations, and direct causes of death were analyzed retrospectively. Medical records for 126 age- and sex-matched PM/DM patients were selected as controls from 982 inpatients successively admitted to the same center during the same period. In addition to the comparison of clinical manifestations between the two groups, binary logistic regression was conducted to explore the risk factors related to PM/DM mortality. Results Over the past 6 years at PUMCH, the in-hospital mortality rate of PM/DM patients was 4.58%. The male gender and the elder patients had a high risk of death (P = 0.031 and P = 0.001 respectively). The three most frequent causes of death for PM/DM patients were pulmonary infection (35%), ILD exacerbation (21%) or both conditions (25%). Pulmonary infection (P<0.001, OR = 5.63, 95% CI, 2.37–13.36), pneumomediastinum (P = 0.041, OR = 11.02, 95%CI, 1.10–110.54), Gottron’s papules (P = 0.010, OR = 3.24, 95%CI, 1.32–7.97), and elevated erythrocyte sedimentation rate (ESR) (P = 0.005, OR = 9.9, 95%CI 2.0–49.0) were independent risk factors for in-hospital mortality of PM/DM patients. Conclusion PM/DM patients continue to display high in-hospital mortality. Pulmonary infection is the strongest predictor of poor prognosis in PM/DM patients, followed by pneumomediastinum, Gottron’s papules, and elevated ESR.

Associations between TNF-α-308A/G Polymorphism and Susceptibility with Dermatomyositis: A Meta-Analysis

Background Some surveys had inspected the effects of the tumor necrosis factor-α (TNF-α)-308A/G polymorphism on susceptibility to dermatomyositis (DM), and showed mixed results. To briefly review these consequences, a comprehensive meta-analysis was carried out to estimate the relationship between them much more accurately. Methods Relevant documents dated to February 2014 were acquired from the PUBMED, MEDLINE, and EMBASE databases. The number of the genotypes and/or alleles for the TNF-α-308A/G in the DM and control subjects was extracted and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were used to calculate the risk of DM with TNF-α-308A/G. Stratified analysis based on ethnicity and control population source was also performed. Results 555 patients with DM and 1005 controls from eight published investigations were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the TNF-α-308A allele were 2.041 (95% CIs 1.528–2.725, P<0.0001) in DM. Stratification by ethnicity indicated the TNF-α-308A allele polymorphism was found to be significantly associated with DM in Europeans (OR = 1.977, 95% CI 1.413–2.765, P<0.0001). The only study conducted on TNF-α-308A/G polymorphism in Asians could not be used in ethnicity-stratified meta-analysis. Meta-analysis of the AA+AG vs. GG (dominant model) and AA vs. GG (additive model) of this polymorphism revealed a significant association with DM in overall populations and Europeans. Conclusions Our meta-analysis demonstrated that the TNF-α-308A/G polymorphism in the TNF gene might contribute to DM susceptibility, especially in European population. However, further studies with large sample sizes and among different ethnicity populations should be required to verify the association.