Objective: Antineutrophil cytoplasmic antibody (ANCA) directed to proteinase 3 (PR3) used to be considered the serologic marker for granulomatosis with polyangiitis (GPA). However, patients with myeloperoxidase (MPO)-ANCA positive GPA have been increasingly reported. The aim of this study was to analyze the clinical and pathological characteristics and outcome of Chinese patients with MPO-ANCA positive GPA. Methods: The clinical and renal histology data, renal outcomes, response to treatment, relapse and mortality were compared between patients with MPO-ANCA positive GPA and MPO-ANCA positive microscopic polyangiitis (MPA) as well as proteinase 3 (PR3)-ANCA positive GPA. Results: 455 patients with ANCA-associated vasculitis (AAV) were recruited in this study. 276/455 patients were classified as MPO-ANCA positive MPA, 4/455 patients were classified as PR3-ANCA positive MPA, 124/455 were MPO-ANCA positive GPA and 51/455 were PR3-ANCA positive GPA. Compared with MPO-ANCA positive MPA patients, MPO-ANCA positive GPA patients had significantly higher level of BVAS and milder renal lesion at diagnosis. The probability of developing ESRD was significantly higher in patients with MPO-ANCA positive MPA than MPO-ANCA positive GPA. MPO-ANCA positive GPA patients were likely to have relapse than MPO-ANCA positive MPA patients. Compared with PR3-ANCA positive GPA patients, MPO-ANCA positive GPA patients had significantly higher proportion of female, less constitutional symptoms and milder renal lesion at diagnosis. Conclusions: Patients with MPO-ANCA positive GPA should be regarded as a unique subset of AAV. This subset of AAV patients had relatively milder renal injury. Although ANCA specificities play an important role in differentiating AAV, taking the disease type together to classify AAV may be more rational. (C) 2018 Elsevier Inc. All rights reserved.
Objective: Gout is the osteoarticular expression of hyperuricemia, resulting from excessive production and/or insufficient elimination of uric acid. Emerging case reports described the deposition of mono sodium urate in the spine as a rare manifestation of gout, we aimed in revealing the full picture of reported axial joint gout (AJG). Methods: We performed a systemic patient level review focused on characteristics of reported cases of axial joint involvement in gout. Results: A total of 127 studies (142 cases) were identified as axial joint gout. Most of the cases were reported by neurosurgeons and orthopedic surgeons (19.7% and 17.6%, respectively),low back and neck pain and weakness of limbs were presented in 113 cases, most of the cases (77.5%) were diagnosed via operation or aspiration. Although CT and MRI was the most popular imaging method, 8 cases underwent DECT avoided surgery had marked improvement. Conclusions: The incidence of AJG was underestimated and the IAJG exist independent of peripheral arthritis. AJG should be suspected when back pain and neurological involvement occurred in the risky populations. DECT would be a promising technique to initiate the earlier intervention complimentary to invasive procedures or operations. (C) 2018 Elsevier Inc. All rights reserved.
Objective: This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia. Methods: In this prospective study, a total of 482 participants without hyperuricemia were enrolled at baseline and followed up for 6 years. Clinical characteristics were recorded, and serum levels of uric acid and BPA were measured. Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Regression models were used to analyze associations of serum BPA with the change in uric acid and the risk of developing hyperuricemia. Results: At baseline, serum concentrations of BPA was 0.51 (0.24-2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid concentration from baseline to the 6-year mark was significantly higher in subjects with higher baseline BPA concentration (0.03 +/- 0.19, 0.07 +/- 0.21, and 0.11 +/- 0.25 mg/dL for low, median, and high tertiles, respectively, P = 0.006). When adjusted for potential confounders, such as age, renal function, and history of diabetes and hypertension, multivariable logistic analyses showed that subjects in the median or high baseline BPA tertiles exhibited a twofold higher risk of 6-year hyperuricemia incidence compared to subjects in the low baseline BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05-4.95) for the median tertile; 2.42 (1.07-5.48) for the high tertile, P-for Trend = 0.043]. Conclusion: In conclusion, serum BPA is an independent risk factor for hyperuricemia. (C) 2018 Elsevier Inc. All rights reserved.
Background: Psoriatic arthritis (PsA) is a chronic and seronegative inflammatory arthritis occurring in patients with psoriasis. The current knowledge about the risk of malignancy associated with psoriatic arthritis (PsA) patients undergoing therapy is controversial. We focused on the relationship between malignancy and therapy and undertook a meta-analysis to address this issue. Methods: A systematic literature search of the PubMed, EMBASE, and Web of Science databases was performed to identify relevant studies and trials. Statistical analysis was conducted using STATA 11.2 software. Results: Nine cohort studies were included, corresponding to a total of 43,115 PsA patients undergoing therapy. A significant positive association between therapy and increased risk for overall malignancy was found relative to the general population as the reference group (pooled RR, 1.29; 95% CI: 1.04-1.60). High heterogeneity was found (I-2 = 71.37%). Subgroup analysis reported that PsA patients treated with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) presented increased cancer risk (pooled RR, 1.75; 95% CI: 1.40-2.18) but patients treated with biological disease modifying antirheumatic drugs (bDMARDs) did not (pooled RR, 0.957; 95% CI: 0.80-1.14). Compared to controls, patients with PsA undergoing treatment specifically are at increased risk for non-melanoma skin cancers (pooled RR, 2.46; 95% CI: 1.84-3.28). Conclusions: This study allowed the estimation of cancer risk in PsA patients during therapy. Large-scale longitudinal studies will be essential to draw firm conclusions regarding PsA-associated risk for treatment-induced malignancy. (C) 2018 Elsevier Inc. All rights reserved.
Objective: SAPHO syndrome is a highly heterogeneous disease with distinct treatment response. We report the largest cohort of SAPHO syndrome and explore its clinical classification with special interest in spinal and sacroiliac involvement. Methods: A total of 354 patients with SAPHO syndrome were recruited in Peking Union Medical College Hospital. The demographic, clinical and imaging data were collected at baseline. Spinal and sacroiliac involvement was determined by the co-existence of related symptoms and imaging evidence of lesions in the spine or sacroiliac joints on either bone scintigraphy, CT or MRI. Results: A total of 197 (55.6%) patients were identified to have spinal or sacroiliac involvement. Compared to those without spinal or sacroiliac lesions, these patients were significantly older at onset (38 +/- 12 vs 35 +/- 10 years old, p = 0.019) but had comparable duration of disease. Therapeutically, patients with spinal or sacroiliac involvement had been treated more aggressively with more frequently prescribed NSAIDs, glucocorticoids, DMARDs, TNF-alpha inhibitors, and bisphosphonates (all p <= 0.001). Nonetheless, greater disease activity was observed for these patients at baseline, supported by both inflammatory markers (ESR and hs-CRP) and visual analog scale (VAS) for pain (all p < 0.001). Conclusions: SAPHO patients with spinal or sacroiliac involvement are older at onset and have greater disease activity despite of more aggressive treatments compared to those without. Stratified management is in urgent need for this rare disease. (C) 2018 The Authors. Published by Elsevier Inc.
Background: Evaluate the comparative effectiveness of treatment strategies for patients with pain due to lumbar disc prolapse (LDP). Methods: PubMed, EMBASE, and the Cochrane Database were searched through September 2017. Randomized controlled trials on LDP reporting on pain intensity and/or global pain effects which compared included treatments head-to-head, against placebo, and/or against conventional care were included. Study data were independently double-extracted and data on patient traits and outcomes were collected. Risk of bias was assessed using the Cochrane risk of bias tool. Separate Bayesian network meta-analyses were undertaken to synthesize direct and indirect, short-term and long-term outcomes, summarized as odds ratios (OR) or weighted mean differences (WMD) with 95% credible intervals (CI) as well as surface under the cumulative ranking curve (SUCRA) values. Results: 58 studies in global effects and 74 studies in pain intensity analysis were included. Thirty-eight (65.5%) of these studies reported a possible elevated risk of bias. Autonomic drugs and transforminal epidural steroid injections (TESIs) had the highest SUCRA scores at short-term follow up (86.7 and 83.5 respectively), while Cytokines/Immunomodulators and TESI had the highest SUCRA values at long-term-follow-up in the global effect's analysis (86.6 and 80.9 respectively). Caudal steroid injections and TESIs had the highest SUCRA scores at short-term follow up (79.4 and 75.9 respectively), while at long-term follow-up biological agents and manipulation had the highest SUCRA scores (86.4 and 68.5 respectively) for pain intensity. Some treatments had few studies and/or no associated placebo-controlled trials. Studies often did not report on co-interventions, systematically differed, and reported an overall elevated risk of bias. Conclusion: No treatment stands out as superior when compared on multiple outcomes and time periods but TESIs show promise as an effective short-term treatment. High quality studies are needed to confirm many nodes of this network meta-analysis. (C) 2019 Elsevier Inc. All rights reserved.
Glucocorticoids are potent anti-inflammatory and immunosuppressant medications and remain the mainstay of systemic lupus erythematosus (SLE) therapy. The potency of a specific glucocorticoid, i.e., the dose of glucocorticoid that is required to produce a specific effect, is dependent on its pharmacokinetic (PK) and pharmacodynamic (PD) properties. In this review, we summarize the PK/PD properties of commonly used glucocorticoids in an attempt to better delineate their role in the management of children with childhood onset SLE (cSLE). We also address glucocorticoid side effects as these play a major role when deciding on the dose, frequency, and duration of use. A better understanding of the pharmacology of glucocorticoids appears useful to achieve improved outcomes in the management of cSLE. (C) 2019 Elsevier Inc. All rights reserved.
Objective: We aimed to characterize the phenotypes and genotypes of Chinese adult patients with systemic autoinfiammatory diseases (SAIDs). Methods: We prospectively evaluated clinical and genetic features of 92 adult patients (>= 16 years) suspected of SAIDs in the period from April 2015 to October 2017, at the adult SAIDs center, Peking Union Medical College Hospital. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. Clinical manifestations of these patients were compared with those from the pediatric populations and patients from other countries. Results: A final diagnosis of SAIDs was reached in 50 patients, including 13 familial Mediterranean fever (FMF), 10 NLRP12-associated autoinflammtory disease (NLRP12-AID), 7 NLRP3-associated autoinfiammatory disease (NLRP3-AID), 5 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), 3 Blau syndrome, 3 Yao syndrome (YAOS) and 9 periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). First disease onset during adulthood was observed in 30 patients, and the final diagnosis was delayed with a median time of 9 years. Adult monogenic SAIDs patients usually carried low-penetrance mutations and all gene variants were presented as heterozygosis or compound heterozygosis. Frequencies of clinical manifestations in Chinese adult SAIDs patients were similar with adult patients in other countries, but different from pediatric populations. Conclusions: FMF, NLRP3-AID, and NLRP12-AID are relatively common monogenic SAIDs in Chinese adults. Adult-onset SAIDs may be related to the presence of low-penetrance mutations, characterized by nonspecific, incomplete or atypical disease patterns compared with child-onset SAIDs, leading to a delay of diagnosis. (C) 2019 Elsevier Inc. All rights reserved.
Objective: To summarize and investigate the comparative efficacy and safety of targeted disease-modifying antirheumatic drugs (DMARDs) for active psoriatic arthritis (PsA). Methods: Randomized clinical trials (RCTs) evaluating efficacy and safety of targeted synthetic DMARDs (tofacitinib, apremilast) as well as biological DMARDs (guselkumab, ustekinumab, secukinumab, ixekizumab, brodalumab, clazakizumab, abatacept, adalimumab, etanercept, infliximab, certolizumab, and golimumab) were identified by systemic literature review. Traditional meta-analysis and network meta-analysis using a random effects model were performed to estimate pooled odds ratios (OR) and 95% CI to compare and rank these treatments according to ACR20 response, 75% improvement in psoriasis area and severity index (PASI75), numbers of adverse events (AE) and serious adverse events (SAE). Similar analyses were conducted among biologic-naive population and biologic-experienced/failed population. Results: We deemed 29 RCTs eligible, including 10,204 participants and 17 treatments. During induction therapy (first 12-16 weeks), all treatments except clazakizumab were more efficacious than placebo in achieving ACR20 and PASI75. Although tofacitinib, apremilast, and ixekinumab 80 mg every 2 weeks had a higher rate of AE, no significant difference was revealed for SAE among all treatments. Network meta-analysis demonstrated that infliximab, golimumab, etanercept, adalimumab, guselkumab, and secukinumab 300 mg outperformed other drugs in achieving both ACR20 and PASI75. Infliximab, guselkumab, adalimumab, golimumab, secukinumab (300 mg and 150 mg), and ustekinumab (45 mg and 90 mg) are characterized by both high efficacy and safety. Similar rankings were observed in the analysis among biologic-naive patients. Moreover, ustekinumab, secukinumab (300 mg and 150 mg), ixekizumab, abatacept, certolizumab pegol, tofacitinib, and apremilast were still associated with higher ACR20 compared to placebo while ustekinumab, secukinumab (300 mg), ixekizumab and tofacitinib with higher PASI75 among biologic-experienced/failed patients. Conclusion: Regarding the overall risk-benefit profile, infliximab, guselkumab, adalimumab, golimumab, secukinumab, and ustekinumab may be safer and more efficacious treatments than the other targeted DMARDs for active PsA during induction therapy. (C) 2019 Elsevier Inc. All rights reserved.
Objectives: To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI <= 3.3) compared to DAS28 remission (DAS28 < 2.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI <= 3.3 and group 2 (n = 43) aimed at DAS28-CRP < 2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months. Results: After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor > 16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair. Conclusions: Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair. (C) 2018 Elsevier Inc. All rights reserved.
Objective: To discuss the utility of F-18-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) in the diagnosis of idiopathic retroperitoneal fibrosis (iRPF). Methods: IRPF patients diagnosed between September 2011 and June 2016 were included. Retroperitoneal malignancy patients were included as control. The morphological features and FDG uptake of retroperitoneal lesions were measured along with lymph node (LN) mapping. Results: Seventy-one iRPF patients were included. Fifteen lymphoma patients and 6 retroperitoneal metastatic malignancy patients were included as control. Significant differences in morphological features were observed between iRPF and lymphoma but not retroperitoneal metastatic carcinoma. Compared with malignancy, iRPF displayed a lower frequency of high-FDG-uptake retroperitoneal lesions (P = 0.017) and a lower mean maximum standardized uptake value (SUVmax) (P < 0.001). LNs located at axillary, retroperitoneal, supraclavicular, inguinal or peritoneal sites were more frequently observed in retroperitoneal malignancy, therefore, were defined as specific LNs. The area under the curve (AUC) for SUVmax was 0.893 with a sensitivity of 85.7% and a specificity of 80.3%, when the cut-off value of the SUVmax was 6.23. The AUC for the logistic regression model combining the lesions above renal arteries, the SUVmax and the number of specific LNs was 0.987 with a sensitivity of 90.5% and a specificity of 98.6%. The risk stratification model analysis indicated that most of the retroperitoneal malignancy patients were at moderate or high level, while most of the iRPF patients were at low risk. Conclusions: Retroperitoneal malignancy can mimic iRPF morphologically. F-18-FDG PET/CT can help to distinguish iRPF from retroperitoneal lymphoma and metastatic malignancy. (C) 2018 Elsevier Inc. All rights reserved.
Background: Cardiovascular diseases (CVD) are the major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) during long-term follow-up. This study investigated risk factors for cardiovascular events (CVE) and CVD-related mortality in Chinese AAV patients. Methods: Five hundred and four AAV patients in our center were retrospectively included. The predictive value of variables associated with CVE- and CVD-related mortality were analyzed. Results: During follow-up of a median duration of 38 (range 1-228) months, 117 out of 504 patients had CVE. Independent predictors of CVE were age [increase by 10 years, hazard ratio (HR) 1.436, 95% confidence interval (CI) 1.187-1.736, p = 0.000], systolic blood pressure (increase by 10 mmHg, HR = 1.171, 95% CI: 1.038-1.321, p = 0.010), estimated glomerular filtration rate (eGFR) (increase by 1 mL/min/1.73 m(2), HR = 0.992, 95% CI: 0.984-0.999, p = 0.020), high-density lipoprotein level (HR = 0.530, 95% CI: 0.303-0.926, p = 0.026) and the Birmingham Vasculitis Activity Score (BVAS) (HR = 1.039, 95% CI: 1.011-1.067, p = 0.006). Forty-one patients died from CVD. Independent predictors of CVD-related mortality were age (increase by 10 years; HR = 1.732, 95% CI: 1.237-2.426, p = 0.001), eGFR (increase by 1 mL/min/1.73 m(2), HR = 0.984, 95% CI: 0.970-0.997, p = 0.016), pre-existing CV disease (HR = 2.872, 95% CI: 1.503-5.487, p = 0.001) and BVAS (HR = 1.064, 95% CI: 1.018-1.113, p = 0.006). We further analyzed CVE- and CVD-related mortality after 2 years since diagnosis, and found BVAS were still an independent predictor of CVE- and CVD-related mortality. Conclusion: Besides the traditional risk factors, BVAS at presentation was an independent predictor of CVE- and CVD-related mortality in patients with AAV. (C) 2018 Published by Elsevier Inc.
Background: Deep knee infection (DKI), consisting of sepsis arthritis (SA) and chronic low-grade infection (CLGI), is a rare but catastrophic adverse event that can result from intra-articular (IA) injections. The purpose of this study was to assess the risk factors for DKI and describe the clinical characteristics of DKI in patients who received IA injections. Methods: Fifty patients with IA injection-induced DKI who underwent surgical treatment between January 2010 and May 2016 served as cases and were matched with non-infected controls who received IA injections in a proportion of 1:5 based on age, gender, and date of admission. All IA injections (both cases and controls) were performed within 6 months of admission at our institution or at a referring institution. Risk factors for injection-induced DKI were analyzed, and the clinical characteristics between SA and CLGI were compared. Results: The final multivariate logistic regression analysis demonstrated that body mass index >= 25 kg/m(2) [odds ratio (OR) = 2.3; 95% confidence interval (CI): 1.1-4.7], corticosteroid injections (OR = 3.21; 95% CI: 1.63-6.31), rheumatoid arthritis (OR = 2.61; 95% CI: 1.20-5.68) and injections performed by general practitioners (OR = 5.23; 95% CI: 2.00-13.67) increased the risk of DKI following IA injections. Of 50 cases, there were 21 SA cases and 29 CLGI cases. SA cases had significantly higher metrics in the categories of fever, local warmth, swelling, rest pain, night pain, limited motion, serum WBC, and CRP levels than CLGI cases. Conclusions: We identified risk factors and clinical characteristics of injection-induced DKI, which may offer improved guidance on IA injections and knowledge of DKI in patients with IA injections, especially in CLGI patients. (C) 2017 Elsevier Inc. All rights reserved.
Objective: Coronary artery involvement significantly increases mortality of patients with Takayasu arteritis (TA); however, the optimal revascularization strategy for this condition has not been established. We aimed to compare the long-term outcomes of TA patients with coronary artery involvement treated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention with stenting (PCI). Methods: Data from 46 TA patients with coronary artery involvement were analyzed according to their revascularization strategies. The resulting events included myocardial infarction, repeated revascularization, cardiac death, and the major adverse cardiac events (MACE), which is a combination of the former events. Results: The risk of MACE was significantly higher in the PCI group than in the CABG group during a median of 41.0 months follow-up (P < 0.001), especially in those who underwent revascularization at the active stage of TA (P = 0.001), whereas no difference was found between PCI and CABG groups in patients who underwent revascularization at the stable stage of TA (P = 0.138). The incidence of MACE was higher in TA patients at the active stage than those at the stable stage in all patients (P < 0.001). For patients at the active stage, the risk of MACE was significantly lower in patients with than those without usage of prednisone (P = 0.028); while no difference was found between patients who were stable not requiring prednisone and patients who were stable on prednisone (P = 0.525). Conclusion: With regard to MACE, CABG is superior to PCI despite medical therapy in TA patients with coronary artery involvement In TA patients at the stable stage, PCI is similar with CABG in prognosis. For patients at the active stage, if emergency revascularization is necessary, CABG is ideal; if not, receiving medical therapy until disease remission and then undergoing PCI may be an alternative choice of CABG. (C) 2017 Elsevier Inc. All rights reserved.
Objective: To assess the clinical features, diagnosis, and treatment of bone sarcoidosis in the United States. Methods: Patients with bone sarcoidosis were identified and matched to sarcoidosis patients based on race, gender, and age. Detailed characteristics were obtained by medical record review. Results: A total of 64 patients with bone sarcoidosis were enrolled in this study. The female:male ratio was 1.46:1 and the white:black ratio was 3:1. Thirty-eight (59.4%) of 64 patients had bone symptoms. Compared to matched cases, bone sarcoidosis patients have more multi-organ involvement and higher incidence with liver, spleen, and extrathoracic lymph node involvement than controls (P < 0.05). Spine was the most commonly affected bone in 44 (68.8%) of patients, followed by pelvis (35.9%), and hands (15.6%). MRI and PET/CT scan was the common imaging technology, which performed in 36 patients and 32 patients, respectively, and with 97.2% and 93.8% positive bone uptake. Laboratory test indicated anemia was more common in bone sarcoidosis group than controls (P = 0.044). Infliximab was more commonly used in bone sarcoidosis patients than controls (P = 0.009). Conclusion: Bone sarcoidosis was associated with multi-organs affection, and high frequency of liver, spleen, or extrathoracic lymph node involvement. Infliximab should be considered in those patients with aggressive and refractory bone sarcoidosis. (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.