X Zeng

A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic Gout

Objectives: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). Methods: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. Results: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except “total body urate pool”. Additional domains were suggested and clarification sought for defining “joint inflammation” and “musculoskeletal function”. Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1–2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. Conclusions: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

Developing a provisional definition of flare in patients with established gout

OBJECTIVE Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. METHODS Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. RESULTS The mean ± SD age of the study participants was 56.2 ± 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). CONCLUSION We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 ± 6.9 and 3.5 ± 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis. Lupus (2008) 17, 93—99.

Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients.

The aim of the study is to assess the clinical characteristics, risk factors and outcome of patients with systemic lupus erythematosus (SLE) complicated with digital gangrene. In all, 2684 consecutive SLE inpatients admitted to Peking Union Medical College Hospital from December 1997 to August 2007 were studied. Demographic data, clinical features, laboratory findings as well as therapeutic regimens were systematically reviewed and a database was established. Cases with digital gangrene were identified and followed up. 1) Eighteen patients with SLE were complicated with digital gangrene, the average age at event was 33.1 ± 11.8 years and the average disease duration was 99.1 ± 60.1 months. 2) Patients with SLE, with long disease duration (≥4 years), Raynaud’s phenomenon and elevated serum C-reactive protein (CRP) were more likely to develop digital gangrene, P = 0.006, 0.001, and 0.031, respectively, OR = 1.03 (95% CI 1.01, 1.04), 35.76 (95% CI 4.67, 273.83) and 9.93 (95% CI 1.23, 80.30), respectively. 3) Fifteen gangrene patients started prednisone ≥1 mg/kg/d, and 18 were treated with cyclophosphamide, although 8 cases failed and ultimately received digital amputation. Prompt corticosteroid treatment (prednisone ≥1 mg/kg/d started within 3 weeks) decreased the hazard of amputation, P = 0.073, HR = 0.13 (95% CI 0.01, 1.21). Long disease duration, Raynaud’s phenomenon and elevated serum CRP were independent predictive factors for SLE to develop digital gangrene. Early and aggressive corticosteroid treatment prevented gangrene from progression and improved prognosis.

Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises

To establish consensus for potential remission criteria to use in clinical trials of gout.

Could pulmonary arterial hypertension be an active index of systemic lupus erythematosus? A successful case of SLE-PAH cured by methylprednisolone pulse therapy

A 35-year-old female patient was diagnosed with pulmonary arterial hypertension (PAH) by right heart catheterization (RHC) in the 3rd month of systemic lupus erythematosus (SLE) duration with high disease activity. Through methylprednisolone pulse therapy, she got total recovery from PAH proven by repeat catheterization and follow-ups. This is the first simultaneously diagnosed, totally recovered, gold standard-proved SLE-PAH case ever reported in the literature. We would like to share this successful case, and at the same time, we want to highlight the relationship between presentation of PAH and active disease manifestations of SLE patients, and to discuss how immune suppressive treatment could benefit this subset of patients.

Chinese SLE Treatment and Research group (CSTAR) registry: V. gender impact on Chinese patients with systemic lupus erythematosus

Introduction Many studies have shown that differences were observed between male and female lupus patients. Although systemic lupus erythematosus (SLE) affects mostly females (female:male ratio 9:1), male SLE patients show higher mortality due to kidney and neurological disease. Currently there are limited epidemiological data concerning lupus in the Chinese population. As such, the Chinese SLE Treatment and Research group (CSTAR) developed the first online registry of Chinese lupus patients in 2009, and represents a multicenter observational study that attempts to describe and compile the major clinical characteristics of lupus in Chinese patients. Objective To investigate the effect of gender on the phenotypes of Chinese SLE patients. Patients and methods Data for 2104 SLE patients were prospectively collected and included in the CSTAR registry. Patients fulfilled the 1997 American College of Rheumatology (ACR) SLE classification criteria. We conducted a cross-sectional case-control study to analyze patient clinical and laboratory data at onset and at enrollment. SLE disease activity scores (SLEDAI) were also measured at enrollment. Results This study included 1914 women and 190 men. Males and females showed no differences in mean ages at onset, delay of diagnosis and disease duration. Males presented more frequently with fever (p = 0.003), while musculoskeletal involvement (p = 0.001) and cytopenia (p = 0.017) was more common in females as the initial manifestation at onset of SLE. For manifestations at enrollment, males presented more frequently with fever (p = 0.005), renal disease (p = 0.019), vasculitis (p = 0.032) and neuropsychiatric lupus (p = 0.007). For cumulative manifestations at enrollment, males presented more frequently with discoid rash (p < 0.001) and neuropsychiatric lupus (p = 0.036), while less frequently with arthritis (p = 0.011). However, the laboratory data showed no significant differences between the two groups at enrollment. Males also had higher SLEDAI scores at enrollment (p = 0.002). Conclusions Renal disease, vasculitis and neuropsychiatric lupus are more common in male SLE patients with higher SLEDAI scores compared to female SLE patients in China.

Clinical Features, Morbidity, and Risk Factors of Intestinal Pseudo-obstruction in Systemic Lupus Erythematosus: A Retrospective Case-control Study

Objective. To analyze the epidemiology, clinical characteristics, and risk factors for systemic lupus erythematosus-related intestinal pseudo-obstruction (SLE-IPO). Methods. We retrospectively examined 85 patients with SLE with IPO as the case group and 255 randomly matched patients with SLE without any gastrointestinal manifestations as the control group, out of 4331 inpatients at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2014. Results. Over the last 11 years at PUMCH, the prevalence of IPO in patients with SLE was 1.96% and the in-hospital fatality rate was 7.1%. Of these patients, 57.6% presented with IPO as the initial affected system of SLE, and the rate of misdiagnosis was about 78%. Pyeloureterectasis was the most common complication (58.9%) in patients with SLE-IPO and the incidence of biliary tract dilation was 7.1%. Patients with SLE with IPO were always diagnosed at an earlier stage of SLE with a higher frequency of hematological disturbance, polyserositis, and hypocomplementemia. Pyeloureterectasis, hypocomplementemia, and elevated C-reactive protein levels in serum were independent risk factors for IPO in SLE disease. Patients with SLE-IPO with long IPO duration and those diagnosed during late stages of SLE or concurrent with pyeloureterectasis and megacholedochus always had an unfavorable outcome. Conclusion. IPO is a rare complication, but commonly presents as the initial affected system of SLE, which can lead to a difficult diagnosis and delayed treatment. SLE-IPO occurrence concomitantly with pyeloureterectasis and megacholedochus showed a severe clinical situation in our cohort. Thus, patients with SLE-IPO with systemic smooth muscular involvement should be diagnosed early and treated aggressively.

Chinese SLE Treatment and Research group (CSTAR) registry VII: prevalence and clinical significance of serositis in Chinese patients with systemic lupus erythematosus

Objectives To investigate both the prevalence and clinical characteristics of serositis in Chinese patients with systemic lupus erythematosus (SLE) in a large cohort in the Chinese SLE Treatment and Research group (CSTAR) database. Methods A prospective cross-sectional study of patients with SLE was conducted based on the data from the CSTAR registry. Serositis was defined according to the 1999 revised American College of Rheumatology (ACR) criteria for SLE – that is, pleuritis/pleural effusion and/or pericarditis/pericardial effusion detected by echocardiography, chest X-ray or chest computerized tomography (CT) scan. Peritonitis/peritoneal effusion were confirmed by abdominal ultrasonography. We analysed the prevalence and clinical associations of serositis with demographic data, organ involvements, laboratory findings and SLE disease activity. Results Of 2104 patients with SLE, 345 were diagnosed with serositis. The prevalence of lupus nephritis (LN), interstitial lung disease and pulmonary arterial hypertension, as well as the presence of leukocytopenia, thrombocytopenia, hypocomplementemia and anti-dsDNA antibodies was significantly higher in patients with serositis (P < 0.05). Significantly higher SLE disease activity scores were found in patients with serositis compared to those patients without serositis (P < 0.05). Lupus-related peritonitis had similar clinical manifestations and laboratory profiles as serositis caused by SLE. Conclusions There is a significant association of nephropathy, interstitial lung disease, pulmonary arterial hypertension, hypocomplementemia, leukocytopenia, thrombocytopenia and elevated anti-dsDNA antibodies with serositis. The results suggest that higher SLE disease activity contributes to serositis development, and should be treated aggressively.

Gastrointestinal system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disorder which can affect the gastrointestinal (GI) system. Although GI symptoms can manifest in 50% of patients with SLE, these have barely been reviewed due to difficulty in identifying different causes. This study aims to clarify clinical characteristics, diagnosis and treatment of the four major SLE-related GI system complications: protein-losing enteropathy (PLE), intestinal pseudo-obstruction (IPO), hepatic involvement and pancreatitis. It is a systematic review using MEDLINE and EMBASE databases and the major search terms were SLE, PLE, IPO, hepatitis and pancreatitis. A total of 125 articles were chosen for our study. SLE-related PLE was characterized by edema and hypoalbuminemia, with Technetium 99m labeled human albumin scintigraphy (99mTc HAS) and alpha-1-antitrypsin fecal clearance test commonly used as diagnostic test. The most common site of protein leakage was the small intestine and the least common site was the stomach. More than half of SLE-related IPO patients had ureterohydronephrosis, and sometimes they manifested as interstitial cystitis and hepatobiliary dilatation. Lupus hepatitis and SLE accompanied by autoimmune hepatitis (SLE-AIH overlap) shared similar clinical manifestations but had different autoantibodies and histopathological features, and positive anti-ribosome P antibody highly indicated the diagnosis of lupus hepatitis. Lupus pancreatitis was usually accompanied by high SLE activity with a relatively high mortality rate. Early diagnosis and timely intervention were crucial, and administration of corticosteroids and immunosuppressants was effective for most of the patients.