C.H. To

Long-term survival of southern Chinese patients with systemic lupus erythematosus: a prospective study of all age-groups.

Abstract: We conducted the current study to determine the clinical determinants of survival and the survival rates in an unselected cohort of Chinese patients with new-onset systemic lupus erythematosus (SLE), including all age-groups. Patients were those newly diagnosed as having SLE or referred within 6 months of diagnosis to the departments of medicine, geriatrics, and pediatrics at Tuen Mun Hospital, Hong Kong, between 1991 and 2003. Patients under the care of all specialists were included for analysis. We obtained demographic data, presenting and cumulative clinical features, disease activity, and serial damage scores. For patients who died or were lost to follow-up, data were censored at the last clinic visit. Survival over time was studied by the Kaplan-Meier method, and factors predictive of mortality were evaluated by the Cox proportional hazard model. We studied 285 new-onset SLE patients (92% women). All were ethnic Chinese and fulfilled at least 4 of the American College of Rheumatology criteria for SLE. The mean age of SLE onset was 30.0 ± 13.5 years. Fifty (18%) patients had first onset of SLE before the age of 16 years (childhood onset), and 22 (8%) had disease onset after the age of 50 years (late onset); 213 (75%) patients had disease onset between the ages of 16 and 50 years (adult onset). Twenty-nine (10%) patients died (4 from the childhood-onset group, 6 from the late-onset group, and 19 from the adult-onset group) and 18 (6%) patients were lost to follow-up. The overall 5-, 10-, and 15-year survival rates were 92%, 83%, and 80%, respectively. Survival was significantly worse in late-onset patients: 5-, 10-, and 15-year survival rates were 66%, 44%, and 44%, respectively; p < 0.0001. Infection was the main cause of death (55%), followed by cardiovascular (17%) and cerebrovascular complications (14%). Unfavorable factors for survival on univariate analysis were increasing age, damage scores at 1 year, and the use of high-dose corticosteroids. Cox regression revealed that damage scores at 1 year and hematologic manifestations were independent predictors of mortality. Long-term survival of Chinese SLE patients is comparable to that reported for white patients in the 1990s. Late-onset SLE patients have the worst prognosis. Early damage predicts mortality. Abbreviations: ACR = American College of Rheumatology, SDI = Systemic Lupus International Collaborating Clinics Damage Index, SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index, SLE = systemic lupus erythematosus.

Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups

Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups A Mak, CC Mok, WP Chu, CH To, SN Wong and TC Au Please note that the following pdf is a corrected version of the article which appears in the printed version of Lupus 16/1. An Erratum will also appear in print in Lupus; 16(2). The corrected line can be found in the abstract. It was changed from: Patients were categorized into childhood (age ≥6 years), adult (between 16 and 50 years) or late onset (≥50 years) SLE. To: Patients were categorized into childhood (age 16 years), adult (between 16 and 50 years) or late onset (50 years) SLE.The objective of this study was to compare the frequency and severity of renal damage in systemic lupus erythematosus (SLE) with regard to the age of disease onset. Among 287 patients with new onset SLE diagnosed between 1991 and 2003 in our hospital, we identified those who fulfilled the American College of Rheumatology (ACR) criteria for renal involvement. Patients were categorized into childhood (age <6 years), adult (between 16 and 50 years) or late onset (≥50 years) SLE. Clinical presentation of renal disease and cumulative renal damage as assessed by the renal domain of the Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were compared. A linear regression model was constructed to study the effect of age on renal damage. One-hundred and forty-nine patients were studied (134 women and 15 men), including 28 childhood, 107 adult and 14 late onset SLE patients. The mean age of SLE onset was 29.7 ± 14 years. The prevalence of renal disease was 53% in childhood onset, 50% in adult onset and 58% in late onset SLE patients (P = 0.66). At renal disease presentation, late onset SLE patients had significantly lower creatinine clearance and were more likely to be hypertensive. Histological classes of nephritis and initial treatment response, however, did not differ significantly among the patients. After a mean observation of 80.3 months, 32 (21%) patients developed renal damage (renal SDI ≥ 1). Late onset SLE patients had accrued more renal damage than the others. In a multiple regression model, age was not a significant determinant of renal damage after adjustment for baseline renal parameters, duration of renal disease, use of cyclophosphamide and initial treatment response. We concluded that the prevalence of renal disease was similar among SLE patients of different ages of onset. Late onset SLE patients had accrued more renal damage but age did not correlate with renal damage after adjustment for various clinical parameters.

Effect of disease activity and damage on quality of life in patients with systemic lupus erythematosus: a 2‐year prospective study

Objectives: To examine the effect of disease activity and damage on health‐related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). Methods: Consecutive SLE patients and matched controls were recruited for a study of HRQoL using the Medical Outcomes Study Short Form‐36 (SF‐36). SLE activity and damage was assessed by the Safety of Oestrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA‐SLEDAI) and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), respectively. Patients were prospectively followed for repeat HRQoL assessment at 2 years. The effects of cumulative disease activity and new damage on changes in SF‐36 scores were evaluated. Results: One hundred and fifty‐five patients were studied (94% women; age 37.8±11.3 years; SLE duration 7.2±5.4 years). Fifty (32%) patients had active disease and 75 (48%) had organ damage at baseline. Compared with age‐ and gender‐matched controls, SLE patients had lower SF‐36 scores, and the difference remained significant after adjustment for income and education level. SF‐36 scores in SLE patients correlated inversely with SDI but not with SELENA‐SLEDAI scores. After 2 years, there was a significant drop in the mental component score of the SF‐36. Regression analysis revealed that new damage was the only determinant for a reduction in SF‐36 scores. Patients with higher cumulative disease activity had a greater drop in bodily pain and general health subscores. Conclusions: Impaired HRQoL is more common in SLE patients than controls, regardless of age, sex, education and poverty. Pre‐existing organ damage is associated with poorer HRQoL and new damage predicts a further decline in HRQoL. Persistent disease activity is associated with deterioration in certain domains of the SF‐36.

Anti–müllerian hormone and ovarian reserve in systemic lupus erythematosus

OBJECTIVE To study the level of anti-müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE). METHODS Consecutive female patients ages 18-52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patients age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS A total of 216 patients were studied (mean±SD age 35.1±10.1 years, mean±SD SLE duration 7.6±5.9 years). The mean±SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58±2.92 versus 1.73±2.11 ng/ml; P=0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4-8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta -0.32, P=0.02) and each 5 gm of CYC exposure (beta -0.28, P=0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.

Neuropsychiatric damage in Southern Chinese patients with systemic lupus erythematosus.

Abstract: We conducted the current study to determine the prevalence and predictors of neuropsychiatric damage in a cohort of Chinese patients with systemic lupus erythematosus (SLE). Patients were those newly diagnosed as having SLE between 1990 and 2004 in our unit. Demographic data, presenting and cumulative clinical features, disease activity score at diagnosis, and serial damage scores were obtained. Neuropsychiatric (NP) manifestations were classified according to the American College of Rheumatology (ACR) nomenclature. NP damage was evaluated by the NP domain of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. Factors predictive of NP damage were studied by regression models. We studied 282 patients who fulfilled ≥4 of the ACR criteria for SLE. The mean age of SLE onset was 31.8 ± 14 years. After a mean follow-up of 6.7 years, 65 patients (23%) had at least 1 NP manifestation and 50 (18%) developed NP damage (SLICC/ACR Damage Index ≥ 1). Cerebrovascular accident was the most common cause of NP damage (35%), followed by seizure (20%), psychosis (12%), cranial/peripheral neuropathy (12%), cognitive dysfunction (12%), and myelopathy (9%). In a multiple regression model, disease activity at diagnosis, cumulative non-NP damage, presence of antiphospholipid antibodies, and ever use of pulse methylprednisolone were independent factors associated with NP damage. New NP damage after the first year of diagnosis was predicted by longer disease duration and the use of pulse methylprednisolone in another multivariate model. Neither early nor cumulative NP damage predicted mortality. NP damage is prevalent in Chinese patients with SLE and is independently associated with more active disease at diagnosis, antiphospholipid antibodies and the use of pulse methylprednisolone therapy. Primary prevention for cerebrovascular disease in high-risk patients may reduce NP damage. Abbreviations: ACR = American College of Rheumatology, NP = neuropsychiatric, SLE = systemic lupus erythematosus, SLEDAI = SLE Disease Activity Index, SLICC/ACR Damage Index = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.

Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus

The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier’s plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 ± 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 ± 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02–1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01–1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02–1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease were independent predictors of work disability.

Annual incidence and standardized incidence ratio of cerebrovascular accidents in patients with systemic lupus erythematosus.

Objectives: To study the annual incidence and standardized incidence ratio (SIR) of cerebrovascular accident (CVA) in patients with systemic lupus erythematosus (SLE). Subjects and methods: The annual incidence of CVA from 1999 to 2007 in a longitudinal cohort of SLE patients was calculated each year and compared with that of the regional population within the same study period. Age-specific SIRs and outcome of CVA in SLE patients were also studied. Results: In 2007, there were 490 SLE patients in our cohort. The mean annual incidence of CVA between 1999 and 2007 was 6.45/1000 patients and no obvious trend over time was observed. Of the 20 CVAs in patients with SLE, 18 (90%) were ischaemic stroke whereas two (10%) were haemorrhagic stroke. The mean SIR of all types of CVA in SLE patients was 2.02 [95% confidence interval (CI) 1.30–3.81; p = 0.002]. The SIR of ischaemic stroke decreased with age and the stroke incidence was no longer significantly higher than that of the population in patients aged ≥ 60 years. Haemorrhagic stroke occurred mainly in younger SLE patients. The duration of hospitalization and the mortality rate for CVA was non-significantly higher in SLE than in non-SLE patients. Conclusions: The incidence of CVA in SLE remained constant over the 8 years between 1999 and 2007. Younger SLE patients are at substantially increased risk of CVA compared to age-matched population. The duration of hospitalization and the mortality rate for CVA are similar in SLE and non-SLE patients.

Bone mineral density and body composition in men with systemic lupus erythematosus: a case control study.

OBJECTIVE To study the bone mineral density (BMD) and body composition in men with systemic lupus erythematosus (SLE). METHODS Consecutive male patients who fulfilled > or =4 ACR criteria for SLE and age-matched healthy men were recruited for measurement of BMD and body composition by DXA scan. Risk factors for low BMD in SLE patients were evaluated. RESULTS 40 male SLE patients were studied (age 42.6+/-12 years; disease duration 84.7+/-79 months). 34 (85%) patients were treated with long-term glucocorticoids. Compared with 40 controls, SLE patients had a significantly lower BMD at the lumbar spine (0.96+/-0.16 vs 1.03+/-0.11 g/cm2; p=0.02) and the hip (0.87+/-0.14 vs 0.94+/-0.12 g/cm2; p=0.04). At the spine, 12 (30%) SLE patients had Z scores< - 2.0 and 2 (5%) had osteoporotic fractures. At the hip, 3 (7.5%) patients had Z scores< - 2.0 but none had hip fractures. The BMD Z scores at the femoral neck and spine were significantly lower in SLE patients than controls. The total lean body mass was also lower in patients than control subjects (46.4+/-7.3 vs 50.5+/-5.9 kg; p=0.01). Multiple regression revealed increasing age, habitual drinking, lower BMI and use of high-dose prednisolone were unfavorably associated with lower BMD at the spine in SLE patients. CONCLUSIONS Reduced BMD and lean body mass are prevalent in men with SLE. Appropriate measures against osteoporosis should be undertaken, especially in older patients with low BMI who receive high-dose glucocorticoids.

Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study

Objective The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. Methods Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥2 immunosuppressive regimens. While prednisolone (≤10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. Results Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V + III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. Conclusions Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.

Mycophenolate mofetil for lupus related myelopathy

Myelopathy is a rare manifestation of systemic lupus erythematosus (SLE). The standard treatment consists of high dose corticosteroids and intravenous pulse cyclophosphamide (CYC).1,2 Despite this, our previous experience indicated that half of the patients with lupus related myelopathy did not respond completely to CYC treatment.3 Moreover, toxicities of CYC are of major concern, particularly severe infections and ovarian failure.4 Therefore, less toxic or more effective alternative treatments are needed. Mycophenolate mofetil (MMF) is a relatively new immunosuppressive agent that has increasingly been used in patients with SLE because of its favourable efficacy and safety.5 Controlled trials have confirmed its efficacy in …