Effect of SARS-CoV2 infection on disease flares in patients with systemic lupus erythematosus: a case-control study.

OBJECTIVES: To study the effect of SARS-CoV2 infection on flares of systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled the ACR/SLICC criteria for SLE and had documented COVID-19 between February and November 2022 were identified retrospectively from our hospital COVID-19 registry. SLE controls who did not have SARS-CoV2 infection were randomly matched for age, sex and the time of infection in a 2:1 ratio with those infected. The primary outcome of interest was clinical flare of SLE within 90 days of COVID-19. The rate of SLE flares (mild/moderate or severe) was compared between SARS-CoV2-infected SLE patients and controls. RESULTS: 91 SLE patients with COVID-19 (age 48.6 ± 14.0 years; 95.6% women) and 182 SLE controls (age 48.7 ± 13.8 years; 95.6% women) were studied. Eleven of 91 (12.1%) SARS-CoV2-infected patients had serious manifestations. One (1.1%) patient died and 7(7.7%) developed severe complications. Within 90 days of SARS-CoV2 infection, 14(15.4%) patients developed mild/moderate clinical SLE flares and 2(2.2%) patients had severe SLE flares. The incidence of SLE flares in SARS-CoV2-infected patients was significantly higher than those without the infection (17.6% vs 5.5%; odds ratio 3.67[1.59-8.46]; p = 0.001). The changes in anti-dsDNA and complement levels, however, were not significantly different between the two groups. Among SARS-CoV2-infected SLE patients, those with clinical SLE flares had significantly lower C3 values (p = 0.004) before the infection than those without. CONCLUSION: Clinical flares within 90 days were significantly more common in SLE patients infected with SARS-CoV2 than matched non-infected SLE controls.

Prevalence and risk factors of herpes zoster infection in patients with biopsy proven lupus nephritis undergoing immunosuppressive therapies.

OBJECTIVES: To study the prevalence of herpes zoster infection in patients with biopsy-confirmed lupus nephritis undergoing immunosuppressive therapies. METHODS: Patients who had histologically active lupus nephritis between 2004 and 2018 were retrospectively reviewed. Clinical and laboratory data at baseline and six months post-therapy were collected. The incidence of herpes zoster reactivation within two years of lupus nephritis treatment was calculated. Risk factors for herpes zoster reactivation were studied by logistic regression. RESULTS: Patients (N = 251) with 311 episodes of lupus nephritis were studied (92% women; age 34.2 ± 14.2 years; histological classes III/IV ± V (69%)). Within two years of therapy, 55 (18%) episodes of lupus nephritis were complicated by herpes zoster infection (incidence 8.84/100 patient-years). Fourteen episodes (25%) of herpes zoster were treated by intravenous anti-viral drugs in hospital but disseminated disease or mortality was not reported. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with herpes zoster reactivation, compared with those without, were more likely to have first-time renal disease and a shorter systemic lupus erythematosus duration at lupus nephritis than those without. Disease activity, treatment response and other clinical/laboratory parameters were not significantly different between patients with and without herpes zoster reactivation. Herpes zoster-infected patients had been treated with a significantly higher dose of prednisolone as induction therapy. Logistic regression revealed that first-time renal disease, peak daily mycophenolate mofetil dose and cumulative cyclophosphamide dose during induction therapy were significantly associated with herpes zoster reactivation. CONCLUSIONS: Herpes zoster reactivation is common in lupus nephritis patients but unpredictable from clinical parameters. Although adverse outcomes of herpes zoster infection are uncommon, using the minimally effective doses of mycophenolate mofetil and cyclophosphamide during induction therapy may help reduce the risk of herpes zoster infection.

Effect of the metabolic syndrome on organ damage and mortality in patients with systemic lupus erythematosus: a longitudinal analysis.

OBJECTIVES: To study the effect of the metabolic syndrome (MetS) on organ damage and mortality in patients with SLE. METHODS: Consecutive patients who fulfilled ≥4 ACR criteria for SLE were assessed for the MetS in October 2010. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity. Longitudinal data on organ damage and mortality were retrieved. The association between MetS and new damage and mortality was studied by logistic regression. RESULTS: A total of 577 SLE patients were followed (93% women; age 41.2±13.4 years; SLE duration 9.3±7.2 years) and 85 (14.7%) patients qualified the MetS. After a follow-up of 66.3±1.8 month, new organ damage and vascular events developed in 128(22%) and 23(4.0%) patients, respectively. Thirty-nine (6.8%) patients succumbed. Patients with the MetS, compared to those without, had significantly more SLICC damage score accrual (0.70±1.0 vs 0.26±0.6; p<0.001), new vascular events (11% vs 2.8%; p=0.001), all-cause (14% vs 5.5%; p=0.003) and vascular (7.1% vs 0.2%; p<0.001) mortality. Logistic regression revealed that the MetS was significantly associated with new damage in the renal (OR 5.48[2.06-14.6]; p=0.001) and endocrine system (OR 38.0[4.50-321]; p=0.001), adjusted for age, sex, SLE duration, ever smoking, antiphospholipid antibodies and the new use of glucocorticoids or hydroxychloroquine since recruitment. Moreover, the presence of the MetS also significantly increased the risk of new vascular events (OR 3.38[1.31-8.74];p=0.01) and vascular mortality (OR 28.3[3.24-247]; p=0.002) after adjustment for the same covariates. CONCLUSION: In this longitudinal study, the MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE.

Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To study the prevalence of remission and its effect on damage and quality of life (QOL) in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled ≥4 American College of Rheumatology criteria for SLE were identified. Their remission status at last clinic visits was determined by the European consensus criteria (complete/clinical remission ± immunosuppressive drugs). The increase in SLE damage index (SDI) in the preceding 5 years was compared between patients who were and were not in remission for ≥5 years. QOL of patients as assessed by the validated Chinese version of the Medical Outcomes Study Short-Form-36 (SF36) and the LupusPRO was also compared between the remission and non-remission groups by statistical analysis. RESULTS: 769 SLE patients were studied (92% women; age: 46.4±14.6 years; SLE duration: 12.6±8.1 years). At last visit, clinical remission was present in 259 (33.7%) patients and complete remission was present in 280 (36.4%) patients. Clinical and complete remissions for ≥5 years were achieved in 64 (8.3%) and 129 (16.8%) of the patients, respectively. Patients remitted for ≥5 years were older, and had significantly lower prevalence of renal involvement, leucopenia or thrombocytopaenia. Fifty-three (6.9%) patients in remission ≥5 years were taken off all medications, including hydroxychloroquine (HCQ) (drug-free). Patients who remitted for ≥5 years but off-therapy (except HCQ) had significantly less SDI increment than those who did not remit (0.17±0.53 vs 0.67±1.10; p<0.001). Among 453 patients who had QOL assessment, remission for ≥5 years was associated with significantly higher SF36 and the total health-related scores of the LupusPRO. CONCLUSIONS: Durable remission can be achieved in a quarter of patients with SLE. Patients with remission for ≥5 years have significantly less damage accrual and better QOL. Prolonged remission is an appropriate criterion for outcome assessment in SLE.

Association of depressive/anxiety symptoms with quality of life and work ability in patients with systemic lupus erythematosus.

OBJECTIVES: To study the association of depressive/anxiety symptoms with health-related quality of life (HRQoL) and work ability in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients with ≥4 ACR criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by the Hospital Anxiety and Depression scale (HADS). HRQoL was assessed by the Chinese version of MOS-Short Form (SF)-36. Disease activity of SLE was assessed by the SLE disease activity index (SLEDAI) and organ damage was assessed by the ACR/SLICC damage index (SDI). The relationship between HAD scores, work ability and HRQoL was studied. RESULTS: A total of 367 SLE patients were studied (95% women; age 40.2±12.9 years; disease duration 9.3±7.2 years). Fifty-five (15%) patients had HADS-depression score ≥10 and 70 (19%) patients had HADS-anxiety score ≥10. Patients with either score ≥10 had significantly lower SF36 score (physical and mental component) than those with score <10. In separate linear regression models, the mental and physical component scores of SF36 were significantly associated with the HAD-depression and HAD-anxiety score after adjustment for age, sex, SLE duration, years of education, religious belief, marital status, employment status, poverty, SDI and mean SLEDAI score in the preceding year. Among those who were working in the preceding year (n=190), 30(16%) patients either quitted their job (n=22) or reduced working hours (n=8). Patients with work disability had significantly higher HAD-depression score than those without (6.31±5.51 vs 3.93±3.72; p=0.03). CONCLUSIONS: Depressive/anxiety symptoms were fairly common in SLE patients and independently associated with poorer HRQoL. Patients with more depressive symptoms were more likely to experience work disability.

Suicidal ideation in patients with systemic lupus erythematosus: incidence and risk factors.

OBJECTIVE: To study the incidence of suicidal ideation in patients with SLE and the associated risk factors. METHODS: Consecutive patients who fulfilled four or more ACR criteria for SLE were recruited. Suicidal thought in the preceding month was assessed by three direct questions. The intensity of suicidal ideation was assessed by the validated Beck Scale for Suicidal Ideation (BSSI). Socio-demographic data, clinical manifestations, Hospital Anxiety and Depression Scale (HADS), SLEDAI and SLICC/ACR Damage Index (SDI) scores were compared between patients with and without suicidal thoughts. Linear regression was used to study the factors associated with higher BSSI scores. RESULTS: Of the 367 SLE patients studied (96% women; mean age 40.2 years (S.D. 13), mean disease duration 9.3 years (S.D. 7.2), 67 (18.3%) patients had clinically active SLE and 137 (37.3%) had organ damage (SDI ≥ 1). Suicidal thoughts were present in 44 (12%) patients. Patients with suicidal thoughts, compared with those without, had significantly higher mean SLEDAI scores in the preceding year [5.1 (S.D. 4.0) vs 2.9 (S.D. 2.7), P < 0.001], higher SDI [1.4 (S.D. 1.7) vs 0.6 (S.D. 1.1), P < 0.001], HADS-depression [11.2 (S.D. 4.7) vs 4.4 (S.D. 3.8), P < 0.001] and anxiety [12.2 (S.D. 4.9) vs 5.6 (S.D. 4.1), P < 0.001] scores, and were more likely to be unemployed (P = 0.02), have a past history of psychiatric disorders (P = 0.03) and previous suicide attempts (P = 0.02), as well as major life events in the preceding month (P = 0.006). Linear regression revealed that the BSSI score correlated significantly with the HADS-depression score (ß = 0.27, P = 0.001), previous suicide attempts (ß = 0.12, P = 0.03), major life events (ß = 0.13, P = 0.01) and cardiovascular SDI score (ß = 0.27, P < 0.001). CONCLUSION: Suicidal ideation is common in SLE and is more intense in patients with depressive symptoms, cardiovascular damage, recent life events and previous suicide attempts.

Postpartum haemorrhage in midwifery care in the Netherlands: validation of quality indicators for midwifery guidelines.

BACKGROUND: Postpartum haemorrhage (PPH) is still one of the major causes of severe maternal morbidity and mortality worldwide. Currently, no guideline for PPH occurring in primary midwifery care in the Netherlands is available. A set of 25 quality indicators for prevention and management of PPH in primary care has been developed by an expert panel consisting of midwives, obstetricians, ambulance personal and representatives of the Royal Dutch College of Midwives (KNOV) and the Dutch Society of Obstetrics and Gynecology (NVOG). This study aims to assess the performance of these quality indicators as an assessment tool for midwifery care and suitability for incorporation in a professional midwifery guideline. METHODS: From April 2008 to April 2010, midwives reported cases of PPH. Cases were assessed using the 25 earlier developed quality indicators. Quality criteria on applicability, feasibility, adherence to the indicator, and the indicator's potential to monitor improvement were assessed. RESULTS: 98 cases of PPH were reported during the study period, of which 94 were analysed. Eleven indicators were found to be applicable and feasible. Five of these indicators showed improvement potential: routine administration of uterotonics, quantifying blood loss by weighing, timely referral to secondary care in homebirth and treatment of PPH using catherisation, uterine massage and oxytocin and the use of oxygen. CONCLUSIONS: Eleven out of 25 indicators were found to be suitable as an assessment tool for midwifery care of PPH and are therefore suitable for incorporation in a professional midwifery guideline. Larger studies are necessary to confirm these results.

Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case-control study.

OBJECTIVE: To study the prevalence and risk factors of low BMD in patients with SSc. METHODS: Consecutive patients with SSc and an equal number of age- and gender-matched healthy subjects were screened for BMD, fat and lean mass by DXA scan. BMD, body composition and osteoporosis risk factors were compared between patients and controls. Associated factors for low BMD in SSc patients were studied by linear regression. RESULTS: A total of 84 patients with SSc were studied [89% women; age 49.4 (11.3) years; 21% diffuse subtype; disease duration 7.8 (6.4) years]. Except for significantly lower BMI (P = 0.001), fat mass (P = 0.02) and lean body mass (P = 0.006) observed in SSc patients, the prevalence of other osteoporosis risk factors was similar to controls. Fourteen (17%) and five (6%) SSc patients had low BMD expected for age (z-score <-2.0) at the lumbar spine and hip, respectively. BMD of the lumbar spine, hip, femoral neck and whole body was significantly lower in SSc patients than controls, adjusted for age, sex, menopause and BMI (P < 0.05 in all; effect size 0.44-0.54). Linear regression revealed increasing age, menopause and low BMI were independently associated with low BMD at the spine or hip in SSc patients. However, BMD did not correlate with the severity of involvement of the skin and other systems. CONCLUSION: BMD of the spine and hip is significantly lower in patients with SSc than in healthy subjects, which is independent of age, sex, menopause, low BMI and altered body composition.

Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies.

OBJECTIVES: The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases. METHODS: Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients. RESULTS: 1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0 years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48 months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection. CONCLUSIONS: Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors. Key Points • Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. • Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. • Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.

To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of 539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLE disease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.

Hesitancy for SARS-CoV-2 vaccines and post-vaccination flares in patients with systemic lupus erythematosus.

OBJECTIVES: To study the rate of SARS-CoV-2 vaccination and post-vaccination disease flares in patients with systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled ≥ 4 of the ACR criteria for SLE were identified and their SARS-CoV-2 vaccination status was traced. Flares of SLE at 6-week post-vaccination were reviewed retrospectively. Clinical characteristics of patients with and without vaccination, and those who did or did not experience post-vaccination flares were compared by statistical analyses. RESULTS: 914 adult patients with SLE were studied (92.5 % women, age 48.6 ± 14.0 years; SLE duration 14.5 ± 8.6 years). Two doses of the SARS-Cov-2 vaccines (61.5 % BioNTech; 38.5 % CoronaVac) were received by 449 (49.1 %) patients. The vaccination rate in SLE was significantly lower than that of the adult general population (77.8 %; p < 0.001) at the time of data analysis. Patients who were hesitant for vaccination were more likely to be hypertensive, have a history of neuromuscular manifestations, and a significantly higher organ damage score (1.10 ± 1.45 vs 0.74 ± 1.15; p < 0.001). However, none of these factors were significantly associated with vaccine hesitancy on multivariate analysis. Among 449 vaccinated patients, 37(8.2 %) experienced SLE flares: mild/moderate in 34; severe in 3. In an equal number of unvaccinated SLE controls randomly matched for the post-vaccination observation period, 28(6.2 %) had SLE flares: mild/moderate in 17; severe in 11 (odds ratio [OR] for flare in vaccinated patients 1.40[0.81-2.43]; p = 0.23, adjusted for age, sex, active serology, SLE duration and prednisolone use). In vaccinated patients, logistic regression revealed that active lupus serology before vaccination (OR 2.63[1.05-6.62]; p = 0.04) and a history of arthritis (OR 2.71[1.05-7.00]; p = 0.04) or discoid skin lesion (OR 4.73[1.90-11.8]; p = 0.001) were associated with SLE flares following vaccination, adjusted for confounders. CONCLUSION: Hesitancy for COVID-19 vaccination is common in SLE patients. Vaccination against SARS-CoV-2 is not significantly associated with increased SLE flares. Patients with active SLE serology or a history of arthritis/discoid lesion are more likely to flare after vaccination.

Estimation of fracture risk by the FRAX tool in patients with systemic lupus erythematosus: a 10-year longitudinal validation study.

BACKGROUND: The fracture risk assessment tool has been widely used to stratify the 10-year fracture risk to guide therapy. Using the actual fracture data of a 10-year longitudinal cohort of older patients with systemic lupus erythematosus, we reported an underestimation of the tool in predicting major symptomatic osteoporotic fractures. Treatment of osteoporosis in systemic lupus erythematosus should not be based on fracture risk estimation alone. Relevant time-dependent risk factors should be taken into account for an individualized decision. OBJECTIVE: To compare the observed fracture incidence in a 10-year longitudinal cohort of patients with systemic lupus erythematosus (SLE) with the fracture risk prediction from the fracture risk assessment (FRAX) tool. METHODS: Adult patients (⩾40 years) with SLE who had a first DEXA scan performed in 2005-2009 were studied. The 10-year rates of major osteoporotic and hip fractures were estimated by FRAX using clinical data at DEXA with adjustment for prednisolone dosage. The actual incidence of clinical fractures at 10 years was compared with the estimated rates. Factors associated with new fractures were studied by logistic regression. RESULTS: A total of 229 SLE patients were studied (age: 50.2 ± 6.6 years, 93% women). Glucocorticoid was used in 148 (65%) patients at baseline (mean dose: 7.3 ± 6.9 mg/day; 34% ⩾ 7.5 mg/day). Osteoporosis (bone mineral density T score ⩽ -2.5) at the hip, femoral neck, or spine was present in 61 (27%) patients. The estimated 10-year risk of major osteoporotic and hip fractures by FRAX was 3.4 ± 4.5% and 0.95 ± 2.3%, respectively. After 10 years, three patients developed hip fracture, 6 patients had limb fractures and 20 patients had symptomatic vertebral fractures (major osteoporotic fracture 12.7%, hip fracture 1.3%). The actual major osteoporotic fracture rate was significantly higher than the FRAX estimation (12.7% vs 3.4%; p < 0.001). Logistic regression revealed that osteoporosis (odds ratio (OR): 4.07 [1.51-10.9]), previous fragility fracture (OR: 3.18 [1.02-9.90]), and a parental history of fracture (OR: 4.44 [1.16-17.0]) were independently associated with new clinical fractures at 10 years. CONCLUSION: The FRAX tool underestimates the major clinical fracture risk at 10 years in patients with SLE.

Trend of Survival of a Cohort of Chinese Patients With Systemic Lupus Erythematosus Over 25 Years.

Objectives: To revisit the trend of survival of systemic lupus erythematosus in a cohort of Chinese patients over 25 years. Methods: Patients who fulfilled the 1997 ACR criteria for SLE and were followed in our hospital since 1995 were included. Patients were stratified into two groups according to the year of diagnosis: (1) 1995-2004 and (2) 2005-2018. Survival of patients was studied by Kaplan-Meier analysis. Organ damage as assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) and causes of death in the first 10 years of SLE onset was compared between the two groups. Cox regression was used to study factors associated with survival. Results: A total of 1,098 SLE patients were registered in our database. After excluding 157 patients diagnosed outside the time period of 1995-2018, 941 patients were studied (92% women). All were ethnic Chinese. The mean age of SLE onset was 35.1 ± 14.4 years, and the mean duration of observation was 13.1 ± 6.6 years. Seventy-seven (8.2%) patients were lost to follow-up. Groups 1 and 2 consisted of 364 and 577 patients, respectively. The mean SDI score at 10 years of disease onset was significantly higher in group 1 than group 2 patients (1.01 ± 1.43 vs. 0.57 ± 0.94; p < 0.01), particularly in the neuropsychiatric, musculoskeletal, and gonadal domains. Within 10 years of SLE onset, 32 (8.8%) patients in group 1 and 25 (4.3%) patients in group 2 died (p = 0.005). The 5- and 10-year cumulative survival rates were 93.6 and 91.0% in group 1 and 96.5 and 94.2% in group 2 patients, respectively (log-rank test p = 0.048). Infection accounted for more than half of the deaths in both groups. More group 1 than group 2 patients died of vascular events, but the difference was not statistically significant. Cox regression showed that the age of SLE onset and damage score accrued at 10 years, but not the time period in which SLE was diagnosed, were significantly associated with mortality. Conclusions: The improvement in survival of our SLE patients is probably related to the accrual of less organ damage in the past 15 years.

Hydroxychloroquine Serum Concentrations and Flares of Systemic Lupus Erythematosus: A Longitudinal Cohort Analysis.

OBJECTIVE: To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients. METHODS: Patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and had been treated with HCQ for >6 months were studied. Blood was assayed for HCQ levels by tandem mass spectrometry. Patients were serially assessed for disease activity, using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and flares (SELENA flares instrument). Comparison of the mean summated SLEDAI scores over time and rates of flares in groups with different HCQ levels was performed by the Kruskal-Wallis test. RESULTS: A total of 276 SLE patients were studied (93% women, mean ± SD age 41.0 ± 13.8 years). The proportion of patients with HCQ levels <10 (total noncompliance), 10-500 (subtherapeutic), and >500 ng/ml (therapeutic) was 11%, 77%, and 12%, respectively. HCQ levels correlated significantly with the prescribed dose but not with body weight or renal function. The prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations. After a mean ± SD observation period of 32.5 ± 5.5 months, the mean summated SLEDAI score and the incidence of SLE flares was not statistically different among patients with different baseline HCQ levels. In a subgroup of 73 patients with serologic and clinical remission and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares was observed. CONCLUSION: Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.

Validation of the LupusPRO in Chinese patients from Hong Kong with systemic lupus erythematosus.

OBJECTIVE: LupusPRO is a disease-targeted, patient-reported outcome (PRO) measure that was developed and validated for assessment of quality of life in US patients with systemic lupus erythematosus (SLE). We present results of adapting the LupusPRO into Chinese and testing its psychometric properties in Chinese patients with SLE. METHODS: LupusPRO was translated into "traditional" Chinese, followed by pretesting among native Cantonese Chinese speakers. The translation version was revised based on the feedback obtained. The Chinese language LupusPRO tool was administered along with a generic PRO tool (the Short Form 36 health survey [SF-36]) to ethnic Chinese SLE patients. At the same time, demographic information, clinical data, disease activity (Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]), and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) were obtained. We performed confirmatory factor analysis of the Chinese LupusPRO and evaluated internal consistency reliability, as well as convergent and criterion validity. RESULTS: Among the 463 SLE patients (95% women) with a mean ± SD age of 42.3 ± 13.5 years, the mean ± SD physician global assessment score was 0.48 ± 0.45, the mean ± SD SELENA-SLEDAI score was 2.9 ± 3.0, and the mean ± SD SDI score was 0.7 ± 1.2. Results of factor analysis conformed to the original LupusPRO model with only minor modifications. The reliability of the LupusPRO domains ranged from 0.60-0.94. LupusPRO domains had correlations as expected with the corresponding SF-36 domains. A significant but weak correlation with disease activity was noted for criterion validity as expected. CONCLUSION: The Chinese language LupusPRO has fair psychometric properties and may be used in SLE clinical trials.