Diffuse alveolar haemorrhage in systemic lupus erythematosus: A multicentre retrospective study in Singapore.

OBJECTIVE: Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival outcomes of SLE patients with DAH in Singapore. METHODS: We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups. RESULTS: A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25-54), with a median disease duration of 8.9 months (IQR: 0.13-102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6-46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026). CONCLUSIONS: The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.

Montreal cognitive assessment as a screening instrument for cognitive impairment in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored. METHODS: This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function. RESULTS: The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance. CONCLUSION: MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Incidence and patterns of malignancies in a multi-ethnic cohort of rheumatoid arthritis patients.

AIM: This study was undertaken to determine the incidence and patterns of malignancies in rheumatoid arthritis (RA) patients in our cohort. METHODS: Between 2001 and 2013, we analyzed 1117 patients in the prospective Tan Tock Seng Hospital (TTSH) RA Registry. Patients who developed malignancies after the onset of RA were identified from this registry. Age- and sex-adjusted standardized incidence ratios (SIRs) were calculated to compare observed to expected numbers of malignancies based on data from the Singapore Cancer Registry. RESULTS: Out of 19 839 person-years of follow-up, 132 incident malignancies were diagnosed during the observation period. There were 114 (86.4%) solid-organ tumors and 18 (13.6%) hematological malignancies. The SIR (95% confidence interval) for all malignancies combined was 1.28 (0.88-1.87) for males and 1.21 (1.00-1.46) for females. Compared to the general population, we found a 4- to 5-fold increase in lymphoma among our RA patients compared to the general population (SIR 5.05 [1.90-13.46] for males and 3.75 [1.95-7.20] for females). The SIR of lung malignancy in male RA patients is 2.36 (1.23-4.53) and SIR of cervical malignancy in female RA patients is 3.72 (2.20-6.23). CONCLUSION: There is a trend toward an overall increased malignancy risk in our RA patients compared to the general population. Specifically, there is an increased risk of lymphomas in all RA patients, lung malignancy in male patients, and cervical malignancy in female patients, compared to the general population.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.

OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter-observer reliability in scoring of synovitis. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at 0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. During image acquisition and interpretation, B-mode scoring showed ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore.

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis.

AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis.

Cross-cultural adaptation of the Systemic Lupus Erythematosus Quality of Life Questionnaire into Chinese.

OBJECTIVE: We have previously validated the English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) in our patients with lupus. Many of our Chinese patients are not fluent in English and therefore a Chinese version (SLEQOL-C) has been adapted for their use. METHODS: Two independent translators translated the SLEQOL into Chinese. A consensus version was derived from both sets of translations. Back translation of this version was performed by another 2 independent translators who had neither been involved in the forward translation nor encountered the SLEQOL. The final version, SLEQOL-C, was finalized after rectifying the discrepancies revealed by the back translation. Linguistic validity was tested in open interviews with bilingual patients with lupus. The SLEQOL-C and SLEQOL were administered to patients to determine whether they displayed differential item functioning (DIF). RESULTS: In general, most of the items in English could be expressed in Chinese precisely, although a few instructions had to be altered slightly to make them more idiomatic. The forward and back translations of the SLEQOL were accomplished without major difficulties. A total of 638 patients were interviewed (62.8% with the SLEQOL and 37.2% with the SLEQOL-C). Using DIF analysis, there was no detectable test bias due to language use after controlling for repeated observations, age, sex, and ethnicity. CONCLUSION: The SLEQOL-C has semantic, idiomatic, and conceptual equivalence to the SLEQOL. The rigorous process of cross-cultural translation provides some measure of quality in the content validity.

Pulmonary hemorrhage in systemic lupus erythematosus.

OBJECTIVE: To determine the clinical features of our systemic lupus erythematosus (SLE) patients presenting with pulmonary hemorrhage (PH). METHODS: We reviewed the records of all SLE patients who had PH between 1994 and 2001, a total of 22. RESULTS: All patients had radiographic infiltrates. The mean drop in hemoglobin was 3.2 +/-1.1 g/dL, hemoptysis occurred in 50%, the Dlco was increased in 10 of 11 patients (91%), and 11 of 14 patients who underwent bronchoscopy had positive findings. All received high-dose prednisolone and most also were given pulse methylprednisolone (MEP) and cyclophosphamide. All patients required care in the intensive/monitored care unit, 14 were intubated, 11 had plasmapheresis, and 8 died as a result of PH (mortality rate, 36%). SLEDAI and SLAM were able to indicate active disease in SLE patients with PH (median SLEDAI, 19 [interquartile range, 10 to 24] and mean SLAM, 16.1 +/- 5.8). There was a statistically significant increase in the SLEDAI from 1 month prior to PH to the time of PH (P =.014), indicating that the patients were having a significant disease flare. The median SLEDAI and SLAM scores of patients who died were slightly higher than that of survivors. CONCLUSION: PH in SLE patients occurred in those with severe, multiorgan involvement, with high SLEDAI scores. A high degree of suspicion should be maintained in lupus patients with active disease and unexplained infiltrates on chest radiographs and dropping red cell indices, even in the absence of hemoptysis. Early aggressive management with high-dose steroids and intravenous pulses of cyclophosphamide is advocated and may explain recent trends of improved survival. Plasmapheresis may be useful for the acutely ill patient who does not respond to the above measures but does not clearly lead to improved survival.