Disease activity assessment in ankylosing spondylitis in a Chinese cohort: BASDAI or ASDAS?

Recently, the Ankylosing Spondylitis Disease Activity Score (ASDAS), a new index, has been shown to be validated and highly discriminatory in assessing ankylosing spondylitis (AS) disease activity. This study is to evaluate the performance of ASDAS in a local Chinese cohort of AS in a cross-sectional setting and to compare it with the existing instrument, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Consecutive patients with AS were recruited from a local rheumatology clinic. Data, including BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Visual Analogue Scale (VAS) for spinal pain, and patient and physician global assessments were gathered during clinic visit. Inflammatory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and high-sensitivity (hs)-CRP were collected. ASDAS was calculated accordingly. The discriminatory capacity of BASDAI and ASDAS was compared by: (1) standardized mean difference statistics, (2) R (2) in linear regressions, and (3) area under receiver operating characteristic curve (AUC) in logistic regression models. Both ASDAS and BASDAI showed satisfactory predictive value on disease activity with reference to patient and physician global assessment. R (2) in linear regression models ranged from 0.6-0.7. Both indices also demonstrated good discriminatory capacity as evidenced by a relatively high AUC (> 0.8) under the logistic regression models using either patient or physician global assessment score ≥4 and <4 as cut off of high and low disease activity status, respectively. Although we could not demonstrate significant differences in the performance between them, subgroup analysis suggested better discriminatory ability of ASDAS in the high inflammatory marker subgroup. ASDAS and BASDAI showed similarly good performance in a cross-sectional setting in a local Chinese AS cohort. ASDAS performed better in subgroup with raised inflammatory markers.

Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition.

OBJECTIVE: Endothelial dysfunction and inflammation are pathogenic mechanisms common to systemic sclerosis (SSc) and atherosclerosis. This study was undertaken to examine the relationship between coronary atherosclerosis, as assessed by the coronary artery calcium score (CACS), and conventional cardiovascular and disease-specific risk factors in SSc patients. METHODS: The CACS was measured by computed tomography, and cardiovascular risk factors were examined in SSc patients and compared with controls matched for age, sex, and glycemic status. Disease activity score, antiphospholipid antibodies, high-sensitivity C-reactive protein level, and erythrocyte sedimentation rate were measured in SSc patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined. RESULTS: We recruited 53 SSc patients (50 women and 3 men) and 106 controls. The patients had a mean ± SD age of 53.1 ± 12.9 years and a median disease duration of 9 years. Compared to controls, SSc patients had significantly lower low-density lipoprotein (LDL) cholesterol levels (P = 0.001), high-density lipoprotein cholesterol levels (P = 0.01), diastolic blood pressure, waist circumference, and body mass index and were more likely to be receiving vasodilators (all P < 0.001). There was a significantly higher proportion of SSc patients among subjects with more severe coronary calcification (CACS ≥ 101) compared to those with lesser severity (CACS <100) (56.5% versus 29.4%; P = 0.01). Multiple logistic regression analysis revealed SSc to be an independent determinant for a CACS ≥ 101 (OR 10.89 [95% CI 2.21-53.75], P = 0.003) together with age and LDL cholesterol level after adjustment for other cardiovascular risk factors. Among disease-specific factors, only disease duration (OR 1.14 [95% CI 1.02-1.27], P = 0.02) was independently associated with more severe coronary calcification (CACS ≥ 101). CONCLUSION: Our findings indicate that SSc is an independent risk factor for coronary calcification, in addition to the conventional risk factors for coronary atherosclerosis, such as age and hypertension.

Comparison of performance of the Assessment of SpondyloArthritis International Society, the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis.

Early diagnosis of spondyloarthritis (SpA) is essential as anti-tumor necrosis factor therapy can achieve significant symptomatic relief and control of disease activity. This study aims to compare the clinical characteristics, disease activity, and functional status of a Chinese cohort of SpA patients who were re-classified into ankylosing spondylitis (AS) patients fulfilling the modified New York (MNY) criteria, those with undifferentiated SpA (USpA) fulfilling the European Spondyloarthropathy Study Group (ESSG) classification criteria only (USpA/ESSG) and those who fulfill Assessment of SpondyloArthritis International Society (ASAS) only (USpA/ASAS). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), severity of morning stiffness, patient global assessment, and C-reactive protein. Functional status was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI), modified Schober index, and dimension of chest expansion. One hundred and twenty-eight patients with disease duration of 16.3 ± 10.4 years were recruited. Patients in USpA/ESSG and USpA/ASAS were significantly younger (p = 0.01), had shorter disease duration (p < 0.01), and lower BASFI (p = 0.03) than established AS patients. All three groups have active disease with comparable BASDAI >3. BASFI correlated inversely with dimension of chest expansion and negatively modified Schober index in AS patients (p < 0.01) and modestly with BASDAI (r = 0.25, p < 0.01). BASFI correlated moderately with BASDAI in USpA/ESSG (r = 0.61, p < 0.01) but not with chest expansion or modified Schober index. Compared with established AS patients recognized by MNY criteria, patients fulfilling USpA defined by ESSG or ASAS criteria had earlier disease, as active disease and less irreversible functional deficit.

The clinical course of polymyalgia rheumatica in Chinese.

Polymyalgia rheumatica (PMR) is diagnosed based on clinical features that may overlap with other rheumatic conditions like rheumatoid arthritis (RA). Furthermore, a proportion of PMR patients may subsequently evolve into RA. The aim of this study was to examine the clinical characteristics of PMR patients in a Chinese cohort compared to a Caucasian series. Patients diagnosed to have PMR during 1997-2008 were reviewed for clinical features and compared to a reported Caucasian series. Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP) antibodies were determined by immunonephelometry and enzyme-linked immunosorbent assay, respectively. Forty-four patients of southern Chinese origin were diagnosed to have PMR according to specialist opinion. Seventy-five percent of patients (n = 33) were >65 years of age at diagnosis (mean +/- standard deviation, 75.8 +/- 9.6 years). The commonest feature at disease onset was elevated erythrocyte sedimentation rate >40 mm/h (100% vs. 95.7%; p = 0.17) and bilateral shoulder pain or stiffness (95.5% vs. 90.8%; p = 0.31), comparable in frequency to the Caucasian cohort. However, Chinese patients had significantly longer duration of symptoms before diagnosis (p < 0.001) but less bilateral upper arm tenderness (p < 0.001) and generalized stiffness (p = 0.01). Twelve (27.3%) patients evolved into RA after a median duration of 2 months from onset of PMR. RF and anti-CCP antibodies were positive in 66.7% and 60% of these patients compared to 9.4% and 6.2%, respectively, among those who did not evolve into RA during the period observed. Chinese patients with PMR have modestly different clinical profile compared to the Caucasian counterpart. RF and anti-CCP antibodies were more likely to be present in those who subsequently developed into RA.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p < 0.001). Serum NO(x) were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO(x) level defined as mean +/- 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Elevated plasma adrenomedullin and vascular manifestations in patients with systemic sclerosis.

OBJECTIVE: Adrenomedullin (ADM), a vasodilating peptide that possesses antiinflammatory properties, may have a regulatory role in the vascular manifestations of scleroderma (systemic sclerosis, SSc). We examined associations between ADM concentrations and vascular manifestations in a cohort of patients with SSc. METHODS: Patients were examined for manifestations of severe Raynaud's phenomenon (RP), defined as digital resorption, previous iloprost infusion, and sympathectomy. Doppler echocardiography and lung function tests were performed to detect elevation in pulmonary arterial pressure (PAP; > 35 mm Hg) and interstitial lung disease (ILD). Plasma ADM was measured by radioimmunoassay. RESULTS: Plasma ADM was measured in 62 SSc patients and 21 healthy controls. Elevated PAP was found in 15 (24.2%) SSc patients (mean PAP 46.5 +/- 11.2 mm Hg, range 37-74). ADM was not found to be related to age, sex, disease duration, or clinical subset. ADM level was significantly higher (median 13.9 pmol/l) in SSc patients with elevated PAP compared to those with lower PAP (median 7.2 pmol/l) (p = 0.01) and controls (median 7.9 pmol/l) (p = 0.04). ADM level was not different among patients who had elevated PAP with (n = 10) and without concomitant ILD (n = 5) (p = 0.21). SSc patients with severe RP (38.7%; median ADM 11.9 pmol/l) were found not to have different ADM levels compared to controls (p = 0.75). Patients who had both severe RP and elevated PAP were found to have significantly higher ADM levels (median 22.3 pmol/l) than patients who had neither manifestation (median 8.0 pmol/l) (p = 0.006) and those with severe RP alone (median 4.2 pmol/l) (p = 0.006). CONCLUSION: Elevated ADM was found in SSc patients with increased PAP regardless of concomitant ILD.

Tuberculosis in systemic lupus erythematosus in an endemic area and the role of isoniazid prophylaxis during corticosteroid therapy.

OBJECTIVE: The efficacy of isoniazid (INAH) prophylaxis against tuberculosis (TB) in patients taking corticosteroid remains controversial. Hong Kong is an endemic area for TB, with an annual risk of 0.11/100 in the general population. Patients with systemic lupus erythematosus (SLE) have an increased susceptibility to TB because of their intrinsic immunocompromised state and the use of corticosteroid therapy. We examined the usefulness of INAH in the prevention of recurrences of TB in patients with SLE receiving high dose corticosteroid therapy. METHODS: Medical records of a cohort of patients with SLE were reviewed. Patients with a history of TB who had previously been adequately treated were retrospectively examined for subsequent recurrence of TB. A comparison was performed based on the use of INAH at the discretion of the attending physician in some patients (INAH group) but not others (non-INAH group) during lupus exacerbation that required the use of prednisolone >/= 15 mg/day or equivalent. RESULTS: A total of 91 episodes of TB from 76 individuals in a cohort of 652 SLE patients with a duration of followup of 13.9 +/- 7.5 years were identified (prevalence of 1.06/100 patient-years). 43 episodes were given INAH while 48 were not. There were 18 recurrences of TB (recurrence rate of 1.66/100 patient-years). Recurrence rates in the INAH and non-INAH groups were 1.59 and 1.74 per 100 patient-years (p = 0.72). However, patients in the INAH group had more lupus exacerbations. Further, extrapulmonary TB was also found to have a higher recurrence rate than pulmonary TB. A case-controlled analysis was thus performed (n = 46) matching patients for the number of lupus exacerbations, cumulative doses of prednisolone, and initial site of TB. There was no difference in the recurrence rates of TB between the matched INAH (0.55/100 patient-years) and non-INAH (1.100 patient-years) groups (p = 0.66). CONCLUSION: Patients with SLE have a higher prevalence of TB infection than the general population. They are at risk of TB recurrence when given immunosuppressive doses of corticosteroid.

Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus.

OBJECTIVE: Different prevalences of antiphospholipid antibodies (aPL) have been reported in different populations of patients with systemic lupus erythematosus (SLE). Chinese are generally believed to have lower risk of vascular thrombosis. We examined the prevalence of aPL including lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies, the level of thrombotic risk, and the association of aPL with thrombotic and pregnancy outcomes in a Chinese cohort with SLE at the university lupus clinic during the period 1986-2003. METHODS: aPL were measured in 272 SLE patients, and medical records were reviewed for vascular thrombosis and pregnancy outcomes. RESULTS: The prevalence of LAC, IgG aCL, and IgG anti-beta2-GPI antibodies was 22.4%, 29.0%, and 7.7%, respectively. There were 38 episodes of thrombosis after a mean duration of followup of 11.0 +/- 6.8 SD years, giving a thrombotic rate of 1.26/100 patient-years. All aPL were shown to be associated with vascular thrombosis. IgG anti-beta2-GPI antibodies were found to be associated with recurrent thrombosis [8.0/100 patient-years or 25.0% (7/28)]. Patients taking hydroxychloroquine were found to have fewer thrombotic complications than those who were not (OR 0.17, 95% CI 0.07-0.44; p < 0.0001). LAC was the strongest factor associated with recurrent miscarriages [relative risk 12.3, 95% CI 1.22-123.31; p = 0.03). The diagnosis of secondary antiphospholipid syndrome was satisfied in 8.9% of patients. CONCLUSION: The lifetime and recurrent thrombotic rates in our patients with aPL were not particularly different from those in the literature. However, the lower prevalence of aPL in our cohort may suggest a role of other prothrombotic factors in predisposition to thrombosis.

Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial.

BACKGROUND: The aim of this study was to report the outcome of pure membranous lupus nephropathy treated with prednisone and azathioprine (AZA). METHODS: Consecutive patients with pure membranous lupus glomerulonephritis (World Health Organization [WHO] Va and Vb) from 4 regional hospitals were recruited for an open-label treatment trial consisting of prednisone and AZA. Remission status was evaluated at 12 months. Maintenance treatment with low-dose prednisone and AZA was continued indefinitely for those who achieved remission. Factors predictive of initial renal remission and subsequent relapse were studied by statistical analyses. RESULTS: Thirty-eight patients (31 women and 7 men) were studied. The mean age was 35.0 +/- 9.2 years, and the duration of systemic lupus erythematosus was 48.5 +/- 59 months. Seventeen (45%) patients had WHO class Va lupus nephritis, whereas 21 (55%) had class Vb disease. Two patients withdrew from the protocol because of idiosyncratic reactions to AZA. At 12 months, 24 (67%) patients achieved complete remission (CR), 8 (22%) achieved partial remission (PR), and 4 (11%) were treatment resistant. Patients who achieved CR or PR were maintained on low-dose prednisone and AZA. Over a mean follow-up period of 90.4 +/- 59 months, 6 (19%) patients had relapse of nephritis (proteinuric flare in 4 and nephritic flare in 2). The cumulative risk of renal relapse was 12% at 36 months and 16% at 60 months. No particular clinical variables were found to predict renal remission or relapses. Over a mean follow-up of 90 months, 13% of patients had decline of creatinine clearance by 20%, but none had doubling of serum creatinine. Renal outcome was not significantly worse in patients presenting with nephrotic syndrome. Treatment generally was well tolerated. CONCLUSION: A combination of prednisone and AZA is reasonably effective for the initial treatment of pure membranous lupus nephritis. Severe adverse effects are uncommon. The additional efficacy of AZA in comparison with prednisone alone has to be confirmed with randomized, controlled trials.