Yu-Sheng Chang

Incidence and risk analysis of aortic aneurysm and aortic dissection among patients with systemic lupus erythematosus: a nationwide population-based study in Taiwan

Objective The objective of our study was to determine the incidence rates and risk factors of aortic aneurysm and aortic dissection among patients with systemic lupus erythematosus (SLE) using a nationwide population-based data set. Methods We conducted a retrospective cohort study using data from the Taiwan National Health Insurance database. Patients with SLE and age-, sex- and comorbidity-matched control patients without SLE were identified. The primary endpoint was the first occurrence of aortic aneurysm or aortic dissection. The incidence rate ratios (IRRs) were calculated based on a 95% confidence interval (CI). A Cox proportional-hazards model was used to evaluate the risk factors for aortic aneurysm and aortic dissection in the SLE cohort. Results Among the 15,209 patients with SLE (89.9% women and mean age of 38.3 years), 20 developed aortic aneurysm and 13 developed aortic dissection (overall incidence rate, 4.26 per 10,000 person-years). Compared with the control patients, the overall IRR for developing aortic aneurysm or aortic dissection was 3.34 (95% CI, 1.71–6.91; p < 0.001). The IRRs for aortic aneurysm or aortic dissection were 2.98 (95% CI, 1.41–6.70, p = 0.018) for women and 5.50 (95% CI, 1.10–53.15, p = 0.020) for men. Multivariate Cox regression analysis showed that age, male sex, an SLE diagnosis greater than three years prior and hypertension were associated with aortic aneurysm and aortic dissection. Conclusion Aortic aneurysm and aortic dissection occur at higher rates in SLE patients than in people without SLE and a longer disease duration is associated with a higher risk of these rare vascular complications.

Effects of annual influenza vaccination on morbidity and mortality in patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study

Studies on the clinical efficacy of influenza vaccination on patients with systemic lupus erythematosus (SLE) are scant. The present study compared the incidence of hospitalization, morbidity, and mortality in patients with SLE between cohorts with and without influenza vaccination. We used the Taiwan’s insurance claims data between 2001 and 2012 for identifying annual adult patients with SLE with (N = 1765) and without (N = 8360) influenza vaccination. The incidence rate ratio and hazard ratio (HR) for morbidities and mortality were measured for the vaccine and nonvaccine cohorts. The vaccine cohort had a lower hospitalization rate than did the nonvaccine cohort, with an adjusted HR of 0.82 (95% CI 0.73–0.92). Furthermore, the vaccine cohort was less likely to be admitted to the intensive care unit [adjusted HR 0.55 (95% CI 0.39–0.79)], to be hospitalized for septicemia, bacteremia, or viremia [adjusted HR 0.48 (95% CI 0.32–0.73)], to undergo in-hospital dialysis [adjusted HR 0.40 (95% CI 0.20–0.81)], and were less predisposed to death [adjusted HR 0.41 (95% CI 0.27–0.61)]. In conclusion, influenza vaccination in patients with SLE is associated with a reduced risk of morbidity and mortality.

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

Thymectomy in patients with myasthenia gravis increases the risk of autoimmune rheumatic diseases: a nationwide cohort study

Objectives Previous studies have shown myasthenia gravis (MG) and autoimmune rheumatic diseases (ARDs) share common pathogenetic mechanisms. Therefore, the present study investigated the possible relationship between MG and ARDs. Methods We analysed Taiwanese medical data from the Registry of Catastrophic Illness and identified patients with MG. From the entire general population data of the National Health Insurance Research Database, we randomly selected a comparison cohort that was frequency-matched by age (in 5-year increments), sex, and index date. We analysed the risk of ARDs by using a Cox proportional hazards regression model stratified by sex, age and treatment. Results In the present study, we enrolled 6478 patients with MG (58.03% women; mean age, 50.55 years) and 25 912 age- and sex-matched controls. The risk of total ARDs was 6.25 times higher in the MG cohort than in the non-MG cohort after adjustment for age and sex. Furthermore, the MG cohort was associated with a significantly higher risk of primary SS (pSS), SLE and other ARD types (adjusted hazard ratios: 15.84 [95% CI: 8.39, 23.91]; 11.32 [95% CI: 5.04, 25.429]; and 4.07 [95% CI: 1.31, 12.62], respectively). The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE (adjusted hazard ratios: 4.41; 15.06; and 23.68, respectively). Conclusion The present nationwide cohort study revealed an association between MG and incident ARDs. The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE. Future studies are needed to elucidate the underlying pathogenesis and to translate this into clinical therapeutic options.

173 Elderly sle patients with previous skin herpes infection and higher dose of steroid enhanced the risk of severe herpes simplex infection: a nationwide study

Background and aims Systemic lupus erythematosus (SLE) patients are susceptible to herpes simplex virus (HSV) infection, which is occasional but often leading to overwhelming disease such as encephalitis and keratitis. However, only few attempts have been made at the associated incidence and risk factors. Methods We enrolled SLE patients from the Taiwanese National Health Insurance research database between 1997 and 2012. We compared the incidence rate (IR) of severe HSV infection, including viral septicemia, meningoencephalitis, ocular infection, visceral infection and those with complications after infection, with those of non-SLE cohort. We also evaluated the risk factors of severe HSV infection by means of Cox multivariable proportional hazards model. Results A total of 1 22 520 subjects (24 504 SLE patients and 98 016 age- and gender-matched subjects as control group) were analysed and revealed a significantly higher IR of severe HSV infection in SLE (Incidence rate ratio=3.52, p<0.001). Previous skin infection (HR=2.17, p=0.047), intravenous steroid pulse therapy (HR=4.48, p<0.001), oral daily steroid dose over 7.5 mg prednisolone or equivalent (HR=1.60, p=0.010) were independent risk factors for severe HSV infection in SLE patients, while age ≤18 (HR=0.47, p=0.021) was a protective factor. Conclusions A higher risk of severe HSV infection was observed in SLE patients The risk factors for severe HSV infection were age over 18, previous skin infection, intravenous steroid pulse therapy and an oral daily steroid dose over 7.5 mg.

407 Using decision tree to identify the itp with high probability of sle development from a nationwide cohort study

Background and aims Idiopathic thrombocytopenic purpura (ITP) is an immune-related thrombocytopenia which may herald the development of systemic lupus erythematosus (SLE), and thus regular following up has been suggested. Whereas widespread surveillance on all ITP patients would be time and cost-consuming; therefore identifying those with high probability of development of SLE among ITP patients should be more practical. Methods We enrolled ITP patients without previous SLE diagnosis from the Taiwan National Health Insurance research database between 1997 and 2012 and identified those with SLE diagnosis during follow up. We also analysed the symptoms and comorbidities as well as the dose of average oral steroid to derive the decision trees, which classified the ITP patients with different probability of development of SLE. Results A total of 10 265 ITP patients were enrolled, among whom 80 patients developed SLE while following-up. The whole ITP patients were allocated to development group (7186 patients including 57 with SLE) and validation group (3079 patients including 23 with SLE); the former was used for derivation of the decision-tree based model (Figure 1) and the latter for validation of the previously mentioned model (Figure 2), and provided high sensitivity (78.2%), specificity (99.2%) and negative prediction value (99.8%). To reduce the complexity, we also proposed another models with different complexity parameters (Figure 3). Conclusions We derived different decision tree models exempt from the necessity of laboratory data and adequate for various clinical scenarios of ITP patients, among whom those with high probability of development of SLE could be identified.

SAT0286 Risk of Severe Herpes Simplex Virus Infection in Patients Sle: A Nationwide Population Cohort Study

Background Severe herpes simplex virus (HSV) infections, especially encephalitis and keratitis, often affect immunocompromised patients and result in severe sequela. However, only few attempts have been made at the association between systemic lupus erythematosus (SLE) and HSV. Objectives To identify the risk of severe HSV infection in SLE patients by means of a nationwide population-based cohort study. Methods We identified SLE patients from the National Health Insurance research database between 1997 and 2012. We compared the incidence rate (IR) of severe HSV infection, including viral septicaemia, CNS infection, ocular infection, visceral infection and those with complications after infection, with that of non-SLE cohort. A Cox multivariable proportional hazards model was applied to evaluate the risk of severe HSV infection in the SLE cohort. Results A total of 122,520 subjects (24,504 SLE patients and 98,016 age- and gender-matched subjects as control group) were analyzed and revealed a significantly higher IR of severe HSV infection in SLE (Incidence rate ratio =3.52, p <0.001). Previous skin infection (HR=2.17, p=0.047), intravenous steroid pulse therapy (HR=4.48, p<0.001), oral daily steroid dose over 7.5mg prednisolone or equivalent (HR=1,60, p=0.010) were independent risk factors for severe HSV infection in SLE patients, while Age ≤18 (Hazard ratio [HR]=0.47, p=0.021) was a protective factor.Table 1. Risk factors of severe HSV infection in patients with SLEa Variable Univariate analysis Multivariable analysisa HR (95% CI) P-value HR (95% CI) P-value Age 1.01 (1.00–1.03) 0.017  ≤18-year-old 0.47 (0.24 – 0.89) 0.021  >18-year-old 1.23 (0.54–2.82) 0.612 Male 0.986 (0.57–1.71) 0.974 Diabetes mellitus 0.56 (0.31–1.02) 0.057 End-stage renal disease 0.96 (0.62–1.49) 0.844 Malignancy 1.12 (0.28–4.54) 0.871 CHF 0.79 (0.46–1.36) 0.399 Previous skin infection 2.21 (1.03–4.73) 0.042 2.17 (1.01–4.65) 0.047 Hydroxychloroquine 1.05 (0.75–1.46) 0.108 Azathioprine 1.60 (1.10–2.3.2) 0.015 – – Mycofenolate mofetil 0.40 (0.06–2.89) 0.367 Cyclosporine 1.58 (0.58–4.26) 0.371 Cyclophosphamide 1.67 (0.87–3.18) 0.122 MTX 1.32 (0.58–2.99) 0.507 Intravenous 5.24 (3.52–7.79) <0.001 4.48 (2.95–6.80) <0.001 Oral daily dose over 7.5mg† 2.03 (1.44–2.86) <0.001 1.60 (1.12–2.30) 0.010 Conclusions A higher risk of severe HSV infection was observed in SLE patients Risk factors for severe HSV infection were age over 18, previous skin infection, intravenous steroid pulse therapy and an oral daily steroid dose over 7.5mg. References Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013 Oct;22(12):1286–94 Bosch X, Guilabert A, Pallarés L, Cerveral R, Ramos-Casals M, Bové A, Ingelmo M, Font J. Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients. Lupus. 2006;15(9):584–9. The nature and outcome of infection in systemic lupus erythematosus. Lupus. 2002;11(4):234–9. Disclosure of Interest None declared

Rituximab Therapy in Chinese Patients with Lupus Nephritis

Background: Systemic lupus erythematosus (SLE) is a common autoimmune disease in Chinese, and there is high morbidity and mortality in patients with initial renal involvement or severe nephritis. We investigated the efficacy of B cell depletion therapy with rituximab as treatment of Chinese patients with lupus nephritis (LN).Methods: We enrolled 14 patients with lupus nephritis (LN) from Taipei Veterans General Hospital beginning in 2009. LN was confirmed by clinical and laboratory evaluation. Rituximab was indicated when a patient had proteinuria ( ＞1 g/day urinary protein) that was poorly responsive to treatment with corticosteroids or immunosuppressants. Laboratory examination, including measurements of CBC, creatinine, albumin, C3, C4, anti-dsDNA antibodies, and urinary protein, were performed before rituximab infusion and at 3-month and 6-month follow-ups. Intravenous rituximab was given twice over 2 weeks at a total dosage of 1 or 2 g. The primary endpoint was renal response status at week 24.Results: A total of 14 patients were enrolled from 2009 to 2011. There were 11 females and 3 males and the age range was 18 to 41 years (median: 31 years, IQR 10.5 years). The median urinary protein was 3.38 g/day (IQR: 1.76 to 6.47) before rituximab infusion, and was 1.25 g/day (IQR: 0.49-3.13) at the 6 month follow-up. At week 24, the overall renal response rate (complete + partial response) was 57% (8 of 14 patients). There were improvements in C3 levels (＞20 mg/dL) in 6 patients (43%), improvements in C4 levels (＞10 mg/dL) in 3 patients (21%), and reductions in anti-dsDNA antibody levels (＞50%) in 8 patients (57%).Conclusion: Rituximab appeared to have acceptable efficacy in our group of 14 LN patients. Future controlled studies should examine the long-term safety and efficacy of rituximab and determine the optimal rituximab regimen for Chinese patients with LN.

Correlation of BASDAI and BASFI with Clinical Features and Treatment in Chinese Patients with Ankylosing spondylitis

Objective: To understand the relationship between disease activity or patient functional ability with different clinical parameters (e.g. age, gender, age at onset, disease duration) in our ankylosing spondylitis (AS) patients in Taiwan.Methods: Chinese version of Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) was recently developed and validated by our AS Study Group. We enrolled 344 AS patients and analyzed their demographic and clinical characteristics, sulfasalazine and non-steroidal anti-inflammatory drugs (NSAIDs) use, and clinical outcome by using the Chinese version of BASDAI and BASFI.Results: The 344 AS patients were predominantly male (255) (M:F = 2.9:1) and Taiwanese (69.3%). Hakka and Mainlander ethnicity was 13.2% and 12.4%, respectively. Mean age in the study was 36.2 (M ± SD: 36.2 ± 11.95). Although the mean age at onset was 24.98, 35% of patients had onset of AS before 16 yrs. Average BASDAI score in AS patients was 3.2(range 0-8.5), and BASFI 2.55 (range 0-9.32). Uveitis was present in 29.9% patients and peripheral arthritis developed in 66.1% AS patients. Many patients (47.1%) reported that their family relatives also had AS. Correlation analysis between clinical features and BASDAI showed a significant correlation only between peripheral arthritis and BASDAI (p＜0.0001). However, age, age above 35 or below 35 or different age distribution, disease duration, peripheral arthritis and NSAID use, showed a significant correlation with BASFI.Conclusion: The presence of peripheral arthritis can significantly influence both BASDAI and BASFI. The old age, longer disease duration and continuous treatment with NSAIDs was associated with a higher score in BASFI but not BASDAI. Early diagnosis and adequate management may prevent AS patients from later functional impairment.

Arthropathy and Tendinopathy in Patients with Tophaceous and Non-tophaceous Gout: A Case-controlled Ultrasonographic Study

Objective: To determine the characteristics of tendon and joint involvement in patients with tophaceous and non-tophaceous gout on ultrasonography (US). Method: We performed a prospective, observational, case-controlled study using US to evaluate the knee, ankle, 1st and 2nd metatarsal-phalangeal (MTP) joints, and the tendons and entheses of the lower limbs. Differences were analyzed by Fisher’s exact or Mann-Whitney U-tests. Results: Twenty-four patients with tophaceous gout and 36 subjects with nontophaceous gout were recruited. Double contour signs (DCS) of the femoral condyles were significantly more prevalent in the tophaceous gout group compared to the non-tophaceous group (50% vs. 15.3%; p=0.001). The 1st and 2nd MTP joints of patients with tophaceous gout had significantly more DCS, periarticular tophi, and bone erosions than patients with non-tophaceous gout (p≤0.002). Intratendinous tophi in the Achilles tendons (43.8% vs. 6.9%), proximal/distal patella tendons (29.2%/41.7% vs. 1.4%/8.3%), tibialis anterior/posterior tendons (14.6%/39.6% vs. 0/1.4%), and peroneus longus and brevis tendons (29.2% vs. 0) were significantly more frequent in patients with tophaceous gout than patients with non-tophaceous gout (p≤0.002). Enthesopathies were commonly observed; specifically 7.5% of proximal patella tendons, 20% of distal patella tendons, and 13.3% of Achilles tendons presented with enthesopathies. No statistical differences existed between groups. Conclusion: Patients with tophaceous gout had significantly more prevalent intra- and extra-articular pathology on US, suggesting a larger quantity of monosodium urate depositions, than patients with non-tophaceous gout. We thus recommend a more aggressive and longer duration of urate-lowering therapy in patients with tophaceous gout.