Increased risk of temporomandibular joint disorders and craniofacial deformities in patients with juvenile idiopathic arthritis: a population-based cohort study.

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that has been proposed to involve the temporomandibular joint (TMJ). The aim of this study was to identify the relationships between JIA, TMJ disorders, and craniofacial deformities. This cohort study included patients diagnosed with clinically active JIA between 1999 and 2013 through a nationwide longitudinal health registry. The primary outcome was the presence of a TMJ disorder. The secondary outcome was the presence of a JIA-associated craniofacial deformity. A total of 2791 patients with JIA were included in the case group; 11,164 propensity score-matched individuals without JIA were selected from the same database as controls. TMJ disorders were present in 142 individuals: 48 (1.72%) in the case group and 94 (0.84%) in the control group (relative risk 2.047, 95% confidence interval 1.446-2.898). Craniofacial deformities were present in 374 individuals: 112 (4.01%) in the case group and 262 (2.35%) in the control group (relative risk 1.722, 95% confidence interval 1.380-2.148). Patients with JIA showed a significantly greater likelihood of developing TMJ disorders and craniofacial deformities compared to matched controls.

Traditional Chinese medicine use may reduce medical utility in patients with asthma: a nationwide population-based retrospective cohort study.

BACKGROUND: Many patients with atopic diseases, including asthma, have sought complementary and alternative medicine and traditional Chinese medicine (TCM) treatments. But, limited clinical studies have yet examined TCM effects on medical utility in asthma patients. AIM: To assess the medical utility of TCM in patients with asthma. DESIGN: Population-based retrospective cohort study. METHODS: We performed a 13-year population-based retrospective cohort study. A total of 5235 asthma patients who were TCM users and 5235 propensity-score matched asthma patients who never used TCM were sampled from the Taiwan National Health Insurance Research Database from 2000 to 2012. We compared these two groups of patients to calculate their medical utility, including numbers of emergency visits and hospitalizations until 2013. Univariate analyses were performed using Chi-square tests for dichotomous variables and t-tests for continuous variables. Cox proportional hazard models were conducted to investigate the medical utility of asthma after TCM use. RESULTS: Compared with non-TCM patients, TCM patients had a significantly decreased medical utility of asthma admission [adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI): 0.46-0.85; P < 0.05], especially in patients who used TCM for >60 days. Asthma medical utility in asthma emergencies was significantly higher for male than for female patients (adjusted OR = 1.45; 95% CI: 1.08-1.96). The most frequently used TCMs for asthma control or cough treatment were antitussive agents. CONCLUSION: This population-based retrospective cohort study showed a significantly decreased medical utility of emergency visits and admissions in TCM patients, especially using TCM for >60 days.

Risk of stroke with antivenom usage after venomous snakebite in Taiwan: a population-based cohort study.

BACKGROUND AND PURPOSE: Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. METHODS: This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. RESULTS: The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41-5.26). CONCLUSION: Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

Association of sepsis with risk for osteoporosis: a population-based cohort study.

We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database to evaluate whether the risk of developing osteoporosis is associated with sepsis. Our study found that adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis. INTRODUCTION: There have been limited studies regarding the osteoporosis risk associated with sepsis. Our purpose is to evaluate whether the risk of developing osteoporosis is associated with sepsis. METHODS: We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,178 patients diagnosed with sepsis from 2000 to 2012 were included in the sepsis cohort, and a propensity score-matched cohort included 13,178 individuals without sepsis. To calculate the incidence of osteoporosis, both groups were followed until 2013. Cox regression analysis was performed to obtain the hazard ratios (HRs) to assess the risk of developing osteoporosis. The Kaplan-Meier method was used to estimate the cumulative incidence of osteoporosis. RESULTS: The overall incidences of osteoporosis (per 1,000 person-years) in the sepsis and non-sepsis groups were 10.2 and 10.7, respectively. The risk of osteoporosis significantly increased in the presence of sepsis (adjusted HR = 1.17, 95% confidence interval (CI) = 1.04-1.31). The risk of osteoporosis in the sepsis group was significantly higher than that in the non-sepsis group for young patients aged 20-49 years and patients aged 50-64 years (adjusted HR = 1.93, 95% CI = 1.08-3.44; adjusted HR = 2.01, 95% CI = 1.52-2.65, respectively). The Kaplan-Meier curves of cumulative probability also showed a significantly increased risk of osteoporosis in patients aged 20-49 years and aged 50-64 years with sepsis compared with non-sepsis (P = 0.025; P < 0.001, respectively). CONCLUSION: Adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.

Association of gout medications and risk of cataract: a population-based case-control study.

BACKGROUND: The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship. AIM: To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout. DESIGN: Population-based nested case-control study. METHODS: We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract. RESULTS: The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract. CONCLUSIONS: In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome.

OBJECTIVES: To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). METHODS: This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. RESULTS: Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). CONCLUSIONS: HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.

Risk of systemic lupus erythematosus in patients with human papillomavirus infection: a population-based retrospective cohort study.

BACKGROUND: Viral infection contributing to systemic lupus erythematosus (SLE) development has been largely reported. However, the SLE risk in patients with human papillomavirus (HPV) infection is unknown. METHODS: Data were retrieved from the Longitudinal Health Insurance Database (2000) in Taiwan. We identified 43,567 patients with HPV infection and 174,268 age- and sex-matched uninfected controls from 2002 to 2012. Individuals were followed up from index date (first date of diagnosis with HPV) until the occurrence of SLE, at the end of the study (December 2013), or when they were withdrawn from the insurance program. The incidence rate ratio (IRR) was calculated using the univariate Poisson regression. The adjusted hazard ratios (aHRs) were calculated, and sensitive and subgroups analyses were also conducted. RESULTS: Compared with the non-HPV controls, the IRR of SLE in HPV patients was 1.52 (95% confidence interval (CI): 1.09-2.12). The risk of SLE in HPV-infected individuals was significantly high (aHR: 1.48, 95% CI: 1.06-2.06) after adjusting for age, sex, and comorbidities. Men aged between 16 and 45 years were more susceptible to developing SLE (aHR: 21.57, 95% CI: 2.52-184.60, p = 0.0051). CONCLUSION: Our study showed a significantly higher risk of SLE among HPV-infected patients, especially in men aged between 16 and 45 years.

Syncope caused by complete heart block and ventricular arrhythmia as early manifestation of systemic lupus erythematosus in a pregnant patient: a case report.

Systemic lupus erythematosus (SLE) can affect all heart structures including the conduction system, with either reversible or permanent derangement. However, only a few cases of adult SLE and complete atrioventricular (AV) block have been reported. We describe a young pregnant woman who initially presented with complete AV block on electrocardiography before the diagnosis of SLE. Syncope subsequently developed during the postpartum period due to frequent nonsustained polymorphic ventricular tachycardia, suggesting lupus myocarditis. The ventricular arrhythmia was successfully treated by intravenous corticosteroids, lidocaine and implantation of a permanent pacemaker. This may represent the first report of complete AV block with polymorphic ventricular tachycardia, which was identified before the other clinical features of SLE fully manifested. SLE should be considered if a patient presents with complete AV block without other clinical features. It may warn for early diagnosis and appropriate treatment of SLE including lupus-related heart disease.

Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis.

BACKGROUND/OBJECTIVES: The purpose of this study was to investigate whether vitamin B(6) supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA). SUBJECTS/METHODS: This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n=15) or vitamin B(6) (5 mg/day folic acid plus 100 mg/day vitamin B(6); n=20) for 12 weeks. Plasma pyridoxal 5'-phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention. RESULTS: In the group receiving vitamin B(6), plasma IL-6 and TNF-alpha levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B(6) group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (beta=-0.01, P=0.01). CONCLUSIONS: A large dose of vitamin B(6) supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-alpha) in patients with RA.

Genetic polymorphisms of the matrix metalloproteinase-3 (MMP-3) and tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) modulate the development of ankylosing spondylitis.

BACKGROUND: The aetiology of ankylosing spondylitis (AS) remains unclear. Inflammation progresses to fibrosis and calcification of the spine and sacroiliac joints in AS development. Fibrosis results from excessive accumulations of the extracellular matrix (ECM). ECM turnover depends on the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). OBJECTIVE: To evaluate the effects of the MMP-3 -1171 and TIMP-1 372 T>C polymorphisms on the modified risk of AS. METHODS: Genotypes of 241 patients with AS and 241 controls were identified by PCR. Disease activity and functional status were assessed by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global (BAS-G) Score. RESULTS: MMP-3 6A/6A carriers had a 2.41-fold (95% confidence interval (CI) 1.55 to 3.74) increased risk of AS compared with 6A/5A and 5A/5A carriers. TIMP-1 C alleles had a greater risk of AS, but this was not significant (odds ratio (OR) = 1.28, 95% CI 0.92 to 1.77). Pairwise analysis of the MMP-3/TIMP-1 alleles showed that 6A/C (OR = 3.23, 95% CI 1.50 to 6.95) and 6A/T (OR = 2.55, 95% CI 1.17 to 5.54) had a significantly greater risk of AS than the 5A/T alleles. After adjustment for the effects of age, gender and disease duration, the MMP-3/TIMP-1 5A/T alleles had the lowest BASDAI (p = 0.02), BASFI (p = 0.05) and BAS-G (p = 0.02) among all MMP-3/TIMP-1 alleles. CONCLUSION: The findings highlight the importance of the MMP-3 and TIMP-1 genes as crucial elements in AS development.

Replication of association of IL1 gene complex members with ankylosing spondylitis in Taiwanese Chinese.

OBJECTIVE: To test the association of interleukin 1 (IL1) gene family members with ankylosing spondylitis (AS), previously reported in Europid subjects, in an ethnically remote population. METHODS: 200 Taiwanese Chinese AS patients and 200 ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (SNPs) and the IL1RN.VNTR, markers previously associated with AS. Allele, genotype, and haplotype frequencies were compared between cases and controls. RESULTS: Association of alleles and genotypes of the markers IL1F10.3, IL1RN.4, and IL1RN.VNTR was observed with AS (p<0.05). Haplotypes of pairs of these markers and of the markers IL1RN.6/1 and IL1RN.6/2 were also significantly associated with AS. The strongest associations observed were with the marker IL1RN.4, and with the two-marker haplotype IL1RN.4-IL1RN.VNTR (both p = 0.004). Strong linkage disequilibrium was observed between all marker pairs except those involving IL1B-511 (D' 0.4 to 0.9, p<0.01). CONCLUSIONS: The IL1 gene cluster is associated with AS in Taiwanese Chinese. This finding provides strong statistical support that the previously observed association of this gene cluster with AS is a true positive finding. These authors contributed equally to the study.

Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity.

OBJECTIVE: To submit serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) to statistical analyses to test their exact degrees of clinical usefulness as biomarkers for detecting high disease activity in ankylosing spondylitis (AS), comparing them with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). METHODS: Serum levels of MMP-1, -3, -9 and TIMP-1 and -2 were measured in 42 AS patients and 20 healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) provided the gold standard for measuring disease activity. Patients with BASDAI > or =4 were regarded as having high disease activity. The results were compared with results for a separate cohort of 41 AS patients. RESULTS: Only MMP-3 levels were significantly higher in AS patients than in healthy controls (P<0.001). Within AS patients, MMP-3 levels were also higher in patients with high disease activity compared with those with low disease activity, and correlated significantly with BASDAI (r = 0.366, P = 0.017) and functional indices (r = 0.344, P = 0.026). The correlation with BASDAI was stable in a 1-yr follow-up (r = 0.464, P = 0.095) and reproducible with two different enzyme-linked immunosorbent assays. For detecting high disease activity, the sensitivity and specificity of MMP-3 level was 69.2 and 68.8% respectively. Most importantly, using receiver operating characteristic plots to analyse the two cohorts, MMP-3 was more accurate than ESR and CRP in detecting AS patients with high disease activity (P = 0.01 and P = 0.009, respectively). CONCLUSION: Using several analytical approaches that have never been reported previously, we showed that MMP-3 is a more useful biomarker than ESR and CRP to detect high disease activity in AS.

Study of undifferentiated spondyloarthropathy among first-degree relatives of ankylosing spondylitis probands.

OBJECTIVE: To estimate in a Chinese population the prevalence of undifferentiated spondyloarthropathy (USpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) probands, and to compare the clinical features of familial USpA with those of sporadic USpA. METHODS: The FDRs of two separate cohorts of consecutive AS probands were evaluated for the prevalence of USpA, using the Modified New York criteria and the European Spondylitis Study Group criteria for AS and SpA, respectively. Sporadic USpA and FDRs of non-SpA rheumatic patient probands served as separate controls. RESULTS: Among the 301 FDRs of 102 AS probands, 7.0% were USpA. This was 1000 times higher than the 147 FDRs of 40 non-SpA probands (P = 0.00230). Within the AS families, USpA was less male-dominated than AS (33.3 vs 72.5%) (P = 0.006). The only feature distinguishing familial from sporadic USpA was that the percentages of HLA B27 were 100 and 50%, respectively (P<0.001). CONCLUSION: USpA and AS coexist in the same Chinese families, both being predisposed by HLA B27. In these families, a female gender favours the development of USpA rather than AS. A significant subset of sporadic USpA (HLA B27-negative group) has a different genetic predisposition compared with familial USpA.

HLA-B60 and B61 are strongly associated with ankylosing spondylitis in HLA-B27-negative Taiwan Chinese patients.

OBJECTIVES: Carriage of HLA-B60 has been shown to increase the risk of ankylosing spondylitis (AS) in B27-positive Caucasian patients, but the association in B27-negative cases is less certain. This study assessed HLA class I gene associations in Chinese HLA-B27-negative AS patients. METHODS: Forty-one Chinese HLA-B27-negative AS patients fulfilling the modified New York diagnostic criteria for AS were recruited, and 11 383 HLA-B27-negative blood donors were used for comparison. HLA-A and -B typing was done with the microlymphocytotoxicity assay. RESULTS: Among the B27-negative AS patients, 21 were male and 20 were female. Of HLA-B alleles, only B60 and B61 significantly increased susceptibility to AS in HLA-B27-negative patients (P<0.001). CONCLUSIONS: In Taiwan Chinese, carriage of B60 is increased in HLA-B27-negative AS patients. The association between B61 and HLA-B27-negative AS patients has not been reported previously. Whether the gene involved is HLA-B60 or B61 or another gene in linkage disequilibrium with these genes is unknown.