Risk factors for herpes zoster in patients with rheumatic diseases: a nationwide cohort study in Korea.

OBJECTIVE: To determine the risk factors for herpes zoster (HZ) in patients with rheumatic diseases in Korea. METHODS: We used the nationwide database of the Health Insurance Review & Assessment Service to analyse patients aged ≥20 years who had visited a hospital more than twice for rheumatic disease as a principal diagnosis from January 2009 to April 2013. HZ was identified using HZ-related Korean Standard Classification of Diseases 6 (KCD-6) codes and the prescription of antiviral agents. The relationship between demographics, comorbidities and medications and HZ risk was analysed by Cox proportional hazards models. RESULTS: HZ developed in 1869 patients. In Cox proportional hazards models, female sex but not age showed an increased adjusted hazard ratio (HR) for HZ. Comorbidities such as haematologic malignancies, hypertension, diabetes mellitus, and chronic lung and liver diseases led to an increased HR. HZ risk was higher in patients with SLE (HR: 4.29, 95% CI: 3.49, 5.27) and Behçet's syndrome (BS, HR: 4.54; 95% CI: 3.66, 5.64) than with RA. The use of conventional DMARDs, immunosuppressants, TNF inhibitors, glucocorticoids and NSAIDs increased the HR. Infliximab and glucocorticoids (equivalent prednisolone dose >15 mg/day) produced the highest HZ risk (HR: 2.91, 95% CI: 1.72, 4.89; HR: 2.85, 95% CI: 2.15, 3.77, respectively). CONCLUSION: Female sex, comorbidities and medications increased HZ risk in patients with rheumatic diseases and even young patients could develop HZ. Compared with RA, SLE and BS are stronger HZ risk factors. Patients with rheumatic diseases and these risk factors are potential target populations for HZ vaccination.

Dependence of the birefringence of polystyrene film on the stretching conditions.

We investigated the dependence of the birefringence of polystyrene (PS) film with a negative optical birefringence on the stretching conditions. We varied the stretching ratio (SR), stretching speed (SS), and stretching temperature (ST), and measured the inplane birefringence and the Nz coefficient of the PS film. The inplane birefringence was increased with greater SR and SS but decreased with greater ST. The Nz coefficient of the stretched PS film was around zero and showed similar dependence on the stretching conditions like inplane birefringence.

Infliximab for refractory oral ulcers.

Recurrent oral ulcer (ROU) is a common condition that significantly impacts quality of life. It is often related to systemic diseases, such as Behçet's disease (BD), Crohn's disease, and ulcerative colitis. Treatment of ROU depends on its severity: from topical agents for mild cases to systemic agents, such as corticosteroids, azathioprine, or other immunosuppressants for severe cases. Recently, good results have been reported with infliximab in refractory ROU. However, the optimal dosage and treatment duration have not been determined and the cost and potential side effects should be considered. We report on four patients who received a single-dose infliximab for refractory ROU. Two patients had refractory ROU with no underlying disease; one of them had soft palate perforation accompanied by severe oral ulcers. The two other patients had ROU of BD without major organ involvement. All patients received a single infusion of infliximab and an additional infusion was given on demand in one patient. Infliximab showed a rapid, good response in three patients and was also effective in improving the acute inflammation in the perforation of the soft palate, which had been resistant to conventional therapies. These effects diminished over a few weeks, but the ROU were tolerable and it was not necessary to increase steroids or add another medicine for about 1 year. We suggest that a single infusion of infliximab can be considered for refractory ROU.

Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.

The diagnostic utilities of anti-agalactosyl IgG antibodies, anti-cyclic citrullinated peptide antibodies, and rheumatoid factors in rheumatoid arthritis.

The purpose of this study was to investigate the diagnostic utilities of anti-agalactosyl IgG antibody (CARF), anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor (RF) in rheumatoid arthritis (RA), non-RA rheumatic diseases, and chronic viral hepatitis. The authors determined serum levels of CARF and anti-CCP2 by ELISA and IgM-RF by a immunonephelometric method in 834 controls and in 397 patients with the following conditions: RA (100), non-RA rheumatic diseases [systemic lupus erythematosus (SLE) 30, primary Sjogren's syndrome 18, systemic sclerosis 30, inflammatory myositis 19], chronic viral hepatitis B and C (HBV 100, HCV 100). The sensitivities of CARF (83%) and anti-CCP (85%) were significantly higher than that of RF (75%, p = 0.01, respectively) in RA, and the specificity of anti-CCP (98%) was significantly higher than those of CARF (92%) and RF (90%, p < 0.001, respectively). A comparison of receiver operating characteristic (ROC) curves revealed that the diagnostic accuracies of CARF and anti-CCP were superior to that of RF (CARF vs. RF, p = 0.008, anti-CCP vs. RF, p = 0.017) in RA. CARF positivity was significantly higher than those of anti-CCP (p = 0.007) and RF (p = 0.008) in systemic sclerosis, and the positivity of CARF was significantly higher than that of anti-CCP in Sjogren's syndrome (p = 0.016). Furthermore, CARF had significantly higher positivity than anti-CCP or RF in chronic viral hepatitis B and C. Finally, the titers of these three markers in RA were significantly higher than in non-RA rheumatic diseases and in chronic viral hepatitis B and C. Our results suggest that anti-CCP is the most useful serologic marker for the differentiation of RA and non-RA rheumatic diseases, and chronic viral hepatitis B and C.

Signalling and putative therapeutic molecules on the regulation of synoviocyte signalling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article: Bone Joint Res 2021;10(4):285-297.

Synovial Fluid of Patient With Rheumatoid Arthritis Enhanced Osmotic Sensitivity Through the Cytotoxic Edema Module in Synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the synovial membrane ultimately leading to permanent damage in the affected joints. For this study, synovial fluids from 16 patients diagnosed with either RA or osteoarthritis (OA) were used to examine volume regulation and cooperative water channels, both of which are involved in the cytotoxic edema identified in RA-fibroblast-like synoviocytes (FLS). The osmolarity and inflammatory cytokine interleukin (IL)-6 of synovial fluids from RA patients were mildly enhanced compared to that from OA patients. RA-FLS demonstrated the enhanced property of regulatory volume increase in response to IL-6 and synovial fluids from RA patients. Although there was no difference in the protein expression of the volume-associated protein sodium-potassium-chloride cotransporter1 (NKCC1), its activity was increased by treatment with IL-6. Membrane localization of NKCC1 was also increased by IL-6 treatment. Additionally, both the protein and membrane expressions of aquaporin-1 were increased in RA-FLS by IL-6 stimulation. The IL-6-mediated enhanced osmotic sensitivity of RA-FLS likely involves NKCC1 and aquaporin-1, which mainly constitute the volume-associated ion transporter and water channel elements. These results suggest that RA-FLS provide enhanced electrolytes and concomitant water movement through NKCC1 and aquaporin-1, thereby inducing cellular swelling ultimately resulting in cytotoxic edema. Attenuation of cytotoxic edema and verification of its related mechanism will provide novel therapeutic approaches to RA treatment within the scope of cytotoxic edema.

Particulate matter (PM10) as a newly identified environmental risk factor for acute gout flares: A time-series study.

OBJECTIVES: This study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10µm in diameter (PM10) on occurrence of acute gout flares in the general population and identify susceptible groups accordingly. METHODS: The data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PM10 and meterological measurements were provided by the Ministry of Environment and the National Meterological Office, respectively. To estimate the risk of daily ED visits due to acute gout flare, these time-series data set were analyzed using generalized additive models with Poisson distribution, including daily average PM10 level, temperature, relative humidity, day of the week, national holiday, season, and date. RESULTS: The risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PM10 levels significantly increased in the cumulative lag 0-7 model (relative risk, 1.018; 95% confidence interval, 1.008-1.027, P<0.001). In particular, men aged≥40 years and those with a history of diabetes mellitus or gout were significantly at a high risk of acute gout flares by subgroup analysis. CONCLUSIONS: Our time-series study demonstrated a modest, but significant effect of short-term exposure to PM10 on ED visits for acute gout flares. Ambient PM10 may be a newly identified environmental risk factor for acute gout flares.

Clinical and radiographic features of adult-onset ankylosing spondylitis in Korean patients: comparisons between males and females.

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

Outcomes and Risk Factors of Systolic Pulmonary Artery Pressure Progression in Patients with Systemic Rheumatic Diseases: Follow-up Results from a Korean Registry.

OBJECTIVES: This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases. PATIENTS AND METHODS: A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up. RESULTS: The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p<0.001). In patients with systemic sclerosis, the majority of patients remained static within their pressure group or rose progressively: the patients with markedly elevated sPAP at follow-up were higher than those at baseline (32% versus 15%, p<0.01). In patients with mixed connective tissue disease (MCTD) or rheumatoid arthritis (RA), the majority of patients remained static within their pressure group or gradually improved: the patients with markedly elevated sPAP at follow-up were lower than those at baseline (RA=14% versus 29%, MCTD=5% versus 16%, p<0.05). CONCLUSION: Persistently high sPAP or increase of sPAP over 60 mmHg at follow-up was associated with increased mortality. There were some differences in the progression of sPAP according to the underlying rheumatic diseases.

Clinical phenotypes of Korean patients with Behcet disease according to gender, age at onset, and HLA-B51.

BACKGROUND/AIMS: The clinical manifestations of Behcet disease (BD) have been reported to differ according to country, region, and race. Gender, onset age, and human leukocyte antigen (HLA)-B51 have also been known as the factors that influence the clinical features of BD. The aim of this study is to investigate the clinical phenotypes of Korean patients who visited the rheumatology clinic with BD with respect to gender, onset age, and HLA-B51. METHODS: Total 193 Korean patients (129 females and 64 males) fulfilling the international criteria for BD were retrospectively assessed. RESULTS: The mean age at disease onset and disease duration of the BD patients were 32.2 ± 11.1 and 14.2 ± 9.3 years, retrospectively. Females suffered more frequently from genital ulcers (90.7% vs. 75.0%, p < 0.01), peripheral arthritis (67.4% vs. 43.8%, p < 0.01), and inf lammatory low back pain (38.8% vs. 23.4%, p = 0.03) than males, while skin involvement was more frequent in males than in females (90.6% vs. 75.2%, p = 0.01). The patients with late onset of BD (> 40 years) suffered from neurologic involvement (15.9% vs. 4.2%, p = 0.007) more frequently than those with early onset of BD. The patients with HLA-B51 showed earlier onset of disease than without HLA-B51 (28.3 ± 11.4 years vs. 33.8±11.6 years, p = 0.02) and the neurologic and gastrointestinal involvements were more frequent in the patients without HLA-B51 than with HLA-B51 (17.2% vs. 2.5%, p = 0.02 and 20.7% vs. 2.5%, p = 0.01, respectively). CONCLUSION: The clinical phenotypes in Korean patients with BD may be influenced by gender, onset age and HLA-B51.

Mean platelet volume as a marker for differentiating disease flare from infection in Behçet's disease.

AIM: The aim of this study was to investigate the association between mean platelet volume (MPV) and clinical manifestations, disease activity or infection in patients with Behçet's disease (BD). METHODS: In total, 193 patients diagnosed with BD according to the international criteria for BD were enrolled. Demographic data, clinical manifestations and laboratory results were collected by medical interviews and reviewing medical records. RESULTS: The female : male ratio was 2 : 1 and the age of symptom onset was 32.2 ± 11.1 years. The age at diagnosis of BD was 44.7 ± 11.1 years and the follow-up duration was 4.7 ± 3.8 years. MPV at diagnosis were significantly lower than of age and sex-matched controls (8.2 ± 1.2 vs. 8.6 ± 1.2 fL, P < 0.0001). Lower MPV was not related to organ involvement except skin diseases. During follow-up, MPV was lower in BD flare than in stable BD (8.2 ± 1.4 vs. 9.1 ± 1.4 fL, P < 0.0001) in the same patients. MPVs were significantly higher in cases of accompanying infections than in those with both BD flare and stable BD (9.3 ± 1.4 vs. 8.1 ± 1.3 fL, P = 0.018 and 9.7 ± 1.4 vs. 8.8 ± 1.0 fL, P = 0.001, respectively). CONCLUSIONS: MPV was significantly lower in patients with BD than controls. MPV declined in BD flare and increased in cases of infection in same patients. MPV may be useful as a marker of BD activity and its monitoring can be helpful for differentiating BD flare from infection in BD patients.

Associations between interferon regulatory factor-1 polymorphisms and Behçet's disease.

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates the functions of type I and II interferons and plays a role in host protection. Behçet's disease (BD) is an idiopathic systemic vasculitis that is often complicated with thrombotic features, and infectious agents have long been postulated to be a disease-triggering factor in its pathogenesis. The authors investigated the distributions of IRF-1 promoter -415 C/A, -410 A/G, and -300 A/G, and 3'-untranslated region (UTR) A/G polymorphisms in 105 BD patients (mean age 41.7 +/- SEM 1.1 years, 44 male and 61 female) and in 105 gender- and age-matched healthy controls. The frequencies of individual alleles and genotypes were not different between the control and BD groups. However, the frequency of AGGG haplotype was significantly higher (73.5% vs 60.2%, odds ratio [OR] = 1.842, 95% confidence interval [95% CI] = 1.219-2.783, p(c) = 0.036) and that of the CAAG haplotype was significantly lower (2.2% vs 9.5%, OR = 0.195, 95% CI = 0.068-0.559, p(c) = 0.02) in BD patients than in healthy controls. In addition, the frequency of the AGGG haplotype was significantly higher (80.3% vs 57.4%, OR = 3.033, 95% CI = 1.716-5.360, p(c) = 0.001) and that of the CAAG haplotype was significantly lower (0.8% vs 12.3%; OR = 0.059, 95% CI = 0.010-0.357, p(c) = 0.005) in female BD patients than female controls. By subgroup analyses, the CAAA haplotype tended to be more common in BD patients with moderate or severe disease than in those with mild disease (25.4% vs 13.6%, OR = 2.158, 95% CI = 1.046-4.440, p = 0.037 before Bonferroni correction). When BD patients were subclassified by a history of deep vein thrombosis (DVT), the CAAA haplotype was found to be significantly increased the risk of DVT (42.1% vs 15.7%, OR = 3.906, 95% CI = 1.836-8.324, p(c) = 0.0015) and the AGGG haplotype tended to reduce this risk (57.9% vs 77.3%, OR = 0.403, 95% CI = 0.195-0.834, p(c) = 0.0685). Furthermore, the frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event than in those that had not (40.5% vs 15.5%, OR = 3.7147, 95% CI = 1.778-7.770, p(c) = 0.0015). These results suggest that IRF-1 is a novel susceptibility gene in BD, especially in women, and furthermore, that IRF-1 polymorphisms may be related to thrombosis in BD patients.

Fibromyalgia with chronic rheumatic diseases in South Korea: a comparison of clinical and American College of Rheumatology criteria.

AIM: To describe the prevalence and characteristics of fibromyalgia (FM) in patients with underlying rheumatic disease, and to compare it by three different measures. METHODS: We studied 546 patients with chronic rheumatic diseases who attended our rheumatology clinic. If patients answered all of a screening questionnaire with yes, then we considered patients to be having widespread pain as assessed by the fibromyalgia impact questionnaire (FIQ), widespread pain index (WPI), and symptom severity (SS). A physician administered the tender point (TP) exam and clinician's judgment of FM. We collected demographics, clinical and laboratory features. RESULTS: One hundred and sixty-four (30.0%) patients among 546 cases had a further exam. The male-to-female count was 25 : 139. The mean age was 49.7 years, disease duration 3.7 years, TP counts 4.2, FIQ score 47.0 and WPI with SS score was 11.1. We classified 17 patients (10.4%) with concomitant FM with widespread pain by tender point exam, 56 patients (34.2%) by WPI with SS, and 36 patients (22.0%) by a clinician's judgment. A total of 70.6% (n = 12) of those classified as FM by 1990 American College of Rheumatology (ACR) criteria wee categorized as FM by clinician's judgment, while 33.3% by clinician's judgment were classified by 1990 ACR criteria. CONCLUSIONS: We found a 10.4~34.2% prevalence of concomitant FM in the patients with chronic widespread pain. The 1990 ACR criteria were the most restrictive except for SLE. Although The 2010 ACR criteria had a wide spectrum, it can be used for FM diagnosis even in the patient with underlying rheumatic diseases.

Validation and reliability of a Behcet's Syndrome Activity Scale in Korea.

BACKGROUND/AIMS: We prepared a cross-cultural adaptation of the Behcet's Syndrome Activity Scale (BSAS) and evaluated its reliability and validity in Korea. METHODS: Fifty patients with Behcet's disease (BD) who attended the Rheumatology Clinic of Gachon University Gil Medical Center were included in this study. The first BSAS questionnaire was administered at each clinic visit, and the second questionnaire was completed at home within 24 hours of the visit. A Behcet's Disease Current Activity Form (BDCAF) and a Behcet's Disease Quality of Life (BDQOL) form were also given to patients. The test-retest reliability was analyzed by intraclass correlation coefficients (ICC). To assess the validity, the total BSAS score was compared with the BDCAF score, the patient/physician global assessment, and the BDQOL by Spearman rank correlation. RESULTS: Twelve males and 38 females were enrolled. The mean age was 48.5 years and the mean disease duration was 6.7 years. Thirty-eight patients (76.0%) returned the questionnaire by mail. For the test-retest reliability, the two assessments were significantly correlated on all 10 items of the BSAS questionnaire (p < 0.05) and the total BSAS score (ICC, 0.925; p < 0.001). The total BSAS score was statistically correlated with the BDQOL, BDCAF, and patient/physician global assessment (p < 0.01). CONCLUSIONS: The Korean version of BSAS is a reliable and valid instrument to measure BD activity.

Cross-cultural adaptation and validation of the Behcet's Disease Current Activity Form in Korea.

BACKGROUND/AIMS: This study was undertaken to perform a cross-cultural adaptation of the Behcet's Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet's disease (BD). METHODS: A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient's/clinician's perception of disease activity and the Korean version of the Behcet's Disease Quality of Life (BDQOL). RESULTS: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient's/clinician's perception of disease activity p < 0.05). CONCLUSIONS: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients.

Delayed diagnosis is linked to worse outcomes and unfavourable treatment responses in patients with axial spondyloarthritis.

The diagnosis of spondyloarthritis (SpA) has a lengthy delay; we investigated the outcomes and factors associated with the delayed diagnosis of SpA. This was a cross-sectional study on patients with SpA who visited a rheumatology clinic at a single tertiary centre. The data were collected from face-to-face interviews, physician assessments of disease status and reviews of medical records. In total, 105 patients with SpA were consecutively enrolled. Of the included patients, 94 had axial SpA and 11 had peripheral SpA. The median diagnostic delay was 8 years (interquartile range, 3-14) for axial SpA. Comparisons between the early and late diagnosis groups were performed to identify the factors related to delayed diagnosis in axial SpA. A definite diagnosis of SpA led to proper management and clinical improvements. The patients with delayed diagnosis showed worse outcomes in disease activity, function, spinal mobility and/or radiographic damage. These patients also demonstrated a less favourable treatment response according to the Bath Ankylosing Spondylitis Disease Activity Index and the rate of radiographic progression. Multivariate analysis indicated that a prior diagnosis of mechanical back pain was an independent factor associated with diagnostic delay. The diagnosis of SpA is often delayed. Delayed diagnosis is associated with worse outcomes and poor treatment responses in SpA patients. Physician and patient awareness of inflammatory back pain are essential for the early diagnosis of SpA, and a referral guideline for patients with suspected SpA is needed.

Clinical risk factors for adverse events in allopurinol users.

Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events. To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study. Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P = .005), more hypertension (42% vs 30%, P = .036), less tumor lysis syndrome (P = .030), higher cholesterol (P = .013), and lower aspartate aminotransferase (P = .002) and alanine aminotransferase levels (P = .033) and more commonly used angiotensin receptor blockers (27% vs 15%, P = .007), colchicines (16% vs 5%, P = .010), or statins (19% vs 8%, P = .002) than those who did not. In multiple logistic regression analysis, the use of colchicines (odds ratio, 3.11; 95% confidence interval, 1.28-7.58; P = .012) and statins (2.10; 1.03-4.25; P = .041) was an independent risk factor predicting adverse events in allopurinol users. In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events.

Anti-cyclic citrullinated peptide antibody is associated with radiographic erosion in rheumatoid arthritis independently of shared epitope status.

Shared epitope (SE) and anti-cyclic citrullinated peptide (CCP) antibody are known to be associated with rheumatoid arthritis (RA). The authors investigated their adjusted effects on RA from Korean population. Clinical features were evaluated in 226 RA patients; 164 healthy controls were enrolled. HLA-DRB1 typing for SE was done by polymerase chain reaction. Anti-CCP antibody levels were determined by enzyme linked immunosorbent assay. Logistic regression analysis method was used for adjusted effects. SE and anti-CCP antibody were associated with RA susceptibility. Anti-CCP antibody was associated with RA susceptibility independent of SE [odds ratio, OR 179.9 (95% confidence interval, CI 40.8-792.2), P < 0.001]. Anti-CCP antibody was associated with radiographic erosive changes independent of SE or rheumatoid factor [OR 3.9 (95% CI 1.1-13.3), P = 0.032]. Anti-CCP antibody was strongly associated with RA susceptibility and radiographic erosion of RA patients, independent of SE in Korean.