Application of Salivary Alpha-1 Antitrypsin in the Diagnosis of Rheumatoid Arthritis: A Pilot Study.

Background and Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually destroyed. Early diagnosis and treatment before joint deformation or destruction is important. The detection of novel RA biomarkers in saliva may facilitate early detection of RA before disease onset. This study aimed to evaluate salivary concentration of α1-antitrypsin (A1AT) in healthy patients and those with RA, and to assess the diagnostic value of salivary A1AT. Materials and Methods: In total, 80 participants were included: 20 healthy participants, and 60 patients with RA. Saliva and serum samples were obtained from all the patients. Levels of A1AT and cytokines, including interleukin-1 beta (IL-1ß), IL-6, and IL-10 in saliva and serum, were evaluated using an enzyme-linked immunosorbent assay kit and Luminex assay. Data were analyzed using SPSS for Windows. Results: There was a higher level of A1AT in the saliva of patients with RA (median: 2388.66 ng/mL) than that in healthy controls (1579.06 ng/mL). There was a positive mild-to-moderate accuracy (area under the curve: 0.57-0.85) of A1AT in saliva to diagnose RA. The cut-off level (ng/mL) of A1AT in saliva for detecting RA was 1689.0. Conclusions: The obtained data can promote the application of the measurements of A1AT in saliva to diagnose RA.

Investigation of periodontitis, halitosis, xerostomia, and serological characteristics of patients with osteoarthritis and rheumatoid arthritis and identification of new biomarkers.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two different types of arthritis. Within RA, the subsets between seronegative RA (snRA) and seropositive RA (spRA) represent distinct disease entities; however, identifying clear distinguishing markers between them remains a challenge. This study investigated and compared the oral health conditions in patients with RA and OA to clarify the differences from healthy controls. In addition, we investigated the serological characteristics of the patients, the factors that distinguished patients with RA from those with OA, and the main factors that differentiated between snRA and spRA patients. A total of 161 participants (mean age: 52.52 ± 14.57 years, 32 males and 129 females) were enrolled in this study and categorized as: normal (n = 33), OA (n = 31), and RA (n = 97). Patients with RA were divided into the following two subtypes: snRA (n = 18) and spRA (n = 79). Demographics, oral health, and serological characteristics of these patients were compared. The prevalence of periodontal diseases was significantly higher in patients with OA (100%) and RA (92.8%) than in healthy controls (0.0%). However, the presence of periodontal diseases was not utilized as a distinguishing factor between OA and RA. Xerostomia occurred more frequently in patients with RA (84.5%) than in patients with OA (3.2%) and healthy controls (0.0%) (all p < 0.001). ROC analysis revealed that periodontal disease was a very strong predictor in the diagnosis of OA compared to healthy controls, with an AUC value of 1.00 (p < 0.001). Additionally, halitosis (AUC = 0.746, 95% CI 0.621-0.871, p < 0.001) and female sex (AUC = 0.663, 95% CI 0.529-0.797, p < 0.05) were also significant predictors of OA. The strongest predictors of RA diagnosis compared to healthy controls were periodontal diseases (AUC = 0.964), followed by xerostomia (AUC = 0.923), age (AUC = 0.923), female sex (AUC = 0.660), and halitosis (AUC = 0.615) (all p < 0.05). Significant serological predictors of RA were anti-CCP Ab (AUC = 0.808), and RF (AUC = 0.746) (all p < 0.05). In multiple logistic regression analysis, xerostomia (odds ratio, OR: 8124.88, 95% CI 10.37-6368261.97, p-value = 0.008) and Anti-CCP Ab (OR: 671.33, 95% CI 2.18-207,074.02, p = 0.026) were significant predictors for RA compared to OA. When diagnosing spRA compared to snRA, anti-CCP Ab (AUC = 1.000, p < 0.001) and RF (AUC = 0.910, 95%CI 0.854-0.967, p < 0.001) had outstanding predictive performances. Therefore, clinicians and researchers should thoroughly evaluate the oral status of both OA and RA patients, alongside serological factors, and consider these elements as potential predictors.

Porous Polyethylene Supports in Reinforcement of Multiblock Hydrocarbon Ionomers for Proton Exchange Membranes.

Hydrocarbon (HC)-based block copolymers have been recognized as promising candidates for proton exchange membranes (PEMs) due to their distinct hydrophilic-hydrophobic separation, which results in improved proton transport compared to that of random copolymers. However, most PEMs derived from HC-based ionomers, including block copolymers, encounter challenges related to durability in electrochemical cells due to their low mechanical and chemical properties. One method for reinforcing HC-based ionomers involves incorporating the ionomers into commercially available low surface tension PTFE porous substrates. Nevertheless, the high interfacial energy between the hydrocarbon-based ionomer solution and PTFE remains a challenge in this reinforcement process, which necessitates the application of surface energy treatment to PTFE. Here, multiblock sulfonated poly(arylene ether sulfone) (SPAES) ionomers are being reinforced using untreated PE on the surface, and this is compared to reinforcement using surface-treated porous PTFE. The PE support layer exhibits a lower surface energy barrier compared to the surface-treated PTFE layer for the infiltration of the multiblock SPAES solution. This is characterized by the absence of noticeable voids, high translucency, gas impermeability, and a physical and chemical stability. By utilizing a high surface tension PE support with a comparable value to the multiblock SPAES, effective reinforcement of the multiblock SPAES ionomers is achieved for a PEM, which is potentially applicable to various hydrogen energy-based electrochemical cells.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Antinociceptive and anti-inflammatory activity of DW-1021, the ionic complex of pelubiprofen and tramadol, in rodents.

Although drugs such as acetaminophen, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), are commonly used for pain management, the side effects of these drugs such as hepatotoxicity, nephrotoxicity, nausea, and vomiting, can not be neglected. Therefore, combinations of analgesics with different mechanisms raise the possibility of developing novel analgesics. Therefore, the aim of the present study was to evaluate whether DW-1021, the ionic complex of pelubiprofen (NSAID) and tramadol (opioid), has synergic antinociceptive and anti-inflammatory effects in nociceptive as well as inflammation-induced nociceptive models compared to pelubiprofen- or tramadol-only administration. Strong synergistic antinociceptive efficacy of DW-1021 was observed in the mouse writhing test and von Frey paw withdrawal threshold test in the carrageenan-induced rats. The hot plate test in mice and the Randall-Selitto mechanical paw pressure test in carrageenan-induced rats revealed that DW-1021 had a preferable effect on relieving pain to pelubiprofen, but not as much as tramadol. In the carrageenan-induced rats, DW-1021 had a more potent effect on reducing paw inflammation (paw volume, width, and thickness) via the suppression of PGE2 production than tramadol, but less than that of pelubiprofen. Taken together, our results suggest that the administration of DW-1021, a combination of pelubiprofen and tramadol, exerted a potent effect and can be used as a potential therapeutic agent for relieving pain and inflammation.

Erratum: Correction of Authors' Name Spelling in the Article "COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology".

This corrects the article on p. e95 in vol. 36, PMID: 33783147.

Progress in Oral Microbiome Related to Oral and Systemic Diseases: An Update.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is an environment that provides various biological niches, such as the teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome also plays an important role in the triggering, development, and progression of oral and systemic diseases. In recent years, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology and is overwhelmingly promising compared to the previous era. It has been found that patients with oral and systemic diseases have variations in their oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that the oral microbiome plays in influencing oral and systemic diseases and furthers the knowledge related to the oral microbiome produced over the past 30 years. A wide range of updates were provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and can help to develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

Segmented Polyurethanes and Thermoplastic Elastomers from Elemental Sulfur with Enhanced Thermomechanical Properties and Flame Retardancy.

The production of elemental sulfur from petroleum refining has created a technological opportunity to increase the valorization of elemental sulfur by the creation of high-performance sulfur based plastics with improved thermomechanical properties, elasticity and flame retardancy. We report on a synthetic polymerization methodology to prepare the first example of sulfur based segmented multi-block polyurethanes (SPUs) and thermoplastic elastomers that incorporate an appreciable amount of sulfur into the final target material. This approach applied both the inverse vulcanization of S8 with olefinic alcohols and dynamic covalent polymerizations with dienes to prepare sulfur polyols and terpolyols that were used in polymerizations with aromatic diisocyanates and short chain diols. Using these methods, a new class of high molecular weight, soluble block copolymer polyurethanes were prepared as confirmed by Size Exclusion Chromatography, NMR spectroscopy, thermal analysis, and microscopic imaging. These sulfur-based polyurethanes were readily solution processed into large area free standing films where both the tensile strength and elasticity of these materials were controlled by variation of the sulfur polyol composition. SPUs with both high tensile strength (13-24 MPa) and ductility (348 % strain at break) were prepared, along with SPU thermoplastic elastomers (578 % strain at break) which are comparable values to classical thermoplastic polyurethanes (TPUs). The incorporation of sulfur into these polyurethanes enhanced flame retardancy in comparison to classical TPUs, which points to the opportunity to impart new properties to polymeric materials as a consequence of using elemental sulfur.

Patient Perspectives and Preferences Regarding Gout and Gout Management: Impact on Adherence.

BACKGROUND: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). METHODS: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. RESULTS: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). CONCLUSION: Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Quality Indicators for Evaluating the Health Care of Patients with Rheumatoid Arthritis: a Korean Expert Consensus.

BACKGROUND: There is increasing interest in the quality of health care and considerable efforts are being made to improve it. Rheumatoid arthritis (RA) is a disease that can result in favorable outcomes when appropriate diagnosis and treatment are provided. However, several studies have shown that RA is often managed inappropriately. Therefore, the Korean College of Rheumatology aimed to develop quality indicators (QIs) to evaluate and improve the health care of patients with RA. METHODS: Preliminary QIs were derived based on the existing guidelines and QIs for RA. The final QIs were determined through two separate consensus meetings of experts. The consensus was achieved through a panel of experts who voted using the modified Delphi method. RESULTS: Fourteen final QIs were selected among 70 preliminary QIs. These included early referral to and regular follow-up with a rheumatologist, radiographs of the hands and feet, early initiation and maintenance of disease-modifying anti-rheumatic drug (DMARD) therapy, periodic assessment of disease activity, screening for drug safety and comorbidities, including viral hepatitis and tuberculosis before biologic DMARD therapy, periodic laboratory testing, supplementation with folic acid, assessment of the risk for cervical spine instability before general anesthesia, patient education, and specialized nurse. CONCLUSION: These QIs can be used to assess and improve the quality of health care for patients with RA.

The bone bridge significantly affects the decrease in bone mineral density measured with quantitative computed tomography in ankylosing spondylitis.

INTRODUCTION AND OBJECTIVE: Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction. METHODS: Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed. RESULTS: A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05). CONCLUSION: Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients.

PURPOSE: To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. MATERIALS AND METHODS: We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. RESULTS: According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with anti-TIF1γ, anti-SRP, and anti-MDA5. CONCLUSION: The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.

Real-world experiences of the diagnosis process in Korean patients with ankylosing spondylitis based on a self-report questionnaire.

OBJECTIVES: The diagnosis of ankylosing spondylitis (AS) is often delayed, which affects various clinical outcomes. This study examined the real-world situation of patients with AS during diagnosis and treatment. METHODS: Data were obtained from 26 tertiary care hospitals in Korea using a self-report questionnaire. The questionnaire assessed symptoms, pain, extra-articular manifestations, the initial pattern of pain before diagnosis, factors leading to delayed referral to rheumatology, time until receiving an AS diagnosis, comorbid diseases, treatment status, and disease education needs. RESULTS: Between September and October 2019, 1012 patients with AS completed the survey. Of these, 75.8% were men and 51.8% were in their 30s or 40s. Median disease duration was 76 months. The median time to diagnosis with AS was 12 months. When pain occurred, the medical departments most frequently visited first were orthopedic (61.5%) and rheumatology (18.7%) departments. The likelihood of the first visit being to the orthopedic department and the frequency of biologics use increased with the disease duration. The rates of uveitis, depressed mood, and comorbid diseases were higher in the group with delayed diagnosis. CONCLUSIONS: Physicians should be aware of subtypes of AS that take longer to diagnose and comorbid diseases in the real-world clinical setting.

COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1-2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.

Alcohol-Treated Porous PTFE Substrate for the Penetration of PTFE-Incompatible Hydrocarbon-Based Ionomer Solutions.

For a mechanically tough proton exchange membrane, a composite membrane incorporated with a porous polymer substrate is of great interest to suppress the ionomer swelling and to improve the dimensional stability and mechanical strength of the ionomers. For the composite membranes, good impregnation of substrate-incompatible ionomer solution into the substrate pores still remains one of the challenges to be solved. Here, we demonstrated a facile process (surface treatment with solvents compatible with both substrate and the ionomer solution) for the fabrication of the composite membranes using polytetrafluoroethylene (PTFE) as a porous substrate and poly(arylene ether sulfone) (SPAES) as a hydrocarbon-based (HC) ionomer. Appropriate solvents for the surface treatment were sought through the contact angle measurement, and it was found that alcohol solvents effectively tuned the surface property of PTFE pores to facilitate the penetration of the SPAES/N-methyl-2-pyrrolidone (NMP) solution into ∼300 nm pores of the substrate. Using this simple alcohol treatment, the SPAES/NMP contact angle was reduced in half, and we could fabricate the mechanically tough PTFE/HC composite membranes, which were apparently translucent and microscopically almost void-free composite membranes.

Predicting Imaging Remission in Rheumatoid Arthritis: a Case-control Ultrasound Study.

BACKGROUND: To elucidate the achievement rates of imaging remission and to examine the characteristics associated with imaging remission status among patients with rheumatoid arthritis (RA) who have attained clinical remission. METHODS: Ninety-seven patients with RA patients who had attained clinical remission, defined by DAS28-ESR < 2.6 were enrolled. Power Doppler ultrasonography (PDUS) was performed on 16 joints and 2 tendons, including the first to third metacarpophalangeal, second and third proximal interphalangeal, radiocarpal (RC), second and third metatarsophalangeal joints, and extensor carpi ulnaris tendons. They were graded based on a dichotomous assessment. The clinical and laboratory data of patients who had attained imaging remission were compared to those of patients who had attained only clinical remission. RESULTS: The imaging remission rate was 51.5% in patients who had attained clinical remission. Forty-seven patients (48.5%) were PDUS positive. Power Doppler was detected most frequently in the right RC joint (n = 40). PDUS positive patients had higher evaluator global assessment (EGA) scores (P < 0.001) than PDUS negative patients. PDUS positive patients also had higher clinical disease activity index and simplified clinical disease activity index scores than PDUS negative patients. Patients who had attained imaging remission had lower pain scores and used nonsteroidal anti-inflammatory drugs less frequently. Patients who had attained imaging remission had higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide levels. A low EGA score was found to be a predictor of imaging remission achievement among patients who had attained clinical remission. CONCLUSION: Only 51.5% of the patients with RA who had attained clinical remission were also in imaging remission. Patients who had attained imaging remission had lower EGA scores and higher RF levels than patients who had attained only clinical remission.

Comparison of the efficacy and safety of CELBESTA® versus CELEBREX® in patients with rheumatoid arthritis: a 6-week, multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority phase 4 clinical trial.

OBJECTIVES: Celecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is commonly used to reduce the incidence of gastrointestinal (GI) complications in patients with rheumatoid arthritis (RA). CELBESTA® is a generic equivalent to CELEBREX®, a celecoxib preparation. This study compared the efficacy and safety of CELBESTA® and CELEBREX® in patients with RA. METHODS: This was a multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority clinical trial. The primary endpoint was a change from baseline in self-assessed pain intensity determined using a 100-mm visual analog scale after 6 weeks of treatment. RESULTS: After a washout period, 119 eligible subjects were randomized to one of two groups (CELBESTA® group, n = 61; CELEBREX® group, n = 58). CELBESTA® was not inferior to CELEBREX® because the upper limit of two-sided 95% confidence interval (CI) for the difference between the two groups (difference in the least square [LS] mean, -8.68 mm; two-sided 95% CI -16.59 mm to -0.77 mm) was less than the non-inferiority margin (10 mm). There were no significant differences in GI complications and renal toxicity. CONCLUSIONS: CELBESTA® was not inferior to CELEBREX® with regard to the pain relief efficacy in RA patients, and the tolerability and safety profiles were excellent and at similar levels for both preparations.

Seasonal Variations and Associated Factors of Gout Attacks: a Prospective Multicenter Study in Korea.

BACKGROUND: We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. METHODS: We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. RESULTS: Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; -0.9%, fall; -1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. CONCLUSION: In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.