Epidemiology and treatment-related concerns of gout and hyperuricemia in Korean

Gout is the most common form of inflammatory arthritis that affects mainly middle-aged men, and there is clear evidence of an association between hyperuricemia and the risk for gout. Increasing prevalence of gout and hyperuricemia has been reported in many countries. The prevalence of gout and hyperuricemia are constantly increasing in Korea with the patients at risk for developing a variety of comorbidities. Although there have been studies on the association between gout or serum uric acid level and several neurodegenerative diseases, cancer, and cardiovascular mortality, the causal relationship between gout and these comorbidities are still unclear. The associations of substantial economic burden with hyperuricemia, gout attack, and suboptimal treatment are well known. Gout is a disease that requires lifelong management including lifestyle modification. However, gout is poorly managed worldwide although effective urate-lowering drugs exist. In this review, we addressed epidemiological studies and treatment-related problems in the Korean population with gout or hyperuricemia to obtain the best clinical outcomes and reduce their medical burden.

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.

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.

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.

The Practice Guideline for Vaccinating Korean Patients With Autoimmune Inflammatory Rheumatic Disease

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and theKorean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measlesmumps- rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Rheumatoid Factor Positivity is Associated with Lower Bone Mass in Korean Male Health Examinees without Clinically Apparent Arthritis

OBJECTIVE: This cross-sectional study aimed to investigate the association between rheumatoid factor (RF) positivity and bone mineral density (BMD) in male Korean subjects without any history of joint disease. METHODS: Of 84,344 males who had undergone a comprehensive health checkup program in 2012, 1,390 male health examinees were recruited, whose BMD and RF results were available. A RF titer ≥20 IU/mL was considered positive. BMD was measured at lumbar spine (L1~L4) or hip (femoral neck and total hip) by dual-energy X-ray absorptiometry. RESULTS: The association between RF positivity and BMD was assessed by multiple linear regression analysis. The mean age was 52.7±10.9 years (range 19~88 years), and RF was detected in 64 subjects (4.6%). Demographics and laboratory data were not different between RF-positive and -negative subjects except hepatitis B surface antigen (HBsAg), which was more frequently seen in RF-positive subjects (15.6% vs. 4.3%, p=0.001). RF-positive subjects had significantly lower BMD compared to RF-negative subjects in lumbar spine but not in total hip regardless of the existence of HBsAg (1.17±0.16 g/cm2 vs. 1.10±0.18 g/cm2, p=0.002 in total subjects; 1.17±0.16 g/cm2 vs. 1.10±0.18 g/cm2, p=0.004 in HBsAg-negative subjects). After adjusting for multiple confounders, RF positivity was negatively associated with lumbar spine BMD (B=−0.088 and standard error=0.035, p=0.011). CONCLUSION: Our results show that the presence of RF could have an unfavorable impact on bone density in apparently normal males. Additional studies to elucidate the osteoimmunological mechanism of rheumatoid factor are warranted.

Drug survival of tumor necrosis factor α inhibitors in patients with ankylosing spondylitis in Korea

BACKGROUND/AIMS: To evaluate drug survival of the tumor necrosis factor α inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). METHODS: We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. RESULTS: Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of 65.1 ± 27.9 months. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. CONCLUSIONS: TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.

A Case of Relapsing Polychondritis Presenting with Diffuse Tracheobronchial Involvement

Relapsing polychondritis is a rare autoimmune disease involving the cartilaginous structures of the whole body. Its diagnosis can be difficult when the typical clinical features such as auricular chondritis are absent. Here, we report on a case of a 51-year-old female who presented with cough, dyspnea, and polyarthritis. Chest computed tomography showed the diffuse involvement of tracheobronchial cartilage. According to Damiani's criteria, she was diagnosed as relapsing polychondritis even though there was no unique involvement of auricular cartilage, and high dose steroid and immunosuppressive therapy were then started. This case indicated that patients who have tracheobronchial cartilage involvement without definite auricular chondritis should be considered for relapsing polychondritis as a differential diagnosis.

A Case of Sweet's Syndrome Diagnosed Concomitantly with Sjogren's Syndrome

Sweet's syndrome is an uncommon reactive dermatoses characterized by fever, polymorphonuclear leukocytosis, painful erythematous plaques, and dense dermal infiltrate of neutrophils. Sweet's syndrome can be associated with several diseases, including infectious diseases, malignant tumors, and autoimmune diseases. However, no case of Sweet's syndrome associated with Sjogren's syndrome (SjS) has been reported in Korea. A 44-year-old woman presented with acute pustular rashes and fever. The patient had multiple papulopustular skin rashes, and complained of fever, chills, and headache. Our patient had the characteristic clinical and histopathological features of Sweet's syndrome, in association with SjS, diagnosed by salivary gland scan, positive anti-SS-A/SS-B antibody, and sicca symptoms simultaneously. Thus, we report on a case of a patient with Sweet's syndrome with concomitant diagnosis of SjS.

Predictive factors of radiographic progression in ankylosing spondylitis

BACKGROUND/AIMS: The course of ankylosing spondylitis (AS) is rather variable, and the factors that predict radiographic progression remain largely obscure. In this study, we tried to determine the clinical factors and laboratory measures that are useful in predicting the radiographic progression of patients with AS. METHODS: In 64 consecutive patients with AS, we collected radiographic and laboratory data over 3 years. Radiographic data included images of the sacroiliac (SI) and hip joints and laboratory data included areas under the curve (AUC) of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alkaline phosphatase (ALP), and hemoglobin (Hb). We investigated associations among changes in radiographic scores, initial clinical manifestations and laboratory measurements. RESULTS: Changes in scores for the SI joint and lumbar spine did not correlate with AUC for ESR, CRP, or ALP. AUC for Hb did not significantly correlate with radiographic progression in any joint. Patients with hip arthritis at the initial visit showed significantly higher radiographic score changes after 3 years in the SI and hip joint compared to those without hip arthritis. Patients who had shoulder arthritis as the initial manifestation had significantly increased AUCs for ESR and CRP compared to those without shoulder arthritis. However, at 3 years, the change of the lumbar spine score was significantly higher in patients without shoulder arthritis. CONCLUSIONS: These results indicate that hip arthritis at presentation is a useful clinical marker for predicting the structural damage to the SI and hip joint, and suggest that initial shoulder arthritis correlates with slower radiographic progression of the lumbar spine.

Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra / 대한내과학회지

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.

Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra / 대한내과학회지

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.

Correlation of DEFA1 Gene Copy Number Variation with Intestinal Involvement in Behcet's Disease

Copy number variation has been associated with various autoimmune diseases. We investigated the copy number (CN) of the DEFA1 gene encoding alpha-defensin-1 in samples from Korean individuals with Behcet's disease (BD) compared to healthy controls (HC). We recruited 55 BD patients and 35 HC. A duplex Taqman(R) real-time PCR assay was used to assess CN. Most samples (31.1%) had a CN of 5 with a mean CN of 5.4 +/- 0.2. There was no significant difference in the CN of the DEFA1 gene between BD patients and HC. A high DEFA1 gene CN was significantly associated with intestinal involvement in BD patients. Variable DEFA1 gene CNs were observed in both BD patients and HC and a high DEFA1 gene CN may be associated with susceptibility to intestinal involvement in BD.

Extracellular High-Mobility Group Box 1 is Increased in Patients with Behcet's Disease with Intestinal Involvement

High-mobility group box 1 (HMGB1) protein has been demonstrated to play an important role in chronic inflammatory diseases including rheumatoid arthritis, and systemic lupus erythematosus. This study investigated the association between extracellular HMGB1 expression and disease activity, and clinical features of Behcet's disease (BD). Extracellular HMGB1 expression in the sera of 42 BD patients was measured and was compared to that of 22 age- and sex-matched healthy controls. HMGB1 expression was significantly increased in BD patients compared to healthy controls (78.70 +/- 20.22 vs 10.79 +/- 1.90 ng/mL, P = 0.002). In addition, HMGB1 expression was significantly elevated in BD patients with intestinal involvement compared to those without (179.61 +/- 67.95 vs 61.89 +/- 19.81 ng/mL, P = 0.04). No significant association was observed between HMGB1 concentration and other clinical manifestations, or disease activity. It is suggested that extracellular HMGB1 may play an important role in the pathogenesis of BD.

Enthesitis in a Patient with Systemic Lupus Erythematosus: The First Case Report / 대한내과학회지

We present the first case of enthesitis in the lumbar spine in a woman with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Enthesopathy is defined as pathological alterations at the site of insertion of a tendon, ligament, joint capsule, or fascia to bone. In particular, enthesitis is the universal hallmark of seronegative spondyloarthropathies (SpA), including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and spondyloarthropathies associated with inflammatory bowel diseases. A 36-year-old female SLE patient with a history of lupus nephritis and thrombosis from APS presented with low back pain that had been gradually worsening for several months. She reported no previous episodes of trauma. Plain radiography indicated sclerosis at the anterior superior bodies of L3 and L5. Magnetic resonance imaging (MRI) showed low-intensity lesions on T1-weighted images and high-intensity lesions on T2-weighted images at the anterior superior bodies of L3, L4, and L5, consistent with osteitis or enthesitis. A nonsteroidal antiinflammatory drug (NSAID) was used as the first-line therapy in this patient, which improved her symptoms. This is the first report of enthesitis in the context of SLE. Although the possibility of coincidental occurrence of SpA and SLE cannot be excluded, the observations in this case suggest that enthesitis may be one of the manifestations of SLE.

Exacerbation of Psoriatic Skin Lesion followed by TNF-alpha Antagonist Treatment / 대한류마티스학회지

TNF-alpha antagonists have been successfully utilized in the treatment of autoimmune diseases, including psoriasis and psoriatic arthritis. Paradoxically, new onset or exacerbation of psoriatic lesions during treatment with TNF-alpha antagonists have been reported. It has been postulated that TNF-alpha blockade may cause disruption in the balance between TNF-alpha and type 1 interferon (IFN)-alpha, which are the key players in the pathogenesis of psoriasis. We report a case of psoriasis exacerbation during TNF-alpha antagonist therapy in a 53-years-old man with ankylosing spondylitis. The patient has been treated with etanercept for 3 years and 7 months when he developed accelerated deterioration of psoriasis. His condition was previously under control solely by local treatment. Physical examination revealed vigorous desquamative lesions with silvery scale in both lower legs. Deterioration of psoriasis was attributed to etanercept therapy and was subsequently discontinued. Clinical improvement of psoriasis has been observed 2 months following cessation of etanercept.

Clinical manifestations and diagnosis of systemic lupus erythematosus / 대한내과학회지

Systemic lupus erythematosus (SLE) is a multi-system, autoimmune disorder of unknown cause, characterized by the production of autoantibodies and wide ranging spectrum of clinical manifestations. SLE can involve any organ system of the body with constitutional symptoms, including musculoskeletal, skin, renal, neuropsychiatric, cardiovascular, respiratory and gastrointestinal system. American College of Rheumatology classifications criteria for SLE can be helpful when establishing the diagnosis of SLE. However, these criteria would not do for physicians to give a diagnosis of SLE because these were designed for classification for research purpose and not for diagnosis. The diagnosis of SLE remains largely clinical. Thus, increasing awareness of the clinical manifestations could lead to earlier diagnosis. The clinical manifestations and diagnosis of SLE are covered in this review.

Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide

Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study, we examined the expression and function of Slug in RA FLS. Slug mRNA expression was measured in the synovial tissue (ST) and FLS obtained from RA and osteoarthritis patients. Slug and Puma mRNA expression in FLS by apoptotic stimuli were measured by real-time PCR analysis. FLS were transfected with control siRNA or Slug siRNA. Apoptosis was quantified by trypan blue exclusion, DNA fragmentation and caspase-3 assay. RA ST expressed higher level of Slug mRNA compared with osteoarthritis ST. Slug was significantly induced by hydrogen peroxide (H2O2) but not by exogenous p53 in RA FLS. Puma induction by H2O2 stimulation was significantly higher in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. After H2O2 stimulation, viable cell number was significantly lower in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. Apoptosis enhancing effect of Slug siRNA was further confirmed by ELISA that detects cytoplasmic histone-associated DNA fragments and caspase-3 assay. These data demonstrate that Slug is overexpressed in RA ST and that suppression of Slug gene facilitates apoptosis of FLS by increasing Puma transactivation. Slug may therefore represent a potential therapeutic target in RA.