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.

Relationship between Urate Crystal Deposits Detected by Dual-energy Computed Tomography and Bone Erosions in Symptomatic Gout Patients without Clinically Apparent Tophi

OBJECTIVE: Dual-energy computed tomography (DECT) allows sensitive detection of monosodium urate (MSU) crystal deposits in gout. However, the role of MSU deposits on DECT during the disease process of gout is not clear. The aim of our study was to evaluate the relationship between joint damage and MSU deposits detected by DECT in symptomatic non-tophaceous gout. METHODS: DECT scans of 51 gout patients without clinically apparent tophi were assessed. Individual ankle and foot joints and Achilles tendon insertion sites were evaluated for the presence of MSU deposits and bone erosions. The total volume of MSU crystal on DECT was quantified using an automated software program. Clinical and laboratory data at the time of the DECT evaluation were obtained from medical record. RESULTS: MSU deposits were detected in 92.2% of the patients evaluated. Median number and total volume of MSU deposit per patient was 5.0 and 0.6 cm3, respectively. Bone erosion was found in 54.9% of patients. MSU deposits in the first (1st) metatarsophalangeal (MTP) joints were significantly associated with presence of bone erosions (odds ratio [OR] 3.77, 95% confidence interval [CI] 1.06~13.38, p=0.040). Older age and frequent gout attack were associated with development of bone erosion in patients with MSU deposits (OR 1.12 and 2.57, 95% CI 1.04~1.22 and 1.02~6.50, p-value 0.004 and 0.047, respectively). CONCLUSION: MSU deposits and erosions were frequently detected by DECT in symptomatic non-tophaceous gout patients, and MSU deposits in 1st MTP joints were associated with presence of bone erosions especially in patients with older age and frequent gout attack.

A Case of Rheumatoid Vasculitis Involving Hepatic Artery in Early Rheumatoid Arthritis

Rheumatoid vasculitis is a rare, but most serious extra-articular complications of long-standing, seropositive rheumatoid arthritis (RA). Vasculitis of hepatic artery is an extremely rare but severe manifestation of rheumatoid vasculitis. A 72-year-old woman who presented with polyarthralgia for 2 months was diagnosed with early RA. Since she had manifestations of livedo reticularis, and liver dysfunction which was atypical for RA patients, a percutaneous needle liver biopsy was performed revealing arteritis of a medium-sized hepatic artery. Extensive investigations did not reveal evidences of other systemic causes such as malignancy or systemic vasculitis. The patient was diagnosed with rheumatoid vasculitis involving hepatic arteries based on Bacon and Scott criteria for rheumatoid vasculitis. With high dose corticosteroid and cyclophosphamide induction and methotrexate and tacrolimus maintenance treatment, she was successfully recovered. Association of rheumatoid vasculitis at very early stages of the disease may represent an early aggressive form of RA.

Prevalence and Risk Factors Associated with Neutropenia in Hospitalized Patients with Systemic Lupus Erythematosus

OBJECTIVE: This study estimated the prevalence and explored possible risk factors associated with neutropenia in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: This review included 160 admissions of 85 SLE patients between 2006 and 2013. Neutropenia was defined as absolute neutrophil count (ANC) below 1,500/mm³. The baseline characteristics of the patients were compared between patients who experienced neutropenia and those who did not. Clinical and serological factors related to neutropenia episodes during admission were analyzed. RESULTS: Thirty-five (21.9%) neutropenic episodes were found among the 160 admissions. Most of the neutropenic episodes were mild to moderate. Severe neutropenia of ANC <500/mm³ occurred in 3.1% of the cases. Patients with neutropenia had higher frequencies of ANA (100.0% vs. 86.8%, p=0.042) and anti-double stranded DNA (87.5% vs. 60.4%, p=0.008), and satisfied more SLE classification criteria at the time of diagnosis than those without (5.1 vs. 4.6, p=0.009). Anemia, leukopenia, thrombocytopenia and low complement levels were frequently accompanied with neutropenia. Chronic kidney disease (odds ratio, 11.17; 95% confidence interval, 1.46∼85.27; p=0.020) was associated with neutropenia. CONCLUSION: This study demonstrates that neutropenia is frequent in hospitalized patients with SLE, and patients with neutropenia have more hematologic and immunologic abnormalities. Renal damage was more frequent among those presenting with neutropenia.

Outcome of Localized Granulomatosis with Polyangiitis: A Case Study

OBJECTIVE: A substantial portion of granulomatosis with polyangiitis (GPA) patients present with localized disease limited to the upper respiratory tract, however; disease spectrum and prognosis of these patients are unclear. The aim of this study is to describe the clinical characteristics and outcome of patients with localized GPA. METHODS: This was a retrospective descriptive case series of patients with a biopsy proven localized GPA presenting to a single tertiary rheumatology service between January 1995 and September 2015. RESULTS: A total of 5 patients, median age 56 years (range 48 to 59 years) at diagnosis and 80% female, were identified. The median follow-up period was 42 months (range 15 to 62 months). Diagnosis was delayed with median time to diagnosis of 12 months (range 3 to 36 months), and patients underwent 1-3 ear, nose, and throat surgeries during the period of diagnostic delay. Sinusitis was the most frequent symptom in all patients, followed by otomastoiditis with cranial nerve palsies (n=2) and orbital mass (n=1). Antineutrophil cytoplasmic antibody (ANCA) was positive initially in 2/5 patients (40%). Two patients with otomastoiditis and cranial nerve palsies progressed to systemic disease with ANCA positive conversion. These two cases along with a case with orbital mass were refractory to standard treatment of cyclophosphamide with glucocorticoids requiring rituximab treatment. CONCLUSION: Patients with localized GPA may progress to systemic disease over the disease course, and may have aggressive disease refractory to standard treatment. Close monitoring for systemic symptoms and repeated ANCA testing is required in patients with localized GPA.

Progressive Pituitary Involvement in a Patient with Localized Granulomatosis with Polyangiitis / 이화의대지

Localized granulomatosis with polyangiitis (loc-GPA) is a milder disease state of GPA restricted to the respiratory tract. Transition from localized form to systemic/generalized disease is predicted to occur in approximately 10% of the patients. We report an unusual case of loc-GPA involving multiple cranial nerves, which in 3 years progressed into systemic disease involving pituitary gland. Initially antineutrophil cytoplasmic antibody (ANCA) was negative, but as symptoms of diabetes insipidus started, ANCA became positive. Clinical course of ANCA negative loc-GPA should be carefully monitored for development of systemic disease. ANCA may be a useful marker for detecting transition from localized to systemic disease.

Impact of Childbearing Decisions on Family Size of Korean Women with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years and has a significant impact on childbearing. We investigated the influence of personal decision on family size among Korean women with SLE and factors that affect the decisions. A case-control study comparing childbearing history and decisions of 112 SLE patients and 135 controls was performed. Women with SLE participating in the Network for Lupus Clinical Research in South Korea and matching controls between ages of 18-45, who are/were married or living with a partner were included. Data regarding socio-demographics, reproductive history, and childbearing decisions were collected through a survey using a standardized questionnaire and medical record review. More women with SLE reported at least one pregnancy (85.7% vs. 71.9%, P = 0.009) or at least one live birth (85.7% vs. 71.9%, P = 0.003) compared with controls. Mean number of pregnancies was significantly higher (2.4 ± 1.6 vs. 1.4 ± 1.3, P < 0.001), and mean number of live births was significantly lower in women with SLE (1.2 ± 0.8 vs. 1.6 ± 0.8, P < 0.001). Significantly more women with SLE made the decision not to have children compared with controls (54.5% vs. 40.7%, P = 0.031), and health-related concerns were the major cause of the decision. Other socio-demographic factors did not influence the decision to limit childbearing in SLE women. The disease-related concerns had significant impact on family size and childbearing decisions among Korean women with SLE.

Clinical Characteristics of Korean Rheumatoid Arthritis Patients with Indications for TNF-alpha Blocker

OBJECTIVE: The aim of this study was to examine clinical characteristics of Korean rheumatoid arthritis (RA) patients with clinically indications for TNF-alpha blocker, and to compare their clinical parameters with the Korean National Health Insurance reimbursement criteria. METHODS: Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym University affiliated hospitals. Among patients who were previously prescribed DMARDs for more than three months, rheumatologists selected patients clinically indicated for TNF-alpha blocker. The clinical characteristics at the time TNF-alpha blocker use was deemed indicated were examined. Radiographic damage was quantified by Modified Sharp van der Heijde score in hand and foot simple AP radiograph. RESULTS: From August 2010 to January 2013, five rheumatologists in four hospitals selected 109 patients clinically indicated for TNF-alpha blocker. When TNF-alpha blocker was considered, mean DAS28 was 5.2 (range 2.1~8.05), mean swollen joint count was 6 (range 0~22), mean tender joint count was 10.6 (range 0~28), mean ESR was 43.2 mm/hr (range 1~140) and mean CRP was 2.5 mg/dL (range 0.1~18.3). The mean total modified Sharp van der Heijde score was 32.72 (range 0~240). Eighty one percent of subjects did not have enough active joints to satisfy the Korean National Health Insurance reimbursement standard. CONCLUSION: Our results show that patients with clinically indications for TNF-alpha blocker had a broad range of disease activity and clinical parameters, and the majority did not meet the Korean National Health Insurance reimbursement criteria.

Comparison Korean National Health Insurance Reimbursement and Other Guidelines for TNF-alpha Blocker in Rheumatoid Arthritis

OBJECTIVE: The aim of this study was to examine how many Korean rheumatoid arthritis (RA) patients fulfilling the 2008 American College of Rheumatology (ACR) recommendation, 2007 British Society for Rheumatology (BSR) guideline and 2010 Japan College of Rheumatology (JCR) guideline for TNF-alpha blocker, meet the Korean National Health Insurance reimbursement criteria and to evaluate the reasons for failing the Korean National Health Insurance reimbursement criteria. METHODS: Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym university affiliated hospitals. Patients who were previously prescribed with methotrexate or leflunomide for more than 3 months and had at least one DAS28 examination were included in the present study. RESULTS: Of 642 patients included, 118 episodes meeting ACR guideline for using TNF-alpha blocker were identified in 88 patients (13.7%). In addition, 19 episodes meeting BSR guideline in 17 patients (2.6%) and 21 episodes meeting JCR guideline in 21 patients (6.2%) were identified. Four episodes (4.8%) meeting ACR recommendation, 0 episodes meeting BSR criteria and 5 episodes (12%) meeting JCR criteria, respectively, were eligible for TNF-alpha blocker according to the Korean National Health Insurance reimbursement guideline. The most common reason for failing the Korean National Health Insurance reimbursement criteria was the number of active joint counts (92.6%). CONCLUSION: Our results show that the majority of RA patients satisfying the ACR guideline, BSR and JCR guideline for use of the TNF-alpha blocker did not meet the Korean National Health Insurance reimbursement criteria. Patients most often failed due to active joint count criteria.

Survey of Current Trends for Diagnosis and Treatment in Korean Gout Patients

OBJECTIVE: The prevalence of gout has increased so accurate diagnosis and constant treatment is important in its management. The purpose this study was to examine the current trends in the diagnosis and treatment of gout patients in Korea. METHODS: We enrolled patients who were diagnosed as having gout and received treatment in university hospital between 2005 and 2008. From the survey, we assessed and analyzed the patient's baseline characteristics, clinical aspects of gout attack, medical institution and specialized department in the first gouty attack, medical institution and specialized department where the gout was initially diagnosed, methods of diagnosis, treatment during gout attack, and knowledge about gout in patients. RESULTS: A total of 136 patients were included in this study, out of which 123 (90.4%) were male and the mean age was 55.2 (range 25~85) years. When patients experienced the first gout attack, the most common medical institution that they attended was a private clinic and the most common specialized department was orthopedics. Medication by oral route was the major method (80.9%) used for the treatment of gout, and the most common medication was a non-steroidal anti-inflammatory drug (NSAID) in 55.9%, allopurinol in 38.2% and colchicine in 20.6% of patients. Many gout patients inappropriately received allopurinol following signs of gout arthritis attack, with little information specifically about gout. CONCLUSION: In our survey, many gout patients received inadequate medications for the treatment of gout and had little knowledge about the disease. For the adequate treatment of gout, patients and doctors need to be educated sufficiently.

Prevalence of Knee Pain and Its Influence on Quality of Life and Physical Function in the Korean Elderly Population: A Community Based Cross-Sectional Study

To investigate the prevalence of knee pain and its influence on physical function and quality of life (QOL), we examined 504 community residents of Chuncheon, aged > or = 50 yr. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee anteroposterior radiographs. Self-reported QOL and function were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12 (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The prevalence of knee pain was 46.2% (32.2% in men and 58.0% in women) and increased with age in women. After adjustment of confounders including the presence of knee OA, the subjects with knee pain had significantly worse WOMAC function and SF-12 scores compared to subjects without knee pain. Among the subjects with knee pain, women had worse WOMAC and SF-12 scores than men. Subjects with knee pain had worse physical performance score compared to those without knee pain, especially among females. In conclusion, the prevalence of knee pain is high (32.2% in men and 58.0% in women) in this elderly community population in Korea. Independent of knee OA and other confounding factors, subjects with knee pain have more than 5-fold increase in the risk of belonging to the worst lower extremity function compared to subjects without knee pain.

Adherence to Uric Acid Lowering Agent of Gouty Patients / 대한류마티스학회지

OBJECTIVE: Gout is crystal-induced arthritis with hyperuricemia. Uric acid lowering agent (UALA) is the maintenance drug of its treatment. Drug adherence is an important factor that influences treatment outcome. The purpose this study was to examine the drug adherence to UALA of 303 gouty patients and to analyze the factors associated with compliance. METHODS: We retrospectively assessed adherence to UALA in 303 patients who visited three hospitals affiliated with Hallym University. Patients were diagnosed as gout and used UALA with at least 6 month follow-up. Two adherence measures were calculated, the percentage of days covered (PDC) and the time until an extended break (at least 60 days) in treatment. A PDC <70% was considered poor adherence and factors associated with poor adherence were examined. RESULTS: Among the 303 patients, 283 (93.4%) were male. Mean age was 55.4+/-13.7 years. Comorbidities included hypertension in 117 (38.6%), diabetic mellitus in 108 (35.6%), angina in 107 (35.3%), myocardial infarction in 108 (35.6%), and heart failure in 113 (37.3%). The mean PDC was 65.8% with 63.4% of patients considered poorly compliant over the study period. Mean treatment duration before an extended break occurred was 203.5 days. Factors associated with good adherence included hypertension and prescription from rheumatologist. CONCLUSION: In our study, adherence to UALA in gouty patient was poor. Understanding the factors associated with adherence to UALA and proper education of gouty patients to improve drug adherence are needed.

HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression / 대한해부학회지

During the prostate cancer (PCa) development and its progression into hormone independency, androgen receptor (AR) signals play a central role by triggering the regulation of target genes, including prostate-specific antigen. However, the regulation of these AR-mediated target genes is not fully understood. We have previously demonstrated a unique role of HOXB13 homeodomain protein as an AR repressor. Expression of HOXB13 was highly restricted to the prostate and its suppression dramatically increased hormone-activated AR transactivation, suggesting that prostate-specific HOXB13 was a highly potent transcriptional regulator. In this report, we demonstrated the action mechanism of HOXB13 as an AR repressor. HOXB13 suppressed androgen-stimulated AR activity by interacting with AR. HOXB13 did neither bind to AR responsive elements nor disturb nuclear translocation of AR in response to androgen. In PCa specimen, we also observed mutual expression pattern of HOXB13 and AR. These results suggest that HOXB13 not only serve as a DNA-bound transcription factor but play an important role as an AR-interacting repressor to modulate hormone-activated androgen receptor signals. Further extensive studies will uncover a novel mechanism for regulating AR-signaling pathway to lead to expose new role of HOXB13 as a non-DNA-binding transcriptional repressor.

A Case of Abdominal Aortic Pseudoaneurysm That Was Treated with Inserting an Endovascular Stent Graft in a Patient with Behcet's Disease / 대한류마티스학회지

Behcet's disease is a chronic inflammatory disease of an unknown etiology, and it is characterized by recurrent oral and genital ulcerations, eye lesions skin lesions, and other involvement such as gastrointestinal ulcerations and lesions of the central nervous system and major vessels. The vascular lesions include deep vein thrombosis, superficial thrombophlebitis, arterial aneurysm and arterial occlusion. Aortic aneurysm or pseudoaneurysm is a rare complication, but it is one of the most common causes of death in Behcet's disease. We report here on a case of a 43 year old female with Behcet's disease that was complicated by an abdominal aortic pseudoaneurysm, and this was all successfully treated with percutaneous endovascular stent graft insertion, steroid pulse therapy and azathioprine.

Exacerbation of Sarcoidosis Following Interferon-alpha Therapy for Chronic Active Hepatitis C / 결핵및호흡기질환

Interferon alpha is an immunomodulator that is used as an antiviral agent to treat chronic active viral hepatitis C. However, interferon can induce or exacerbate sarcoidosis. We report a case of 42-year-old man with an exacerbation of pulmonary sarcoidosis after the cessation of interferon and ribavirin therapy for chronic hepatitis C. The patient's sarcoidosis improved spontaneously and he continues to be monitored regularly without steroid therapy.

Delayed Ventricular Septal Rupture after Percutaneous Coronary Intervention in Acute Myocardial Infarction

In the era before reperfusion therapy, ventricular septal rupture complicated 1~3% of acute myocardial infarctions (AMI) usually 3-5 days after onset. Studies have reported a positive correlation between the incidence of septal perforation and total occlusion of the coronary arteries. A 70-year old female patient was referred to the emergency room with the diagnosis of acute anterior myocardial infarction (MI) and recent cerebral infarction. The coronary angiogram showed a 90% stenosis at the mid-portion of the left anterior descending artery (LAD), and the lesion was successfully treated by percutaneous coronary intervention (PCI) with stent implantation. After PCI, the anterior wall motion improved on the follow-up echocardiogram. However, on the 20th hospital day, the patient condition deteriorated suddenly with pulmonary congestion. The echocardiography revealed a 1.3 cm ventricular septal defect at the apical septum with a left-to-right shunt. We report this rare case of delayed septal rupture in a patient with patent LAD after PCI and recovery of wall motion.