Effect of tumor necrosis factor α inhibitors on spinal radiographic progression in patients with ankylosing spondylitis.

AIM: To evaluate the effect of tumor necrosis factor α inhibitors (TNFi) on spinal radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Subjects were selected from patients at a single tertiary hospital between 1995 and 2014. Patients who used TNFi with baseline and paired follow-up radiographic data with a minimum interval of 2 years were included. Time to start TNFi was defined as the time from symptom onset to the start of TNFi use. TNFi index was defined as the ratio of the period of TNFi use to the entire period of disease. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Univariable and multivariable linear regression analyses were used to identify factors associated with radiographic progression. RESULTS: A total of 151 patients were included in the analysis. Seventeen (11.3%) patients were female and mean ΔmSASSS/year was 1.01 units/year. Mean X-ray follow-up duration was 102.9 ± 54.9 months. Mean time from symptom onset to start of TNFi use was 104.8 ± 83.6 months (median 84 months) and mean TNFi index was 42.9 ± 23.8% (median 40.9%). In multivariable analysis, initial mSASSS, initial C-reactive protein, body mass index, current smoker, and delayed start of TNFi use were associated with radiographic progression. Presence of peripheral arthritis and the TNFi index were negatively associated with radiographic progression. CONCLUSIONS: A delay in starting TNFi use and low TNFi index were associated with radiographic progression. Early and long-term use of TNFi appear to reduce spinal radiographic progression in patients with AS.

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.

Clinical characteristics and outcomes of 61 patients with chronic periaortitis including IgG4-related and non-IgG4-related cases.

AIM: Chronic periaortitis (CP) is a disease characterized by a fibro-inflammatory periaortic cuff and adventitia-predominant fibrosis. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (AAA), and recent studies have documented overlap between CP and immunoglobulin G4-related disease (IgG4-RD). This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP. METHOD: CP patients were identified by retrospective review of 1245 patients with International Classification of Diseases 10th edition code of aortitis or aortic disease. Patients were further classified into IgG4-related and non-IgG4-related CP according to the criteria proposed by a Japanese study. RESULTS: A total of 61 CP patients were identified. Patients showed a male predominance (70%) with median age of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), while the thoracic aorta was affected in 46% of patients. Twenty-three (38%) patients had accompanying aortic aneurysm. Approximately 60% of patients achieved remission without further relapse during the course. Ten patients were classified as IgG4-related and 25 as non-IgG4-related. There was no significant difference in clinical features and outcomes between groups, with the exception of older age and greater pancreas involvement in IgG4-related patients. CONCLUSION: We documented 61 CP patients including 10 IgG4-related cases. CP involved the abdominal aorta in most patients and the thoracic aorta in approximately 50% of patients. IgG4-related CP patients were older and had greater pancreas involvement, but disease outcomes appeared to be similar between IgG4-related and non-IgG4-related CP.

Comorbidities and health-related quality of life in Koreans with knee osteoarthritis: Data from the Korean National Health and Nutrition Examination Survey (KNHANES).

OBJECTIVES: This study aimed to evaluate the association of knee osteoarthritis (OA) with comorbidities and health-related quality of life (HRQOL). METHODS: A total of 8,907 (weighted n = 13,687,058) participants aged ≥50 years who had undergone knee radiography were selected from the 2010-2012 Korea National Health and Nutrition Examination Survey. OA was classified into four subgroups based on the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-), pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA was defined as Kellgren-Lawrence grade ≥ 2. HRQOL measurements including EuroQOL visual analogue scale (EQ-VAS) scores and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable logistic regression and linear regression analyses were performed. RESULTS: After adjustment for socioeconomic and lifestyle characteristics, cardiovascular disease, malignancy, and other comorbidities were not significantly associated with OA. Pain only and painful ROA were each significantly associated with limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07-3.44, p < 0.001 and OR 2.83, 95% CI 2.25-3.58, p < 0.001, respectively), lower EQ-VAS (ß-coefficient = -10.95, p < 0.001 and ß-coefficient = -9.75, p < 0.001, respectively), and EQ-5D index (ß-coefficient = -0.10, p < 0.001 and ß-coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only was not associated with limitations in physical activity or lower HRQOL score. CONCLUSIONS: Comorbidities were not significantly associated with knee OA after adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee OA, with or without ROA, was more strongly associated with decreased physical activity and lower quality of life than ROA without pain.

Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model.

BACKGROUND: Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is also more severe in males. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. This study aimed to evaluate the effect of estrogen on the disease activity of spondyloarthritis (SpA). METHODS: The effects of estrogen on the development of arthritis were evaluated by performing ovariectomy and 17ß-estradiol (E2) pellet implantation in zymosan-treated SKG mice. Clinical arthritis scores were measured, and 18F-fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography performed to quantify joint inflammation. The expression of inflammatory cytokines in joint tissue was measured. RESULTS: E2-treated mice showed remarkable suppression of arthritis clinically and little infiltration of inflammatory cells in the Achilles tendon and intervertebral disc. 18F-FDG uptake was significantly lower in E2-treated mice than in sham-operated (sham) and ovariectomized mice. Expression of TNF, interferon-γ, and IL-17A was significantly reduced in E2-treated mice, whereas expression of sclerostin and Dickkopf-1 was increased in E2-treated mice compared with sham and ovariectomized mice. CONCLUSIONS: Estrogen suppressed arthritis development in SKG mice, a model of SpA. Results of this study suggest that estrogen has an anti-inflammatory effect on the spondyloarthritis manifestations of the SKG arthritis model.

Correction: Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey.

[This corrects the article DOI: 10.1371/journal.pone.0176260.].

Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey.

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

Characteristics of hip involvement in patients with ankylosing spondylitis in Korea.

BACKGROUND/AIMS: To evaluate the clinical course of hip arthritis and the risk factors for hip joint replacement in patients with ankylosing spondylitis (AS). METHODS: In this retrospective analysis, we evaluated 488 AS patients at a single tertiary hospital. At baseline and the most recent visit to the outpatient clinic from the patients with hip arthritis in AS, radiographic hip arthritis was evaluated using the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h). Also the average of the hip joint space width (interbone distance) at three distinct sites between the acetabulum and femoral head was recorded. RESULTS: Among 488 patients with AS, 60 patients (12.3%) had hip arthritis. Erythrocyte sedimentation rate were associated with hip involvement (odds ratio, 1.01; 95% confidence interval [CI], 1.00 to 1.02; p = 0.004). Long disease duration and advanced axial disease were associated with severe hip arthritis (3 ≥ BASRI-h) at baseline. BASRI-h and interbone distance did not significantly change in patients with hip involvement during the follow-up period of 81.4 ± 35.7 months. Five patients had hip joint replacement surgery during follow-up period. The body mass index (BMI) and BASRI-h at baseline were associated with joint replacement surgery (hazard ratio [HR], 1.30; 95% CI, 1.00 to 1.67; p = 0.049 and HR, 20.64; 95% CI, 2.39 to 178.11; p = 0.006, respectively). CONCLUSIONS: Most of the patients with hip arthritis in AS showed no significant radiographic progression during the follow-up period. High BMI and advanced hip arthritis at baseline were associated with hip joint replacement surgery in patients with AS.

Evaluation of Audiometric Test Results to Determine Hearing Impairment in Patients with Rheumatoid Arthritis: Analysis of Data from the Korean National Health and Nutrition Examination Survey.

This study aimed to evaluate the association between rheumatoid arthritis (RA) and hearing impairment in the Korean adult population. Audiometric and laboratory test data from the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used for analysis. The relationship between RA and hearing impairment was analyzed, adjusting for various known risk factors associated with hearing impairment. RA was defined in the questionnaire as "RA diagnosed by a physician (yes/no) through a standardized interview." We defined hearing impairment according to 2 categories of frequency (low/mid and high) as follows (average values in kHz): low/mid frequency, 0.5, 1.0, and 2.0, and high frequency, 3.0, 4.0, and 6.0. Of the subjects, 15,158 (weighted n = 32,035,996) completed the audiometric tests. The overall weighted prevalence of RA was 1.5%. The prevalence of hearing impairment was higher in the subjects with RA than in those without RA, in both, the low/mid- and high-frequency categories (21.1% vs 7.5%, p < 0.001 and 43.3% vs. 26.2%, p < 0.001, respectively). In the multivariable logistic analysis, RA (odds ratios [OR] 1.47, 95% confidence interval [CI] 1.05-2.06, p = 0.025) was an independent risk factor of low/mid-frequency hearing impairment along with age (OR 1.12, 95% CI 1.12-1.13, p < 0.001), current smoking (OR 1.27, 95% CI 1.03-1.56, p = 0.026), and college graduation (OR 0.53, 95% CI 0.39-0.72, p < 0.001). In the multivariable analysis of high-frequency hearing impairment, RA did not show any association with hearing impairment. This study suggests that RA is associated with low/mid-frequency hearing impairment after adjustment for various known risk factors. Further study is needed to verify the hearing impairment in RA.

Wernicke's encephalopathy after total parenteral nutrition in patients with Crohn's disease.

Micronutrient deficiencies in Crohn's disease (CD) patients are not uncommon and usually result in a combination of reduced dietary intake, disease-related malabsorption, and a catabolic state. Decreased serum thiamine levels are often reported in patients with CD. Wernicke's encephalopathy (WE) is a severe form of thiamine deficiency that can cause serious neurologic complications. Although WE is known to occur frequently in alcoholics, a number of non-alcoholic causes have also been reported. Here, we report two cases of non-alcoholic WE that developed in two severely malnourished CD patients who were supported by prolonged total parenteral nutrition without thiamine supplementation. These patients complained of sudden-onset ophthalmopathy, cerebellar dysfunction, and confusion. Magnetic resonance imaging allowed definitive diagnosis for WE despite poor sensitivity. The intravenous administration of thiamine alleviated the symptoms of WE dramatically. We emphasize the importance of thiamine supplementation for malnourished patients even if they are not alcoholics, especially in those with CD.

Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.