Differential Diagnosis of Inflammatory Arthropathy Accompanying Active Tuberculosis Infection.

Objective: The study aimed to ascertain the clinical manifestations of inflammatory arthritis accompanying tuberculosis (TB) for the differential diagnosis. Methods: We retrospectively reviewed patients with active TB who presented with inflammatory arthropathy at Seoul Medical Center. Among 2,872 patients with active TB infection, 47 had inflammatory arthropathy 14 had crystal-induced arthropathy; 12, TB arthritis; 12, Poncet's disease (PD); 8, Rheumatoid arthritis (RA); and 1, septic arthritis. The clinical characteristics and laboratory and radiographic findings of each group were analyzed. Results: In TB arthritis, weight-bearing joints were more commonly affected than the elbow and wrist joints. When compared to TB arthritis, PD demonstrated a significantly higher proportion of polyarthritis and involved both large and small-to-medium-sized joints. The duration of arthritis symptoms after anti-TB treatment was significantly shorter in patients with PD (56 days vs. 90 days, p=0.028). When compared to PD, RA flares during active TB infection involved only small-to-medium-sized joints rather than a mixed distribution (62.5% vs. 16.7%, p=0.035). Patients with PD more commonly had fever at onset and showed a good response to nonsteroidal anti-inflammatory drugs alone or were in remission within 3 months after anti-TB treatment. The presence of rheumatoid factor or anti-cyclic citrullinated peptide and radiographic progression after 12 months was frequently observed in patients with RA flares. Conclusion: The differential diagnosis of inflammatory arthritis accompanying active tuberculosis infection is challenging. Comprehensive history taking and physical examination, synovial fluid analysis, and a high level of clinical suspicion are essential to avoid delayed diagnosis and to reduce the significant morbidity involved.

Isolated Tuberculous Myositis: A Systematic Review and Multicenter Cases.

Objective: To investigate the clinical features and associated underlying conditions of isolated tuberculous myositis (ITBM), a rare extrapulmonary tuberculosis (TB). Methods: A systematic literature search and a multicenter survey were performed using a triangulation strategy. Data from the identified ITBM cases were extracted and analyzed to determine the underlying conditions, clinical presentations, treatments, and outcomes. Results: Based on the systematic review, we identified 58 ITBM, including 9 pediatric, cases in the literature published from 1981 to 2021 25 (43.1%) immunocompromised and 33 (56.9%) non-immunocompromised patients. Immunocompromised cases had a significant shorter symptom duration (median 30.0 vs. 75.0 days) and a higher prevalence of multilocular involvement (20.8% vs. 0%). Among 24 immunocompromised adult patients, dermatomyositis/polymyositis (DM/PM; n=10, 41.7%) were the most common underlying diseases in adults with ITBM identified in the systematic review. Over the past 20 years, 11 Korean adults with ITBM were identified in the multicenter survey. Of 7 immunocompromised cases, two (28.6%) were DM/PM patients. TB death rate of immunocompromised patients was 0.0% and 5/23 (21.7%) in the pediatric and adult ITBM cases identified in the systematic review, respectively, and 3/7 (42.9%) in survey-identified ITBM cases. Conclusion: ITBM has a unique clinical presentation including fever, tenderness, local swelling, overlying erythema, abscess formation and was associated with a grave outcome, especially in immunocompromised hosts. DM/PM was a highly prevalent underlying disease in both systematic review-identified and survey-identified immunocompromised ITBM patients.

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.

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.

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.

Health-related Quality of Life Outcomes of Adalimumab for Patients With Rheumatoid Arthritis in Korea.

Objective: Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients' overall health-related quality of life (HRQOL) In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. Methods: Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints >32 and were biologics-naïve All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24 Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. Results: In total, 91 Korean patients were included Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 61 within all patients The mean change from baseline in HAQ-DI scores were -046 at week 12 and∼067 at week 24 (p<00001) Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p<00001) compared to baseline SF-36 at weeks 12 and 24 had significantly improved (p<00001, p=00001) compared to baseline. Conclusion: Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient.

Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study.

To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography-computed tomography (PET-CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK.Trial registration number NCT02457585.

CXCL10/CXCR3 axis is associated with disease activity and the development of mucocutaneous lesions in patients with Behçet's disease.

The objective of this study was to investigate CXC chemokines and its receptor in patients with Behcet's disease (BD) and their associations with disease activity. Blood samples were collected from 109 BD patients and 36 age- and sex-matched healthy controls (HCs). Twenty-two follow-up blood samples were collected in BD patients. Serum CXC chemokines (CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) and cell surface marker expression (CD3, CD4 and CXCR3) in peripheral blood mononuclear cells (PBMCs) were assayed. Clinical features including disease activity were evaluated at the time of blood collection. CXCR3 expression in skin and intestinal lesions from BD patients and HCs was assessed via immunohistochemistry. Serum CXCL10 levels were correlated with disease activity in terms of Behçet's Disease Current Activity Form (BDCAF) (p < 0.001). In follow-up BD patients, changes in serum CXCL10 levels tended to be correlated with those of BDCAF. The percentage of CXCR3 expression in CD3-positive cells in PBMCs was inversely correlated with serum CXCL10 levels in BD patients (p = 0.022). By immunohistochemistry, the number of CXCR3-positive mononuclear cells was higher in skin and intestinal lesions of BD patients than in those of HCs. These results suggest that the CXCL10/CXCR3 axis may contribute to the pathogenesis of BD.

Heart Rate Variability for Quantification of Autonomic Dysfunction in Fibromyalgia.

OBJECTIVE: To quantify autonomic dysfunction in fibromyalgia patients compared to healthy controls using heart rate variability (HRV). METHODS: Sixteen patients with fibromyalgia and 16 healthy controls were recruited in this case control study. HRV was measured using the time-domain method incorporating the following parameters: total heartbeats, the mean of intervals between consecutive heartbeats (R-R intervals), the standard deviation of normal to normal R-R intervals (SDNN), the square root of the mean squared differences of successive R-R intervals (RMSSD), ratio of SDNN to RMSSD (SDNN/RMSSD), and difference between the longest and shortest R-R interval under different three conditions including normal quiet breathing, rate controlled breathing, and Valsalva maneuver. The severity of autonomic symptoms in the group of patients with fibromyalgia was measured by Composite Autonomic Symptom Scale 31 (COMPASS 31). Then we analyzed the difference between the fibromyalgia and control groups and the correlation between the COMPASS 31 and aforementioned HRV parameters in the study groups. RESULTS: Patients with fibromyalgia had significantly higher SDNN/RMSSD values under both normal quiet breathing and rate controlled breathing compared to controls. Differences between the longest and shortest R-R interval under Valsalva maneuver were also significantly lower in patients with fibromyalgia than in controls. COMPASS 31 score was negatively correlated with SDNN/RMSSD values under rate controlled breathing. CONCLUSION: SDNN/RMSSD is a valuable parameter for autonomic nervous system function and can be used to quantify subjective autonomic symptoms in patients with fibromyalgia.

Serum 25-Hydroxyvitamin D3 and BAFF Levels Are Associated with Disease Activity in Primary Sjogren's Syndrome.

The study investigated the association between disease activity and serum 25-hydroxyvitamin D3 (25(OH)-D3), B cell activation of the tumor necrosis factor family (BAFF), or ß2 microglobulin in patients with primary Sjogren's syndrome (SS). Sixty-nine primary SS patients and 22 sicca control patients were included in the study. Disease activity was measured with EULAR Sjogren's syndrome disease activity index (ESSDAI). Serum levels of 25(OH)-D3 and ß2 microglobulin were measured by radioimmunoassay and BAFF was measured by an enzyme-linked immunosorbent assay. Serum levels of 25(OH)-D3 were significantly lower in SS patients compared to the sicca controls (p = 0.036). Serum levels of BAFF tended to be higher (p = 0.225) and those of ß2 microglobulin were significantly higher in patients with SS than in sicca controls (p = 0.023). In univariate regression analyses, ESSDAI was significantly associated with serum levels of 25(OH)-D3, BAFF, and ß2 microglobulin. After stepwise backward multivariate linear regression analyses including age and acute phase reactants, ESSDAI was associated with 25(OH)-D3 (ß = -0.042, p = 0.015) and BAFF (ß = 0.001, p = 0.015) in SS patients. In SS patients, ESSDAI is negatively associated with serum levels of 25(OH)-D3 and positively associated with BAFF.

Prevalence and clinical impact of fibromyalgia in patients with primary Sjögren's syndrome.

OBJECTIVES: Clinical features of primary Sjögren's syndrome (pSS) overlap with those of fibromyalgia (FM). This cross-sectional study was conducted to investigate the prevalence of FM in pSS patients and to compare the clinical features of pSS patients with FM to those without FM. METHODS: One hundred pSS patients were consecutively assessed to identify the presence of FM according to the American College of Rheumatology (ACR) 2010 criteria. Clinical and laboratory data were collected from all patients. Additional assessments included EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). The severity of depression was measured by Hamilton depression rating scale 17-items (HAM-D scale). RESULTS: The prevalence of FM was 31.0% (31/100) in pSS. Widespread pain index and symptom severity scale were significantly correlated with ESSPRI (r=0.6542 and r=0.7173, both p<0.0001) and HAM-D scale (r=0.6734 and r=0.6471, both p<0.0001) in pSS. In multivariate analysis, ESSPRI and HAM-D scale were independently associated with increase of tender point count and symptom severity scale. ESSPRI was significantly higher in pSS patients with FM compared to those without FM (p<0.0001). The prevalence of FM in pSS patients with moderate-to-severe depression was significantly higher than those with mild depression or without depression (odds ratio= 10.62, p=0.0009). Serum 25-hydroxy vitamin D3 levels in pSS patients with FM were significantly (p=0.0072) decreased compared to those without FM. CONCLUSIONS: Our study showed that FM was prevalent in pSS. FM was associated with higher ESSPRI and more severe depression.

Chronic Periodontitis Is Associated With Spinal Dysmobility in Patients With Ankylosing Spondylitis.

BACKGROUND: Although microbes have been suggested to play a role in the pathogenesis of ankylosing spondylitis (AS), several studies present contradictory results regarding the association between AS and chronic periodontitis (CP). METHODS: Clinical, laboratory, and medication data were collected from 84 patients with AS and 84 age- and sex-matched controls. Periodontal measurements, including probing depths (PDs), clinical attachment loss (AL), serum anti-Porphyromonas gingivalis titers, and the detection of P. gingivalis DNA in gingival crevicular fluid, were recorded. All participants with periodontitis with PD ≥4 to <7 mm received scaling and root planing and were re-evaluated at 12 weeks; those still exhibiting periodontitis with PD of ≥4 to <7 mm at 12 weeks were followed at 24 weeks. RESULTS: The prevalence of moderate-to-severe CP was not different between patients with AS and controls (70.2% versus 66.6%). The P. gingivalis detection rate was not different between patients with AS and controls or between patients with AS receiving and not receiving anti-tumor necrosis factor (TNF)-α agents. However, CP was positively associated with impaired spinal mobility of patients with AS in multivariate analyses. After periodontal treatment, PD and AL levels were improved in both groups, but the change was significantly greater in patients with AS than in controls. Patients with AS receiving anti-TNF-α agents exhibited a greater improvement in PD and AL than those who did not. CONCLUSIONS: Although AS was not associated with the presence of CP, CP was associated positively with the severity of spinal dysmobility in Korean patients with AS. These results suggest that periodontitis can have a negative effect on axial movement in AS.

Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis.

The aim of our observational study was to investigate the clinical significance of interleukin (IL)-34, a novel osteoclastogenic cytokine, for predicting structural damage in patients with rheumatoid arthritis (RA). Serum IL-34 levels were measured in 100 RA patients, 36 patients with ankylosing spondylitis (AS), and 59 gender- and age-matched healthy individuals using an enzyme-linked immunosorbent assay. We also measured IL-34 concentrations in synovial fluid (SF) samples from 18 RA patients and 19 osteoarthritis (OA) patients. Progression of structural damage was assessed in 81 patients with RA by plain radiographs using the modified Sharp/van der Heijde score (SHS) at baseline and after an average 1.6-year follow-up period. Serum IL-34 levels were significantly higher in patients with RA (p < 0.001) or AS (p < 0.001) than in healthy controls. SF IL-34 levels were also significantly higher in RA patients than in OA patients (p < 0.001). In RA, serum IL-34 levels were associated with rheumatoid factor positivity (p = 0.01), current smoking (p < 0.01), erythrocyte sedimentation rate (p = 0.01), and C-reactive protein levels (p < 0.01), but not with disease activity score 28. ΔSHS/year was positively correlated with serum IL-34 levels (r = 0.443, p < 0.001). In multivariate logistic regression analyses, serum IL-34 level was an independent risk factor for radiographic progression. These results suggest that IL-34, a novel osteoclastogenic cytokine, plays a role in RA-associated joint damage and is a potential biomarker for predicting subsequent radiographic progression in patients with RA.