Korean treatment recommendations for patients with axial spondyloarthritis

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Inflammation is responsible for systemic bone loss in patients with seropositive rheumatoid arthritis treated with rituximab

Background/Aims@#We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). @*Methods@#Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. @*Results@#In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the develgroup with the second cycle but remained stable in the group with one cycle. @*Conclusions@#Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

Korean treatment recommendations for patients with axial spondyloarthritis

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors.Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

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.

A Rare Case of Limited Muscle Involvement in Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic vasculitis involving small- and medium-sized arteries, which presents with necrotizing inflammation. PAN occurs as a systemic disease or as a limited form confined to a single organ. Few cases have been reported with single organ involvement, and even fewer have been reported with skeletal muscle involvement. Herein, we report the ultrasonography and magnetic resonance imaging findings in a rare case of PAN with limited muscle involvement in a 66-yearold man.

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.

A Rare Case of Limited Muscle Involvement in Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic vasculitis involving small- and medium-sized arteries, which presents with necrotizing inflammation. PAN occurs as a systemic disease or as a limited form confined to a single organ. Few cases have been reported with single organ involvement, and even fewer have been reported with skeletal muscle involvement. Herein, we report the ultrasonography and magnetic resonance imaging findings in a rare case of PAN with limited muscle involvement in a 66-yearold man.

PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

Prevalence of osteoporosis in patients with systemic lupus erythematosus: A multicenter comparative study of the World Health Organization and fracture risk assessment tool criteria

Objectives@#Osteoporosis and fracture are known complications of systemic lupus erythematosus (SLE). We assessed the prevalence and risk factors for osteoporosis in patients with SLE. @*Methods@#A total of 155 female SLE patients were recruited retrospectively in 5 university hospitals. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the fracture risk assessment tool (FRAX) for high-risk osteoporotic fractures was calculated with and without BMD. @*Results@#The mean age was 53.7 ± 6.8 years, and osteoporotic fractures were detected in 19/127 (15.0%) patients. The proportion of patients having a high-risk for osteoporotic fractures in the FRAX with and without BMD, and osteoporosis by the World Health Organization (WHO) criteria were 25 (16.1%), 24 (15.5%), and 51 (32.9%), respectively, and 48.0–68.6% of them were receiving treatment. On multivariate logistic analysis, nephritis (odds ratio [OR] 11.35) and cumulative dose of glucocorticoid (OR 1.1) were associated with high-risk by the FRAX with BMD, and low complement levels (OR 4.38), erythrocyte sedimentation rate (ESR) (OR 1.04), and cumulative dose of glucocorticoid (OR 1.05) were associated with osteoporosis by the WHO criteria in patients with SLE. @*Conclusions@#Among Korean female patients with SLE, the proportion of patients having a high-risk of osteoporotic fractures by the FRAX tool was 15.5%–16.1% and the proportion of patients having osteoporosis by the WHO criteria was 32.9%. In SLE, nephritis, low level of complement, ESR, and cumulative dose of glucocorticoids may contribute to fracture risk.

Prevalence of osteoporosis in patients with systemic lupus erythematosus: A multicenter comparative study of the World Health Organization and fracture risk assessment tool criteria

Objectives@#Osteoporosis and fracture are known complications of systemic lupus erythematosus (SLE). We assessed the prevalence and risk factors for osteoporosis in patients with SLE. @*Methods@#A total of 155 female SLE patients were recruited retrospectively in 5 university hospitals. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the fracture risk assessment tool (FRAX) for high-risk osteoporotic fractures was calculated with and without BMD. @*Results@#The mean age was 53.7 ± 6.8 years, and osteoporotic fractures were detected in 19/127 (15.0%) patients. The proportion of patients having a high-risk for osteoporotic fractures in the FRAX with and without BMD, and osteoporosis by the World Health Organization (WHO) criteria were 25 (16.1%), 24 (15.5%), and 51 (32.9%), respectively, and 48.0–68.6% of them were receiving treatment. On multivariate logistic analysis, nephritis (odds ratio [OR] 11.35) and cumulative dose of glucocorticoid (OR 1.1) were associated with high-risk by the FRAX with BMD, and low complement levels (OR 4.38), erythrocyte sedimentation rate (ESR) (OR 1.04), and cumulative dose of glucocorticoid (OR 1.05) were associated with osteoporosis by the WHO criteria in patients with SLE. @*Conclusions@#Among Korean female patients with SLE, the proportion of patients having a high-risk of osteoporotic fractures by the FRAX tool was 15.5%–16.1% and the proportion of patients having osteoporosis by the WHO criteria was 32.9%. In SLE, nephritis, low level of complement, ESR, and cumulative dose of glucocorticoids may contribute to fracture risk.

Evaluating the Outcome of Multi-Morbid Patients Cared for by Hospitalists: a Report of Integrated Medical Model in Korea

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.

Palisaded Neutrophilic Granulomatous Dermatitis in a Patient with Systemic Sclerosis-Rheumatoid Arthritis Overlap Syndrome

No abstract available.

Tumor Necrosis Factor Blockade Stimulates Circulating Osteoblastic Lineage Cells Activity while Reducing Circulating Osteoclasts

OBJECTIVE: This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. METHODS: Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. RESULTS: The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. CONCLUSION: The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.

Bone Mineral Density Measurement Intervals for Rheumatoid Arthritis Patients Not Treated for Osteoporosis / 대한내과학회지

BACKGROUND/AIMS: Osteoporosis occurs more frequently in rheumatoid arthritis (RA) patients than in healthy individuals. This study investigated the appropriate bone mineral density (BMD) measurement interval and risk factors associated with osteoporosis for RA patients. METHODS: A retrospective study was performed on 511 RA patients aged more than 40 years old who had undergone BMD testing more than once and who had normal BMD or osteopenia at the baseline BMD test and no history of any fracture of the spine or femur. The subjects were categorized into four subgroups: normal BMD (T-score > -1), mild (-1 ≥ T-score > -1.5), moderate (-1.5 ≥ T-score > -2), and advanced (-2 ≥ T-score > -2.5) osteopenia. The BMD testing interval was defined as the estimated time for 10% of the RA patients to make the transition to osteoporosis without osteoporotic fracture or the administration of any osteoporosis drug. RESULTS: The observation period was 2,214 patient-years, with an average of 4.3 years. The estimated BMD testing interval was more than 10 years for normal, 4.3 years for mild, 2.5 years for moderate, and 1.5 years for advanced osteopenia in each of the RA patient groups. CONCLUSIONS: Our study indicated that in normal or osteopenic RA groups, a baseline BMD T-score is the most important factor in estimating the interval in which osteoporosis is predicted to occur. In addition, we recommend that the BMD measuring interval should be greater than 10 years in normal BMD RA patients, 4 years in mild, 2 years in moderate, and 1 year in advanced osteopenic RA patients on the basis of L-spine BMD.

A Case of Eosinophilic Granulomatosis with Polyangiitis Presenting with Subarachnoid Hemorrhage and Mononeuritis Multiplex

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, is an anti-neutrophil cytoplasmic antibody associated vasculitis, accompanied by asthma, hypereosinophilia, nonfixed pulmonary infiltrates, and sinusitis. Peripheral neuropathy is common in patients with EGPA; however, a few cases of EGPA with central nervous system (CNS) involvement have been reported. A 45-year-old female referred for right side weakness and posterior neck pain was diagnosed as EGPA with subarachnoid hemorrhage and mononeuritis multiplex. She was effectively treated with a high dose glucocorticoid, cyclophosphamide, and intravenous immunoglobulin. EGPA with CNS involvement is uncommon and causes significant morbidity and mortality. Therefore more rapid and accurate diagnostic evaluation may be required. EGPA should be considered in patients with neurological symptoms and hypereosinophilia.

A Case Report of SAPHO Syndrome Treated with Oral Alendronate

SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis is rare compared to other spondyloarthropathies. It is also difficult to diagnose, and treatment methods have not yet been fully identified. Approximately 72% of patients are diagnosed with at least one other disease before a final diagnosis of SAPHO syndrome. In addition, SAPHO syndrome is subject to a delayed diagnosis period of 4.5 to 9.1 years. Medications such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and tumor necrosis factor inhibitors are used in treatment of SAPHO syndrome. Bisphosphonate is also used for refractory SAPHO syndrome; however, most reports on this relate to intravenous injection of medication. The authors experienced and subsequently reported on a case involving a patient with SAPHO syndrome accompanied by fracture and infection of the left second finger who was treated with the oral biphosphonate, alendronate.

Digital Thermography of the Fingers and Toes in Raynaud's Phenomenon

The aim of this study was to determine whether skin temperature measurement by digital thermography on hands and feet is useful for diagnosis of Raynaud's phenomenon (RP). Fifty-seven patients with RP (primary RP, n = 33; secondary RP, n = 24) and 146 healthy volunteers were recruited. After acclimation to room temperature for 30 min, thermal imaging of palmar aspect of hands and dorsal aspect of feet were taken. Temperature differences between palm (center) and the coolest finger and temperature differences between foot dorsum (center) and first toe significantly differed between patients and controls. The area under curve analysis showed that temperature difference of the coolest finger (cutoff value: 2.2degrees C) differentiated RP patients from controls (sensitivity/specificity: 67/60%, respectively). Temperature differences of first toe (cutoff value: 3.11degrees C) also discriminated RP patients (sensitivity/specificity: about 73/66%, respectively). A combination of thermographic assessment of the coolest finger and first toe was highly effective in men (sensitivity/specificity : about 88/60%, respectively) while thermographic assessment of first toe was solely sufficient for women (sensitivity/specificity: about 74/68%, respectively). Thermographic assessment of the coolest finger and first toe is useful for diagnosing RP. In women, thermography of first toe is highly recommended.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Prevention of Comorbidity and Acute Attack of Gout by Uric Acid Lowering Therapy

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA) or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

Effects of Gout Web based Self-management Program on Knowledge Related to Disease, Medication Adherence, and Self-management

PURPOSE: This study was conducted to examine the changing patterns of knowledge related to disease, medication adherence, and self-management and to determine if outcomes were more favorable in the experimental group than in the comparison group through 6 months after providing a web-based self-management intervention. METHODS: A non-equivalent control group quasi-experimental design was used and 65 patients with gout, 34 in experimental group and 31 in comparison group, were selected from the rheumatic clinics of two university hospitals. Data were collected four times, at baseline, at 1 month, 3 months, and 6 months after the intervention. RESULTS: According to the study results, the changing patterns of knowledge and self-management were more positive in the experimental group than in the control group, whereas difference in the changing pattern of medication adherence between two groups was not significant. CONCLUSION: The results indicate that the web-based self-management program has significant effect on improving knowledge and self-management for middle aged male patients with gout. However, in order to enhance medication adherence, the web-based intervention might not be sufficient and other strategies need to be added.