Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians’ discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs −0.18, −0.38, and −0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus antiTNF therapy than with multiple cDMARDs (BGD −0.18, −0.19, and −0.19 points, respectively; all p≤0.024). Conclusion In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Background/Aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Background/Aims: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.

Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, is therapeutically effective in patients diagnosed with rheumatoid arthritis (RA) compared with placebo. However patients treated with tocilizumab are at increased risk of several adverse effects including anaphylaxis and serious infections that may lead to hospitalization or death. Therefore, the risks and benefits of treatment with tocilizumab should be considered carefully and close monitoring of patients for development of signs and symptoms of side effects is required during and after treatment. Here, we report on a rare case of anaphylaxis and severe sepsis caused by cellulitis in a patient with RA after tocilizumab treatment.
Anaphylaxis ; Arthritis, Rheumatoid* ; Cellulitis* ; Hospitalization ; Humans ; Interleukin-6 ; Risk Assessment ; Sepsis*

Septic arthritis is the infection of a joint by an infectious agent, leading to arthritis. It is therefore important to identify and treat the correct bacteria in septic arthritis. However, accurate identification of bacteria by conventional methods is difficult because of the distinct biochemical characteristics of individual bacteria. This case report aims at assessing septic arthritis caused by Streptococcus dysgalactiae subsp. equisimilis(SDSE) using nucleotide sequences and discusses the associated treatment. Here, Streptococcus agalactiae was determined to be the causative bacteria for septic arthritis in a 77 year-old woman using the conventional method of hemolysis pattern interpretation and morphology. However, nucleotide sequence analysis of 16S ribosomal RNA revealed that SDSE was the causative strain. 16S rRNA gene sequencing can correctly identify bacteria strains that are difficult to be identified by traditional method, and this correct identification can provide patients with the opportunity for adequate treatment using the proper antibiotics.
Anti-Bacterial Agents ; Arthritis ; Arthritis, Infectious ; Bacteria ; Base Sequence ; Female ; Genes, rRNA* ; Hemolysis ; Humans ; Joints ; Knee* ; Methods ; RNA, Ribosomal, 16S ; Streptococcus agalactiae ; Streptococcus*

The systemic vasculitides are a group of diverse diseases characterized by blood vessel inflammation. The existing classification criteria are intended to create homogeneous patient groups for research and not to diagnose individual patients. However, they have been misused as diagnostic criteria, in both practice and research. The existing classification systems for vasculitis are limited by the overlapping features of disease entities and unrecognized pathogenic mechanisms. This review discusses the benefits and limitations of the widely used American College of Rheumatology criteria and Chapel Hill Consensus Conference nomenclature, updated in 2012. Improved diagnostics, including antineutrophil cytoplasmic antibody (ANCA) testing and imaging, argue for updating the established classification criteria. International efforts are underway to build a more effective classification and diagnostic criteria that reflect a better understanding of the pathophysiology of vasculitis and recent discoveries of genetics and biomarkers.
Antibodies, Antineutrophil Cytoplasmic ; Biomarkers ; Blood Vessels ; Classification* ; Consensus ; Genetics ; Humans ; Inflammation ; Rheumatology ; Systemic Vasculitis ; Vasculitis*

A 33-year-old male presented with an acute onset of back pain and abdominal pain. He was 189.9 cm tall and had an arm span of 194 cm, and had mild pectus carinatum as well as arachnodactyly. Plain radiographs showed kyphoscoliosis of the lumbar spine, bamboo spine of the thoracic spine, and sacroiliitis of the pelvis. Abdominal computed tomography revealed debakey type 3 aortic dissection. We prescribed beta blockers to control his blood pressure. According to the modified New York criteria, we diagnosed him with HLA negative ankylosing spondylitis and initiated therapy with nabumetone and sulfasalazine. We later diagnosed Marfan syndrome based on the Ghent criteria and mutation screening at the fibrillin-1. After treatment, he has been followed up without symptoms or complications.
Abdominal Pain ; Arachnodactyly ; Arm ; Back Pain ; Blood Pressure ; Butanones ; Humans ; Male ; Marfan Syndrome ; Mass Screening ; Microfilament Proteins ; New York ; Pelvis ; Sacroiliitis ; Spine ; Spondylitis, Ankylosing ; Sulfasalazine

Acute generalized exanthematous pustulosis (AGEP) is characterized by acute nonfollicular sterile pustules on a background of edematous erythema. Hydroxychloroquine (HCQ), an antimalarial drug, widely used to treat rheumatic and dermatologic diseases. HCQ has been reported to be an uncommon cause of AGEP. We report a 60-year-old woman with rheumatoid arthritis requiring the use of HCQ presented fever and erythematous eruption on the trunk with sterile pustules. Leukocytosis and elevated erythrocyte sedimention rate noted on laboratory examination. On the histopathological examination of the skin biopsy specimen showed neutrophilic infiltration and scattered eosinohpils. The lesions were resolved with removal of HCQ. The clinical course was consistent with the diagnosis of AGEP associated with HCQ. We reported a case of typical AGEP associated with HCQ in a patient with Rheumatoid arthritis. The patient presented resolution from cutaneous lesions with withdrawal of culprit drug, without the need of systemic steroid.
Acute Generalized Exanthematous Pustulosis ; Arthritis, Rheumatoid ; Biopsy ; Erythema ; Erythrocytes ; Female ; Fever ; Humans ; Hydroxychloroquine ; Leukocytosis ; Neutrophils ; Skin

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase alpha1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of alpha1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.
Adenosine Triphosphatases ; Astrocytes ; Brain Injuries ; Glucose ; Ischemia ; L-Lactate Dehydrogenase ; Neuroglia ; Neurons ; RNA, Messenger ; Sodium Azide