A large pulmonary nodule in a rheumatoid arthritis patient treated with tofacitinib.

Pulmonary rheumatoid nodules are rare extra-articular manifestations of rheumatoid arthritis (RA). They are usually asymptomatic but may form cavities and cause clinical symptoms. These nodules are difficult to differentiate clinically and radiologically from tuberculosis, fungal infection, or lung malignancies. Histopathological studies help in the differential diagnosis of pulmonary nodules in patients with RA; however, an effective treatment for rheumatoid lung nodules has not yet been established. This study reports a case of active RA with interstitial lung disease and a large inflammatory lung nodule that was improved with tofacitinib treatment.

Association between knee osteoarthritis and mortality: a serial propensity score-matched cohort study.

BACKGROUND/AIMS: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. METHODS: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010-2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren-Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. RESULTS: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77-1.65), knee pain (HR 0.61; 95% CI 0.27-1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89-2.17). No association was found between the all-cause/cancer mortality and other groups. CONCLUSION: When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

Efficacy of Pirfenidone According to Dose in Patients with Idiopathic Pulmonary Fibrosis: A Prospective, Observational, Single-Center Cohort Study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor prognosis. Pirfenidone is approved and widely used for the treatment of IPF and reduces lung function decline. The aim of this study was to evaluate the efficacy of different doses of pirfenidone for the prevention of disease progression in patients with IPF. METHODS: This was a prospective, observational, single-center cohort study conducted in Haeundae Paik Hospital, Republic of Korea, from April 2021 to March 2023. IPF patients were assigned to three groups according to the dose of pirfenidone (600 mg, 1200 mg, 1800 mg). Disease progression was defined as an absolute decline to ≥5% of forced vital capacity (FVC) (% predicted value) or an absolute decline to ≥10% of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted value) over 12 months. The primary endpoint was to evaluate the clinical effects of pirfenidone of each dosage on disease progression in IPF patients by comparing the FVC (% predicted value) and DLco (% predicted value) values over 12 months. The secondary endpoint was to evaluate the prognostic value of Krebs von den Lungen-6 (KL-6) in the disease progression in IPF patients using the baseline KL-6 value and the change in KL-6 values between the baseline and 12 months. RESULTS: A total of 44 patients were enrolled, of whom 39 completed the study, with 13 patients assigned to each of the three groups. The median age was 71.7 years, and 79.5% of patients were men. The baseline characteristics were similar across groups, except the 600 mg group was older (75.9 vs. 69.2 vs. 68.2 years, p = 0.016). The overall median change in FVC and DLco over 12 months was -2.7% (IQR: -9.1%, -1.2%) and -3.8% (IQR: -13.6%, -3.7%), respectively. There was no difference in the decline in FVC (change in FVC, % predicted value: -3.23 vs. -4.08 vs. -1.54, p = 0.621) and DLco (change in DLco, % predicted value: 0.00 vs. -3.62 vs. -3.15, p = 0.437) among the three groups. Fourteen patients (35.9%) suffered disease progression. The rate of disease progression did not differ according to the dose of pirfenidone (38.5 vs. 38.5 vs. 30.8%, p = 1.000). In multivariable logistic regression analysis, KL-6 was not a statistically significant predictor of disease progression. CONCLUSIONS: In our study, regardless of dose, consistent pirfenidone use for 12 months resulted in similar efficacy for the prevention of disease progression in patients with IPF. Large-scale, randomized, double-blind, placebo-controlled clinical trials are needed.

Septic arthritis and osteomyelitis due to Roseomonas; Case report and review of soft tissue, joint and bone infection.

Roseomonas gilardii rarely causes infection in humans. We report that a patient with underlying rheumatoid arthritis and diabetes developed wrist septic arthritis and osteomyelitis due to Roseomonas after steroid joint injection. After antibiotic and surgical treatment, the condition of the patient improved. We reviewed previously reported cases of soft tissue, joint and bone infection related to Roseomonas to understand the characteristics of joint and bone infection of Roseomonas.

A Novel Missense Mutation (L44V) of PAX2 Associated with Adult-Onset End-Stage Renal Disease and No Syndromic Features.

Paired box (PAX) 2, encoded on chromosome 10 in humans, plays a key role in kidney development. The first 3 exons of the gene are highly conserved among species. PAX2 mutations in autosomal dominant papillorenal syndrome (OMIM #120330) are associated with congenital anomalies of the kidney, urinary tract, and eye. A 37-year-old male was admitted to our transplant center for kidney transplantation due to end-stage renal disease (ESRD) caused by chronic glomerulonephritis. Interestingly, 5 members of his family also suffered from ESRD requiring hemodialysis in adulthood. Other ocular or brain anomalies were not reported in this pedigree. We extracted genomic DNA from buccal swabs or peripheral blood samples from the proband and his family members. We identified a novel heterozygous c.130C>G (p.Leu44Val) missense PAX2 mutation in this family by exome sequencing analysis, which we confirmed by Sanger sequencing in the affected family members. This mutation is located in the N-terminus of the paired box domain of PAX2 and predicted to be a pathogenic mutation by in-silico analysis. We report a novel PAX2 mutation identified by exome sequencing in a family with adult ESRD in the absence of other congenital syndromic features.

Repurposing and reshaping of hospitals during the COVID-19 outbreak in South Korea.

During the extensive outbreak of coronavirus disease 2019 (COVID-19) in South Korea, many strategies in the hospital setting, such as stratified patient care, the assignment of hospitals/beds by a task force team, and the establishment of dedicated COVID-19 hospitals, dedicated COVID-19 emergency centers, COVID-19 community facilities, and respiratory care split hospitals, were adopted to mitigate community transmission and prevent nosocomial infection. Most of these strategies were used during the Middle East Respiratory syndrome outbreak and were applied again successfully during the COVID-19 outbreak. The reallocation of health care capacity, repurposing of hospitals, and close collaboration between the government and the health care committee might have been the key to successfully addressing the crisis of COVID-19 given the shortage of health care resources.

How Is COVID-19 Affecting South Korea? What Is Our Current Strategy?

The outbreak of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 is expanding globally. South Korea is one of the countries most affected by COVID-19 from the very early stages of this pandemic. Explosive outbreaks occurred across South Korea in the first two months, and efforts to control this new virus have involved everyone across the country. To curb the transmission of the virus, health-care professionals, committees, and governments have combined many approaches, such as extensive COVID-19 screening, effective patient triage, the transparent provision of information, and the use of information technology. This experience could provide some valuable ideas and lessons to others who are fighting against COVID-19.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome: MRI features of intraosseous fat necrosis involving the feet and knees.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is extremely rare and presents as a triad of the three diseases. The patient usually presents with mild or absent abdominal symptoms. Here, we report on a case of a 66-year-old male who presented with pain and swelling in both legs and mild abdominal pain. He was diagnosed with acute pancreatitis by pancreatic enzyme analysis and abdominal computed tomography (CT) and with skin lesions of panniculitis through a biopsy. Magnetic resonance imaging (MRI) revealed multifocal intraosseous fat necrosis and arthritis involving both the feet and the knees. Therefore, we report a case of PPP syndrome with intraosseous fat necrosis involving both the feet and the knees.

Alterations in immune function with biologic therapies for autoimmune disease.

Autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, are characterized by dysregulation of various aspects of normal immunity and inflammation. Biologic agents targeting key components of the dysregulated immune response have dramatically improved patient outcomes and transformed treatment paradigms for a number of systemic inflammatory autoimmune diseases. Despite their excellent efficacy, because they do affect normal immune responsiveness, biologic agents can potentially be associated with a variety of adverse effects. Important potential adverse effects related to the use of biologic agents include immunosuppression, which might result in outcomes such as infection, and autoimmunity, that could result in paradoxical inflammation or even autoimmune disease. In this article the current clinical evidence and immunologic mechanisms of the adverse effects related to biologic agents are discussed.

Advances in use of immunomodulatory agents--a rheumatology perspective.

With the advent of biologic agents such as TNF inhibitors, the treatment paradigm for autoimmune systemic inflammatory diseases has progressed tremendously. Despite some distinct treatments, similarities exist in several aspects of the treatment of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), IBD and psoriasis. With a so-called treat-to-target strategy aiming at remission, the intensive and early application of disease-modifying antirheumatic drugs within a 'window of opportunity', and in combination with TNF inhibitors, has become the overarching principle of RA therapy. In this Perspective, the concept of treatment approaches using immunomodulatory agents and the latest advances of therapies in autoimmune systemic inflammatory diseases, especially RA, are overviewed from a rheumatology perspective to provide insights into possible approaches to the treatment of inflammatory gastrointestinal disease.

Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions.

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.

A review of disease activity measures for psoriatic arthritis: what is the best approach?

The measuring tools for disease activity of rheumatoid arthritis have long been adapted for assessing the disease activity of psoriatic arthritis (PsA), particularly as regards peripheral arthritis. However, because of the multifactorial aspects and multiple domains of PsA, such as axial and peripheral joints, skin and nails, enthesitis and dactylitis, must also be considered when measuring activity. After the introduction of biologic agents, it became clear that more objective measuring tools were needed to assess the varied aspects of disease activity, as well as the effect of treatment. Collaborations among international groups of rheumatologists and dermatologists have helped define key or core domains of PsA that were recommended for inclusion in clinical trials and potentially clinical practice. Groups such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have tried to develop and validate new outcome measures in PsA. Several new composite measures for specific PsA have been recently developed. The domains, instruments and traditional and new composite measures for PsA are reviewed herein.

Treatment of spondyloarthropathy: the potential for agents other than TNF inhibitors.

PURPOSE OF REVIEW: Inhibitors of tumor necrosis factor (TNF) have demonstrated dramatic clinical efficacy in patients with spondyloarthropathy (SpA). However, not all patients respond, and some patients who initially improve, subsequently lose response. Therefore, there is still an unmet clinical need for additional therapies. Herein we describe the recent data on newer treatments for SpA patients. RECENT FINDINGS: Treatments targeting various cytokines, cell surface molecules, and signaling molecules have been assessed. The effects of taregeting B cells with rituximab, T-cell costimulation with abatacept, and interleukin (IL)-6 with tocilizumab have been disappointing in ankylosing spondylitis (AS). Abatacept appears to have a modest effect in patients with psoriatic arthritis (PsA). Targeting IL-17 with secukinumab, IL-12/23 with ustekinumab, and phosphodiesterase 4 (PDE4) with apremilast may prove to be promising treatments for SpA. SUMMARY: There are several newer therapies that may emerge for SpA, particularly those targeting IL-17, IL-23/IL-12, and PDE4.

Critical analysis of economic tools and economic measurement applied to rheumatoid arthritis.

Rheumatoid arthritis (RA) is chronic, progressive systemic inflammatory disease that if uncontrolled may lead to significant joint damage, dysfunction, work disability and other sequelae that result in large economic losses. A rich literature estimating the economic burden of RA, has been intensified recently, driven by costly biologic agents that have had a notable effect improving the outcomes of patients with RA. In order to optimally assess the value of therapies, it is best to take a comprehensive approach, considering all related costs of illness. This includes direct costs (e.g. the costs of the medications themselves and the monitoring required), indirect costs (e.g. loss of productivity, such as employment due to uncontrolled disease) and intangible cost (e.g. effects on pain and quality of life). Indirect costs constitute a substantial part of total cost in the patient with RA. In order to help assess the impact of RA on productivity, various tools for measuring productive loss like absenteeism and presenteeism have been introduced. No single tool reflects the entire spectrum of the productive loss clearly, as other factors such as use of a human capital approach or friction cost approach affect the valuation of productive loss monetarily. Although favourable outcomes are achieved with the use of biologic agents, their higher acquisition costs, as compared to traditional disease-modifying anti-rheumatic drugs (DMARDs) remain a barrier to their use. Assessments of the cost effectiveness of novel therapies are critically important, but published results have been contradictory, in some measure due to the heterogeneity of instruments utilised. While the various instruments appear to be valid and reliable, correlations between instruments has been modest, driven by factors such as differences in recall times, attribution and other confounders.

Patient-reported outcomes in rheumatoid arthritis.

PURPOSE OF REVIEW: In recent years, there has been increasing interest, as indicated by a growing number of citations in the medical literature, on the assessment of outcomes in patients with rheumatoid arthritis (RA) focusing on the patient's perspective. This article describes the domains of patient-reported outcomes (PROs), instruments for measuring responses, as well as the use of PRO in clinical trials with newer agents, including biologic agents. RECENT FINDINGS: At the 10th Outcome Measure in Rheumatology Clinical Trials (OMERACT) conference, several methodological issues about the choice of PRO domains, the development of instruments measuring these domains, and the methods for assessing response criteria were addressed. Composite domains like the RA impact of disease (RAID) score and core outcomes for the RA patient priorities for pharmacologic interventions (RAPP-PI) were introduced. Minimally clinically important differences in various PROs have been used to measure responsiveness to change in clinical trials. Many randomized clinical trials show significant improvements in PRO, such as the health assessment questionnaire disability index, and the medical outcomes study short form with effective treatment. SUMMARY: PRO has become an essential part when assessing patients with RA. This trend will likely continue into the future, in both clinical trials as well as clinical practice.

G109T polymorphism of SLC22A12 gene is associated with serum uric acid level, but not with metabolic syndrome.

SLC22A12 gene, encoding urate transport 1, has been known to be responsible to urate metabolism. This study sought to determine the association between the novel G109T polymorphism in SLC22A12 with serum uric acid and the development of metabolic syndrome in Korean male subjects. A total of 132 healthy male subjects were enrolled in this study. Metabolic syndrome was determined using the modified guidelines for metabolic syndrome proposed by the National Cholesterol Education Program's Third Adult Treatment Panel. Genotyping for the SLC22A12 gene was assessed using denaturing high-performance liquid chromatography analysis. Serum uric acid and fractional excretion of uric acid (FEUA) from blood and urine samples were measured. Frequencies of the 109GG, 109GT, and 109TT genotypes were 57.6, 38.6, and 3.8%, respectively. Serum uric acid levels and FEUAs were significantly different among the three genotypes of the G109T polymorphism (P = 0.035 and P = 0.033, respectively). In addition, subjects of genotypes with the T allele had lower uric acid levels and higher FEUAs compared to those with the 109GG genotype (P = 0.007 and P = 0.031, respectively). The G109T polymorphism of the SLC22A12 gene has no association with metabolic syndrome. However, a number of metabolic syndrome components were related to serum uric acid level (r = 0.285, P = 0.001) and also significantly different between genotype with and without T allele (P = 0.008). The novel G109T polymorphism of the SLC22A12 gene is related to serum uric acid level, but not to the development of metabolic syndrome.

Korean Observational Study Network for Arthritis (KORONA): establishment of a prospective multicenter cohort for rheumatoid arthritis in South Korea.

OBJECTIVES: The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA. METHODS: The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. RESULTS: A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010. CONCLUSIONS: KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable "real-world" information for Korean RA patients.

Expression of galectin-9 by IFN-γ stimulated human nasal polyp fibroblasts through MAPK, PI3K, and JAK/STAT signaling pathways.

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) may play important roles in the selective recruitment of eosinophils in nasal polyp tissues through the production of galectin-9. These findings suggest that galectin-9 expression is associated with eosinophil infiltration in polyps of patients with nasal polyposis.

Leuconostoc bacteremia in a patient with amyloidosis secondary to rheumatoid arthritis and tuberculosis arthritis.

Leuconostoc infections are rare and usually occur in immunocompromised patients. This report describes a case of Leuconostoc lactis bacteremia in a patient with coexisting rheumatoid arthritis and tuberculosis arthritis. A disrupted gastrointestinal barrier due to gastrointestinal amyloidosis in long-standing rheumatoid arthritis and tuberculosis arthritis could be a risk factor for Leuconostoc bacteremia. Despite aggressive antibiotic treatment, the patient progressed to septic shock and multi-organ failure. The fatal course might have been caused by rapid progression of gastrointestinal pathology, which could be a risk factor for Leuconostoc bacteremia.

Liver enzyme abnormalities in systemic lupus erythematosus: a focus on toxic hepatitis.

Although subclinical liver disease is common in systemic lupus erythematosus (SLE), strikingly high levels of liver enzymes are rare. Our aim was to determine the cause of high levels of liver enzymes in lupus patients, particularly in patients diagnosed with toxic hepatitis. We performed a retrospective chart review of SLE patients treated at the Inje University Hospital between 2001 and 2008. We defined liver enzyme abnormality as a twofold or greater increase in two or more of the following four components: total bilirubin, AST, ALT and LDH or ALP. Acute toxic hepatitis was diagnosed by a score ≥ 5 in the Roussel Uclaf Causality Assessment Method. Of 141 SLE patients 46 (32.6%) met strict criteria for the liver enzyme abnormality. In total, 11 patients (7.8%) in this study had presumed toxic hepatitis associated with either herbal medicines (n = 6), anti-tuberculosis medications (n = 3), antibiotics (n = 1) or valproic acid (n = 1). There were striking laboratory abnormalities in the groups diagnosed with toxic hepatitis (mean peak values: AST 775 ± 464 U/L, ALT 400 ± 447 U/L, ALP 767 ± 408 U/L, LDH 1,469 ± 779 U/L). All six patients with herbal-induced toxic hepatitis were in the active SLE state. After cessation of the suspected causative medication and subsequent administration of steroids, liver enzyme levels were improved. Herbal medicines and anti-tuberculosis medications, known to cause toxic hepatitis, can also induce increased liver enzyme levels in lupus patients. However, since most herbal medicines contain a mixture of various products, we could not ascertain what specific ingredient induced the increase in liver enzyme levels.