Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Background/Aims@#We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. @*Methods@#A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). @*Results@#Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. @*Conclusions@#Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

A Case of Macrophage Activation Syndrome During the Treatment of Adult-onset Still’s Disease With Tocilizumab

Macrophage activation syndrome (MAS) is a fatal complication of adult-onset Still’s disease (AOSD). Although anti-cytokine agents have been recommended for refractory AOSD or complicated with MAS, MAS cases have been rarely reported during anticytokine treatment. Herein, we describe the first AOSD case complicated with MAS during the treatment with tocilizumab in Korea. Two years after tocilizumab maintenance therapy, high fever and hypertransaminasemia recurred. MAS was diagnosed based on hyperferritinemia, elevated soluble IL-2 receptor levels, and the presence of hemophagocytic histiocytes in the bone marrow.However, she had normal white blood cell counts and acute phase reactant levels. High-dose glucocorticoid and anakinra therapies were not effective, but her disease improved with etoposide. This case shows that tocilizumab may not prevent MAS development and can modify clinical features making it challenging to diagnose. Cytotoxic therapy such as etoposide may be required in MAS cases that develop during anti-cytokine therapy.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients

Purpose@#To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. @*Materials and Methods@#We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. @*Results@#According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with antiTIF1γ, anti-SRP, and anti-MDA5. @*Conclusion@#The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients

Purpose@#To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. @*Materials and Methods@#We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. @*Results@#According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with antiTIF1γ, anti-SRP, and anti-MDA5. @*Conclusion@#The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.

Multisystem Inflammatory Syndrome in an Adult after COVID-19 Vaccination: a Case Report and Literature Review

As the number of people vaccinated increases, people who complain of adverse reactions continue to occur. We experienced a case characterized by low blood pressure, persistent fever, edema due to increased systemic vascular permeability, and systemic inflammation confirmed by image and laboratory examinations after ChAdOx1 coronavirus disease 2019 (COVID-19) vaccination. The diagnostic criteria for multisystem inflammatory syndrome (MIS) in adults are known as fever of 3 days or more in adults, 2 or more mucocutaneous/ gastrointestinaleurologic symptoms, elevation of inflammatory markers, and clinical/ imaging diagnosis of heart failure. A 67-year-old man who was medicated for hypertension and diabetes was admitted complaining of fever, maculopapular rash, diarrhea, headache, chills, and dizziness 6 days after the first vaccination of ChAdOx1 nCoV-19 in Korea.The COVID-19 test was negative but with low blood pressure, leukocytosis, skin rash, pulmonary edema, and increased inflammation markers. His lab findings and clinical course were consistent with those of MIS after COVID-19 vaccination. He was medicated with methylprednisolone 1 mg/kg and diuretics and recovered rapidly. He was discharged after 2 weeks and confirmed cure at outpatient clinic. We report an MIS case after COVID-19 vaccination in Korea.

Two Cases of Neonatal Lupus and Literature Review

Neonatal lupus is a rare rheumatic disease. Clinical manifestations include characteristic annular or macular rashes, congenital heart block, cytopenias, and hepatitis. Neonatal lupus is caused by transmission of maternal immunoglobulin G autoantibodies such as anti-SSA/Ro antibody or anti-SSB/La antibody to the fetus through the placenta. We report two cases of neonatal lupus. The first case refers to an 18-day-old male with annular rashes on both cheeks, neutropenia, positive tests for antinuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody. His mother was diagnosed with systemic lupus erythematosus characterized by positive tests for antinuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody. The second case represents a 32-day-old female with annular rash on both hands, soles, and the genital area, neutropenia, hepatitis, positive tests for antinuclear antibody, and anti-SSA/Ro antibody. Skin punch biopsy was conducted. Her mother did not have history of connective tissue diseases. We referred her mother to the division of rheumatology of the department of internal medicine. The mother was suspected with primary Sjögren's syndrome because of arthralgia and dry eye symptoms with positive tests for antinuclear antibody, anti-SSA/Ro antibody, anti-SSB/La antibody, and rheumatoid factor. It is necessary to suspect neonatal lupus in neonates or infants with characteristic annular rash with or without maternal history of connective tissue disorders.

Survey of Depression in the Elderly Patients with Diabetes Mellitus / 신경정신의학

OBJECTIVES: Depression is commonly comorbid in elderly patients with physical illness. This study examined the prevalence of depression in the elderly with Diabetes Mellitus (DM). METHODS: Eighty-nine patients, over 60 years old, with DM were enrolled. The medical and psychiatric history, Hamilton Rating Scale for Depression (HDRS), Patient Health Questionnaire-9 (PHQ-9), Geriatric Depression Scale-Short form Korean (GDS-SF-K), and Mini-Mental Status Examination Korean version were examined. RESULTS: The prevalence of depression was estimated as 21.3% (male 4.5% ; female 16.9%) in HDRS, 32.6% (male 9.0% ; female 23.6%) in PHQ-9, and 24.7% (male 5.6% ; female 19.1%) in GDS-SF-K. CONCLUSION: The self-reporting scale, such as GDS-SF-K, PHQ-9 is an effective screening test for depression. The prevalence of elderly depression with DM ranged from 20% to 30%, the prevalence of depression is almost three times more common in women.

Depression and Quality of Life in Patients with Systemic Lupus Erythematosus

OBJECTIVE: The objective of this study is to examine the prevalence of depression and its related factors including quality of life, brain-derived neurotrophic factor (BDNF), and vitamin D in patients with systemic lupus erythematosus (SLE). METHODS: Depression was assessed using the center for epidemiologic studies depression (CES-D) scale. Disease activity, disease-related organ damage, the EuroQol-5 dimensions (EQ-5D), sociodemographic features, and laboratory tests including serum vitamin D level were surveyed. Serum BDNF was measured using an enzyme-linked immunosorbent assay. RESULTS: Depression was observed in 22.8% of 180 SLE patients (n=41). Patients with marital status of single/divorced/separated/widowed, a higher patient global assessment (PGA) score, and extreme pain/discomfort showed significant association with depression. The EQ-5D index showed negative correlation with CES-D score (r=-0.56, p<0.05). In each EQ-5D dimension, depression showed significant association with moderate to severe problems in self-care and usual activities, and extreme pain/discomfort. Serum BDNF levels were not associated with depression (p=0.75) but associated with SLE disease activity index (SLEDAI; r=-0.21, p<0.05). Serum vitamin D levels were not associated with depression (p=0.60) but showed negative correlation with SLEDAI (r=-0.23, p<0.05) and mean glucocorticoid dose over the previous 3 months (r=-0.21, p<0.05) after adjustment for use of vitamin D supplement. CONCLUSION: Depression was prevalent in patients with SLE and was associated with low quality of life, and a higher PGA but not with SLEDAI. Serum BDNF and vitamin D levels were not associated with depression but showed snegative correlation with SLEDAI.

TNF-alpha Inhibitor Treatment in an Ankylosing Spondylitis Patient with Secondary Amyloidosis that Manifest with Diarrhea: A Case Report / 대한내과학회지

Secondary amyloidosis (Amyloid A amyloidosis) occurs when serum amyloid S accumulates in various tissues and organs. It often accompanies chronic inflammatory disease, especially rheumatoid arthritis, as well as ankylosing spondylitis (AS) and Crohn's disease. Although amyloid deposits were reported in 7% of the abdominal fatty tissue samples from AS patients, most of the patients had no symptoms. In a large study, 1.1% of 730 patients with AS were diagnosed with amyloidosis. Most of them showed renal involvement, while none had gastrointestinal symptoms. In South Korea, only a few cases of gastrointestinal involvement of secondary amyloidosis have been reported in AS patients, and there is no report on the effect of a tumor necrosis factor (TNF)-alpha inhibitor. We report a case of secondary amyloidosis in an AS patient who improved with the TNF-alpha inhibitor etanercept.

A Case of a 14-Year-Old Girl Who Developed Dermatomyositis Associated with Mycoplasma pneumoniae Infection

Extrapulmonary manifestations of Mycoplasma pneumoniae infection are not uncommon and involvement of every organ system has been reported. However, association of inflammatory myositis with M. pneumoniae infection is rare. Here, we describe a patient who developed polymyositis associated with mycoplasma infection, who was treated successfully with glucocorticoid, intravenous immunoglobulin, and methotrexate.

Isolated Lenticulostriate Artery Aneurysm Rupture in a Patient with Behcet's Disease

Behcet's disease (BD) is characterized by recurrent oro-genital ulcers, skin lesions, and intraocular inflammation, but can also affect various internal organs. Vascular BD usually presents with luminal stenosis, thrombosis, or aneurysm formation in aorta and peripheral arteries. However, intracranial artery involvement has been uncommonly reported in patients with BD and BD cases with lenticulostriate artery aneurysm have been rarely described in the English-language literature. We hereby reported the first case of a Korean BD patient presenting with a ruptured lenticulostriate artery aneurysm, who received medical treatment, and reviewed the literature on reported cases of BD with intracranial aneurysms.

Treatment with Rituximab in a Patient with Refractory Felty Syndrome and Low Rheumatoid Arthritis Disease Activity: A Case Report

Felty syndrome (FS) is a rare manifestation in rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Treatment for FS is not well established because there has been no randomized controlled study. A few recent reports found rituximab effective in patients with refractory FS. According to those reports, most patients with RA and FS had active arthritis. Here we report a case of a patient with glucocorticoid dependent and disease-modifying anti-rheumatic drugs (DMARDs) refractory FS and quiescent RA who was successfully treated with rituximab.

Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis

BACKGROUND/AIMS: To investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results. METHODS: A total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records. RESULTS: The overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 x 10(-6)). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 x 10(-4)). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 x 10(-5)). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 x 10(-14)), and the kappa value was 0.108. CONCLUSIONS: Although several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.

Rituximab Treatment for the Patients with Refractory Inflammatory Myopathy

OBJECTIVE: To assess the efficacy and safety of rituximab (RTX) on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. METHODS: Four inflammatory myopathy patients who had been refractory to glucocorticoids, one or more immunosuppressive therapies and intravenous immunoglobulin were treated on an open-label basis. Each patient received two 500 mg doses of RTX 2 weeks apart in one cycle. In one patient who did not respond after the first cycle of RTX, the infusion schedule was modified by the physician. We measured muscle enzyme including CPK, LDH and assessed muscle strength individually to evaluate RTX response. Additionally anti-CD19 antibody was measured. RESULTS: Three patients responded to the first cycle of RTX treatment with improvements in muscle enzyme and muscle strength, and then maintained physical function over the duration of several infusion cycles. In one patient, muscle enzyme did not decrease after the first cycle of RTX, and a high dose glucocorticoid was given. After modifying the treatment schedule with monthly RTX infusion, his muscle enzyme level and muscle strength improved. Anti-CD19 antibody decreased after RTX generally, but responses were variable. Herpes zoster infection occurred in two patients. CONCLUSION: Rituximab may be a therapeutic choice in refractory inflammatory myopathy. However a further trial is needed to confirm the efficacy and prove the safety.

A Case of Caplan's Syndrome Presenting as Acute Onset Polyarthritis

Caplan originally described distinctive pulmonary nodules in miners who had suffered from rheumatoid arthritis. Later, the pulmonary nodules, together with a history of rheumatoid arthritis and exposure to inorganic dust were called Caplan's syndrome. This syndrome has been described by case reports in many countries but only two cases have been reported in Korea up to now. The patient in this case report was a 70-years-old man who had worked in the construction field for 20 years mainly demolishing buildings. He was diagnosed with silicosis by a lung biopsy 1 year prior to admission. He suddenly developed arthralgia and morning stiffness in multiple joints 2 weeks prior to admission. Chest imaging revealed aggravation of the bilateral pulmonary nodules. He was diagnosed with seropositive rheumatoid arthritis. The lung nodules, arthralgia, and morning stiffness improved clinically after treatment with the corticosteroid and disease modifying anti-rheumatic drugs.

A Case of Typical Cogan's Syndrome with Aortitis / 대한류마티스학회지

Cogan's syndrome can accompany a variety of systemic vasculitides including aortitis. A 45-year-old woman with a history of typical Cogan's syndrome presented with orthopnea and exertional dyspnea. Echocardiography demonstrated severe aortic valve insufficiency. Computed tomographic angiography demonstrated active vasculitis affecting the ascending and descending aortas and also showed stenosis of the left subclavian artery, both renal arteries, the celiac axis, the superior mesenteric artery, and the right common iliac artery. She received high dose corticosteroid and then underwent an aortic valve replacement. This is the first case of Cogan's syndrome with aortitis in Korea.

A Case of Churg-Strauss Syndrome with Endomyocardial Fibrosis / 대한류마티스학회지

Cardiac involvement is an important cause of mortality in patients with Churg-Strauss syndrome. The typical cardiac presentation of Churg-Strauss syndrome includes pericarditis, myocarditis, and cardiomyopathy. Endomyocardial fibrosis has rarely been described in patients with Churg-Strauss syndrome. We experienced a patient with Churg-Strauss syndrome who exhibited exertional dyspnea and endomyocardial fibrosis visualized as delayed enhancement on cardiac magnetic resonance imaging (MRI). After glucocorticoid treatment, the patient's symptom resolved, and the eosinophil count decreased to normal. Nine months later, the delayed-enhanced lesion on the cardiac MRI nearly disappeared. Here, we report a case of endomyocardial fibrosis in a patient with Churg-Strauss syndrome with a literature review.

A Case of Wegener's Granulomatosis with Periaortitis and Pachymeningitis / 대한류마티스학회지

Wegener's grandulomatosis (WG) is a systemic small-vessel vasculitis characterized by necrotizing granulomatous lesions and anti-neutrophil cytoplasmic antibodies (ANCA). WG frequently affects the upper and lower respiratory tracts and kidney but involvement of the pachymeninges or large vessels has rarely been reported. We report the first case of WG with periaortitis and pachymeningitis in Korea. A 57-year-old female complained of a stabbing headache, paresthesia below the thoracic 4th nerve level, and lower extremity weakness. During her course, she developed otitis media with sensorineural hearing loss, nodular scleritis, and microhematuria. A neuroimaging study showed an intradural mass in the area from the cervical 7th spine to the thoracic 5th spine, left cerebral convexity, and the left petrous area. A chest computed tomography scan revealed an enhanced and thickened aortic arch. A dural biopsy showed necrotizing granulomatous inflammation, and anti-MPO ANCA was positive. Under a diagnosis of WG, she received high-dose glucocorticoid and oral cyclophosphamide with improvement.