Real-world effectiveness of a single conventional diseasemodifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study

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.

Simplified disease activity changes in real-world practice: a nationwide observational study of seropositive rheumatoid arthritis patients with moderate-to-high disease activity

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.

Effect of biologics in the level of cytokines in the synovial fluid of patients with ankylosing spondylitis

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.

Identification of streptococcus dysgalactiae subsp. equisimilis from septic knee by 16S rRNA gene sequencing / 고신대학교의과대학학술지

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.

A Case of Sepsis Caused by Cellulitis in a Patient with Rheumatoid Arthritis after Tocilizumab Treatment

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.

Update on the Classification Criteria for Vasculitis / 대한내과학회지

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.

A Case of Aortic Dissection with Marfan Syndrome and Ankylosing Spondylitis / 대한내과학회지

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.

Acute generalized exanthematous pustulosis due to hydroxychloroquine in a rheumatoid arthritis patient

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.

Comparison of Effectiveness and Safety of Tramadol/Acetaminophen and Non-steroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Knee Osteoarthritis in Elderly Patients

OBJECTIVE: To compare the analgesic effectiveness and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/acetaminophen) with non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthrits in elderly patients. METHODS: This randomized controlled study enrolled 48 patients with chronic knee osteoarthritis where the diagnostic period was over 3 months. Patients with at least moderate pain [visual analog scale (VAS) with scores > or =40/100 mm] after the washout period were randomized to tramadol/acetaminophen or NSAID. All patients received tramadol/acetaminophen 1 tablet TID or NSAID (naproxen 500 mg) BID. The primary outcome measures were the final pain VAS scores. Secondary measures included pain relief (5 point Likert scale), adverse events, and overall medication assessments. RESULTS: In total, 43 intent-to-treat (ITT) patients received tramadol/acetaminophen (n=21) or NSAID (n=22). Mean baseline pain VAS scores showed no difference between two groups. ITT analysis showed significantly better mean final VAS scores (38.45 vs 31.24, p=0.004) and mean final pain relief scores (2.18 vs 2.95; p=0.007) for tramadol/acetaminophen rather than for NSAID. The most common treatment related adverse events with tramadol/acetaminophen were nausea/vomiting (47.6%) and constipation (33.3%). Epigastric soreness and heartburn was more frequent in NSAID treatment. CONCLUSION: Tramadol/acetaminophen combination showed better effectiveness in pain reduction compared with NSAIDs when used for the treatment of osteoarthritis in elderly patients.

Hearing Loss in Patients with Rheumatoid Arthritis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In patients with rheumatoid arthritis (RA), sensorineural (SN), conductive, and mixed hearing loss (HL) have been reported in increased rates compared with persons without RA. The object of this study was to evaluate the prevalence and type of HL in patients with RA. We also examined the correlation between HL and the clinical data and determined which factors may be involved in the pathogenesis of RA-related HL. SUBJECTS AND METHOD: In this prospective controlled study, we compared 40 RA patients with 40 age and sex-matched controls. All patients underwent rheumatologic evaluation including ESR, CRP, rheumatoid factor, rheumatoid nodule, etc. Audiologic assessment consisting of pure tone, speech, impedence audiometry, and tone decay test was performed. Statistical analysis of the two groups was carried out. RESULTS: The prevalence of the SNHL (air conduction threshold of >30 dB at > or =1 frequency or >25 dB at > or =2 frequencies and both air and bone conduction thresholds within 10 dB of each other) was significantly higher in the RA group (42.5%), and the majority was bilateral and cochlear type. Air conduction threshold at 8,000 Hz differed significantly between the patients and the control group (p< 0.05). Speech and impedence audiometry did not differ in both groups. The presence of SNHL in patients with RA was related to ESR, CRP, patients' age, and medication such as prednisolone. CONCLUSION: SNHL of the cochlear type is increased in patients with RA especially at 8,000 Hz.

A Case of Treatment with Etanercept in Rheumatoid Arthritis Patient on Hemodialysis / 대한류마티스학회지

Disease-modifying antirheumatic drugs (DMARDs) have been used for rheumatoid arthritis (RA) with the aim of controlling synovitis and reducing radiologic progression. Although methotrexate (MTX) is one of the most effective DMARDs, it may cause severe adverse effects. Especially, hematologic toxicity including leukopenia, thrombocytopenia, and fatal pancytopenia is reported in patients with impaired renal function, since renal excretion constitutes the major route of MTX elimination. Tumor necrosis factor-alpha (TNF alpha) inhibitors are well-established biologic agents for the treatment of RA and their clinical efficacy and safety are already demonstrated. But there were few reports on the efficacy and safety in dialysis patients. We described a case of hemodialysis patient with refractory RA that was successfully treated with etanercept, and discussed with literature review.

Bucillamine-Induced Pemphigus Vulgaris in a Patient with Rheumatoid Arthritis and Polymyositis Overlap Syndrome

Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.

Chronic Finger Tip Pain / 대한류마티스학회지

No abstract available.

Pathogenesis of Ankylosing Spondylitis / 대한류마티스학회지

The hallmark of ankylosing spondylitis (AS) is acute and chronic spinal inflammation initiating in the sacroiliac joints, often coupled with enthesitis, presenting as chronic inflammation at the sites of ligamentous and tendinous insertions into bone. Peripheral joint synovitis can be a prominent feature as well. Reactive arthritis (ReA) is a sterile synovitis arising after enteric or urogential tract infections. A great progression has been recently achieved in revealing the causes, and making plans for the treatments for AS and other types of spondyloarthropathy. The human leukocyte antigen (HLA)-B27 has been well known to be associated with disease susceptibility in AS and ReA. But the pathogenesis of AS and ReA is still not well defined. Although the clinical manifestations of AS and ReA may differ, in this review we discuss the two diseases together and focus on recent developments on the pathogenesis of both diseases.

Eosinophilic Fasciitis Associated with Autoimmune Thyroiditis

Eosinophilic fasciitis (EF) is scleroderma-like disease without Raynaud's phenomenon or visceral involvement. It is characterized by painful swelling of the extremities, accompanied by rapid weight gain, fever and myalgia. The acute state of disease is associated with significant peripheral blood eosinophilia, an elevated erythrocyte sedimentation rate and hypergammaglobulinemia. EF is also frequently associated with hematological abnormalities, including malignant lymphoproliferative diseases, but rarely associated with autoimmune thyroiditis. In the present study we report a case of eosinophilic fasciitis associated with autoimmune thyroiditis.

A case of relapsed renal plasmacytoma after complete remission of multiple myeloma / 대한내과학회지

Extramedullary plasmacytoma is a rare presentation of plasma cell dyscrasia. Most such tumors arise on the upper aerodigestive tract and renal plasmacytoma is very rare. The patient was 44 years old female presented with a 3 month-history of palpable mass in the right flank. There was a past history of complete remission after a chemotherapy for multiple myeloma (6 cycles of VAD chemotherapy) for the two years following the first diagnosis. After surgical resection, histologic and immunofluorescence studies of resected specimens revealed that the renal parenchyma was destroyed by sheets of mature plasma cells producing monoclonal protein (IgG-lambda) and by deposits of amorphous eosinophilic substance stained with anti-lambda antisera. Treatment with chemotherapy of Hyper-CVAD and local irradiation was done. The patient has been disease-free for 3 months after treatment. We report a case of relapsed renal plasmacytoma after complete remission of multiple myeloma.

Correlation of ST Segment Elevation in Lead V1 and the Conal Branch of Right Coronary Artery in Patients with Acute Anterior Wall Myocardial Infarction

BACKGROUND AND OBJECTIVES: Dual blood supply to the anterior interventricular septum (IVS), derived from the septal branches of the left anterior descending artery (LAD) and the conal branch of the right coronary artery (RCA), may prevent ST segment elevation in lead V1 during an anterior acute myocardial infarction (AMI), and predict a favorable in-hospital clinical course. SUBJECTS AND METHODS: The admission 12-lead electrocardiogram (ECG), and the coronary angiograms performed within 10 days of hospital admission, were evaluated in 67 patients with anterior wall AMI, as defined by a ST segment elevation > or =2mm in at least 2 of the V1 to 4 leads. The patients were divided into two groups according to the magnitude of the ST segment elevation in V1 lead: group 1 (ST or =1.5 mm, n=45). The conal branch types were classified into small (a diameter 0.5 mm), reaching the IVS. RESULTS: A large conal branch was found in 11 patients of each group 50 and 24%, respectively (p=0.04). There was no significant relation between the sites of the LAD lesion, whether proximal or distal to the first septal branch, and the presence of ST segment elevation in lead V1. The serum cardiac enzymes, Killip class and the incidence of in-hospital congestive heart failure, were not significantly different. CONCLUSION: The absence of ST segment elevation in lead V1 during an anterior AMI suggested that the IVS is protected by a large conal branch, in addition to the septal branch of the LAD, but this did not influence the in-hospital clinical course.

A Case of Gastric Submucosal Tumor Suspected to be Caused by Anisakis / 대한소화기내시경학회지

Anisakiasis is a parasitic disease following eating raw fishes infected with Anisakis larvae. The endoscopic features of the gastric mucosa are edema, erosion, ulceration and hemorrhage. Gastric anisakiasis forming submucosal tumor is rare. Twenty six-year-old man who complained of severe epigastric pain was admitted. The pain began approximately three hours after eating slices of raw Astroconger myriaster. Gastric endoscopy revealed a submucosal tumor with central erosion on the gastric fundus. Endoscopic ultrasonography detected a thickening of the gastric wall made of mainly thickened submucosal layer. Abdominal CT scan showed a gastric mass lesion with hypodensity in the gastric fundus and subsequently wedge resection was performed. The pathologic finding of the resected mass was eosinophilic abscess in the submucosal layer. We report a case of gastric submucosal tumor which seems to be caused by Anisakis, with a review of relevant literature.

A Case of Mantle Cell Lymphoma Presenting as Multiple Lymphomatous Polyposis Involving Skeletal Muscles / 대한소화기내시경학회지

Multiple lymphomatous polyposis (MLP) is an uncommon type of primary non-Hodgkin's gastrointestinal B cell-lymphoma characterized by the presence of multiple lymphomatous polyps along the gastrointestinal tract. Unlike MALT-lymphoma, MLP has a strong tendency for histologically monomorphic character, extra-digestive localization, rare lymphoepithelial lesion and poor prognosis. The malignant cells of MLP share morphological, immunohistologic and cytogenetic similarities with cells of node-based mantle cell lymphoma. We report a case of mantle cell lymphoma presenting with MLP involving various segments of the gastrointestinal tract, skeletal muscles of the right thigh and bone marrow observed in a 71-year-old woman who complained of lower abdominal pain and a palpable right thigh mass.

A Case of Impending Paradoxical Embolus in a Patient with Acute Pulmonary Embolism

Paradoxical embolism refers to the embolic entry of a venous thrombus into the systemic circulation through a right-to-left shunt. Impending paradoxical embolism, in which a venous thrombus extends from the right atrium through a patent foramen ovale (PFO) into the left atrium, is usually diagnosed with echocardiography. The most common cause of paradoxical embolism through a PFO is the acute pulmonary embolism. We report a case of a 78-year-old woman with acute pulmonary embolism, complicated by impending paradoxical embolism.