Tumor necrosis factor (TNF) inhibitors are increasingly used in treatment of rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel diseases including Crohn's disease and ulcerative colitis. Rarely, anti-TNF therapy is associated with neurological complications, including both central and peripheral nervous system disorders. To the best of our knowledge, only one case of infliximab-associated multifocal motor neuropathy with conduction block in a patient with spondyloarthropathy has been reported to date in Korea. Here, we report on the case of a 58-year-old Korean woman affected by RA who developed multifocal motor neuropathy after infliximab treatment.
Arthritis, Psoriatic ; Arthritis, Rheumatoid* ; Colitis, Ulcerative ; Crohn Disease ; Female ; Humans ; Inflammatory Bowel Diseases ; Infliximab ; Korea ; Middle Aged ; Peripheral Nervous System Diseases ; Spondylarthropathies ; Spondylitis, Ankylosing ; Tumor Necrosis Factor-alpha

In the present study, we investigated if priming of autoreactive CD8+ T cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of Kb-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for Kb binding inhibited IFN-gamma production and proliferation of TRP2-180-specific CD8+ T cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific CD8+ T cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive CD8+ T cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific CD8+ T cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.
Animals ; Autoimmune Diseases ; Immunization ; Major Histocompatibility Complex ; Mice ; Peptides ; T-Lymphocytes ; Vitiligo

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder that usually affects adults over 50 years of age. It is characterized by pain and stiffness of the neck, shoulders and hips. Laboratory tests have shown marked elevation of acute phase reactants (ESR and CRP), but there is no specific test to diagnose PMR. Recently, the European League Against Rheumatism and the American College of Rheumatology jointly proposed a new set of classification criteria for PMR. The mainstay of PMR treatment is low-dose glucocorticoids (prednisolone 10-20 mg/day). patients with PMR usually respond very well to steroid therapy within a few days to one week, but will often relapse despite treatment.
Acute-Phase Proteins ; Adult ; Classification ; Diagnosis* ; Glucocorticoids ; Hip ; Humans ; Neck ; Polymyalgia Rheumatica* ; Recurrence ; Rheumatic Diseases ; Rheumatology ; Shoulder

BACKGROUND: Antiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS. METHODS: We retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006–2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups. RESULTS: On multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025–162.343), low PE severity index (OR, 0.948; 95% CI, 0.917–0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040–1.307). Model II included age (OR, 0.930; 95% CI, 0.893–0.969) and aPTT (OR, 1.104; 95% CI, 1.000–1.217). CONCLUSION: We conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I–II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.
Antibodies, Antiphospholipid* ; Antiphospholipid Syndrome* ; Chungcheongnam-do ; Demography ; Hemoptysis ; Humans ; Logistic Models ; Partial Thromboplastin Time ; Phenotype* ; Pregnancy ; Pulmonary Embolism* ; Recurrence ; Retrospective Studies ; Risk Factors ; Thrombophilia ; Thrombosis

Objective: . Hydronephrosis, a common complication of idiopathic retroperitoneal fibrosis (iRPF), may lead to poor renal outcomes unless resolved in a timely manner. IgG4-related diseases characterized by elevated serum IgG4 levels are responsible for a few iRPF cases. However, the underlying immunologic features of most iRPF cases have not been clearly defined, and these cases exhibit varied responses to medical treatment. Thus, we investigated the predictive factors for hydronephrosis-associated outcomes among iRPF patients. Methods: . We retrospectively included 18 iRPF patients with hydronephrosis in a tertiary referral hospital from 2012 to 2019. Hydronephrosis improvement was assessed on images taken 6 months after diagnosis. Categorical variables were compared using chi-square or Fisher’s exact test. Continuous variables were compared using Mann–Whitney U-test. Results: . On follow-up images, 8 patients (44.4%) showed an improvement in hydronephrosis. Patients with improvement more frequently had reverse serum IgG4/IgG3 ratio (87.5% vs. 30%, p=0.025), abdominal aorta involvement (87.5% vs. 30%, p=0.025) and glucocorticoid treatment administration (87.5% vs. 30%, p=0.025) than those without improvement. The proportion of elevated serum IgG4 level did not differ between the two groups.Even in the 14 cases with normal serum IgG4 levels, reverse serum IgG4/IgG3 ratio was more frequently observed in patients with improvement than in those without improvement (83.3% vs. 12.5%, p=0.026). Conclusion . The reverse serum IgG4/IgG3ratio was associated with hydronephrosis improvement in iRPF patients, suggesting it to be a suitable serologic marker for predicting favourable responses to glucocorticoid treatment.

OBJECTIVE: The aim of this study is to determine the clinical characteristics of patients with rheumatoid arthritis (RA) sustaining high erythrocyte sedimentation rate (ESR) despite clinical remission. METHODS: This cross-sectional study involved 91 patients, who visited a tertiary medical center. Patients underwent laboratory tests and a physical examination by a rheumatologist. The disease activity score (DAS) was calculated and patients who were in remission (defined as DAS28-CRP <2.6) were selected. Patients were divided into two groups: those with high and low ESRs (> or =40 and <40 mm/hr, respectively). RESULTS: DAS 28-CRP scores revealed that 61 of the 91 patients were in remission. Of these 61 patients, 15 and 46 were allocated to the high and low ESR groups, respectively. Compared to the low ESR group, the high ESR group had a longer disease duration (99.2+/-60.2 vs. 59.1+/-48.9 months), significantly higher white blood cell counts, and CRP levels, total modified Sharp radiographic joint scores, and erosion scores, as well as significantly lower hemoglobin, albumin and alanine aminotransferase levels. CONCLUSION: Patients who have high ESRs despite their remission status may show progressive radiographic change. In such patients, additional treatments that decreases the inflammation and prevents radiological progression should be considered.
Alanine Transaminase ; Arthritis, Rheumatoid* ; Blood Sedimentation* ; Cross-Sectional Studies ; Erythrocytes* ; Humans ; Inflammation ; Joints ; Leukocyte Count ; Physical Examination

BACKGROUND/AIMS: In some Western countries, up to 50% of patients with ankylosing spondylitis (AS) have subclinical gut inflammation. This study was conducted to evaluate the prevalence and severity of gut inflammation and to determine clinical factors associated with colonic inflammation in Korean AS patients who performed ileocolonoscopy without evidence of established inflammatory bowel diseases before. METHODS: One hundred and eight AS patients who underwent ileocolonoscopy were included in this study. Patients were divided into two groups based on gross ileocolonoscopic findings; patients with inflammatory lesions, and patients without inflammatory lesions. RESULTS: Inflammatory lesions in ileocolonoscopic findings were found in 40 patients. The Ankylosing Spondylitis Disease Activity Score C-reactive protein was higher in the group with inflammatory lesions and gut lesions were found often in the terminal ileum. The risk of inflammatory lesions was higher for AS patients whose symptoms required ileocolonoscopy than for AS patients who underwent routine ileocolonoscopy screening (odds ratio, 3.96). However, abnormal lesions were detected also in 17.6% of the patients who underwent ileocolonoscopy for routine screening and most of them were erosion and ulcer. Among patients with inflammatory lesions (n = 40), 23 showed subclinical gut inflammation associated with AS and 17 were diagnosed finally as Crohn's disease (n = 12), intestinal tuberculosis (n = 4), and ulcerative colitis (n = 1). CONCLUSIONS: Our findings suggest that ileocolonoscopy might be recommended regularly in AS patients even without gastrointestinal symptoms, especially in the patients with high AS activity.
C-Reactive Protein ; Colitis, Ulcerative ; Colon ; Colonoscopy ; Crohn Disease ; Gastrointestinal Diseases ; Humans ; Ileum ; Inflammation ; Inflammatory Bowel Diseases ; Mass Screening ; Prevalence ; Retrospective Studies* ; Spondylitis, Ankylosing* ; Tuberculosis ; Ulcer

OBJECTIVE: The purpose of this study is to evaluate the outcome of uveitis in ankylosing spondylitis (AS) during tumor necrosis factor (TNF)-inhibiting therapy and to compare the incidence rate of uveitis in infliximab, adalimumab, and etanercept. METHODS: A retrospective evaluation was performed in AS patients who had started TNF-inhibiting therapy from June 2003 to June 2011. The clinical characteristics of patients with documented uveitis were evaluated. RESULTS: Among 316 patients treated with TNF inhibitor, 26 patients (8%) had experienced uveitis during TNF-inhibiting therapy. Among them, 15 patients were treated with etanercept, eight with adalimumab, and three with infliximab. The overall incidence rate of uveitis flare during therapy with TNF inhibitor was 46 per 1,000 person-years (pys) (95% confidence interval [CI], 32 to 64). The incidence rate did not differ between TNF inhibitors, with 54/1,000 pys (95% CI, 34 to 81) for etanercept, 46/1,000 pys (95% CI, 21 to 87) for adalimumab, and 22/1,000 pys (95% CI, 5 to 64) for infliximab. Fourteen patients experienced a first episode of uveitis. The overall incidence rate of new onset-uveitis after therapy with TNF inhibitor was 19 per 1,000 pys (95% CI, 10 to 31). The incidence rate for etanercept was 24/1,000 pys (95% CI, 12 to 45); adalimumab, 15/1,000 pys (95% CI, 3 to 45); and infliximab, 7/1,000 pys (95% CI, 0 to 40). There was no statistical difference in the incidence of uveitis flare or the cumulative uveitis-free rate among the three TNF inhibitors. CONCLUSION: The relative rate of uveitis, including the first episode, was determined using the TNF inhibitor. However, there was no difference in the incidence rate of uveitis among the three TNF inhibitors.
Humans ; Incidence* ; Korea* ; Retrospective Studies ; Spondylitis, Ankylosing* ; Tumor Necrosis Factor-alpha* ; Uveitis* ; Adalimumab ; Infliximab ; Etanercept

BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100 RA-ILD patients who visited our tertiary care medical center between 2004 and 2011, identified those treated with an anti-TNF agent, divided patients into non-survivor and survivor groups and evaluated their clinical characteristics and causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was significantly higher in the nonsurvivor versus survivor group (76 years [range, 66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean duration of anti-TNF treatment in the non-survivor group was shorter (7 months [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The duration of anti-TNF therapy in all nonsurviving patients was < 12 months. Pulmonary function test results at ILD diagnosis, and cumulative doses of disease-modifying drugs and steroids, did not differ between groups. Five of the six deaths (83%) were related to lung disease, including two diffuse alveolar hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The sixth patient died of septic shock following septic arthritis of the knee. CONCLUSIONS: Lung complications can occur within months of initial anti-TNF treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used with caution in these patients.
Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/complications/diagnosis/*drug therapy/immunology/mortality ; Female ; Humans ; Lung Diseases, Interstitial/diagnosis/etiology/*mortality ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors