Search

Objectives To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). Methods The Korean Rheumatoid Arthritis–Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. Results This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were ‘improving’ [n = 11 (7.9%)], ‘stable’ [n = 68 (38.4%)], ‘slowly declining’ [n = 54 (48.6%)] and ‘rapidly declining’ [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. Conclusion Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.

Objective To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). Methods The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. Results Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. Conclusion None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting primarily joints and an increased risk of developing malignant lymphomas in RA has been well reported. However, primary lymphoma in a joint in RA patient is rare. We report the case of a 65-year-old man with RA suffering from pain and swelling of left sternoclavicular (SC) joint, which was not relieved by adding low-dose glucocorticoid. Magnetic resonance imaging (MRI) showed a para-osseous soft tissue swelling around the SC joint and a fracture of proximal clavicle. Histology of the soft tissue demonstrated diffuse large B-cell lymphoma and the patient subsequently underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. He was successfully treated with six cycles of R-CHOP chemotherapy, with discontinuation of MTX, resulting in a complete response. We performed a literature review and identified nine cases of lymphoma which involved joints in patients with rheumatoid arthritis. This is the first described case of a primary large B-cell lymphoma involving the unilateral SC joint in a patient with RA, which was initially confused with aggravation of RA. Therefore, malignant lymphoma should be considered in the differential diagnosis when a RA patient develops monoarthritis with spontaneous fracture, even without B symptoms.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is an environment that provides various biological niches, such as the teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome also plays an important role in the triggering, development, and progression of oral and systemic diseases. In recent years, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology and is overwhelmingly promising compared to the previous era. It has been found that patients with oral and systemic diseases have variations in their oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that the oral microbiome plays in influencing oral and systemic diseases and furthers the knowledge related to the oral microbiome produced over the past 30 years. A wide range of updates were provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and can help to develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

Background/aims This study aimed to investigate the inf luence of poor sleep quality on clinical features of primary Sjogren's syndrome (pSS). Methods Sleep quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index (PSQI), and demographic, clinical, and laboratory data were collected from 115 Korean patients with pSS. The patients completed questionnaires on the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and patient global assessment (PGA) were evaluated with a 100-mm visual analogue scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity Index (ESSDAI) were calculated at study enrollment. Results Fifty-three patients (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra-glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were significantly higher and immunoglobulin G levels tended to decrease in poor sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI. Multivariate analysis revealed that poor sleep quality remained the independent determinants of the unsatisfactory symptom state (ESSPRI ≥ 5). Conclusion Our results showed that poor sleep quality could significantly affect the patient-oriented outcomes and physician-reported activity index of pSS patients through the various effects of sleep quality on the psychological or somatic symptoms and the immune system.

Headaches are common in patients with systemic lupus erythematosus (SLE). It is important to identify the exact cause of headaches in SLE to avoid unnecessary steroid or immunosuppressive therapy like in neuropsychiatric SLE. A 35-year-old woman with SLE suddenly developed severe headache. Magnetic resonance angiography showed multifocal segmental narrowing of cerebral arteries, suggestive of central nervous system vasculitis. However, lack of abnormal enhancement in vessel wall imaging indicated reversible cerebral vasoconstriction syndrome (RCVS) rather than central nervous system vasculitis. The patient was treated with oral nimodipine and she recovered over a period of two months. Following magnetic resonance angiography on day 90 was normal. Herein we report a case of reversible cerebral vasoconstriction syndrome in an SLE patient with literature review.

Systemic vasculitis is a group of diverse diseases characterized by immune-mediated inflammation of blood vessels. Current treatments for vasculitis, such as glucocorticoids and alkylating agents, are associated with significant side effects. In addition, the management of both small and large vessel vasculitis is challenging due to a lack of robust markers of disease activity. Recent research has advanced our understanding of the pathogenesis of both small and large vessel vasculitis, and this has led to the development of novel biologic therapies capable of targeting key cytokine and cellular effectors of the inflammatory cascade. It is anticipated that these novel treatments will lead to more effective and less toxic treatment regimens for patients with systemic vasculitis.

Introduction and objective Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction. Methods Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed. Results A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05). Conclusion Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.

Background: The aim of this study was to investigate clinicoserologic biomarkers associated with the development, progression, and prognosis of connective tissue diseases associated interstitial lung disease (CTD-ILD). Methods: We conducted a single center, a retrospective study including 70 incident patients diagnosed with CTD-ILD and 70 age-, sex-, and type of CTD-matched patients without ILD. Clinical informations, pulmonary function test, and chest CT findings were reviewed using medical records. To identify serologic biomarkers, serum interferon-r-induced protein 10 (IP-10), interleukin (IL)-6, IL-8, IL-10, and matrix metalloproteinase 7 (MMP-7) in patients with CTD-ILD and CTD without ILD were measured. Results: A total of 140 patients were enrolled. The mean was 63.3 ± 11.2 years, and 102 (72.9%) patients were female. Raynaud`s phenomenon (OR 5.96, 95% CI 2.11–16.86) was proved to be a risk factor for developing ILD in CTD by multivariable logistic regression analysis. To analyze distinctive features according to the onset of ILD, CTD-ILD was stratified into three groups: ILD-preceding, simultaneous, and CTD-preceding. The majority of the ILD-preceding group (75%) had worse baseline pulmonary function requiring treatment (DLCO

Background SinceBohan and Peter first described their diagnostic criteria foridiopathic inflammatorymyopathies (IIM) in 1975, new discoveries suchas myositis-specific and myositis-associated autoantibodies (Abs) have been made. Objectives To investigate correlations between specificmyositis Abs and their frequenciesand clinical associationsacross different IIM groups, collectively demonstrating theutility of the new clinicoserologic classification in Koreanadult patients with IIM. Methods We conducted a multicenter cohort study including 67adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria.Immunoblot assay with Euroline strip(EUROIMMUN, Germany)was performed using the sera of definite deramatomyositis (DM, n=36), definite polymyositis (PM, n=25), amyopathic DM (n=4), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (IMNM, n=1). Patients were classifiedbased on three classifications: 1) novel clinicoserologic classification suggested by Troyanov et al. in 2017. 2) 2017 EULAR/ACR classification criteria. 3) 2004 European neuromuscular center (ENMC) criteria.Associations ofmyositis Absand clinical subsets of IIM were investigated. Results The distribution of the various IIM differed strikingly from those using the 3 classifications (Fig1). According to the 2004 ENMC classification and 2017 EULAR/ACR classification criteria, DM and PM was the most and the second frequent entities (DM: 55.2%, 56.7%; PM: 35.8%, 37.3%). But, using the new clinicoserologic classification,overlapmyositis(OM) is the major type of IIM and the frequency of PM is significantly decreased.Anti-ARS Abs specificity included anti-Jo-1(16.4%), -OJ(4.6%), -EJ(6.2%) -PL-7(3.1%), and -PL-12(4.6%). Interstitial lung disease was closely associated with anti-MDA5,and anti-ARS Abs, while DM-specific skin lesion was frequently observed in patients with anti-TIF1γ and anti-ARS Abs. Sevenpatients with cancer-associated DM were identified. They were positive for anti-TIFγ (5/7) and anti- SRP(3/7) (table 1). Conclusion Novel classification based on distinctive features and new myositis Absreflects the clinical phenotype of IIM better. Establishment of a system routinely available to screen myositis Abs is needed. Thiswill be beneficial to providemore precise diagnosis and proper management for patients with IIM. Reference: [1] Jean-Luc Senecal, Jean-Pierre Raynauld, Yves Troyanov. A New Classification of Adult Autoimmune Myositis. Arthritis Rheum2017;69:878-884. Disclosure of Interests None declared

Background: Myositis-specific and myositis-associated autoantibodies (MSA and MAA) have been used for more detailed classification and prediction of clinical course of idiopathic inflammatory myopathies (IIM). Interstitial lung disease (ILD) is known to be complicated with approximately 50% of IIM patients, having poor prognosis. Objectives: The aim of this study is to investigate clinical features of ILD in Korean adult patients with IIM according to the autoantibody profile including MSA and MAA. Methods: We conducted a multicenter cohort study including 108 adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria MSA and MAA were screened with Immunoblot assay using Euroline strip (EUROIMMUN, Germany). Clinical information including the time of developing ILD and imaging findings of chest CT was reviewed using by medical record. Results: ILD was found in about half (52.8%, 57 of 108) of enrolled patients and closely associated with the presence of anti-ARS Abs, anti-MDA5 and anti-Ro52. Among 43 patients, Anti-ARS Abs were most common (46.5%) and included anti-Jo-1 (23.3%), -OJ (2.3%), -EJ (9.3%), -PL7 (14%), and -PL12 (7%) (Figure 1). To analyze the correlation of autoantibodies with pattern of ILD onset, we stratified the 43 patients into three groups: into ILD-preceding (7/43, 16.3%), simultaneous (31/43, 72.1%) and myopathy-preceding (6/43, 14%). In the ILD-preceding group, anti-ARS antibodies were frequent. ILD preceded myopathy by 19.5 months on average. The imaging pattern of ILD in the ILD-preceding group were Cryptogenic Organizing Pneumonia (COP) 6, Nonspecific Interstitial Pneumonia (NSIP) 1 and no Usual interstitial pneumonia (UIP). A half of patient in ILD-preceding group had Raynaud`s phenomenon, and one patient had mechanic hand. On the other hand, in myopathy-preceding group, 30% of patients (2/6) were UIP and a half of patients had pulmonary function which required treatment (DLCO Conclusion: In our study, ILDs were accompanied by over half of the cases of IIM and most of them had autoantibodies. There are characteristic clinical features by onset time of ILD, so paying attention to them will help early diagnosis and prognosis prediction of ILDs. Reference [1] Yoshifuji H. Clin Med Insights Circ Respir Pulm Med. 2016 Apr 3;9 (Suppl 1):141-6. Disclosure of Interests: None declared

Aim This study aimed to investigate the clinical features and risk factors of gout attacks during anti-tuberculosis (TB) treatment in South Korea. Method We investigated the clinical characteristics of 49 patients who suffered from gout attacks while taking anti-TB medications. Among them, 25 TB patients having newly developed gout attacks without prior history of gout were set to the gout group. Seventy-five age- and sex-matched TB patients without gout attacks during anti-TB therapy were randomly selected as the control group. The demographics, clinical features, and laboratory findings between the two groups were compared to establish risk factors of gout attack during anti-TB treatment. Results The gout patients had a mean age of 67.7 ± 13.2 years and 39 patients (79.6%) were male. Approximately half of the patients experienced an attack within 2 months of treatment initiation. The attacks typically involved lower extremity joints (87.8%). The serum uric acid (SUA) levels were significantly elevated at 2 and 6 months after starting anti-TB medication compared with those at baseline. In the case-control study, the factors associated with gout attack were higher body mass index (BMI), higher pre-treatment SUA levels, dyslipidemia, and reduced renal function. In the multivariate model, higher BMI, chronic kidney disease (CKD), and pre-treatment hyperuricemia (SUA ≥ 6.8 mg/dL) were independent risk factors of gout attack while taking anti-TB medication. Conclusions Patients with high BMI, CKD, and pre-treatment hyperuricemia are at a higher risk of gout attack during TB treatment.

Background Hip pain is a common musculoskeletal complaint in general practice. Although comprehensive diagnostic approach on hip pain is mandatory for adequate treatment, un- or mis-diagnosis is not rare in primary care. The aim of this study was to analyze descriptively un- or mis-diagnosed hip pain cases referred from primary care to a tertiary hospital, especially in young adults ≤ 50 years old. Methods We retrospectively analyzed a consecutive cohort of 150 patients (≤ 50 years old) with chronic hip pain (≥ 6 weeks), which was not diagnosed or misdiagnosed based on the information provided on the referral form. Results Overall an average 32 cases/month were referred due to hip pain without a diagnosis or with an incorrect diagnosis. Among them, 150 patients were enrolled in this study and 146 (97.3%) could be allocated to a specific disease by using data from routine clinical practice. Four common final diagnoses were femoroacetabular impingement (FAI) syndrome (55.3%), hip dysplasia (HD, 13.3%), referred pain from the lumbar spine (9.3%), and spondyloarthritis (SpA, 7.3%). In patients with FAI syndrome, 37 (44.0%) had pincer-type FAI and 33 (39.8%) had combined-type. Although the pain site or gender was not tightly clustered, the distribution of final diagnosis was significantly different according to hip pain location or gender. Especially, SpA or HD was not observed in younger women subgroup or elder men subgroup, respectively, when stratified by the mean age of participants. Conclusion Most (> 80%) young patients with hip pain, a difficult issue to diagnosis for many primary physicians, had FAI syndrome, HD, spine lesions, and SpA. This study could give a chance to feedback information about cases with un- or mis-diagnosed hip pain, and it suggests that primary physicians need to be familiar with the diagnostic approach for these 4 diseases., Graphical Abstract

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 anti-TIF1γ, 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.

Spondyloepiphyseal dysplasia (SED) tarda is an inherited skeletal arthropathy. Because SED tarda involves the joints and resemble the clinical findings of chronic arthropathies, this disease is frequently misdiagnosed as juvenile idiopathic arthritis (JIA). We report here on three patients (father and his two daughters) in one family with SED tarda. All patients had back pain and polyarthralgia. Their radiographs revealed typical changes for SED tarda including platyspondyly and dysplastic bone changes. This rare disease has major clinical importance in that it is similar with JIA or rheumatoid arthritis.

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that frequently affects the lungs and kidneys. However, GPA limited to a single organ has also been reported. A 73-year-old man was admitted for back pain and fever. We detected elevated levels of inflammatory markers and myeloperoxidase-ANCA. Magnetic resonance imaging indicated diffuse inflammation of the back and psoas muscles. Histology showed degenerated muscle fibers and granulomatosis vasculitis with mixed lymphoplasma cell infiltration. High-dose methylprednisolone therapy improved his symptoms. A final diagnosis of GPA limited to the muscles was made.

Rationale Rituximab is recommended to induce remission of severe granulomatosis with polyangiitis (GPA). Plasma exchange (PE) may be considered in the setting of rapidly progressive glomerulonephritis (RPGN) with a serum creatinine increase of more than 5.6 mg/dl or diffuse alveolar hemorrhage (DAH). However, there are no sufficient studies on combination therapy with rituximab and PE in GPA. Patient concerns A 23-year-old woman was admitted with fever, abdominal pain, and diarrhea on suspicion of infectious colitis. Colonoscopy showed hemorrhagic colitis and antibiotic treatment was ineffective. Physical examination revealed episcleritis and skin lesions similar to Janeway lesions or Osler nodes on her palms and soles. Transesophageal echocardiogram (TEE) revealed mitral valve vegetation mimicking infective endocarditis. However, no pathogen was grown in the blood culture. Ten days after admission, blood-tinged sputum and respiratory distress developed. Imaging studies of lung, bronchoscopy, and bronchoalveolar lavage indicated DAH. Moreover, serum creatinine levels rapidly increased from 0.8 mg/dl to 6.1 mg/dl with proteinuria. Diagnosis The patient was diagnosed with GPA and non-infectious endocarditis, DAH, and RPGN, based on a biopsy which revealed pauci-immune crescentic glomerulonephritis with granuloma and leukocytoclastic vasculitis and antineutrophil cytoplasmic antibodies against proteinase 3- positivity. Interventions Initial methylprednisolone pulse therapy (1 g daily for 3 days) proved unsuccessful. After initiating PE, creatinine levels began to slowly decline, but DAH continued to deteriorate. Rituximab combined with PE therapy was considered. We performed PE every 2 to 3 days for 5 total treatments combined with rituximab (375 mg/m, once weekly for 4 weeks). Outcomes After the combination treatment of rituximab and PE, alveolar hemorrhage stopped. Chest X-ray and laboratory data, including serum creatinine and hemoglobin, notably improved. Mitral valve vegetation was no longer observed in follow-up TEE. GPA remained stable with low dose prednisolone and immunosuppressants over a follow-up period of 5 years. Lessons This case suggests that the use of rituximab and concurrent PE may represent a promising combination for severe and refractory GPA.

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p<0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p=0.001) and IL-6 (p<0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p=0.007) and TNF-α (p=0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p=0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p=0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily involving the spine and sacroiliac joint and rarely the kidneys. This study aimed to define the clinical and histological features and biology of renal disease in AS. We reviewed the medical records of 681 patients diagnosed with AS from November 2008 to November 2009. Baseline characteristics and laboratory and urinalysis results were reviewed. We identified patients with proteinuria or hematuria and analyzed their risk factors. After providing informed consent, 6 patients underwent a renal biopsy to determine the cause of proteinuria or hematuria. Of the 681 enrolled patients, 547 were men and 134 were women; 81 % were HLA B27 positive, and 8 % had abnormal urinalysis findings (proteinuria, 5.9 %; hematuria, 2.8 %; both, 0.7 %). Incidences of peripheral arthritis and uveitis were 29 % and 18.6 %, respectively. Immunoglobulin (Ig)A and uric acid levels were significantly different between patients with and without proteinuria. Erythrocyte sedimentation rate (ESR), total cholesterol, creatinine, and C-reactive protein (CRP) levels were not statistically significantly different between the 2 groups nor were there any significant differences in IgA, uric acid, ESR, total cholesterol, creatinine, and CRP levels between patients with and without hematuria. Six patients who had >1 g/day proteinuria underwent a renal biopsy; 2 were diagnosed with IgA nephropathy, 1 with amyloidosis, and 3 with non-specific glomerulonephropathy. In the amyloidosis patient, severe proteinuria was the dominant feature. For patients with renal amyloidosis and other forms of glomerulonephritis who initially had normal creatinine levels, tumor necrosis factor (TNF)-alpha blocker therapy resolved proteinuria, but this was not the case for patients with initial renal insufficiency. Renal involvement is not a rare complication of AS, and prognoses differ depending on kidney pathology. Serum levels of uric acid and IgA may predict renal involvement in AS. In cases where abnormal urine sediment is identified, renal biopsy is required to determine prognosis and decide the treatment protocol. Baseline serum creatinine level is important for predicting treatment response.

Chip curling occurred during cutting process for difficult-to-cut material detracts product qualities and productivity. Among of method preventing the phenomenon, high pressure injecting cutting oil is an alterative. In this study, the optimal nozzle was designed by CFD method and it was conducted to analyse on the effect of high pressure injection on chip shape generated during cutting process and wear of insert by experimental method. As the result, it could be confirmed that high pressure injection is favorable for preventing chip curling and insert from wearing.

Sparganosis in humans is an incidental infection and is known to be associated with eating insufficiently cooked meat of frogs and snakes or drinking unboiled stream water. Although it can involve various internal organs, pulmonary and pleural involvement due to sparganum is rare. Because we recently experienced two cases involving lung parenchyma and pleura that were misdiagnosed as bacterial pneumonia and lung cancer, we herein intend to present them in detail. Keywords: Sparganosis, Multiple pulmonary nodules, Parasites, Pleural effusion

To the Editor: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton and large peripheral joints. The efficacy of tumor necrosis factor (TNF) antagonists in the treatment of AS has been documented in several metaanalyses of randomized trials, in which significant improvements in disease activity were observed1. However, there is no evidence that anti-TNF-α agents prevent radiographic progression in patients with AS. In rheumatoid arthritis (RA), anti-TNF-α agents can prevent bone erosion and radiographic progression by suppressing osteoclast activity2,3. Unlike new bone formation in the axial spine, synovial inflammation within the hip joint induces bone erosion and subsequent joint destruction4,5 in AS. Additionally, the histological appearance of the synovial membrane of the hip joint in patients with AS is similar to that observed in RA6. These results suggest that both osteoproliferative and osteodestructive changes may occur in parallel at different sites in AS. In the present case series, we reviewed 6 patients with AS whose hip joint space … Address correspondence to Professor S.H. Lee, Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, 892 Dongnam-ro, Gangdong-gu, Seoul 134-727, Republic of Korea. E-mail: boltaguni{at}yahoo.co.kr

To investigate the psychosocial aspect of the family members of the patients with rheumatoid arthritis (RA), we conducted a population-based analysis to examine the psychosocial characteristics of family members of RA patients in comparison with the general population. From the Fifth Korea National Health and Nutrition Examination Survey dataset (KNHANES V) (2010-2012), we identified 363 RA patients and selected family members of these patients who were aged 20 years or older (n = 367). The control group was randomly sampled from members of families without RA patients and matched for sex and age (n = 1101). We compared the psychosocial characteristics of family members of RA patients with the control group. Additionally, serial conditional logistic regression models were performed to evaluate the factors that affect psychosocial status of the RA family members, after adjusting for covariates. No significant differences were found in socioeconomic status between the two groups. For psychological factors, stress (85.8 vs 74.7 %, p < 0.001) and depression (7.9 vs 3.3 %, p < 0.001) were more common in the family members of RA patients. The presence of a RA patient in the family showed a positive association with stress [odds ratio (OR) 2.07; 95 % confidence interval (CI) 1.48-2.88, p < 0.001] and depression (OR 2.59, CI 1.55-4.32, p < 0.001), after adjusting for socioeconomic status. Our data show that the family members of RA patients have an increased prevalence of stress and depression. Physicians who treat RA patients should also consider the needs and the burden of family members.

Background High risk of cancers in patients with myositis is partly explained by common expression of myositis-associated autoantigens in cancer tissues and in regenerating muscles. Malignancies found in myositis patients would be either cancers directly involved in myositis development or cancers that are not different from those found in general population. Objectives To compare the standardized incidence ratio (SIR) of cancers related and unrelated to myositis activity in Korean patients with myositis Methods Medical records of 283 patients with polymyositis (PM) or dermatomyositis (DM) were reviewed to identify 52 cancer cases. SIR was calculated using cancer incidence of period-, age- and sex-matched Korean population. Under the hypothesis that cancer tissues should temporally overlap with active myositis in patients whose cancers are involved in myositis development, cancer cases were divided according to the presence (group A, cancers related to myositis activity, n=32) or absence (group B, cancers unrelated to myositis activity, n=20) of either newly diagnosed, remnant, or recurred cancers at any time during active phase of myositis. SIRs of groups A and B were compared. Results The mean (±standard deviation) age at myositis diagnosis was 47.7±15.1 years in all patients and 77.7% were female. The overall SIR was 3.0 [2.2-4.0] (4.4 [2.6-6.8] in men; 2.51 [1.7-3.6] in women). Although a majority of cancers were found from 509s to 709s, the highest SIR, 22.8 [4.7-66.5], was observed in 209s. When stratified by intervals between myositis and cancer diagnoses, no elevated SIR was noted except for 10.3 [6.8-15.1] within 1 year of myositis diagnosis, and for 3.2 [1.2-6.9] during the next 2 years. The most frequent cancer was non-Hodgkin9s lymphoma (NHL, 23.0 [9.3-47.4]). SIRs of esophageal cancer (23.6 [4.9-68.8]), multiple myeloma (MM, 22.9 [2.8-82.7]), lung cancer (6.4 [2.9-12.1]), and adenocarcinoma of unknown primary (ACUP, 25.7 [7.0-65.7]) were also higher than general population. When compared groups A and B, group A tended to be more male-predominant (14/30 vs 5/22, p=0.077) and had an older age at myositis diagnosis than group B (60.5±11.1 vs 49.3±16.6 years, p=0.022). There was no difference in PM and DM distribution. The SIR in group A was 1.8 [1.2-2.6] (3.0 [1.6-5.1] in men; 1.3 [0.8-2.2] in women) while in group B, it was 1.2 [0.8-1.9] (1.4 [0.5-3.0] in men; 1.2 [0.6-2.0] in women). Elevated SIRs were observed in 609s in group A (2.6 [1.4-4.5]) and in 209s in group B (22.8 [4.7-66.5]). The SIR within 1 year of myositis diagnosis was 9.9 [6.4-14.7] in group A while in group B, there was no temporal relationship between myositis and cancer. Elevated SIRs were observed for esophageal cancer (23.6 [4.9-68.8]), NHL (16.4 [5.3-38.3]), and ACUP (25.6 [7.0-65.7]) in group A while lung cancer (3.6 [1.2-8.3]) in group B. Conclusions Cancer risk in Korean patients with myositis was approximately 3 times higher than general population. SIRs of NHL (23.0 [9.3-47.4]), esophageal cancer (23.6 [4.9-68.8]), MM (22.9 [2.8-82.7]), lung cancer (6.4 [2.9-12.1]), and ACUP (25.7 [7.0-65.7]) were significantly higher than general population. Two distinctive groups of cancers were noted according to the relationship with myositis activity in terms of incidence, temporal relationship with myositis, age distribution, and histologic types of cancers. Disclosure of Interest None declared

Background Red blood cell distribution width (RDW) is a biomarker quantifying the variability of red blood cell size (anisocytosis) in the peripheral blood. High RDW is associated with inflammatory burden and it has been suggested as a potential marker for cardiovascular prognosis, mortality, or reflecting renal function in the various clinical conditions 1 . A recent study found the significant association between serum uric acid level and RDW in patients with untreated essential hypertension 2 . Gouty arthritis is an acute and severe inflammatory arthritis attributable to hyperuricemia, and closely associated with renal dysfunction and cardiovascular diseases. However, few studies have yet investigated the clinical significance of RDW in patients with gout. Objectives The aim of this study was to investigate the potential association of RDW value with clinical features in patients presenting with acute gout attack. Methods The medical records of patients who visited emergency room of Seoul National University Bundang Hospital for acute gout attack, from March 2003 to April 2014, were retrospectively reviewed. Cases were stratified into three groups according to the RDW tertiles ( 13.4%) and clinically relevant differences were evaluated by the ANOVA test or the chi-square test. The Pearson9s correlation approach was used to analyze the correlation between two continuous variables. To identify significant determinants influencing RDW, we used multiple linear regression analysis. Results Two-hundred and thirty-six patients with acute gout attack were included. The mean age was 49.38±16.85 years and the male ratio was 92.3% (n=218). The patients in the highest RDW tertile tended to be older, had higher levels of hemoglobin and lower levels of albumin, and had more recurrence of gout attack and renal impairment. RDW showed significant weak positive correlation with age (γ=0.224, p =0.001) and creatinine level (γ=0.237, p p p p =0.009) (Table 1). Conclusions Our data shows that high RDW in acute gout attack is related to the recurrence of gout attack and coexistence of chronic kidney disease. In acute gout attack, RDW, an easy and quick measurable index, may represent renal dysfunction rather than inflammatory burden or uric acid level, and physicians who treat acute gouty arthritis with high RDW should pay attention to the recurrence of gout attack and treatment. References Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009;133:628-32. Luo M, Li ZZ, Li YY, Chen LZ, Yan SP, Chen P, et al. Relationship between red cell distribution width and serum uric acid in patients with untreated essential hypertension. Sci Rep 2014;4:7291. DOI: 10.1038/srep07291 Disclosure of Interest None declared

Background Ankylosing spondylitis (AS) is a chronic inflammatory arthropathy, which primarily affects the sacroiliac joints and axial skeleton. In AS, involvement of the facet joints results in both back pain, and limitation of spinal mobility. Involvement of facet joint in AS have been reported in several articles. Improvements in spinal mobility in AS after treatment with tumor necrosis factor (TNF) inhibitors have been reported. However, TNF inhibitors were reported to increase or to not inhibit structural damage progression in AS, as assessed using plain radiography. It seems logical that improvement in spinal mobility by TNF inhibitors would result from their effects on facet joint. Objectives To study the effect of TNF inhibitors on progressive facet joint damage in AS patients. Methods AS patients who were treated with TNF inhibitors and had 2 sets of spinal computed tomography (CT) scans, a median of 50.96±5.47 months apart, were included (n=25). Radiographic severity of facet joints was assessed by a new scoring system using CT. Total facet joints from C2-C3 to L5-S1 were scored: erosions 1, subchondral sclerosis 2, partial ankyloses 3, and total ankyloses 4. We compared the longitudinal effects of TNF inhibitors with non-TNF inhibitor treatment by scoring of facet joint of 25 AS patients who were not treated by TNF inhibitors. Results The mean age were 30.9±6.7 years and no significant differences in gender distribution (male, 84% vs. 88%). The only significant difference between two groups was that TNF inhibitor treated group had longer disease duration (years, 4.15±4.02 vs. 2.13±1.73, p=0.001). Significant increases in CT score in the total spine and T-spine were observed in both groups at follow-up time points (Table 1). The rates of increase in CT score of the total spine were similar in both groups, whereas, the rates of increase in CT score of the T-spine was lower in the TNF inhibitor treated group than in the non-TNF group. However, the difference was not statistically significant (p=0.387; Fig. 1). Conclusions Treatment with TNF inhibitors did not prevent the radiographic progression of facet joints damage in AS patients References Wilkinson M, Bywaters EG. Clinical features and course of ankylosing spondylitis; as seen in a follow-up of 222 hospital referred cases. Ann Rheum Dis. 1958;17:209-28. 2Machado MA, Barbosa MM, Almeida AM et al. Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis. Rheumatol Int. 2013;33:2199-213. Disclosure of Interest None declared

Background Polymyositis (PM) and dermatomyositis (DM) is known to be associated with certain HLA alleles in several ethnic groups including Caucasians, African-Americans, and the Japanese. Objectives To investigate the profile of HLA class II alleles in Korean patients with PM and DM Methods Sequencing based genotyping for HLA-DRB1 and -DPB1 was performed in 140 Korean patients with DM (n=104) or PM (n=36) and in 207 healthy controls. Associations of each HLA-DR or -DP allele with myositis or clinical subsets of myositis were examined. Results HLA-DRB1*14:54 (odds ratio [95% confidence interval] 1.05 [1.01-1.09]), -DRB1*15:02 (2.44 [1.03-5.81]), -DRB1*16:02 (1.04 [1.00-1.07], and -DPB1*09:01 (2.44 [1.03-5.81]) were found to be susceptibility alleles while HLA-DRB1*14:01 (0.93 [0.90-0.97]) and -DRB1*15:01 (0.38 [0.18-0.79]) to be protective alleles for inflammatory myositis (Table 1). In DM, HLA-DRB1*15:02 (3.14 [1.30-7.62]) and -DPB1*09:01 (2.87 [1.17-7.05]) carriers were more frequent while HLA-DRB1*14:01 (0.93 [0.90-0.97]), -DRB1*15:01 (0.30 [0.12-0.74]), and -DPB1*04:02 (0.44 [0.20-0.94]) carriers were less frequent than controls. In PM, HLA-DRB1*14:03 (6.52 [1.78-23.81]), and -DRB1*14:54 (1.13 [1.00-1.23]) carriers were more frequently observed. When PM and DM were compared, HLA-DRB1*14:03 carriers were more frequently observed in PM (5.43 [1.23-24.02]). When the association between each allele and clinical subsets was examined, patients with interstitial lung disease (ILD) carried HLA-DRβ1*04:03 (6.34 [1.35-29.76]), -DRβ1*07:01 (0.22 [0.08-0.64]), -DRβ1*09:01 (0.16 [0.05-0.60]) -DRβ1*12:02 (2.91 [1.16-8.01]) DRβ1*15:01 (0.10 [0.01-0.80]), -DPβ1*14:01 (8.90 [1.08-73.21]), and -DPβ1*17:01 (0.11 [0.01-0.92]) more frequently than patients without. DM patients with ILD showed higher frequency of HLA-DRβ1*04:05 than DM patients without ILD (4.68 [1.24-17.74]). Other associations included dysphagia with HLA-DRβ1*08:02 (6.73 [1.51-30.00]), -DRβ1*14:54 (5.19 [1.09-24.57]), and -DPβ1*03:01 (5.19 [1.09-24.57]), arthralgia with HLA-DRβ1*03:01 (4.79 [1.21-18.98]) and -DPβ1*02:01 (2.30 [1.10-4.82]), and mechanic9s hand with HLA-DRB1*08:03 (3.25 [1.12-9.45]) and -DRB1*12:02 (5.04 [1.66-15.29]). Regarding skin rashes, heliotrope rash was associated with HLA-DRβ1*09:01 (2.98 [1.05-8.46]) and -DPβ1*05:01 (0.41 [0.18-0.87]), Gottron9s papules with HLA-DRβ1*14:05 (8.77 [1.07-72.17]), -DPβ1*02:01 (2.29 [1.11-4.73]), -DPB1*02:02 (0.086 [0.01-0.67]), and -DPB1*05:01 (0.41 [0.20-0.85]), and shawl sign with HLA-DRB1*14:05 (4.67 [1.15-18.99]) and -DPB1*14:01 (4.67 [1.15-18.99]). Cancer development was associated with HLA-DRB1*12:01 (7.25 [1.65-31.89]) and -DRB1*13:02 (0.81 [0.74-0.88]). No HLA-DRB1 or -DPB1 allele was found to be associated with anti-Jo1 antibody. Conclusions Korean patients with inflammatory myositis showed a unique profile of HLA-DR and -DP alleles compared with other ethnic groups. Alleles associated with disease susceptibility were different between PM and DM. Clinical subsets, particularly ILD, showed different immunogenetic backgrounds. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis with female-predominance, and is 2-4 times more likely to develop in women than in man. Hence, researchers have suggested that immunological aspects of sex hormones may influence the induction of autoimmunity, and several epidemiological studies have tried to find relevant reproduction factors on the development of RA. However, results of these studies are inconsistent and most study populations were Caucasian. Objectives To investigate the contributions of breastfeeding and other reproductive factor in relation to RA in Korean population. Methods From the Fifth Korean National Health and Nutrition Examination Surveys (KNHANES V) (2010-2012) dataset, we identified 279 female patients who were diagnosed as RA by physician and ten age-matched female controls for every cases were randomly selected. Data on reproductive factors were derived from a self-administered questionnaire. The relationship between potential risk factors, including smoking, socioeconomic status, breastfeeding, parity, age at first birth, age at menarche, use of oral contraceptives, and use of postmenopausal hormones and RA was estimated using logistic regression models. Results Two hundred and seventy-nine women with RA were compared with 2790 age-matched controls. The mean age of RA diagnosis was 47.9±15.3 years. Female patients with RA were significantly more likely to have low waist circumference and multiparity. There was no difference in the age at menarche, age at menopause, use of oral contraceptives, and use of postmenopausal hormones between those with and without RA. Among women who had at least one live birth, those who ever breastfed were associated with low risk of having RA after adjusting related risk factors (odds ratio 0.211; 95% CI 0.127-0.349). Also, RA risk was significantly decreased with increasing duration of breastfeeding (Table 1). Neither parity nor use of female hormone drugs had any significant effect on the risk of RA. Conclusions In this study, breastfeeding was inversely related to having RA, and this effect was significantly related to the duration of breastfeeding in Korean population. Other reproductive factors were not associated with RA risk. References Karlson EW, Mandl LA, Hankinson SE, Grodstein F. Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses9 Health Study. Arthritis Rheum 2004;50:3458-67. Marder W, Somers EC. Is pregnancy a risk factor for rheumatic autoimmune diseases? 2014;26:321-8. Disclosure of Interest None declared

supplementary table of "Isolated lenticulostriate artery aneurysm rupture in a patient with Behcet’s disease"

Mycobacterium szulgai is a rare nontuberculous mycobacterium found in Korea. It is an opportunistic pathogen and is usually isolated from patients with a history of alcoholism, chronic pulmonary disease, or an immunocompromising condition. We present here a case of M. szulgai isolated from a patient with a history of pulmonary tuberculosis. A 54-year-old man was admitted with dyspnea and febrile sensation. He had a history of pulmonary tuberculosis which occurred 30 years earlier and treatment with anti-tuberculosis medication. His chest computed tomography scan showed cavitary consolidation in both upper lungs. A sputum acid-fast bacilli (AFB) smear was positive and anti-tuberculous medication was started. However, a polymerase chain reaction for mycobacterium tuberculosis was negative and anti-tuberculous medication was stopped. M. szulgai was isolated on 3 separate sputum and bronchial wash fluid AFB cultures. He was treated with clarithromycin, rifampicin, and ethambutol. After 1 month, a sputum AFB smear and culture became negative and no additional M. szulgai were isolated during a 16-month treatment.