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.

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.

Productivity Loss of Rheumatoid Arthritis Patients according to the Their Stages of the Disease Activity Score

OBJECTIVE: Productivity loss was compared by 3-stage of disease activity and associations between higher disease activity and high productivity loss were identified. METHODS: Data were extracted from Rheumatoid Arthritis (RA) Patient-reported Outcomes Research, which enrolled 2,000 RA patients (>20-year) on disease-modifying-antirheumatic-drugs (DMARDs) (≥6-month) from December 2012 to June 2013. This included 1,457 RA patients with the disease activity score (DAS-28-ESR) in their medical charts. Productivity loss in time and indirect cost was estimated using The World Health Organization Health and Work Performance Questionnaire (HPQ). Baseline characteristics and productivity loss outcomes were compared according to DAS-28-ESR groups. RESULTS: 84.4% were females, 54.2% had low DAS-28-ESR ( 5.1). Patients with moderate to high DAS-28-ESR had higher lost productivity time (LPT) and monthly costs of LPT than those with low DAS-28-ESR (time in hours: 110.0±58.4 vs. 132.4±57.2 vs. 71.5±52.0, p < 0.0001; monthly costs of LPT in 1,000 Korean won: 1,097±607 vs. 1,302±554 vs. 741±531, p < 0.0001). Multiple regression analyses revealed significant associations with high LPT in high (adjusted odds ratio [OR]=3.87, 95% confidence interval [CI]: 2.18∼6.87) and moderate DAS-28-ESR (adjusted OR=1.88, 95% CI: 1.41∼2.52) compared to low DAS-28-ESR. In addition, positive associations with high monthly costs of LPT were observed in high (adjusted OR=3.45, 95% CI: 1.98∼5.99) and moderate DAS-28-ESR (adjusted OR=1.93, 95% CI: 1.43∼2.54) compared to low DAS-28-ESR. CONCLUSION: Timely therapeutic strategies should be taken into consideration given that the RA patients with moderate to high DAS-28-ESR showed strong associations with high productivity loss for effective management of RA.

Genetic Associations of Mitochondrial DNA Polymorphisms with Behcet's Disease in a Korean Population: A Pilot Study

OBJECTIVE: Pathogenesis of Behcet's disease (BD) is known to be multifactorial and accumulating data suggest genetic mechanisms. Variations in nuclear DNAs have been largely investigated, while studies on mitochondrial DNAs are limited. The purpose of the current study is to investigate associations of mitochondrial single nucleotide polymorphisms and haplotypes with BD. METHODS: Complete mitochondrial DNAs were sequenced using chip array with blood samples collected from 20 patients and 10 control subjects. Haplotypes were searched in hypervariable region 1 and 2. Chi square or Fisher's exact test was used to analyze associations of mitochondrial single nucleotide polymorphisms between two groups and associations between clinical characteristics and mitochondrial single nucleotide polymorphisms. RESULTS: From a total of 16,569 for each individual, 16,545 mitochondrial DNA nucleotides were sequenced. m.248A>G, m.709G>A, m.3970C>T, m.6392T>C, m.6962G>A, m.10310G>A, m.10609T>C, m.12406G>A, m.12882C>T, m.13928G>C, m.16129G>A, and m16304T>C were observed more frequently in the patient group, although without statistical significance, while m.304C>A, m.3010G>A, m.4883C>T, m.5178C>A, and m.14668C>T were more frequent in the control group (p=0.008, 0.026, 0.007, 0.007, and 0.026, respectively). m.16182A>C, m.16183A>C, and m.16189T>C were associated with uveitis (p=0.041, 0.022, and 0.014, respectively). None of the haplotypes we searched were statistically associated with BD risk, but B4a was observed more frequently in the patient group. CONCLUSION: We report the first association study between BD and mitochondrial single nucleotide polymorphisms in a Korean population. In the current study, m.248A>G, m.709G>A, m.3970C>T, m.6392T>C, m.6962G>A, m.10310G>A, m.10609T>C, m.12406G>A, m.12882C>T, m.13928G>C, m.16129G>A, and m16304 T>C could be candidate mitochondrial single nucleotide polymorphisms in BD.

A Case of Cryptococcal Meningoencephalitis Mimicking Lupus Psychosis

No abstract available.

Vaccination in Inflammatory Rheumatic Diseases

Infection is a critical and challenging situation encountered in treatment of inflammatory rheumatic diseases (IRDs). It is associated with the disease activity itself and/or the immunosuppressant treatments. Vaccine preventable infections could be controlled by use of a timely vaccination protocol. Immunosuppressed situations observed in IRDs require some modification of the recommendation for the general population in each national society. Live attenuated vaccines are generally contraindicated in IRDs, except for varicella-zoster vaccination, which is solely permitted live vaccine and could be given on a case by case basis in autoimmune IRDs. Influenza and pneumococcal vaccines are strongly recommended due to increased mortality in patients with IRDs. The vaccination protocol reflects the current national medical environment and requirements; therefore, it could change with time. The Korean Rheumatology Society now requires that vaccination be recommended for patients with IRDs, with the possibility of both an adult and child version.

Multiple Gastric Ulcers as a Manifestation of Cytomegalovirus Infection in a Patient with Adult-onset Still's Disease

Cytomegalovirus (CMV) is a relatively common viral pathogen, and CMV infection is generally assumed asymptomatic in general hosts. In immunologically compromised patients, CMV infection can cause further serious diseases such as pneumonitis, retinitis, encephalitis, and enterocolitis. A 40-year-old man is being presented with acute fever, myalgia, and sore throat. Laboratory findings have revealed elevated ESR, CRP, and ferritin levels. The patient was being treated for adult-onset Still's disease (AOSD). Three weeks later, although AOSD activity was under control, the patient began to complain about oral soreness, epigastric pain, and diarrhea. Endoscopy revealed multiple round ulcers with white patches in the esophagus and the stomach, sparing the colon. Anti-fungal agent is being administered but failed to bring improvements after 2 weeks of therapy. CMV infection is confirmed with pathology, antiviral agents were initiated after the ulcers subsided. Currently, clinical associations between CMV infection and AOSD are suggested. CMV infection may be considered as a differential diagnosis when multiple upper gastrointestinal ulcerative lesions develop within patients whom have been treated AOSD with immunosuppressive agents.

A Case of Behcet's Disease with Splenic Infarction / 대한내과학회지

Behcet's disease is a multisystem autoimmune disease with vasculitic features, and major vascular involvement occurs in 7.7-60% of patients. Venous lesions are more common than arterial lesions and arterial thrombotic events are relatively rare. We report a patient with Behcet's disease who developed a splenic infarct associated with splenic thrombotic arteritis. A 44-year-old man who had been diagnosed with Behcet's disease 5 years earlier presented with left flank pain lasting for 5 days. Laboratory tests revealed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Computed tomography (CT) and three-dimensional CT showed a wedge-shaped splenic infarct and thrombus in the splenic artery. We treated him with low-molecular-weight heparin and prednisolone. The symptoms improved within 6 days of hospitalization, after which we stopped the heparin and added methotrexate and azathioprine. Splenic infarct should be ruled out if patients with Behcet's disease complain of new left-sided abdominal pain.

A Case of Behcet's Disease with Splenic Infarction / 대한내과학회지

Behcet's disease is a multisystem autoimmune disease with vasculitic features, and major vascular involvement occurs in 7.7-60% of patients. Venous lesions are more common than arterial lesions and arterial thrombotic events are relatively rare. We report a patient with Behcet's disease who developed a splenic infarct associated with splenic thrombotic arteritis. A 44-year-old man who had been diagnosed with Behcet's disease 5 years earlier presented with left flank pain lasting for 5 days. Laboratory tests revealed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Computed tomography (CT) and three-dimensional CT showed a wedge-shaped splenic infarct and thrombus in the splenic artery. We treated him with low-molecular-weight heparin and prednisolone. The symptoms improved within 6 days of hospitalization, after which we stopped the heparin and added methotrexate and azathioprine. Splenic infarct should be ruled out if patients with Behcet's disease complain of new left-sided abdominal pain.

A Case of Spontaneous Hemoperitoneum Presenting as the Initial Manifestation of Systemic Lupus Erythematosus

Thrombocytopenia is included in the classification criteria for systemic lupus erythematosus (SLE). However, severe thrombocytopenia causing spontaneous bleeding is rare. Here, we describe a 22-year-old woman who presented with spontaneous hemoperitoneum as the first manifestation of SLE. Laboratory findings compatible with SLE included positive antinuclear antibody and a false-positive venereal disease research laboratory. Symptoms suggesting the disease were not prominent early after admission, but headache and seizures that developed on the 3rd day of admission led to the diagnosis of SLE. The brain magnetic resonance imaging and angiography findings were compatible with the neuropsychiatric manifestations of SLE. High-dose steroid and monthly intravenous cyclophosphamide pulse therapy were effective at improving the headache and seizure, as well as the hemoperitoneum.

Diffuse Idiopathic Skeletal Hyperostosis with Syndesmophytes on the Iliac Spine / 대한류마티스학회지

No abstract available.

A Case of Behcet's Disease with Multiple Cavitary Lung Lesion / 결핵및호흡기질환

Behcet's disease is a systemic vasculitis of an unknown etiology involving the arteries and veins of all sizes. There are reports showing that a pulmonary artery aneurysm or thromboembolism and superior vena cava thrombosis are present in 5-10% of patients with Behcet's disease and that lung parenchymal lesions are mainly airway consolidations resulting from hemorrhage or infarction. We encountered a patient with increasing pulmonary cavitary changes and localized aspergilloma. The patient was a 43-year-old man diagnosed with Behcet's disease with a history of recurrent oro-genital ulceration and uveitis, and who was administered methotrexate, colchicines, prednisolone. During the follow up he developed progressive dyspnea upon exertion and finger clubbing. Therefore further evaluations were performed. Chest computed tomography showed more advanced consolidations and cavitations than the previous film with the previously known aspergilloma still observable. An open lung biopsy was carried out to determine the presence of malignant changes, which revealed nonspecific vasculitis. Azathioprine was added resultion in an improvement of symptoms.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Korean Patients with Systemic Sclerosis

To determine whether angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is associated with the development and clinical features of systemic sclerosis (SSc) in Korean, we studied seventy two Korean patients with SSc fulfilling the ACR preliminary classification criteria. The controls were 114 healthy, disease free Koreans. ACE I/D genotypes were determined by PCR method using oligonucleotides. Sixty eight patients (94.4%) were women and age at diagnosis was 43.5+/-12.6 yr old (mean+/-SD). Thirty nine patients (54.2%) had a diffuse type of SSc. There were no statistical differences in the frequencies of all ACE I/D genotypes and D allele between patients and controls, and neither between diffuse and limited types of SSc. ACE I/D gene polymorphism was not associated with the development of SSc in Korea. The investigation for the pathogenesis of SSc requires more studies about the role of other candidate genes such as endothelin, TGF-beta, nitric oxide, or angiotensin II receptor in addition to the ACE genes.

The efficacy and safety of etanercept in patients with active rheumatoid arthritis receiving methotrexate / 대한내과학회지

BACKGROUND: This study was performed to investigate the efficacy and safety of etanercept in active rheumatoid arthritis patients with stable dose of methotrexate in Korean. METHODS: In a 12 week, single arm, open trial, we assigned 76 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Patients received twice-weekly subcutaneous injections of etanercept 25 mg while continuing to receive methotrexate at a stable dose of 7.5~25 mg per week. The clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR) at 12 weeks. RESULTS: Etanercept led to significant improvements in disease activity and was safe and well tolerated. At 12 week, 84.4% of the patients receiving 25 mg of etanercept achieved a 20% ACR response, and 53.1% of those receiving etanercept achieved a 50% ACR response. The most common adverse event was injection-site reaction. Other adverse events were upper respiratory infection, nausea, and facial edema, but there were no serious adverse events associated with etanercept. CONCLUSION: In active rheumatoid arthritis patients, etanercept was safe, well tolerated, and provided rapid clinical improvements.

Lack of Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and Carotid Atherosclerosis in Korean Patients with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: Studies have suggested that the 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation (alanine -- or =1 mg/day) were studied. The genetic polymorphism was detected by the polymerase chain reaction. We measured intima-media thickness (IMT) and plaques of the common carotid arteries by ultrasonography, and evaluated relations among the known risk factors for atherosclerosis, the genetic polymorphism, RA outcomes (Steinbrocker's radiological stage and functional class defined by the ACR criteria) and markers of inflammation (erythrocyte sedimentation rate and C-reactive protein). RESULTS: Among the 40 subjects, 12 had MTHFR genotype CC, 24 genotype CT, and 4 genotype TT. The frequencies of the MTHFR C and T allele were 0.6 and 0.4, respectively. Between the subjects with the CC genotype and those with the mutant T allele, there was no difference in age, body mass index, blood pressure (BP), lipid, duration of RA, RA outcome indices, rheumatoid factor, acute phase reactants and IMT. Carotid IMT was positively associated with age, systolic BP and antihypertensive drug use. There was no significant association between carotid IMT and the MTHFR C677T mutation. CONCLUSION: It is assumed that there was no significant relationship between the MTHFR C677T polymorphism and carotid atherosclerosis in Korean postmenopausal RA women.

Association of Polymorphism in Glutathione S-transferase Gene with Susceptibility and Severity of Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: We examined the genetic polymorphisms of glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) in Korean patients with rheumatoid arthritis (RA) and studied to determine whether GSTs influence susceptibility or outcome in RA. METHODS: RA patients with disease duration above 2 years (n=267) and healthy control (n=400) were enrolled. Genetic polymorphism were determined using polymerase chain reaction-based assays. We assumed stage I (Steinbroker's radiologic stage by the ACR criteria) regarded as mild RA and stage II, III, IV as severe RA. Data were analysed using multiple regression analysis with correction for age, sex, disease duration, and rheumatoid factor positivity. RESULTS: The frequency of GSTM1 null genotype in Korean RA patients was significantly higher than that of control (61.7% vs 53.5%, p=0.04). No significant differences in the frequency of the GSTT1 null genotype and GSTP1 genotypes between RA patients and normal controls were identified. The GSTM1 null genotype significantly influence the disease progression and bony erosive change in severe RA groups (p=0.03) compared with in mild RA groups. CONCLUSION: The GSTM1 null genotype increases the risk of rheumatoid arthritis in Korean patients. More severe erosive damage was associated with GSTM1 null genotype. Our study suggests that GSTM1 null genotype may be an independent marker for development of more erosive disease in RA.

Glutathione S-transferase Gene Polymorphisms and Systemic Lupus Erythematosus / 대한류마티스학회지

OBJECTIVE: To determine whether GSTM1, GSTT1 and GSTP1 polymorphisms are associated with susceptibility or disease manifestations in patients with SLE. METHODS: Two hundred eighty-six SLE patients who fulfilled the American College of Rheumatology (ACR) criteria were compared with 271 cases of age and sex matched controls to examine association between GST genotypes and susceptibility to SLE. The effect of genotype on SLE manifestations was assessed using the comparison of ACR diagnostic criteria. GST gene polymorphisms were determined by a multiplex polymerase chain reaction and antibodies to SS-A and SS-B were determined by double immunodiffusion. RESULTS: No association was found in the comparison of GSTM1 null, GSTT1 null, GSTP1 Ile105--