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.

Tocilizumab Increases Body Weight and Serum Adipokine Levels in Patients with Rheumatoid Arthritis Independently of Their Treatment Response: a Retrospective Cohort Study

Background@#Causes of weight change after tocilizumab treatment are unclear. We aimed to investigate the effects of tocilizumab treatment on body weight and serum adipokine levels in patients with rheumatoid arthritis (RA). @*Methods@#In this retrospective cohort study, we evaluated weight changes in patients with RA who received methotrexate (Cohort I) or tocilizumab with methotrexate (Cohorts II and III) for 24 weeks. Adipokine concentrations at baseline and 24 weeks were analyzed in Cohorts I and III. Cohorts I and II received tocilizumab therapy for an additional 48 weeks, during which weight changes were monitored (24–72 weeks). @*Results@#No significant weight change occurred after 24 weeks of methotrexate treatment (mean difference, −0.2 kg; P = 0.630), but was observed after 24 weeks of tocilizumab treatment (mean difference, +0.9 kg; P = 0.010). Weight changed regardless of the treatment response in both treatment groups. The leptin–adiponectin ratio (P = 0.015) and levels of adiponectin (P < 0.001), leptin (P < 0.001), and resistin (P = 0.003) increased significantly after 24 weeks of tocilizumab, but not methotrexate treatment. After 24, 48 and 72 weeks of tocilizumab treatment in Cohort II, mean (95% confidence interval [CI]) weight changes from baseline were +0.7 (0.0–1.4), +1.2 (0.4–2.0) and +1.1 (0.2–2.0) kg, respectively, and mean (95% CI) percent weight changes from baseline were +1.3% (0.1%–2.6%), +2.2% (0.7%–3.6%), and +2.0% (0.4%–3.7%) at 24, 48, and 72 weeks, respectively. @*Conclusion@#Weight and the leptin–adiponectin ratio increased after tocilizumab treatment. Given that cardiovascular (CV) risk factors may deteriorate in patients with RA who receive tocilizumab, further studies are required to determine the effects of weight gain on CV outcomes in these patients.

Performance of the 2015 American College of Rheumatology/European League against Rheumatism Classification Criteria for Gout in Korean Patients with Acute Arthritis

BACKGROUND: We aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification. METHODS: Patients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals. RESULTS: The study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis. CONCLUSION: In Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.

Periodontal pathogens and the association between periodontitis and rheumatoid arthritis in Korean adults

PURPOSE: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. METHODS: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. RESULTS: The RA group had significantly higher values than the control group for all investigated periodontal indices (P < 0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r = 0.125, P = 0.049), RA disease duration (r = 0.253, P < 0.001), erythrocyte sedimentation rate (ESR) (r = 0.162, P = 0.010), and anti-CCP antibody titer (r = 0.205, P = 0.004). Probing pocket depth (PPD) was correlated with ESR (r = 0.139, P = 0.027) and anti-Pg antibody titer (r = 0.203, P = 0.001). Bleeding on probing (BOP) was correlated with DAS28 (r = 0.137, P = 0.030), RA disease duration (r = 0.202, P = 0.001), ESR (r = 0.136, P = 0.030), anti-Pg antibody titer (r = 0.177, P = 0.005), and anti-CCP antibody titer (r = 0.188, P = 0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r = 0.201, P = 0.002; the latter r = 0.175, P = 0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r = 0.148, P = 0.020). CONCLUSIONS: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

Perspectives and Challenges for Geriatric Medicine / 대한내과학회지

Korean society is aging rapidly. Overall, 13.1% of the Korean population was elderly (age ≥ 65 years) in 2015, and this rate is expected to reach 40.1% in 2060. To prepare for this change, the Korean government has developed a long-term care insurance service and supports regional medical centers for the aged. It has established laws about life-sustaining treatment and directives to improve end-of-life care. Although the long-term care insurance currently provides ‘ in-home service’ and ‘ aged care facilities,’ it does not cover rehabilitation hospitals, which can prevent elderly individuals from accessing certain medical services. With the changing demographics, medical care requires change. Conventional medical care must be upgraded to provide suitable care for an aged society. It is important to support the activities of daily living, rather than simply prolonging life. This will require providing homeand community-oriented medical care to improve quality of life. It will also be necessary to train more geriatricians who understand the characteristics of elderly patients, provide comprehensive geriatric assessments, and lead other physicians in team-based medicine. Internists are already engaging in multidisciplinary collaboration and end-of-life care, which are critical qualities of leading geriatricians. Further discussion and consensus is needed regarding the training of geriatric medicine specialists in Korea.

Comparison of the Disease Activity Score-28 Based on the Erythrocyte Sedimentation Rate and C-reactive Protein in Rheumatoid Arthritis

OBJECTIVE: Assessing the disease activity is a key part of clinical decision-making in rheumatology. In particular, a high disease activity, which is represented by a disease activity score-28 (DAS28) score >5.1, is used as a cutoff value for the use of biologics in many countries, including Korea. This study compared the DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) to determine if these indices can be used interchangeably in patients with high disease activity. METHODS: This cross-sectional study enrolled 1,117 patients with rheumatoid arthritis and examined the initial registration data from the Korean Biologics Registry. RESULTS: In general, DAS28-CRP showed an excellent correlation with DAS28-ESR (r2=0.889, p <0.001). On the other hand, DAS28-CRP tended to underestimate the disease activity in those with moderate-to-high disease activity. The best agreement between DAS28-ESR and DAS28-CRP for defining a high disease activity was achieved using a cutoff value of 4.5 for the latter (kappa, 0.68; sensitivity, 85.9%; specificity, 88.1%). CONCLUSION: DAS28-CRP correlates well with DAS28-ESR; however, the cutoff value of the former needs to be reduced to 4.5 if these two indices are to be used interchangeably to define a high disease activity.

Periodontitis is associated with rheumatoid arthritis: a study with longstanding rheumatoid arthritis patients in Korea

BACKGROUND/AIMS: A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA). METHODS: Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients. RESULTS: The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively). CONCLUSIONS: The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope.

A Case of Hemophagocytic Lymphohistiocytosis in a Patient with Rheumatoid Arthritis / 대한내과학회지

Hemophagocytic lymphohistiocytosis (HLH) is a condition caused by excessive activation and expansion of T lymphocytes and macrophagic histiocytes that exhibit hemophagocytic activity. It is a life-threatening condition, and the reported mortality rates reach 20% to 30%. It is usually associated with infection, malignancy, or autoimmune disease, but rarely with rheumatoid arthritis (RA). We recently experienced a case of HLH with rapid progression resulting in mortality in a 38-year-old female patient with long-standing RA. She visited the clinic for evaluation of a common cold-like illness. She had hypotension, liver enzyme elevation, and pancytopenia. After admission, her hypotension continued and disseminated intravascular coagulation and metabolic acidosis developed and progressed with the appearance of azotemia. Despite supportive management, she died on the fifth hospital day. HLH should be considered as a differential diagnosis when patients with RA show acute illness with fever, cytopenia, hepatic failure, and coagulopathy.

Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis

Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 +/- 1.83 vs 0.51 +/- 1.77, P = 0.038; for sum, -0.50 +/- 1.72 vs 1.57 +/- 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 +/- 0.58 vs 1.06 +/- 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 +/- 0.93 to -0.14 +/- 0.48, P = 0.009; for JSN, 0.47 +/- 0.64 to 0.03 +/- 0.40, P = 0.032), as was change of sum score (1.09 +/- 1.27 to -0.10 +/- 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA.

Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis

Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 +/- 1.83 vs 0.51 +/- 1.77, P = 0.038; for sum, -0.50 +/- 1.72 vs 1.57 +/- 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 +/- 0.58 vs 1.06 +/- 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 +/- 0.93 to -0.14 +/- 0.48, P = 0.009; for JSN, 0.47 +/- 0.64 to 0.03 +/- 0.40, P = 0.032), as was change of sum score (1.09 +/- 1.27 to -0.10 +/- 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA.

A Refractory Case of Granulomatous Mastitis Treated with Methotrexate / 대한내과학회지

Granulomatous mastitis (GM) is an uncommon chronic inflammatory disease of the breast that can mimic breast carcinoma or infection. The treatment options include expectant management, complete resection, and corticosteroid therapy, although no standard treatment has been established. Recently, several case reports have suggested that methotrexate is another effective treatment for GM. Here, we describe the first Korean case of recurrent GM successfully treated with low-dose weekly methotrexate and review the relevant literature.

A Case of Macrophagic Myofasciitis Initially Thought to Be a Metastatic Infection

Macrophagic myofasciitis (MMF) is a rare disease, often associated with the pathological persistence of aluminum hydroxide used in some vaccines, and is characterized by macrophage infiltration of the muscle. We report a case of MMF, initially thought to be a metastatic infection. A 38-year-old woman presented with fever, as well as pain and weakness in both thighs. On physical examination both thighs were swollen and lower-extremity motor-power was decreased to grade III. Laboratory tests showed leukocytosis and elevation of acute phase reactants, but all muscle enzymes except lactate dehydrogenase (LDH) were within normal range. Initially metastatic infection was suspected but she was diagnosed with MMF by muscle biopsy showing heavy CD68 positive macrophage infiltration. Her myalgia and muscle weakness improved after systemic steroid treatment. This case suggests that MMF might be considered for a patient with unexplained inflammatory myopathy with or without a history of vaccination.

A Refractory Case of Granulomatous Mastitis Treated with Methotrexate / 대한내과학회지

Granulomatous mastitis (GM) is an uncommon chronic inflammatory disease of the breast that can mimic breast carcinoma or infection. The treatment options include expectant management, complete resection, and corticosteroid therapy, although no standard treatment has been established. Recently, several case reports have suggested that methotrexate is another effective treatment for GM. Here, we describe the first Korean case of recurrent GM successfully treated with low-dose weekly methotrexate and review the relevant literature.

Updates in the management of gouty arthritis / 대한내과학회지

Gout is the most common inflammatory arthritis in men over 40 years old and the prevalence is increasing. Asymptomatic hyperuricemia is predisposing condition of gout but the frequency of progression to acute gout is not high enough to need prophylactic treatment. In acute gout flare, first line therapy is non-steroid anti-inflammatory agents (NSAIDs) or corticosteroids, depending on comorbidities. Colchicine is now second line therapy. Urate lowering therapy for gout needs to be initiated when the second attack occurs in a year. Allopurinol, a xanthine oxidase inhibitor, has been the most widely used agent for the treatment of chronic gout. Now, febuxostat has emerged as a new xanthine oxidase inhibitor that is expected to be useful in patients with mildly decreased renal function. Uricosuric agents are alternative therapies for patients with preserved renal function and no history of nephrolithiasis. During urate lowering therapy, the dose should be titrated upward until the serum uric acid level is kept less than 6mg/dL. When initiating urate lowering therapy, concurrent prophylactic therapy with NSAIDs or low dose colchicine for more than six months is recommended for reducing flare-ups. In chronic gout treatment, dietary modification seems to have minimal effect, but alcohol drinking and weight control can be recommended.