Vol.32 No.1, January 01, 2025 Article TypeCase ReportClinical ImageEditorialErratumLetter to the EditorOriginal ArticleReview Article

• Editorial 2025-01-01

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  Optimization of biological therapy selection in rheumatoid arthritis: insights into anemia and interleukin-6 pathway

  Bora Nam , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 1-2

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• Review Article 2025-01-01

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  Assessment of disease activity and quality of life of Korean patients with rheumatoid arthritis

  Young Ho Lee , M.D., Ph.D., Jae-Bum Jun , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 3-7

  Abstract

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  Abstract : The management of rheumatoid arthritis (RA) follows a treat-to-target approach, as recommended by guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). RA treatment recommendations include an emphasis on frequent disease activity assessments to optimize therapy, recognizing the possibility of timely therapies to slow progression and improve long-term results. The evaluation of joint inflammation, pain, physical function, and clinical indicators is required for comprehensive RA therapy. Current therapeutic goals include achieving low disease activity or remission to enhance the quality of life (QoL) for patients. ACR-endorsed RA disease activity measures, such as the Disease Activity Score in 28 Joints with erythrocyte sedimentation rate or C-reactive protein level, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Scale-II, and Routine Assessment of Patient Index Data 3, are recommended for their precision and sensitivity in supporting treat-to-target strategies. The ACR and EULAR have implemented Boolean-based and index-based remission criteria (SDAI and CDAI, respectively) to evaluate therapeutic effectiveness. The use of these markers regularly aligns with the ACR guidelines, improving adherence to quality indicators in clinical practice and confirming the provision of high-quality RA therapy. This review examines disease activity, function, and QoL measurements in line with the ACR and EULAR guidelines to aid doctors in treating Korean patients with RA.

• Review Article 2025-01-01

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  The pathogenesis of gout

  Eun Young Ahn , M.D., Min Wook So , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 8-16

  Abstract

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  Abstract : Gout is the most common inflammatory arthritis in adults, associated with hyperuricemia and the chronic deposition of monosodium urate (MSU) crystals. Hyperuricemia results from increased production of uric acid and decreased excretion by the kidneys and intestines. Urate excretion is regulated by a group of urate transporters, and decreased renal or intestinal excretion is the primary mechanism of hyperuricemia in most people. Genetic variability in these urate transporters is strongly related to variances in serum urate levels. Not all individuals with hyperuricemia show deposition of MSU crystals or develop gout. The initiation of the inflammatory response to MSU crystals is mainly mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) inflammasome. The activated NLRP3 inflammasome complex cleaves pro-interleukin-1β (IL-1β) into its active form, IL-1β, which is a key mediator of the inflammatory response in gout. IL-1β leads to the upregulation of cytokines and chemokines, resulting in the recruitment of neutrophils and other immune cells. Neutrophils recruited to the site of inflammation also play a role in resolving inflammation. Aggregated neutrophil extracellular traps (NETs) trap and degrade cytokines and chemokines through NET-bound proteases, promoting the resolution of inflammation. Advanced gout is characterized by tophi, chronic inflammatory responses, and structural joint damage. Tophi are chronic foreign body granuloma-like structures containing collections of MSU crystals encased by inflammatory cells and connective tissue. Tophi are closely related to chronic inflammation and structural damage.

• Original Article 2025-01-01

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  Efficacy of Curcuma longa in relieving pain symptoms of knee osteoarthritis patients: a systematic review and metaanalysis of clinical trials

  Rudy Hidayat , M.D., Ph.D., Faisal Parlindungan , M.D., Jihan Izzatun Nisa , M.D., Arya Ivan Mahendra , M.D., Muhammad Izza Indika , M.D., Cristopher Efendi , M.D.

  J Rheum Dis 2025; 32(1): 17-29

  Abstract

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  Abstract : Objective: Osteoarthritis (OA), particularly knee OA, affects 24% of adults and is a significant cause of disability. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but have many adverse effects. Antioxidant and anti-iflammatory properties of Curcuma longa might decrease pain thus improving joint function.
  Methods: This systematic review and meta-analysis evaluated randomized controlled trials (RCTs) on Curcuma longa efficacy for knee OA. We reported mean differences (MD) with 95% confidence interval (CI) for continuous outcomes and evaluated Visual Analog Scale (VAS) for pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score over 4 to 6 weeks for treatment effects.
  Results: Ten RCTs with 786 patients were included. Curcuma longa significantly improved VAS for pain than placebo (MD: 18.25, 95% CI: 7.79 to 28.72, p=0.0006). It was not inferior to NSAIDs in WOMAC total score improvement (MD: –11.99, 95% CI: –39.21 to 15.23, p=0.39). Both dosages (<1,000 and ≥1,000 mg/day) of Curcuma longa demonstrated similar improvement in VAS for pain compared to placebo (MD: 27.02, 95% CI: 1.45 to 52.60, p=0.04; MD: 21.48, 95% CI: 1.78 to 41.18, p=0.03).
  Conclusion: Curcuma longa benefits knee OA pain and function, being more effective than placebo and comparable to NSAIDs. Despite positive results, limitation and heterogeneity of the studies necessitates further research to explore optimal dosages and administration methods of Curcuma longa as therapeutic option for knee OA.

• Original Article 2025-01-01

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  An erythrocyte macrocytosis by methotrexate is associated with early initiation of biologic or targeted synthetic agents in patients with rheumatoid arthritis

  In-Woon Baek , M.D., Kyung-Su Park , M.D., Ph.D., Ki-Jo Kim , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 30-37

  Abstract

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  Abstract : Objective: An association between increased erythrocyte mean corpuscular volume (MCV) and treatment response in patients with inflammatory arthritis receiving methotrexate (MTX) has been reported. We investigated the frequency of red blood cell (RBC) macrocytosis and its clinical implications regarding the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients starting MTX for rheumatoid arthritis (RA).
  Methods: RBC macrocytosis (MCV >100 fL) and clinical characteristics were retrospectively examined in 1,156 patients starting MTX for RA. Multivariable logistic regression analyses were performed to identify the independent predictors of RBC macrocytosis. The initiation of b/tsDMARDs was assessed using a multivariable Cox proportional hazards regression model.
  Results: RBC macrocytosis was observed in 21.6% of RA patients over 35 [8, 89] months following MTX initiation and was persistent in 63.6% of the patients during MTX treatment. Anemia coexisted in only 20.0% of the patients with RBC macrocytosis. The occurrence of RBC macrocytosis was independently associated with age, MTX dose, and concomitant use of sulfasalazine or leflunomide (all p<0.001). A higher dose of MTX and double- or triple-DMARDs therapy were more frequently used in the group with RBC macrocytosis than in the group with normal MCV. Patients experiencing RBC macrocytosis were more likely to use b/ tsDMARDs (hazard ratio: 1.45 [95% confidence interval: 1.13, 1.87], p=0.003).
  Conclusion: RBC macrocytosis was possibly associated with the use of b/tsDMARD and could be a supplementary marker for assessing MTX resistance.

• Original Article 2025-01-01

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  Impact of disease-related indicators on pain measures in rheumatoid arthritis: a biopsychosocial perspective

  Hee Jun Kim , R.N., Ph.D., Ju-Yang Jung , M.D., Ph.D., Ji-Won Kim , M.D., Chang-Hee Suh , M.D., Ph.D., Hyoun-Ah Kim , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 38-47

  Abstract

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  Abstract : Objective: Pain is a significant and debilitating symptom of rheumatoid arthritis (RA) that significantly affects the quality of life and functional ability of patients. In the present study, we examined the association between pain variables and disease activity markers in patients with RA.
  Methods: We enrolled 133 patients with RA and assessed their clinical characteristics, socioeconomic and psychological factors, and pain measures. The psychological factors assessed included depressive symptoms and pain catastrophizing.
  Results: The study cohort comprised predominantly female patients with RA with an average age of 55.5±10.1 years. Depressive symptoms had a mean score of 5.83±4.71, while pain catastrophizing had an average score of 14.36±10.70. The mean scores for pain intensity, and pain interference, were 2.98±1.75 and 19.54±16.17, respectively, with significant positive correlations observed with depressive symptoms. Hemoglobin and hematocrit levels were negatively correlated with pain intensity. Multivariable linear regression analysis revealed significant associations between depressive symptoms and pain intensity, catastrophizing, and interference. Other factors associated with pain intensity included tender joint count. Pain catastrophizing was associated with education and economic status. Pain interference was associated with sex and economic status.
  Conclusion: This study shows the influence of disease-related indicators and psychological factors on pain in patients with RA, with depressive symptoms playing a crucial role in predicting pain experience. Effective pain management strategies for RA should include the management of depressive symptoms, in addition to addressing disease-related indicators.

• Original Article 2025-01-01

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  Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis

  Young Ho Lee , M.D., Ph.D., Gwan Gyu Song , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 48-56

  Abstract

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  Abstract : Objective: This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD).
  Methods: A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects.
  Results: The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein.
  Conclusion: This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.

• Case Report 2025-01-01

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  Juvenile lupus-like with negative serology: a clinical dilemma and diagnostic challenge

  Alhanouf Adnan Alsharif , M.B.B.S., Abdulaziz Marzouq Almutairi , M.D., Emtenan Badar Basahl , M.B.B.S., Abdulaziz Abdulllah Alshathri , M.D., Jameela Abdulaziz Kari , M.D., Mohammed Ahmad Shalaby , M.D., Mohammed Ahmad Nashawi , M.D.

  J Rheum Dis 2025; 32(1): 57-62

  Abstract

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  Abstract : Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect various organs. Juvenile-onset SLE (jSLE) may be more severe than the adult-onset form, but the diagnosis and classification remain challenging due to the complex nature of the condition and its resemblance to other conditions. Antinuclear antibodies (ANA) are the immunological hallmark of SLE, but their limited specificity poses challenges. The 2019 (European Alliance of Associations for Rheumatology/American College of Rheumatology) SLE proposed a weighted multi-criteria system for classifying SLE, with ANA serving as an entry criterion. However, seronegative SLE, in which a patient's clinical features and laboratory values are consistent with SLE but their ANA serology test is negative, is a rare subtype of SLE that has been reported in several cases worldwide. Here, we present two rare cases of jSLE in 13- and 11 years old girls with negative ANA. The first case presented as lupus cerebritis and lupus nephritis (LN) class IV and V which showed improvement with treatment. The other one was also diagnosed as LN class IV but showed poor outcome despite aggressive immunosuppressive treatment. These cases highlight the importance of considering lupus-like symptoms in children with negative serology and the need for further research into current diagnostic protocols and calls for a re-evaluation using a more inclusive set of criteria that does not centralize immunological serology.

• Letter to the Editor 2025-01-01

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  The future of Korean rheumatology

  Bon San Koo , M.D., Ph.D., Jae-Bum Jun , M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 63-65

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• Clinical Image 2025-01-01

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  Calcific periarthritis of the hand showing a variable disease course

  Kyung-Su Park , M.D., Seung Min Jung , M.D., Yune-Jung Park , M.D., Ki-Jo Kim , M.D.

  J Rheum Dis 2025; 32(1): 66-67

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• Erratum 2025-01-01

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  Erratum: Implication of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis for the first cycle of rituximab: a pilot study in a single Korean center

  Hyunsue Do, M.D., Jung Yoon Pyo, M.D., Jason Jungsik Song, M.D., Ph.D., Yong-Beom Park, M.D., Ph.D., Sang-Won Lee, M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 68-68

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• Erratum 2025-01-01

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  Erratum: Circulating leptin and its correlation with rheumatoid arthritis activity: a meta-analysis

  Young Ho Lee , M.D., Ph.D, Gwan Gyu Song, M.D., Ph.D.

  J Rheum Dis 2025; 32(1): 69-69

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