Hae-Rim Kim

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) significantly affects disease prognosis and patient survival. The impact of conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic DMARDs (b/tsDMARDs) on RA-ILD prognoses remains unclear. This study aimed to investigate the effects of csDMARDs and b/tsDMARDs on RA-ILD progression and prognosis based on pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and symptom changes. Methods: This multicenter, retrospective, observational study included patients with RA-ILD at 13 referral hospitals in South Korea. The participants were categorized into csDMARD-only and b/tsDMARD-exposed groups. RA-ILD prognosis was assessed over a 24-month follow-up period using serial PFTs (the forced vital capacity [FVC] and diffusing capacity of the lungs for carbon monoxide [DLCO]), HRCT findings, and clinical symptom changes. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare disease progression risk while adjusting for baseline lung function, RA disease activity, and glucocorticoid use. Results: Among 127 eligible patients, 22 (17.3%) were exposed to b/tsDMARDs, predominantly abatacept and tocilizumab. During a mean follow-up of 2.8 years, 65 (51.2%) patients experienced RA-ILD progression. A higher baseline Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR) (adjusted hazard ratio [aHR]: 1.344, 95% confidence interval [CI]: 1.136–1.590, p = 0.001) and initially prescribed prednisone dose (aHR: 1.078, 95% CI: 1.011–1.151, p = 0.023) were significant prognostic factors for ILD progression. No statistically significant difference in progression risk was observed between the csDMARD-only and b/tsDMARD-exposed groups (aHR: 0.937, p = 0.851). Conclusions: The RA-ILD prognosis was more strongly influenced by disease activity, rather than the type of DMARD used. These findings emphasize the importance of maintaining low RA disease activity to improve RA-ILD prognosis.

Background: Osteoarthritis (OA) is the most common arthritis globally. Besides cartilage loss, all surrounding structures of the joint, including the synovium, capsule, ligament, bone, nerve, and muscle, are affected by this disease, resulting in joint failure. The traditional diagnosis of OA depends on clinical symptoms, physical examination, and radiographic findings. Ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI) are imaging modalities commonly used for assessing OA.Current Concepts: US findings of OA indicate synovitis, hyaline and fibrous cartilage damage, ligament and tendon changes, and bony abnormalities. US is clinically useful because it correlates with the clinical pain index and radiographic and MRI findings, differentiates the various causes of OA pain, helps diagnose early disease, predicts prognosis, and increases the accuracy and safety of intra-articular injections in OA joints.Discussion and Conclusion: Although US has some limitations as a tool for examining whole joint structures, its use is predicted to increase in the future because it is beneficial and easily accessible for assessing OA. To produce accurate US results, the examiner should have deep anatomical knowledge and skilled practice techniques, and a clinical diagnosis should be performed based on clinical symptoms and physical examination.

Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Full Papers; Authors: H.K. Min, J.-Y. Lee, S.-H. Lee, J.H. Ju, H.-R. Kim

Corrigendum: Computed tomography-based assessment of radiographic progression in spine and sacroiliac joints after pregnancy in women with radiographic axial spondyloarthritis

Background/Aims: We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP).Methods: Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined.Results: A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern.Conclusions: NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

A 22-year-old male patient was admitted to the rheumatology clinic due to neck and back pain with morning stiffness for 12 months. He suffered from right knee and heel pain six months ago. He showed increased levels of high-sensitivity C-reactive protein (2.20 mg/dL, reference range: 0.01-0.3 mg/dL) and erythrocyte sedimentation rate (67 mm/h, reference range: 0-15 mm/h). To evaluate neck and back pain, the physician performed computed tomography (CT) of the whole spine. The CT finding was absence for herniated nucleus pulposus nor neural foramen stenosis. All vertebral corners of whole spine were clear (Figure 1a), except for bony spur at odontoid process of C2 (Figure 1b, white arrow). Upon suspicious of ankylosing spondylitis (AS), CT scan for sacroiliac joints and sacroiliac joint, and human leukocyte antigen (HLA)-B27 was tested. The CT scan showed bilateral Grade 2 sacroiliitis which was compatible with AS Figure 1c), and positive result for HLA-B27. The most widely used method for evaluating spinal structural damage, the modified Stoke Ankylosing Spondylitis Spinal Score only includes anterior aspect of C2 lower border to T1 upper border and T12 lower border to sacrum upper border,[1] and novel method using CT of whole spine (CT syndesmophyte score) includes lower border of C2 to upper border of sacrum.[2] These methods do not count the syndesmophyte on odontoid process of C2. The patient showed a rare case of AS which only showed syndesmophyte on odontoid process of C2. Risks of osteoporosis and consequent vertebral fracture are increased in AS patients[3] and rarely fracture on odontoid process is reported.[4] Also, the low bone mineral density is associated with syndesmophyte progression in patients with AS.[5] Therefore, physicians should be aware of possibility of fracture or syndesmophyte progression on odontoid process when pain on upper cervical area occurs in AS patients.

OBJECTIVES: This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA).METHODS: We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups.RESULTS: Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups.CONCLUSIONS: In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.

Tae Hwan Lee, M.D., Minjeong Nam, M.D., Ph.D., Jong Do Seo, M.D., Hanah Kim, M.D., Ph.D., Hae-Rim Kim, M.D., Ph.D., Mina Hur, M.D., Ph.D., Yeo-Min Yun, M.D., Ph.D., and Hee-Won Moon, M.D., Ph.D.. Ann Lab Med 2023;43:290-4. https://doi.org/10.3343/alm.2023.43.3.290

Background: Mechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations.Materials and methods: This retrospective study included women with r-axSpA aged 19–49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2–4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0–522) and SIJ scores (0–40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs.Results: A total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1–Q3) CTSS at baseline in the delivery group and controls was 19 (16–23) and 20 (13.25–27.75), and the median progression was 1 (0–3) and 0 (0–1) during the median 2.9-year follow-up, respectively. The median (Q1–Q3) SIJ score at baseline in the delivery group and controls was 13 (8–22) and 11 (6–22), and the median progression was 1.5 (0–3) and 1 (0–2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method.Conclusion: Pregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.