Flare prediction after tapering the dose of tumour necrosis factor inhibitors in patients with axial spondyloarthritis: A nationwide cohort study.

OBJECTIVES: To develop a model for predicting flares after tapering the dose of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS: Data were obtained from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. In total, 526 patients who received the standard-dose TNFi for at least 1 year and tapered their dose were included in the derivation cohort. The main outcome was a flare occurrence defined as an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) score of ≥ 2.1 after 1 year of TNFi tapering. The final prediction model was validated using an independent cohort. RESULTS: Among 526 patients, 127 (24.1%) experienced flares. The final prediction model included negative human leucocyte antigen B27 (ß = 1.088), inflammatory back pain (ß = 1.072), psoriasis (ß = 1.567), family history of SpA (ß = 0.623), diabetes mellitus (ß = 1.092), TNFi tapering by ≥ 50% of the standard-dose (ß = 0.435), ASDAS-CRP at tapering (ß = 1.029), and Bath Ankylosing Spondylitis Functional Index score at tapering (ß = 0.194) as covariates. It showed an excellent discrimination performance (AUC = 0.828). According to the predictive risk, patients were classified into three groups (low-, intermediate-, and high-risk). The probabilities of flares in these groups were 4.5%, 18.1%, and 61.8%, respectively. The performance of the model in the validation cohort was also comparable. CONCLUSION: The established prediction model accurately predicted the risk of flares after TNFi dose tapering in patients with axSpA using eight simple clinical parameters, which could be helpful to select appropriate patients for tapering their TNFi without flare in daily clinical practice.

Corrigendum: Korean treatment recommendations for patients with axial spondyloarthritis.

[This corrects the article on p. 151 in vol. 30, PMID: 37476674.].

Immunoglobulin G4-related hypertrophic pachymeningitis with an isolated scalp mass mimicking a brain tumor: a case report and literature review.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disorder associated with fibroinflammatory conditions that can affect multiple organs. Hallmark histopathological findings of IgG4-RD include lymphocytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. However, little is known about central nervous system involvement of IgG4-RD. Hypertrophic pachymeningitis (HP) has recently been reported as a manifestation of IgG4-RD, which may have previously been demonstrated in a significant percentage of idiopathic cases. Herein, we report a rare case of a 63-year-old male who presented with a scalp mass that mimicked a brain tumor. He was diagnosed with IgG4-related HP (IgG4-RP) after surgery. This case suggests that awareness of a possibility of IgG4-RP in patients with isolated scalp masses, even in the absence of systemic symptoms, is crucial. A combination of careful history taking, evaluation of serum IgG4-levels and imaging as an initial work-up, followed by tissue biopsy, is important for the differential diagnosis of IgG4-RP, malignancy, and other infectious diseases.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5-12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13-16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications.

OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.

Association between oxidative balance score and neck circumference in Korean adults.

The relationship between oxidative stress and central obesity is contradictory. Here, we investigated the association between oxidative balance (OB) score and neck circumference (NC). Data obtained from the 2019 to 2020 Korean National Health and Nutrition Examination Surveys were analyzed for 5807 adults with available OB scores and NCs. Multivariate regression models adjusted for potential confounders including demographics, comorbidities, and total energy intake revealed that subjects with a higher OB score had a significantly smaller NC in men and women. Our results indicate that oxidative imbalance indicates the presence of central obesity.

Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms.

Background: Proliferative vasculopathy (PV) associated antiphospholipid syndrome (APS) in the central nervous system is a rare un(der)recognized form of extra-criteria manifestations of APS. This study investigated the angiographic characteristics of cerebral and cervical arteries in patients with PV associated with antiphospholipid antibodies (aPLs). Methods: Patients with aPLs, neurologic symptoms and diffuse luminal narrowing on brain or neck magnetic resonance angiography were selected from electronic medical records. Vascular wall and intraluminal pathology were examined by high-resolution vessel wall MR imaging (VW-MRI). Results: A total of 11 patients (six men and five women) with PV-aPL, of median (interquartile range) age 42 (34-61) years, were included. Median anticardiolipin antibodies IgG titer was 78.9 (28.2-134.0) units and anti-beta 2 glycoprotein I antibodies (aB2GPIs) IgG titer was 227.2 (0.0-1012.1) units. All patients had diffuse luminal narrowing in the carotid basilar and/or cerebral arteries, five in the internal carotid artery (ICA); two each in the middle cerebral artery (MCA) and vertebral artery; and one each in the basilar artery (BA) and posterior cerebral artery. On VW-MRI, four patients showed concentric thickening of the vascular walls of the ICA and/or MCA and two showed mild eccentric wall thickening of the ICA or BA. All patients received antithrombotic treatment. In two patients with extremely high aB2GPIs titer, diffuse narrowing progressed despite treatment with antithrombotic agents on follow-up imaging. Conclusions: This study suggests that PV-aPL might be a distinct extra-criteria manifestation of APS that can manifest as long-segmental diffuse stenosis of cerebral and cervical arteries. It should be considered in relatively young patients with neurologic symptoms and aPLs.

Angiographic characteristics of vasculopathy in patients with idiopathic inflammatory myopathies and systemic sclerosis.

To describe the peripheral angiographic features of vasculopathy in idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc) in comparison to polyarteritis nodosa (PAN). Angiograms of 47 extremities (24 upper and 23 lower) of 11 patients with IIM (n = 5) and SSc (n = 6), and 12 patients with PAN who presented with critical limb ischemia were retrospectively analyzed with regards to the presence of stenosis, occlusion, aneurysms and delayed distal flow, and degree of neovascularization. Diffuse narrowing was more frequent (66.1 vs. 38.0%, p = 0.001), whereas multifocal stenosis (6.5% vs. 26.8%, p = 0.002), abrupt occlusion (11.3% vs. 29.6%, p = 0.010) and aneurysm formation (1.6% vs. 11.3%, p = 0.037) were less frequent in IIM/SSc than PAN. In distal arteries, tapered occlusion (95.5% vs. 76.0%, p = ns) and delayed flow (77.3% vs. 48.0%, p = 0.039) were more common in IIM/SSc than PAN. After 1 year, auto- or surgical amputation tended to be more frequent in IIM/SSc than PAN (36.4% vs. 16.7%, p = ns). In conclusion, diffuse narrowing, tapered occlusion and delayed distal flow on conventional angiograms tend to be more frequent in IIM/SSc than PAN. Further studies are needed to verify these findings in a larger prospective cohort.

Pulmonary arterial hypertension due to antiphospholipid syndrome initially mimicking chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is the second most common lung complication in antiphospholipid syndrome (APS) patients. However, the concurrent development of APS-related nonthrombotic PAH is rarely reported. Lack of awareness for group 1 PAH in APS patient may contribute to underdiagnosis of this condition. Herein, we reviewed the case of a 56-year-old female who was diagnosed with PAH related to APS that mimicked chronic thromboembolic pulmonary hypertension (CTEPH). It is crucial to be aware of the possibility of a group 1 PAH diagnosis, even though patients have already been diagnosed with CTEPH. Furthermore, a multidisciplinary approach and serial follow-up right heart catheterization with echocardiography are important to make a timely diagnosis and provide optimal treatment for APS-related PAH in patients with CTEPH-like clinical features.

Utility of the breath-holding test in patients with systemic sclerosis.

OBJECTIVES: Cardiopulmonary involvement is a major cause of death in patients with SSc. This study evaluated the clinical utility and reliability of breath-holding test (BHT) in evaluating cardiopulmonary function in patients with SSc. METHODS: Seventy-two prospectively enrolled patients with SSc underwent BHT and the 6 min walk test (6MWT), along with measurements of the Borg dyspnoea scale and Scleroderma Health Assessment Questionnaire (SHAQ). Data on pulmonary function test and echocardiography were also collected. Validity was assessed based on the correlations between the best BHT and relevant clinical parameters. To assess the reliability of BHT, an additional 31 patients with SSc underwent BHTs twice within 2 week intervals. RESULTS: Mean (s.d.) best BHT time was 38.4 (15.7) s, and 6MWT distance was 473.5 (95.5) m. BHT showed significant correlations with the Borg dyspnoea scale before (r = -0.367, P < 0.001) and after (r = -0.285, P = 0.016) testing, whereas 6MWT were correlated with the Borg dyspnoea scale after (r = -0.351, P = 0.002) but not before (r = -0.113, P = 0.343) testing. BHT time was correlated with diffusing capacity for carbon monoxide (%, r = 0.426, P < 0.001), forced vital capacity (litres, r = 0.373, P = 0.001), pulmonary arterial systolic pressure (mmHg, r = -0.272, P = 0.031) and SHAQ score (r = -0.470, P < 0.001), but not with left ventricular ejection fraction (%, r = -0.135, P = 0.263). BHT showed excellent reliability, with an intraclass correlation coefficient (2, 1) of 0.943 (95% CI: 0.88, 0.97). CONCLUSION: BHT, a simple and less time-consuming test, shows excellent reliability and significant correlation with the Borg scale, SHAQ and pulmonary parameters. These results suggest that BHT might be a useful surrogate marker of pulmonary capacity in SSc patients. TRIAL REGISTRATION NUMBER: NCT04484948.

Cytoplasmic zinc promotes IL-1ß production by monocytes and macrophages through mTORC1-induced glycolysis in rheumatoid arthritis.

The essential micronutrient zinc regulates immune responses by affecting signaling pathways. In activated monocytes and macrophages, signaling networks mediate the metabolic reprogramming that meets the demands of participation in immune responses. Here, we demonstrated that cytoplasmic, bioavailable zinc was essential for promoting IL-1ß production in activated human monocytes and macrophages downstream of glycolysis induced by the kinase-containing multiprotein complex mTORC1. The concentration of cytoplasmic zinc was determined by that of extracellular zinc, which was brought into cells through the zinc-specific importer Zip8. The abundance of Zip8 was increased in monocytes from patients with rheumatoid arthritis (RA), as well as in LPS-stimulated monocytes and macrophages from healthy individuals. The mTORC1-mediated phosphorylation of S6 kinase (S6K) was enhanced by zinc-mediated inhibition of PP2A, a phosphatase that targets S6K. As a result, IL-1ß production was increased due to the activation of mTORC1-induced glycolysis. In monocytes of patients with RA, the expression of Zip8 and the zinc-inducible metallothionein isoform MT2A and the phosphorylation of S6K were enhanced compared with those of healthy controls. Furthermore, Zip8 expression correlated with more severe RA clinical parameters, suggesting that Zip8-mediated zinc influx is related to inflammatory conditions. These results provide insight into the role of cytoplasmic, bioavailable zinc in the metabolic reprogramming of human monocytes and macrophages in inflammatory responses.

Evaluation of Serum Matrix Metalloproteinase-3 as an Objective Indicator for the Disease Activity in Rheumatoid Arthritis Patients Treated With Methotrexate Versus Tocilizumab: 24-week Results From a Prospective Randomized Controlled Study.

Objective: This study aims to evaluate the change in serum metalloproteinase-3 (MMP-3) following the management of active rheumatoid arthritis (RA) and define the relationships between MMP-3 and disease activity indices. Methods: Data from a previously reported a 24-week, randomized controlled trial to investigate efficacy of tocilizumab in active RA refractory to methotrexate were analyzed. The serum level of MMP-3 were measured at week 0, 12, 20, and 24. The changes in MMP-3, and the relationship between MMP-3 and clinical parameters was assessed based on treatment group, methotrexate with or without tocilizumab. Results: A total of 95 patients were included in this study. The serum MMP-3 significantly decreased and showed similar pattern with other disease activity indices during treatment period in both treatment groups (p<0.001). The MMP-3 was positively correlated with ESR, CRP, DAS28, SDAI, and CDAI for 302 visits throughout 24 weeks (p<0.001). In another correlation analysis to evaluate the treatment effect at 24 week time point, methotrexate group showed significant correlation between serum markers MMP-3 (r=0.321, p=0.043); ESR (r=0.450, p=0.002); and CRP (r=0.536, p<0.001), with DAS28, but tocilizumab group didn't show meaningful correlation between serum markers and DAS28 (p>0.05). Conclusion: Serum MMP-3 showed positive correlation with disease activity indices in active RA patients. Furthermore, serum MMP-3 significantly decreased from baseline to week 20. As there is no single serum marker that can represent the disease activity particularly in tocilizumab treatment, MMP-3 might be a useful adjunct indicator to evaluate the treatment response in active RA patients.

A Case of Overlap Syndrome of Systemic Sclerosis and Cryoglobulinemic Vasculitis With Central Nervous System Involvement.

Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.

An Updated Meta-analysis on the Risk of Urologic Cancer in Patients with Systemic Lupus Erythematosus.

BACKGROUND: The risk of urologic cancers in patients with systemic lupus erythematosus (SLE) remains uncertain. We investigated the association between SLE and incident urologic cancers through a systematic review and meta-analysis. METHODS: We searched the PubMed, EMBASE, and the Cochrane Library to identify articles that recorded prostate, bladder, or kidney cancers in SLE patients from inception to August 31, 2018. We included observational, case-control, or cohort studies with no language restriction. Two investigators screened and extracted the data independently. RESULTS: Fourteen cohort studies with 83,860 SLE patients were finally analyzed. Overall, SLE patients were at increased risk of bladder cancer (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.15-3.21) but not of prostate or kidney cancer. However, subgroup analyses showed a reduced risk of prostate cancer in <10-year follow-up studies (HR, 0.68; 95% CI, 0.51-0.89) and an elevated risk of kidney cancer in patients with SLE in Western studies (HR, 2.00; 95% CI, 1.02-3.92), community-based studies (HR, 4.54; 95% CI, 2.17-9.52), prospective studies (HR, 6.84; 95% CI, 2.71-17.26), <10-year follow-up studies (HR, 1.88; 95% CI, 1.38-2.57), and low-quality studies (HR, 2.05; 95% CI, 1.50-2.80). CONCLUSION: This study indicates that SLE increases the risk of bladder cancer but not prostate or kidney cancer. Well-designed long-term studies are required to confirm these associations.

Outcomes and Risk Factors of Systolic Pulmonary Artery Pressure Progression in Patients with Systemic Rheumatic Diseases: Follow-up Results from a Korean Registry.

OBJECTIVES: This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases. PATIENTS AND METHODS: A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up. RESULTS: The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p<0.001). In patients with systemic sclerosis, the majority of patients remained static within their pressure group or rose progressively: the patients with markedly elevated sPAP at follow-up were higher than those at baseline (32% versus 15%, p<0.01). In patients with mixed connective tissue disease (MCTD) or rheumatoid arthritis (RA), the majority of patients remained static within their pressure group or gradually improved: the patients with markedly elevated sPAP at follow-up were lower than those at baseline (RA=14% versus 29%, MCTD=5% versus 16%, p<0.05). CONCLUSION: Persistently high sPAP or increase of sPAP over 60 mmHg at follow-up was associated with increased mortality. There were some differences in the progression of sPAP according to the underlying rheumatic diseases.

Risk of pancreatic cancer in patients with systemic lupus erythematosus: a meta-analysis.

OBJECT: Accumulating evidences suggest that the incidence of several cancers is higher in systemic lupus erythematosus (SLE) than in general population. However, the finding on pancreatic cancer risk is inconsistent. This meta-analysis aimed to determine whether SLE patients are at risk for pancreatic cancer. METHODS: We searched PubMed, Embase, and the Cochrane database to screen the studies meeting our criteria. The hazard ratios (HRs) and its 95% confidence interval (CIs) were calculated from a meta-analysis. RESULTS: Eleven cohort studies were included in the final analysis. Overall, patients with SLE had an increased risk of pancreatic cancer (HR = 1.42, CI = 1.32-1.53). In subgroup analysis, hospital-based (HR = 1.43, CI = 1.32-1.54), retrospective (HR = 1.42, CI = 1.32-1.54), over 10 years followed (HR = 1.44, CI = 1.33-1.55), and low-quality studies (HR = 1.42, CI = 1.31-1.53) remained robust. Significant publication bias was not observed among the studies (p = 0.533). CONCLUSIONS: The synthesized evidence from our meta-analysis demonstrated that SLE was associated with increased risk for pancreatic cancer. A well-designed, long-period followed study is needed to confirm this association. Key Points • Cancer incidence in SLE patients is increasing, but the data concerning pancreatic cancer remains inconclusive. • Our meta-analysis indicated that the risk of pancreatic cancer was significantly increased in SLE patients. • A well-designed, long-period followed study is needed to confirm the association.

Sphingorhabdus buctiana sp. nov., isolated from fresh water, and reclassification of Sphingopyxis contaminans as Sphingorhabdus contaminans comb. nov.

A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strain, designated T5T, was isolated from the Chishui River in Maotai town, Guizhou Province, Southwest of China. Strain T5T was found to grow optimally at pH 9.0 and 25 °C. The 16S rRNA gene sequence analysis indicated that strain T5T belongs to the family Sphingomonadaceae within the phylum Proteobacteria; the strain T5T clustered with the type strains of Sphingopyxis contaminans, Sphingorhabdus wooponensis and Sphingorhabdus rigui, with which it exhibits 16S rRNA gene sequence similarity values of 96.2-96.9%. The DNA G+C content was 58.5 mol%. The major respiratory quinone was Q-10 and the major polar lipid was phosphatidylethanolamine. The major polyamine was homospermidine and the major fatty acids were C18:1 ω7c (37.5%) and C16:1 ω7c (30.1%). On the basis of phylogenetic, phenotypic and genetic data, strain T5T represents a novel species of the genus Sphingorhabdus, for which the name Sphingorhabdus buctiana sp. nov. is proposed. The type strain is T5T (= CGMCC 1.12929T = JCM 30114T). It is also proposed that Sphingopyxis contaminans should be reclassified as a member of the genus Sphingorhabdus.