Search

Abstract Background Bombina variegate peptide 8 (Bv8) is a small protein secreted by frog skin. Recently it has been shown to contribute to tumor angiogenesis in mouse model. The purpose of this study was to investigate Bv8 in mice with type II collagen-induced arthritis (CIA). Methods We induced CIA in male DBA/1J mice. The severity of arthritis was evaluated based on an arthritis score. RNA was extracted from the joint, and examined for Bv8 mRNA expression by RT-PCR and real-time RT-PCR. Synovial tissue and bone marrow were immunohistochemically examined using anti-Bv8 antibody. Results The level of Bv8 mRNA expression in the joint was below the detection limit in the control group, but was elevated in the CIA group, and was correlated with the arthritis score. In addition, an increase in Bv8-positive cells was observed in the synovium and bone marrow in the CIA group. Conclusion Bv8 was elevated in the synovium and bone marrow of CIA mice, suggesting that Bv8 plays an important role in the pathogenesis of arthritis.

Objective: Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features., Methods: New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics., Results: Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, P = 0.005), perimysium (OR 6.0, P = 0.014) and fascia (OR 16.9, P < 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, P < 0.001) and Gottron sign (OR 8.05, P = 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, P = 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, P = 0.006) and malignancy (OR 8.49, P = 0.002)., Conclusion: Muscle MRI holds promise in predicting muscle pathology, disease subtypes and clinical manifestations of IIMs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: This study aimed to analyze the muscle magnetic resonance imaging (MRI) findings of patients with antineutrophilic cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) presenting with clinical symptoms in the extremities., Methods: Retrospective analysis was conducted on short tau inversion recovery MRI findings, with a focus on intramuscular vessels displaying abnormal perivascular signals, in 22 and eight patients with AAV and PAN, respectively. The number per unit area (4 cm 2 ) and diameter of abnormal vessels on muscle MRI were compared between patients with AAV and those with PAN. Cut-off values, clinical sensitivity, and specificity for these indices were calculated from the receiver operating characteristic curves to distinguish between AAV and PAN, and the relationship between the indices and clinical findings in AAV was analyzed., Results: The number of abnormal vessels per unit area was significantly higher in AAV compared to PAN (p < .05). Additionally, the diameter of the abnormal vessels was significantly higher in PAN than in AAV (p < .05). The presence of >6.44 abnormal vessels per unit area or ≤3.61 mm diameter of abnormal vessels was able to predict AAV (sensitivity, 0.955; specificity, 0.625). AAV patients with peripheral neuropathy exhibited a significantly higher number of abnormal vessels per unit area than those without peripheral neuropathy (p < .05)., Conclusions: Muscle MRI can detect small- to medium-vessel vasculitis and be a valuable tool for distinguishing between patients with AAV and PAN experiencing clinical symptoms in the extremities., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Anti-differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which has been described as clinically amyopathic dermatomyositis, complicates rapidly progressive interstitial lung disease (ILD). Owing to the absence of significant muscle symptoms, musculoskeletal MRI is often not performed. In this study, we aimed to devise a simple evaluation method using musculoskeletal MRI findings to elucidate the relationship between MRI findings and ILD prognosis and development., Methods: The medical records and MRI scans of the proximal muscles at the time of diagnosis were retrospectively reviewed for 28 patients with anti-MDA5 antibody-positive dermatomyositis who were admitted to The Jikei University Hospital and The Jikei University Kashiwa Hospital between January 2008 and March 2022. Three observers evaluated nine proximal muscles for high signals on either short-tau inversion recovery images and/or fat-saturated gadolinium-enhanced T1-weighted images in the fascia and/or in the margins of the muscles in contact with the fascia (fascial pattern), and/or high signals in the muscles away from the fascia (intramuscular pattern), and a consensus was reached., Results: Of the 28 patients, 15 presented with 'radiological myositis', where an intramuscular pattern was observed at any site. Patients with radiological myositis had significantly higher survival rates than those without radiological myositis, despite the lower rate of triple therapy with prednisolone, calcineurin inhibitors and cyclophosphamide. The spread of ILD on chest CT negatively and significantly correlated with the proportion of intramuscular lesions., Conclusion: The detection of intramuscular lesions on musculoskeletal MRI using our novel evaluation method could be clinically useful as a favourable prognostic marker., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Central sensitivity syndrome (CSS) comprises various symptoms caused by central sensitisation (CS). Using the central sensitisation inventory (CSI), a screening questionnaire developed for detecting CSS, this syndrome was recently identified in patients with long-standing rheumatoid arthritis (RA). However, the descriptors of CS-related pain and the effects of CSS on symptoms in patients with rheumatoid arthritis (RA) remain unknown. We examined the characteristics of pain and influence of CSS on patient and evaluator global assessment among multiple clinical variables., Methods: We used the central sensitisation inventory (CSI) and short-form McGill pain questionnaire to evaluate CSS and characteristics of pain in 240 outpatients with RA. Disease activity, fibromyalgia, neuropathic pain, anxiety, depression, pain catastrophising, and health-related quality of life were evaluated. We used multivariate analysis to analyse the characteristics of CS-related pain according to CSI and the effect of CSS on patient global assessment (PGA), evaluator global assessment (EGA), and PGA minus EGA among relevant clinical variables., Results: In patients with RA, the main descriptors of pain according to severity of CSI scores were "sharp" and "stabbing", whereas those of pain according to disease activity were "tender" and "throbbing". CSS was associated with EGA (p=0.000, β=- 0.199) and PGA minus EGA (p=0.021, β=0.147), but not with PGA., Conclusions: In patients with RA, descriptors for CS-related pain differ from those for disease activity-related pain. CSS may have an important impact on EGA and PGA minus EGA. Additionally, CSI may be helpful in identifying why there is discordance between PGA and EGA.

Objectives: Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients., Methods: The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses., Results: The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, β=0.266)., Conclusions: NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.

Objective: To establish predictive models for mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) using a combination of initial serum biomarker levels., Methods: The Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risk factors predictive of all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and those without anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between subgroups using the Breslow test., Results: In the derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6) levels were identified as independent risk factors for mortality in both anti-MDA-5-positive and anti-MDA-5-negative patients. We then developed a prediction model based on anti-MDA-5 antibody status, CRP level, and KL-6 level, termed the "MCK model," to identify patients at low (<15%), moderate (15-50%), or high (≥50%) risk of mortality, based on the number of risk factors. The MCK model successfully differentiated cumulative survival rates in anti-MDA-5-positive patients (P < 0.01 for low versus moderate risk and P = 0.03 for moderate versus high risk) and in anti-MDA-5-negative patients (P < 0.001 for low versus moderate risk). The utility of the MCK model was replicated in the validation cohort., Conclusion: Our findings indicate that an evidence-based risk prediction model using CRP and KL-6 levels combined with anti-MDA-5 antibody status might be useful for predicting prognosis in patients with PM/DM-ILD., (© 2020, American College of Rheumatology.)

Rationale: Chronic intestinal pseudo-obstruction (CIPO) and pneumatosis cystoides intestinalis (PCI) are rare abdominal diseases and the pathological mechanisms have not been fully elucidated. Systemic sclerosis (SSc), which is characterized by the progressive sclerotic changes of skin and internal organs, is a refractory collagen disease and is frequently associated with digestive disorders including CIPO., Patient Concerns: A 68-year-old woman who has been well managed for SSc over the long term, who presented with abdominal fullness for the first time., Diagnoses: Abdominal X-ray and computed tomography (CT) images showed PCI with pneumoperitoneum findings. Based on the diagnosis of CIPO, we evaluated the intestinal peristalsis of the patient by using cine magnetic resonance imaging (MRI)., Interventions: Oral medications of 15 g/d of Daikenchuto, 750 mg/d of Metronidazole and Sodium Picosulfate were started for improving the bowel peristaltic movement and decreasing intestinal gas production., Outcomes: A great improvement of CIPO and PCI by multidrug therapy without any surgical treatments for such an unusual case., Lessons: This case indicates that SSc can be accompanied with not only CIPO but also PCI as digestive disorders and that cine MRI, which is a definitely beneficial imaging modality, can intelligibly visualize the peristalsis of the intestines and lead to successful medical control by noninvasive treatment.

Objective: To define the characteristic findings on MRI of skeletal muscles in patients with dermatomyositis (DM) relative to those in patients with other idiopathic inflammatory myopathies (IIMs) and to assess their diagnostic performance in DM., Methods: Thirty-six patients with DM, 17 patients with amyopathic DM, 19 patients with polymyositis and 16 patients with non-IIM classified by the 2017 European League Against Rheumatism/American College of Rheumatology criteria were included in this study. The following MRI findings (short-tau inversion recovery [STIR] and gadolinium-enhanced fat-suppressed T1-weighted imaging [Gd-T1WI]) for proximal limb muscles were compared between the disease groups and between myositis-specific autoantibodies/myositis-associated autoantibodies (MSAs/MAAs)-positive and MSAs/MAAs-negative groups: structures with high signal intensity (HSI) (subcutaneous, fascia, muscle); distributions of HSI areas in muscle (diffuse, patchy, peripheral) and patterns of HSI in muscle (honeycomb, foggy, strong HSI). Univariate, multivariate and receiver-operating characteristic [ROC] analyses were performed to assess the diagnostic performance of MRI in DM., Results: The characteristic MRI findings in patients with DM were subcutaneous HSI, fascial HSI, peripheral distribution and honeycomb pattern. The MRI findings in the MSAs/MAAs-positive group included more frequent fascial HSI but less frequent foggy pattern compared with the MSAs/MAAs-negative group. Likelihood of DM score ≥ 3 (obtained by counting the number of characteristic MRI findings in patients with DM) showed good diagnostic performance in DM (STIR: sensitivity 72.2%, specificity 88.5%, area under ROC curve [AUC] 84.9%; Gd-T1WI: sensitivity 81.2%, specificity 91.5%, AUC 89.9%)., Conclusion: The characteristic MRI findings of skeletal muscles can predict patients with DM as well as patients with MSAs/MAAs., Competing Interests: Competing interests: None declared.

Objective: To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD)., Methods: We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses., Results: JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2)., Conclusion: We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We previously demonstrated that fasciitis is a common lesion in dermatomyositis (DM) and that DM-associated fasciitis is detectable, as the result of the increased vascularity in the fascia, by power Doppler ultrasonography. We aimed to investigate whether angiogenesis and vascular endothelial growth factor (VEGF)-expressing cells in the fascia are histologically demonstrated during the early phase of DM, and whether inflammation is involved in angiogenesis and an increased number of VEGF-expressing cells., Methods: We prospectively evaluated 22 patients with DM and 11 patients with polymyositis (PM). Immunohistochemical staining for CD31, VEGF, and tumor necrosis factor-α (TNF-α) were performed on paraffin-embedded sections. The total vascular inflammation score (TVIS), angiogenesis score (AS), and numbers of VEGF-expressing and TNF-α-expressing cells were analyzed in the fascia and muscle., Results: Significant fasciitis was detected in most of the patients DM with or without myositis-specific/associated antibodies, while mild fasciitis was detected in four patients with PM, two of whom were positive for anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies. The AS and the number of VEGF-expressing cells in the fascia of patients with DM were significantly greater than those of patients with PM; no significant difference was observed in muscle in patients with DM and PM. The number of VEGF-expressing cells in the fascia correlated with the AS of DM patients. In early-phase DM, the AS, the number of VEGF-expressing cells, and the TVIS in the fascia were significantly higher than in muscle. However, no significant differences were observed in these scores excluding the TVIS between muscle and the fascia in late-phase DM. In DM patients, the TVIS correlated with the AS in the fascia, while the number of TNF-α-expressing cells correlated with the TVIS and the number of VEGF-expressing cells in the fascia., Conclusion: Angiogenesis, the number of VEGF-expressing cells, and the degree of inflammation were higher in the fascia in DM than in PM, and were increased predominantly in the fascia rather than in the muscle in early-phase DM. The degree of inflammation correlated with that of angiogenesis in the fascia of DM. The fascia can therefore be a primary site of inflammation and angiogenesis in the pathogenesis of DM.

Objective: To determine the association between fasciitis and the clinical variables in patients with dermatomyositis (DM) and polymyositis (PM)., Methods: We retrospectively reviewed the medical records of 32 patients (24 DM, 8 PM) with newly diagnosed DM and PM and in whom fascia and muscle specimens were histopathologically examined. The relationship between fasciitis and the clinical variables was statistically analyzed. These included age, sex, myalgia, muscle weakness, creatine kinase (CK) and aldolase activities, anti-Jo1 antibody, interstitial lung disease, and malignancy., Results: Twenty (62.5%) of the 32 patients who underwent the histopathological examination of a fascia specimen had fasciitis, including 18 (75%) of 24 patients with DM and 2 (25%) of 8 patients with PM. The frequency of fasciitis was significantly higher among the patients with DM than among the patients with PM (p < 0.05). Histopathologically, fasciitis in PM was very mild in comparison to that in DM. The frequency of myalgia in patients with fasciitis was significantly higher than that in patients without fasciitis (p < 0.05). However, myalgia was not associated with myositis. There were no significant differences in the patients with and without fasciitis in age, sex, manual muscle test 8 scores, CK or aldolase activities, or the presence of anti-Jo1 antibodies and malignancy., Conclusion: The frequency of fasciitis was significantly higher among patients with DM than among those with PM. Fasciitis, rather than myositis, was associated with myalgia.

Objective: We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM., Methods: We prospectively evaluated 7 patients with DM and 7 patients with polymyositis (PM) for the detection of fasciitis with PDUS. MRI and PDUS were both performed in all patients. Fasciitis was histologically confirmed by en bloc biopsy., Results: Among all patients with DM, 4 showed signs of fasciitis on MRI, while increased blood flow signals were observed along the fascia by PDUS in 6 DM patients, including 4 patients with early disease (<2 months after the onset of muscle symptoms). Histologically, significant fasciitis was confirmed in 4 patients with DM. In the remaining 3 patients with DM, significant fasciitis was not evident histologically, but mild proliferation of capillaries and mild inflammation were notable in the area of the fascia. Immunohistochemical staining for CD31 indicated abnormal neovascular proliferation in the fascia in patients with DM. None of the PM patients showed signs of fasciitis or increased vascularity by MRI, PDUS, or en bloc biopsy., Conclusion: In our limited population, PDUS was useful for the detection of fasciitis associated with DM, especially in the early stage of disease. The increased blood flow signal as detected by PDUS is involved in angiogenesis accompanying fasciitis in patients with DM., (© 2016, American College of Rheumatology.)

A 15-year-old young woman received the Human papillomavirus (HPV) vaccines. Following the second HPV vaccination, intermittent fever, myalgia, arthritis and malar rash developed, and she was admitted to our hospital. Laboratory studies showed positive results for antinuclear antibody, anti-dsDNA antibody and anti-Sm antibody. Systemic lupus erythematosus (SLE) was diagnosed according to the Systemic Lupus International Collaborative Clinics 2012. Magnetic resonance imaging showed abnormal hyperintense areas in the fascia, and en bloc biopsy showed fasciitis. Treatment with prednisolone resulted in an amelioration of the symptoms. Reportedly, SLE developed after HPV vaccinations in some patients. Most such patients have a past or family history of autoimmune disease and presented SLE symptoms after the second vaccination. We describe herein a patient in whom SLE developed in association with HPV vaccination.

We report a 39-year-old female admitted for fever. She showed physical findings of bilateral granulomatous uveitis, swelling of the bilateral parotid glands, and paralysis of the left second branch of the trigeminal nerve. Her chest X-ray showed evidence of bilateral hilar lymphadenopathy. We performed biopsy of her parotid gland, and leading to a diagnosis of noncaseating epithelioid granuloma characterized by lymphocyte and multinucleated giant cell invasion. Therefore, she was diagnosed with the abortive type of Heerfordt syndrome which is a subtype of sarcoidosis. This is the only case associated with paralysis of the trigeminal nerve without paralysis of facial nerves to be reported in Japan.

Objective: To investigate whether fasciitis is histopathologically demonstrable in patients with dermatomyositis (DM), and to analyze the process of inflammatory progression in myopathy accompanying DM., Methods: STIR or fat-suppressed T2-weighted magnetic resonance imaging (MRI) and en bloc biopsy were performed in 14 patients with newly diagnosed adult-onset DM. The severity of inflammatory cell infiltration around the fascial and intramuscular small blood vessels was evaluated using the total vascular inflammation score (TVIS)., Results: In all patients, MRI revealed abnormal hyperintensity in the fascia and in marginal sites of the muscle, predominantly over central sites. En bloc biopsy revealed the presence of fasciitis in most of the patients, as shown by inflammatory infiltrates around the fascial small blood vessels. In those patients who underwent en bloc biopsy earlier than 2 months after the appearance of muscle symptoms, the TVIS of the fascia was significantly higher than the TVIS of the muscle. In contrast, in those patients who underwent en bloc biopsy >2 months after muscle symptom onset, the TVIS of the fascia did not differ significantly from the TVIS of the muscle., Conclusion: Fasciitis was histopathologically demonstrated in patients with newly diagnosed adult-onset DM as early as 2 months after the onset of muscle symptoms. These results indicate that fasciitis is a common lesion of DM and suggest that the fascial microvasculature is the primary site of inflammatory cell infiltration in DM. Fasciitis may contribute to muscle symptoms in patients with DM without myositis.

Objective: To evaluate the clinical significance of serum levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in patients with rheumatoid arthritis (RA)., Methods: The subjects were 70 patients with RA. Serum VEGF, Ang-1, and Ang-2 levels were determined by ELISA. As indices of disease activity, serum levels of C-reactive protein (CRP) and matrix metalloprotease (MMP)-3 were examined, and the 28-joint count Disease Activity Score (DAS28)-CRP was calculated. Power Doppler ultrasonography was performed in the bilateral wrists, elbows, shoulders, knees and ankles. The synovial blood flow signals were scored using a 3-grade scale (0-2), and the total of the scores in the 10 joints was regarded as the total signal score (TSS)., Results: Serum VEGF level showed significant correlations with serum CRP and MMP-3 levels, DAS28-CRP, and TSS. Serum Ang-1 level showed significant correlations with serum MMP-3 level and DAS28-CRP. Serum Ang-2 level showed significant correlations with serum CRP level and TSS., Conclusion: The serum VEGF level is important as an index of the activity of RA based on angiogenesis and a prognostic factor regarding joint destruction. Serum Ang-1 level may be useful as an index of sustained arthritis based on the maintenance of newly formed vessels. Serum Ang-2 level may reflect a state of marked angiogenesis.

The objective of the study is to examine the relationship between synovial blood flow signals and vascular endothelial growth factor (VEGF) involved in angiogenesis by Doppler ultrasound. Twenty-one patients meeting the diagnostic criteria of the American College of Rheumatology (ACR) were enrolled in this study. Doppler ultrasound signals of blood flow in the wrist synovial membrane were measured and classified into three grades: grade 1 = no flow; grade 2 = mild flow; grade 3 = intense flow. A significant correlation was observed between blood flow signals in the wrist synovial membrane and serum VEGF levels (r = 0.5681, P = 0.0072). These results suggest that the measurement of Doppler ultrasound signals of blood flow in the wrist synovial membrane is useful in the evaluation of angiogenesis.