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We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments.In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52 weeks).In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044 mm at 0.1 mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024).Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.

Purpose Rheumatoid arthritis (RA) causes joint space narrowing (JSN) as a form of joint destruction. We developed an automatic system that can detect joint locations and compute the joint space difference index (JSDI), which was defined as the chronological change in JSN between two radiographs. This study aims to evaluate the application of "machine vision" for radiographic image of the finger joints. Materials and methods Fifteen RA patients with long-term sustained clinical low disease activity were recruited. All patients underwent hand radiography and power Doppler ultrasonography (PDUS). The JSN was evaluated using the Genant-modified Sharp scoring (GSS) method and the automatic system. Synovial vascularity (SV) was assessed quantitatively using ultrasonography. Results There were no significant differences in the JSDI between the joints with JSN and those without JSN on GSS (p = 0.052). The JSDI of the joints with SV was significantly higher than those without SV (p = 0.043). The JSDI of the no therapeutic response group was significantly higher than those of the response group (p < 0.001). Conclusion Our software can automatically evaluate temporal changes of JSN, which might free rheumatologists / radiologists from the burden of scoring hand radiography.

Objective To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. Methods At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at Results Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) Conclusions After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.

The purpose of this study was to illustrate the clinical and imaging properties of giant intraosseous cyst-like lesions (GICLs) of the metacarpal bones extending beyond the central diaphysis in rheumatoid arthritis (RA) patients on magnetic resonance (MR) images. A keyword search was conducted to extract GICLs of the metacarpal bones out of MR reports in RA patients. There were nine GICLs extending from the subchondral bone region beyond the central diaphysis of the metacarpal bones on MR images in eight subjects with RA (seven females, one male). The age range was from 60 to 87 years with a median age of 65.5 years. The average disease duration was 13.1 years. As for the disease activity, one was low, six were moderate and one was high. None of the nine lesions were visible on radiography. The Steinbrocker stage distribution was as follows: I (n = 3), II (n = 2), and III (n = 3). Intraosseous cyst-like lesion of the metacarpal bones on MR images is a relatively rare manifestation in patients with long-standing RA. Although the lesion seems to be derived from subcortical bone break, it is not necessarily erosive in nature.

Ultrasonography is useful for assessment of synovitis in the hand of rheumatoid arthritis (RA) patients. The aim of this study was to investigate the predictive value of the quantitative power Doppler (PD) signal assessment in the subchondral bone region of the metacarpophalangeal (MCP) joint in patients with RA showing radiographic progression of the hand by comparing with those of previously reported scoring systems. Twenty-two patients (20 women) with RA who underwent power Doppler ultrasonography (PDUS) of the bilateral one to five MCP joints at baseline were included in the study. Radiography of both hands was performed at baseline and at 1 year. PDUS of the synovial space was evaluated according to semi-quantitative scoring (0–3) and quantitative measurement (0–100%). The PD signal in the subchondral bone region was qualitatively (0, 1) and quantitatively (mm2) assessed. The performance of PDUS assessment was compared using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the risk ratio (RR). As a predictor for radiographic progression, the quantitative PD signal assessment in the subchondral bone region (AUC = 0.842, p

No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA.This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints.Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30],Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.

Hypophosphatasia (HPP) is caused by mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene in an autosomal recessive or dominant manner and characterized by defective mineralization of bone and low serum ALP levels. In this report, we present a family with HPP mother (case 1) and HPP child (case 2) who have identical TNSALP gene mutation (c.1015G>A p.Gly339Arg heterozygous mutation) but distinct clinical phenotypes. Whereas case 1 appeared to be asymptomatic despite extremely low levels of serum ALP, case 2 had several HPP-related symptoms, such as tooth loss, fractures, short stature, with slightly decreased ALP levels. Upon the diagnosis of HPP, case 1 discontinued denosumab, which was used to treat her rheumatoid arthritis, concerning the risk of atypical femoral fractures. The clinical course of this family was suggestive in a genotype-phenotype imbalance in HPP, the underdiagnosis of HPP in adults, and the risk of atypical femoral fractures using bone resorption inhibitors.

This research aimed to study the application of deep learning to the diagnosis of rheumatoid arthritis (RA). Definite criteria or direct markers for diagnosing RA are lacking. Rheumatologists diagnose RA according to an integrated assessment based on scientific evidence and clinical experience. Our novel idea was to convert various clinical information from patients into simple two-dimensional images and then use them to fine-tune a convolutional neural network (CNN) to classify RA or nonRA. We semi-quantitatively converted each type of clinical information to four coloured square images and arranged them as one image for each patient. One rheumatologist modified each patient’s clinical information to increase learning data. In total, 1037 images (252 RA, 785 nonRA) were used to fine-tune a pretrained CNN with transfer learning. For clinical data (10 RA, 40 nonRA), which were independent of the learning data and were used as testing data, we compared the classification ability of the fine-tuned CNN with that of three expert rheumatologists. Our simple system could potentially support RA diagnosis and therefore might be useful for screening RA in both specialised hospitals and general clinics. This study paves the way to enabling deep learning in the diagnosis of RA.

To identify the incidence and risk factors for hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with resolved HBV receiving biological disease-modifying antirheumatic drugs (bDMARDs).Rheumatoid arthritis patients in whom bDMARD therapy was initiated in our departments from April 2009 to July 2016 were reviewed. The patients diagnosed with resolved HBV and whose HBV-DNA levels had been repeatedly measured were enrolled. The endpoint was HBV reactivation (a positive conversion of HBV-DNA or unquantifiable cases with positivity20 IU/mL). Nucleic acid analogues (NAAs) were administered when the HBV-DNA levels increased beyond 20 IU/mL. The associations between HBV reactivation and the clinical findings were retrospectively analyzed.One hundred and fifty-two RA patients with resolved HBV were enrolled; 133 (88%) patients had antibodies against HBV surface antigen (anti-HBs). The medicines that were administered included: abatacept (n = 29), golimumab (n = 26), etanercept (n = 25), tocilizumab (n = 25), adalimumab (n = 19), infliximab (n = 17) and certolizumab pegol (n = 11). During the observation period (15 [interquartile range 4.0-34] months), 7 (4.6%) patients developed HBV reactivation. In 5 of these patients, the HBV-DNA levels became negative or remained at20 IU/mL (+) without NAA therapy. HBV-DNA levels of20 IU/mL were observed in 2 patients but the HBV-DNA levels became negative after NAA treatment. Patients who were negative for anti-HBs showed a significantly higher incidence of HBV reactivation (P = 0.013).HBV reactivation occurred in 4.6% of RA patients with resolved HBV during the treatment with bDMARDs and the absence of anti-HBs may be a risk factor for the reactivation of resolved HBV.

We have developed a refined computer-based method to detect joint space narrowing (JSN) progression with the joint space narrowing progression index (JSNPI) by superimposing sequential hand radiographs. The purpose of this study is to assess the validity of a computer-based method using images obtained from multiple institutions in rheumatoid arthritis (RA) patients. Sequential hand radiographs of 42 patients (37 females and 5 males) with RA from two institutions were analyzed by a computer-based method and visual scoring systems as a standard of reference. The JSNPI above the smallest detectable difference (SDD) defined JSN progression on the joint level. The sensitivity and specificity of the computer-based method for JSN progression was calculated using the SDD and a receiver operating characteristic (ROC) curve. Out of 314 metacarpophalangeal joints, 34 joints progressed based on the SDD, while 11 joints widened. Twenty-one joints progressed in the computer-based method, 11 joints in the scoring systems, and 13 joints in both methods. Based on the SDD, we found lower sensitivity and higher specificity with 54.2 and 92.8%, respectively. At the most discriminant cutoff point according to the ROC curve, the sensitivity and specificity was 70.8 and 81.7%, respectively. The proposed computer-based method provides quantitative measurement of JSN progression using sequential hand radiographs and may be a useful tool in follow-up assessment of joint damage in RA patients.

Background Recent papers suggest that finger joints with positive synovial vascularity (SV) assessed by ultrasonography under clinical low disease activity (CLDA) in rheumatoid arthritis (RA) patients may cause joint space narrowing (JSN) progression. Purpose To investigate the performance of a computer-based method by directly comparing with the conventional scoring method in terms of the detectability of JSN progression in hand radiography of RA patients with CLDA. Material and Methods Fifteen RA patients (13 women, 2 men) with long-term sustained CLDA of >2 years were included. Radiological progression of finger joints was measured or scored using the computer-based method which can detect JSN progression between two radiographic images as the joint space difference index (JSDI), as well as the Genant-modified Sharp score (GSS). We also quantitatively assessed SV of these joints using ultrasonography. Results Out of 270 joints, we targeted 259 finger joints after excluding nine damaged joints (four ankylosis, three complete luxation, and two subluxation) and two improved joints according to the GSS results. The JSDI of finger joints with JSN progression was significantly higher than those without JSN progression ( P = 0.018). The JSDI of finger joints with ultrasonographic SV was significantly higher than those without ultrasonographic SV ( P = 0.004). Progression in JSDI showed stronger associations with ultrasonographic SV than progression in GSS (odds ratio [95% confidence interval]: 7.19 [3.37–15.36] versus 5.84 [2.76–12.33]). Conclusion The computer-based method was comparable to the conventional scoring method regarding the detectability of JSN progression in RA patients with CLDA.

Objectives: To preliminarily evaluate the feasibility of maintenance therapy with reduced dose of intravenous abatacept (ABT) to 250 mg/body/month after achieving remission or low disease activity (LDA). Patients and methods: RA patients treated with ABT at 13 sites were enrolled in this prospective interventional pilot study during the period between March 2013 and March 2015. Inclusion criteria were (1) age at 20 years or older, (2) under treatment with monthly intravenous ABT at approved doses, (3) DAS28-CRP lower than 2.7 at least for 6 months, (4) agreed to join this trial with written informed consent and (5) body weight under 125 kg. Enrolled patients were maintained with intravenous monthly ABT at a reduced dose of 250 mg/body (MATADOR protocol). The primary end point was the proportion of the patients continued with MATADOR protocol at week 48. MATADOR protocol was discontinued upon disease flare or other reasons such as patients’ request or severe adverse event (AE). Disease activities and structural changes were also evaluated. Results: Fifty-three patients fulfilled the entry criteria and were followed for 1-year. MATADOR protocol was continued for 1-year in 43 (81%) of the evaluated patients. Three patients experienced severe AEs. Mean DAS28-CRP and remission rate were 1.56 and 88% when ABT reduced and 1.80 and 81% at 1-year, respectively. Structural remission was achieved in 34 out of 42 evaluated patients. Conclusions: Reduced dose of intravenous ABT was proposed as a feasible choice for maintenance therapy for RA after achievement of remission/LDA, although further randomized trials would be awaited.

Aim To clarify the relationship between active synovitis/osteitis and subsequent residual synovitis (R-synovitis) in patients with rheumatoid arthritis (RA). Methods Three hundred and twenty finger joints of 16 patients with active RA at baseline (Disease Activity Score with 28 joints – erythrocyte sedimentation rate > 3.2) who subsequently achieved clinical low disease activity or remission afterwards were analyzed. Synovial vascularity (SV) was assessed according to a semi-quantitative ultrasound score (grades 0–3). Active synovitis was defined by SV positivity at baseline. R-synovitis was defined by the presence of grade > 2 SV at the 24th week. Osteitis was detected by magnetic resonance imaging (MRI) at baseline as trabecular bone lesions with water content and indistinct margins. Results Ultrasonography detected active synovitis in 116 joints at baseline. Forty-seven joints had R-synovitis at the 24th week. MRI detected osteitis in 12 joints at baseline. The presence of active synovitis with osteitis at baseline was significantly correlated with R-synovitis at the 24th week. Conclusions Active synovitis in the presence of osteitis predicted R-synovitis regardless of whether there was a clinical improvement in RA.

ObjectivesTo evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX.MethodsIn this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups.ResultsOverall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; pConclusionsCompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

Objective In this study we investigated the relationship between synovial vascularity (SV) and structural alteration of finger joints in patients with RA and long-term sustained clinical low disease activity (CLDA). Methods RA patients with CLDA of >2 years (minimum 1 year of CLDA for study entry plus 1 year of observation) were analysed. Quantitative SV values were sequentially measured in each finger joint using power Doppler ultrasonography (0, 8, 20 and 52 weeks). Radiological progression of local finger joints was evaluated according to the Genant-modified Sharp score (0-52 weeks). Results Of the 25 patients enrolled, 15 patients were finally analysed after excluding 10 patients who failed to maintain CLDA during the observational period. Changes in radiological progression of MCP and PIP joints with positive SV were significantly greater than those in joints with negative SV. Joint space narrowing (JSN) was strongly related to structural alteration of finger joints. In joints with positive SV, changes in structural alteration did not relate to total SV values, which reflect total exposure to inflammation in an observational period. Conclusion Even in patients with a long period of CLDA, finger joints with positive SV showed structural alteration, especially in the progression of JSN. Trial registration University Hospital Medical Information Network Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000007305.

Objective To evaluate the efficacious noninferiority of subcutaneous tocilizumab injection (TCZ-SC) monotherapy to intravenous TCZ infusion (TCZ-IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to synthetic and/or biologic disease-modifying antirheumatic drugs (DMARDs). Methods This study had a double-blind, parallel-group, double-dummy, comparative phase III design. Patients were randomized to receive TCZ-SC 162 mg every 2 weeks or TCZ-IV 8 mg/kg every 4 weeks; no DMARDs were allowed during the study. The primary end point was to evaluate the noninferiority of TCZ-SC to TCZ-IV regarding the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) response rates at week 24 using an 18% noninferiority margin. Additional efficacy, safety, pharmacokinetic, and immunogenicity parameters were assessed. Results At week 24, ACR20 response was achieved in 79.2% (95% confidence interval [95% CI] 72.9, 85.5) of the TCZ-SC group and in 88.5% (95% CI 83.4, 93.5) of the TCZ-IV group; the weighted difference was −9.4% (95% CI −17.6, −1.2), confirming the noninferiority of TCZ-SC to TCZ-IV. Remission rates of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and the Clinical Disease Activity Index at week 24 were 49.7% and 16.4% in the TCZ-SC group and 62.2% and 23.1% in the TCZ-IV group, respectively. Serum trough TCZ concentrations were similar between the groups over time. Incidences of all adverse events and serious adverse events were 89.0% and 7.5% in the TCZ-SC group and 90.8% and 5.8% in the TCZ-IV group, respectively. Anti-TCZ antibodies were detected in 3.5% of the TCZ-SC group; no serious hypersensitivity was reported in these patients. Conclusion TCZ-SC monotherapy demonstrated comparable efficacy and safety to TCZ-IV monotherapy. TCZ-SC could provide additional treatment options for patients with RA.

The visual assessment of joint space narrowing (JSN) on radiographs of rheumatoid arthritis (RA) patients such as the Genant-modified Sharp score (GSS) is widely accepted but limited by its subjectivity and insufficient sensitivity. We developed a software application which can assess JSN quantitatively using a temporal subtraction technique for radiographs, in which the chronological change in JSN between two radiographs was defined as the joint space difference index (JSDI). The aim of this study is to prove the superiority of the software in terms of detecting fine radiographic progression in finger JSN over human observers. A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. We compared the smallest detectable changes in JSW between the JSDI and visual assessment using phantom images. In a clinical study, 222 finger joints without interval score change on GSS in 15 RA patients were examined. We compared the JSDI between joints with and without synovial vascularity (SV) on power Doppler ultrasonography during the follow-up period. True JSW difference was correlated with JSDI for JSW differences ranging from 0.10 to 1.00 mm at increments of 0.10 mm (R2 = 0.986 and P

RA is a condition of multiple synovitis. Abnormal synovial vascularity (SV) is evident with the onset of joint inflammation. The idea of estimating the level of joint inflammation by sonographic SV was conceived with the advancement of US. The ideal treatment strategy, called treat to target (T2T), requires early diagnosis and assessment of RA. Detection of positive SV can be useful for proving the presence of synovitis and finally diagnosing RA. In the assessment of RA, US-based global scores aimed at assessing overall disease activity have the potential to be useful for the achievement of T2T because US can directly detect changes in synovitis. Remaining SV in local joints increases the risk of structural deterioration. RA requires both improvement of overall disease activity and the disappearance of local SV for remission. The evaluation of SV provides various information and contributes to the clinical treatment of RA.

Objective To investigate the relationship between synovial vascularity and progression of structural bone damage in each finger joint in patients with rheumatoid arthritis (RA) and to demonstrate synovial vascularity as a potential therapeutic marker. Methods We studied 250 metacarpophalangeal (MCP) and 250 proximal interphalangeal (PIP) joints of 25 patients with active RA who were administered adalimumab or tocilizumab. Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at the fourth and eighth weeks. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and the twentieth week. Results Clinical indices such as the 28-joint Disease Activity Score, the Clinical Disease Activity Index, and the Simplified Disease Activity Index were significantly decreased by biologic agents. The MCP and PIP joints with no response in synovial vascularity between baseline and the eighth week (vascularity improvement of ≤70% at the eighth week) showed a higher risk of radiographic progression compared with responsive joints (vascularity improvement of >70% at the eighth week; relative risk 2.33–9). Radiographic progression at the twentieth week was significantly lower in responsive joints than in nonresponsive joints. Conclusion The improvement of synovial vascularity following treatment with biologic agents led to suppression of radiographic progression of RA in each finger joint. The alteration in synovial vascularity numerically reflected therapeutic efficacy. Using vascularity as a marker to determine the most suitable therapeutic approach would be beneficial for patients with active RA.

Objective To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA). Methods We studied 190 metacarpophalangeal (MCP) joints and 190 proximal interphalangeal (PIP) joints of 19 patients with active RA who had initial treatment with disease-modifying antirheumatic drugs (DMARDs). Patients were examined by clinical and laboratory assessments throughout the study. Hand and foot radiography was performed at baseline and the twentieth week. Magnetic resonance imaging (MRI) was performed at baseline. PDS was performed at baseline and the eighth week. Synovial vascularity was evaluated according to both quantitative and semiquantitative methods. Results Quantitative PDS was significantly correlated with the enhancement rate of MRI in each single finger joint. Comparing quantitative synovial vascularity and radiographic change in single MCP or PIP joints, the level of vascularity at baseline showed a significant positive correlation with radiographic progression at the twentieth week. The change of vascularity in response to DMARDs, defined as the percentage change in vascularity by the eighth week from baseline, was inversely correlated with radiographic progression in each MCP joint. The quantitative PDS method was more useful than the semiquantitative method for the evaluation of synovial vascularity in a single finger joint. Conclusion The change of synovial vascularity in a single finger joint determined by quantitative PDS could numerically predict its radiographic progression. Using vascularity as a guide to consider a therapeutic approach would have benefits for patients with active RA.

To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. PDUS reflected infliximab’s effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.

Power Doppler ultrasonography (PD-US) has proved to be a useful technique to measure synovial vascularity due to its capability to provide data that can be used to evaluate the level of joint inflammation and assess rheumatoid arthritis (RA). We have developed a novel PD-US finger joint scoring method that introduces quantitative measurements into the conventional PD-US assessment method. A comparison of the two methods revealed that our novel PD-US method strongly correlates with the conventional method in terms of RA assessment. We performed finger joint PD-US on 69 patients with RA and 70 patients who had multiple joint pain but showed no evidence of inflammatory diseases (non-inflammatory disease, NI) and measured the synovial vascularity of the metacarpophalangeal joints 1–5 and proximal interphalangeal (PIP) joints 1–5 for each patient. We analyzed the data with receiver operating characteristic analysis and, based on the results for the total vascularity of 20 finger joints, defined a cut-off value of 36% as discriminating between RA and NI. This cut-off value was found to be a valuable tool in screening for RA. We conclude that our finger joint PD-US scoring system is both useful and applicable for diagnosing RA.

We conducted a prospective multicenter study to assess early changes in the dynamics of bone metabolism in patients with systemic connective tissue diseases following commencement of high-dose glucocorticoid therapy and the benefits of early treatment with bisphosphonate and vitamin D analogue. The subjects of this randomized controlled trial were 106 female patients with systemic connective tissue diseases treated for the first time with glucocorticoids at doses equivalent to prednisolone ≥20 mg/day (age ≥ 18 years). One week after initiation of glucocorticoid therapy, patients were randomly assigned to treatment with alfacalcidol at 1 μg/day (n = 33), alendronate 35 mg/week (n = 37), and alfacalcidol plus alendronate (n = 36). The primary endpoints were changes in lumbar spine bone density at 6 months of treatment and the frequency of bone fracture at 12 months. Commencement of glucocorticoid therapy was associated with a rapid and marked bone resorption within 1 week. The combination of alfacalcidol and alendronate administered after the first week of glucocorticoid therapy halted the pathological processes affecting bone metabolism, increased bone density, and reduced the incidence of bone fracture over a period of 12 months. Taken together, the use of the combination of alfacalcidol and alendronate improved bone metabolism, increased bone density, and significantly reduced the incidence of bone fracture during 1-year high-dose glucocorticoid therapy.

The patient was a 61-year-old man diagnosed with rheumatoid arthritis (RA) in 2001. He initially received treatment at a nearby clinic, but his condition could not be satisfactorily controlled. He subsequently consulted our hospital during the same year. Although his symptoms improved in response to treatment at our hospital, slight fever, cough, and then high fever and dyspnea subsequently developed. A diagnosis of interstitial pneumonia was made on the basis of findings of diagnostic imaging. The time course of changes in serological markers, including surfactant protein A (SP-A), surfactant protein D (SP-D), and KL-6, as well as markers of inflammatory reaction and lactate dehydrogenase was examined to determine the clinical significance of serological markers in the management of interstitial pneumonia.

This pilot multicenter exercise aimed to evaluate the inter-observer reproducibility of synovial power Doppler (PD) signals in rheumatoid arthritis (RA) patients and to determine the factors influencing the measurements.Two representative RA patients were assessed by four independent experienced sonographers. The influence of machine difference, deterioration of the transducer and pulse repetition frequency (PRF) on the assessment of synovial PD signals was investigated.Intra-class correlation coefficient (ICC) for the scanner-reader reproducibility of semi-quantitative PD score was high (0.867). ICC for the inter-scanner reproducibility of synovial PD pixel count was higher than that of semi-quantitative PD score. The assessment of PD signals significantly differed between two machines with quantitative measurements but did not with semi-quantitative score. The assessment of PD signals with a deteriorated transducer was much less sensitive than that with an intact one. The semi-quantitative scores for PD signals were comparable between three different PRFs (500/800/1,300 Hz), whereas the pixel count was significantly lower with the highest one in the knee joint.Measurement of PD signal can be substantially affected by deteriorated quality of the transducer, whereas the differences are relatively modest between machines with similar specifications and also between PRF settings within a low range.

Objective. To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. Methods. We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. Results. Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. Conclusion. Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www. umin.ac.jp/ctr/; UMIN000004476.

The objective of this study was to assess interobserver uncertainties in power Doppler (PD) examination of the fingers of patients with rheumatoid arthritis (RA), by separating the source of the discrepancy into (1) acquisition of the images and (2) criteria for assessment of the images.Twenty patients who had been diagnosed with RA were enrolled in this study. Ultrasound examinations were performed by one inexperienced and two experienced sonographers. Interobserver variation was measured using a conventional semiquantitative image grading scale. Interobserver variation of the quantitative PD (QPD) index (the summation of the colored pixels in a region of interest) was also assessed.The agreement was higher between the two experienced sonographers (kappa value of 0.8) than between experienced and inexperienced sonographers (kappa value, 0.6-0.7) in the semiquantitative image grading scale. Results suggest that the difference in the assessment on the image grading scale was due more to the difference in the acquisition of the images than to variations in the grading criteria between sonographers. An excellent relationship was noted between the image grading scale and the QPD index for Doppler signal with a Spearman's coefficient of rank correlation of 0.83 (P0.0001).Interobserver discrepancies in the image grading and QPD index methods were due more to the difference in the acquisition of the image than to the grading criteria used. The QPD index seems to be as reliable as the image grading scale with reasonable interobserver agreement between experienced sonographers.

The purpose of this study was to investigate whether improvement of regional inflammatory findings in knee joints of rheumatoid arthritis (RA) could be detected by positron-emission tomography (PET) using 18F-Fluorodeoxyglucose (FDG) after acupuncture treatments, as well as improvement of systemic inflammatory markers. Six RA patients (all female, 61 ± 12 years old) received 10 acupuncture treatments in 2 months, to 11 traditional acupuncture points around a knee joint considered effective on RA. A visual analogue scale (VAS) for intensity of pain, knee joint range of motion (ROM), face scale for patient mood, and modified health assessment questionnaire (MHAQ) for disability of daily activities were assessed just before and after acupuncture. Maximum standardized uptake value (SUVmax) and the volume with SUV more than 1.0 [Volume(SUV > 1)] on FDG–PET images as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured before and after the treatments. VAS, ROM, face scale and MHAQ improved in all patients and significantly after acupuncture, but no significant change was detected in ESR, CRP, SUVmax, or Volume(SUV > 1). Acupuncture relieves symptom, remedies physical function, and improves quality of life in RA patients, but may have no or very limited anti-inflammatory effect systemically. The regional effects of acupuncture are unlikely to be induced through reduction of regional inflammation. We believe this clinical study is the first step for elucidating therapeutic mechanisms of acupuncture, which must be important for the rational use and further development of acupuncture.

広範な解離性胸腹部大動脈瘤の発症をみたMarfan症候群の1例を発端者とし,常染色体優性遺伝により伝播したMarfan症候群の多発家系を発見した.発端者は35才,女性で,解離性大動脈瘤,水晶体脱臼, arachnodactylyをはじめとする様々な骨格異常を有していた.さらに家系調査により一卵性双生児例や,幼児のMarfan症候群例をも発見しえた.本症候群患者の家系調査は症状の顕性化していない患者を発見する可能性があり,合併症に対する早期の対策の上からも重要と思われる.また,本症候群の一卵性双生児例は本邦第1例目と思われ,文献的考察を加え報告する.

A 57-year-old female suffered from Hashimoto's thyroiditis since 1959. When she was hospitalized in Nov. 1979 for acute bronchitis, her home doctor pointed out her sera showed marked hypergammaglobulinemia. She was referred to our hospital for further examination. Her case was diagnosed as multiple myeloma according to the findings; increasement of IgG1, k monoclonal gammaglobulin, increasement of immature plasmacytes in bone marrow and multiple osteolytic lesions in the skull. Her sera also showed anti-microsome antibody activity at a dilution of 1: 25, 600.The monoclonal protein was purified from her sera to testify the presence of anti-microsome antibody activity. The results were as follows.1) Patient's purified IgG, F (ab')2 and light chain kappa F (ab')2 showed anti-microsome antibody activity at a dilution of 1: 102, 400, 1: 102, 400 and 1: 25, 600 respectively. However, light chain lambda F (ab')2 did not show this antibody activity.2) Anti-idiotypic antybody was prepared by immunizing rabbit with F (ab')2 fragment of patient's IgG followed by absorption with IgG of Cohn's fraction II. This anti-idiotypic antibody binded only F (ab')2 of patient's IgG but not IgG of Cohn's fraction II. This anti-idiotypic antibody inhibited the binding between the monoclonal protein and microsome antigen.These results suggested that patient's monoclonal protein was the antibody to microsome.This is the first case reported in the literature whose serum monoclonal protein has been proved to be anti-microsome antibody.

A seventy-two-year old female had chest pain since October 1981. In July 1982, she was admitted for congestive heart failure. In October 1982, compression fractures of vertebrae on Th12 and L1, and Bence Jones protein in the urine were found. She was transferred to our hospital for further examination about multiple myeloma in November 1982. Her laboratory data included mild normocytic normochromic anemia, leukocytes 9, 600/cmm, plasma cells 34% in peripheral blood, total protein 4.5g/dl, decreased all classes of immunoglobulins, BUN 99mg/dl, and creatinine 6.9mg/dl. Her serum and urine showed M-bow only against anti-λ antiserum in immunoelectrophoresis. She was diagnosed as Bence Jones λ type plasma cell leukemia associated with renal failure. Her renal function was gradually improved after chemotherapy and plasmapheresis were started. After a month her renal function became worse, but the response to further treatments including chemotherapy and plasmapheresis could not be obtained. She was died of renal failure on 19th December 1982. In autopsy specimen, many tubular casts and Bence Jones λ type proteins in tubular epithelial cells were found. Bence Jones proteins were purified from patient's urine by ammonium sulfate precipitation method followed by DEAE column chromatography. This purified λ type Bence Jones proteins were used as a standard marker in the measurement of λ type free light chains in the patient's serum. Patient's serum free light chains were serially measured during her clinical course, and were markedly decreased after initial treatment. We discussed about the negative role of Bence Jones proteins on renal function in multiple myeloma. Plasmapheresis treatment along with chemotherapy shows beneficial effect on renal function mainly by removing free light chains from the serum in the patient with Bence Jones type multiple myeloma.

自己免疫性溶血性貧血(AIHA)とBasedow病との合併例を経験したので報告する.患者は28才の女性で,高熱,動悸,全身倦怠感,軽度の黄痩のため入院した.クームス試験陽性.ハプトグロビン消失,赤血球形態正常であるためAIHAと診断した.また,甲状腺機能亢進症状があり.123I摂取率高値, TRHテストにてTSHが無反応, T3抑制試験にて1231摂取率抑制されず,さらにTSH受容体抗体(TBII)を認め, Basedow病と診断した.赤血球自己抗体は,温式の血液型特異性をもたないIgGκ型の抗体が検出されたほか,冷式抗体の存在も疑われた. AIHAとBasedow病の確実な合併例は文献上本例が3例目で,両疾患の免疫学的な関係について考察を加えた。

SLEの発症をみた二組の一卵性双生児例を経験した.一組は20才の姉妹例で,両者ともSLEを発症している.両者の間では発症時期の違いの他,免疫学的検査等の一部に不一致を認めたが,両者の間の環境因子に特に違いはなく,日光曝露が発症時期に影響を与えたと考えられた.もう一組は22才の兄弟例で,兄はSLEであつたが,弟はBFP以外は特記すべきものがなかつた.この両者も環境因子は同等であつた.以上の二組の血縁者調査では,姉妹例では,他に免疫学的異常を認める者はなかつたが,兄弟例では,他に抗核抗体弱陽性者を認め,父方のHLAハプロタイプが一致していた.この両組について, MLC,免疫グロブリン産生能, ALAについて検討した.

当科126例のSLE群と, 70例の非SLEリウマチ疾患群においてARA新旧両基準について検討した. SLE群の臨床症状では関節炎90%,蝶形紅斑62%が多く, Tanらの報告と比較すると新基準では漿膜炎が低頻度である以外に有意差はなかつた. ARA新基準に加えられた項目では,抗核抗体99%,抗DNA抗体83%と高かつた. Sm抗体は陽性率26%であるがLE細胞やBFPと同様に特異度はきわめて高かつた. ARA基準の平均陽性項目数はSLE群では旧基準5.40項目,新基準5.61項目であり, 4項目以上陽性症例の割合はそれぞれ88.1%, 96.8%と有意に増加が認められた.対照群の特異度は98.6%から95.7%と減少したが有意差はなく,新基準は感度に勝ることが示された.

目的:超音波パルスドプラー法(以下PDE)を用い,当科全身性エリテマトーデス(以下SLE)患者を対象に肺高血圧症(PH)の検索を行い,臨床検査所見について比較検討した.方法:超音波断層法とPDEの複合システムを用い,右室流出路又は肺動脈弁口部での血流速度パターンを表示しPH patternを検討した.結果: SLE 42例中7例にPH patternが認められ,この群ではRaynaud現象,抗RNP抗体,血小板減少が高頻度に認められた.