Masakazu Matsushita

Autofeedback from ultrasound images provides rapid improvement in palpation skills for identifying joint swelling in rheumatoid arthritis.

Objective. Joint swelling, an important factor in the classification criteria and disease activity assessment in rheumatoid arthritis (RA), renders joint palpation a necessary skill for physicians. Ultrasound (US) examination that visualizes soft tissue abnormalities is now used to assess musculoskeletal disease. We assessed the usefulness of US assessments in enhancing physical joint examination skills. Methods. We examined 1944 joints (bilateral shoulder, elbow, wrist, metacarpophalangeal joints 1–5, and knee joints) in 108 patients with RA during April–July 2011. We first physically examined and confirmed joint swelling; subsequently, the same rheumatologist conducted US examinations and multiple assessors graded the joint swelling. When the 2 results differed, we received autofeedback from the US results to improve the physical examination skills. Results. The sensitivities and specificities of physical examination for US-detected swollen joint, the correlation coefficient (CC) of the swollen joint counts, and the concordance rate in each patient for joint swelling sites and power Doppler (PD)-positive sites with the κ coefficients between the physical and US examinations were compared over time. We found that the sensitivity of physical examination increased by 42 percentage points (pp), while the specificity decreased by 18 pp. The average CC in June–July was greater than that in April–May. The percentage of κ coefficients > 0.8 increased from 8.8% to 17% for joint swelling and from 8.3% to 14% for PD-positive sites. Conclusion. Our results suggest that autofeedback from US assessment provides quick improvement in palpation skills for identifying joint swelling in patients with RA.

Changes of CD4/CD8 ratio and interleukin-16 in systemic lupus erythematosus.

Abstract: The authors investigated changes in the ratio of CD4+ to CD8+ T cells (CD4/CD8 ratio) and T-cell activation, indicated by human leukocyte antigen (HLA)-DR expression, in patients with systemic lupus erythematosus (SLE) following treatment. An increase was observed in the CD4/CD8 ratio as well as a decrease in the expression of HLA-DR on T cells with the improvement of clinical manifestations on treatment with steroids or cyclosporine (CSA). In addition, steroid treatment suppressed whereas CSA treatment exerted no perceptible influence on the serum interleukin (IL)-16 level, concurrent with changes in T-cell phenotypes. This indicated that the mechanism of the change in the CD4/CD8 ratio differed depending on the drug, and CD8+ T cells could play an important role in reducing this ratio. The CD4/CD8 ratio and HLA-DR expression may be good indicators of therapeutic efficacy in some SLE patients.

Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody–positive inflammatory myositis

Objective The aim of this study was to evaluate the clinical characteristics of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive inflammatory myositis, and the change in anti-MDA5 antibody titres before and after onset. Method For 105 PM/DM patients, newly diagnosed in our hospital within the period 2008-2016, serum anti-MDA5 antibody levels were measured at diagnosis and after treatment by ELISA using the MESACUP anti-MDA5 test. The relationships between anti-MDA5 antibody levels and clinical manifestations, laboratory data, and mortality were examined. Result Compared with patients who were anti-MDA5 antibody negative, those who were antibody positive demonstrated more frequent dermatitis, clinically amyopathic DM, interstitial lung disease and rapid-progressive interstitial lung disease, as well as significantly higher serum ferritin, significantly lower creatine kinase and aldolase, and significantly less frequent ANA (⩾1:160) and anti-cytoplasmic pattern of ANA staining positivity. Anti-MDA5 antibody titres were examined before disease onset in two patients; one showed antibody positivity with low titres 2 years earlier, while both exhibited increased titres at onset. Anti-MDA5 antibody titres declined significantly less in survivors than in non-survivors after treatment; however, there was no significant difference between the two groups when the rate was compared at 2 months after treatment. Conclusion An initial decrease in anti-MDA5 antibody titre after commencement of treatment was observed in most of the patients, including in fatal cases, suggesting that this may not necessarily be a useful marker for treatment of patients with DM.

Predictive grade of ultrasound synovitis for diagnosing rheumatoid arthritis in clinical practice and the possible difference between patients with and without seropositivity

Objective. To determine the degree of contribution and the contributing factors of ultrasound in the diagnosis of rheumatoid arthritis (RA) in daily clinical practice and the predictive differences depending on seropositivity. Methods. We included 122 patients who presented with the main complaint of finger and/or wrist joint pain but for whom no definite diagnosis was reached or treatment strategy was provided. Ultrasound was performed on at least 22 joints (both wrist joints, proximal interphalangeal joint, and metacarpophalangeal joints), and patients were followed for ≥6 months. Factors contributing to RA diagnosis were determined and compared between seropositive and seronegative RA patients. Results. RA was diagnosed in 52 of 122 patients, in whom the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria (odds ratio [OR] = 4.74, P = 0.01) and gray scale (GS) grade of 3 (OR = 3.64, P = 0.04) for ≥ 1 joint were the contributing factors. In seropositive RA, the ACR/EULAR criteria (OR = 15.53, P < 0.001) and power Doppler (PD) ≥ 2 for ≥ 1 joint (OR = 10.48, P = 0.0048) were the contributing factors. In seronegative RA, PD ≥ 1 for ≥ 1 joint contributed the most (OR = 20.00, P = 0.0044), but the ACR/EULAR criteria did not contribute to RA diagnosis (P = 0.57). Conclusion. Ultrasound findings contributed to RA diagnosis in clinical practice. The contributing factors are different in the presence or absence of seropositivity, and ultrasound complementation was particularly useful in seronegative RA patients.

Anti-proteasome activator 28α is a novel anti-cytoplasmic antibody in patients with systemic lupus erythematosus and Sjögren’s syndrome

We evaluated the extent to which anti-proteasome activator (PA) 28α antibodies act as anti-cytoplasmic antibodies in systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). Sera from 46 SLE patients without SS, 11 SLE patients with SS, and 45 primary SS patients were tested. Using anti-PA28α and anti-PA28γ (Ki) antibodies purified from nitrocellulose membranes onto which recombinant PA28α and Ki had been transferred, the cellular distributions of the targeted antigens were analyzed immunohistochemically. In addition, the incidence of anti-PA28α antibodies was compared with those of other anti-cytoplasmic antibodies. Immunofluorescent staining showed that purified anti-PA28α antibodies reacted with the cytoplasm of HEp-2 cells, whereas purified anti-Ki antibodies reacted with nucleoplasm. Among the 15 SLE patients without SS, the six SLE patients with SS, and the 30 primary SS patients who were anti-cytoplasmic-antibody positive, anti-SS-A/Ro antibodies were the most frequently detected (53, 67, and 70%, respectively); anti-PA28α antibodies were, respectively, detected in 33, 50, and 40% of those patient groups, incidences that were higher than those of anti-ribosomal P, anti-smooth muscle and anti-mitochondrial M2 antibodies. These results show that anti-PA28α antibodies are major anti-cytoplasmic antibodies in patients with SLE and SS, and the distinct cellular distributions of PA28α and Ki suggest these proteins are associated with different cellular functions.

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension

BACKGROUND Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH. METHODSANDRESULTS Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm(-5)(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH. CONCLUSIONS Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. ( TRIAL REGISTRATION JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483).

Weighting with the Lansbury articular index improves the correlation of ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid arthritis patients

Abstract Objective. To determine whether weighting improves the correlation of ultrasound (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid arthritis (RA). Methods. As ultrasound examination was performed on 100 RA patients, and the severity of synovial effusion and synovial hypertrophy and the blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores, as well as the respective scores weighted using the Lansbury articular index (LAI, shoulder and elbow, × 12; wrist, × 8; and knee, × 24)—Lans GS28 and Lans PD28 scores. Result. The Lans PD28 score showed a higher correlation with MMP-3 (r = 0.591; 95% confidence interval, 0.446–0.705, p < 0.0001) than the existing measures. The scores of the large joints—the knee, shoulder, and elbow—correlated well with the serum MMP-3 level. Conclusion. Weighting with the LAI can improve the correlation of US findings with serum MMP-3 level. Bidirectional approach based on both serum MMP-3 level and US scores can further improve the assessment of disease activity in RA patients.

Analysis of the Structure of Proteasome‐Proliferating Cell Nuclear Antigen (PCNA) Multiprotein Complex and Its Autoimmune Response in Lupus Patients

We have recently found that the PCNA multiprotein complexes (PCNA complexes) associated with cell proliferation can be purified using monoclonal antibodies (mAbs) to PCNA.1 We attempted to analyze the structure of the complexes and found that proteasome, which had been known as an ATP-dependent proteolytic enzyme involved in antigen presentation on class I major histocompatibility molecules, was one of the elements of the PCNA complex. We also found that there was an autoimmune-response linkage between PCNA and proteasome.

Predictive markers and prenatal management of isolated fetal complete atrioventricular block: A retrospective review at a single institution

The study was conducted to determine an effective method for identifying patients at high risk of developing isolated complete atrioventricular block (CAVB) and to review the efficacy of prenatal anti‐inflammatory treatment.

A case of ankylosing spondylitis with concurrent Takayasu arteritis

We herein report a case involving a 56-year-old man who had experienced neck and lower back pain since the age of 23 years. Ankylosing spondylitis (AS) was diagnosed at 41 years of age, and treatment with sulfasalazine was initiated. At 44 years of age, the patient developed respiratory distress on exertion and chest pain. Aortic regurgitation (AR) was diagnosed via echocardiography, and the patient presented to our hospital for close examination and treatment. Coronary computed tomography angiography revealed no lesions in the coronary artery; however, magnetic resonance angiography revealed stenotic lesions in the left common carotid artery and left subclavian artery. Based on the findings of a physical examination, fundus examination, and blood tests, the patient was diagnosed with AS with concurrent Takayasu arteritis (TA). Upon administration of steroids to alleviate inflammation caused by an autoimmune mechanism, the patient’s chest symptoms and inflammatory findings improved. AR was treated with aortic valve replacement and prosthetic blood vessel replacement, after which the patient progressed well. Intraoperative aortic biopsy revealed findings pathologically consistent with TA. Although AS with concurrent AR is well described, AS with concurrent TA, as in the present case, is rare.