Kurisu Tada

Involvement of Mucosal-associated Invariant T cells in Ankylosing Spondylitis

Objective. Ankylosing spondylitis (AS) is characterized by chronic inflammation of the axial and peripheral joints and ligamentous attachments. Gut immunity is thought to be involved in AS, because a prominent coexistence of gut and joint inflammation has been observed in patients with AS. Mucosal-associated invariant T (MAIT) cells are preferentially located in the gut lamina propria and produce inflammatory cytokines such as interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α), which are therapeutic targets for AS. This study aimed to investigate the involvement of MAIT cells in AS. Methods. The frequency of MAIT cells and their cytokine production were determined in patients with AS and healthy controls (HC). The expression of a MAIT cell activation marker (CD69) was analyzed in patients with AS by using flow cytometry. Results. The frequency of MAIT cells in the peripheral blood was lower in patients with AS compared with HC. The levels of IL-17 produced by MAIT cells after activation were higher in patients with AS than in the HC. CD69 expression on MAIT cells correlated with the Ankylosing Spondylitis Disease Activity Score in patients with AS. Conclusion. These results suggest the involvement of MAIT cells in the pathogenesis of AS.

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.

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.

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.

Clinical Images: Nonradiographic axial spondyloarthritis with sacroiliitis detected by tomosynthesis

Plain radiographs of the sacroiliac (SI) joint are widely used for diagnosing ankylosing spondylitis (AS). Patients are classified as having nonradiographic axial spondyloarthritis (SpA) based on a lack of radiographic changes. However, the interpretation of radiographic findings in the SI joint is very difficult to standardize; there are interobserver and intraobserver variations in the assessment of radiographic sacroiliitis. It has been reported that radiologic assessment of the SI joint does not improve after individual training and workshops (1). These difficulties in interpretation are due to the intricate anatomic structure of the SI joint. We used tomosynthesis, which provides images at a variety of arbitrary heights in a single session, to image the SI joint. A plain radiograph showed no visible changes in the SI joints of a patient with SpA (a and b). In contrast, tomosynthesis clearly demonstrated erosions and sclerotic changes in the left inferior SI joint (arrow in c). Similar findings were recognized on the computed tomography (CT) image (arrow in d). Since tomosynthesis is not affected by the structures around the SI joint, such as intestinal gas and muscles, it is possible to visualize morphologic changes in the joint not seen on plain radiographs. The tomosynthesis examination takes only a few seconds for each site. The dose of radiologic exposure is about twice that of plain radiography and almost one-tenth that of a CT scan (2). Magnetic resonance imaging is also commonly used to detect morphologic changes along with active inflammation (3), but it takes longer (;30 minutes) and is more expensive. Therefore, tomosynthesis is useful for evaluating morphologic changes in the SI joint, and contributes to the diagnostic evaluation of AS and nonradiographic axial SpA.

HLA-B46 is associated with severe sacroiliitis in Japanese patients with psoriatic arthritis

Abstract Objectives: The aim of the present study was to determine if the HLA phenotype is related to severe sacroiliitis in Japanese patients with psoriatic arthritis. Methods: This study was a single-center, retrospective, cross-sectional, observational study. We reviewed the clinical information and radiologic examinations of patients with psoriatic arthritis (PsA) who visited our hospital from January 2011 to December 2016. Radiographic changes in the sacroiliac joints were assessed by four independent investigators according to the recommendations of the Assessment of Spondyloarthritis International Society. Results: Of 113 PsA patients, 63 (55.8%) had sacroiliitis. The HLA phenotype was investigated in 39 patients. Ordered logistic regression analysis revealed that the presence of HLA-B46 was an independent risk factor for severe sacroiliitis in Japanese PsA patients (odds ratio 3.2; 95% confidence interval 1.16–9.81). Therefore, the clinical features were divided into two groups according to the presence of HLA-B46. Both the Nail Psoriasis Severity Index and grade of sacroiliitis were significantly higher in the HLA-B46–positive group (Mann-Whitney U test; p = .0003 and p = .028, respectively). Conclusion: HLA-B46 is considered a risk factor for severe sacroiliitis in Japanese patients with PsA.

Rapid glucocorticoid tapering therapy to reduce mortality from pneumocystis pneumonia in patients with rheumatic disease

Abstract Objective: Pneumocystis pneumonia (PCP) is a serious complication in patients with rheumatic diseases who are receiving immunosuppressive therapy. These patients have a higher mortality from PCP than those with human immunodeficiency virus. We examined factors associated with poor prognosis in patients with rheumatic diseases and evaluated PCP treatment in this population. Methods: This retrospective, single-center, observational cohort study included 31 patients with rheumatic diseases who were admitted to Juntendo University Hospital for PCP treatment from June 2006 to December 2017. The primary outcome was non–disease-specific mortality at discharge. Results: The median age at PCP diagnosis was 64 years. The survival rate was 61.3% (19/31). Twelve patients died, in all cases due to respiratory failure due to PCP. Among variables at PCP diagnosis and those related to PCP treatment, the presence of coexisting pulmonary diseases and greater glucocorticoid dose at PCP diagnosis were associated with higher mortality. The mortality related to biological agents for PCP was low. Rapid tapering of glucocorticoids improved survivability. Conclusion: In the treatment of PCP in patients with rheumatic diseases, rapid tapering of glucocorticoids was associated with a higher survival rate than the use of conventional therapy.

Association of five-factor score with the mortality in Japanese patients with polyarteritis nodosa

Abstract Aim: To determine mortality and its predictive factors in Japanese patients with polyarteritis nodosa (PAN). Methods: This retrospective single-center study determined the mortality of 18 patients with PAN who were admitted to Juntendo University Hospital from 1994 to 2016. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality. Results: The median age of onset was 57.0 years. The 1-year survival rate was 100% (16/16) and the 5-year survival rate was 80.0% (8/10). The relationship between mortality, as defined by the survival rate and each variable was evaluated by Cox univariate analysis. A higher 2009 five-factor score (FFS) was associated with increased mortality, with a hazard ratio of 2.34 (p = .04). Analysis of the secondary outcome of relapse-free survival time revealed an association with rapid progressive renal failure, Birmingham Vasculitis Activity Score (BVAS), the 1996 FFS, and the 2009 FFS, with hazard ratios of 7.28 (p = .048), 1.26 (p = .02), 2.32 (p = .03), and 1.82 (p = .04), respectively. Conclusion: We investigated mortality, relapse-free survival, and their predictive factors in Japanese patients with PAN. The BVAS and the 1996 FFS at diagnosis may be prognostic factors for relapse-free survival, and the 2009 FFS at diagnosis may be a prognostic factor for both mortality and relapse-free survival.

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.