Comprehensive Management of Takayasu Arteritis Using Immunologic and Antithrombotic Interventions With Cerebral Circulation Support: A Case Report.

A 20-year-old woman with bilateral common carotid artery stenosis was diagnosed with Takayasu arteritis (TA). She suffered from a recurrent stroke, and repeated transient ischemic attacks (TIAs) occurred due to middle cerebral artery (MCA) stenosis. The clinical course indicated that TA contributed to MCA stenosis despite the negative results for serological inflammation markers. Immunotherapy with tocilizumab and methotrexate effectively reduced disease activity and improved symptoms. Bed rest and hydration prevented further TIAs and ischemic stroke progression. Long-term monitoring of neurological symptoms and angiography findings is essential to evaluate disease severity and treatment efficacy in TA patients with negative inflammatory markers.

Reduced Rate of Disease Flares in Japanese Patients with Systemic Lupus Erythematosus: An Altered Balance between the Use of Glucocorticoids and Immunosuppressants in Recent Decades.

Objective This study examined whether or not the disease control in Japanese patients with systemic lupus erythematosus (SLE) had improved in recent years and its possible association with altered balance between the use of glucocorticoids and immunosuppressants. Methods We enrolled Japanese patients with SLE who visited our medical center during 2013-2017 (Group A, 75 patients) and compared them with patients encountered during 1999-2003 (Group B, 69 patients; not overlapping with Group A). Patient background characteristics, doses of glucocorticoids, and the use of immunosuppressants at the times of SLE onset and disease flares were reviewed from the medical records. Disease flare was defined as new British Isles Lupus Assessment Group 2004 A or B scores in at least one system. Results Lupus nephritis and neuropsychiatric manifestations were less frequently observed in Group A than in Group B (p=0.042 and p=0.045, respectively). Although the initial glucocorticoid dosage was similar between the groups, the inclusion rate of immunosuppressants in the initial SLE treatment was significantly higher in Group A than in Group B (56% vs. 6% in Group B, p<0.001). The median number of SLE flares per person-year was significantly lower in Group A than in Group B (0 vs. 0.3, respectively, p<0.001), and a propensity score-matched analysis indicated the association of SLE flare with the non-use of immunosuppressants in the initial treatment (p=0.012). The rates of infectious diseases and other complications were similar between the groups. Conclusion The recent aggressive use of immunosuppressants in Japan resulted in a reduction in the rate of SLE flare.

Performance of the Revised Classification Criteria for Systemic Autoimmune Rheumatic Diseases and Their Overlap Syndromes.

Objective We evaluated the performance of the revised classification criteria for assessing different systemic autoimmune rheumatic diseases and their overlap syndromes. Methods A total of 652 patients with or highly suspected of having systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM) or rheumatoid arthritis (RA) were included in this study. The 1997 revised American College of Rheumatology (ACR) and the 2019 European League Against Rheumatism (EULAR)/ACR criteria for SLE, the 1980 ACR and the 2013 ACR/EULAR criteria for SSc, the criteria by Bohan and Peter and the 2017 EULAR/ACR criteria for PM/DM, and the 1987 revised ACR and 2011 ACR/EULAR criteria for RA were used for disease classification. Results The old and new criteria and a clinical diagnosis were used to respectively classify 103, 106 and 105 SLE patients; 35, 47 and 58 SSc patients; 18, 23 and 33 PM/DM patients; and 297, 389 and 468 RA patients. Sensitivity increased from 82.9% to 92.4% in SLE, from 56.9% to 79.3% in SSc, from 54.5% to 66.7% in PM/DM, and from 62.6% to 80.8% in RA. SLE-SSc was the predominant type of clinical overlap syndrome, while SLE-RA was the most classifiable. Conclusion The revised classification criteria for all the diseases showed an improved sensitivity, and SLE-overlap syndrome was predominant, regardless of the criteria sets.

Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission.

To elucidate the disease-flare process in rheumatoid arthritis (RA) after discontinuing biological disease-modifying antirheumatic drugs (bDMARDs), we first focused on RA-flare prediction after achieving stringent remission criteria. Patients with RA who maintained a simplified disease activity index ≤ 3.3 for ≥ 3 months during November 2014-January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28-erythrocyte sedimentation rate ≥ 3.2 with increase from baseline > 0.6) within 2 years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2-3 months for 2 years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan-Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2 years; median treatment period with discontinued bDMARD, 2 years; median remission duration, 18 months) were enrolled. Twenty patients (55.6%) experienced RA flare 43-651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan-Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p = 0.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p = 0.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.

Finger Joint Cartilage Evaluated by Semiquantitative Ultrasound Score in Patients With Rheumatoid Arthritis.

OBJECTIVE: Joint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. Since joint space narrowing (JSN) is not a direct evaluation of cartilage using radiography, we aimed to examine the validity of ultrasound (US) cartilage evaluation using a semiquantitative method in patients with RA. METHODS: We enrolled 103 patients with RA who were in remission or showing low disease activity and 42 healthy subjects. The cartilage thickness of the bilateral metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the second to fifth fingers was measured by US, and the recorded images were scored semiquantitatively using a scale of 0-2. In addition, the JSN of the corresponding joints was scored using a hand radiograph. The relationships between total cartilage thickness, its semiquantitative score, and JSN score were assessed using Spearman's rank correlation coefficients. RESULTS: Total cartilage thickness was significantly thinner in patients with RA compared to healthy subjects for both the MCP and PIP joints (both P < 0.001). The semiquantitative sum of 16 joints ranged from 2 to 26 (median 8) in patients with RA, which was significantly greater than the 0-11 (median 4) in healthy subjects (P < 0.001). In patients with RA, the semiquantitative score showed a significant negative correlation with cartilage thickness (ρ = -0.64, P < 0.001) and a significant positive correlation with JSN score (ρ = 0.66, P < 0.001). Furthermore, these scores showed a significant correlation with RA disease duration. CONCLUSION: A simplified and direct evaluation of finger joint cartilage damage by semiquantitative US score is valid and useful for patients with RA.

Development and exacerbation of pulmonary nontuberculous mycobacterial infection in patients with systemic autoimmune rheumatic diseases.

Objectives: To examine the development and exacerbation of pulmonary nontuberculous mycobacterial (NTM) infection in patients with systemic autoimmune rheumatic diseases (SARD).Methods: We conducted a case-control study. Seventeen of 7013 patients with SARD fulfilling the criteria for pulmonary NTM infection were enrolled in the NTM group. The control group was matched for age, sex, and SARD at a ratio of 2:1.Results: Eight patients with rheumatoid arthritis, four with systemic vasculitis, three with Sjögren's syndrome, and one each with dermatomyositis and systemic lupus erythematosus were included in the NTM group. Mycobacterium avium was detected in 12 (71%) patients, M. chelonae in 2, and M. intracellulare, M. abscessus, and M. kansasii in 1 patient each. Preexisting lung disease was more common in the NTM group than in the control group (88% versus 38%, p = .0009), particularly bronchiectasis (65% versus 29%, p = .033). The body mass index and serum albumin level were significantly lower in the NTM group than in the control group. Six patients (35%) experienced NTM exacerbation during observation. Clinical immune status at the time of NTM diagnosis, as indicated by the peripheral blood leukocyte/lymphocyte count and serum immunoglobulin G level, was unremarkable and comparable between patients with and without exacerbation, as were the treatments for SARD.Conclusions: In patients with SARD, pulmonary NTM infection may develop and exacerbate without clinically apparent immunosuppression.

Global assessments of disease activity are age-dependent determinant factors of clinical remission in rheumatoid arthritis.

OBJECTIVE: The aim of the study is to assess the factors associated with clinical remission of patients with rheumatoid arthritis (RA) in daily clinical practice. METHODS: This analysis was based on the data of 304 RA patients in our center between May 2014 and March 2015. The following information was included: tender, swollen, and symptomatic joint counts, patient's and physician's global assessments, functional disability, laboratory and radiographic data, and RA treatments received. RESULTS: The patients were predominantly female (77.6%), with a median age of 71 years and a median disease duration of 5.8 years. Clinical remission rate, determined using the simplified disease activity index (SDAI), was 49.7%. Patient's and physician's global assessments (/10cm) showed a higher score among patients who did not achieve SDAI remission than among those who did (median: 3.2 versus 0.3, p < 0.0001; and median: 1.8 versus 0.3, p < 0.0001, respectively). The contribution of serum C-reactive protein values (mg/dL) to SDAI was limited (median: 0.19 versus 0.06; p < 0.0001), as well as tender or swollen joint counts (median = 0 or 1). On multivariate analysis of factors not directly related to the disease activity, age was an independent risk factor for non-remission, and global assessment scores by patients and physicians showed an age-dependent increase, while counts of tender, swollen and symptomatic joints were comparable among elderly and non-elderly patients. CONCLUSION: Global assessment of disease activity was age-dependent and independent of joint counts, and it provides a critical determinant of clinical non-remission.

Concordance of Patient-Reported Joint Symptoms, Physician-Examined Arthritic Signs, and Ultrasound-Detected Synovitis in Rheumatoid Arthritis.

OBJECTIVE: Ultrasonography has been prevalently used as a valid and objective modality for joint examination in patients with rheumatoid arthritis (RA). This study aimed to examine and compare the concordance between ultrasound, clinical assessment, and patient-reported assessment of joint synovitis in RA. METHODS: Fifty patients with RA (84% female, median age 69 years, median disease duration 31 months, and median Disease Activity Score in 28 joints 3.8) completed the self-evaluation of joint symptoms, including pain and considerable stiffness in the (proximal) interphalangeal, metacarpophalangeal, wrist, elbow, shoulder, knee, and ankle joints. These joints were also examined by a physician in order to assess the presence of tenderness or swelling; the presence of imaging synovitis was assessed by ultrasonography. RESULTS: In a total of 1,492 evaluated joints, symptoms (pain and stiffness), tenderness, and swelling were noted in 288 (19.3%), 182 (12.2%), and 220 (14.7%) joints, respectively, while ultrasound indicated synovitis in 317 (21.2%) joints. Overall concordance with ultrasound findings was lowest for joint tenderness (κ = 0.30), followed by symptoms (κ = 0.39), and by swelling (κ = 0.43), irrespective of the evaluated joint, except for the elbow. Moreover, the percentages of inflamed joints detected only on the basis of symptoms, tenderness, or swelling were 18.6%, 2.2%, and 8.5%, respectively, of all joints with signs of synovitis on ultrasonography. CONCLUSION: Joint swelling showed the best concordance with ultrasonography, followed by patient-reported joint symptoms, and joint tenderness. Joint symptoms, rather than tenderness evaluation, may be a better clinical indicator of synovitis in RA patients.