Kaoru Minegishi

A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis

Abstract Objectives. To investigate the optimal number and combination of joints to be assessed by power Doppler ultrasonography (PDUS) in daily practice for rheumatoid arthritis (RA). Methods. PDUS were performed in 24 joints, including all proximal interphalangeal, metacarpophalangeal (MCP), and bilateral wrist and knee joints in 234 patients with RA. PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD score-24 was calculated by summing them up as comprehensive assessment. Results. Positive PD signals were more frequently found in bilateral wrist, knee, and the second and third MCP joints than the other joints. The individual PD scores of these 8 joints also showed higher correlation coefficients with total PD score-24 (rs ≥ 0.4). Among the sum PD scores of various selected joint combinations, the score of the combination of 8 joints (total PD score-8), including bilateral second and third MCP, wrist, and knee joints, showed the highest sensitivity and negative predictive value (98.1% and 96.2%, respectively). Total PD score-8 showed high correlation with the total PD score-24 (rs = 0.97, p < 0.01). Conclusions. Total PD score-8 is simple and efficient enough for monitoring disease activity and judging imaging remission of RA in daily practice.

Ultrasonography predicts achievement of Boolean remission after DAS28-based clinical remission of rheumatoid arthritis

Abstract Objectives. To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria. Methods. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint. Results. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score. Conclusions. Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of “deeper remission” of RA.

Distinct clinical features between acute and chronic progressive parenchymal neuro-Behçet disease: meta-analysis

Neuro-Behçet’s disease (NBD) is subcategorized into parenchymal-NBD (P-NBD) and non-parenchymal-NBD types. Recently, P-NBD has been further subdivided into acute P-NBD (A-P-NBD) and chronic progressive P-NBD (CP-P-NBD). Although an increasing number of studies have reported the various clinical features of A-P-NBD and CP-P-NBD over the last two decades, there was a considerable inconsistency. Two investigators systematically searched four electrical databases to detect studies that provided sufficient data to assess the specific characteristics of A-P-NBD and CP-P-NBD. All meta-analysis was carried out by employing the random-model generic inverse variance method. We included 11 reports consisted of 184 A-P-NBD patients and 114 CP-P-NBD patients. While fever (42% for A-P-NBD, 5% for CP-P-NBD, p < 0.001, I2 = 93%) was more frequently observed in A-P-NBD cases; sphincter disturbances (9%, 34%, P = 0.005, I2 = 87%), ataxia (16%, 57%, P < 0.001, I2 = 92%), dementia (7%, 61%, P < 0.001, I2 = 97%), confusion (5%, 18%, P = 0.04, I2 = 76%), brain stem atrophy on MRI (4%, 75%, P < 0.001, I2 = 98%), and abnormal MRI findings in cerebellum (7%, 54%, P = 0.02, I2 = 81%) were more common in CP-P-NBD. Cerebrospinal fluid cell count (94/mm3, 11/mm3, P = 0.009, I2 = 85%) was higher in A-P-NBD cases. We demonstrated that A-P-NBD and CP-P-NBD had clearly different clinical features and believe that these data will help future studies investigating P-NBD.

Clinical manifestations of Behçet’s disease depending on sex and age: results from Japanese nationwide registration

Objective This report aimed to scrutinize the prevalence of Behçets disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçets Disease were selected and analysed. Results Among 6627 International Criteria for Behçets Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.

Brain FDG-PET reflecting clinical course of depression induced by systemic lupus erythematosus: Two case reports

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multisystem involvement, frequently with neuropsychiatric manifestations. Without well-established biomarkers of neuropsychiatric SLE (NPSLE), it is difficult to differentiate psychiatric symptoms due to SLE from primary mental disorder, particularly in cases of depression [3]. We report two cases of brain [F]-fluoroD-glucose positron emission tomography (FDG-PET) with the threedimensional stereotactic surface projection (3D-SSP) analysis [2] (the details are written in the appendix) on SLE patients with major depressive-like episodes. Written informed consent for publication was obtained from both patients.

The ocular involvement did not accompany with the genital ulcer or the gastrointestinal symptoms at the early stage of Behçet’s disease

Abstract Objectives: This study aimed to identify patients with high-probability of ocular involvement of Behçet’s disease (BD). Methods: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. Results: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30–49 years). The median duration between onset and registration was 0 year (IQR 0–3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53–0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18–1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23–0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30–0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. Conclusion: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.

Successful treatment of a patient with refractory haemophagocytic syndrome in systemic lupus erythematosus with mycophenolate mofetil

Abstract Haemophagocytic syndrome (HPS) is one of the most severe complications of systemic lupus erythematosus (SLE). Although corticosteroids are usually selected as an initial treatment, some patients are corticosteroid-resistant and require additional immunosuppressants. Here, we report a case of SLE-associated HPS patient who was resistant to prednisolone, calcineurin inhibitors, cyclophosphamide, plasma exchange and infliximab but was successfully treated with mycophenolate mofetil (MMF). MMF could be an alternative treatment for intractable HPS complicated with SLE.

Musculoskeletal ultrasonography delineates ankle symptoms in rheumatoid arthritis

Abstract Objectives: To clarify the use of musculoskeletal ultrasonography (US) of ankle joints in rheumatoid arthritis (RA). Methods: Consecutive RA patients with or without ankle symptoms participated in the study. The US, clinical examination (CE), and patients’ visual analog scale for pain (pVAS) for ankles were assessed. Prevalence of tibiotalar joint synovitis and tenosynovitis were assessed by grayscale (GS) and power Doppler (PD) US using a semi-quantitative grading (0–3). The positive US and CE findings were defined as GS score ≥2 and/or PD score ≥1, and joint swelling and/or tenderness, respectively. Multivariate analysis with the generalized linear mixed model was performed by assigning ankle pVAS as a dependent variable. Results: Among a total of 120 ankles from 60 RA patients, positive ankle US findings were found in 21 (35.0%) patients. The concordance rate of CE and US was moderate (kappa 0.57). Of the 88 CE negative ankles, US detected positive findings in 9 (10.2%) joints. Multivariate analysis revealed that ankle US, clinical disease activity index, and foot Health Assessment Questionnaire, but not CE, was independently associated with ankle pVAS. Conclusion: US examination is useful to illustrate RA ankle involvement, especially for patients who complain ankle pain but lack CE findings.

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder

OBJECTIVES Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. METHODS We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. RESULTS Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. CONCLUSION Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship.

Successful treatment of extensive venous thrombosis with combination of immunosuppressants and a direct Xa inhibitor in Behçet’s disease

Abstract Behçet’s disease (BD) is a systemic and chronic inflammatory disease of unknown etiology. Vascular involvement can develop in both arterial and venous systems and can cause life-threatening complications. Here, we report a case of vasculo-BD with acute onset of thrombosis in the inferior vena cava (IVC). A 44-year-old woman diagnosed with BD based on recurrent oral aphtha, uveitis and multiple intestinal ulcers for four years, was admitted to our hospital with fever, blurred vision and the right lower abdominal pain. She was positive for HLA-A26 but negative for HLA-B51. Abdominal ultrasonography on admission revealed a thrombosis extending from the bilateral femoral vein to the IVC without intestinal abnormality. Diagnosis of vasculo-BD was made after ruling out other possible diseases. Treatment with rivaroxaban in addition to prednisolone and azathioprine resulted in subsiding of clinical manifestations with the gradual improvement of laboratory data and imaging findings. The present case report suggests a beneficial role of anticoagulation therapy including direct oral anticoagulants for thrombotic lesions of BD patients, in addition to generally recommended immunosuppressive therapy.