論文 Promoting awareness of terminology related to unmet medical needs in context of rheumatic diseases in Japan: a systematic review for evaluating unmet medical needs. Rheumatology international,43(11):2021-2030 2023(Nov.) Author:Susumu Yamazaki; Kazushi Izawa; Masakazu Matsushita; Akinori Moriichi; Dai Kishida; Hajime Yoshifuji; Ken Yamaji; Ryuta Nishikomori; Masaaki Mori; Takako Miyamae Abstract:To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes.
Immunopathological features of myopathy associated with small-to-medium-sized vessel vasculitis and differences from autoimmune myositis. Clinical and experimental rheumatology 2023(Sep. 14) Author:Shun Nomura; Yasuhiro Shimojima; Takanori Ichikawa; Daigo Miyazaki; Akinori Uruha; Dai Kishida; Yoshiki Sekijima Abstract:OBJECTIVES: Patients with systemic vasculitis may develop myalgia as an initial symptom. However, the immunopathology of vasculitic myopathy remains unclear. We investigated the immunopathological features of skeletal muscle in small-to-medium-sized vessel vasculitis. METHODS: We analysed muscle tissue biopsies from 15 patients with vasculitis, including antineutrophil cytoplasmic antibodyassociated vasculitis and polyarteritis nodosa, and 15 patients with autoimmune myositis (AIM), including polymyositis and immune-mediated necrotising myopathy, as comparison disease controls. Immunohistochemical staining for CD56/neural cell adhesion molecule (NCAM), major histocompatibility complex class I, C5b-9/membrane attack complex (MAC), and CD31 was performed. The vascularity score was defined as the total number of CD31-expressing blood vessels. The association between CD56/NCAM-expressing myofibers and clinical findings was evaluated in patients with vasculitis. RESULTS: Patients with vasculitis had a significantly lower frequency of CD56/NCAM-expressing myofibers than those with AIM and a positive correlation between the frequency of CD56/NCAM-expressing myofibers and serum aldolase levels. Patients with vasculitis had significantly fewer major histocompatibility complex class I-expressing myofibers and C5b-9/MAC deposits on the sarcolemma than those with AIM. C5b-9/MAC deposits in blood vessels were observed in >70% of patients with vasculitis. Patients with vasculitis had significantly higher vascularity scores in the endomysium than those with AIM. CONCLUSIONS: Patients with vasculitis demonstrated mild myofiber damage based on the lower involvement of CD56/NCAM-expressing myofibers compared to those with AIM. Complement component deposits on the vessel walls and hypervascularity in the endomysium areas may be immunopathological features of vasculitic myopathy.
The Association of Grit With Burnout Components (Professional Efficacy, Exhaustion, and Cynicism) Among Academic Rheumatologists: The TRUMP 2 -SLE Study. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases,29(6):268-274 2023(Sep. 01) Author:Yoshia Miyawaki; Ken-Ei Sada; Kenta Shidahara; Shoichi Nawachi; Yosuke Asano; Yu Katayama; Keigo Hayashi; Eri Katsuyama; Takayuki Katsuyama; Mariko Takano-Narazaki; Yoshinori Matsumoto; Nao Oguro; Nobuyuki Yajima; Yuichi Ishikawa; Natsuki Sakurai; Chiharu Hidekawa; Ryusuke Yoshimi; Takanori Ichikawa; Dai Kishida; Yasuhiro Shimojima; Jun Wada; Noriaki Kurita Abstract:OBJECTIVES: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists. METHODS: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children). RESULTS: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04). CONCLUSIONS: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit.
Neuromyelitis optica spectrum disorder with a familial Mediterranean fever gene E84K mutation. Journal of neurology,270(9):4529-4532 2023(Sep.) Author:Naoko Nakamura; Hidehiro Ishikawa; Hirofumi Matsuyama; Akihiro Shindo; Dai Kishida; Masayuki Maeda; Hidekazu Tomimoto
Immune-mediated necrotizing myopathy with concomitant development of Kikuchi-Fujimoto disease. International journal of rheumatic diseases 2023(Aug. 31) Author:Takanori Ichikawa; Ryo Furukawa; Yasuhiro Shimojima; Yumi Hoshino; Dai Kishida; Yoshiki Sekijima Abstract:Immune-mediated necrotizing myopathy (IMNM) is a distinct type of idiopathic inflammatory myositis, pathologically characterized by myofiber necrosis and degeneration in the absence of lymphocyte infiltration. Herein, we present a case of IMNM with concomitant development of Kikuchi-Fujimoto disease (KFD), characterized by histiocytic necrotizing lymphadenitis, in a 36-year-old woman who had a treatment history for rheumatoid arthritis (RA). Treatment with oral prednisolone and tacrolimus as immunosuppressants resulted in the remission of the skeletomuscular involvement and lymphadenopathy. To the best of our knowledge, this is the first report of IMNM and KFD developing concomitantly during the clinical course of RA.
Impact of online health information-seeking behavior on shared decision-making in patients with systemic lupus erythematosus: The TRUMP2-SLE project. Lupus,:9612033231200104-9612033231200104 2023(Aug. 31) Author:Takanori Ichikawa; Dai Kishida; Yasuhiro Shimojima; Nobuyuki Yajima; Nao Oguro; Ryusuke Yoshimi; Natsuki Sakurai; Chiharu Hidekawa; Ken-Ei Sada; Yoshia Miyawaki; Keigo Hayashi; Kenta Shidahara; Yuichi Ishikawa; Yoshiki Sekijima; Noriaki Kurita Abstract:OBJECTIVE: Providing appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behaviors affect shared decision-making (SDM) in patients with SLE. METHODS: This cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the internet per day, divided into four categories (none, <1 h, 1- < 2 h, ≥2 h). Participants categorized their preferred first source of health information as physicians, the internet, or other media. The outcome was the degree of SDM measured via the 9-item Shared Decision-Making Questionnaire (SDM-Q-9). A general linear model was applied. RESULTS: Compared to no internet use, longer internet use was associated with a higher SDM-Q-9 score: <1 h, 6.9 points (95% confidence interval [CI] 0.32 to 13.6) and ≥2 h, 8.75 points, (95% CI 0.61 to 16.9). The SDM-Q-9 did not differ between the individuals who chose physicians and those who chose the Internet as their preferred first source of health information (-2.1 points, 95% CI -6.7 to 2.6). Individuals who chose other media had significantly lower SDM-Q-9 scores than those who chose physicians (-7.6 points, 95% CI -13.2 to -1.9). CONCLUSIONS: The present study suggests that SDM between physicians and patients is positively associated with online information-seeking behavior, with no negative influence associated with accessing the Internet before clinical consultations. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a good physician-patient relationship for SDM.
Variables for differential diagnosis of familial Mediterranean fever: multiple correspondence analysis of a large Japanese cohort. Modern rheumatology 2023(Aug. 12) Author:Dai Kishida; Akinori Nakamura; Masahide Yazaki; Ayako Tsuchiya-Suzuki; Takanori Ichikawa; Yasuhiro Shimojima; Yoshiki Sekijima Abstract:OBJECTIVES: We investigated differential diagnoses that should be noted with familial Mediterranean fever (FMF) and useful variables for differentiation in a large Japanese cohort. METHODS: Patients aged ≥13 years who were clinically suspected of having FMF by Livneh criteria were studied 1 year after MEFV genetic testing. Patients ultimately diagnosed with other diseases were studied, and the association among each disease, patient characteristics, and clinical variables were analyzed using multiple correspondence analysis. RESULTS: In total, 504 patients were included in this study; 34 (6.7%) were diagnosed with a disease other than FMF. The most common diagnosis was Behçet's disease, followed by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, inflammatory bowel disease, myelodysplastic syndromes (MDS), and infectious diseases. Although none of the non-FMF patients had exon 10 variants, some responded to colchicine treatment. Multiple correspondence analysis suggested that atypical symptoms such as stomatitis were associated with Behçet's disease and PFAPA syndrome, whereas characteristic situations such as disease onset ≥40 years were associated with MDS and infectious diseases. CONCLUSION: Careful follow-ups and reanalysis of the diagnosis should be performed for patients with atypical findings and no exon 10 variants, even if their symptoms meet the clinical criteria for FMF.
Features of BAFF and APRIL receptors on circulating B cells in antineutrophil cytoplasmic antibody-associated vasculitis. Clinical and experimental immunology,213(1):125-137 2023(Jul. 05) Author:Yasuhiro Shimojima; Dai Kishida; Takanori Ichikawa; Ryota Takamatsu; Shun Nomura; Yoshiki Sekijima Abstract:To investigate the features of circulating B cells, their expressing receptors, serum levels of B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Blood samples from 24 patients with active AAV (a-AAV), 13 with inactive AAV (i-AAV), and 19 healthy controls (HC) were included in this study. The proportion of B cells and their expressing BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen were analyzed via flow cytometry. Serum levels of BAFF, APRIL, and interleukin (IL)-4, IL-6, IL-10, and IL-13 were also evaluated using an enzyme-linked immunosorbent assay. The proportion of plasmablasts (PB)/plasma cells (PC) and serum levels of BAFF, APRIL, IL-4, and IL-6 were significantly higher in a-AAV than in HC. Higher serum levels of BAFF, APRIL, and IL-4 were observed in i-AAV than in HC. Lower expression of BAFF-R on memory B cells and higher expression of TACI on CD19+ cells, immature B cells, and PB/PC were demonstrated in a-AAV and i-AAV than in HC. The population of memory B cells was positively associated with serum APRIL levels and BAFF-R expression in a-AAV. In conclusion, decreased expression of BAFF-R on memory B cells and increased expression of TACI on CD19+ cells, immature B cells, and PB/PC, as well as increased serum levels of BAFF and APRIL, were sustained even in the remission phase of AAV. Persistent aberrant signaling of BAFF/APRIL may contribute to disease relapse.
Grit personality of physicians and achievement of treatment goals in patients with system lupus erythematosus. Rheumatology (Oxford, England),62(6):2154-2159 2023(Jun. 01) Author:Ken-Ei Sada; Yoshia Miyawaki; Kenta Shidahara; Shoichi Nawachi; Yu Katayama; Yosuke Asano; Keigo Hayashi; Keiji Ohashi; Eri Katsuyama; Takayuki Katsuyama; Mariko Takano-Narazaki; Yoshinori Matsumoto; Nao Oguro; Yuichi Ishikawa; Natsuki Sakurai; Chiharu Hidekawa; Ryusuke Yoshimi; Dai Kishida; Takanori Ichikawa; Yasuhiro Shimojima; Noriaki Kurita; Nobuyuki Yajima Abstract:OBJECTIVES: Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. METHODS: This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. RESULTS: The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS. CONCLUSIONS: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.
Trust in the attending rheumatologist, health-related hope and medication adherence among Japanese systemic lupus erythematosus patients. Rheumatology (Oxford, England),62(6):2147-2153 2023(Jun. 01) Author:Noriaki Kurita; Nao Oguro; Yoshia Miyawaki; Chiharu Hidekawa; Natsuki Sakurai; Takanori Ichikawa; Yuichi Ishikawa; Keigo Hayashi; Kenta Shidahara; Dai Kishida; Ryusuke Yoshimi; Ken-Ei Sada; Yasuhiro Shimojima; Nobuyuki Yajima Abstract:OBJECTIVE: Poor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one's physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians. METHODS: This cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one's physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications. RESULTS: Altogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one's physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence. CONCLUSIONS: This study demonstrated that patients' health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE.
The impact of attending rheumatologist's Big Five personality traits on systemic lupus erythematosus patients' trust in their rheumatologist: the TRUMP2-SLE project medRxiv (プレプリント),:2023.05.22.23290279 2023(May 29) Author:Nao Oguro; Nobuyuki Yajima; Yuichi Ishikawa; Natsuki Sakurai; Chiharu Hidekawa; Takanori Ichikawa; Dai Kishida; Keigo Hayashi; Kenta Shidahara; Yoshia Miyawaki; Ryusuke Yoshimi; Ken-ei Sada; Yasuhiro Shimojima; Noriaki Kurita† (†last author) Abstract:ABSTRACT
Objectives
Differences in communication styles according to physicians’ personality traits have been identified, and such physician-related factors can be important in building patient-physician trust. This study examined the impact of rheumatologists’ Big Five personality traits on patients’ trust in their attending rheumatologists.
Methods
This cross-sectional study included Japanese patients with systemic lupus erythematosus (SLE) at five academic medical centres between June 2020 and August 2021. The exposure was the Big Five personality traits of their attending rheumatologists using the Japanese version of the Ten-Item Personality Inventory Scale (2-14 points each). The outcome was the patient’s trust in attending rheumatologist using the Japanese version of the 5-item Wake Forest Physician Trust Scale (0-100 points). A general linear model was fitted to adjust for rheumatologists’ and patients’ characteristics, while correcting for the clustering effect of the same attending rheumatologists.
Results
The study included 505 patients with a mean age of 46.8 years, and 88.1% were women. Forty-three attending rheumatologists (mean age, 39.6 years, 23.3% women) were identified. Higher extraversion and agreeableness were associated with higher trust in attending rheumatologists (per 1-point increase, 1.85 points [95% CI 0.52 –3.19] and 2.24 points [95% CI 0.86 –3.61], respectively), and higher conscientiousness was associated with lower trust (per 1-point increase, −1.07 points [95% CI −1.64 – −0.49]).
Conclusions
While higher extraversion and agreeableness of attending rheumatologists led to higher patient trust in their rheumatologist, overly high conscientiousness may lead to lower trust resulting from the physician’s demand of dutifulness from patients with SLE.
KEY MESSAGES
What is already known on this topic
Although physicians’ personality traits are known to influence their attitudes and performance, little is known about how they affect trust through rheumatology patient-physician interactions.
What this study adds
Some Big Five personality traits of an attending rheumatologist were associated with patients’ trust in their rheumatologist; extraversion and agreeableness were linked to higher trust and conscientiousness was associated with lower trust.
How this study may affect research, practice, or policy
Through reflection on their personality traits, attending rheumatologists are expected to become aware of their habits in patient-physician interactions and adapt their communication to strengthen the relationships with their patients.
Effect of Communicative and Critical Health Literacy on Trust in Physicians Among Patients With Systemic Lupus Erythematosus (SLE): The TRUMP2-SLE Project. The Journal of rheumatology,50(5):649-655 2023(May) Author:Nao Oguro; Nobuyuki Yajima; Yoshia Miyawaki; Ryusuke Yoshimi; Yasuhiro Shimojima; Ken-Ei Sada; Keigo Hayashi; Kenta Shidahara; Natsuki Sakurai; Chiharu Hidekawa; Dai Kishida; Takanori Ichikawa; Yuichi Ishikawa; Noriaki Kurita Abstract:OBJECTIVE: Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one's physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit. RESULTS: A total of 362 patients with SLE were included. Trust in one's physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference -6.88, 95% CI -11.72 to -2.04, respectively). Longer internet use was associated with both higher communicative and critical HL. CONCLUSION: The findings suggest that rheumatologists need to improve their communication to match each patient's HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.
＜Editors' Choice＞ Myelodysplastic syndrome with trisomy 8 presenting periodic fever and multiple MEFV gene variants outside exon 10: a case report. Nagoya journal of medical science,85(1):195-203 2023(Feb.) Author:Noriyuki Takahashi; Ryo Hanajiri; Masashi Suzuki; Chise Anan; Atsushi Inagaki; Dai Kishida; Shohei Ozawa; Sho Kohri; Nobuhide Kamiya; Motoki Sato; Juichi Sato Abstract:Myelodysplastic syndrome is associated with the development of autoinflammatory conditions, such as recurrent fever, polymyalgia, arthralgia, and erythema. Trisomy 8 is a common chromosomal abnormality in patients with myelodysplastic syndrome. Myelodysplastic syndrome with trisomy 8 involves autoinflammatory conditions, especially Behçet's disease-like symptoms with intestinal mucosal damage. MEFV variants, particularly those in exon 10, are pathogenic in familial Mediterranean fever, the most common autoinflammatory disease, presenting typical symptoms such as periodic fever and pleuritis/pericarditis/peritonitis. MEFV variants outside exon 10 are common in Japanese patients with familial Mediterranean fever and are associated with atypical symptoms, including myalgia and erythema. MEFV variants in myelodysplastic syndrome with trisomy 8 have rarely been investigated, although myelodysplastic syndrome with trisomy 8 might develop autoinflammatory conditions similar to those in familial Mediterranean fever. We encountered a 67-year-old man who had myelodysplastic syndrome with trisomy 8 and multiple MEFV variants outside exon 10. He presented with periodic fever, as well as chest/abdominal pain, myalgia, and erythema, although the symptoms did not fulfill the diagnostic criteria of familial Mediterranean fever. We discussed the possibility that these symptoms are modified by MEFV variants outside exon 10 in myelodysplastic syndrome with trisomy 8.
Testicular vasculitis in eosinophilic granulomatosis with polyangiitis: a case-based review. Clinical rheumatology,42(1):293-299 2023(Jan.) Author:Takanori Ichikawa; Yasuhiro Shimojima; Shun Nomura; Dai Kishida; Masashi Shiozaki; Jun Tanimura; Yoshiki Sekijima Abstract:Testicular vasculitis (TV) develops when an organ is involved in systemic vasculitis. A 47-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA) developed TV as the first clinical episode. The patient had bronchial asthma for 8 years and developed left testicular pain before developing arthralgia, abdominal involvement, and sensory polyneuropathy, which led to the diagnosis of EGPA. The induration of the affected testicle persisted even after initiating immunosuppressive therapy with corticosteroids and cyclophosphamide, raising concern for testicular neoplasm, while testicular pain and other symptoms resolved. The patient underwent inguinal orchiectomy, and a histology examination of the resected testicle revealed fibrinoid necrotizing vasculitis. Only three cases of biopsy-proven TV in patients with EGPA have been reported in our review of published English-language articles. Two of the three patients in the reviewed cases developed TV before being diagnosed with EGPA. Moreover, all patients underwent extirpation of the affected testicle, leading to a pathological diagnosis of TV. This report suggests that TV may develop and be the presenting condition in EGPA, although urogenital involvement is rare.
The impact of normal serum complement levels on the disease classification and clinical characteristics in systemic lupus erythematosus. Advances in rheumatology (London, England),62(1):49-49 2022(Dec. 27) Author:Ryota Takamatsu; Yasuhiro Shimojima; Dai Kishida; Takanori Ichikawa; Yoshiki Sekijima Abstract:BACKGROUND: Some patients have normal levels of complement during the diagnosis of systemic lupus erythematosus (SLE), although decreased serum levels of complement are a hallmark of the active phase of the disease. This study investigated the clinical characteristics, impact on the classification of SLE, and the prognosis of patients with SLE who had normal serum complement levels at initial diagnosis (N-com). METHODS: We evaluated 21 patients with N-com and 96 patients with hypocomplementemia at the initial diagnosis of SLE (H-com). The classification rates among the American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, European League Against Rheumatism (EULAR)/ACR 2019 criteria, and clinical and immunological involvements were compared between SLE patients with N-com and H-com. Relapse and organ damage based on the SLICC/ACR damage index were also evaluated. RESULTS: The classification rates of SLE were not significantly different in the ACR, SLICC, and EULAR/ACR criteria between the N-com and H-com groups. Patients with N-com had no significant differences in the classification rates among the three criteria, whereas patients with H-com had lower classification rates in the ACR criteria than in the SLICC criteria. A lower incidence of renal manifestation, less positivity for anti-dsDNA antibody, and a higher incidence of fever were observed in patients with N-com than in those with H-com. The occurrence of relapse and organ damage was not significantly different between patients with N-com and H-com. CONCLUSION: Patients with N-com were less involved in renal manifestation and anti-dsDNA antibody positivity but had a higher incidence of fever than those with H-com, while having no disadvantage in SLE classification processes. Serum complement levels at the initial diagnosis of SLE may not predict prognosis.
A randomised, double-blind, placebo-controlled phase III trial on the efficacy and safety of tocilizumab in patients with familial Mediterranean fever. Clinical and experimental rheumatology,40(8):1535-1542 2022(Sep.) Author:Tomohiro Koga; Shuntaro Sato; Naoko Hagimori; Hiroshi Yamamoto; Masataka Ishimura; Takahiro Yasumi; Yohei Kirino; Kei Ikeda; Akihiro Yachie; Kiyoshi Migita; Dai Kishida; Tatsuya Atsumi; Atsushi Kawakami Abstract:OBJECTIVES: To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in a subset of Japanese patients with familial Mediterranean fever (FMF). METHODS: We performed a double-blind, randomised, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF) (UMIN000028010). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study (UMIN000032557). RESULTS: We randomly assigned 23 patients to either TCZ (n=1) or placebo (n=12). The TCZ-placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189-2.531; p=0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240-0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. CONCLUSIONS: Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.
Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS). Arthritis research & therapy,24(1):204-204 2022(Aug. 23) Author:Yasuhiro Shimojima; Dai Kishida; Takanori Ichikawa; Takashi Kida; Nobuyuki Yajima; Satoshi Omura; Daiki Nakagomi; Yoshiyuki Abe; Masatoshi Kadoya; Naoho Takizawa; Atsushi Nomura; Yuji Kukida; Naoya Kondo; Yasuhiko Yamano; Takuya Yanagida; Koji Endo; Shintaro Hirata; Kiyoshi Matsui; Tohru Takeuchi; Kunihiro Ichinose; Masaru Kato; Ryo Yanai; Yusuke Matsuo; Ryo Nishioka; Ryota Okazaki; Tomoaki Takata; Takafumi Ito; Mayuko Moriyama; Ayuko Takatani; Yoshia Miyawaki; Toshiko Ito-Ihara; Takashi Kawaguchi; Yutaka Kawahito; Yoshiki Sekijima Abstract:BACKGROUND: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. METHODS: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. RESULTS: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001). CONCLUSION: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.
Clinical characteristics and treatment of elderly onset adult-onset Still's disease. Scientific reports,12(1):6787-6787 2022(Apr. 26) Author:Dai Kishida; Takanori Ichikawa; Ryota Takamatsu; Shun Nomura; Masayuki Matsuda; Wataru Ishii; Tatsuo Nagai; Sadahiro Suzuki; Ken-Ichi Ueno; Naoki Tachibana; Yasuhiro Shimojima; Yoshiki Sekijima Abstract:Adult-onset Still's disease (AOSD)-a systemic inflammatory disease-often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008-December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.
Hypertrophic pachymeningitis in polyarteritis nodosa: a case-based review. Clinical rheumatology,41(2):567-572 2022(Feb.) Author:Shun Nomura; Yasuhiro Shimojima; Yasufumi Kondo; Dai Kishida; Yoshiki Sekijima Abstract:Hypertrophic pachymeningitis (HP) is a rare neurological disorder with focal or diffuse thickening of the dura mater, which usually causes headache, cranial neuropathies, seizures, and motor or sensory impairments. The development of HP is attributed to an immune-mediated mechanism, and some autoimmune diseases have been implicated in the development of HP. Herein, we describe the case of a 73-year-old woman with persistent headache ascribable to HP, which developed approximately 3 years after a diagnosis of polyarteritis nodosa (PAN). She was treated with high-dose corticosteroid and cyclophosphamide that resulted in immediate disappearance of headache and improved radiological findings of thickened dura mater. In addition, she was subsequently administered methotrexate, ultimately resulting in maintenance of remission and regular reduction of prednisolone. In our review of published English articles, only two cases of HP in patients with PAN have been reported to date, suggesting that HP is a rare complication in PAN. However, it should be recognized that HP may develop as a neurological involvement related to PAN.
The implication of interferon-gamma-producing immunocompetent cells for evaluating disease activity and severity in adult-onset Still's disease INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES,24(9):1176-1185 2021(Sep.) Author:Ichikawa, Takanori; Shimojima, Yasuhiro; Kishida, Dai; Ueno, Ken-ichi; Sekijima, Yoshiki Abstract:OBJECTIVE: To investigate the relationship between interferon-γ (IFN-γ), IFN-γ-producing immunocompetent cells, their related cytokines, and the clinical features in adult-onset Still's disease (AOSD). METHODS: Twenty-five patients with AOSD before initiating treatment (acute AOSD), 9 patients after remission (remission AOSD), and 12 healthy controls (HC) were included. Circulating IFN-γ-producing CD4+ and CD8+ cells, natural killer (NK) cells, and IFN-γ production in NK cells were evaluated by flow cytometry. Serum levels of IFN-γ, interleukin (IL)-6, IL-12, IL-15, and IL-18 were also measured. The obtained results were statistically analyzed with clinical findings. RESULTS: Serum levels of IFN-γ, IL-6, IL-12, IL-18, intracellular expression of IFN-γ in CD4+, CD8+, and NK cells were significantly higher in acute AOSD than in HC. The proportion of NK cells was significantly lower in acute AOSD than in HC. Serum levels of IFN-γ and IFN-γ expression in CD4+ cells were significantly correlated with serum ferritin levels. The proportion of NK cells had a significant inverse correlation with serum IFN-γ levels. A lower proportion of NK cells was significantly noted in patients refractory to initial immunosuppressive treatment. In remission AOSD, serum levels of IL-6, IL-12, and IL-18 were significantly higher than in HC. CONCLUSION: Increased serum levels of IFN-γ, increased expression of IFN-γ in CD4+ cells, and decreased NK cell proportion correlate with disease activity in AOSD. Moreover, a lower proportion of NK cells may be useful for predicting a refractory clinical course. Meanwhile, increased serum levels of IL-6, IL-12, and IL-18 may persist after clinical remission.
Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review RHEUMATOLOGY INTERNATIONAL,41(5):1009-1017 2021(May) Author:Ichikawa, Takanori; Shimojima, Yasuhiro; Kishida, Dai; Kaneko, Tomoki; Sekijima, Yoshiki Abstract:Primary central nervous system lymphoma (PCNSL) sometimes occurs in immune-compromised hosts or patients with autoimmune diseases. Some cohort studies have previously reported an increased risk of non-Hodgkin's lymphoma in systemic lupus erythematosus (SLE), while some cases of PCNSL in patients with SLE were reported. We present the case of PCNSL which developed in a patient with the active phase of neuropsychiatric SLE (NPSLE). Furthermore, we reviewed published English articles to confirm the characteristics of PCNSL related to SLE. To our knowledge, this is the first report of PCNSL occurring in NPSLE. Histology demonstrated B-cell lymphoma with a positive Epstein-Barr virus-encoded RNA. This patient recovered following surgical resection of the lymphoma, whole brain radiation therapy, intravenous infusion of rituximab (RTX), and administration of belimumab after RTX. Given the series of reviews, our report suggests that the persistence of damage in the central nervous system (CNS) and long-term exposure to immunosuppressants may impact oncogenic immune responses within the CNS, leading to PCNSL development.
Circulating regulatory T cells in adult-onset Still's disease: Focusing on their plasticity and stability CLINICAL AND EXPERIMENTAL IMMUNOLOGY,206(2):184-195 2021 Author:Shimojima, Yasuhiro; Ichikawa, Takanori; Kishida, Dai; Takamatsu, Ryota; Sekijima, Yoshiki Abstract:We investigated the characteristics of regulatory T cells in adult-onset Still's disease (AOSD) with a focus on their plasticity, stability and relationship to disease severity. The proportion of circulating CD4+ CD25+ forkhead box protein 3 (FoxP3+ ) cells (Tregs ) and intracellular expression of effector cytokines, including interferon (IFN)-γ, interleukin (IL)-17 and IL-4, was analysed in 27 untreated patients with AOSD (acute AOSD), 11 of the 27 patients after remission and 16 healthy controls (HC) using flow cytometry. The suppressive ability of Tregs was also evaluated. Regression analyses of the results were performed. The proportion of Tregs was significantly lower in patients with acute AOSD than in the HC. The expression levels of IFN-γ, IL-17 and IL-4 in Tregs were significantly increased in patients with acute AOSD. IFN-γ and IL-4 expression levels were inversely correlated with the proportion of Tregs and positively correlated with serum ferritin levels. Decreased expression of FoxP3 in CD4+ CD25+ cells, which was correlated with increased expression of IL-17, and impaired suppressive function were observed in Tregs in acute AOSD. However, these aberrant findings in Tregs , including the reduced circulating proportion and functional ability and altered intracellular expression levels of cytokines and FoxP3, were significantly improved after remission. In acute AOSD, Tregs show plastic changes, including effector cytokine production and reductions in their proportion and functional activity. IFN-γ and IL-4 expression levels in Tregs may be associated with disease severity. Also, down-regulation of FoxP3 may be related to IL-17 expression in Tregs . Importantly, the stability of Tregs can be restored in remission.
Painless Panniculitis upon the Treatment of Clinically Amyopathic Dermatomyositis with Anti-MDA5 Antibody INTERNAL MEDICINE,60(16):2697-2700 2021 Author:Kishida, Dai; Ushiyama, Satoru; Shimojima, Yasuhiro; Ueno, Ken-ichi; Kurashina, Jun-ichi; Shirai, Takushi; Sekijima, Yoshiki Abstract:Panniculitis, a rare cutaneous manifestation in patients with dermatomyositis (DM), usually presents as a painful erythematous lesion. We herein report a 32-year-old woman with panniculitis that appeared as an indurated plaque without pain or redness after a 4-month episode of clinically amyopathic DM during treatment with prednisolone and tacrolimus. She experienced no pain; however, the firmness and extent gradually worsened. Based on our findings, including the histopathological results, DM panniculitis was diagnosed. Azathioprine was additionally administered, leading to remission. DM panniculitis can develop as a painless induration during immunosuppressive treatment, and azathioprine may be a useful treatment.
Oxidative Stress Promotes Instability of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Frontiers in immunology,12:789740-789740 2021 Author:Yasuhiro Shimojima; Dai Kishida; Takanori Ichikawa; Ryota Takamatsu; Shun Nomura; Yoshiki Sekijima Abstract:We investigated the characteristics of regulatory T cells (Tregs), focusing on the relationship between their stability and reactive oxygen species (ROS), in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Intracellular expressions of effector cytokines, forkhead box protein 3 (FoxP3), ROS, phosphorylated mammalian target of rapamycin (mTOR), and sirtuin 1 (SIRT1) in Tregs from peripheral blood mononuclear cells (PBMCs) of patients with AAV and healthy controls (HC) were analyzed. The alterations in and functional ability of Tregs were compared before and after resveratrol (RVL) treatment of PBMCs in patients with AAV. Significantly higher expressions of interferon (IFN)-γ, interleukin (IL)-17, IL-4, ROS, and phosphorylated mTOR (pho-mTOR) and lower expression of SIRT1 in CD4+CD25+FoxP3+ cells were found in patients with AAV than in the HC. FoxP3 expression in CD4+CD25+ cells and suppressive function of Tregs were significantly lower in patients with AAV than in the HC. Tregs after RVL treatment demonstrated significant decreases in IFN-γ, ROS, and pho-mTOR levels and increases in FoxP3, SIRT1 levels, and functional activity. Conversely, the direct activation of SIRT1 by SRT1720 resulted in decreased FoxP3 expression, with no reduction in ROS levels. The pho-mTOR levels were significantly higher in Tregs after activation by SRT1720 than in those after RVL treatment. This study suggested that imbalanced changes in Tregs could be attributed to mTOR activation, in which ROS overproduction was predominantly implicated. Therefore, ROS is a key mediator for promoting Tregs instability in AAV.
Moyamoya syndrome related to systemic lupus erythematosus developing during pregnancy: a case-based review CLINICAL RHEUMATOLOGY,39(12):3861-3867 2020(Dec.) Author:Tanaka, Rika; Shimojima, Yasuhiro; Ueno, Ken-ichi; Takasone, Ken; Ichikawa, Takanori; Kishida, Dai; Sekijima, Yoshiki Abstract:Moyamoya syndrome (MMS) is a chronic cerebrovascular disorder characterized by occlusion or stenosis of the internal carotid arteries with the formation of abnormal collateral vascular networks. Moreover, the development of MMS, which is a distinct category from "moyamoya disease," is attributed to the underlying disease, while some cases of MMS related to systemic lupus erythematosus (SLE) have been previously reported. Herein, we present the case of a 29-year-old Japanese woman with SLE in whom intracranial hemorrhage ascribable to MMS developed during pregnancy. Craniotomy was performed to remove hematoma, and prednisolone, tacrolimus, and hydroxychloroquine were consecutively administered. She ultimately achieved remission and childbearing without the relapse of cerebrovascular event. To our knowledge, this is the first report of MMS associated with SLE in pregnancy. Through reviewing published English articles and our case, it was suggested that the pathogenesis of SLE is implicated in the development of moyamoya vasculopathy leading to cerebrovascular events. Moreover, pregnancy may affect the bleeding from the fragile collateral vessel wall.
Normal Pressure Hydrocephalus in Systemic Lupus Erythematosus A Severe Case of Recurrent Cerebral Infarctions After Ventriculoperitoneal Shunt JCR-JOURNAL OF CLINICAL RHEUMATOLOGY,26(7):E246-E248 2020(Oct.) Author:Sakaguchi, Noriko; Shimojima, Yasuhiro; Ushiyama, Satoru; Ichikawa, Takanori; Ikeda, Junji; Ueno, Ken-ichi; Kishida, Dai; Sekijima, Yoshiki Abstract:J Clin Rheumatol.
Clinical characteristics of patients with myalgia as the initial manifestation of small and medium-sized vasculitis: a retrospective study RHEUMATOLOGY INTERNATIONAL,40(10):1667-1674 2020(Oct.) Author:Ushiyama, Satoru; Shimojima, Yasuhiro; Ueno, Ken-ichi; Kishida, Dai; Miyazaki, Daigo; Sekijima, Yoshiki Abstract:Myalgia is a common symptom in small and medium-sized systemic vasculitis, sometimes occurring as the initial or only clinical manifestation of vasculitis. This study investigated the clinical features and diagnostic process in patients presenting with myalgia as the initial symptom of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) or polyarteritis nodosa (PAN). We included 93 patients diagnosed with AAV or PAN by retrospectively reviewing their clinical records at the initial diagnosis. Clinical findings and diagnostic methods were assessed in patients with myalgia. Of 93 patients, myalgia was observed in 21 (22.6%) patients, with diagnostic classifications of microscopic polyangiitis (MPA) in 12 (52.4%), granulomatosis with polyangiitis in 2 (9.5%), eosinophilic granulomatosis with polyangiitis in 2 (9.5%), and PAN in 5 (23.8%). Myalgia was present in the lower extremities of all patients; more than 80% of patients had pain in the calf muscle. In 10 patients with myalgia, including 7 with MPA and 3 with PAN, muscle biopsy was performed because myalgia was the main symptom and no other impaired organs were suitable for biopsy. Consequently, 8 patients had necrotizing vasculitis, leading to MPA or PAN diagnosis, although muscle pathology was not evaluated in patients without myalgia. Muscle magnetic resonance imaging was useful in determining the biopsy site. Myalgia, especially in the lower limbs, may be an initial clinical sign of vasculitis, particularly in MPA or PAN patients. Moreover, the histological evidence of muscular vasculitis can contribute to a definite diagnosis especially in patients presenting with myalgia as an early symptom of AAV or PAN.
Cerebrospinal fluid levels of BAFF and APRIL as direct indicators of disease activity in anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis CLINICAL RHEUMATOLOGY,39(10):3145-3148 2020(Oct.) Author:Shimojima, Yasuhiro; Kishida, Dai; Nomura, Shun; Sekijima, Yoshiki
Macrophage activation syndrome in adult dermatomyositis: a case-based review RHEUMATOLOGY INTERNATIONAL,40(7):1151-1162 2020(Jul.) Author:Kishida, Dai; Sakaguchi, Noriko; Ueno, Ken-ichi; Ushiyama, Satoru; Ichikawa, Takanori; Yoshinaga, Tsuneaki; Shimojima, Yasuhiro; Sekijima, Yoshiki Abstract:Macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases, characterized by fever, hepatosplenomegaly, and pancytopenia. Dermatomyositis (DM) is one of the causes of MAS; however, its clinical characteristics in DM patients remain unclear. This study aimed to present a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM complicated by MAS in a 29-year-old woman and to review the literatures including similar cases. Even though symptoms and cytopenia of our patient were refractory to combination therapy, including glucocorticoids, immunosuppressants, and plasma exchange, the administration of rituximab (RTX) resulted in rapid clinical improvement and glucocorticoid reduction. The literature review revealed 18 adult patients with DM associated MAS. Most patients developed MAS within 3 months from DM onset. A monotherapy of glucocorticoid was insufficient to control the disease, and the mortality of MAS in DM was higher than that of MAS in other rheumatic diseases, despite being treated by various means. RTX may be an effective treatment for patients with DM complicated by MAS who are refractory to conventional therapy. Anti-MDA5 antibody could influence the development of MAS; however, further investigations are needed to elucidate the association between myositis-specific antibody and MAS.
Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis. Clin Rheumatol.,39(6):1803-1811 2020 Author:Ikeda J, Shimojima Y, Usami Y, Ueno KI, Kishida D, Sekijima Y. Abstract:Clin Rheumatol.
Familial Mediterranean Fever Is Important in the Differential Diagnosis of Recurrent Aseptic Meningitis in Japan. Intern Med.,59(1):125-128 2020 Author:Hosoi T, Ishii K, Tozaka N, Kishida D, Sekijima Y, Tamaoka A. Abstract:Intern Med.
Triggering factors for febrile attacks in Japanese patients with familial Mediterranean fever CLINICAL AND EXPERIMENTAL RHEUMATOLOGY,38(5):S76-S79 2020 Author:Kishida, D.; Nakamura, A.; Yazaki, M.; Oka, K.; Tsuchiya-Suzuki, A.; Ichikawa, T.; Shimojima, Y.; Sekijima, Y. Abstract:OBJECTIVES: We occasionally encounter patients with familial Mediterranean fever (FMF) whose attacks are triggered by specific factors; however, information regarding these factors is limited. Our purpose was to identify the factors that trigger febrile attacks in Japanese patients with FMF. METHODS: Our retrospective study included 372 patients (229 women, 143 men) with FMF, who were diagnosed between April 2007 and June 2018. We retrospectively investigated clinical features, genetic variants, and the factors that the patients perceived to have triggered their attacks. Patients completed a questionnaire that included the following triggering factors, anxiety, psychological stress, tiredness, excitement, environmental change, and menstruation. RESULTS: Of 372 patients, 180 (49.4%) reported some triggering factors. Psychological stress and tiredness were commonly reported factors regardless of sex; however, menstruation (39.7%, n=91) was the most commonly reported triggering factor in female patients with FMF. Menstrual-related patients had a younger age of onset and diagnosis, a higher frequency of peritonitis, and a higher rate of patients with endometriosis compared with the non-menstrual-related patients. CONCLUSIONS: Gaining an understanding of these triggering factors could help to reduce attacks and educate the patients. Clinicians may need to consider FMF for patients who have fever and serositis that occurs with every menstrual period.
Development of Arthritis as the Initial Involvement in Adult-Onset Cutaneous Polyarteritis Nodosa: Two Cases and Literature Review. Case reports in rheumatology,2020:8897358-8897358 2020 Author:Ryota Takamatsu; Yasuhiro Shimojima; Dai Kishida; Yasufumi Kondo; Ken-Ichi Ueno; Yoshiki Sekijima Abstract:Articular symptoms are commonly present in polyarteritis nodosa (PAN). Meanwhile, they may occur as the initial and main involvement of PAN, raising a concern of a delay in a definitive diagnosis of disease unless the histological evidence is obtained. Herein, we report two cases of cutaneous PAN (c-PAN) in which arthritis developed as the initial clinical episode of disease and we argued, through a review of the literature, the clinical feature of patients presenting with arthritis as the initial symptom of PAN. To our knowledge, only six cases have been reported in the English literature, and all six patients were categorized as having c-PAN. Of those patients, four had arthritis with indicating destructive changes. A median of 9 years elapsed prior to the induction of immunosuppressive treatment despite the fact that the other reviewed cases as well as our two patients, who received treatment significantly earlier, showed no evidence of joint destruction. Taken together, this report suggests that the early induction of therapy based on the definitive diagnosis of PAN may be required for preventing joint disruption even though it is not easy to make a diagnosis of PAN unless biopsied tissue can provide the evidence of necrotizing vasculitis.
Vertebral artery dissection associated with familial Mediterranean fever and Behcet's disease ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY,6(5):974-978-978 2019(May) Author:Ishikawa, Hidehiro; Shindo, Akihiro; Ii, Yuichiro; Sakano, Shoko; Asahi, Masaru; Matsuura, Keita; Kishida, Dai; Umino, Maki; Maeda, Masayuki; Tomimoto, Hidekazu Abstract:Vertebral artery dissection and recurrent meningitis are rare complications in Behçet's disease. Behçet's disease may be associated with familial Mediterranean fever. Here, we describe a 52-year-old woman with severe headache who exhibited recurrent meningitis and vertebral artery dissection. Cerebrospinal fluid showed high levels of interleukin-6. Magnetic resonance imaging revealed right vertebral artery dissection. The patient had three heterozygous mutations in the familial Mediterranean fever gene (MEFV) gene. She fulfilled criteria for diagnosis of Behçet's disease and familial Mediterranean fever. In conclusion, mutations of the MEFV gene may cause neuro-inflammatory disorders and cerebrovascular disorders by reducing anti-inflammatory activity of pyrin.
A Patient with Limbic Encephalitis Associated with Anti-leucine-rich Glioma-inactivated 1 (LGI1) Antibody Presenting with Slowly Progressive Cognitive Impairment and Fluctuating Striatal Lesions INTERNAL MEDICINE,58(2):287-291 2019 Author:Sato, Mitsuto; Kishida, Dai; Miyazaki, Daigo; Sekijima, Yoshiki Abstract:INTERNAL MEDICINE
Late-onset familial Mediterranean fever in Japan MODERN RHEUMATOLOGY,30(3):--567 2019 Author:Kishida, Dai; Yazaki, Masahide; Nakamura, Akinori; Tsuchiya-Suzuki, Ayako; Shimojima, Yasuhiro; Sekijima, Yoshiki Abstract:MODERN RHEUMATOLOGY
Acquired Amegakaryocytic Thrombocytopenia in Adult-onset Still's Disease: Successful Combination Therapy with Tocilizumab and Cyclosporine. Intern Med.,58(23):3473-3478 2019 Author:Ichikawa T, Shimojima Y, Otuki T, Ueno KI, Kishida D, Sekijima Y. Abstract:Intern Med.
Characteristics of Circulating Natural Killer Cells and Their Interferon-γ Production in Active Adult-onset Still Disease. J Rheumatol.,46(10):1268-1276 2019 Author:Shimojima Y, Kishida D, Ueno KI, Ushiyama S, Ichikawa T, Sekijima Y. Abstract:J Rheumatol.
Diagnostic approach for patients with unidentified fever according to the classical criteria of fever of unknown origin in the field of autoimmune disorders. Immunol Med.,42(4):176-184 2019 Author:Watanabe R, Sakuraba H, Hiraga H, Kishida D, Ota S, Hasui K, Kikuchi H, Akemoto Y, Tanaka N, Maeda T, Murai Y, Yoshida S, Tatsuta T, Sawaya M, Chinda D, Mikami T, Ishiguro Y, Fukuda S. Abstract:Immunol Med.
Long-term maintenance of the mucosal healing induced by azacitidine therapy in a patient with intestinal Behçet's-like disease accompanied with myelodysplastic syndrome involving trisomy 8. Immunol Med.,42(3):135-141 2019 Author:Tanaka N, Sakuraba H, Hiraga H, Mayama K, Kikuchi H, Kishida D, Akemoto Y, Hasui K, Ota S, Watanabe R, Murai Y, Maeda T, Kamata K, Tatsuta T, Sawaya M, Chinda D, Mikami T, Yamagata K, Ishiguro Y, Tana Abstract:Immunol Med.
Familial Mediterranean fever type 2 with heterozygous mutations of E148Q and M694I in a Japanese patient with progressive systemic AA amyloidosis Modern Rheumatology Case Reports,3(1):79-85 2019 Author:Mayumi Ito, Hironobu Nobata, Hirokazu Imai, Masabumi Yoshino, Shogo Banno, Yasuhiko Ito, Hideaki Ito & Dai Kishida Abstract:Modern Rheumatology Case Reports
MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease. Ann Clin Transl Neurol.,6(12):2595-2600 2019 Author:Ishikawa H; Shindo A; Ii Y; Kishida D; Niwa A; Nishiguchi Y; Matsuura K; Kato N; Mizutani A; Tachibana K; Hirata Y; Matsuyama H; Ogawa-Ito A; Taniguchi A; Tomimoto H Abstract:Mediterranean fever (MEFV) gene mutations are associated with familial Mediterranean fever (FMF). Recent studies have suggested that MEFV gene mutations may act as disease modifiers in neuro-Behçet's (NBD) disease and neuro-Sweet disease (NSD). We investigated MEFV genes and clinical features in 17 patients with NBD or NSD. MEFV gene mutations were frequently observed (70.6%). Headaches and exertional leg pain were associated with MEFV gene mutations (P < 0.05). Moreover, higher frequency of white matter lesions without sites predilection (P < 0.05) and non-parenchymal lesions (P < 0.05) were also observed. MEFV gene mutations may be associated with particular findings and lesion sites.
Atypical type of familial Mediterranean fever: An underdiagnosed cause of chronic aseptic meningitis. Neurology and clinical neuroscience,6(6):191-193 2018(Nov.) Author:Masayuki Sugie; Takahiro Ouchi; Dai Kishida; Shunji Yasaki Abstract:We report an atypical case of familial Mediterranean fever (FMF) concomitant with chronic aseptic meningitis. The patient experienced fever, abdominal and back pain because of serositis, and headache because of aseptic meningitis for 4 weeks. Blood examinations revealed increased white blood cells and serum amyloid A level. Medications, including steroids, did not improve his symptoms. However, the patient experienced immediate relief after the administration of colchicine. We diagnosed him as having atypical FMF based on the symptoms, especially positive response to colchicine, and heterozygous mutations on exon2 and 5 (E148Q/S503C) in MEFV gene. Unlike typical FMF, a cause of recurrent aseptic meningitis, atypical FMF might be an underdiagnosed cause of chronic aseptic meningitis.
Mediterranean fever gene mutations in patients with possible neuro-Sweet disease: a case series. Journal of neurology, neurosurgery, and psychiatry,89(10):1119-1121 2018(Oct.) Author:Hidehiro Ishikawa; Akihiro Shindo; Yuichiro Ii; Atsushi Niwa; Keita Matsuura; Dai Kishida; Hidekazu Tomimoto
T-wave alternans in a case with systemic lupus erythematosus-related myocarditis. Journal of cardiology cases,18(4):119-122 2018(Oct.) Author:Mikiko Harada; Hirohiko Motoki; Yuichiro Kashima; Chie Nakamura; Naoto Hashizume; Dai Kishida; Hiroshi Imamura; Koichiro Kuwahara Abstract:A 42-year-old woman presented with fever, dyspnea, lower-leg edema, significant pulmonary congestion, pleural effusion, and severely reduced left ventricular contractions. She was resistant to treatment for heart failure, including catecholamines, furosemide, phosphodiesterase III inhibitors, and human atrial natriuretic peptide, and antibiotics failed to reduce her inflammation. She had renal dysfunction and hypocomplementemia and was positive for anti-nuclear and anti-ds-DNA antibodies. The patient was diagnosed with myocarditis and pleurisy associated with systemic lupus erythematosus (SLE). Prednisolone administration improved her general condition, reducing inflammation and improving left ventricular function. On day 1, an electrocardiography (ECG) revealed a T-wave inversion similar to a T-U complex configuration in leads II, aVF, and V3-6. By day 8, however, ECG showed prolonged corrected QT (QTc) and T-wave alternans (alternating beat-to-beat T-wave patterns) in lead V3-6. Careful ECG monitoring should be used to identify potentially fatal ventricular arrhythmias during the recovery phase of SLE-related myocarditis. .
Atypical familial Mediterranean fever developed in a long-term hemodialysis patient Hemodialysis International,22(2):E19-E22 2018(Apr. 01) Author:Toshiyuki Makino; Yoshitatsu Ohara; Namiko Kobayashi; Yohei Kono; Ayumu Nomizu; Mariko Ichijo; Yutaro Mori; Noriaki Matsui; Dai Kishida; Takayuki Toda Abstract:Familial Mediterranean Fever (FMF) is usually an autosomal recessive autoinflammatory disease characterized by recurrent attacks of fever and serositis. FMF develops before the age of 20 years in 90% of patients. It has intervals of 1 week to several years between attacks, which leads to renal dysfunction—amyloidosis. We report a case of atypical FMF that developed in a long-term hemodialysis patient. A 65-year-old Japanese female undergoing hemodialysis for 32 years was referred to our hospital with a fever of unknown origin (FUO) following cervical laminoplasty. The fever occurred as recurrent attacks accompanied by oligoarthralgia of the left hip and knee. We suspected FMF because of recurrent self-limited febrile attacks, although the patient showed atypical clinical features such as late-onset and highly frequent attacks. After receiving treatment, she achieved a complete response to colchicine. Therefore, a diagnosis of FMF was made based on the Tel-Hashomer criteria, which was confirmed by genetic testing. The case suggests that FMF may be of note in long-term hemodialysis patients developing FUO.
One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study Rheumatology International,38(1):105-110 2018(Jan. 01) Author:Dai Kishida; Masahide Yazaki; Akinori Nakamura; Fumio Nomura; Takeshi Kondo; Takanori Uehara; Masatomi Ikusaka; Akira Ohya; Norihiko Watanabe; Ryuta Endo; Satoshi Kawaai; Yasuhiro Shimojima; Yoshiki Sekijima Abstract:Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent episodes of fever and polyserositis. To date, over 317 MEFV mutations have been reported, only nine of which account for almost all Japanese patients with FMF. Therefore, the prevalence of rare MEFV variants and their clinical characteristics remains unclear. This study identified MEFV mutations previously unreported in the Japanese population and described their clinical features. We performed MEFV genetic testing in 488 Japanese patients with clinically suspected FMF. Of these patients, we retrospectively analyzed three patients with novel or very uncommon MEFV mutations. In all patients, the clinical diagnosis of FMF was made according to Tel-Hashomer’s criteria. One novel missense mutation (N679H) and two rare mutations (T681I and R410H) were identified in the MEFV gene. These mutations were found in compound heterozygous or complex genotypes with other known mutations in exons 1 or 2. According to clinical images, all three patients exhibited typical FMF symptoms. A number of patients with FMF caused by novel or uncommon MEFV variants might exist in the Japanese population
therefore, careful genetic testing is required for accurate diagnosis of this curable genetic disorder.
Propylthiouracil-induced Otitis Media with Antineutrophil Cytoplasmic Antibody-associated Vasculitis INTERNAL MEDICINE,57(20):3029-3033 2018 Author:Tanaka, Rika; Shimojima, Yasuhiro; Moteki, Hideaki; Kishida, Dai; Ueno, Ken-ichi; Sekijima, Yoshiki Abstract:INTERNAL MEDICINE
T-cell receptor-mediated characteristic signaling pathway of peripheral blood T cells in dermatomyositis and polymyositis Autoimmunity,50(8):481-490 2017(Nov. 17) Author:Yasuhiro Shimojima; Masayuki Matsuda; Wataru Ishii; Dai Kishida; Yoshiki Sekijima Abstract:The characteristics of T cell expression in peripheral blood have been previously described in dermatomyositis (DM) and polymyositis (PM)
however, their intracellular signaling profiles remain unknown. The purpose of this study was to investigate the T-cell receptor (TCR)-mediated intracellular signaling in peripheral blood T cells in DM and PM. Peripheral blood T cells from 86 patients with DM (n = 57) and PM (n = 29) were used for experimental investigations. T-cell subtypes and TCR-induced phosphorylated zeta-chain-associated protein kinase 70 (pZAP70) were analyzed by flow cytometry. Signal transducer and activator of transcription (STAT) and some inhibitory factors in T cells with TCR stimulation were also investigated by quantitative real-time polymerase chain reaction. T cell counts were significantly lower in DM than in PM. In addition, STAT, forkhead box transcription factor (FoxP3), and pZAP70 expression in CD4+ T cells was suppressed in DM, whereas STAT and pZAP70 expression in CD8+ T cells was induced in PM. Especially in DM, a positive correlation between CD4+ T cell counts and STAT expression was detected. In addition, low CD4+ T cell counts as well as reduced STAT expression were prominent in patients with interstitial lung disease. STAT and pZAP70 expression significantly improved after clinical remission in both DM and PM, although expression of FoxP3 remained suppressed. Besides, upregulation of suppressor of cytokine signaling-3 (SOCS3) and downregulation of interleukin 6 signal transducer (IL6ST) in CD4+ T cells were observed in both DM and PM
however, no significant improvements were detected after clinical remission. The results of the present study suggested that TCR-mediated signaling may be a key pathway to determine the different characteristics of peripheral blood T cells between DM and PM. In addition, upregulation of SOCS3 and downregulation of IL6ST and FoxP3 in CD4+ T cells may cause an imbalance in intracellular signaling, especially in DM, suggesting that further studies are required to identify how the impaired signaling contributes to the development of the disease.
Increased BAFF and APRIL levels in the cerebrospinal fluid of patients with anti-neutrophilcytoplasmic antibody-related hypertrophic pachymeningitis CYTOKINE,99:305-309 2017(Nov.) Author:Yasuhiro Shimojima; Dai Kishida; Yoshiki Sekijima Abstract:Hypertrophic pachymeningitis (HP) is an inflammatory disorder involving intracranial or spinal thickened dura mater. It has been recognized that anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis may lead to HP; however, the immune-mediated pathogenesis of ANCA-related HP (ANCA-HP) remains elusive. In the present study, we analyzed B-cell activation factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) expression in the cerebrospinal fluid (CSF) and serum of patients with ANCA-HP, multiple sclerosis (MS), and non-inflammatory neurological disorders (NIND). BAFF and APRIL levels in the CSF were significantly higher in patients with ANCA-HP than in those with MS and NIND. In addition, a positive correlation between BAFF levels in the CSF and IgG-index was found in patients with ANCA-HP. On the other hand, no correlation was detected between CSF and serum levels of BAFF or APRIL. The results suggest that increased levels of BAFF and APRIL produced in the central nervous system may influence the development of ANCA-HP.
Hypertrophic pachymeningitis is a characteristic manifestation of granulomatosis with polyangiitis: A retrospective study of anti-neutrophil cytoplasmic antibody-associated vasculitis INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES,20(4):489-496 2017(Apr.) Author:Yasuhiro Shimojima; Dai Kishida; Akiyo Hineno; Masahide Yazaki; Yoshiki Sekijima; Shu-ichi Ikeda Abstract:Aim: To elucidate the characteristics of patients with hypertrophic pachymeningitis (HP) in a population with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Methods: We retrospectively investigated the clinical records of 39 patients who were diagnosed with AAV. To determine the characteristics of HP in AAV, the epidemiological and clinical data from patients with HP were statistically compared with those from patients without HP.
Results: Of 39 patients with AAV, seven (17.9%) had associated HP. All patients with HP were classified as having granulomatosis with polyangiitis (GPA), whereas only five of 32 patients without HP were diagnosed as having GPA (P < 0.0001). The frequencies of myeloperoxidase (MPO)-ANCA and proteinase 3-ANCA positivity in patients with HP were equivalent, while MPO-ANCA positivity was obviously dominant in patients without HP. HP occurred as the initial clinical episode of AAV in three patients (7.7% of all AAV). Frequent significant characteristics of patients with HP were headache, cranial neuropathy and paranasal involvement (P < 0.05), and histopathological findings from paranasal involvement were useful for the diagnosis of GPA in some patients with HP. Combination therapy of corticosteroid and an immunosuppressant, such as methotrexate, cyclophosphamide or rituximab, was effective for achieving remission and improving radiographic findings of HP.
Conclusion: AAV is a common cause of HP; epidemiological features of AAV patients with HP are different from those of patients without HP. Additionally, HP impacts diagnosis because it may be an initial clinical sign of AAV.
Effective Use of Calcineurin Inhibitor in Combination Therapy for Interstitial Lung Disease in Patients With Dermatomyositis and Polymyositis JCR-JOURNAL OF CLINICAL RHEUMATOLOGY,23(2):87-93 2017(Mar.) Author:Yasuhiro Shimojima; Wataru Ishii; Masayuki Matsuda; Dai Kishida; Shu-ichi Ikeda Abstract:Objective The current study demonstrated the potential use of calcineurin inhibitor (CNI) in combination therapy for interstitial lung disease (ILD) complicated with dermatomyositis (DM) and polymyositis (PM).
Methods Thirty DM/PM patients with ILD were enrolled in this study. Continuous intravenous administration of cyclosporine A (IV-CsA) was simultaneously started with corticosteroid in patients presenting more than two respiratory distress factors as follows: <70 mmHg of PaO2, percentage of vital capacity <70%, and/or exertional dyspnea. Other patients took CNI orally with corticosteroid. When a patient presented exacerbation of ILD, intravenous cyclophosphamide pulse therapy (IVCY) was additionally administrated. Clinical outcomes were compared with those of 21 patients who had been previously treated in our hospital before starting this study, as the historical comparison group.
Results Seven patients underwent IV-CsA, maintaining the drug concentration in blood between 300 and 350 ng/mL, and six of them had favorable outcomes without any adverse events. Eight out of the 30 patients additionally required IVCY. Meanwhile, the frequency of death ascribable to respiratory failure was 6.7%, which was significantly lower than that of the historical comparison group (P = 0.043). Furthermore, longer survival free from exacerbation and severe adverse event was significantly shown (P = 0.029).
Conclusions For repressing the activity of ILD in DM/PM patients, stabilizing the blood concentration of CNI immediately is a reasonable treatment as well as initiating immunosuppressive therapy in the early phase of the illness. IV-CsA may be a useful option for achieving this purpose in patients with severe ILD.
Imbalanced expression of dysfunctional regulatory T cells and T-helper cells relates to immunopathogenesis in polyarteritis nodosa MODERN RHEUMATOLOGY,27(1):102-109 2017(Jan.) Author:Yasuhiro Shimojima; Wataru Ishii; Dai Kishida; Kazuhiro Fukushima; Shu-ichi Ikeda Abstract:Objectives: We investigated the characteristics of circulating T-helper (Th) cells and CD4(+) regulatory T cells (Tregs) in polyarteritis nodosa (PAN).
Methods: Peripheral blood samples were obtained from 14 patients with PAN. Nine patients having granulomatosis with polyangiitis (GPA) and 11 healthy individuals (HC) were enrolled as controls. Th cells and Tregs were analyzed by flow cytometry. Suppression assay of Tregs was simultaneously performed by evaluating the proliferation of conventional CD4(+) T cells cocultured with Tregs.
Results: The frequencies of Th cells were significantly higher in PAN than in HC. In comparison with GPA, the expression of Th1 cells was higher but that of Th17 cells was lower. Additionally, significant increase in Tregs was observed in PAN, which was correlated with the expression of Th1 cells; however, defects in suppressive ability and CTLA-4 expression were observed. The Th1-cell frequency was significantly decreased after immunosuppressive therapy in PAN; however, there were no improvements in other phenotypes or in Treg function.
Conclusion: T-helper cell expansion and Treg dysfunction are thought to be associated with the pathogenesis of PAN. Th1 cells show a response to immunosuppressive therapy; however, the persistent immune abnormalities may interfere with complete recovery in patients with PAN.
Intractable Cutaneous Nontuberculous Mycobacteriosis (Mycobacterium abscessus) during Treatment for Systemic Lupus Erythematosus INTERNAL MEDICINE,56(10):1253-1257 2017 Author:Dai Kishida; Mitsuto Sato; Chinatsu Kobayashi; Ken-ichi Ueno; Tomomi Kinoshita; Minori Kodaira; Yasuhiro Shimojima; Wataru Ishii; Atsuhito Ushiki; Shu-ichi Ikeda Abstract:Mycobacterium abscessus infection tends to occur in patients with an advanced immunocompromised status. We encountered a case of intractable cutaneous M. abscessus infection that developed in a patient with systemic lupus erythematosus (SLE) during maintenance therapy. A 28-year-old woman developed a fever and redness of the skin on her buttocks. General antibacterial therapy was ineffective, and acid-fast bacteria were detected in the biopsy that was conducted to differentiate the dermal symptoms of SLE. The clinical findings eventually improved; however, the symptoms recurred multiple times during treatment. Despite recent advances in SLE treatment, M. abscessus infection remains a considerable complication of SLE.
Protein-losing Gastroenteropathy Related to Mixed Connective Tissue Disease: A Case Report of a Successful Outcome and Literature Review INTERNAL MEDICINE,56(15):2057-2062 2017 Author:Yuya Kobayashi; Yasuhiro Shimojima; Yasufumi Kondo; Ryota Takamatsu; Daigo Miyazaki; Dai Kishida; Yoshiki Sekijima; Shu-ichi Ikeda Abstract:We herein report the case of a 44-year-old woman who developed protein-losing gastroenteropathy (PLGE) with hypoalbuminemia as the first manifestation of mixed connective tissue disease (MCTD). Albumin leakage from the stomach and intestinal tract was demonstrated by Tc-99m-labeled human serum albumin scintigraphy. The patient's response to prednisolone therapy was insufficient; therefore, additional cyclosporin A (CsA) treatment was administered, and clinical remission was achieved. We concluded that although PLGE is a rare complication of MCTD, it may manifest as an initial clinical episode of MCTD. Furthermore, CsA can be a useful treatment option for refractory PLGE related to MCTD.
Effective Administration of Rituximab in Anti-MDA5 Antibody-Positive Dermatomyositis with Rapidly Progressive Interstitial Lung Disease and Refractory Cutaneous Involvement: A Case Report and Literature Review. Case reports in rheumatology,2017:5386797-5386797 2017 Author:Yuka Ogawa; Dai Kishida; Yasuhiro Shimojima; Koichi Hayashi; Yoshiki Sekijima Abstract:We describe the case of a 48-year-old man with dermatomyositis (DM) who demonstrated rapidly progressive interstitial lung disease (RP-ILD) and refractory cutaneous involvement together with high levels of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab). Even after combination immunosuppressive therapy including a corticosteroid, cyclosporine A, and intravenous cyclophosphamide, his respiratory insufficiency and cutaneous involvement progressively worsened. However, the administration of rituximab (RTX) resulted in clinical remission as well as a visible reduction in anti-MDA5-Ab levels, suggesting that RTX could be a useful remedy in cases refractory to conventional immunosuppressive agents, especially those of RP-ILD related to anti-MDA5-Ab-positive DM.
Recurrent pleural effusion is an important diagnostic clue to distinguish familial Mediterranean fever from Behçet's disease. Clinical and experimental rheumatology,35 Suppl 108(6):135-135 2017 Author:Fumihiro Yamaguchi; Miku Tajika; Daisuke Inoue; Yusuke Shikama; Dai Kishida; Akinori Nakamura
Advantage of administering tacrolimus for improving prognosis of patients with polymyositis and dermatomyositis INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES,19(12):1322-1330 2016(Dec.) Author:Ken-ichi Ueno; Yasuhiro Shimojima; Dai Kishida; Yoshiki Sekijima; Shu-ichi Ikeda Abstract:Aim: The purpose of this study was to investigate the therapeutic advantage of administering tacrolimus (TAC) in patients with polymyositis (PM) and dermatomyositis (DM).
Methods: We retrospectively analyzed the clinical outcomes after initiating treatment in 66 patients with PM/DM (28 PM and 38 DM). After initiating treatment, the prognosis was compared between patients who received TAC in combination with prednisolone (PSL) (the concomitant TAC group), and patients who were treated with PSL alone. The therapeutic efficacy of TAC was also evaluated for patients in the concomitant TAC group as well as patients who started additional TAC treatment after relapse (the additional TAC group), by analyzing clinical results, including serum creatine kinase (CK) levels, muscle strength and the daily dose of PSL.
Results: Patients in the concomitant TAC group had significantly lower frequency of relapse and longer periods of remission than patients who were treated with PSL alone (P = 0.0001, P = 0.001, respectively). Significant decreases in CK levels were observed 1 month after starting TAC treatment in both the concomitant TAC group and the additional TAC group. Moreover, the significant effects of withdrawing PSL were also demonstrated in both groups.
Conclusion: Concomitant use of TAC with PSL clearly provides a favorable outcome in patients with DM/PM. Furthermore, additional treatment with TAC is useful for improving prognosis even after recurrence.
Hypertrophic Pachymeningitis in a Population with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Study in a Single Japanese Institution ARTHRITIS & RHEUMATOLOGY,68:- 2016(Oct.) Author:Shimojima, Yasuhiro; Kishida, Dai; Hineno, Akiyo; Yazaki, Masahide; Sekijima, Yoshiki; Ikeda, Shu-ichi
Hypertrophic Pachymeningitis as an Early Manifestation of Relapsing Polychondritis: Case Report and Review of the Literature. Case reports in neurology,8(3):211-217 2016(Sep.) Author:Ushiyama S; Kinoshita T; Shimojima Y; Ohashi N; Kishida D; Miyazaki D; Nakamura K; Sekijima Y; Ikeda SI Abstract:Neurological involvement in relapsing polychondritis (RP) is relatively rare. We describe the case of an 80-year-old man who presented with hypertrophic pachymeningitis (HP) together with arthritis as the first manifestation of RP. Auricular chondritis, which subsequently determined the diagnosis of RP, occurred a few weeks after the detection of HP. The neurological symptoms, as well as arthritis, were promptly improved by treatment with corticosteroids. It is generally difficult to diagnose RP in the absence of typical cartilaginous involvement; however, the present case suggests that HP may occur as an early clinical manifestation of RP.
A Case of Abdominal Aortic Retroperitoneal and Mesenteric Amyloid Light Chain Amyloidoma. Case reports in rheumatology,2016:4146030-4146030 2016 Author:Kazuhiro Yokota; Dai Kishida; Hidekazu Kayano; Masahide Yazaki; Yuki Shimada; Yuji Akiyama; Toshihide Mimura Abstract:We report the case of a Japanese woman with amyloid light chain (AL) amyloidoma in the abdominal aortic retroperitoneum and mesentery. Irregular soft tissue mass lesions with calcification in the abdominal aortic retroperitoneum and mesentery were initially detected by computed tomography at another hospital. The lesions gradually compressed the duodenum, causing symptoms of bowel obstruction. The patient was clinically diagnosed with retroperitoneal fibrosis, and prednisolone was administered at a dose of 40 mg/day. However, the lesions did not change in size and her symptoms continued. She was transferred to our hospital and underwent mesenteric biopsy for histopathology using abdominal laparotomy. The histopathological and immunohistological findings of the mesenteric specimen demonstrated lambda light chain deposition. Accordingly, the patient was finally diagnosed with AL amyloidoma with no evidence of systemic amyloidosis. After laparotomy, her general condition worsened because of complications of pneumonia and deep vein thrombosis. She died suddenly from acute myocardial infarction. We have concluded that abdominal aortic retroperitoneal and mesenteric AL amyloidoma may have very poor prognoses in accordance with previous reports. In addition, the size and location of AL amyloidoma directly influence the prognosis. We suggest that early histopathology is important for improving prognosis.
[Fever of unknown origin in the outpatient setting: A retrospective analysis of 30 cases of familial Mediterranean fever]. Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology,39(2):130-9 2016 Author:Junwa Kunimatsu; Junko Maeda; Riri Watanabe; On Kato; Dai Kishida; Masahide Yazaki; Akinori Nakamura Abstract:BACKGROUND: In Japan, familial Mediterranean fever (FMF) is a rare cause of fever of unknown origin (FUO). However, we experienced an extraordinary number of FMF cases over 3 years. This suggests that many patients with FMF remain misdiagnosed in Japan. This study examines the clinical picture of FMF to assist Japanese clinicians in daily practice dealing with FUO. PATIENTS AND METHODS: Three years of medical records were reviewed, and 38 patients with FMF or suspected FMF were collected from our patient database. We applied the Tel-Hashomer criteria to those patients. RESULTS: Of the 38 patients, 30 were classified as having FMF in this investigation. The mean patient age was 27.8 years. MEFV gene mutations were detected in 14 patients. Three cases were colchicine-resistant. CONCLUSION: Clinicians should recognize the pattern of short, spontaneously resolving attacks of fever with fever-free intervals, especially when they see patients with recurrent FUO in the outpatient setting.
Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever PLOS ONE,10(5):- 2015(May) Author:Michio Yasunami; Hitomi Nakamura; Kazunaga Agematsu; Akinori Nakamura; Masahide Yazaki; Dai Kishida; Akihiro Yachie; Tomoko Toma; Junya Masumoto; Hiroaki Ida; Tomohiro Koga; Atsushi Kawakami; Katsumi Eguchi; Hiroshi Furukawa; Tadashi Nakamura; Minoru Nakamura; Kiyoshi Migita Abstract:Objectives
The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes.
Methods
Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment.
Results
The carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni's correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1*15:02 was completely disappeared in the co-existence of B*40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B*35:01 allele, giving OR of 4.82 (p = 0.0041).
Conclusions
The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations.
Multifocal Fibrosclerosis with Hypertrophic Pachymeningitis and a Soft Tissue Mass around the Thoracic Vertebral Bodies: A Case Report with Review of the Literature INTERNAL MEDICINE,54(17):2267-2272 2015 Author:Mitsuto Sato; Minori Kodaira; Wataru Ishii; Michitaka Nakagawa; Dai Kishida; Daigo Miyazaki; Yasuhiro Shimojima; Masayuki Matsuda; Takeshi Uehara; Shu-ichi Ikeda Abstract:Multifocal fibrosclerosis is the term used to represent a combination of similar fibrous lesions occurring at different anatomical sites. We herein report a hypertrophic pachymeningitis patient with a soft tissue mass around the thoracic vertebral bodies. A histopathological analysis of the biopsied tissues from both lesions showed dense fibrosis and a marked infiltration of lymphocytes and plasma cells, which lead to the diagnosis of multifocal fibrosclerosis. This pathological condition closely resembles that of IgG4-related disease and is a very rare combination of manifestations. Our case suggests that hypertrophic pachymeningitis patients need to also undergo a whole body examination.
Familial Mediterranean Fever Genotype-Phenotype Correlations in Japanese Patients MEDICINE,93(3):158-164 2014(May) Author:Kiyoshi Migita; Kazunaga Agematsu; Masahide Yazaki; Fumiaki Nonaka; Akinori Nakamura; Tomoko Toma; Dai Kishida; Ritei Uehara; Yoshikazu Nakamura; Yuka Jiuchi; Junya Masumoto; Hiroshi Furukawa; Hiroaki Ida; Chihiro Terai; Yoshikazu Nakashima; Atsushi Kawakami; Tadashi Nakamura; Katsumi Eguchi; Michio Yasunami; Akihiro Yachie Abstract:Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV) mutations. In Japan, patients with FMF have been previously reported, including a mild or incomplete form. Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF. We conducted the current study to investigate the correlation of variable clinical presentations and MEFV genotypic distributions in Japanese FMF patients.
We analyzed demographic, clinical, and genetic data for 311 FMF patients enrolled in the study. Clinically, we classified FMF into 2 phenotypes: 1) the "typical" form of FMF, and 2) the "atypical" form of FMF according to the Tel Hashomer criteria. Patients with the typical FMF phenotype had a higher frequency of febrile episodes, a shorter duration of febrile attacks, more frequent thoracic pain, abdominal pain, a family history of FMF, and MEFV exon 10 mutations. Conversely, patients with the atypical FMF phenotype had a lower frequency of fever episodes and more frequent arthritis in atypical distribution, myalgia, and MEFV exon 3 mutations. Multivariate analysis showed that the variable associated with typical FMF presentation was the presence of MEFV exon 10 mutations. Typical FMF phenotype frequencies were decreased in patients carrying 2 or a single low-penetrance mutations compared with those carrying 2 or a single high-penetrance mutations (M694I), with an opposite trend for the atypical FMF phenotype. In addition, patients having more than 2 MEFV mutations had a younger disease onset and a higher prevalence of thoracic pain than those carrying a single or no mutations. Thus, MEFV exon 10 mutations are associated with the more typical FMF phenotype. In contrast, more than half of the Japanese FMF patients without MEFV exon 10 mutations presented with an atypical FMF phenotype, indicating that Japanese FMF patients tend to be divided into 2 phenotypes by a variation of MEFV mutations.
Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations ARTHRITIS RESEARCH & THERAPY,16(5):--439 2014 Author:Dai Kishida; Akinori Nakamura; Masahide Yazaki; Ayako Tsuchiya-Suzuki; Masayuki Matsuda; Shu-ichi Ikeda Abstract:Introduction: Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients.
Methods: We analyzed the MEFV genotypes and clinical manifestations in 116 patients clinically diagnosed as having FMF and with at least one mutation.
Results: The most frequent mutation in Japanese patients was E148Q (40.2%), followed by M694I (21.0%), L110P (18.8%), P369S (5.4%), and R408Q (5.4%). In contrast, common mutations seen in Mediterranean patients, such as M694V, V726A, and M680I, were not detected in this population. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not.
Conclusions: Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.
Clinical and Serial MRI Findings of a Sialidosis Type I Patient with a Novel Missense Mutation in the NEU1 Gene INTERNAL MEDICINE,52(1):119-124 2013 Author:Yoshiki Sekijima; Katsuya Nakamura; Dai Kishida; Aya Narita; Kaori Adachi; Kosaku Ohno; Eiji Nanba; Shu-ichi Ikeda Abstract:The case of a Japanese sialidosis type I patient with a novel NEU1 gene mutation is described. The patient developed an unsteady gait at age 14 and was referred to our hospital at age 16. On admission, subnormal intelligence, dysarthria, myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular cherry-red spots were observed. An enzymological analysis revealed a primary deficiency of neuraminidase. An NEU1 gene analysis identified two heterozygous missense mutations: p.P80L and p.D135N. The p.D135N mutation is a novel mutation that is considered to be associated with the mild clinical phenotype of sialidosis. Serial brain MRI showed diffuse brain atrophy progressing rapidly over the 41-month observation period.
First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan HEPATOLOGY RESEARCH,42(9):934-939 2012(Sep.) Author:Masahide Yazaki; Akiyo Hineno; Akira Matsushima; Kazuki Ozawa; Dai Kishida; Ko-ichi Tazawa; Kazuhiro Fukushima; Koichi Urata; Toshihiko Ikegami; Shinichi Miyagawa; Shu-ichi Ikeda Abstract:We report the first two cases of adult-onset type II citrullinemia (CTLN2) successfully treated by liver transplantation from deceased donors in Japan. One patient was a 34-year-old female, who had suffered from depression since the age of 28 years and developed consciousness disturbance at 34 years old. The other patient was a 41-year-old man who began to experience consciousness disturbance with abnormal behavior at 37 years old. Both patients were first treated with non-surgical therapies, including low-carbohydrate diet, arginine granules and sodium pyruvate. However, their therapeutic efficacy was limited and attacks of encephalopathy occurred frequently with elevation of plasma ammonia despite treatment. While both patients and their families desired liver transplantation, no candidate donors for live-donor liver transplantation were available. Fortunately, within a relatively short period after enrollment for liver transplant from deceased donors in Japan (13 and 43 days, respectively), they underwent cadaveric liver transplantation. The clinical courses after the operation were uneventful in both cases and no attacks of hepatic encephalopathy have occurred. Although there have been no reports of good therapies for CTLN2 patients with resistance to non-surgical therapies and no live-donor candidates, our observations indicate that cadaveric liver transplantation can be a promising therapeutic option for CTLN2 patients.
ANCA-associated Vasculitis with Central Retinal Artery Occlusion Developing during Treatment with Methimazole INTERNAL MEDICINE,51(22):3177-3180 2012 Author:Takuji Yasude; Dai Kishida; Ko-ichi Tazawa; Masayuki Matsuda; Wataru Ishii; Masahide Yazaki; Shu-ichi Ikeda Abstract:A 63-year-old woman suddenly developed central retinal artery occlusion following a slight fever while being treated with methimazole (MMI) for hyperthyroidism. She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on increased inflammatory reactions with positive myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite immediate treatment with corticosteroids and cyclophosphamide after cessation of MMI, which may have played a role in the pathogenesis of AAV. Central retinal artery occlusion is a rare manifestation of AAV; however, it is important with regard to the possibility of serious sequelae.
Successful tocilizumab treatment in a patient with adult-onset Still's disease complicated by chronic active hepatitis B and amyloid A amyloidosis MODERN RHEUMATOLOGY,21(2):215-218 2011(Apr.) Author:Dai Kishida; Yasuaki Okuda; Makoto Onishi; Masashi Takebayashi; Kenichiro Matoba; Kazuo Jouyama; Akihiro Yamada; Naoya Sawada; Sho Mokuda; Kiyoshi Takasugi Abstract:We report successful tocilizumab (TCZ) use in a patient with adult-onset Still's disease (AOSD) complicated by chronic hepatitis B (CHB) and AA amyloidosis (AAA). Treatments with corticosteroid and various types of immunosuppressants were unsuccessful. Aggravation of CHB ensued, and entecavir was started. Normalisation of liver function and hepatitis B virus (HBV) DNA were confirmed. TCZ was then started. His arthritis and AAA improved dramatically. TCZ is an excellent treatment for refractory AOSD and is feasible in an HBV-infected patient.
A case with rheumatoid arthritis and systemic reactive AA amyloidosis showing rapid regression of amyloid deposition on gastroduodenal mucosa after a combined therapy of corticosteroid and etanercept RHEUMATOLOGY INTERNATIONAL,31(2):247-250 2011(Feb.) Author:Wataru Ishii; Dai Kishida; Ayako Suzuki; Yasuhiro Shimojima; Masayuki Matsuda; Yoshinobu Hoshii; Shu-ichi Ikeda Abstract:Systemic reactive amyloid A (AA) amyloidosis is one of the critical complications associated with rheumatoid arthritis (RA). Recently, there are several useful reports of anti-tumor necrosis factor therapy for RA-related systemic reactive AA amyloidosis patients. However, the time-kinetic transition between effective anti-inflammatory therapies and regression of AA amyloid deposits remains uncertain. Here, we report a RA patient with systemic reactive AA amyloidosis who was successfully treated with prednisolone and etanercept, showing marked regression of gastroduodenal mucosal amyloid deposits within only 4 months. This is the first case report of RA-related systemic reactive AA amyloidosis histopathologically demonstrating rapid regression of amyloid deposits on gastroduodenal mucosa after adequate suppression of the underlying inflammatory condition.
Leukoencephalopathy Induced by Low-dose Methotrexate in a Patient with Rheumatoid Arthritis INTERNAL MEDICINE,50(19):2219-2222 2011 Author:Masayuki Matsuda; Dai Kishida; Tomomi Kinoshita; Akiyo Hineno; Yasuhiro Shimojima; Kazuhiro Fukushima; Shu-ichi Ikeda Abstract:We report a patient with rheumatoid arthritis (RA) who developed leukoencephalopathy while being treated with low-dose methotrexate (MTX). She suddenly developed loss of recent memory and left homonymous hemianopsia ascribable to the bilateral but right-predominant occipitotemporal lesions. Intravenous administration of dexamethasone and cessation of MTX quickly relieved her clinical symptoms. Low-dose MTX-induced leukoencephalopathy is a rare complication in RA, but is important with regard to the possibility of serious neurological sequellae.
Periodic Peritonitis due to Familial Mediterranean Fever in a Patient with Systemic Lupus Erythematosus INTERNAL MEDICINE,49(20):2259-2262 2010 Author:Masayuki Matsuda; Dai Kishida; Ayako Tsuchiya-Suzuki; Kazuhiro Fukushima; Yasuhiro Shimojima; Masahide Yazaki; Shu-ichi Ikeda Abstract:We report a patient with systemic lupus erythematosus (SLE) who showed periodic peritonitis with spontaneous remission. She showed compound heterozygous mutations in the MEFV gene, leading to the diagnosis of familial Mediterranean fever (FMF). Oral colchicine successfully reduced the severity and frequency of her peritonitis. SLE occasionally manifests abdominal symptoms, but in cases with periodic peritonitis, associated FMF should be considered as a possible cause.
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