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Article ; Online: Evaluation of Medication Withdrawal in Patients with Non-systemic Juvenile Idiopathic Arthritis in Japan Using a Web-based Survey.

Ebato, Takasuke / Kishi, Takayuki / Akamine, Keiji / Nozawa, Tomo / Imagawa, Tomoyuki / Bando, Yuki / Miyamae, Takako

2024

Abstract: Objective: Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non- ...

Abstract	Objective: Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non-systemic JIA treatment. Methods: A web-based questionnaire was distributed to Pediatric Rheumatology Association of Japan members. Results: According to 126 responses, the most significant factors influencing JIA treatment tapering were the duration of clinically inactive disease, medication toxicity, and a history of arthritis flares. Respondents were often cautious about discontinuing medication if symptoms, e.g., 'morning stiffness' or 'intermittent joint pain', persisted. Among subtypes, oligoarticular JIA was more amenable to treatment tapering, whereas rheumatoid factor-positive polyarticular JIA proved less amenable. Most respondents started medication tapering after a continuous clinical inactive duration exceeding 12 months, and >50% of them required >6 months to achieve treatment discontinuation. Additionally, 40% of respondents consistently underwent imaging before treatment tapering. Conclusions: The relative risks of treatment continuation and withdrawal should be considered, and decisions should be made accordingly. To obtain improved understanding of and more robust evidence for the optimal strategies for safely discontinuing JIA treatment, it is crucial to continue investigations, including long-term outcomes.
Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roae016
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Article ; Online: Lipschütz ulcer induced by acute Epstein-Barr virus infection in a young girl.

Miyazawa, Takuya / Hayashibe, Ren / Nozawa, Tomo / Nishimura, Kenichi / Ito, Shuichi

Pediatrics international : official journal of the Japan Pediatric Society

2022 Volume 64, Issue 1, Page(s) e15022

MeSH term(s)	Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Female ; Herpesvirus 4, Human ; Humans ; Ulcer/diagnosis ; Ulcer/etiology ; Vulvar Diseases
Language	English
Publishing date	2022-04-28
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1470376-2
ISSN	1442-200X ; 1328-8067
ISSN (online)	1442-200X
ISSN	1328-8067
DOI	10.1111/ped.15022
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Zs.A 848: Show issues

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Article ; Online: Purple eyelid sign in multisystem inflammatory syndrome in children.

Komatsu, Yosuke / Nozawa, Tomo / Kamiyama, Yuji / Hattori, Seira / Nishimura, Kenichi / Ito, Shuichi

Pediatrics international : official journal of the Japan Pediatric Society

2023 Volume 65, Issue 1, Page(s) e15510

MeSH term(s)	Child ; Humans ; Systemic Inflammatory Response Syndrome/diagnosis ; Mucocutaneous Lymph Node Syndrome
Language	English
Publishing date	2023-02-20
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1470376-2
ISSN	1442-200X ; 1328-8067
ISSN (online)	1442-200X
ISSN	1328-8067
DOI	10.1111/ped.15510
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Article ; Online: Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study.

Hattori, Seira / Nozawa, Tomo / Nishimura, Kenichi / Hara, Ryoki / Murase, Ayako / Ohara, Asami / Ohnishi, Ai / Ohya, Takashi / Ito, Shuichi

Scientific reports

2023 Volume 13, Issue 1, Page(s) 9890

Abstract: Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this ... ...

Abstract	Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.
MeSH term(s)	Humans ; Infant ; Mucocutaneous Lymph Node Syndrome/complications ; Mucocutaneous Lymph Node Syndrome/diagnosis ; Mucocutaneous Lymph Node Syndrome/drug therapy ; Retrospective Studies ; Fever/etiology ; Arthritis/drug therapy ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Immunoglobulins, Intravenous
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-36308-9
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Article ; Online: Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

Nozawa, Tomo / Pullenayegum, Eleanor M / Bell-Peter, Audrey / Marcuz, Jo-Anne / Whitney, Kristi / Vinik, Ophir / Shupak, Rachel / Dover, Saunya / Feldman, Brian M

Rheumatology (Oxford, England)

2024

Abstract: Objectives: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory ...

Abstract	Objectives: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. Methods: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. Results: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. Conclusion: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae027
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article: Early Abnormal Nailfold Capillary Changes Are Predictive of Calcinosis Development in Juvenile Dermatomyositis.

Nozawa, Tomo / Bell-Peter, Audrey / Marcuz, Jo-Anne / Whitney, Kristi / Vinik, Ophir / Shupak, Rachel / Dover, Saunya / Feldman, Brian M

The Journal of rheumatology

2022 Volume 49, Issue 11, Page(s) 1250–1255

Abstract: Objective: The long-term outcomes of juvenile dermatomyositis (JDM) are more favorable in recent years. However, calcinosis is still among the complications that can cause serious functional impairment. Little is known about the pathogenesis and risk ... ...

Abstract	Objective: The long-term outcomes of juvenile dermatomyositis (JDM) are more favorable in recent years. However, calcinosis is still among the complications that can cause serious functional impairment. Little is known about the pathogenesis and risk factors of calcinosis. The aim of this study is to determine risk factors for the development of calcinosis in JDM. Methods: This was a single-center, retrospective cohort study. All patients were diagnosed and followed at the multidisciplinary JDM clinic of The Hospital for Sick Children, from January 1, 1989, until May 31, 2018. To investigate predictors of incident calcinosis, Cox regression analysis was performed. Results: A total of 172 patients met inclusion criteria, with a median age at diagnosis of 7.7 years (IQR 4.9-12.1), and a median follow-up of 8.5 years (IQR 3.4-12.6, range 0.1-28.3). The only risk factor significantly associated with the development of calcinosis in the univariate analysis was nailfold abnormality at baseline (hazard ratio [HR] 4.86, Conclusion: The presence of abnormal nailfold capillary changes at baseline is predictive for the development of calcinosis in children with idiopathic inflammatory myopathies.
MeSH term(s)	Child ; Humans ; Child, Preschool ; Dermatomyositis/complications ; Retrospective Studies ; Calcinosis/etiology ; Capillaries ; Risk Factors
Language	English
Publishing date	2022-08-01
Publishing country	Canada
Document type	Journal Article
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.220249
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Zs.A 1168: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 135: Show issues

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Article ; Online: Impaired Interleukin-18 Signaling in Natural Killer Cells From Patients With Systemic Juvenile Idiopathic Arthritis.

Ohya, Takashi / Nishimura, Kenichi / Murase, Ayako / Hattori, Seira / Ohara, Asami / Nozawa, Tomo / Hara, Ryoki / Ito, Shuichi

ACR open rheumatology

2022 Volume 4, Issue 6, Page(s) 503–510

Abstract: Objective: Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, rash, hepatosplenomegaly, and macrophage activation syndrome; however, its pathogenesis is still unclear. Elevated serum interleukin (IL)-18 concentrations ... ...

Abstract	Objective: Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, rash, hepatosplenomegaly, and macrophage activation syndrome; however, its pathogenesis is still unclear. Elevated serum interleukin (IL)-18 concentrations and decreased natural killer (NK) cell activity are characteristic of active disease; thus, we examined IL-18 signaling in NK cells from sJIA. Methods: We analyzed mitogen-activated protein kinase (MAPK) p38 and nuclear factor κ light chain enhancer of activated B cells (NFκB) p65 phosphorylation in NK cells after in vitro recombinant IL-18 (rIL-18) stimulation in 31 patients with sJIA. Associations between clinical features, serum IL-18, and phosphorylation intensity were analyzed. Furthermore, we investigated the effects of high IL-18 concentrations on phosphorylation in NK cells. Results: Patients were divided according to their disease activity: systemic features (n = 8), chronic arthritis (n = 7), remission on medication (n = 10), and remission off medication (n = 6). MAPK p38 and NFκB p65 phosphorylation intensity were the highest in healthy controls, followed by remission off medication, remission on medication (vs. control; MAPK p38, P < 0.01; NFκB p65, P < 0.05), chronic arthritis (P < 0.001, P < 0.001), and systemic features (P < 0.001, P < 0.001). The systemic features group showed a complete defect in phosphorylation. Serum IL-18 was the highest in the systemic features group followed by chronic arthritis, remission on medication (P < 0.01), remission off medication (P < 0.01), and healthy controls (P < 0.01). Phosphorylation intensity was negatively correlated with serum IL-18 (MAPK p38, r Conclusion: Impaired IL-18 signaling in NK cells correlated with disease activity in sJIA. High serum IL-18 exposure induces impaired MAPK and NFκB phosphorylation in NK cells.
Language	English
Publishing date	2022-03-11
Publishing country	United States
Document type	Journal Article
ISSN	2578-5745
ISSN (online)	2578-5745
DOI	10.1002/acr2.11426
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Article ; Online: Difficulties of Diagnosing Idiopathic Hypertrophic Pachymeningitis in Children: Case Report and Literature Review.

Nicho, Naoki / Nozawa, Tomo / Murase, Ayako / Hayashibe, Ren / Tanoshima, Reo / Okubo, Risa / Hattori, Seira / Nishimura, Kenichi / Ohya, Takashi / Ito, Shuichi

Modern rheumatology case reports

2022

Abstract: Hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial and spinal dura mater. HP occurs owing to idiopathic or secondary causes, including autoimmune disease, infection, and trauma. ... ...

Abstract	Hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial and spinal dura mater. HP occurs owing to idiopathic or secondary causes, including autoimmune disease, infection, and trauma. HP has mainly been reported in adults, with few reported cases in children. We encountered an 11-year-old boy with idiopathic HP who presented with chronic inflammation and daily occipital headache. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) helped us to diagnose him with HP. He was successfully treated with corticosteroids and azathioprine with no recurrence. We also conducted a literature review of childhood-onset HP and found only 16 cases including our patient. Seven patients had idiopathic HP and the remaining nine had secondary HP, including two with rheumatic disease. The most common clinical symptoms were headache (68.8%) and cranial nerve-related symptoms (68.8%). Inflammatory laboratory markers were elevated in 60% of patients with available data. Fifteen cases were diagnosed using Gd-enhanced MRI. The main initial treatment was steroids and/or immunosuppressants, to which 87.5% of patients responded. However, two patients with HP associated with trauma and neuroblastoma (12.5%) died, and seven patients (43.8%) had left cranial nerve-related sequelae. As the prognosis for childhood HP is poor, early diagnosis and treatment are essential. Children with headache, cranial nerve symptoms, and elevated inflammatory marker levels should be suspected of having HP and Gd-enhanced MRI should be considered.
Language	English
Publishing date	2022-03-28
Publishing country	England
Document type	Journal Article
ISSN	2472-5625
ISSN (online)	2472-5625
DOI	10.1093/mrcr/rxac026
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Article ; Online: The clinical features of juvenile dermatomyositis: A single-centre inception cohort.

Cancarini, Paola / Nozawa, Tomo / Whitney, Kristi / Bell-Peter, Audrey / Marcuz, Jo-Anne / Taddio, Andrea / Guo, Jessica / Dover, Saunya / Feldman, Brian M

Seminars in arthritis and rheumatism

2022 Volume 57, Page(s) 152104

Abstract: Introduction: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort.: Methods: We studied an inception ... ...

Abstract	Introduction: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort. Methods: We studied an inception cohort (0-18 years old) referred for diagnosis to the JDM clinic at The Hospital for Sick Children (SickKids), between January 1989 and September 2017. Probable or definite diagnosis of JDM was done according to the 2017 ACR/EULAR Criteria. We excluded children who had treatment started at another hospital. The data were collected retrospectively from clinical charts and the SickKids JDM database. Results: 172/230 (74.8%) patients were included. They were most often female (female:male = 1.8:1); the age at diagnosis was 8.5±4.3 years. There was a positive family history for autoimmune disease in 52%, mainly rheumatoid arthritis. No patient died. The most common signs at inception were muscle weakness (85.5%), nailfold capillary abnormalities (83.4%), Gottron papules (78.5%), heliotrope rash (66.3%), abnormal gait (55.8%), and malar/facial rash (54.7%). The prevalence of Gottron papules, heliotrope rash, facial/malar rash, nailfold capillary abnormalities, Raynaud phenomenon, dysphonia/dysphagia (a frequent cause of hospitalization), mouth ulcers, calcinosis, eye problems, joint involvement, acanthosis nigricans and lipodystrophy increased during follow-up. Muscle enzymes, namely CK, ALT, AST, were often normal or only slightly raised despite active muscle disease; conversely LD was often high. Anti-Nuclear Autoantibodies were positive in 49.7% of patients at diagnosis. The course of the disease was: 29.1% monocyclic, 5.3% polycyclic, 33.1% chronic. The course of 56 patients (32.5%) was not classifiable due to length of follow-up. Corticosteroids were used as treatment in almost all our patients and 30% required intravenous therapy due to the severity of the presentation; methotrexate was added in 64%, more often in recent years. Unresponsive patients were treated mostly with intravenous immunoglobulins (IVIG). Conclusions: The information obtained from this relatively large number of patients adds to the growing knowledge base of this rare disease. Trial registration: SickKids Research Ethics Board approved the study.
MeSH term(s)	Humans ; Male ; Female ; Child, Preschool ; Child ; Infant, Newborn ; Infant ; Adolescent ; Dermatomyositis/diagnosis ; Dermatomyositis/drug therapy ; Retrospective Studies ; Myositis ; Autoimmune Diseases ; Exanthema
Language	English
Publishing date	2022-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2022.152104
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Article ; Online: Coronary-Artery Aneurysm in Tocilizumab-Treated Children with Kawasaki's Disease.

Nozawa, Tomo / Imagawa, Tomoyuki / Ito, Shuichi

The New England journal of medicine

2017 Volume 377, Issue 19, Page(s) 1894–1896

Language	English
Publishing date	2017--09
Publishing country	United States
Document type	Letter
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1709609
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