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Pediatric and Adolescent Rheumatology: A Rapidly Developing Field
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Pediatric and Adolescent Rheumatology: A Rapidly Developing Field

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (15 January 2021) | Viewed by 25126

Special Issue Editor

Dr. Takako Miyamae

E-Mail Website
Guest Editor
Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
Interests: pediatric rheumatology; autoinflammatory diseases

Special Issue Information

Dear Colleagues,

The area of pediatric and adolescent rheumatology is on the move. Pediatric rheumatology is closely linked to the field of immunology and the rheumatic diseases often referred to loosely as “autoimmune” conditions. It also includes autoinflammatory monogenic diseases and autoinflammatory multifactorial diseases with complex inheritance. In addition, pediatric rheumatology has important links to other clinical specialties including orthopedics, ophthalmology, rehabilitation medicine, nephrology, gastroenterology, cardiology, infectious disease, and dermatology. It is notable for its close working relationships with allied health professions including physical and occupational therapy, nursing, social services, and psychology.

Dramatic advances in our understanding of the nature of inflammation and the possibility of specifically regulating the aberrant immune inflammatory response are revolutionizing the treatment of rheumatic diseases of childhood. Our better understanding of the genetics of rheumatic diseases is pointing the way to therapeutic targeting at an even more fundamental level: the gene. Recognition of the autoinflammatory diseases and their genetic basis illuminates a heretofore obscure and confusing group of childhood disorders.

The present Special Issue aims to deepen and broaden the specificity of predictors across pediatric and adolescent rheumatology. We also highlight the need to ensure that research is integral to transitional care pathways.

Dr. Takako Miyamae
Guest Editor

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Keywords

  • new autoinflammatory disorders
  • new treatment (biologics, JAK inhibitors, and others)
  • pathogenesis and genetics in childhood onset rheumatic diseases
  • long-term outcome of childhood-onset rheumatic diseases
  • transitional medical care

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Published Papers (6 papers)

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Research

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12 pages, 770 KiB  
Article
Enthesitis Related Arthritis in a Longitudinal Southeast Asian Registry: High Prevalence of HLA-B27, Different Sacroiliitis Risk Factors and Less Common Drug-Free Remission
by Thaschawee Arkachaisri, Kai Liang Teh, Yun Xin Book, Sook Fun Hoh, Xiaocong Gao and Lena Das
J. Clin. Med. 2021, 10(4), 568; https://doi.org/10.3390/jcm10040568 - 3 Feb 2021
Cited by 14 | Viewed by 2892
Abstract
Objective. To describe the clinical characteristics, predictors and treatment of children with Enthesitis Related Arthritis (ERA) in a Singapore longitudinal cohort over 11 years. Methods. ERA patients were recruited from our registry (2009–2019). Nonparametric descriptive statistics including median (interquartile range, IQR) [...] Read more.
Objective. To describe the clinical characteristics, predictors and treatment of children with Enthesitis Related Arthritis (ERA) in a Singapore longitudinal cohort over 11 years. Methods. ERA patients were recruited from our registry (2009–2019). Nonparametric descriptive statistics including median (interquartile range, IQR) were used to describe data. Kaplan–Meier survival and logistic/Cox regression analyses were used to estimate the probabilities and determine predictors of clinical variables, respectively. The significance level was set at <0.05. Results. One hundred and forty-six ERA patients (87% male, 82% Chinese) were included. Median onset age was 11.9 years (IQR 9.4–14.0) and median disease duration was 4.9 years (IQR 2.6–8.3). Family history of Human Leukocyte Antigen (HLA)-B27 associated diseases was positive in 7.5%. Acute uveitis occurred in 3.4%. Oligoarthritis was present in 89.7%. Hip, knee and ankle joints were among the most common joints involved. One-fourth had enthesitis at diagnosis (Achilles tendon entheses, 82.9%). Sacroiliitis occurred in 61%. Probabilities of sacroiliitis development were 0.364, 0.448 and 0.578 at 1, 2 and 5 years after onset, respectively. Negative HLA-B27, female, older age at onset and hip arthritis at diagnosis were associated with shorter time for sacroiliitis development (p = 0.001–0.049). Methotrexate (MTX) remained the most common disease modifying anti-rheumatic drug (DMARD) used (77.4%). However, 77.9% required anti-TNF (aTNF) therapy secondary to MTX failure. Among MTX-treated sacroiliitis patients, 85.3% failed, requiring aTNF, as compared to 63.2%patients without axial disease. Longer duration to diagnosis (p = 0.038) and MTX use (p = 0.007) predicted aTNF therapy. None had joint deformity. Conclusions. This study underscores differences in ERA clinical characteristics, predictors and treatment responses. Our ERA population had many unique findings but good functional outcomes. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
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Review

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7 pages, 229 KiB  
Review
Clinical Features and Cutaneous Manifestations of Juvenile and Adult Patients of Dermatomyositis Associated with Myositis-Specific Autoantibodies
by Naoko Okiyama
J. Clin. Med. 2021, 10(8), 1725; https://doi.org/10.3390/jcm10081725 - 16 Apr 2021
Cited by 13 | Viewed by 2671
Abstract
Dermatomyositis is one of the idiopathic inflammatory myopathies, which is characterized with specific skin manifestations, and considered as an autoimmune disease. Dermatomyositis is a heterogeneous disorder with various presences, severities and characteristics of myositis, dermatitis, and interstitial lung disease. Our and others’ data [...] Read more.
Dermatomyositis is one of the idiopathic inflammatory myopathies, which is characterized with specific skin manifestations, and considered as an autoimmune disease. Dermatomyositis is a heterogeneous disorder with various presences, severities and characteristics of myositis, dermatitis, and interstitial lung disease. Our and others’ data showed that myositis-specific autoantibodies have been associated with distinct clinical features. This article reviewed the epidemiology and characteristic clinical features of the different types of antibody-associated dermatomyositis in adult and juvenile patients, which include the severity of myopathy, the potential complication of interstitial lung disease, potential association with malignancies, and characteristic cutaneous manifestations. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
10 pages, 1230 KiB  
Review
Non-Criteria Manifestations of Juvenile Antiphospholipid Syndrome
by Takako Miyamae and Tomohiro Kawabe
J. Clin. Med. 2021, 10(6), 1240; https://doi.org/10.3390/jcm10061240 - 17 Mar 2021
Cited by 12 | Viewed by 4034
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder mainly characterised by increased risks of thrombosis and pregnancy morbidity and persistent positive test results for antiphospholipid antibodies (aPLs). The criteria for diagnosing juvenile APS have yet to be validated, while the Sydney classification criteria [...] Read more.
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder mainly characterised by increased risks of thrombosis and pregnancy morbidity and persistent positive test results for antiphospholipid antibodies (aPLs). The criteria for diagnosing juvenile APS have yet to be validated, while the Sydney classification criteria do not contain several non-thrombotic clinical manifestations associated with the presence of aPLs. As such, difficulties have been encountered in the diagnosis of patients who have no certain thrombotic occlusions. Moreover, extra-criteria manifestations (i.e., clinical manifestations not listed in the classification criteria), including neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease have been reported, which suggests that the clinical spectrum of aPL-related manifestations extends beyond that indicated in the classification criteria. Studies have demonstrated that more than 40% of children with aPLs demonstrated non-thrombotic aPL-related clinical manifestations alone. Moreover, our results showed that the pathogenesis of non-criteria manifestations is characterised by “APS vasculopathy”. The present review introduces the characteristics and findings of non-criteria manifestations observed in juvenile APS. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
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9 pages, 557 KiB  
Review
The Coming-of-Age Transition Care for Adolescents with Rheumatic Disease—Where Are We and What Have We Done in Asia?
by Kai Liang Teh, Sook Fun Hoh and Thaschawee Arkachaisri
J. Clin. Med. 2021, 10(4), 821; https://doi.org/10.3390/jcm10040821 - 17 Feb 2021
Cited by 8 | Viewed by 3194
Abstract
The transition from pediatric to adult health care is a challenging yet important process in rheumatology as most childhood-onset rheumatic diseases persist into adulthood. Numerous reports on unmet needs as well as evidence of negative impact from poor transition have led to increased [...] Read more.
The transition from pediatric to adult health care is a challenging yet important process in rheumatology as most childhood-onset rheumatic diseases persist into adulthood. Numerous reports on unmet needs as well as evidence of negative impact from poor transition have led to increased efforts to improve transition care, including international guidelines and recommendations. In line with these recommendations, transition programs along with transition readiness assessment tools have been established. Despite these efforts, there are still a lot of work to be done for transition care in rheumatology. This review article focuses on how transition care in rheumatology has developed in recent years and highlights the gaps in current practices. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
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16 pages, 5795 KiB  
Review
Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology
by Shumpei Yokota, Takako Miyamae, Yoshiyuki Kuroiwa and Kusuki Nishioka
J. Clin. Med. 2021, 10(4), 801; https://doi.org/10.3390/jcm10040801 - 17 Feb 2021
Cited by 35 | Viewed by 6437
Abstract
The Novel Coronavirus Disease 2019 (COVID-19) has swept the world and caused a global pandemic. SARS-CoV-2 seems to have originated from bats as their reservoir hosts over time. Similar to SARS-CoV, this new virus also exerts its action on the human angiotensin-converting enzyme [...] Read more.
The Novel Coronavirus Disease 2019 (COVID-19) has swept the world and caused a global pandemic. SARS-CoV-2 seems to have originated from bats as their reservoir hosts over time. Similar to SARS-CoV, this new virus also exerts its action on the human angiotensin-converting enzyme 2. This action causes infections in cells and establishes an infectious disease, COVID-19. Against this viral invasion, the human body starts to activate the innate immune system in producing and releasing proinflammatory cytokines such as IL-6, IL-1β, IL-8, TNF-α, and other chemokines, such as G-CSF, IP10 and MCPl, which all develop and increase the inflammatory response. In cases of COVID-19, excessive inflammatory responses occur, and exaggerated proinflammatory cytokines and chemokines are detected in the serum, resulting in cytokine release syndrome or cytokine storm. This causes coagulation abnormalities, excessive oxidation developments, mitochondrial permeability transition, vital organ damage, immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure. Additionally, the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress. This damages cells and mitochondria, leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage-associated molecular patterns. Thus, the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome, including vascular endothelial cell damage and coagulation-fibrinolysis system disorders. This condition causes central nervous system disorders, renal failure, liver failure and, finally, multiple organ failure. Regarding treatment for COVID-19, the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients. First, administering of favipiravir to suppress SARS-CoV-2 and nafamostat to inhibit ACE2 function should be considered. Second, anti-rheumatic drugs (monoclonal antibodies), which act on the leading cytokines (IL-1β, IL-6) and/or cytokine receptors such as tocilizumab, should be administered as well. Finally, melatonin may also have supportive effects for cytokine release syndrome, resulting in mitochondrial function improvement. This paper will further explore these subjects with reports mostly from China and Europe. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
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9 pages, 278 KiB  
Review
Childhood-Onset Systemic Lupus Erythematosus: Southeast Asian Perspectives
by Swee Ping Tang, Sern Chin Lim and Thaschawee Arkachaisri
J. Clin. Med. 2021, 10(4), 559; https://doi.org/10.3390/jcm10040559 - 3 Feb 2021
Cited by 25 | Viewed by 5086
Abstract
Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include [...] Read more.
Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include haematological, renal, and mucocutaneous. Fever, malar rash, and cutaneous vasculitis are common. Lupus nephritis is typically proliferative especially Class IV and contributes to both disease activity and damage. Antinuclear antibody and anti-dsDNA positivity are both prevalent in this region. Disease activity is higher than Western cohorts at onset but responds to therapy reducing to low disease activity by six months. However, organ damage occurs early and continues to accumulate over the time, a consequence of both active disease (neurological and renal systems) and steroid-related complications especially in the eye (cataract and glaucoma) and musculoskeletal systems (avascular necrosis). Infections remain the leading cause of death and mortality in this region is highly variable contributed by the heterogeneity in social economic status, healthcare access, and availability of paediatric rheumatology expertise in the region. Full article
(This article belongs to the Special Issue Pediatric and Adolescent Rheumatology: A Rapidly Developing Field)
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