New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review
<b>Background:</b> Juvenile scleroderma (JS) comprises a group of rare chronic autoimmune and fibrosing disorders in children, primarily presenting as juvenile localized scleroderma (jLS) or juvenile systemic sclerosis (jSS). While jLS predominantly affects the skin and subcutaneous tiss...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/5/643 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849327096248139776 |
|---|---|
| author | Chiara Sassetti Claudia Borrelli Martha Mazuy Cristina Guerriero Donato Rigante Susanna Esposito |
| author_facet | Chiara Sassetti Claudia Borrelli Martha Mazuy Cristina Guerriero Donato Rigante Susanna Esposito |
| author_sort | Chiara Sassetti |
| collection | DOAJ |
| description | <b>Background:</b> Juvenile scleroderma (JS) comprises a group of rare chronic autoimmune and fibrosing disorders in children, primarily presenting as juvenile localized scleroderma (jLS) or juvenile systemic sclerosis (jSS). While jLS predominantly affects the skin and subcutaneous tissues, jSS may involve multiple internal organs and is associated with increased morbidity and mortality. Due to the scarcity of pediatric-specific clinical trials, the current treatment strategies are largely empirical and often adapted from adult protocols. <b>Objective:</b> This narrative review aims to provide a comprehensive update on emerging systemic therapies for juvenile scleroderma, focusing on biologics, small molecule inhibitors, and advanced cellular interventions, to support the development of more personalized and effective pediatric treatment approaches. <b>Methods:</b> A literature search was conducted through PubMed and a manual bibliographic review, covering publications from 2001 to 2024. Only English-language studies involving pediatric populations were included, comprising randomized controlled trials, reviews, and case reports. Additional searches were performed for drugs that are specifically used in juvenile scleroderma. <b>Results</b>: Biologic agents such as tocilizumab, rituximab, and abatacept, along with small molecules including Janus kinase (JAK) inhibitors and imatinib, have demonstrated potential in managing refractory cases by reducing skin fibrosis and pulmonary involvement. Novel approaches—such as pamrevlumab, nintedanib, and chimeric antigen receptor (CAR-T) cell therapy—target fibrotic and autoimmune pathways but remain investigational in children. Autologous stem cell transplantation (ASCT) has also been explored in severe, treatment-resistant cases, although data are extremely limited. The overall evidence base is constrained by small sample sizes, a lack of controlled pediatric trials, and reliance on adult extrapolation. <b>Conclusions:</b> While innovative systemic therapies show promise for juvenile scleroderma, their widespread clinical application remains limited by insufficient pediatric-specific evidence. Large, multicenter, long-term trials are urgently needed to establish safety, efficacy, and optimal treatment algorithms that are tailored to the pediatric population. |
| format | Article |
| id | doaj-art-79b51ee434284586979bd9016838d86d |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-79b51ee434284586979bd9016838d86d2025-08-20T03:47:58ZengMDPI AGPharmaceuticals1424-82472025-04-0118564310.3390/ph18050643New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive ReviewChiara Sassetti0Claudia Borrelli1Martha Mazuy2Cristina Guerriero3Donato Rigante4Susanna Esposito5Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyPediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyPediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyUnit of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyDepartment of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyPediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy<b>Background:</b> Juvenile scleroderma (JS) comprises a group of rare chronic autoimmune and fibrosing disorders in children, primarily presenting as juvenile localized scleroderma (jLS) or juvenile systemic sclerosis (jSS). While jLS predominantly affects the skin and subcutaneous tissues, jSS may involve multiple internal organs and is associated with increased morbidity and mortality. Due to the scarcity of pediatric-specific clinical trials, the current treatment strategies are largely empirical and often adapted from adult protocols. <b>Objective:</b> This narrative review aims to provide a comprehensive update on emerging systemic therapies for juvenile scleroderma, focusing on biologics, small molecule inhibitors, and advanced cellular interventions, to support the development of more personalized and effective pediatric treatment approaches. <b>Methods:</b> A literature search was conducted through PubMed and a manual bibliographic review, covering publications from 2001 to 2024. Only English-language studies involving pediatric populations were included, comprising randomized controlled trials, reviews, and case reports. Additional searches were performed for drugs that are specifically used in juvenile scleroderma. <b>Results</b>: Biologic agents such as tocilizumab, rituximab, and abatacept, along with small molecules including Janus kinase (JAK) inhibitors and imatinib, have demonstrated potential in managing refractory cases by reducing skin fibrosis and pulmonary involvement. Novel approaches—such as pamrevlumab, nintedanib, and chimeric antigen receptor (CAR-T) cell therapy—target fibrotic and autoimmune pathways but remain investigational in children. Autologous stem cell transplantation (ASCT) has also been explored in severe, treatment-resistant cases, although data are extremely limited. The overall evidence base is constrained by small sample sizes, a lack of controlled pediatric trials, and reliance on adult extrapolation. <b>Conclusions:</b> While innovative systemic therapies show promise for juvenile scleroderma, their widespread clinical application remains limited by insufficient pediatric-specific evidence. Large, multicenter, long-term trials are urgently needed to establish safety, efficacy, and optimal treatment algorithms that are tailored to the pediatric population.https://www.mdpi.com/1424-8247/18/5/643juvenile sclerodermasystemic sclerosischildhoodpersonalized medicineinnovative biotechnologies |
| spellingShingle | Chiara Sassetti Claudia Borrelli Martha Mazuy Cristina Guerriero Donato Rigante Susanna Esposito New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review Pharmaceuticals juvenile scleroderma systemic sclerosis childhood personalized medicine innovative biotechnologies |
| title | New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review |
| title_full | New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review |
| title_fullStr | New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review |
| title_full_unstemmed | New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review |
| title_short | New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review |
| title_sort | new challenging systemic therapies for juvenile scleroderma a comprehensive review |
| topic | juvenile scleroderma systemic sclerosis childhood personalized medicine innovative biotechnologies |
| url | https://www.mdpi.com/1424-8247/18/5/643 |
| work_keys_str_mv | AT chiarasassetti newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview AT claudiaborrelli newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview AT marthamazuy newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview AT cristinaguerriero newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview AT donatorigante newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview AT susannaesposito newchallengingsystemictherapiesforjuvenilesclerodermaacomprehensivereview |