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Zhang C, Wang C, Gao S, Ma M, Wang W, Zhang T, Zhang Y, Tang X, Li Z, Sun Z, Wang L, Jin H, Zeng X, Song H. Application of the Scleroderma Clinical Trials Consortium Damage Index in patients with juvenile systemic sclerosis. Pediatr Rheumatol Online J 2025; 23:53. [PMID: 40369653 PMCID: PMC12079982 DOI: 10.1186/s12969-025-01110-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 05/08/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Juvenile systemic sclerosis (jSSc) can lead to permanent and irreversible anatomical or physiological dysfunction. The Scleroderma Clinical Trials Consortium-Damage Index (SCTC-DI), which has been employed and validated in adult patients, can quantify organ damage and predict mortality and morbidity. However, its application in paediatric patients remains unexplored. METHODS Clinical data, laboratory results, and prognostic information were collected for patients with jSSc at Peking Union Medical College Hospital (PUMCH) from January 2012 and January 2024. Differences between the SCTC-DI and the juvenile systemic sclerosis severity score (J4S) were recorded and compared. Furthermore, we compared the SCTC-DI between jSSc and adult systemic sclerosis (SSc) patients. RESULTS A total of 64 jSSc patients were included. Facet joint contractures, fingertip ulcers and interstitial lung disease are common manifestations. Compared with adult SSc patients, jSSc patients had a lower incidence of gastrointestinal and urinary system involvement. The baseline J4S levels were significantly correlated with SCTC-DI levels at follow-up. A higher baseline SCTC-DI score was associated with a greater progression of organ damage (P = 0.001). CONCLUSION There are differences in clinical presentations between adult SSc patients and jSSc patients. The SCTC-DI can be applied to JSSc patients, and it is recommended that JSSc patients undergo regular evaluations of the J4S as well as the SCTC-DI.
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Affiliation(s)
- Caihui Zhang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Changyan Wang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Sihao Gao
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Mingsheng Ma
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Wei Wang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Tianyu Zhang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Yu Zhang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Xiaoyan Tang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Zhuo Li
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Zhixing Sun
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Lin Wang
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Hongzhong Jin
- Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hongmei Song
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
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Ciurtin C, Jelusic M, Ozen S. Do We Need Distinct Pediatric Classification Criteria for Rheumatic Diseases That Affect Both Children and Adults? Arthritis Rheumatol 2025; 77:521-525. [PMID: 39542846 PMCID: PMC12039469 DOI: 10.1002/art.43058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/31/2024] [Accepted: 11/06/2024] [Indexed: 11/17/2024]
Affiliation(s)
- Coziana Ciurtin
- Centre for Adolescent RheumatologyUniversity College LondonLondonUnited Kingdom
| | - Marija Jelusic
- University Hospital Center Zagreb, University of Zagreb School of MedicineZagrebCroatia
| | - Seza Ozen
- Hacettepe University Faculty of MedicineAnkaraTürkiye
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Sassetti C, Borrelli C, Mazuy M, Guerriero C, Rigante D, Esposito S. New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review. Pharmaceuticals (Basel) 2025; 18:643. [PMID: 40430462 PMCID: PMC12114888 DOI: 10.3390/ph18050643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2025] [Revised: 04/20/2025] [Accepted: 04/23/2025] [Indexed: 05/29/2025] Open
Abstract
Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
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Affiliation(s)
- Chiara Sassetti
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (C.S.); (C.B.); (M.M.)
| | - Claudia Borrelli
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (C.S.); (C.B.); (M.M.)
| | - Martha Mazuy
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (C.S.); (C.B.); (M.M.)
| | - Cristina Guerriero
- Unit of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Donato Rigante
- Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
- Università Cattolica Sacro Cuore, 00168 Rome, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; (C.S.); (C.B.); (M.M.)
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Liguoro I, Simonini G, Martini G. The burden of extracutaneous manifestations in juvenile localized scleroderma: A literature review. Autoimmun Rev 2025; 24:103812. [PMID: 40189033 DOI: 10.1016/j.autrev.2025.103812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 04/14/2025]
Abstract
OBJECTIVES Juvenile Localized Scleroderma (JLS) is an autoimmune disease leading to fibrosis of skin and subcutaneous tissues affecting children, that is characterized by extracutaneous manifestations (ECM) in about 20 % of patients. JLS and ECM can cause severe disabilities, potentially impacting patients' quality of life (QoL). We aimed to systematically review studies reporting ECM in young patients with JLS. METHODS Pubmed, Cochrane and Scopus databases were approached to identify studies evaluating ECM in children with LS. Selected papers focusing on QoL and multidisciplinary approach were separately analysed. RESULTS At the end of the selection process, 15 papers (encompassing 3604 children) focused on the description of ECM were included. Overall, ECM were reported in 958/3604 (26.5 %) children, and the 3 most frequent ones were musculoskeletal (24 %), neurological (10.3 %) and odontostomatological (7.6 %). Six papers (435 patients) focusing on QoL in children with JLS resulted comparable. Three studies focusing on the role of a multidisciplinary team in the management of children and adolescents with JLS and ECM were also selected (216 children). CONCLUSIONS Almost one-third of patients with JLS may present several clinical problems other than skin lesions that should be managed by a multidisciplinary team. However, evidence on the efficacy of a multispecialty management is still lacking. The impact of ECM on QoL of these patients may be underestimated, as no specifically developed assessment tool has been applied so far, but recently proposed overall disease severity and disease-specific patient-reported outcome measures may improve the evaluation of this important clinical aspect.
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Affiliation(s)
- Ilaria Liguoro
- Pediatric Division, University Hospital S Maria della Misericordia, Udine, Italy
| | - Gabriele Simonini
- Rheumatology Unit, ERN ReCONNET center, Meyer Children's Hospital IRCCS, Italy; Neurofarba Department, University of Florence, Italy
| | - Giorgia Martini
- Pediatric Division, University Hospital S Maria della Misericordia, Udine, Italy; Department of Medicine, University of Udine, Udine, Italy.
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Jacquel L, Bechara R, Terzic J, Rameau AC, Chatelus E, Rossi-Semerano L, Kone-Paut I, Meinzer U, Lemelle I, Rebelle C, Urbina D, Pillet P, Choquet P, El Maamari J, Zaloszyc A. An updated overview of Juvenile systemic sclerosis in a French cohort. Pediatr Rheumatol Online J 2025; 23:13. [PMID: 39923051 PMCID: PMC11807294 DOI: 10.1186/s12969-024-01043-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 12/01/2024] [Indexed: 02/10/2025] Open
Abstract
BACKGROUND Systemic sclerosis encompasses a range of disorders characterized by vascular and connective tissue abnormalities. Although rare in pediatrics, juvenile systemic sclerosis (jSSc) is a severe and life-threatening condition that significantly impacts children's development. This study aimed to provide an overview of JSSc in France over the past decade. METHODS Patients with disease onset before the age of 16 were included following a request for observations sent via email to member practitioners of the SOFREMIP (French pediatric Rheumatology society). RESULTS Our study included 18 patients from 8 different French centers. While our cohort exhibited a balanced distribution between limited and diffuse subsets of the disease, we observed a higher prevalence of the diffuse subset in children above the age of 10. Skin induration was the most reported symptom, while Raynaud's phenomenon was present in 61% of the children at initial clinical evaluation. All children tested positive for antinuclear antibodies, with anti-Scl70 being the most common specificity, even among children with limited cutaneous subsets. Interestingly, we found a high sensitivity of the ACR / EULAR criteria for diagnosing jSSc in our cohort with 83% of patients meeting these criteria, except for 3 children who presented with overlap syndromes. Despite the frequent use of corticosteroids at the onset, no deaths or renal crises were reported. Three patients received treatment with biological agents, specifically Rituximab and Tocilizumab. CONCLUSION JSSc is a rare but severe disease requiring rapid, specialized, and multidisciplinary care. Further studies are needed to validate proper diagnosis criteria including overlap syndromes and evaluate the use of biotherapies in children.
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Affiliation(s)
- Léa Jacquel
- Department of Clinical Immunology and Internal Medicine, University Hospital of Strasbourg, Strasbourg, France.
- Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France.
| | - Rouba Bechara
- Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France
| | - Joëlle Terzic
- Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France
| | - Anne-Cécile Rameau
- Department of Pediatrics, Groupe Hospitalier de la région de Mulhouse et Sud Alsace, Mulhouse, France
| | - Emmanuel Chatelus
- Department of Rheumatology, University Hospital of Strasbourg, Strasbourg, France
| | - Linda Rossi-Semerano
- Department of Paediatric Rheumatology, CEREMAIA, Hôpital de Bicêtre, APHP, Le Kremlin Bicêtre, France
| | - Isabelle Kone-Paut
- Department of Paediatric Rheumatology, CEREMAIA, Hôpital de Bicêtre, APHP, Le Kremlin Bicêtre, France
| | - Ulrich Meinzer
- Department of General Pediatrics, Hôpital Robert Debré, Paris, France
| | - Irène Lemelle
- Department of Pediatrics, Nancy University Hospital, Nancy, France
| | - Charlotte Rebelle
- Department of Pediatrics, Hôpital Marseille Saint Joseph, Marseille, France
| | - Diego Urbina
- Department of Pediatrics, University Hospital of Marseille, Marseille, France
| | - Pascal Pillet
- Department of Pediatrics, Pellegrin Hôpital des enfants, University Hospital of Bordeaux, Bordeaux, France
| | - Pauline Choquet
- Department of Pediatrics, Hospital of Annecy Genevois, Annecy, France
| | - Jad El Maamari
- Division of Pediatric Hematology / Oncology, BC Children's Hospital, Vancouver, Canada
| | - Ariane Zaloszyc
- Department of Pediatrics, University Hospital of Strasbourg, Strasbourg, France
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Kalampokis I, Wong CS, Ma J, Smith LM, Masten BJ, Chabot-Richards D, Pisetsky DS. The Limitation of HLA Diversity as a Risk Factor for Pediatric-Onset Autoimmune Rheumatic Disease. J Clin Med 2025; 14:916. [PMID: 39941587 PMCID: PMC11818087 DOI: 10.3390/jcm14030916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/22/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: HLA homozygosity of specific alleles at a single locus is associated with increased risk for autoimmunity and/or more severe clinical phenotypes. However, the contribution of the overall limitation of HLA diversity across multiple loci to autoimmunity risk remains to be determined. Methods: We conducted a proof-of-concept case-control study of 413 individuals (279 cases with pediatric-onset autoimmune rheumatic diseases, 134 matched controls) examining the "Limitation of HLA Diversity" (LoHLAD) across multiple loci as an allele-independent risk factor for autoimmunity. We examined the association of LoHLAD with pediatric-onset autoimmune rheumatic diseases at five HLA loci (A, B, DQB1, DRB1, DRB3/4/5). LoHLAD was defined as (1) homozygosity at any of the examined loci, and/or (2) the presence of a single allele or the complete lack of an allele at the HLA-DRB3/4/5 locus. Results: The frequency of LoHLAD at any locus was significantly higher in cases compared to controls (65.95% vs. 30.60%, OR 4.39 [2.82-6.84], p < 0.0001). Higher frequencies of LoHLAD in cases compared to controls were observed at both class I (19.35% vs. 10.45%, OR 2.06 [1.10-3.86], p = 0.031) and class II (54.48% vs. 20.15%, OR 4.74 [2.92-7.69], p < 0.0001) loci. Specifically, significant differences between cases and controls were observed at the B (OR 8.63 [1.14-65.55], p = 0.016), DQB1 (OR 3.34 [1.27-8.78], p = 0.016), and DRB3/4/5 (OR 4.64 [2.77-7.75], p < 0.0001) loci. Multiple logistic regression models confirmed the ability of LoHLAD to positively predict autoimmunity. Conclusions: LoHLAD is a significant allele-independent risk factor for pediatric-onset autoimmune rheumatic disease.
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Affiliation(s)
- Ioannis Kalampokis
- University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.M.); (L.M.S.)
- University of New Mexico, Albuquerque, NM 87106, USA; (C.S.W.); (B.J.M.); (D.C.-R.)
| | - Craig S. Wong
- University of New Mexico, Albuquerque, NM 87106, USA; (C.S.W.); (B.J.M.); (D.C.-R.)
| | - Jihyun Ma
- University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.M.); (L.M.S.)
| | - Lynette M. Smith
- University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.M.); (L.M.S.)
| | - Barbara J. Masten
- University of New Mexico, Albuquerque, NM 87106, USA; (C.S.W.); (B.J.M.); (D.C.-R.)
- Tricore Reference Laboratories, Albuquerque, NM 87102, USA
| | | | - David S. Pisetsky
- Duke University Medical Center, Durham, NC 27710, USA;
- Durham Veterans Administration Medical Center, Durham, NC 27705, USA
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Durmus S, Sahin S, Adrovic A, Barut K, Gelisgen R, Uzun H, Kasapcopur O. Interplay of NF-κB and PPAR-γ transcription factors in patients with juvenile systemic lupus erythematosus. Lupus Sci Med 2025; 12:e001263. [PMID: 39779243 PMCID: PMC11751921 DOI: 10.1136/lupus-2024-001263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 11/22/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVE Juvenile SLE (jSLE) is an autoimmune disease characterised by the presence of high levels of autoantibodies, predominantly targeting nuclear antigens, resulting in a breakdown of self-tolerance. However, its pathogenesis is multifactorial and poorly understood. The aim of this study was to evaluate the potential of nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as biomarkers for jSLE. METHODS In this study, serum NF-κB and PPAR-γ levels were determined by immunoassay in 42 patients with jSLE. In addition, 19 juvenile systemic sclerosis (jSSc) and 25 age-matched healthy children were selected as patient control and healthy control, respectively. RESULTS Serum NF-κB levels in patients with jSLE demonstrated a positive trend towards elevation compared with the controls with no significant difference (p=0.030). In addition, serum NF-κB levels in patients with jSSc were significantly higher than that of the healthy controls (p=0.005). Serum PPAR-γ levels were tend to be lower in both patients with jSLE and jSSc compared with the controls, with no significant difference. Specifically, NF-κB levels were significantly higher in patients with jSLE with cumulative damage (PedSDI≥1) compared with those without, at p=0.044. Logistic regression showed that PPAR-γ levels lower than 2.42 ng/mL were associated with the development of jSLE (OR 7.59) and lower than 2.16 ng/mL for jSSc (OR 10.90). The combined high levels of NF-κB with low PPAR-γ increased the risk of developing jSSc by 21.33-fold. CONCLUSIONS The observed trend of elevated NF-κB levels and decreased PPAR-γ levels in our study suggests their potential as biomarkers associated with increased proinflammatory signalling in jSLE and jSSc. However, our findings must be regarded as hypothesis-generating and confirmed in larger datasets. Moreover, their roles in monitoring the course of a disease and guiding therapeutic strategies in juvenile systemic autoimmune diseases need to be clearly investigated. Further extension of these findings may lead to better management and improvement in the outcomes of such patients.
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Affiliation(s)
- Sinem Durmus
- Department of Medical Biochemistry, İzmir Katip Çelebi University Faculty of Medicine, Izmir, Türkiye
| | - Sezgin Sahin
- Department of Child Health and Diseases, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
| | - Amra Adrovic
- Department of Child Health and Diseases, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
| | - Kenan Barut
- Department of Child Health and Diseases, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
| | - Remise Gelisgen
- Department of Medical Biochemistry, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
| | - Hafize Uzun
- Department of Medical Biochemistry, Istanbul Atlas University Faculty of Medicine, Istanbul, Türkiye
| | - Ozgur Kasapcopur
- Department of Child Health and Diseases, Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
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Di Pasquale G, Caione N, Di Berardino A, Di Donato G. Pulmonary manifestations of juvenile vs. adult systemic sclerosis: insights into pathophysiological and clinical features. Pediatr Pulmonol 2025; 60:e27347. [PMID: 39545645 DOI: 10.1002/ppul.27347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/16/2024] [Accepted: 10/08/2024] [Indexed: 11/17/2024]
Abstract
Juvenile systemic sclerosis (jSSc), the pediatric counterpart of systemic sclerosis (SSc), is a rare autoimmune disorder characterized by vasculopathy and fibrotic disorders. It ranks among the rheumatologic diseases with the highest rates of morbidity and mortality, predominantly impacting females. Although a universally accepted classification for jSSc remains elusive, a provisional classification proposed in 2007 integrates major and minor criteria, reflecting the involvement of diverse organs and tissues. Pulmonary manifestations are relatively common in jSSc, occurring in 36% to 55% of cases. Particularly lung complications include children s interstitial lung disease (chILD), pulmonary arterial hypertension (PAH) and nodules. The aim of this paper is to describe the main pulmonary manifestations of patients with jSSc in relation to SSc, highlighting fundamental pathophysiological, and clinical features based on the latest literature data.
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Affiliation(s)
| | - Nicholas Caione
- Pediatric Department, University of L'Aquila, L'Aquila, Italy
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Sahu UP, Hasan O, Kumari Y, Mobin N, Shankar M. A Rare Case of Juvenile Systemic Sclerosis With Concurrent Disseminated Tuberculosis: Diagnostic and Therapeutic Challenges. Cureus 2024; 16:e75136. [PMID: 39640412 PMCID: PMC11618662 DOI: 10.7759/cureus.75136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2024] [Indexed: 12/07/2024] Open
Abstract
We present the case of a 13-year-old female diagnosed with juvenile systemic sclerosis, diffuse cutaneous subtype, along with active disseminated tuberculosis. This co-occurrence poses unique diagnostic and therapeutic challenges, particularly given the risk of tuberculosis exacerbation due to immunosuppressive therapy required for systemic sclerosis. The patient had signs/symptoms like progressive skin tightening and Raynaud's phenomenon; the diagnosis was confirmed by the presence of anti-Scl-70 antibodies. Concurrently, active disseminated tuberculosis was identified by a cartridge-based nucleic acid amplification test (CBNAAT) and supported by high-resolution computed tomography (HRCT) thorax and fine needle aspiration cytology (FNAC) of the submandibular lymph node. Treatment involved anti-tuberculosis therapy prior to initiating immunosuppression, ensuring a careful balance between managing autoimmunity and infection. The case emphasizes the importance of multidisciplinary collaboration and vigilant follow-up in managing complex autoimmune conditions coexisting with infectious diseases. Early diagnosis and an individualized approach were crucial to achieving clinical improvement in this adolescent pediatric patient.
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Affiliation(s)
- Upendra Prasad Sahu
- Department of Pediatrics, Rajendra Institute of Medical Sciences, Ranchi, IND
| | - Omar Hasan
- Department of Pediatrics, Rajendra Institute of Medical Sciences, Ranchi, IND
| | - Yuthika Kumari
- Department of Pediatrics, Rajendra Institute of Medical Sciences, Ranchi, IND
| | - Naghma Mobin
- Department of Pediatrics, Rajendra Institute of Medical Sciences, Ranchi, IND
| | - Mani Shankar
- Department of Pediatrics, Rajendra Institute of Medical Sciences, Ranchi, IND
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10
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Denton CP, De Lorenzis E, Roblin E, Goldman N, Alcacer-Pitarch B, Blamont E, Buch MH, Carulli M, Cotton C, Del Galdo F, Derrett-Smith E, Douglas K, Farrington S, Fligelstone K, Gompels L, Griffiths B, Herrick A, Hughes M, Pain C, Pantano G, Pauling JD, Prabu A, O’Donoghue N, Renzoni EA, Royle J, Samaranayaka M, Spierings J, Tynan A, Warburton L, Ong VH. The 2024 British Society for Rheumatology guideline for management of systemic sclerosis. Rheumatology (Oxford) 2024; 63:2956-2975. [PMID: 39255973 PMCID: PMC11534099 DOI: 10.1093/rheumatology/keae394] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 06/06/2024] [Indexed: 09/12/2024] Open
Abstract
This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1.
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Affiliation(s)
| | - Enrico De Lorenzis
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Elen Roblin
- Centre for Rheumatology, Royal Free London NHS Foundation Trust, London, UK
| | - Nina Goldman
- Division of Medicine, University College London, London, UK
| | | | | | - Maya H Buch
- Department of Rheumatology, University of Manchester, Manchester, UK
| | - Maresa Carulli
- Department of Rheumatology, Hammersmith Hospitals NHS Foundation Trust, London, UK
| | - Caroline Cotton
- Department of Rheumatology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Francesco Del Galdo
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | | | - Karen Douglas
- Department of Rheumatology, The Dudley Group NHS Foundation Trust, Dudley, UK
| | | | - Kim Fligelstone
- Centre for Rheumatology, Royal Free London NHS Foundation Trust, London, UK
| | - Luke Gompels
- Department of Rheumatology, Somerset NHS Foundation Trust, Taunton, UK
| | | | - Ariane Herrick
- Department of Rheumatology, University of Manchester, Manchester, UK
| | - Michael Hughes
- Department of Rheumatology, University of Manchester, Manchester, UK
| | - Clare Pain
- Department of Rheumatology, Alder Hey Childrens Hospital, Liverpool, UK
| | | | - John D Pauling
- Department of Rheumatology, North Bristol NHS Foundation Trust, Bristol, UK
| | | | - Nuala O’Donoghue
- Department of Dermatology, Northern Care Alliance, Salford Royal, UK
| | | | - Jeremy Royle
- Department of Rheumatology, University Hospitals NHS Foundation Trust, Leicester, UK
| | | | - Julia Spierings
- Department of Rheumatology, University of Utrecht, Utrecht, Netherlands
| | - Aoife Tynan
- Centre for Rheumatology, Royal Free London NHS Foundation Trust, London, UK
| | | | - Voon H Ong
- Division of Medicine, University College London, London, UK
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11
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Tirelli F, Zanatta E, Moccaldi B, Binda M, Martini G, Giraudo C, Vittadello F, Meneghel A, Zulian F. Systemic sclerosis sine scleroderma is more aggressive in children than in adults. Rheumatology (Oxford) 2024; 63:SI215-SI218. [PMID: 38775723 DOI: 10.1093/rheumatology/keae304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 05/09/2024] [Indexed: 09/10/2024] Open
Abstract
OBJECTIVES To compare the clinical and laboratory features of paediatric SSc sine scleroderma (ssJSSc) with adult-onset ssSSc. METHODS Demographic, clinical and laboratory data of ssJSSc, retrospectively retrieved from our hospital medical records, case reports from the literature and from the Pediatric Rheumatology European Society JSSc registry, were compared with the Padua cohort of adult patients with ssSSc. Patients were defined as having ssSSc if they never had skin involvement but all the following features: (i) RP and/or digital vasculopathy, (ii) positive ANA, (iii) internal organs involvement typical of scleroderma and (iv) no other defined CTD. RESULTS Eighteen juvenile and 38 adult-onset ssSSc patients, mean disease duration 5.8 and 9.7 years, respectively, entered the study. The frequency of females affected was significantly lower in ssJSSc (38.9% vs 89.5%, P < 0.0001). When compared with adults, ssJSSc displayed fewer SSc-specific capillaroscopy abnormalities (68.8% vs 94.7%, P = 0.02) while having significantly higher vascular (digital pitting scars, ulcers 35.3% vs 10.5%, P = 0.042), respiratory (50.0% vs 23.7%, P = 0.02) and cardiac (50.0% vs 2.6%, P < 0.0001) involvement. The outcome was significantly worse in ssJSSc as six patients (33%) died (n = 3) or reached an end-stage organ failure (n = 3) in comparison with only two deaths (5.3%) in the adult cohort. ACA were significantly lower in children (20.0% vs 68.4%, P = 0.001) while no difference was noted for other SSc-specific autoantibodies. CONCLUSION Compared with adults where ssSSc generally has an indolent course, children present with aggressive disease that heralds a worse prognosis characterized by high cardiorespiratory morbidity and mortality.
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Affiliation(s)
- Francesca Tirelli
- Department of Woman's and Child's Health, University of Padua, Padua, Italy
| | - Elisabetta Zanatta
- Rheumatology Division, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Beatrice Moccaldi
- Rheumatology Division, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Marco Binda
- Rheumatology Division, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Giorgia Martini
- Department of Woman's and Child's Health, University of Padua, Padua, Italy
| | - Chiara Giraudo
- Unit of Advanced Clinical and Translational Imaging, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Fabio Vittadello
- Explora-Research and Statistical Analysis, Vigodarzere (Padua), Italy
| | | | - Francesco Zulian
- Department of Woman's and Child's Health, University of Padua, Padua, Italy
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12
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Samad A, Wobma H, Casey A. Innovations in the care of childhood interstitial lung disease associated with connective tissue disease and immune-mediated disorders. Pediatr Pulmonol 2024; 59:2321-2337. [PMID: 38837875 DOI: 10.1002/ppul.27068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 04/05/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024]
Abstract
Childhood interstitial lung disease (chILD) associated with connective tissue and immune mediated disorders is the second most common chILD diagnostic category. As knowledge of the molecular and genetic underpinnings of these rare disorders advances, the recognized clinical spectrum of associated pulmonary manifestations continues to expand. Pulmonary complications of these diseases, including ILD, confer increased risk for morbidity and mortality and contribute to increased complexity for providers tasked with managing the multiple organ systems that can be impacted in these systemic disorders. While pulmonologists play an important role in diagnosis and management of these conditions, thankfully they do not have to work alone. In collaboration with a multidisciplinary team of subspecialists, the pulmonary and other systemic manifestations of these conditions can be managed effectively together. The goal of this review is to familiarize the reader with the classic patterns of chILD and other pulmonary complications associated with primary immune-mediated disorders (monogenic inborn errors of immunity) and acquired systemic autoimmune and autoinflammatory diseases. In addition, this review will highlight current, emerging, and innovative therapeutic strategies and will underscore the important role of multidisciplinary management to improving outcomes for these patients.
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Affiliation(s)
- Aaida Samad
- Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Holly Wobma
- Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Alicia Casey
- Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
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13
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Ożga J, Mężyk E, Kmiecik W, Wojciechowski W, Żuber Z. Magnetic resonance imaging of the musculoskeletal system in the diagnosis of rheumatic diseases in the pediatric population. Reumatologia 2024; 62:196-206. [PMID: 39055724 PMCID: PMC11267661 DOI: 10.5114/reum/190262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 06/20/2024] [Indexed: 07/27/2024] Open
Abstract
Magnetic resonance imaging (MRI) of the musculoskeletal system is an examination increasingly performed for suspected juvenile idiopathic arthritis, chronic nonbacterial osteomyelitis and juvenile idiopathic inflammatory myopathies, as well as other rheumatic diseases of developmental age. T1-, T2- and PD-weighted with or without fat suppression or short tau inversion recovery/turbo inversion recovery magnitude (STIR/TIRM) sequences and post-contrast sequences are evaluated to diagnose pathological changes in the synovial membrane, subchondral bone marrow and surrounding soft tissues. Magnetic resonance imaging allows detection of synovitis, tenosynovitis, bursitis, and enthesitis as well as bone marrow edema and soft tissue edema. Several pediatric-specific MRI scoring systems have been developed and validated to standardize and facilitate the assessment of the extent of the inflammatory process and disease activity in MRI. Early detection of inflammatory changes allows the inclusion of comprehensive pharmacotherapy giving the possibility of permanent remission and objective measurement of the effectiveness of treatment.
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Affiliation(s)
- Joanna Ożga
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland
- Clinical Department of Pediatrics and Rheumatology, St. Louis Regional Specialised Children's Hospital, Krakow, Poland
| | - Elżbieta Mężyk
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland
- Clinical Department of Pediatrics and Rheumatology, St. Louis Regional Specialised Children's Hospital, Krakow, Poland
| | - Wojciech Kmiecik
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland
- Clinical Department of Pediatrics and Rheumatology, St. Louis Regional Specialised Children's Hospital, Krakow, Poland
| | - Wadim Wojciechowski
- Clinical Department of Pediatrics and Rheumatology, St. Louis Regional Specialised Children's Hospital, Krakow, Poland
- Department of Radiology, Jagiellonian University Medical College, Krakow, Poland
| | - Zbigniew Żuber
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland
- Clinical Department of Pediatrics and Rheumatology, St. Louis Regional Specialised Children's Hospital, Krakow, Poland
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14
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Zhang MD, Huang WY, Luo JY, He RQ, Huang ZG, Li JD, Qin F, Chen G, Lei L. The 'whole landscape' of research on systemic sclerosis over the past 73 years. Autoimmun Rev 2024; 23:103538. [PMID: 38556034 DOI: 10.1016/j.autrev.2024.103538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 04/02/2024]
Abstract
OBJECTIVE This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry. METHODS Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots. RESULTS From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations. CONCLUSION In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.
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Affiliation(s)
- Meng-Di Zhang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Wan-Ying Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Jia-Yuan Luo
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Zhi-Guang Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Jian-Di Li
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Fang Qin
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China.
| | - Ling Lei
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China.
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15
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Kim YD. Juvenile systemic sclerosis. JOURNAL OF RHEUMATIC DISEASES 2024; 31:65-67. [PMID: 38562277 PMCID: PMC10973353 DOI: 10.4078/jrd.2024.0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 04/04/2024]
Affiliation(s)
- Young Dae Kim
- Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
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16
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Felix A, Osei L, Delion F, Suzon B, Abel A, Drame M, Hatchuel Y, Deligny C, Louis-Sidney F. Longitudinal follow-up of mixed connective tissue disease and overlapping autoimmune diseases of childhood onset in the Afro-descendant population of the French West Indies. Pediatr Rheumatol Online J 2024; 22:13. [PMID: 38212775 PMCID: PMC10785358 DOI: 10.1186/s12969-023-00951-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/26/2023] [Indexed: 01/13/2024] Open
Abstract
INTRODUCTION Overlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood. METHODS Retrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa's criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM). RESULTS Sixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4-17) with median follow up of 7.9 years (2.1-19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1-7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure. CONCLUSION This is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.
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Affiliation(s)
- Arthur Felix
- Department of General Pediatrics, Competence Centre for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE) Antilles-GuyaneEpiCliV Research Unit, University of the French West Indies, Martinique University Hospital, Fort-de France, France.
- MFME, CHU de la Martinique La Meynard, Fort-de-France, 97261, France.
| | - Lindsay Osei
- Department of Pediatrics, Andrée Rosemon Hospital, Cayenne, France
| | - Frederique Delion
- Department of Pediatrics, Guadeloupe University Hospital, Pointe-à-Pitre, France
| | - Benoit Suzon
- Department of Internal Medicine, Martinique University Hospital, Fort-de-France, France
| | - Aurore Abel
- Department of Internal Medicine, Martinique University Hospital, Fort-de-France, France
| | - Moustapha Drame
- Department of Clinical Research and Innovation, Martinique University Hospital, Fort-de-France, France
| | - Yves Hatchuel
- Department of General Pediatrics, Competence Centre for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE) Antilles-GuyaneEpiCliV Research Unit, University of the French West Indies, Martinique University Hospital, Fort-de France, France
| | - Christophe Deligny
- Department of Internal Medicine, Martinique University Hospital, Fort-de-France, France
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17
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Jeong JE, Kim SH. Clinical characteristics of juvenile systemic sclerosis in Korea: 31-year single-center study. JOURNAL OF RHEUMATIC DISEASES 2024; 31:25-32. [PMID: 38130955 PMCID: PMC10730803 DOI: 10.4078/jrd.2023.0046] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/28/2023] [Accepted: 10/30/2023] [Indexed: 12/23/2023]
Abstract
Objective To evaluate the clinical and laboratory characteristics, therapeutic drugs, and prognosis of juvenile systemic sclerosis (JSSc) at a single center in Korea. Methods This study was a retrospective analysis of patients with JSSc aged <16 years at disease onset and who were treated at our hospital between January 1992 and April 2023. All patients met the Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc, and those with localized scleroderma (morphea) were excluded. Results Among the 13 patients, proximal skin sclerosis (100%), Raynaud's phenomenon (RP) (84.6%), and sclerodactyly (69.2%) were present at the time of diagnosis. The most common symptom before diagnosis was RP, which was present in 10 patients (76.9%), whereas proximal skin sclerosis was observed in only five patients (38.5%). Thirteen patients had positive anti-nuclear antibody (ANA). At the time of diagnosis, five individuals had findings suggestive of interstitial lung disease (ILD) on a pulmonary function test (PFT) or chest computed tomography (CT), two of whom were asymptomatic. During follow-up, three patients developed ILD, one developed renal dysfunction, one developed heart disease, and none died. Conclusion This study was the first descriptive analysis of clinical features of JSSc in South Korea. Clinical suspicion is essential for diagnosing JSSc in patients with RP, especially if ANA is positive; however, proximal skin sclerosis, which is crucial for diagnosing JSSc, was unrecognized in the early phase of the disease. PFT should be considered even if a patient is asymptomatic or has normal chest CT.
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Affiliation(s)
- Ji Eun Jeong
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seong Heon Kim
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
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18
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Klotsche J, Torok KS, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, Katsicas M, Sztajnbok F, Marrani E, Sifuentes-Giraldo A, Stanevicha V, Anton J, Feldmann B, Kostik M, Nemcova D, Santos MJ, Appenzeller S, Avcin T, Battagliotti C, Berntson L, Bica B, Brunner J, Eleftheriou D, Harel L, Horneff G, Kallinich T, Minden K, Nielsen S, Patwardhan A, Helmus N, Foeldvari I. Application and performance of disease activity indices proposed for patients with systemic sclerosis in an international cohort of patients with juvenile systemic sclerosis. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2023; 8:183-191. [PMID: 37744052 PMCID: PMC10515993 DOI: 10.1177/23971983231164700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 02/25/2023] [Indexed: 09/26/2023]
Abstract
OBJECTIVES Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. METHODS The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians' and the patients' global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. RESULTS Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. CONCLUSION Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.
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Affiliation(s)
- Jens Klotsche
- German Rheumatism Research Center, A Leibniz Institute, Berlin, Germany
| | - Kathryn S Torok
- University of Pittsburgh, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | | | | | - Maria Katsicas
- Hospital de Pediatria J.P. Garrahan, Buenos Aires, Argentine
| | | | | | | | - Valda Stanevicha
- Department of Pediatrics, Riga Stradins University, University Children Hospital, Riga, Latvia
| | - Jordi Anton
- Pediatric Rheumatology, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
| | - Brian Feldmann
- SickKids, The Hospital for Sick Children, Toronto, ON, Canada
| | - Mikhail Kostik
- Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russia
| | | | | | - Simone Appenzeller
- School of Medical Science, State University of Campinas, Campinas, Brazil
| | - Tadej Avcin
- University Children’s Hospital, University Medical Center Ljubljana, Ljubljana, Slovenia
| | | | - Lillemor Berntson
- Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
| | - Blanca Bica
- Hospital Universitário Clementino Fraga Filho (HUCFF), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jürgen Brunner
- Department of Pediatrics, Pediatric Rheumatology, Medical University Innsbruck, Innsbruck, Austria
| | | | - Liora Harel
- Schneider Children’s Medical Center, Tel Aviv University, Petah Tikva, Israel
| | - Gerd Horneff
- Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany
| | - Tilmann Kallinich
- Charité University Medicine and German Rheumatism Research Center Berlin, Berlin, Germany
| | - Kirsten Minden
- German Rheumatism Research Center, A Leibniz Institute, Berlin, Germany
- Charité University Medicine and German Rheumatism Research Center Berlin, Berlin, Germany
| | | | | | - Nicola Helmus
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | - Ivan Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
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19
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Adrovic A, Karatemiz G, Esatoglu SN, Yildiz M, Sahin S, Barut K, Ugurlu S, Hatemi G, Kasapcopur O, Seyahi E. Juvenile and adult-onset scleroderma: Different clinical phenotypes. Semin Arthritis Rheum 2023; 60:152197. [PMID: 37031645 DOI: 10.1016/j.semarthrit.2023.152197] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023]
Abstract
OBJECTIVES Systemic sclerosis (SSc) represents extremely rare disease with majority of data coming from adults. Studies comparing juvenile- (jSSc) and adult-onset (aSSc) patients are limited. We aimed to compare clinical features, treatment modalities and survival rates of jSSc and aSSc patients. METHODS A retrospective study among pediatric and adult Scl patients has been performed. Demographic characteristics, clinical features, autoantibody profiles, and treatment data were retrieved from the databases. Survival analysis was done using Kaplan-Meier plot and factors associated with mortality were identified with multiple regression analysis. RESULTS A total of 158 adults and 58 juvenile Scl patients were identified. The mean age at the disease onset was 37±14.7 vs. 8.8 ± 4.1 years, mean age at diagnosis 42±15.2 vs. 10.4 ± 3.8 years and mean follow-up duration was 6.3 ± 4.9 years vs. 6.6 ± 4.9 years for aSSc and jSSc patients, respectively. The frequency of interstitial lung disease (ILD) (50.9% vs 30%, p<0.001) and systemic hypertension (17.9% vs 0, p = 0.009) was significantly higher among aSSc. While aSSc patients had presented mostly with limited cutaneous subset (74.1%), diffuse cutaneous subset was the dominant subset among jSSc (76.7%), (p<0.001). The mortality rate was significantly higher among adults (p = 0.005). The ILD (p = 0.03) and cardiac insufficiency (p = 0.05) were independent risk factors of mortality in both aSSc and jSSc patients. CONCLUSION Juvenile and adult-onset Scl represent rarely seen conditions with different clinical phenotypes. Pediatric patients with LS are more commonly seen by pediatric rheumatologists, in contrary to adults. Diffuse disease subset is the dominant form among juvenile patients, whereas limited form is the main disease subset among adults. On the other hand, juvenile-onset patients have a better survival than those with adult-onset.
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Affiliation(s)
- A Adrovic
- Koc University Hospital, Department of Pediatric Rheumatology, Turkey
| | - G Karatemiz
- Istanbul Sisli Hamidiye Etfal Training and Research Hospital, Rheumatology Department, Turkey
| | - S N Esatoglu
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Rheumatology, Turkey
| | - M Yildiz
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Pediatric Rheumatology, Turkey
| | - S Sahin
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Pediatric Rheumatology, Turkey
| | - K Barut
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Pediatric Rheumatology, Turkey
| | - S Ugurlu
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Rheumatology, Turkey
| | - G Hatemi
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Rheumatology, Turkey
| | - O Kasapcopur
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Pediatric Rheumatology, Turkey
| | - E Seyahi
- Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Department of Rheumatology, Turkey.
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20
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Johnson SR, Foeldvari I. Approach to Systemic Sclerosis Patient Assessment. Rheum Dis Clin North Am 2023; 49:193-210. [PMID: 37028831 DOI: 10.1016/j.rdc.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
Abstract
Systemic sclerosis (SSc) is a heterogeneous disease comprising of a wide spectrum of ages of onset, sex-based differences, ethnic variations, disease manifestations, differential serologic profiles, and variable response to therapy resulting in reduced health-related quality of life, disability, and survival. The ability to subset groups of patients with SSc can assist with refining the diagnosis, guide appropriate monitoring, inform aggressiveness of immunosuppression, and predict prognosis. The ability to subset patients with SSc has several important practical implications for patient care.
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Mueller M, Gschwandtner ME, Emminger W, Kiener H, Schnaubelt S, Giurgea GA, Ristl R, Perkmann T, Koppensteiner R, Schlager O. Associations between nailfold capillary aberrations and autoantibodies in children and adults with Raynaud's phenomenon. RMD Open 2023; 9:e003077. [PMID: 36972928 PMCID: PMC10069575 DOI: 10.1136/rmdopen-2023-003077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/13/2023] [Indexed: 03/29/2023] Open
Abstract
OBJECTIVE To characterise associations between individual nailfold capillary aberrations with autoantibodies in a cross-sectional study on children and adults with Raynaud's phenomenon (RP). METHODS Consecutive children and adults with RP and without previously known connective tissue disease (CTD) systemically underwent nailfold capillaroscopy and laboratory tests for the presence of antinuclear antibodies (ANA). The prevalence of individual nailfold capillary aberrations and ANA was assessed, and the associations between individual nailfold capillary aberrations and ANA were analysed separately in children and adolescents. RESULTS In total, 113 children (median age 15 years) and 2858 adults (median age 48 years) with RP and without previously known CTD were assessed. At least one nailfold capillary aberration was detected in 72 (64%) of included children and in 2154 (75%) of included adults with RP (children vs adults p<0.05). An ANA titre ≥1:80, ≥1:160 or≥1:320 was observed in 29%, 21% or 16% of included children, and in 37%, 27% or 24% of screened adults, respectively. While the occurrence of individual nailfold capillary aberrations was related to the presence of an ANA titre of ≥1:80 in adults (reduced capillary density, avascular fields, haemorrhages, oedema, ramifications, dilations and giant capillaries: each p<0.001), no comparable association between nailfold capillary aberrations and ANA was observed in children with RP without previously known CTD. CONCLUSION In contrast to adults, the association between nailfold capillary aberrations and ANA might be less pronounced in children. Further studies are warranted to validate these observations in children with RP.
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Affiliation(s)
- Markus Mueller
- Division of Angiology, Department of Medicine II, Medical University of Vienna, Austria, Medical University of Vienna, Vienna, Austria
| | - Michael E Gschwandtner
- Division of Angiology, Department of Medicine II, Medical University of Vienna, Austria, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Emminger
- Department of Pediatrics, University Children's Hospital, Wien, Austria
| | - Hans Kiener
- Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Georgiana-Aura Giurgea
- Division of Angiology, Department of Medicine II, Medical University of Vienna, Austria, Medical University of Vienna, Vienna, Austria
| | - Robin Ristl
- Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Renate Koppensteiner
- Division of Angiology, Department of Medicine II, Medical University of Vienna, Austria, Medical University of Vienna, Vienna, Austria
| | - Oliver Schlager
- Division of Angiology, Department of Medicine II, Medical University of Vienna, Austria, Medical University of Vienna, Vienna, Austria
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22
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Foeldvari I, Klotsche J, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, Stanevicha V, Sztajnbok F, Anton J, Feldman B, Alexeeva E, Katsicas M, Smith V, Avcin T, Marrani E, Kostik M, Lehman T, Sifuentes-Giraldo WA, Vasquez-Canizares N, Appenzeller S, Janarthanan M, Moll M, Nemcova D, Patwardhan A, Santos MJ, Sawhney S, Schonenberg-Meinema D, Battagliotti C, Berntson L, Bica B, Brunner J, Costa-Reis P, Eleftheriou D, Harel L, Horneff G, Kaiser D, Kallinich T, Lazarevic D, Minden K, Nielsen S, Nuruzzaman F, Uziel Y, Helmus N, Torok KS. Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort. Arthritis Care Res (Hoboken) 2022; 74:1575-1584. [PMID: 33787070 DOI: 10.1002/acr.24609] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 03/01/2021] [Accepted: 03/25/2021] [Indexed: 11/10/2022]
Abstract
OBJECTIVE To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. METHODS A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. RESULTS At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.
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Affiliation(s)
- Ivan Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | | | - Ozgur Kasapcopur
- Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Amra Adrovic
- Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | | | | | - Valda Stanevicha
- Riga Stradins University, University Children Hospital, Riga, Latvia
| | | | - Jordi Anton
- Hospital Sant Joan de Déu, Esplugues, Universitat de Barcelona, Barcelona, Spain
| | - Brian Feldman
- SickKids, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Ekaterina Alexeeva
- National Medical Research Center of Children's Health, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Maria Katsicas
- Hospital de Pediatria J. P. Garrahan, Buenos Aires, Argentina
| | - Vanessa Smith
- Ghent University and Ghent University Hospital, Ghent, Belgium
| | - Tadej Avcin
- University Children's Hospital University Medical Center Ljubljana, Ljubljana, Slovenia
| | | | - Mikhail Kostik
- Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russia
| | | | | | | | | | | | | | | | | | | | | | - Dieneke Schonenberg-Meinema
- Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | | | | | - Blanca Bica
- Hospital Universitário Clementino Fraga Filho and Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | - Liora Harel
- Schneider Children's Medical Center of Israel Sackler Faculty of Medicine, Tel Aviv University, Petah-Tikva, Israel
| | - Gerd Horneff
- Asklepios Klnik Sankt Augustin, Sankt Augustin, Germany
| | - Daniela Kaiser
- Luzerner Kantonsspital, Kinderspital, Luzern, Switzerland
| | - Tilmann Kallinich
- Charité University Medicine and German Rheumatism Research Center Berlin, Berlin, Germany
| | | | - Kirsten Minden
- Charité University Medicine and German Rheumatism Research Center Berlin, Berlin, Germany
| | | | | | - Yosef Uziel
- Meir Medical Center, Kfar Saba, Tel Aviv University, Tel Aviv, Israel
| | - Nicola Helmus
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | - Kathryn S Torok
- University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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23
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Mastrangelo G, Meneghel A, Martini G, Moretti C, Zulian F. Juvenile diabetes and systemic sclerosis: just a coincidence? Pediatr Rheumatol Online J 2022; 20:81. [PMID: 36089600 PMCID: PMC9465903 DOI: 10.1186/s12969-022-00741-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 09/06/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Limited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with scleroderma-like syndromes such as diabetic sclerodactyly. While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described. CASE PRESENTATION We describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc. CONCLUSIONS LJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin. This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy.
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Affiliation(s)
- Greta Mastrangelo
- Division of Rheumatology, Department of Paediatrics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
| | - Alessandra Meneghel
- grid.5608.b0000 0004 1757 3470Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Giorgia Martini
- grid.5608.b0000 0004 1757 3470Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Carlo Moretti
- grid.5608.b0000 0004 1757 3470Diabetology Unit, Department of Women’s and Children’s Health, University of Padova, Padova, Italy
| | - Francesco Zulian
- grid.5608.b0000 0004 1757 3470Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
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24
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Melsens K, Cutolo M, Schonenberg-Meinema D, Foeldvari I, Leone MC, Mostmans Y, Badot V, Cimaz R, Dehoorne J, Deschepper E, Frech T, Hernandez-Zapata J, Ingegnoli F, Khan A, Krasowska D, Lehmann H, Makol A, Mesa-Navas MA, Michalska-Jakubus M, Müller-Ladner U, Nuño-Nuño L, Overbury R, Pizzorni C, Radic M, Ramadoss D, Ravelli A, Rosina S, Udaondo C, van den Berg MJ, Herrick AL, Sulli A, Smith V. Standardised nailfold capillaroscopy in children with rheumatic diseases: a worldwide study. Rheumatology (Oxford) 2022; 62:1605-1615. [PMID: 36005889 PMCID: PMC10070071 DOI: 10.1093/rheumatology/keac487] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/11/2022] [Accepted: 07/17/2022] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) versus healthy controls (HC). METHODS In consecutive jRMD children and matched HC from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. 95 patients with juvenile idiopathic arthritis (JIA), 22 with dermatomyositis (JDM), 20 with systemic lupus erythematosus (cSLE), 13 with systemic sclerosis (jSSc), 21 with localized scleroderma (lSc), 18 with mixed connective tissue disease (MCTD) and 20 with primary Raynaud's phenomenon (PRP) were included. NVC differences between juvenile subgroups and HC were calculated through multivariable regression analysis. RESULTS A total number of 6474 images were assessed from 413 subjects (mean age 12.1-years, 70.9% female). The quantitative NVC-characteristics were significantly lower (↓) or higher (↑) in the following subgroups compared to HC: For density: ↓ in jSSc, JDM, MCTD, cSLE and lSc; For dilations: ↑ in jSSc, MCTD and JDM; For abnormal shapes: ↑ JDM and MCTD; For haemorrhages: ↑ in jSSc, MCTD, JDM and cSLE. The qualitative NVC-assessment of JIA, lSc and PRP did not differ from HC, whereas the cSLE and jSSc, MCTD, JDM, cSLE subgroups showed more non-specific and scleroderma patterns respectively. CONCLUSION This analysis resulted from a pioneering registry of NVC in jRMD. The NVC-assessment in jRMD differed significantly from HC. Future prospective follow up will further elucidate the role of NVC in jRMD.
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Affiliation(s)
- Karin Melsens
- Dpt of Rheumatology, Ghent University Hospital; Dpt of Internal Medicine, Ghent University, Ghent, Belgium
| | - Maurizio Cutolo
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Dpt of Internal Medicine, University of Genova; IRCCS San Martino Polyclinic, Genoa, Italy
| | - Dieneke Schonenberg-Meinema
- Dpt of Pediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centres, Amsterdam, Netherlands
| | - Ivan Foeldvari
- Centre for Paediatric and Adolescent Rheumatology, An der Schön Klinik, Hamburg, Germany
| | - Maria C Leone
- Dpt of Rheumatology, Ghent University Hospital, Ghent, Belgium; Medical and rheumatological clinic, S. Maria Hospital, Terni, Italy
| | - Yora Mostmans
- Dpt of Immunology-Allergology, CHU Brugmann, Université Libre de Bruxelles (ULB); Dpt of Dermatology, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Valérie Badot
- Dpt of Rheumatology, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Rolando Cimaz
- Pediatric Rheumatology Unit, Gaetano Pini Hospital, Dpt of Clinical Sciences and Community Health, Research Centre for Adult and Pediatric Rheumatic Diseases, Università degli Studi di Milano, Milan, Italy
| | - Joke Dehoorne
- Dpt of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium
| | - Ellen Deschepper
- Dpt of Public Health and Primary Care, Biostatistics Unit, Ghent University, Ghent, Belgium
| | - Tracy Frech
- University of Utah, Dpt of Internal Medicine, Div of Rheumatology; Salt Lake Veterans Affair Medical Centre, Utah Vascular Research Laboratory, Salt Lake City, Utah, USA
| | | | - Francesca Ingegnoli
- Clinical Rheumatology Unit, Gaetano Pini Hospital, Dpt of Clinical Sciences and Community Health, Research Centre for Adult and Pediatric Rheumatic Diseases, Università degli Studi di Milano, Milan, Italy
| | - Archana Khan
- Dpt of Pediatric Rheumatology, SRCC Children's Hospital, Mumbai, India
| | - Dorota Krasowska
- Dpt of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Hartwig Lehmann
- Dpt of Pediatrics, University Medicine Gießen, Gießen, Germany
| | - Ashima Makol
- Div of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Miguel A Mesa-Navas
- Rheumatology Section, Clínica Universitaria Universidad Pontificia Bolivariana, Medellín, Colombia
| | | | - Ulf Müller-Ladner
- Dpt of Rheumatology and clinical immunology, Campus Kerckhoff, Justus-Liebig University, Gießen; Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
| | | | - Rebecca Overbury
- University of Utah, Dpt of Internal Medicine, Div of Rheumatology; University of Utah, Dpt of Pediatrics, Div of Pediatric Rheumatology, Salt Lake City, Utah, USA
| | - Carmen Pizzorni
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Dpt of Internal Medicine, University of Genova; IRCCS San Martino Polyclinic, Genoa, Italy
| | - Mislav Radic
- University of Utah, Dpt of Internal Medicine, Div of Rheumatology, Salt Lake City, Utah, USA; University Hospital Split, Split, Croatia
| | - Divya Ramadoss
- Dpt of Pediatric Rheumatology, SRCC Children's Hospital, Mumbai, India
| | - Angelo Ravelli
- Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini; University of Genoa, Genoa, Italy; Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Silvia Rosina
- Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Clara Udaondo
- Pediatric Rheumatology Dept., La Paz Children's Hospital, Madrid, Spain
| | - Merlijn J van den Berg
- Dpt of Pediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Ariane L Herrick
- Centre for Musculoskeletal Research, The University of Manchester; Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Alberto Sulli
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Dpt of Internal Medicine, University of Genova; IRCCS San Martino Polyclinic, Genoa, Italy
| | - Vanessa Smith
- Dpt of Rheumatology, Ghent University Hospital; Dpt of Internal Medicine, Ghent University; Unit for Molecular Immunology and Inflammation, Inflammation Research Centre, VIB-Ghent University, Ghent, Belgium
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25
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Huang H, Hu Y, Wu Y, Ding F, Xu X, Jin Y, Jin Y, Bao Y. Lung involvement in children with newly diagnosed rheumatic diseases: characteristics and associations. Pediatr Rheumatol Online J 2022; 20:71. [PMID: 35987688 PMCID: PMC9392295 DOI: 10.1186/s12969-022-00731-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 08/11/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pulmonary complications of rheumatic diseases may cause functional impairment and increase mortality. However, reports regarding detection of lung involvement in children with treatment-naive, newly diagnosed rheumatic diseases are scarce. Herein, we aimed to describe the characteristics of such patients and explore the association between lung involvement and rheumatic disease. METHODS From January 2019 to June 2021, 48 pediatric patients with treatment-naive, newly diagnosed rheumatic diseases at Department of Rheumatology and Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University were included with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) findings, and 51 age-matched healthy controls were examined based on PFTs. Univariate and multivariable logistic regression analyses were used to investigate the clinical characters and laboratory parameters associated with lung involvement in these patients. RESULTS Asymptomatic patients had a faster respiratory rate and a higher ratio of forced expiratory volume in 1 s/forced vital capacity than the controls (P < 0.05). More patients than controls were observed to have a decreased DLCO below the lower limit of normal (18 of 45 [40.0%] vs. 6 of 36, respectively; P = 0.041). Among the 48 patients, 8 (16.7%) had abnormal HRCT findings and 27 (56.3%) had abnormal PFT results. Thirty-one (64.6%) patients had lung involvement. Logistic regression revealed that increases in the erythrocyte sedimentation rate (ESR) and CD4/CD8 ratio were associated with increased odds ratio of lung involvement (1.037, 95% CI: 1.003-1.072; 9.875, 95% CI: 1.296-75.243, respectively). CONCLUSIONS Pediatric patients with treatment-naive, newly diagnosed rheumatic diseases are prone to pulmonary involvement. Increased ESR and CD4/CD8 are associated with elevated odds of lung involvement in patients. We recommend routine pulmonary evaluation in such patients, especially in high-risk patients, even in the absence of respiratory symptoms, once they are diagnosed with rheumatic disease.
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Affiliation(s)
- Hua Huang
- grid.16821.3c0000 0004 0368 8293Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678, Dongfang RD., Pudong district, Shanghai, 200127 China
| | - Yabin Hu
- grid.16821.3c0000 0004 0368 8293Department of Clinical Epidemiology and Biostatistics, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yufen Wu
- grid.16821.3c0000 0004 0368 8293Department of Respiratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fei Ding
- grid.16821.3c0000 0004 0368 8293Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678, Dongfang RD., Pudong district, Shanghai, 200127 China
| | - Xuemei Xu
- grid.16821.3c0000 0004 0368 8293Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678, Dongfang RD., Pudong district, Shanghai, 200127 China
| | - Yingying Jin
- grid.16821.3c0000 0004 0368 8293Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678, Dongfang RD., Pudong district, Shanghai, 200127 China
| | - Yanliang Jin
- Department of Rheumatology and Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678, Dongfang RD., Pudong district, Shanghai, 200127, China.
| | - Yixiao Bao
- Shanghai Tonxin Clinic, No. 118, Zhengheng RD., Yangpu district, Shanghai, 200000, China.
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26
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Allen J, Rajbhandari P, Schroer B. Systemic Sclerosis and Hypereosinophilic Syndrome in a 3-Year-Old Child. Ann Allergy Asthma Immunol 2022; 129:548-551. [PMID: 35995101 DOI: 10.1016/j.anai.2022.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 10/15/2022]
Affiliation(s)
- Jennifer Allen
- Akron Children's Hospital, One Perkins Square, Akron, OH.
| | | | - Brian Schroer
- Akron Children's Hospital, One Perkins Square, Akron, OH
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27
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Koker O, Aktay Ayaz N. Autoimmune and autoinflammatory diseases with mucocutaneous manifestations: A pediatric rheumatology perspective. Int J Dermatol 2022; 62:723-736. [PMID: 35843911 DOI: 10.1111/ijd.16352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 04/25/2022] [Accepted: 06/24/2022] [Indexed: 12/01/2022]
Abstract
The presence of mucocutaneous manifestations has clinical significance, as it may be a part of the initial presentation or activation stage of both autoimmune and autoinflammatory rheumatic diseases. The cutaneous signs may display a particular morphological and topographic distribution according to taxonomy, whereas heterogeneity is likely observed among the individuals. The review aims to cluster and systematically approach the mucocutaneous manifestations met in autoimmune and autoinflammatory rheumatic diseases of childhood. The search strategy involved a comprehensive inquiry on Web of Science, PubMed, MEDLINE, and Embase databases using relevant search terms such as "dermatologic, cutaneous, mucocutaneous, skin, rash" for each disease and category. The awareness of the distinctive mucocutaneous manifestations and their correlation with rheumatic diseases provides a convenient definition, well-timed control of the underlying condition, and prevention of cosmetic issues. In the management of rheumatic diseases, planning the pertinent differential diagnosis and determining the requirement of histopathological assessment are essential with a multidisciplinary approach to rheumatology, dermatology, and allergy-immunology specialties.
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Affiliation(s)
- Oya Koker
- Istanbul Faculty of Medicine, Department of Pediatric Rheumatology, Istanbul University, Istanbul, Turkey
| | - Nuray Aktay Ayaz
- Istanbul Faculty of Medicine, Department of Pediatric Rheumatology, Istanbul University, Istanbul, Turkey
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28
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Emi Aikawa N, Andrade Balbi V, Borba EF, Coracini Tonacio A, Maluf Elias Sallum A, Maria Arruda Campos L, Tomie Kozu K, Borges Vendramini M, Fontoura N, de Souza Azevedo A, Dias Schwarcz W, Marli Christovam Sartori A, Antonangelo L, Artur Silva C, Bonfá E. Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases. Vaccine X 2022; 10:100131. [PMID: 34977552 PMCID: PMC8686021 DOI: 10.1016/j.jvacx.2021.100131] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/25/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022] Open
Abstract
We examined 17DD yellow fever vaccine in juvenile autoimmune rheumatic disease patients under low immunosuppression during the recent epidemic in Sao Paulo-Brazil. No serious adverse events were reported and frequencies of mild adverse events were comparable between patients and healthy controls. Immunogenicity parameters against yellow fever vaccine were not hampered in juvenile autoimmune rheumatic disease patients. Peripheral white-blood-cells kinetics after yellow fever vaccination was demonstrated with transient decreases in lymphocytes at D5 and neutrophil levels at D10 with complete recovery at D30. Yellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (∼5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293;p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas.
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Affiliation(s)
- Nádia Emi Aikawa
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
- Corresponding authors at: 455, 3rd floor, room 3190 – Cerqueira Cesar, São Paulo, SP CEP 05403010, Brazil.
| | - Verena Andrade Balbi
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
- Corresponding authors at: 455, 3rd floor, room 3190 – Cerqueira Cesar, São Paulo, SP CEP 05403010, Brazil.
| | - Eduardo Ferreira Borba
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Adriana Coracini Tonacio
- Division of Infectology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Adriana Maluf Elias Sallum
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Lucia Maria Arruda Campos
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Kátia Tomie Kozu
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Margarete Borges Vendramini
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Nicole Fontoura
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Adriana de Souza Azevedo
- Institute of Technology in Immunobiologicals, Bio-Manguinhos, Fundação Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro, RJ, Brazil
| | - Waleska Dias Schwarcz
- Institute of Technology in Immunobiologicals, Bio-Manguinhos, Fundação Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro, RJ, Brazil
| | - Ana Marli Christovam Sartori
- Division of Infectology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Leila Antonangelo
- Central Laboratory, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Clovis Artur Silva
- Pediatric Rheumatology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
| | - Eloisa Bonfá
- Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, Brazil
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Schonenberg-Meinema D, Bergkamp SC, Nassar-Sheikh Rashid A, Gruppen MP, Middelkamp-Hup MA, Armbrust W, Dolman K, Hak AE, Hissink Muller PCE, van Onna M, Swart JF, Kuijpers TW, Kamphuis SSM, Smith V, van den Berg JM. Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal follow-up. Lupus Sci Med 2022; 9:9/1/e000572. [PMID: 35140136 PMCID: PMC8830289 DOI: 10.1136/lupus-2021-000572] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/24/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the 'fast track algorithm' from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as 'microangiopathy'. RESULTS Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5-15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8-16), median SLEDAI at follow-up was 2 (IQR 1-6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud's phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ2, p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage.
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Affiliation(s)
- Dieneke Schonenberg-Meinema
- Department of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | - Sandy C Bergkamp
- Department of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Mariken P Gruppen
- Department of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | - Maritza A Middelkamp-Hup
- Department of Dermatology, University of Amsterdam, Amsterdam Universitair Medische Centra, Amsterdam, The Netherlands
| | - Wineke Armbrust
- University Medical Centre Groningen, University of Groningen, Department of Pediatric Rheumatology and Immunology, Beatrix Children's Hospital, Groningen, The Netherlands
| | - Koert Dolman
- Department of Pediatrics, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.,Department of Pediatric Rheumatology, Reade, Amsterdam, The Netherlands
| | - A Elisabeth Hak
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
| | - Petra C E Hissink Muller
- Department of Paediatric Rheumatology, Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands
| | - Marieke van Onna
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
| | - Joost F Swart
- Department of Paediatric Immunology, Wilhelmina Children's Hospital, University of Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Taco W Kuijpers
- Department of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | - Sylvia S M Kamphuis
- Department of Paediatric Rheumatology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Vanessa Smith
- Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.,Faculty of Internal Medicine, Ghent University, Ghent, Belgium
| | - J Merlijn van den Berg
- Department of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
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Rutkowska-Sak L, Gietka P, Gazda A, Kołodziejczyk B. Juvenile systemic sclerosis - observations of one clinical centre. Reumatologia 2022; 59:367-372. [PMID: 35079180 PMCID: PMC8768038 DOI: 10.5114/reum.2021.112350] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 12/06/2021] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVES The systemic form of scleroderma (SSc) in children is a very rare disease; therefore, it is recognized relatively late, which increases the risk of complications. The aim of the study was to assess the clinical symptoms of juvenile systemic sclerosis (JSSc) in our cohort patients. MATERIAL AND METHODS A group of (N = 22) scleroderma patients aged between 2 and 16 years were observed. Demographic data and all clinical results obtained during 16 years of observation in the clinic of rheumatic diseases of developmental age were collected and analysed. RESULTS In all observed children the major JSSc criterion was found, i.e. skin thickening proximal to the metacarpal phalangeal and/or metatarsophalangeal joints. Other symptoms are presented as follows: nailfold capillary abnormalities - 100%, Raynaud's phenomenon - 90.9%, sclerodactyly - 27.3%, digital tip ulcers - 27.3%, dysphagia - 18.2%, gastroesophageal reflux - 27.3% (assessed in only 10 children), arrhythmias - 22.7%, heart failure - 9.1%, new-onset arterial hypertension - 9.1%, pulmonary fibrosis - 72.7%, pulmonary arterial hypertension - 9.1%, neuropathy - 13.6%, carpal tunnel syndrome - 4.5%, tendon friction rubs - 4.5%, arthritis - 22.7%, and myositis - 13.6%. There were no cases of renal crisis. Decreased diffusing capacity of oxygen was confirmed in 12 patients (58.3%). The presence of antinuclear antibodies was noticed in 86.7% of patients, and among SSc selective autoantibodies: anticentromere - 31.8%, anti-topoisomerase I - 18.2%, anti-PM-Scl 100 or 75 - 45.5%, anti-RP11, Th/To, PCNA in total in 27.3% were presented. In 4.5% of cases, apart from the presence of anti-PM-Scl autoantibodies, positive lupus band test, reduced concentration of complement, and antiphospholipid antibodies were also found. In 59% of studied children, the body mass index was below the 25th percentile. CONCLUSIONS The presented retrospective analysis shows that the occurrence of Raynaud's phenomenon with changes in nailfold capillaroscopy is the best screening toll for the assessment of risk of JSSc. All patients of developmental age with Raynaud's phenomenon, especially in the case of the appearance of antinuclear antibodies, should be monitored with capillaroscopy regardless of other laboratory or imaging tests.
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Affiliation(s)
- Lidia Rutkowska-Sak
- Clinic of Developmental-Age Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw, Poland
| | - Piotr Gietka
- Clinic of Developmental-Age Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw, Poland
| | - Agnieszka Gazda
- Clinic of Developmental-Age Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw, Poland
| | - Beata Kołodziejczyk
- Clinic of Developmental-Age Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw, Poland
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Furusawa A, Wakiguchi H, Okazaki F, Korenaga Y, Azuma Y, Yasudo H, Hasegawa S. Successful treatment of children with juvenile systemic sclerosis using mycophenolate mofetil after methylprednisolone pulse therapy: A 3-year follow-up. Int J Rheum Dis 2021; 25:95-96. [PMID: 34866347 DOI: 10.1111/1756-185x.14260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/17/2021] [Accepted: 11/20/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Akinori Furusawa
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hiroyuki Wakiguchi
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Fumiko Okazaki
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yuno Korenaga
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yoshihiro Azuma
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hiroki Yasudo
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shunji Hasegawa
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
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El-Beheidy R, Domouky AM, Zidan H, Amer YA. Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study. Reumatismo 2021; 73. [PMID: 34814656 DOI: 10.4081/reumatismo.2021.1399] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 06/27/2021] [Indexed: 11/23/2022] Open
Abstract
This study was aimed to evaluate serum KL-6 levels to determine if this marker can be used for diagnosing and assessing severity of interstitial lung disease (ILD) in children with connective tissue disorders. In total, 40 patients [18 patients with juvenile systemic lupus erythematosus (JSLE), 10 patients with juvenile idiopathic arthritis (JIA), 8 patients with juvenile mixed connective tissue disease (JMCTD), 3 patients with juvenile systemic sclerosis (JSSc), and 1 patient with juvenile dermatomyositis (JDM)] and 20 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. 20 of the 40 patients with CTD (50%) had ILD, 12 were mild and 8 were severe as assessed by spirometry. The median serum KL-6 level was 102.7 U/mL (76.1-180.8) in the CTD with severe ILD group, 72.2 U/mL (58.4- 100.5) in the CTD with mild ILD group, 56.7 U/mL (35.8-68.5) in the CTD without ILD group, and 52.3 U/mL (32.8-62.4) in the control group. KL-6 levels were significantly higher in the CTD with ILD (p<0.05), at a cutoff of 63.4 U/ml identified by ROC curve, serum KL-6 showed a sensitivity of 95.2% and specificity of 89.7%. KL-6 is a valuable biomarker for diagnostic purposes and to detect severity in ILD in childhood CTD.
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Affiliation(s)
- R El-Beheidy
- Pulmonology, Immunology and Allergy Unit, Pediatrics Department, Faculty of Medicine, Zagazig University.
| | - A M Domouky
- Pulmonology, Immunology and Allergy Unit, Pediatrics Department, Faculty of Medicine, Zagazig University, Egypt; Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University.
| | - H Zidan
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University.
| | - Y A Amer
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig University.
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Zulian F, Lanzoni G, Castaldi B, Meneghel A, Tirelli F, Zanatta E, Martini G. Systemic sclerosis sine scleroderma in children. Rheumatology (Oxford) 2021; 61:2555-2562. [PMID: 34605913 PMCID: PMC9157094 DOI: 10.1093/rheumatology/keab738] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/17/2021] [Indexed: 11/20/2022] Open
Abstract
Objective Juvenile systemic sclerosis (JSSc) is a rare condition in childhood and its variety with no skin involvement, sine scleroderma (ssJSSc), is anecdotal. We report the first case series of patients with ssJSSc. Methods Demographic, clinical and laboratory data of patients with JSSc followed at our centre were retrospectively collected. Patients with no skin involvement but with all of the features RP, positive ANA, intestinal dysmotility and/or interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH) and/or cardiac or renal involvement typical of scleroderma were defined as having ssJSSc and compared with those with classic JSSc (cJSSc). Results Among 52 JSSc patients seen in 20 years, five (9.6%) presented with ssJSSc. Their clinical features and those of the only two patients reported in the literature so far were compared with classic JSSc with available complete data. Six patients had cardiac involvement as presenting feature, three primary cardiomyopathy, three secondary to PAH. Two patients died after a brief disease course and one rapidly underwent heart transplantation. In comparison with cJSSc, ssJSSc showed a significantly longer diagnostic delay (20.1 vs 8.3 months, P = 0.017), higher frequency of cardiac involvement (85.7 vs 15.6%, P = 0.001) and worse outcome, intended as mortality or end-stage organ failure rates (42.9% vs 6.2%, P < 0.001). Conclusion Cardiac involvement represents the most important characteristic of ssJSSc and carries a high morbidity and mortality rate. The longer delay in diagnosis underlines the need for a comprehensive rheumatological work-up in patients with isolated cardiomyopathy or PAH/ILD.
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Affiliation(s)
| | - Gloria Lanzoni
- University of Padua, Department of Woman and Child Health
| | - Biagio Castaldi
- Universita degli Studi di Padova, Department of Woman and Child Health
| | | | | | - Elisabetta Zanatta
- University of Padua, Department of Medicine-DIMED, Rheumatology Division
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Yamashita Y, Yamano Y, Muro Y, Ogawa-Momohara M, Takeichi T, Kondoh Y, Akiyama M. Clinical significance of anti-NOR90 antibodies in systemic sclerosis and idiopathic interstitial pneumonia. Rheumatology (Oxford) 2021; 61:1709-1716. [PMID: 34282441 DOI: 10.1093/rheumatology/keab575] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/09/2021] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE Anti-NOR90 antibodies are usually found in patients with systemic sclerosis (SSc); however, their clinical relevance remains obscure. We developed an enzyme-linked immunosorbent assay (ELISA) for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies. METHODS Serum samples from 1,252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation. RESULTS Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, 3 with limited cutaneous SSc, and 1 with Raynaud's disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs. 0/936, P<0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs. 0/528, P<0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the 4 anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and 2 of those 4 had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All 3 of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and 2 of those 3 had cancer or skin lesions observed in SSc. CONCLUSIONS Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients.
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Affiliation(s)
- Yuta Yamashita
- Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Yasuhiko Yamano
- Department of Respiratory and Allergic Medicine, Tosei General Hospital, Seto, Aichi 489-8642, Japan
| | - Yoshinao Muro
- Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Mariko Ogawa-Momohara
- Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Takuya Takeichi
- Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory and Allergic Medicine, Tosei General Hospital, Seto, Aichi 489-8642, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
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Kittivisuit S, Lerkvaleekul B, Soponkanaporn S, Ngamjanyaporn P, Vilaiyuk S. Assessment of transition readiness in adolescents in Thailand with rheumatic diseases: a cross-sectional study. Pediatr Rheumatol Online J 2021; 19:101. [PMID: 34193176 PMCID: PMC8243449 DOI: 10.1186/s12969-021-00602-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/10/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Most childhood-onset rheumatic diseases are chronic health conditions, which need long-term care throughout adulthood. A well-organized transition care is challenging and patient assessment of transition skills is needed for transfer preparation to an adult care setting. The Transition Readiness Assessment Questionnaire (TRAQ) is used to assess transition skills in chronically ill patients. Currently, limited transition skill assessment data exist in pediatric patients with rheumatic diseases, especially in Asian countries. This study aimed to determine the transition readiness skills in patients with rheumatic diseases and ascertain predictive factors contributing to high transition readiness skills. METHODS This is a cross-sectional study. All patients with rheumatic diseases aged 15-20 years were recruited. The TRAQ was cross-culturally adapted into the Thai language with good internal consistency and reliability. Patients completed the Thai TRAQ at the recent clinic visit and took the retest at a 2-week interval. Demographic data, baseline characteristics, clinical manifestations, and disease status were collected. Descriptive and logistic regression analyses were performed. RESULTS A total of 111 patients with a mean age of 17.4 ± 1.8 years were included. Median (IQR) disease duration was 6.4 (3.2-9.0) years. The most common rheumatic disease was juvenile idiopathic arthritis (48.6%), followed by systemic lupus erythematosus (35.1%). The mean TRAQ score was 3.85 ± 0.69. Independent visits (OR 4.35, 95% CI 1.23-15.37) was a predictor of a high TRAQ score. Furthermore, dependent visits (OR 7.84, 95% CI 2.41-25.50) was a predictor of low TRAQ score in the "appointment keeping" domain, whereas inactive disease (OR 4.54, 95% CI 1.25-16.55) was a predictor of a low TRAQ score in "tracking health issues" domain. Lack of knowledge and skills on health insurance coverage, financial management, appointment arrangement, and coping with their illness were issues causing lower TRAQ score. CONCLUSIONS Patients, who had independent visits, had a higher chance to obtain higher TRAQ scores, whereas patients, who had an inactive disease or dependent visits, had less transition readiness skills. Physicians and parents should prepare to transfer patients to adult care settings, mainly encouraging independent living skills.
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Affiliation(s)
- Sirinthip Kittivisuit
- grid.10223.320000 0004 1937 0490Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, 10400 Bangkok, Thailand ,grid.7130.50000 0004 0470 1162Division of Rheumatology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Butsabong Lerkvaleekul
- grid.10223.320000 0004 1937 0490Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, 10400 Bangkok, Thailand
| | - Sirisucha Soponkanaporn
- grid.10223.320000 0004 1937 0490Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, 10400 Bangkok, Thailand
| | - Pintip Ngamjanyaporn
- grid.10223.320000 0004 1937 0490Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Soamarat Vilaiyuk
- Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, 10400, Bangkok, Thailand.
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Review for best practice in clinical rheumatology juvenile systemic sclerosis - Updates and practice points. Best Pract Res Clin Rheumatol 2021; 35:101688. [PMID: 33896752 DOI: 10.1016/j.berh.2021.101688] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Juvenile systemic sclerosis (jSSc) is a rare, severe autoimmune disease associated with life-threatening multiorgan inflammatory-driven fibrosis. Recognition early in the disease process, when treatment is more effective, is critical. We outline insights from the authors, who specialize and host jSSc cohorts, combined with recent literature review combining available juvenile-onset and applicable adult-onset studies regarding SSc evaluation, which can be extrapolated to children. Practice tips are provided for each main organ system.
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Civieri G, Castaldi B, Martini G, Meneghel A, Milanesi O, Zulian F. Early detection of ventricular dysfunction in juvenile systemic sclerosis by speckle tracking echocardiography. Rheumatology (Oxford) 2021; 60:103-107. [PMID: 32572491 PMCID: PMC7785305 DOI: 10.1093/rheumatology/keaa208] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Cardiac involvement is the most important cause of mortality in juvenile systemic sclerosis (JSSc). Recent reports in adult patients underline that traditional techniques of imaging are inadequate to assess the subclinical cardiac involvement, while speckle tracking echocardiography (STE) is able to identify ventricular dysfunctions in the early stages. The aim of our study was to assess the role of STE in JSSc. METHODS Demographic, clinical and laboratory data were collected from patients with JSSc. Cardiac investigations performed at baseline (T0) and 18 (T18) and 36 months (T36) follow-up included electrocardiography, conventional echocardiography with measurement of the ejection fraction (EF) and STE with assessment of left and right ventricular global longitudinal strain (LV-GLS and RV-GLS). Cardiac parameters have been compared with demographic characteristics and disease severity, assessed by the Juvenile Systemic Sclerosis Severity Score (J4S). RESULTS A total of 18 patients, 12 (67%) females, entered the study. At T0, electrocardiography was abnormal in three patients, EF was reduced in one, LV-GLS was abnormal in three (16.7%) and RV-GLS was abnormal in five (27.8%). At T18, EF remained stable while at T36 the result decreased in seven of nine patients. At the same time, LV-GLS also worsened (from -21.6% to -18.2%, P = 0.01). LV-GLS and RV-GLS at baseline showed a significant correlation with J4S (P = 0.012 and P = 0.02, respectively). CONCLUSION STE is more sensitive than standard echocardiography to identify cardiac involvement in JSSc. Over time, we observed a gradual worsening of LV-GLS, a sign of left ventricular dysfunction, that anticipated by several months the decrease of EF.
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Affiliation(s)
- Giovanni Civieri
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Biagio Castaldi
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Giorgia Martini
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Alessandra Meneghel
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Ornella Milanesi
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Francesco Zulian
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
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Foeldvari I, Culpo R, Sperotto F, Anton J, Avcin T, Baildam E, Boros C, Chaitow J, Constantin T, Kasapcopur O, Knupp Feitosa de Oliveira S, Pilkington C, Toplak N, van Royen A, Saad Magalhaes C, Vastert SJ, Wulffraat N, Zulian F. Consensus-based recommendations for the management of juvenile systemic sclerosis. Rheumatology (Oxford) 2021; 60:1651-1658. [PMID: 33147624 DOI: 10.1093/rheumatology/keaa584] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 06/18/2020] [Accepted: 07/11/2020] [Indexed: 12/29/2022] Open
Abstract
Juvenile systemic sclerosis (JSSc) is a rare disease of childhood and currently no international consensus exists with regard to its assessment and treatment. This SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative, based on expert opinion informed by the best available evidence, provides recommendations for the assessment and treatment of patients with JSSc with a view to improving their outcome. Experts focused attention not only on the skin assessment but also on the early signs of internal organ involvement whose proper treatment can significantly affect the long-term outcome. A score for disease severity is proposed in order to perform a structured assessment of outcome over time but a validation in a wider patient population is recommended. Finally, a stepwise treatment approach is proposed in order to unify the standard of care throughout Europe with the aim to reduce morbidity and mortality in this disease.
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Affiliation(s)
- Ivan Foeldvari
- Hamburger Zentrum für Kinder- und Jugendrheumatologie, Schoen Clinic, Hamburg-Eilbek, Germany
| | - Roberta Culpo
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Francesca Sperotto
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
| | - Jordi Anton
- Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
| | - Tadej Avcin
- Department of Allergy, Rheumatology and Clinical Immunology, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Eileen Baildam
- Clinical and Academic Paediatric and Adolescent Rheumatology Unit, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
| | - Christina Boros
- Rheumatology, Women's and Children's Hospital, University of Adelaide, Adelaide, Australia
| | - Jeffrey Chaitow
- Rheumatology, The Children's Hospital Westmead, Australia, Sydney
| | - Tamas Constantin
- 2nd Department of Pediatrics, Semmelweis Hospital, Budapest, Hungary
| | - Ozgur Kasapcopur
- Department of Pediatrics, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Sheila Knupp Feitosa de Oliveira
- Pediatric Rheumatology Unit, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Clarissa Pilkington
- Centre for Adolescent Rheumatology, Institute of Child Health University College London, London, UK
| | - Natasa Toplak
- Department of Allergy, Rheumatology and Clinical Immunology, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Annet van Royen
- Paediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands
| | | | - Sebastiaan J Vastert
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands
- The European Reference Network RITA
| | - Nico Wulffraat
- Department of Paediatric Rheumatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands
- The European Reference Network RITA
| | - Francesco Zulian
- Department of Woman's and Child's Health, University of Padova, Padua, Italy
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Tanaka R, Tani Y, Kaburaki Y, Kinoshita M, Kawaguchi Y, Okazaki Y, Kuwana M, Harigai M, Nagata S, Miyamae T. Joint contractures responsive to immunosuppressive therapy in a girl with childhood-onset systemic sclerosis double-seropositive for rare anti-nucleolar autoantibodies: a case report. Pediatr Rheumatol Online J 2021; 19:37. [PMID: 33743728 PMCID: PMC7981830 DOI: 10.1186/s12969-021-00525-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 03/05/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Systemic sclerosis (SSc; scleroderma) is an autoimmune connective tissue disease that affects the skin and subcutaneous tissue, in addition to the internal organs of the whole body. Onset in childhood is uncommon; however, both patients with childhood-onset and adult-onset SSc are positive for anti-nuclear antibodies (ANAs).Detection of SSc-related anti-nuclear antibodies is often useful for predicting clinical features, disease course, and outcomes. CASE PRESENTATION A 5-year-old Japanese female manifested gradually progressive abnormal gait disturbance, regression of motor development, Raynaud's phenomenon, and the shiny appearance of the skin of the face and extremities at age 2. On admission, she presented a mask-like appearance, loss of wrinkles and skin folds, puffy fingers, moderate diffuse scleroderma (18/51 of the modified Rodnan total skin thickness score), and contracture in the ankle and proximal interphalangeal joints. Grossly visible capillary hemorrhage on nail fold and severe abnormal capillaroscopy findings including bleeding, giant loop and disappearance of capillaryconsistent with the late phase in SSc. A skin biopsy showed fibrous thickening of the dermis, entrapment of an eccrine sweat glands, and thickened fiber. Chest high-resolution computed tomographic scanning demonstrated patchy areas of ill-defined air-space opacity and consolidation predominantly involving the posterior basilar aspects of the lower lobes presenting withinterstitial lung disease. Positive ANA (1:160 nucleolar and homogeneous nuclear staining by indirect fluorescent antibody technique) and double-seropositive for anti-Th/To and anti-PM-Scl antibodies were identified. She was diagnosed with diffuse cutaneous SSc based on the Pediatric Rheumatology European Society/American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Juvenile Systemic Sclerosis and was successfully treated with immunosuppressive agents, including methylprednisolone pulses and intravenous cyclophosphamide. CONCLUSIONS We experienced the first case of juvenile SSc with anti-PM-Scl and anti-Th/To antibodies. ILD was identified as a typical feature of patients with these autoantibodies; however, diffuse cutaneous SSc and joint contraction were uncharacteristically associated. The case showed unexpected clinical findings though the existence of SSc-related autoantibodies aids in determining possible organ involvement and to estimate the children's outcome.
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Affiliation(s)
- Riki Tanaka
- Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Yumi Tani
- Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Yoichiro Kaburaki
- Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Manao Kinoshita
- Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan, Shimokato, Chuo, 1110, 409-3898 Yamanashi, Japan
| | - Yasushi Kawaguchi
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Yuka Okazaki
- Department of Allergy and Rheumatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, 113- 8602 Tokyo, Japan
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, 113- 8602 Tokyo, Japan
| | - Masayoshi Harigai
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Satoru Nagata
- Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
| | - Takako Miyamae
- Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
- Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 8-1 Kawada-Cho, Shinjuku- Ku, 162-8666 Tokyo, Japan
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Abstract
Children with rheumatic disease have rare pulmonary manifestations that may cause significant morbidity and mortality. These children are often clinically asymptomatic until disease has significantly progressed, so they should be screened for pulmonary involvement. There has been recent recognition of a high mortality-related lung disease in systemic-onset juvenile idiopathic arthritis; risk factors include onset of juvenile idiopathic arthritis less than 2 years of age, history of macrophage activation syndrome, presence of trisomy 21, and history of anaphylactic reaction to biologic therapy. Early recognition and treatment of lung disease in children with rheumatic diseases may improve outcomes.
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Zulian F, Dal Pozzolo R, Meneghel A, Castaldi B, Marcolongo R, Caforio ALP, Martini G. Rituximab for rapidly progressive juvenile systemic sclerosis. Rheumatology (Oxford) 2021; 59:3793-3797. [PMID: 32442284 DOI: 10.1093/rheumatology/keaa193] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/26/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Juvenile systemic sclerosis (JSSc) with rapidly progressive course is a life-threatening condition associated with a poor prognosis. Recently, rituximab (RTX) has been shown to be a promising treatment for adult patients with SSc. We present a series of four patients with rapidly progressive JSSc successfully treated with RTX. METHODS Clinical, laboratory and functional parameters were collected from four patients with rapidly progressive JSSc treated with RTX for at least 1 year. All patients underwent four yearly courses of i.v. RTX 375 mg/m2 on day 0 and 14, at 3-month intervals. Low dose oral prednisone and MMF were also administered. Data were recorded at baseline and every 6 months and included pulmonary and myocardial function parameters, muscular, vascular and skin changes. The Juvenile Systemic Sclerosis Severity Score (J4S) estimated the overall disease severity over time. RESULTS Four patients (three males, one female), aged 8-17 years, entered the study. Three patients presented with prevalent cardiac involvement, one with severe pulmonary involvement. After 1 year of RTX treatment, all patients showed significant improvement of J4S, Raynaud's phenomenon and cutaneous involvement. Among those with prevalent cardiac involvement, two showed an improvement of the myocardial function (left ventricular ejection fraction [EF] +37% and +19%, respectively) and in the third arrhythmias disappeared. The patient with severe pulmonary involvement showed a significant improvement of the respiratory function (forced vital capacity +46%, forced expiratory volume in 1 s +33%, diffusing capacity of the lung for carbon monoxide [DLCO] +30%). No major side effects were reported. CONCLUSIONS Our data suggest that a combination of RTX and MMF is effective in arresting the rapid progression of JSSc.
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Affiliation(s)
| | | | | | | | | | - Alida Linda Patrizia Caforio
- Department of Cardiological, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
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Adrovic A, Yildiz M, Haslak F, Koker O, Aliyeva A, Sahin S, Barut K, Kasapcopur O. Tocilizumab therapy in juvenile systemic sclerosis: a retrospective single centre pilot study. Rheumatol Int 2021; 41:121-128. [PMID: 33108799 DOI: 10.1007/s00296-020-04732-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 10/12/2020] [Indexed: 01/11/2023]
Abstract
To evaluate the efficacy and safety of anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) as a treatment option of juvenile systemic sclerosis (JSS). Nine JSS patients were assigned to a TCZ, additionally to conventional treatment (steroids, methotrexate, mycophenolate-mofetil). The modified Rodnan skin score (mRSS), carbon-monoxide diffusion capacity (DLCO), thorax high-resolution tomography (HRCT), patient global assessment (PGA) and Juvenile Systemic Sclerosis Severity (J4S) score were used to explore the efficacy of treatment. Nine JSS patients were treated with TCZ with a median treatment duration of 10 (1-21) months. Nine patients (77.8%) had radiologically confirmed improvement on thorax HRCT, 7 (77.8%) had decreased PGA (mean pre-treatment PGA 3.7 vs. 2.3 post-treatment PGA 2), 6 (66.7%) had increased DLCO (mean pre-treatment DLCO 69.14% vs. post-treatment DLCO 79.50%) after the TCZ treatment. In all patients mRSS and the J4S decreased: 26.1 vs. 19.7 and 8.2 vs. 4.7, respectively. Changes in mRSS, DLCO, PGA and J4S were statistically significant: p = 0.012, 0.04, 0.026 and 0.007, respectively. All patients tolerated well TCZ treatment. JSS is a rare condition characterized with skin fibrosis and internal organ involvement. Tocilizumab represents a potential treatment option for patients unresponsive to conventional treatment. Long-term prospective studies with higher number of patients are needed to provide more relevant data.
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Affiliation(s)
- Amra Adrovic
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Mehmet Yildiz
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Fatih Haslak
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Oya Koker
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ayten Aliyeva
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.
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Volkmann ER, Hoffmann-Vold AM, Chang YL, Lagishetty V, Clements PJ, Midtvedt Ø, Molberg Ø, Braun J, Jacobs JP. Longitudinal Characterisation of the Gastrointestinal Tract Microbiome in Systemic Sclerosis. EUROPEAN MEDICAL JOURNAL (CHELMSFORD, ENGLAND) 2020; 7:110-118. [PMID: 36711108 PMCID: PMC9881192 DOI: 10.33590/emj/20-00043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Objectives To evaluate changes in microbial composition and the evolution of gastrointestinal tract (GIT) symptoms in systemic sclerosis (SSc). Methods Adult SSc patients provided stool specimens every 3 months over the course of 1 year. Participants completed the University of California, Los Angeles (UCLA) GIT 2.0 questionnaire to assess GIT symptom severity at each stool collection. The microbiota from these samples were determined by Illumina HiSeq 2500 16S ribosomal RNA sequencing (Illumina, Inc., San Diego, California, USA). Mixed effect models evaluated changes in GIT symptoms and microbial composition over time. Results Among 19 patients with SSc (female; 89.5%; median age: 51.3 years), the median disease duration was 7 years and the baseline total GIT 2.0 score was 0.7 (standard deviation: 0.6). The majority of participants (63%) provided at least four stool samples over the course of the 12-month study. Patients with longer disease durations had increased GIT symptoms over the course of the study. There was no difference in the course of GIT symptoms over time between patients with limited versus diffuse cutaneous disease. The relative abundances of specific genera did not change over time within individual subjects. After controlling for age, sex, ethnicity, disease duration, and SSc subtype (i.e., limited versus diffuse), low abundance of Bacteroides was associated with increased GIT symptoms over time. Conclusion This study is the first to have longitudinally characterised the lower GIT microbiome in SSc patients and demonstrated relative stability of genera abundance over the course of 1 year. The findings provide additional evidence that specific genera are associated with SSc-GIT symptoms and warrant further evaluation in larger SSc studies.
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Affiliation(s)
- Elizabeth R. Volkmann
- Department of Medicine, University of California, David
Geffen School of Medicine, Los Angeles, California, USA,Correspondence to
| | | | - Yu-Ling Chang
- Department of Pathology and Laboratory Medicine,
University of California, David Geffen School of Medicine, Los Angeles, California,
USA
| | - Venu Lagishetty
- The Vatche and Tamar Manoukian Division of Digestive
Diseases, Department of Medicine, University of California, David Geffen School of
Medicine, Los Angeles, California, USA
| | - Philip J. Clements
- University of California, David Geffen School of Medicine,
Los Angeles, California, USA
| | - Øyvind Midtvedt
- Department of Rheumatology, Oslo University Hospital,
Oslo, Norway,Institute of Clinical Medicine, Faculty of Medicine,
University of Oslo, Oslo, Norway
| | - Øyvind Molberg
- Department of Rheumatology, Oslo University Hospital,
Oslo, Norway
| | - Jonathan Braun
- Department of Medicine, Cedars Sinai Medical Center, Los
Angeles, California, USA
| | - Jonathan P. Jacobs
- The Vatche and Tamar Manoukian Division of Digestive
Diseases, Department of Medicine, University of California, David Geffen School of
Medicine, Los Angeles, California, USA,Division of Gastroenterology, Hepatology, and Parenteral
Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, California,
USA
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Kilinc AA, Arslan A, Yildiz M, Kucur M, Adrovic A, Barut K, Sahin S, Cokugras H, Kasapcopur O. Serum KL-6 level as a biomarker of interstitial lung disease in childhood connective tissue diseases: a pilot study. Rheumatol Int 2020; 40:1701-1706. [PMID: 31784789 DOI: 10.1007/s00296-019-04485-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 11/23/2019] [Indexed: 12/24/2022]
Abstract
Krebs von den Lungen-6 (KL-6) has been described as a promising biomarker in the diagnosis and determining the severity of interstitial lung disease in adults with connective tissue disease. This study was performed to determine whether the serum KL-6 level is useful as a biomarker for detecting the interstitial lung disease (ILD) in pediatric cases of connective tissue disease (CTD). In total, 88 patients [36 patients with systemic juvenile idiopathic arthritis (sJIA), 27 patients with juvenile systemic lupus erythematosus (JSLE), 14 patients with juvenile dermatomyositis (JDM), and 11 patients with juvenile systemic sclerosis (JSSc)] and 68 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. Eleven of the 88 patients with CTD (12.5%) had ILD and all of them were symptomatic. Subgroup analysis indicated that eight patients had JSSc, two had JSLE, and one had systemic JIA. The median serum KL-6 level was 1450.5 U/mL (interquartile range (IQR) 742.9-2603.2) in the CTD with ILD group, 415.9 U/mL (IQR 233.4-748.4) in the CTD without ILD group, and 465.9 U/mL (IQR 273.6-1036) in the control group. KL-6 levels were significantly higher in the CTD with ILD group than the CTD without ILD group and the control group (p = 0.003). At a cut-off of 712.5 U/ml identified by ROC curve, serum KL-6 yielded a sensitivity of 81% and specificity of 72% for CTD with ILD group. There was no significant difference in serum KL-6 level among the disease subgroups (sJIA, JSLE, JSSc, JDM), in either the CTD with ILD group or the CTD without ILD group (p > 0.05). In conclusion, KL-6 is a useful biomarker of CTD with ILD in pediatric patients.
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Affiliation(s)
- Ayse Ayzit Kilinc
- Department of Pediatric Pulmonology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Asli Arslan
- Department of Pediatric Pulmonology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Mehmet Yildiz
- Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Mine Kucur
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Haluk Cokugras
- Department of Pediatric Pulmonology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, İstanbul University-Cerrahpasa, İstanbul, Turkey.
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Aygun D, Kuskucu MA, Sahin S, Adrovic A, Barut K, Yıldız M, Sharifova S, Midilli K, Cokugras H, Camcıoglu Y, Kasapcopur O. Epstein-Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity. Lupus 2020; 29:1263-1269. [PMID: 32646294 DOI: 10.1177/0961203320940029] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Clinical and laboratory investigations have revealed that Epstein-Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease - juvenile systemic sclerosis (jSS) - and healthy individuals. METHODS Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. RESULTS A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. CONCLUSION The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.
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MESH Headings
- Adolescent
- Adult
- Antibodies, Viral/blood
- Antigens, Viral/blood
- Antigens, Viral/immunology
- BK Virus/immunology
- BK Virus/isolation & purification
- Capsid Proteins/immunology
- Case-Control Studies
- Child
- Cytomegalovirus/immunology
- Cytomegalovirus/isolation & purification
- Disease Progression
- Epstein-Barr Virus Infections
- Herpesvirus 4, Human/immunology
- Herpesvirus 4, Human/isolation & purification
- Humans
- Lupus Erythematosus, Systemic/blood
- Lupus Erythematosus, Systemic/virology
- Scleroderma, Localized/blood
- Scleroderma, Localized/virology
- Scleroderma, Systemic/blood
- Scleroderma, Systemic/virology
- Viral Load
- Young Adult
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Affiliation(s)
- Deniz Aygun
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Mert Ahmet Kuskucu
- Department of Microbiology and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Mehmet Yıldız
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Sabina Sharifova
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Kenan Midilli
- Department of Microbiology and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Haluk Cokugras
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Yıldız Camcıoglu
- Department of Pediatric Infectious Disease, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey
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Abstract
OBJECTIVES (A) To investigate the specialty of observers involved in imaging-based assessment of bone fracture union in recent orthopaedic trials and (B) to provide a general overview of observer differences (in terms of interobserver reliability) in radiologic fracture union assessment that have been reported between surgeons and radiologists. DATA SOURCES Two separate systematic reviews (A, B) of English-, German-, and French-language articles in MEDLINE and Embase databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were done, with the following time frames: (A) January 2016-August 2017 and (B) through November 2017. STUDY SELECTION (A) Clinical trials of surgical fracture treatment evaluating radiologic (non) union. (B) Interobserver studies reporting kappa-values or intraclass correlation coefficients as reliability coefficient for radiologic fracture union assessment. Inclusion criteria for both reviews were fractures of the appendicular skeleton and the use of radiographs or computed tomography. DATA EXTRACTION Data were independently retrieved by 2 reviewers. DATA SYNTHESIS Descriptive statistics and percentages were reported. RESULTS (A) Forty-eight trials were included, whereof 33 (68%) did not report the observer's specialty. Six trials (13%) reported surgeon observers only, and 6 (13%) reported radiologist observers only. The median number of observers is 1 (interquartile range, 1-2). (B) Thirty-one interobserver studies were included, whereof 11 (35%) included at least 1 surgeon and 1 radiologist. Interobserver reliability varied considerably across the various fracture types studied and outcome scale used and was often unsatisfactory (kappa or intraclass correlation coefficients of <0.7). CONCLUSIONS In most trials providing observer's characteristics, radiologic fracture union was either rated by 1 surgeon or 1 radiologist. As interobserver reliability can be unsatisfactory, we recommend surgeons and radiologists to further intensify collaboration and trials to include at least 2 observers and associated reliability statistics.
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Ambartsumyan L, Zheng HB, Iyer RS, Soares J, Henstorf G, Stevens AM. Relationship Between Esophageal Abnormalities on Fluoroscopic Esophagram and Pulmonary Function Testing in Juvenile Systemic Sclerosis. Arthritis Care Res (Hoboken) 2019; 71:1444-1449. [DOI: 10.1002/acr.23778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 09/25/2018] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Ramesh S. Iyer
- Seattle Children's HospitalUniversity of Washington Seattle
| | | | | | - Anne M. Stevens
- Seattle Children's HospitalUniversity of Washington, and Seattle Children's Research Institute Seattle Washington
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48
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Karadağ ŞG, Sönmez HE, Tanatar A, Çakmak F, Çakan M, Ayaz NA. Profile of new referrals to a single pediatric rheumatology center in Turkey. Rheumatol Int 2019; 40:313-321. [PMID: 31440813 DOI: 10.1007/s00296-019-04421-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 08/10/2019] [Indexed: 01/03/2023]
Abstract
To describe the demographic characteristics and clinical features of patients referred to a pediatric rheumatology outpatient clinic in Turkey and to compare the final diagnoses with the previous literature data. All new patients referred to pediatric rheumatology outpatient clinic of Kanuni Sultan Süleyman Research and Training Hospital between March 2018 and March 2019 were enrolled to the study. Demographic data, referral patterns, disease related features, physical examination findings and final diagnoses of new referrals were collected prospectively. A total of 2982 new referrals were evaluated in 1-year period. Among them 1561 (52%) had a diagnosis of a rheumatic disease. The frequencies of most common rheumatic diseases were; periodic fever syndromes (47.3%), juvenile idiopathic arthritis (18%) and vasculitis (14.4%), respectively. Non-rheumatic conditions were diagnosed in 1243 patients, among them orthopedic/mechanic problems (27.4%) were the most frequent ones followed by vitamin D deficiency (17.5%) and dermatological problems (9.8%). Patients with non-rheumatic conditions comprised a large part of the pediatric rheumatology outpatient clinic. National registries are required to establish the frequencies of pediatric rheumatic diseases in Turkey.
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Affiliation(s)
- Şerife Gül Karadağ
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey
| | - Hafize Emine Sönmez
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey
| | - Ayşe Tanatar
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey
| | - Figen Çakmak
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey
| | - Mustafa Çakan
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey
| | - Nuray Aktay Ayaz
- Division of Rheumatology, Department of Pediatrics, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Science, No: 46/1, 34303, Kucukcekmece, Istanbul, Turkey.
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49
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Rodrigues Fonseca A, Felix Rodrigues MC, Sztajnbok FR, Gerardin Poirot Land M, Knupp Feitosa de Oliveira S. Comparison among ACR1997, SLICC and the new EULAR/ACR classification criteria in childhood-onset systemic lupus erythematosus. Adv Rheumatol 2019; 59:20. [PMID: 31092290 DOI: 10.1186/s42358-019-0062-z] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 05/01/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND To date there are no specific classification criteria for childhood-onset systemic lupus erythematosus (cSLE). This study aims to compare the performance among the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics criteria (SLICC) and the new European League Against Rheumatism (EULAR)/ACR criteria, in a cSLE cohort. METHODS We conducted a medical chart review study of cSLE cases and controls with defined rheumatic diseases, both ANA positive, to establish each ACR1997, SLICC and EULAR/ACR criterion fulfilled, at first visit and 1-year-follow-up. RESULTS Study population included 122 cSLE cases and 89 controls. At first visit, SLICC criteria had higher sensitivity than ACR 1997 (89.3% versus 70.5%, p < 0.001), but similar specificity (80.9% versus 83.2%, p = 0.791), however performance was not statistically different at 1-year-follow-up. SLICC better scored in specificity compared to EULAR/ACR score ≥ 10 at first visit (80.9% versus 67.4%, p = 0.008) and at 1-year (76.4% versus 58.4%, p = 0.001), although sensitivities were similar. EULAR/ACR criteria score ≥ 10 exhibited higher sensitivity than ACR 1997 (87.7% versus 70.5%, p < 0.001) at first visit, but comparable at 1-year, whereas specificity was lower at first visit (67.4% versus 83.2%, p = 0.004) and 1-year (58.4% versus 76.4%, p = 0.002). A EULAR/ACR score ≥ 13 against a score ≥ 10, resulted in higher specificity, positive predictive value, and cut-off point accuracy. Compared to SLICC, a EULAR/ACR score ≥ 13 resulted in lower sensitivity at first visit (76.2% versus 89.3%, p < 0.001) and 1-year (91% versus 97.5%, p = 0.008), but similar specificities at both assessments. When compared to ACR 1997, a EULAR/ACR total score ≥ 13, resulted in no differences in sensitivity and specificity at both observation periods. CONCLUSIONS In this cSLE population, SLICC criteria better scored at first visit and 1-year-follow-up. The adoption of a EULAR/ACR total score ≥ 13 in this study, against the initially proposed ≥10 score, was most appropriate to classify cSLE. Further studies are necessary to address if SLICC criteria might allow fulfillment of cSLE classification earlier in disease course and may be more inclusive of cSLE subjects for clinical studies.
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Affiliation(s)
- Adriana Rodrigues Fonseca
- Pediatric Rheumatology Unit, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rua Bruno Lobo, 50-Cidade Universitária, Rio de Janeiro, Brazil.
| | - Marta Cristine Felix Rodrigues
- Pediatric Rheumatology Unit, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rua Bruno Lobo, 50-Cidade Universitária, Rio de Janeiro, Brazil
| | - Flavio Roberto Sztajnbok
- Pediatric Rheumatology Unit, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rua Bruno Lobo, 50-Cidade Universitária, Rio de Janeiro, Brazil
| | - Marcelo Gerardin Poirot Land
- Internal Medicine Post-graduation Program, Faculty of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Sheila Knupp Feitosa de Oliveira
- Pediatric Rheumatology Unit, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rua Bruno Lobo, 50-Cidade Universitária, Rio de Janeiro, Brazil
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50
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Malagón C, Gomez MDP, Mosquera C, Vargas C, Gonzalez T, Arango C, Martin L, Perez P, Amaya-Uribe L, Molano-Gonzalez N, Anaya JM. Juvenile polyautoimmunity in a rheumatology setting. Autoimmun Rev 2019; 18:369-381. [DOI: 10.1016/j.autrev.2018.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 11/10/2018] [Indexed: 02/06/2023]
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