-
Frontiers in Immunology 2019Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also... (Review)
Review
Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.
Topics: Autoantibodies; Child; Child, Preschool; Female; HLA Antigens; Humans; Macrophages; Male; RNA-Seq; Scleroderma, Localized; Skin; T-Lymphocytes, Helper-Inducer
PubMed: 31114575
DOI: 10.3389/fimmu.2019.00908 -
Annals of the Rheumatic Diseases Aug 2018Recent studies demonstrate autoantibodies are powerful tools to interrogate molecular events linking cancer and the development of autoimmunity in scleroderma.... (Observational Study)
Observational Study
OBJECTIVES
Recent studies demonstrate autoantibodies are powerful tools to interrogate molecular events linking cancer and the development of autoimmunity in scleroderma. Investigating cancer risk in these biologically relevant subsets may provide an opportunity to develop personalised cancer screening guidelines. In this study, we examined cancer risk in distinct serologic and phenotypic scleroderma subsets and compared estimates with the general population.
METHODS
Patients in the Johns Hopkins Scleroderma Center observational cohort were studied. Overall and site-specific cancer incidence was calculated in distinct autoantibody and scleroderma phenotypic subsets, and compared with the Surveillance, Epidemiology and End Results registry, a representative sample of the US population.
RESULTS
2383 patients with scleroderma contributing 37 686 person-years were studied. 205 patients (8.6%) had a diagnosis of cancer. Within 3 years of scleroderma onset, cancer risk was increased in patients with RNA polymerase III autoantibodies (antipol; standardised incidence ratio (SIR) 2.84, 95% CI 1.89 to 4.10) and those lacking centromere, topoisomerase-1 and pol antibodies (SIR 1.83, 95% CI 1.10 to 2.86). Among antipol-positive patients, cancer-specific risk may vary by scleroderma subtype; those with diffuse scleroderma had an increased breast cancer risk, whereas those with limited scleroderma had high lung cancer risk. In contrast, patients with anticentromere antibodies had a lower risk of cancer during follow-up (SIR 0.59, 95% CI 0.44 to 0.76).
CONCLUSIONS
Autoantibody specificity and disease subtype are biologically meaningful filters that may inform cancer risk stratification in patients with scleroderma. Future research testing the value of targeted cancer screening strategies in patients with scleroderma is needed.
Topics: Adult; Antibodies, Antinuclear; Autoantibodies; Breast Neoplasms; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phenotype; Registries; Risk Assessment; Scleroderma, Diffuse; Scleroderma, Localized; United States
PubMed: 29678941
DOI: 10.1136/annrheumdis-2018-212999 -
Orphanet Journal of Rare Diseases Apr 2015Progressive Hemifacial Atrophy (PHA) is an acquired, typically unilateral, facial distortion with unknown etiology. The true incidence of this disorder has not been... (Review)
Review
BACKGROUND
Progressive Hemifacial Atrophy (PHA) is an acquired, typically unilateral, facial distortion with unknown etiology. The true incidence of this disorder has not been reported, but it is often regarded as a subtype of localized scleroderma. Historically, a debate existed whether PHA is a form of linear scleroderma, called morphea en coup de sabre (ECDS), or whether these conditions are inherently different processes or appear on a spectrum (; Adv Exp Med Biol 455:101-4, 1999; J Eur Acad Dermatol Venereol 19:403-4, 2005). Currently, it is generally accepted that both diseases exist on a spectrum of localized scleroderma and often coexist. The pathogenesis of PHA has not been delineated, but trauma, autoimmunity, infection, and autonomic dysregulation have all been suggested. The majority of patients have initial manifestations in the first two decades of life; however, late presentations in 6th and 7th decades are also described [J Am Acad Dermatol 56:257-63, 2007; J Postgrad Med 51:135-6, 2005; Neurology 61:674-6, 2003]. The typical course of PHA is slow progression over 2-20 years and eventually reaching quiescence. Systemic associations of PHA are protean, but neurological manifestations of seizures and headaches are common [J Am Acad Dermatol 56:257-63, 2007; Neurology 48:1013-8, 1997; Semin Arthritis Rheum 43:335-47, 2013]. As in many rare diseases, standard guidelines for imaging, treatment, and follow-up are not defined.
METHODS
This review is based on a literature search using PubMed including original articles, reviews, cases and clinical guidelines. The search terms were "idiopathic hemifacial atrophy", "Parry-Romberg syndrome", "Romberg's syndrome", "progressive hemifacial atrophy", "progressive facial hemiatrophy", "juvenile localized scleroderma", "linear scleroderma", and "morphea en coup de sabre". The goal of this review is to summarize clinical findings, theories of pathogenesis, diagnosis, clinical course, and proposed treatments of progressive hemifacial atrophy using a detailed review of literature.
INCLUSION- AND EXCLUSION CRITERIA
Review articles were used to identify primary papers of interest while retrospective cohort studies, case series, case reports, and treatment analyses in the English language literature or available translations of international literature were included.
Topics: Facial Hemiatrophy; Humans; Scleroderma, Localized
PubMed: 25881068
DOI: 10.1186/s13023-015-0250-9 -
Frontiers in Immunology 2021
Topics: Animals; Autoimmunity; Disease Susceptibility; Humans; Scleroderma, Systemic
PubMed: 33828566
DOI: 10.3389/fimmu.2021.663381 -
Medicina (Kaunas, Lithuania) Nov 2021Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms... (Review)
Review
Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms responsible for different clinical-pathological pictures. The absence of antinuclear antibodies (ANA), Raynaud's phenomenon and capillaroscopic anomalies constitutes an important element of differential diagnosis with systemic sclerosis. When scleroderma can be excluded, on the basis of the main body sites, clinical evolution, any associated pathological conditions and specific histological features, it is possible to make a correct diagnosis.
Topics: Antibodies, Antinuclear; Humans; Raynaud Disease; Scleroderma, Localized; Scleroderma, Systemic; Skin
PubMed: 34833493
DOI: 10.3390/medicina57111275 -
Cytokine Aug 2011Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue... (Review)
Review
Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future.
Topics: Autoantibodies; Cytokines; Humans; Receptors, Interleukin; Scleroderma, Localized; T-Lymphocytes, Helper-Inducer
PubMed: 21536453
DOI: 10.1016/j.cyto.2011.04.001 -
Dermatology (Basel, Switzerland) 2020Scleroderma is a heterogeneous group of diseases that can be localized or systemic. Localized scleroderma is a fibrosis of the skin characterized by inflammation and... (Review)
Review
BACKGROUND
Scleroderma is a heterogeneous group of diseases that can be localized or systemic. Localized scleroderma is a fibrosis of the skin characterized by inflammation and thickening due to excessive collagen deposition, and systemic sclerosis (SSc) is characterized by vasculopathy, immune dysregulation and skin fibrosis. In general, the prognosis of scleroderma highly depends on the degree of visceral involvement and relates to the degree of skin fibrosis. Despite the numerous therapies used for patients with scleroderma, the disease-related morbidity and mortality are high. Studies have explored the effects of extracorporeal photopheresis (ECP) in scleroderma treatment. Originally used in the treatment of cutaneous T-cell lymphoma, ECP is an immunomodulatory procedure in which a patient's white blood cells are treated with 8-methoxypsoralen and exposed to UVA radiation to inhibit cell proliferation and induce immunosuppression.
SUMMARY
Multiple lines of evidence suggest that ECP may be a safe and possibly effective therapy for patients with scleroderma, specifically demonstrating improvement in patients with cutaneous manifestations of the disease. However, future studies assessing its role in managing visceral involvement are needed. Our review aims to examine and consolidate the results of clinical studies and propose a possible role for ECP in the management of scleroderma.
KEY POINTS
ECP may be an effective and safe procedure for the treatment of SSc.
Topics: Humans; Photopheresis; Scleroderma, Systemic
PubMed: 31362294
DOI: 10.1159/000501591 -
Rheumatology (Oxford, England) May 2022Juvenile systemic sclerosis (JSSc) is a rare condition in childhood and its variety with no skin involvement, sine scleroderma (ssJSSc), is anecdotal. We report the...
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.
Topics: Child; Delayed Diagnosis; Humans; Lung Diseases, Interstitial; Retrospective Studies; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 34605913
DOI: 10.1093/rheumatology/keab738 -
Pediatric Clinics of North America Apr 2012Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common... (Review)
Review
Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage.
Topics: Anti-Inflammatory Agents; Child; Dermatologic Agents; Humans; Immunosuppressive Agents; Prognosis; Scleroderma, Localized; Scleroderma, Systemic; Treatment Outcome; Ultraviolet Therapy
PubMed: 22560576
DOI: 10.1016/j.pcl.2012.03.011 -
Autoimmunity Reviews Jun 2022We conducted a systematic review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases (EULAR SG MC/RD), to investigate the value of nailfold... (Review)
Review
Standardised interpretation of capillaroscopy in autoimmune idiopathic inflammatory myopathies: A structured review on behalf of the EULAR study group on microcirculation in Rheumatic Diseases.
OBJECTIVE
We conducted a systematic review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases (EULAR SG MC/RD), to investigate the value of nailfold videocapillaroscopy (NVC) in idiopathic inflammatory myopathies (IIM).
METHODS
Three electronic databases were systematically searched to find all relevant manuscripts reporting NVC outcomes in IIM patients. Articles were assessed based on study design, population, NVC methodology and description of NVC results. To allow comparison between the articles, all NVC results were interpreted according to standardised capillaroscopic terminology, as previously consented by the EULAR SG MC/RD and the Scleroderma Clinical Trials Consortium (SCTC) Group on Capillaroscopy.
RESULTS
Of the 653 identified records; five were retained after critical appraisal on title, abstract and manuscript level. A marked difference in NVC was observed between (juvenile) dermatomyositis [(j)DM] versus polymyositis, healthy controls and systemic sclerosis patients. In addition, reduced capillary density and scleroderma pattern seem to be associated with active disease in (j)DM, while immunosuppressive treatment appears to reduce NVC abnormalities.
CONCLUSION
This is the first systematic review investigating NVC in IIM, interpreting the results according to an international consented standardised manner, as proposed by the EULAR SG MC/RD and SCTC Group on Capillaroscopy. We can conclude that NVC presents a promising asset in the diagnosis of (j)DM. Moreover, NVC could be a biomarker for organ involvement and follow-up. Large multicentre prospective standardised studies are further needed to definitely describe associations with clinical and laboratory parameters in the different IIM subtypes.
Topics: Autoimmune Diseases; Capillaries; Dermatomyositis; Humans; Microcirculation; Microscopic Angioscopy; Myositis; Nails; Prospective Studies; Rheumatic Diseases; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35421608
DOI: 10.1016/j.autrev.2022.103087