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Anais Brasileiros de Dermatologia 2015Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known:... (Review)
Review
Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.
Topics: Biopsy; Female; Humans; Male; Scleroderma, Localized; Scleroderma, Systemic; Skin
PubMed: 25672301
DOI: 10.1590/abd1806-4841.20152890 -
Immunity, Inflammation and Disease Dec 2021Morphea (localized scleroderma) is a rare autoimmune connective tissue disease with variable clinical presentations, with an annual incidence of 0.4-2.7 cases per... (Review)
Review
Morphea (localized scleroderma) is a rare autoimmune connective tissue disease with variable clinical presentations, with an annual incidence of 0.4-2.7 cases per 100,000. Morphea occurs most frequently in children aged 2-14 years, and the disease exhibits a female predominance. Insights into morphea pathogenesis are often extrapolated from studies of systemic sclerosis due to their similar skin histopathologic features; however, clinically they are two distinct diseases as evidenced by different demographics, clinical features, disease course and prognosis. An interplay between genetic factors, epigenetic modifications, immune and vascular dysfunction, along with environmental hits are considered as the main contributors to morphea pathogenesis. In this review, we describe potential new therapies for morphea based on both preclinical evidence and ongoing clinical trials. We focus on different classes of therapeutics, including antifibrotic, anti-inflammatory, cellular and gene therapy, and antisenolytic approaches, and how these target different aspects of disease pathogenesis.
Topics: Child; Disease Progression; Female; Humans; Prognosis; Scleroderma, Localized; Scleroderma, Systemic; Skin
PubMed: 34272836
DOI: 10.1002/iid3.475 -
Actas Dermo-sifiliograficas Oct 2013Morphea or localized scleroderma is a distinctive inflammatory disease that leads to sclerosis of the skin and subcutaneous tissues. It comprises a number of subtypes... (Review)
Review
Morphea or localized scleroderma is a distinctive inflammatory disease that leads to sclerosis of the skin and subcutaneous tissues. It comprises a number of subtypes differentiated according to their clinical presentation and the structure of the skin and underlying tissues involved in the fibrotic process. However, classification is difficult because the boundaries between the different types of morphea are blurred and different entities frequently overlap. The main subtypes are plaque morphea, linear scleroderma, generalized morphea, and pansclerotic morphea. With certain exceptions, the disorder does not have serious systemic repercussions, but it can cause considerable morbidity. In the case of lesions affecting the head, neurological and ocular complications may occur. There is no really effective and universal treatment so it is important to make a correct assessment of the extent and severity of the disease before deciding on a treatment approach.
Topics: Algorithms; Aminoquinolines; Clinical Trials as Topic; Eosinophilia; Fasciitis; Glucocorticoids; Humans; Imiquimod; Immunosuppressive Agents; Methotrexate; Photochemotherapy; Physical Therapy Modalities; Recurrence; Scleroderma, Localized; Severity of Illness Index
PubMed: 23948159
DOI: 10.1016/j.adengl.2012.10.012 -
American Journal of Clinical Dermatology Aug 2017Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which... (Review)
Review
Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.
Topics: Administration, Cutaneous; Administration, Oral; Algorithms; Biopsy; Calcitriol; Dermatologic Agents; Diagnosis, Differential; Disease Progression; Drug Therapy, Combination; Eosinophilia; Evidence-Based Medicine; Fasciitis; Glucocorticoids; Humans; Methotrexate; Phototherapy; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Scleroderma, Localized; Skin; Tacrolimus; Treatment Outcome; United States
PubMed: 28303481
DOI: 10.1007/s40257-017-0269-x -
Giornale Italiano Di Dermatologia E... Apr 2018Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for... (Review)
Review
Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for Systemic Sclerosis, developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for a patient to be classified as having scleroderma. Histological examination is not included in the diagnostic criteria and is not routinely performed. Skin biopsy is recommended only in the case of diagnostic doubt with other scleroderma like disorders (scleromyxedema, scleredema, nephrogenic systemic fibrosis). Alternatively, skin biopsy is also often performed for research purposes. Indeed, the first step analysis of new cytokines or pathways that may contribute to the pathogenesis of the disease requires the evaluation of their expression or activation in the skin of scleroderma patients compared to healthy controls. The histological picture of the skin in bot localized and systemic scleroder shows initially microvascular alterations and chronic inflammation while in the more advanced stages skin fibrosis prevails. Localized scleroderma (LS) or morphea includes a number of subtypes which are classified more according to their clinical presentation rather than histopathological pictures. However, some histopathologic changes may be useful in differentiating each entity from the others and from other sclerodermoid disorders.
Topics: Biopsy; Cytokines; Diagnosis, Differential; Humans; Scleroderma, Localized; Scleroderma, Systemic; Skin Diseases
PubMed: 29368844
DOI: 10.23736/S0392-0488.18.05922-9 -
Clinical Reviews in Allergy & Immunology Jun 2023Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality... (Review)
Review
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.
Topics: Humans; Hypertension, Renal; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Scleroderma, Systemic; Scleroderma, Localized
PubMed: 35648373
DOI: 10.1007/s12016-022-08945-x -
Gaceta Medica de Mexico 2019Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with... (Review)
Review
Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with extracutaneous manifestations. Its etiology is not fully understood, but it is believed that there is genetic predisposition, in addition to environmental triggering factors. Classification of the disease is not simple due to its multiple presentations; however, it is useful in order to define the treatment, which should be individualized and started early to avoid cosmetic and functional complications. In this review, we summarize the most important practical aspects of the classification, diagnostic methods and evaluation of morphea activity, as well as available therapeutic options, with an emphasis on existing clinical evidence regarding their efficacy and safety.
Topics: Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Rare Diseases; Scleroderma, Localized
PubMed: 31695234
DOI: 10.24875/GMM.18004288 -
Current Opinion in Rheumatology Nov 2022The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high... (Review)
Review
PURPOSE OF REVIEW
The majority of patients with systemic sclerosis (SSc) will experience involvement of their gastrointestinal over the course of their disease. Despite the high prevalence of gastrointestinal involvement in SSc, the strategies pertaining to the assessment and treatment for this clinical dimension of SSc have historically been limited. However, the present review highlights recent research contributions that enhance our understanding of SSc-GI patient subsets and provides updates on pathogenic mechanisms of disease, assessment and symptom-directed management.
RECENT FINDINGS
In the past few years, several studies have identified risk factors for more severe gastrointestinal disease in SSc and have provided insight to optimize diagnosis and management of SSc-GI symptoms. This article also provides a review of currently available investigations and therapies for individual SSc-GI disease manifestations and reflects on actively evolving areas of research, including our understanding the role of the gut microbiome in SSc.
SUMMARY
Here, we provide important updates pertaining to the risk stratification, assessment, diagnosis and management of SSc patients with gastrointestinal symptoms. These findings provide opportunities to enhance patient care and highlight exciting opportunities for future research.
Topics: Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Risk Factors; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35993874
DOI: 10.1097/BOR.0000000000000899 -
Medicine Nov 2022The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc... (Review)
Review
The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.
Topics: Adult; Male; Female; Humans; Scleroderma, Localized; Prospective Studies; Quality of Life; Scleroderma, Systemic; Gastrointestinal Diseases
PubMed: 36397401
DOI: 10.1097/MD.0000000000031780 -
Autoimmunity Reviews Jun 2023Systemic sclerosis is a rare autoimmune vasculopathy associated with dysregulated innate and adaptive immunity that leads to generalized systemic fibrosis. Renal... (Review)
Review
Systemic sclerosis is a rare autoimmune vasculopathy associated with dysregulated innate and adaptive immunity that leads to generalized systemic fibrosis. Renal involvement occurs in a significant proportion of systemic sclerosis patients, and is associated with worse outcome. Scleroderma renal crisis (SRC) is the most studied and feared renal complication described in systemic sclerosis. However, with the emergence of ACE inhibitors and better management, the mortality rate of SRC has significantly decreased. Renal disease in systemic sclerosis offers a wide array of differential diagnoses that may be challenging for the clinician. The spectrum of renal manifestations in systemic sclerosis ranges from an isolated decrease in glomerular filtration rate, increased intrarenal arterial stiffness, and isolated proteinuria due to SRC to more rare manifestations such as association with antiphospholipid antibody nephropathy and ANCA-associated vasculitis. The changes observed in the kidneys in systemic sclerosis are thought to be due to a complex interplay of various factors, including renal vasculopathy, as well as the involvement of the complement system, vasoactive mediators such as endothelin-1, autoimmunity, prothrombotic and profibrotic cytokines, among others. This literature review aims to provide an overview of the main renal manifestations in systemic sclerosis by discussing the most recent epidemiological and pathophysiological data available and the challenges for clinicians in making a diagnosis of renal disease in patients with systemic sclerosis.
Topics: Humans; Kidney; Scleroderma, Systemic; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Scleroderma, Localized
PubMed: 37031831
DOI: 10.1016/j.autrev.2023.103330