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Heidi Jacobe - One of the best experts on this subject based on the ideXlab platform.
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Morphea progress to date and the road ahead
Annals of Translational Medicine, 2021Co-Authors: Laila F Abbas, Elaine Kunzler, Adrienne Joseph, Heidi JacobeAbstract:Morphea is a rare autoimmune condition causing inflammation and sclerosis of the skin and underlying soft tissue. It is characterized by periods of activity (inflammation admixed with fibrosis), ultimately resulting in permanent damage (pigment change and tissue loss). Damage resulting from unchecked activity can lead to devastating, permanent cosmetic and functional sequelae including hair loss; cutaneous, soft tissue and bony atrophy; joint contractures; and growth restriction of the affected body site in children. This makes the early identification of activity and initiation of appropriate treatment crucial to limiting damage in Morphea. To this end, recent investigative work has focused on validation of clinical, biomarker, imaging, and histologic outcomes aimed at accurately quantifying activity and damage. Despite promising results, further work is needed to better validate these measures before they can be used in the clinic and research settings. Although there has been recent approval of less toxic, targeted therapies for many inflammatory skin conditions, none have been systematically investigated in Morphea. The mainstays of treatment for active Morphea are corticosteroids and methotrexate. These are often limited by substantial toxicity. The paucity of new treatments for Morphea is the result of a lack of studies examining its pathogenesis, with many reviews extrapolating from research in systemic sclerosis. Recent studies have demonstrated the role of dysregulated immune and fibrotic pathways in the pathogenesis of Morphea, particularly interferon (IFN) gamma related pathways. Active Morphea lesions have been found to display an inflammatory Morphea signature with CXCR3 receptor ligands, as well as a distinct fibrotic signature reflecting fibroblast activation and collagen production. CXCL9 and 10 have been associated with increased measures of disease activity. While immune dysfunction is thought to play the primary role in Morphea pathogenesis, there are other factors that may also contribute, including genetic predisposition, environmental factors, and vascular dysregulation. There remains an essential need for further research to elucidate the pathogenesis of Morphea and the mode of action of dysregulated upstream and downstream immune and fibrotic pathways. These studies will allow for the discovery of novel biomarkers and targets for therapeutic development.
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an evaluation of the performance of current Morphea subtype classifications
JAMA Dermatology, 2021Co-Authors: Smriti Prasad, Kathryn S. Torok, Jane L Zhu, Kaila Schollaertfitch, Heidi JacobeAbstract:Importance Numerous classification systems for Morphea subtypes exist, but none have been systematically evaluated for their ability to categorize patients with Morphea into demographically and clinically coherent groups. Although some subtypes, such as linear Morphea, are present across all the classification schemes, others list unique subtypes. This creates confusion among investigators and practitioners and impairs accurate categorization of patients for study and clinical evaluation. Objective To evaluate how frequently the commonly used Morphea classification systems categorize patients with Morphea into clinically relevant subtypes using cross-sectional analysis of 2 large patient cohorts. Design, setting, and participants This cross-sectional study comprised 944 adults and children from 2 prospective cohorts-the Morphea in Adults and Children at the University of Texas Southwestern Medical Center (Dallas, Texas), which enrolled participants from July 20, 2007, to September 21, 2018, and the National Registry for Childhood-Onset Scleroderma at the University of Pittsburgh (Pittsburgh, Pennsylvania), which enrolled participants from October 23, 2002, to November 13, 2018. Main outcomes and measures Patient demographic characteristics, Morphea subtype, quality-of-life measures, disease activity, and damage as measured by Localized Scleroderma Cutaneous Assessment Tool scores during initial visits. Results A total of 944 participants (444 patients with adult-onset Morphea and 500 patients with pediatric-onset Morphea; 741 female participants [78%]; median age at onset, 16 years [interquartile range, 8-44 years]) were included in this study. Most participants were White (723 [77%]) and had the linear (474 [50%]) or generalized subtype of Morphea (244 [26%]). With the use of the previously published Padua criteria, most patients were classified to have linear Morphea (474 [50%]), followed by generalized Morphea (244 [26%]), plaque Morphea (141 [15%]), mixed Morphea (38 [4%]), and pansclerotic Morphea (3 [0.3%]). Overall, the Padua criteria successfully classified 900 patients (95%) in comparison with the Peterson criteria (533 [56%]) and the European Dermatology Forum classification (487 [52%]). Conclusions and relevance In this cross-sectional study of Morphea subtype classification systems, the Padua criteria performed best in classifying patients into subgroups with cohesive demographic and clinical features, supporting its widespread use. However, they have ambiguities that might lead to misclassification, particularly in terms of generalized and pansclerotic Morphea and descriptors such as Morphea profunda. Consensus-based approaches are needed to address these ambiguities and develop a unified classification scheme.
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evaluation of the effectiveness and tolerability of mycophenolate mofetil and mycophenolic acid for the treatment of Morphea
JAMA Dermatology, 2020Co-Authors: Megan Arthur, Nicole Fett, Heidi Jacobe, Elaine Kunzler, Stephanie Florezpollack, Smriti Prasad, Emile Latour, Jacob Houser, Shivani Sharma, Alisa N FemiaAbstract:Importance First-line systemic therapy for Morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)—referred to herein asmycophenolate—is recommended; however, evidence to support this recommendation remains weak. Objective To evaluate the effectiveness and tolerability of mycophenolate for the treatment of Morphea. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with Morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures The primary outcome was Morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of Morphea. Results There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized Morphea (37 [48%]), pansclerotic Morphea (12 [16%]), and linear Morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of Morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe Morphea.
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using the localized scleroderma cutaneous assessment tool loscat to classify morphoea by severity and identify clinically significant change
British Journal of Dermatology, 2020Co-Authors: Noelle M Teske, Heidi JacobeAbstract:Background Validated scoring measures in morphoea can facilitate clinical trials. Objectives To ascertain the clinical significance of scores on the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and identify the change in scores correlated with clinically meaningful change. Methods A prospective study of 120 participants from the Morphea in Adults and Children (MAC) cohort was undertaken. Physician's subjective assessments of severity and of improvement were completed at each visit. Receiver operating characteristic analysis determined LoSCAT scores corresponding with mild, moderate and severe disease, and absolute and percentage changes in scores corresponding with improved or worsened disease activity or damage. Results Mild, moderate and severe activity corresponded with LoSCAT activity index (LoSAI) scores of 0-4, 5-12 and 13 and over, and with Physician's Global Assessment of activity (PGA-A) scores of 0-10, 11-30 and 31 and over. Mild, moderate and severe damage corresponded with LoSCAT damage index (LoSDI) scores of 0-10, 11-15 and 16 and over, and with PGA of damage (PGA-D) scores of 0-18, 19-30 and 31 and over. Improved activity was best indicated by LoSAI decrease of at least 2 points or 27·5%, or PGA-A decrease of at least 6 points. Improved damage was best indicated by LoSDI score decrease of at least 2 points. Worsening activity was best indicated by LoSAI increase of at least 2 points or 19·5%, or PGA-A increase of at least 4 points. Worsening damage was best indicated by LoSDI increase of at least 25·5%. Conclusions The LoSCAT can be used to classify patients with morphoea by disease severity, and identify clinically significant improvement in activity. What's already known about this topic? The Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) is a clinical tool that separately quantifies disease activity and damage in morphoea, and prior studies have demonstrated validity and reliability. What does this study add? The LoSCAT can be used to classify patients with morphoea by disease severity into mild, moderate and severe groups, and to identify clinically significant improvement in disease activity in patients with morphoea. The LoSCAT may be limited in its ability to detect clinically significant changes in disease damage.
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linear Morphea clinical characteristics disease course and treatment of the Morphea in adults and children cohort
Journal of The American Academy of Dermatology, 2019Co-Authors: Noelle M Teske, Elaine Kunzler, Stephanie Florezpollack, Jack C Obrien, Smriti Prasad, Heidi JacobeAbstract:Background Prospective, longitudinal studies examining the features of linear Morphea are limited. Objective To utilize the Morphea in Adults and Children cohort to determine clinical characteristics, impact on life quality, and disease course of linear Morphea in a prospective, longitudinal manner. Methods Characteristics of linear Morphea versus other subtypes were compared in a cross-sectional manner. Next, linear Morphea participants were examined in depth over a 3-year period. Results Linear Morphea was the most common Morphea subtype (50.1%, 291/581) in the cohort. Deep involvement was more common in linear (64.3%, 187/291) than other Morphea subtypes. Linear Morphea participants with deep involvement were more likely to have a limitation in range of motion (28.6%, 55/192) than those without (11.1%, 11/99, P Limitations Results of the study are associative, and the University of Texas Southwestern Medical Center is a tertiary referral center. Conclusion A substantial number of linear Morphea patients have adult-onset disease. In all age groups, linear Morphea with deep involvement was associated with functional limitations.
Nicole Fett - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effectiveness and tolerability of mycophenolate mofetil and mycophenolic acid for the treatment of Morphea
JAMA Dermatology, 2020Co-Authors: Megan Arthur, Nicole Fett, Heidi Jacobe, Elaine Kunzler, Stephanie Florezpollack, Smriti Prasad, Emile Latour, Jacob Houser, Shivani Sharma, Alisa N FemiaAbstract:Importance First-line systemic therapy for Morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)—referred to herein asmycophenolate—is recommended; however, evidence to support this recommendation remains weak. Objective To evaluate the effectiveness and tolerability of mycophenolate for the treatment of Morphea. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with Morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures The primary outcome was Morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of Morphea. Results There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized Morphea (37 [48%]), pansclerotic Morphea (12 [16%]), and linear Morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of Morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe Morphea.
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scleroderma nomenclature etiology pathogenesis prognosis and treatments facts and controversies
Clinics in Dermatology, 2013Co-Authors: Nicole FettAbstract:Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with Morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of Morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although Morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for Morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in Morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc.
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Morphea evidence based recommendations for treatment
Indian Journal of Dermatology Venereology and Leprology, 2012Co-Authors: Nicole FettAbstract:Morphea is a rare fibrosing disorder of the skin. Evidence-based treatment strategies in Morphea are lacking. This review summarizes the available data on Morphea treatment and provides therapeutic strategies based on Morphea subtypes. The Cochrane Library, Medline and Embase from inception until May of 2011 were searched using the key words "Morphea" and "Morphea treatment." Reference lists of the resultant articles, as well as relevant reviews, were also searched. This review focuses on randomized controlled trials, prospective interventional trials without controls and retrospective reviews with greater than five subjects.
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update on Morphea part ii outcome measures and treatment
Journal of The American Academy of Dermatology, 2011Co-Authors: Nicole Fett, Victoria P. WerthAbstract:Morphea is a rare fibrosing disorder of the skin and underlying tissues. The underlying pathogenesis of Morphea is not completely understood at this time, but ultimately results in an imbalance of collagen production and destruction. Evidence-based treatment options of Morphea are limited secondary to the rarity of the disease, and the lack of universally used validated outcome measures. The most commonly used outcome measures are skin scores, computerized surface area measurement, durometer, cutometer, thermography, and ultrasound measurements. The Localized Scleroderma Cutaneous Assessment Tool is a promising recently validated skin scoring tool that allows differentiation between activity and damage, is sensitive to change, and requires no additional equipment. The most robust data in the treatment of Morphea exists for methotrexate in combination with systemic steroids and ultraviolet A1.
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Update on Morphea: Part I. Epidemiology, clinical presentation, and pathogenesis
Journal of the American Academy of Dermatology, 2011Co-Authors: Nicole Fett, Victoria P. WerthAbstract:Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and underlying tissues. Morphea is differentiated from systemic sclerosis based on the absence of sclerodactyly, Raynaud phenomenon, and nailfold capillary changes. Patients with Morphea commonly have systemic symptoms, such as malaise, fatigue, arthralgias, and myalgias, as well as positive autoantibody serologies. However, involvement of Morphea is almost uniformly limited to those tissues derived from the mesoderm. The underlying pathogenesis of Morphea is incompletely understood at this time, but ultimately results in an imbalance of collagen production and destruction.
Rebecca Vasquez - One of the best experts on this subject based on the ideXlab platform.
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recurrence of Morphea after successful ultraviolet a1 phototherapy a cohort study
Journal of The American Academy of Dermatology, 2014Co-Authors: Rebecca Vasquez, Chul Ahn, Aysha Jabbar, Fatima Khan, Douglas Buethe, Heidi JacobeAbstract:Background Studies support efficacy of ultraviolet (UV)A1 phototherapy, but little is known about recurrence after successful UVA1 treatment. Objective We sought to determine the frequency of recurrent activity after UVA1 phototherapy and variables associated with recurrence. Methods This was a case series and prospective cohort study of patients treated with UVA1 phototherapy with minimum 6 months of follow-up. Demographics, clinical features, and cumulative UVA1 dose were analyzed for association with recurrence. Results Of 37 patients, 46% (n = 17) had recurrence of active Morphea lesions after successful UVA1 phototherapy. Two-year and 3-year (after the last UVA1 phototherapy treatment) recurrence rates were 44.5% (95% confidence interval 30.1%-62.2%) and 48.4% (95% confidence interval 33.2%-66.1%), respectively. The only variable associated with recurrence was duration of Morphea before UVA1 (P value = .02, hazard ratio 1.15, 95% confidence interval 1.06-1.27). Limitations The sample size limits conclusions. Conclusion With the exception of increased duration of Morphea, risk of recurrence is no different in adults and children, or between Morphea subtypes, skin types, and medium- to high-dose regimens. This indicates treatment doses in the medium-high UVA1 range are adequate with respect to frequency of recurrence.
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clinical features of patients with Morphea and the pansclerotic subtype a cross sectional study from the Morphea in adults and children cohort
The Journal of Rheumatology, 2014Co-Authors: Andrew Kim, Nicholas Marinkovich, Rebecca Vasquez, Heidi JacobeAbstract:Objective Pansclerotic Morphea is a poorly described form of Morphea with little information on prevalence, demographics, and clinical features. Classification criteria for this subtype varies and the distinction from other forms of Morphea, such as extensive generalized Morphea and pansclerotic Morphea, is not always clear. The purpose of our study was to clarify classification criteria for pansclerotic Morphea by identifying its prevalence in the Morphea in adults and children (MAC) cohort and describing its demographic and clinical features as compared with generalized Morphea. Methods Patients who met predefined criteria for generalized and pansclerotic Morphea were identified using a modified Laxer and Zulian classification system. Baseline demographic and clinical features of the patients were compiled and then analyzed for traits characteristic of pansclerotic Morphea versus those of generalized Morphea. One hundred and thirteen patients met the criteria for inclusion: pansclerotic (n = 13) and generalized Morphea type (n = 100). Results Patients with pansclerotic Morphea were more frequently male (46.2% vs 6%; p Conclusion Our results suggest demographic and clinical features are sufficient to define the pansclerotic subtype as they represent a distinct clinical phenotype with a more rapidly progressive and severe course commonly accompanied by disability. Presence of features of the pansclerotic phenotype should alert practitioners to the possibility of significant morbidity and the need for early aggressive treatment.
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Morphea and other localized forms of scleroderma
Current Opinion in Rheumatology, 2012Co-Authors: Rebecca Vasquez, Chelsea Sendejo, Heidi JacobeAbstract:PURPOSE OF REVIEW Morphea, also known as localized scleroderma, is a disorder of excessive collagen deposition leading to thickening of the dermis and/or subcutaneous tissues and may cause significant morbidity. This review will describe new developments in the evaluation and management of Morphea as well as its pathophysiology. The reader will be able to apply these findings to patient management. RECENT FINDINGS The recent development of validated outcome measures (i.e. the localized scleroderma cutaneous assessment tool) as well as consensus treatment recommendations provide a platform for collaboration among specialties to develop both standardized assessment tools and therapeutic trials. New studies have also begun to investigate the immunological underpinnings of Morphea. SUMMARY The promise of evidence-based treatments for Morphea in the near future will provide better care for patients with Morphea and understanding its pathophysiology will lay groundwork for the development of new treatments.
Chul Ahn - One of the best experts on this subject based on the ideXlab platform.
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major histocompatibility complex class i and class ii alleles may confer susceptibility to or protection against Morphea findings from the Morphea in adults and children cohort
Arthritis & Rheumatism, 2014Co-Authors: Heidi Jacobe, Chul Ahn, Frank C Arnett, John D ReveilleAbstract:Objective To determine the HLA class I and class II alleles of the human major histocompatibility complex showing an association with Morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort, using a nested case–control association study. Methods Patients with Morphea were identified from the MAC cohort, and matched controls were obtained from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Scleroderma Family Registry and DNA Repository and from the Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA class II genotyping and single-strand conformational polymorphism typing were performed to identify HLA–A, B, and C alleles. Associations between HLA class I and class II alleles and Morphea, as well as its subphenotypes, were determined. Results Two hundred eleven patients with Morphea and 726 matched controls were available for HLA class I typing, and 158 patients with Morphea and 1,008 matched controls were available for HLA class II typing. The strongest associations were found with DRB1*04:04 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4–4.0, P = 0.002), and HLA–B*37 conferred the highest OR among the class I alleles (OR 3.2, 95% CI 1.5–6.5, P = 0.001). Comparison of the risk allele profile in this cohort with the risk alleles previously identified in patients with systemic sclerosis, determined using the same methods and same control population, revealed one allele in common, DRB*04:04. Conclusion These results demonstrate that specific HLA class I and class II alleles are associated with Morphea and are also likely to be associated with generalized and linear subtypes of Morphea. The Morphea-associated alleles are different from those found in scleroderma, suggesting that Morphea is immunogenetically distinct. Risk alleles in Morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population-based studies have indicated that patients with RA have an increased risk of Morphea, and therefore a common susceptibility allele may be implicated.
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recurrence of Morphea after successful ultraviolet a1 phototherapy a cohort study
Journal of The American Academy of Dermatology, 2014Co-Authors: Rebecca Vasquez, Chul Ahn, Aysha Jabbar, Fatima Khan, Douglas Buethe, Heidi JacobeAbstract:Background Studies support efficacy of ultraviolet (UV)A1 phototherapy, but little is known about recurrence after successful UVA1 treatment. Objective We sought to determine the frequency of recurrent activity after UVA1 phototherapy and variables associated with recurrence. Methods This was a case series and prospective cohort study of patients treated with UVA1 phototherapy with minimum 6 months of follow-up. Demographics, clinical features, and cumulative UVA1 dose were analyzed for association with recurrence. Results Of 37 patients, 46% (n = 17) had recurrence of active Morphea lesions after successful UVA1 phototherapy. Two-year and 3-year (after the last UVA1 phototherapy treatment) recurrence rates were 44.5% (95% confidence interval 30.1%-62.2%) and 48.4% (95% confidence interval 33.2%-66.1%), respectively. The only variable associated with recurrence was duration of Morphea before UVA1 (P value = .02, hazard ratio 1.15, 95% confidence interval 1.06-1.27). Limitations The sample size limits conclusions. Conclusion With the exception of increased duration of Morphea, risk of recurrence is no different in adults and children, or between Morphea subtypes, skin types, and medium- to high-dose regimens. This indicates treatment doses in the medium-high UVA1 range are adequate with respect to frequency of recurrence.
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Morphea in adults and children cohort iii nested case control study the clinical significance of autoantibodies in Morphea
JAMA Dermatology, 2013Co-Authors: Jennifer Warner Dharamsi, Sandra Victor, Nancy Aguwa, Chul Ahn, Frank C Arnett, Maureen D Mayes, Heidi JacobeAbstract:Importance Small studies have implicated the association of specific autoantibodies with Morphea subtype or severity, but no large-scale studies have been conducted. This prospective case-control study confirmed the presence of antinuclear antibodies (ANAs) and other autoantibodies in Morphea but found they are of limited significance. Objective To determine the prevalence of ANAs, extractable nuclear antigens such as antihistone antibodies (AHAs), and anti–single-stranded DNA antibodies (ssDNA abs) in patients with Morphea vs a healthy control population and their association with clinical measures of Morphea severity. Design, Setting, and Participants Nested case-control study, conducted at the University of Texas Southwestern Medical Center, Dallas, and University of Texas Health Science Center, Houston. Study participants included individuals enrolled in the Morphea in Adults and Children (MAC) cohort and Scleroderma Family Registry and DNA Repository. Main Outcomes and Measures Prevalence of ANAs, AHAs, ssDNA abs in patients with Morphea vs matched controls and association of the presence of autoantibodies with clinical indicators of Morphea severity. Results The prevalence of ANAs, AHAs, and ssDNA abs in patients with Morphea was 34%, 12%, and 8%, respectively. Antinuclear antibodies and AHAs, but not ssDNA abs, were present more frequently in cases than in controls. There was no difference in ANA prevalence among Morphea subtypes. Among patients with linear Morphea, the presence of autoantibodies was associated with clinical indicators of severe Morphea including functional limitation (ssDNA ab, P = .005; and AHA, P = .006), extensive body surface area involvement (ssDNA ab, P = .01; and ANA, P = .005), and higher skin scores (ANA, P = .004). The presence of autoantibodies was not associated with clinical measures of Morphea activity. Conclusions and Relevance Our results demonstrate that ANAs and AHAs are more prevalent among patients with Morphea but are of limited clinical utility except in linear Morphea, where their presence, although infrequent, is associated with greater lesion burden and functional impairment.
Elke M. G. J. De Jong - One of the best experts on this subject based on the ideXlab platform.
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Morphea and Eosinophilic Fasciitis: An Update
American Journal of Clinical Dermatology, 2017Co-Authors: Jorre S. Mertens, Marieke M.b. Seyger, Rogier M. Thurlings, Timothy R. D. J. Radstake, Elke M. G. J. De JongAbstract: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.
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Efficacy of topical tacrolimus 0.1 in active plaque Morphea: Randomized, double-blind, emollient-controlled pilot study
American Journal of Clinical Dermatology, 2009Co-Authors: Elisabeth B.m. Kroft, Tamara J. Groeneveld, Marieke M.b. Seyger, Elke M. G. J. De JongAbstract:BACKGROUND: Tacrolimus, a calcineurin inhibitor, is an immunomodulating and anti-inflammatory drug that inhibits T-cell activation and production of cytokines. The elevated level of cytokines in Morphea causes fibroblast proliferation and subsequent overproduction of collagen. Theoretically, tacrolimus could inhibit the pathophysiologic process of Morphea. OBJECTIVE: To assess whether tacrolimus 0.1% ointment is an effective treatment for active plaque Morphea in a double-blind, placebo (petroleum emollient)-controlled pilot study. METHODS: Ten patients with active plaque Morphea were included. All patients were treated with tacrolimus 0.1% ointment and with an emollient (petrolatum) on two selected Morphea plaques, applied twice daily for 12 weeks. Initial and final assessment included surface area measurements, photography, durometer scores, and clinical feature scores. Adverse reactions were recorded. RESULTS: The scleroderma plaques treated with topical tacrolimus 0.1% improved, resulting in a significant reduction in durometer and clinical feature scores. Overall, a significant difference could be found between topical tacrolimus and petrolatum with regard to durometer score (p < 0.005) and the clinical feature score (p = 0.019). CONCLUSION: In this first double-blind, placebo-controlled pilot study comparing tacrolimus 0.1% ointment with petrolatum in active plaque Morphea, tacrolimus 0.1% ointment was shown to be an effective treatment for this condition.
