Capturing the Range of Disease Involvement in Localized Scleroderma: The Localized Scleroderma Total Severity Scale.

OBJECTIVE: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. METHODS: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. RESULTS: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. CONCLUSION: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies.

Serum vitamin D levels and vitamin D receptor gene ApaI and TaqI polymorphisms in patients with morphea: a case-control study.

A uncommon inflammatory condition called morphea causes fibrosis in the skin and subcutaneous tissue. The key stages in the pathophysiology are vascular damage, immunological response, and fibrosis. Numerous research have examined the relationships between the immune system, fibrosis, and vitamin D, but the exact pathogenetic pathways of morphea remain poorly understood. The purpose of this study was to investigate serum 25(OH)D levels and the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the vitamin D receptor (VDR) in morphea patients. There were 48 age- and sex-matched controls and 41 morphea patients total. VDR polymorphisms were found using PCR tests and gel electrophoresis, and serum 25(OH)D levels were determined using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The patient group consisted of 37 females (90.2%) and 4 males (9.8%). The patients' mean age was 38.68 ± 17.54 years. In terms of VDR ApaI and TaqI polymorphisms, there was no discernible difference between the patient and control groups. TaqI polymorphism heterozygosity was discovered in all patients with progressive disease, and this finding was statistically significant (p = 0.012). Patients' mean serum 25(OH)D levels were 16.98 ± 11.55 ng/mL, while those in the control group were 18.02 ± 14.30 ng/mL. VDR polymorphisms, vitamin D levels, disease subtype, age of onset, and responsiveness to treatment did not significantly correlate. In our research, we discovered that TaqI polymorphism may be related to the severity of the disease and that the polymorphisms of the VDR ApaI and TaqI were not associated with morphea susceptibility.

ENDOTHELIAL DYSFUNCTION AND PATHOGENETIC PHENOTYPES OF LOCALIZED SCLERODERMA.

There are several pathogenetic models of localized scleroderma. At the same time, studies examining the role of endothelin-1, vascular endothelial growth factor (VEGF-A) and cell adhesion molecule-1 (VCAM) are limited. Objectives - to learn the nature of disorders of vascular, proliferative, adhesive functions of the endothelium on the content of endothelin-1, VEGF-A and VCAM-1 in localized scleroderma. The study included 78 patients with localized scleroderma and 35 healthy individuals (mean age - 44.2±17.6 years, 73 women (64.6%), 40 men (35.4%). All patients underwent clinical, laboratory, enzyme-linked immunosorbent assay examination (endothelin-1, VEGF-A, VCAM-1). In the local form of scleroderma, there are the number of disorders of vascular, proliferative and adhesive functions of the endothelium, with an increase in endothelin-1 (p<0.05), VEGF-A (p<0.05) and VCAM-1 (p<0.05) content. In idiopathic atrophodermia, the level of endothelin-1 was probably higher (p<0.05). The vasospastic type of pathogenesis of localized scleroderma was established in patients under 20 years of age (p<0.05) and in patients older than 70 years (p<0.05). U-shaped age dependence of pathogenesis was noted: high content of VEGF-A in patients under 20 years of age (p<0.05) and after 35 years (p<0.05). Higher levels of VCAM-1 were found in women compared to men (p<0.05). The analysis of the age dependence of the content revealed a U-shaped dependence of VCAM-1 - the highest content in patients under 20 years (p<0.05) and in patients 55-70 years (p<0.05). The level of biomarkers of endothelial dysfunction in patients with localized scleroderma - endothelin-1, VEGF and VCAM is associated with different phenotypes of the disease course - vasospastic, proliferative or adhesive.

Effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma.

OBJECTIVES: The purpose of the study was to examine the effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma (JS). METHODS: Sixteen patients with juvenile localized scleroderma (JLS), 14 patients with Juvenile Systemic Sclerosis (JSS), and 30 healthy controls were included. Light touch-deep pressure sensation was assessed by Semmes-Weinstein monofilament test (SWMT). Localization sensation testing was performed by lightly stroking the patient's skin. The hand joint range of motion was measured with a goniometer, hand grip strength with Dynomometer, the pinch gripping force with pinch meter, and the hand mobility with modified Hand Mobility in Scleroderma (mHAMIS). Children completed their activity and participant performance status with 'Childhood Health Assessment Questionnaire (CHAQ)' and 'Jebson Taylor Hand Function Test (JTHFT)' questionnaire tests. The quality of life was evaluated using the 'Scleroderma Health Assessment Questionnaire (SHAQ)'. RESULTS: There were significantly differences among evaluated three groups in light of touch-deep pressure sensation, sense of touch localization, range of motion, mHAMIS scores, JTHFT scores, all CHAQ scores, and almost all SHAQ score (p < .05). Over than half of patients with JSS (57.1%) and almost half of patients with JLS stated that their diseases obstructed them from doing any activity (p < .001). A significant percent of JSS patients (64.3%) had hand and wrist joint involvement. CONCLUSION: Sensory and functional disorders caused by hand involvement in JS patients result in limitation of daily living activities and affect negatively the effective usage of the hand. Approximately half of the JS patients had disabilities in performing pinch motor skills of hands. The assessment of sensory symptoms that affect the functionality, activity level and participation of JSS and JLS patients should be considered during the routine clinical examination. We suggest the sensory therapies as an important factor in increasing the effectiveness of rehabilitation.

Progressive hemifacial atrophy or Parry-Romberg syndrome: A pediatric case report. / Atrofia hemifacial progresiva o síndrome de Parry-Romberg: reporte de caso pediátrico.

Progressive hemifacial atrophyor Parry-Romberg syndromeis a rare disease, classified as one of the forms of localized morphea or scleroderma. Its cause is unknown. It is characterized by atrophy of the skin, fat, muscles and underlying osteocartilaginous structures that usually affects the face and neck unilaterally, and is associated with neurological symptoms (secondary epilepsy) and involvement of other organs and systems. Its course is slow and progressive and begins in the first two decades of life. Predilection for female sex has been observed. We report the case of a 10-year-old girl diagnosed at the Hipólito Unánue Hospital in Tacna, Peru. Knowledge of this condition is important in the differential diagnosis of localized morpheas or scleroderma.

La atrofia hemifacial progresiva o síndrome de Parry-Romberg es una enfermedad rara, clasificada como una de las formas de morfea o esclerodermia localizada. Su causa es desconocida. Se caracteriza por la atrofia de la piel, tejido celular subcutáneo, músculos y estructuras osteocartilaginosas subyacentes que afecta usualmente unilateralmente la cara y cuello, se asocia a síntomas neurológicos y afección de otros órganos y sistemas. Su curso es lento y progresivo y se inicia generalmente en las primeras dos décadas de la vida. Se ha observado predilección por el sexo femenino. Presentamos el caso de una niña de 10 años, diagnosticada en el Hospital Hipólito Unánue de Tacna, Perú.

Quality of Life in Patients with Morphea: A Cross-Sectional Study and a Review of the Current Literature.

OBJECTIVE: The aim of the study was to evaluate QoL in patients suffering from morphea. Material and Methods. Sixty-five patients with morphea were recruited into this cross-sectional, prospective parallel study. QoL among adult patients was assessed with the Dermatology Life Quality Index (DLQI) and Euro-QoL-5D questionnaire; patients aged <17 years used the Children's Dermatology Life Quality Index (CDLQI). The severity of morphea was assessed using the Localized Scleroderma Cutaneous Assessment Tool. The results of QoL and its association with disease severity were compared between patients with various morphea subtypes. RESULTS: The mean DLQI scoring was 3.8 ± 4.1 points and the CDLQI was 2.3 ± 3.0. The mean value of Visual Analogue Scale thermometer (EQ VAS) was 66.9 ± 17.5 points. The disease activity of morphea based on mLoSSI correlated significantly with QoL impairment according to the DLQI (R = 0.41, p = 0.001). No significant correlation was observed between morphea-induced damage and QoL (p = 0.99). CONCLUSIONS: Evaluation of QoL in patients with morphea is still challenging due to lack of good assessment tools dedicated specifically for morphea patients. In general, QoL in morphea patients is significantly correlated with the disease activity, but not with disease-induced skin damage.

Changes in Disease Activity and Damage Over Time in Patients With Morphea.

Importance: Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. Objective: To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. Design, Setting, and Participants: Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. Exposures: All patients received standard-of-care therapy. Main Outcomes and Measures: Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survival analysis with the log-rank test to compare differences between morphea subtypes. Results: In total, 130 adults and children (663 study visits) were included in this study. The mean (SD) age of patients was 34.4 (23.8) years, and 101 of 130 (78%) were female. The mean (SD) follow-up was 4.3 (1.7) years. Fifty patients had at least 5 years of follow-up. Most patients were white individuals (96 of 130 [74%]) and had linear subtype (72 of 130 [55%]) or generalized subtype (40 of 130 [31%]). Overall, 13 of 30 (43%) with generalized subtype had recurrence of disease activity compared with 14 of 66 (21%) with linear subtype (hazard ratio, 3.28; 95% CI, 1.38-7.79). The median (interquartile range) time to first recurrence of disease activity after initial resolution of disease activity was 1.1 (0.8-1.9) years for generalized subtype and 2.3 (1.0-3.3) years for linear subtype. Of the 50 patients followed up for at least 5 years, 18 (36%) had recurrence of disease activity. Conclusions and Relevance: Disease activity appeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.

Ultrasound Surface Wave Elastography for Assessing Scleroderma.

Scleroderma, or systemic sclerosis (SSc), is a multi-organ connective tissue disease characterized by immune dysregulation and tissue fibrosis. Skin disease is both a disabling feature of SSc and a predictor of visceral involvement and increased mortality. The Modified Rodnan Skin Score (MRSS) is currently the most common clinical method for assessing skin. We developed ultrasound surface wave elastography (USWE) techniques to measure skin surface wave speeds and analyze skin viscoelasticity. The objective of this research was to determine the correlations of skin surface wave speed and skin viscoelasticity with MRSS. Twenty-six SSc patients were studied using USWE and the MRSS. The subject was tested in a sitting position while his or her left or right forearm and upper arm were placed horizontally on a pillow in a relaxed state. The skin of both left and right forearms and upper arms of patients was tested using USWE. Surface wave speeds are positively correlated with the MRSS. Skin elasticity is also positively correlated with the MRSS. However, there was no correlation between skin viscosity and the MRSS for these SSc patients. We will further study if skin viscosity is sensitive enough to detect early edema from inflammation changes of SSc.

Inter-rater reliability of modified hand mobility in scleroderma test.

AIM: Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology characterized by excessive collagen production, endothelial cell injury, microvascular obliteration, cutaneous fibrosis and progressive visceral disease. The hands are frequently involved during the progression of the disease, with symmetrical skin thickening as a prominent feature. Modified hand mobility in scleroderma (mHAMIS) test is a measurement method to assess hand mobility in patients with SSc. Knowing the inter-rater reliability of the instrument is important in order for the results from different examiners to be accurately interpreted. The aim of this study was to test inter-rater reliability of the mHAMIS test. METHOD: Hand mobility for both hands was assessed in 25 female patients with SSc by 2 physiotherapists who have different years of experience. Patients who had flexion contracture in at least 1 finger and undergone hand surgery in the last year due to any injuries, were excluded from the study since hand mobility was prevented. Inter-rater reliability was determined using intra-class correlation coefficients (ICCs). RESULT: The ICCs were excellent between raters for dominant and non-dominant hands. The values were 0.92 and 0.93, respectively. CONCLUSION: The inter-rater reliability of the mHAMIS was found to be excellent. This research contributes to the literature by proving that the test can be used without causing bias in clinical trials.

Challenges in the diagnosis and treatment of disabling pansclerotic morphea of childhood: case-based review.

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.

Changes in disability and their relationship with skin thickening, in diffuse and limited cutaneous systemic sclerosis: a retrospective cohort study.

OBJECTIVE: The burden of disability associated with systemic sclerosis (SSc) is being increasingly recognized. Our aim was to test the hypothesis that changes in functional ability over time differ between patients with limited (lcSSc) and diffuse cutaneous (dcSSc) subtypes, and that in dcSSc (but not lcSSc) these changes correlate with skin thickening. METHOD: This was a retrospective analysis of data collected prospectively between 2005 and 2016 at a single centre. Data recorded at annual review visits included modified Rodnan skin score (mRSS) and Health Assessment Questionnaire Disability Index (HAQ-DI). Yearly rates of mRSS and HAQ-DI change were assessed by individual linear regressions, and those gradients were compared between disease groups (lcSSc/dcSSc) for each of early/late disease (less/greater than 5 years' duration). RESULTS: The study included 402 patients (110 dcSSc, 292 lcSSc), with mean length of follow-up of 5.5 years (sd 3.5). Mean baseline HAQ-DI was 1.4 in dcSSc and 1.2 in lcSSc. In dcSSc, increased mRSS was associated with worsening disability (ρ = 0.36, p = 0.004) during early but not late disease (ρ = 0.12, p = 0.331). In lcSSc, changes in mRSS were not associated with changes in disability for early (ρ = -0.15, p = 0.173) or late disease (ρ = 0.10, p = 0.137). CONCLUSION: These findings confirm high disability in patients with SSc. A relationship between HAQ-DI and mRSS (worsening mRSS associated with increasing disability) was found only in patients with early dcSSc, suggesting that in other patient subgroups other factors play the major role.

Focal Epilepsy in a Teenager With Facial Atrophy and Hair Loss.

There is increasing evidence to demonstrate that Parry-Romberg syndrome and linear scleroderma en coup de sabre are both forms of linear scleroderma, representing localized autoimmune conditions affecting the skin, eyes, brain, and surrounding tissues. We present a case highlighting the clinical presentation of a 12-year-old boy with focal seizures and physical examination findings of facial atrophy and hair loss. This article reviews the literature related to the presentation, epidemiology, diagnosis, and treatment of Parry-Romberg syndrome and linear scleroderma en coupe de sabre with focus on the significant correlation with neurologic disease, particularly seizures.

[Localized scleroderma: about 24 cases]. / Sclérodermie localisée: à propos de 24 cas.

Morphea, also known as localized scleroderma, is defined as a sclerosus skin condition that can extend to the subcutaneous tissue but with no Raynaud's phenomenon or visceral involvement. Some clinical forms may have a functional and aesthetic impact, hence the interest of treatment of early stage inflammation. We here describe the epidemio-clinical, therapeutic and evolutionary features of different forms of morphea, by reporting a series of 24 cases.

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently.

"I'm still dad": The Impact of Scleroderma on being a Father.

The purpose of this study was to describe the experiences of fathers with scleroderma. Ten fathers with scleroderma were interviewed by telephone. Interviews were tape-recorded and transcribed verbatim. Two key themes emerged related to the emotional impact of the illness and the day to day realities of the illness with the unpredictability and rareness of the illness leading to ongoing feelings of isolation and fear of mortality. The negative influences of being a father with scleroderma included the inability of the fathers to participate in physical activities with their children such as outdoor sports and throwing balls. Being able to spend quality time with the child was a positive influence of the illness.

Scleroderma with an update about clinico-pathological correlation.

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.