Localized Scleroderma Skin Severity Index Research Articles

Evaluation of autologous fat grafting in the treatment of juvenile localized scleroderma with facial involvement

Objectives: The objective of this study was to evaluate the effect of autologous fat grafting in patients with juvenile localized scleroderma with facial involvement. Methods: We retrospectively studied patients with juvenile localized scleroderma who were followed at the Hamburg Center for Pediatric and Adolescent Rheumatology at least 6 months post-operative follow-up and received at least one autologous fat transplantation for a facial lesion. Autologous fat grafting was conducted independent of disease-modifying treatment and/or disease activity. The effectiveness of the intervention was evaluated by assessing the immediate volume enhancement after injection of fat tissue compared with volume retained after 6 months. The volume enhancement was calculated from three-dimensional photo images analyzed in Mirror Medical Imaging Software, Canfield Scientific (New Jersey, USA). Results: Data of 22 juvenile patients were assessed from March 2006 to September 2021. In six patients, the photos could not be evaluated for the study. The median age of the remaining 16 patients at the beginning of the first fat graft was 8 years (range = 2.5–22 years). Patients underwent mean three interventions (range = 1–9). Evaluation of three-dimensional images showed that the volume retention at 6 months post autologous fat grafting is approximately 50%. The Modified Localized Scleroderma Skin Severity Index value did not correlate to volume changes at 6 months. In 4 of 16 patients, a decrease of the Localized Scleroderma Damage Index occurred. In all seven patients with cheek involvement, mean tragus-nose distance difference decreased (mean decrease 1.09 cm). We did not observe any significant clinical side effects. Conclusion: In this first bigger pediatric case series, the mean facial lesion volume increased around 50% after a mean of three interventions at 25 months of follow-up. No flares of the underlying disease were noted. Autologous fat grafting is a promising method to improve the cosmetic appearance of those patients.

Color Doppler Ultrasound Assessment of Subclinical Activity With Scoring of Morphea.

Detection of activity in morphea is paramount for adequately managing the disease. Subclinical ultrasound involvement on inactive lesions or healthy skin areas adjacent to morphea has not been described to date. The study aimed to detect morphea's subclinical activity by Color Doppler ultrasound not identified with the clinical scorings. This cross-sectional retrospective study was done from January 2014 to July 2019 in patients with a clinicopathological diagnosis of morphea. The modified Localized Scleroderma Skin Severity Index (mLoSSI) and The Ultrasound Morphea Activity Score (US-MAS) were used to correlate clinical and subclinical activity. A total of 36 patients met the inclusion criteria. 54% of cases presented subclinical activity in areas adjacent to the clinically active lesion, 23% in nonadjacent regions, and 23% demonstrated activity at a clinically inactive lesion site.100% of patients with morphea "en coup de sabre" involving the frontal region of the face concomitantly presented both subclinical activities of morphea on the frontal facial region and the scalp following the same axis.A positive relationship was observed between the degree of clinical activity measured by mLoSSI and US-MAS scoring.The main limitations of our study were the low number of patients and the inability to detect alterations < 0.1 mm. Subclinical activity is frequent in morphea, can extend beyond the lesional areas, including apparently noninvolved adjacent and distant corporal regions, and can be detected by color Doppler ultrasound.

Optimization of treatment of morphea associated with metabolic syndrome

Objective. To study the efficacy of statins in the treatment of morphea in patients with metabolic syndrome and to study the dynamics of inflammatory markers on the background of atorvastatin use.Materials and methods. Atorvastatin at a dose of 20 mg per day was included in the treatment of patients with morphea asociated with metabolic syndrome. Clinical efficacy was evaluated after 3, 6, and 9–12 months on the basis of the dynamics of the modified localized scleroderma skin severity index mLoSSI, changes of laboratory markers of inflammation (C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha)), which was evaluated in 27 patients.Results. In patients whose treatment complex included atorvastatin, there was a persistent clinical improvement, which was manifested in a more pronounced decrease in the modified severity index of morphea mLoSSI relative to the control group after 6, 9-12 months of taking the drug, a marked decrease in the number of recurrences of the disease. When taking atorvastatin in patients with morphea with concomitant metabolic syndrome, there was a statistically significant decrease in the levels of inflammatory markers: CRP and TNF-alpha (p &lt; 0.05).Conclusion. The use of Atorvastatin at a dose of 20 mg per day in patients with limited scleroderma in combination with metabolic syndrome showed pronounced clinical efficacy, reduced the number of recurrences of the disease. There was a decrease in the levels of proinflammatory markers (CRP, TNF-alpha) when taking atorvastatin in patients with morphea associated with metabolic syndrome. The use of atorvastatin in patients with morphea and concomitant metabolic syndrome is effective in preventing relapses of morphea, reducing its severity.

Radiation-induced morphea: Association with autoimmune comorbidities, severity, and response to therapy

Radiation-induced morphea: Association with autoimmune comorbidities, severity, and response to therapy

Reliability of LoSCAT score for activity and tissue damage assessment in a large cohort of patients with Juvenile Localized Scleroderma

ObjectivesTo assess reliability of the two indexes of Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), the modified Localized Scleroderma Skin Severity Index (mLoSSI) and the Localized Scleroderma Skin Damage Index (LoSDI), when applied by clinicians with different experience in scoring and managing patients with JLS. Secondary aim was to compare LoSCAT and infrared thermography (IRT) in monitoring lesions over time.MethodsConsecutive children with Juvenile Localized Scleroderma (JLS) were blindly evaluated by three examiners with different experience in Paediatric Rheumatology and with no experience in LoSCAT use. At each visit, patients were assessed by LoSCAT and IRT. Sensitivity to change of LoSCAT and IRT was assessed in a group of patients 3–6 months later. Inter-rater reliability was assessed by Intraclass Correlation Coefficient (ICC) and variance analysis (ANOVA).FindingsForty-seven patients (129 lesions) entered the study, and 26 (79 lesions) were re-evaluated with same modality after 4.5 (SD 1.5) months. mLoSSI showed excellent inter-rater reliability expressed by ICC 0.965 confirmed by ANOVA. Similarly, inter-rater reliability for LoSDI was good (ICC = 0.774) but worse concordance among examiners was observed. A comparable improvement of mLoSSI in all anatomic sites was noted by all examiners in 79 lesions examined in two subsequent visits and was consistent with thermography.ConclusionsDifferent clinical experience in JLS did not influence clinical judgement in mLoSSI which showed excellent concordance, whereas LoSDI is less precise in damage assessment and not completely reliable in monitoring skin changes. Infrared thermography confirms to be a helpful tool for detecting disease activity and reliable in monitoring lesions over time.

449 CXCL9 as a biomarker for disease activity in patients with morphea

Management of morphea (localized scleroderma) is centered on detecting disease activity of lesions in order to promptly shut down inflammation with immunosupressants to prevent progression. Because determining disease activity is challenging based on clinical findings alone, use of blood biomarkers may be a useful adjunct to therapeutic decision making. Our group identified interferon-regulated cytokine CXCL9 as a candidate biomarker for disease activity in a small sample (N=87) of morphea patients. To validate our results in a larger population with a wider range of disease characteristics, we performed a cross-sectional study to determine CXCL9 levels via enzyme-linked immunosorbent assay (ELISA) from 387 morphea patients, and the clinical features associated with increased concentrations of CXCL9. We determined a normal reference range as the mean of CXCL9 concentration of 26 controls plus two standard deviations. Disease activity was determined by the Localized Scleroderma Skin Severity Index (LoSSI), a validated clinical measure of disease activity in morphea. Overall, CXCL9 was positive in 22% of all morphea patients, in 33% patients with active disease (LoSSI > 3), and 10% of patients with inactive disease (LoSSI ≤ 3). In patients with active disease, CXCL9 serum levels correlated with LoSSI scores (r=0.36, p<0.0001). CXCL9 levels were highest in generalized morphea versus other subtypes (p=0.0002), and highest in adult-onset disease versus pediatric onset disease (p<0.001). Clinical features associated with high CXCL9 levels included the presence of functional sequelae (p=0.008), with limitation of range of motion being the most common (84%). In summary, CXCL9 is present in substantial numbers of morphea patients and is associated with clinically active disease, confirming its utility as a biomarker for active morphea. In addition, elevated CXCL9 may be a marker for severe disease.

Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea

IFN-related pathways have not been studied in morphea, and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and IFN-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy control subjects. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and used double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (P < 0.0001), as were other T helper type 1 cytokines. CXCL9 serum concentration correlated with the modified Localized Scleroderma Skin Severity Index (r= 0.44, P= 0.0001), a validated measure of disease activity. CXCL9 gene expression was also increased in inflammatory lesional morphea skin (fold change= 30.6, P= 0.006), and preliminary transcriptional profiling showed little evidence for IFN signature in whole blood. Double-staining immunohistochemistry showed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory morphea is characterized by T helper type 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea.

Effects of UVA1 Phototherapy on Expression of Human Endogenous Retroviral Sequence (HERV)-K10 gag in Morphea: A Preliminary Study.

BackgroundMorphea, also known as localized scleroderma, is a rare autoimmune connective tissue disease characterized by skin fibrosis. UVA1 phototherapy is an important asset in the reduction of clinical manifestations in morphea. There are studies claiming that UV light modulates the expression of some human endogenous retroviral sequences.The aim of this study was to determine if the expression of HERV-K10 gag element is lowered by UVA1 phototherapy in morphea, a disease in which such irradiation has a soothing effect.Material/MethodsThe expression levels of the HERV-K10 gag were assessed by real-time PCR (polymerase chain reaction) in peripheral blood mononuclear cells (PBMC) and skin-punch biopsies of healthy volunteers and 9 morphea patients before and after phototherapy. Additionally, correlations between the HERV-K10 gag expression and age, disease duration, the Localized Scleroderma Skin Severity Index (LoSSI), and antinuclear antibody (ANA) titers were assessed.ResultsIn PBMC, HERV-K10 gag mRNA was significantly elevated after UVA1 phototherapy compared to healthy controls. Most of the patients responded with an increased expression level of this sequence. However, we found no statistical evidence at this point that phototherapy indeed has an effect on the HERV-K10 gag expression (there were no statistical differences in PBMC of morphea patients before and after phototherapy). Similarly, there was no statistically relevant effect of the UVA1 on the expression of HERV-K10 gag in skin.ConclusionsAt this point, the effect of UVA1 phototherapy on the expression of HERV-K10 gag cannot be statistically confirmed.

The role of local temperature and other clinical characteristics of localized scleroderma as markers of disease activity.

Determining the activity of localized scleroderma (LS) remains crucial for decision making, and reliable clinical indicators of activity are lacking. Our objective in this study was to analyze the utility of infrared thermography (IRT) in assessing the activity of LS according to existing clinical scales. A secondary objective was to study whether clinical characteristics of patients and/or IRT have any role in predicting the activity of LS. In this cross-sectional study, the activity of LS was determined using a visual analog scale (VAS), a dyspigmentation-induration-erythema-telangiectasias (DIET) scale, and a localized scleroderma skin severity index (LoSSI). Local temperature was measured by IRT. We studied 56 patients with a median age of 14.2 years. The mean difference in temperature between the affected and unaffected skin was 0.29°C. The comparison of patients with active versus inactive LS (using a 50% composite score cutoff) according to differences in temperature was not significant. An exploratory regression analysis showed an insignificant association of difference in temperature and other clinical characteristics for activity of LS. Our relatively small sample size consisted primarily of patients with low to moderate activity, and the lack of a standard definition of activity of LS was another limitation. There is a possible role for temperature and other clinical characteristics as predictors of activity of LS. More studies and better definitions of activity in LS are needed.

A case report of generalized morphea treated with herbal medication and moxibustion

A 56-year-old Korean female patient developed generalized morphea over three months. We focused on imbalance of the neuroendocrine-immune axis, mainly using Jiawei-Renshengyangrong-tang and Jiawei-Siqi-tang. Moxibustion on LU9 was conducted for skin symptoms. The patient’s modified localized scleroderma skin severity index score decreased from 22 to 6 over 22 weeks of treatment and to 4 during a 3-month follow-up. Her verbal rating scale score for general symptoms decreased from 17 to 1 during the 22-week treatment.

The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress Toward Development of Localized Scleroderma Outcome Measures

The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress Toward Development of Localized Scleroderma Outcome Measures

The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress Toward Development of Localized Scleroderma Outcome Measures

To develop and evaluate a Localized Scleroderma (LS) Skin Severity Index (LoSSI) and global assessments' clinimetric property and effect on quality of life (QOL). A 3-phase study was conducted. The first phase involved 15 patients with LS and 14 examiners who assessed LoSSI [surface area (SA), erythema (ER), skin thickness (ST), and new lesion/extension (N/E)] twice for inter/intrarater reliability. Patient global assessment of disease severity (PtGA-S) and Children's Dermatology Life Quality Index (CDLQI) were collected for intrarater reliability evaluation. The second phase was aimed to develop clinical determinants for physician global assessment of disease activity (PhysGA-A) and to assess its content validity. The third phase involved 2 examiners assessing LoSSI and PhysGA-A on 27 patients. Effect of training on improving reliability/validity and sensitivity to change of the LoSSI and PhysGA-A was determined. Interrater reliability was excellent for ER [intraclass correlation coefficient (ICC) 0.71], ST (ICC 0.70), LoSSI (ICC 0.80), and PhysGA-A (ICC 0.90) but poor for SA (ICC 0.35); thus, LoSSI was modified to mLoSSI. Examiners' experience did not affect the scores, but training/practice improved reliability. Intrarater reliability was excellent for ER, ST, and LoSSI (Spearman's rho = 0.71-0.89) and moderate for SA. PtGA-S and CDLQI showed good intrarater agreement (ICC 0.63 and 0.80). mLoSSI correlated moderately with PhysGA-A and PtGA-S. Both mLoSSI and PhysGA-A were sensitive to change following therapy. mLoSSI and PhysGA-A are reliable and valid tools for assessing LS disease severity and show high sensitivity to detect change over time. These tools are feasible for use in routine clinical practice. They should be considered for inclusion in a core set of LS outcome measures for clinical trials.