Morphea Research Articles

Therapeutic and Reconstructive Management Options in Scleroderma (Morphea) en Coup de Sabre in Children and Adults. A Systematic Literature Review.

Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of evidence, primarily case reports and case series-supported by expert opinions. The aim of this article was to systematically analyze current data related to the treatment of localized scleroderma en coup de sabre. The databases Scopus, PubMed, and EBSCO were searched for all reports discussing the treatment of localized scleroderma en coup de sabre. The keywords en coup de sabre, “facial linear scleroderma”, and “morphea linearis”, combined with “treatment” or “therapy” were used as search terms. A total of 34 articles analyzed treatment outcomes for patients with localized scleroderma en coup de sabre including 4 retrospective cohort studies, 2 prospective cohort studies, 4 case series, and 24 case reports, representing a total of 69 patients (38 children and 31 adults). Methotrexate was the most commonly investigated treatment (26 patients) with a highest response rate (26/26, 100%). Other treatments included systemic glucocorticosteroids (nine patients), followed by UVA1 (four patients), mycophenolate mofetil (two patients), hydroxychloroquine (five patients), abatacept (two patients), tocilizumab (three patients), cyclosporine (one patient), interferon gamma (one patient), PUVA therapy (two patients), NB-UVB therapy (one patient), and pulsed dye laser (one patient). Reconstructive and surgery treatment was successfully used for lesions with settled disease activity to improve the cosmetic aspect of the lesions. Conclusion: methotrexate is the most often-studied treatment and reported good clinical outcomes in children and adults with localized scleroderma en coup de sabre.

Juvenile localized scleroderma: clinical picture, diagnosis, therapeutic update (literature review and own observations)

Among rheumatic diseases in children, a special place belongs to juvenile localized scleroderma, which is highlighted as a separate form in the structure of scleroderma diseases and is characterized by: the onset of the disease up to 16 years, skin lesions, often focal or linear (hemiforma), a tendency to form contractures and the development of limbs abnormalities. This form of the disease is characterized by damage to the skin mainly involving the surrounding muscles. The cause of juvenile localized scleroderma is unclear. Three main components underlie the development of the disease: damage to the vascular bed, activation of the immune system with a violation of its regulation and release of cytokines, as well as altered collagen synthesis with proliferation of fibroblasts and the subsequent development of fibrosis. Several forms of juvenile localized scleroderma have been identified, differing in clinical manifestations and depth of lesion of subjacent tissues, and among the skin manifestations, five subtypes are distinguished: plaque, generalized, linear, pansclerotic, and mixed. Diagnosis is based on an analysis of the history and typical clinical picture of the disease. Specific laboratory tests to confirm the disease has not been developed. Modern treatment principles for juvenile localized scleroderma involve the use of different groups of drugs, including methotrexate, corticosteroids, tacrolimus, cyclosporine, imatinibum, mycophenolate mofetil, retinoids, PUVA therapy (Psoralen + UltraViolet A), use of slow calcium channel antagonists (nifedipinum group), bosentan. The studies currently being conducted in the world on the standardization of basic therapy of juvenile localized scleroderma are likely to reveal the optimal variant and duration of treatment for each form of the disease and improve the prognosis of the disease. The article also presents the results of own clinical observations.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma.

Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Rarities in rare: illuminating the microvascular and dermal status in juvenile localised scleroderma. A case series.

To assess the (structural and functional) characteristics of the microvascular and dermal status in juvenile localised scleroderma (jLoS), using novel non-invasive standardised research tools commonly used in adult systemic sclerosis (SSc). Ten consecutive patients with a confirmed jLoS diagnosis were studied cross-sectionally in this two-centre case series. For each patient, the most prominent lesion (i.e., "target lesion") was chosen for further examination of the centre, edge and contralateral unaffected site. High-frequency ultrasonography was used to determine dermal thickness, durometer for skin hardness, and laser speckle contrast analysis (LASCA) for a dynamical evaluation of the microcirculation. The structure of the microcirculation was evaluated at the nailfolds of the 2nd-5th finger bilaterally, using nailfold videocapillaroscopy (NVC). 6 linear and 4 plaque subtype jLoS lesions were included. Dermal thickness was thinner at the centre of the "target lesions" vs. the edges (p<0.001) and control sites (p<0.001). Skin hardness was harder at the centre of the "target lesions" vs. the edges (p=0.012) and control sites (p=0.003). A higher perfusion was found in the centre of the "target lesion" (124.87±66.40 PU) vs. the edges (87.27±46.40 PU; p<0.001) and control sites (67.85±37.49; p<0.001). Of note, all patients had a "non-scleroderma" pattern on NVC. This case series suggests the supportive value of both microcirculatory and dermal assessments of skin lesions using novel non-invasive research tools, adopted from adult SSc, for (j)LoS.

Linear scleroderma of the face treated by a superficial circumflex iliac artery perforator flap.

Linear scleroderma of the face treated by a superficial circumflex iliac artery perforator flap.

Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation.

Juvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA-Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype. RNA-Seq was performed on sections of paraffin-embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA-Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman's rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS. We identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA-DPB1, HLA-DQA2, HLA-DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon-γ signaling. Among children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation-related pathways were up-regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis-related pathways were up-regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up-regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis.

Dermatologic ultrasound in the management of childhood linear morphea

Linear morphea is the most common subtype of localized scleroderma in the pediatric population. This condition can be quite disabling, with complications such as growth defects and painful flexion contractures. Assessment of disease progression and early intervention are key to minimize morbidity. We report linear morphea in a previously healthy 12-year-old girl. The patient presented with a one-year history of a linear plaque crossing her left antecubital fossa, measuring 7x3cm. The diagnosis was confirmed by biopsy, in which deep tissue involvement was noted. Subsequent management and evaluation of the disease activity was done by ultrasound, which allowed precise guidance of pharmacotherapy. The patient improved both clinically and sonographically with a methotrexate course. Sonographic changes accurately described the disease activity on follow up assessments. Features suggestive of an active phase include a thickened and hypoechoic dermis contrasting hyperechoic subcutaneous tissue. The atrophic stage is characterized by a thinned-out dermis and subcutaneous area. Typical vascular traits of each disease phase can also contribute to the assessment. Ultrasound is a grossly underused tool in the field of dermatology. It can provide accurate and sensitive information about disease activity in linear morphea, allowing for more timely intervention and optimal patient management.

28336 Outcomes of cosmetic procedures for treatment of morphea: A retrospective cohort study

Reconstructive surgery is recommended for cosmetic sequelae of morphea. We examined a retrospective cohort of 15 morphea patients who underwent a total of 41 procedures followed for 1-60 months postprocedure. The majority of patients were white (60%), female (60%), with facial linear morphea (93%). The most common procedure was fat grafting for facial morphea (75%, n = 30). Other procedures included gingival grafting (10%) and filler injections (7.5%). Recurrent disease activity was noted 8-36 months postprocedure in 4 patients, 3 after fat transfer and 1 after osteoplasty.

A Case Report on Scleroderma: A Diagnostic Dilema

Scleroderma is a rare heterogenous group of autoimmune fibrosing disorder that mainly exists in two forms; localized scleroderma (LS) and systemic sclerosis (SSc). It involves thickening of the skin at fingers region extending from proximal to metacarpophalangeal joints. The diagnostic criteria of scleroderma include past history of patient, symptoms of patient, serology, and skin biopsy. The morbidity and mortality are much worse for SSc with the patients are at risk for life threatening lung, heart and other visceral organ fibrosis and vasculopathy. There is no drug that can cure or stop scleroderma over fibrosis, but certain drugs regulate the symptoms associated with it and boost the patient's quality of life, particularly steroidal creams that help alleviate swelling, joint pain, loosen tight skin; blood pressure drugs that dilate blood vessels; immunosuppressive agents. If the disease is severe amputation is necessary.

Methotrexate in Linear Scleroderma: Long-Term Efficacy in Fifty Children From a Single Pediatric Rheumatology Center.

To study disease course and long-term outcome in children with linear scleroderma (SSc) treated with methotrexate (MTX) since diagnosis. The present study was retrospective and cross-sectional and included consecutive children with linear SSc who were treated with MTX for >1 year and were followed up for at least 2 years. Disease course was analyzed by the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis, comparing patients with linear SSc and those with other juvenile localized scleroderma (JLS) disease subtypes. Disease activity and damage were assessed by the Localized Scleroderma Cutaneous Assessment Tool and thermography. Fifty patients with a mean follow-up duration of 7.8 years and a mean MTX treatment duration of 3.1 years were included. Sixteen percent of patients did not respond to the first course of MTX, and 16% had at least 1 flare. Complete remission was observed in 18.2% of patients who were followed up for 2-5 years, in 80.0% of patients followed up for 10 years, and in 87.5% of patients followed up for >10 years. No significant difference in relapse-free survival between patients with linear SSc and in 17 patients with other JLS disease subtypes was observed. Tissue damage was mild in 42% of patients, moderate in 32%, and severe in 26%. The correlations between severity of tissue damage and linear SSc subtype, disease duration, relapses, and remission were not significant. The relationships between treatment duration and disease relapses (P < 0.05) and severity of tissue damage (P < 0.005) were significant. Most patients with linear SSc who are treated with MTX achieve complete and long-lasting remission. Overall aesthetic and functional sequelae are moderate, most likely because tissue damage is established early and treatment likely stabilizes the damage. Early diagnosis and MTX treatment, as well as long-term monitoring, are crucial to improve outcome and promptly identify flares.

Laser Therapy for the Treatment of Morphea: A Systematic Review of Literature.

Morphea, also known as localized scleroderma (LoS), comprises a set of autoimmune sclerotic skin diseases. It is characterized by inflammation and limited thickening and induration of the skin; however, in some cases, deeper tissues might also be involved. Although morphea is not considered a life-threatening disease, the apparent cosmetic disfigurement, functional or psychosocial impairment affects multiple fields of patients’ quality of life. Therapy for LoS is often unsatisfactory with numerous treatments that have only limited effectiveness or considerable side effects. Due to the advances in the application of lasers and their possible beneficial effects, the aim of this study is to review the reported usage of laser in morphea. We present a systematic review of available literature, performed with MEDLINE, Cinahl, Central, Scopus, Web of Science, and Google Scholar databases. We identified a total of twenty relevant studies (MEDLINE n = 10, Cinahl n = 1, Central n = 0, Scopus n = 2, Web of Science n = 5, Google Scholar n = 2) using laser therapy for LoS. Eight studies were focused on the use of PDL, six on fractional lasers (CO2 and Er:YAG), four on excimer, and two on either alexandrite or Nd:YAG.

Serological Evidence of Borrelia burgdorferi in Patients with Morphea from West-Central Poland: An Original Paper and Review of Literature.

Morphea (localized scleroderma) is an inflammatory connective tissue disease. Borrelia burgdorferi, as a causative factor, has been discussed controversially. The aim of this original study was to evaluate the frequency of IgM and IgG classes of anti-Borrelia antibodies in groups of morphea and psoriasis patients using the traditional ELISA method. Blood samples of 82 patients with morphea and 112 patients with psoriasis vulgaris were examined for the presence of IgM and IgG classes of anti-Borrelia antibodies (ELISA). IgM and IgG classes of anti-Borrelia antibodies were detected in 4% of blood samples taken from morphea patients, while 4.5% of blood samples from patients with psoriasis vulgaris. There is one major limitation in this study that could be addressed in future research. First, the study focused on the determination of IgM and IgG classes of anti-Borrelia antibodies as a risk factor for morphea, but other infectious agents also require further testing, such as Hepatitis B, Hepatitis C, and other viral or bacterial infections. The results of this study showed no significant relationship between Borrelia infection and morphea. Detection of IgM and IgG classes of anti-Borrelia antibodies is not recommended for routine diagnostics of patients with morphea at this time.

Bilateral linear scleroderma with transition into progressive facial hemiatrophy

A 15-year-old girl presented to our outpatient clinic with a 10-year history of two band-like atrophic grooves located on the left part of the forehead (figure A, B). Within the previous 2 years, the lesions had considerably progressed and resulted in a marked atrophy of subcutaneous tissue and bone structures on the left side of the face (figure C). There was no history of preceding trauma, but the patient had experienced several episodes of focal seizures and recurrent hemiplegic migraine in the past 6 months.

Upcoming treatments for morphea.

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.

Possibilities of skin ultrasound examination in the management of patients with localized scleroderma

With the help of ultrasound examination (ultrasound), it is possible to visualize the skin of patients with suspected localized scleroderma, as well as to objectively determine the stage of the disease and assess the effectiveness of therapy.&#x0D; Three patients with linear, plaque forms of scleroderma, as well as lichen sclerosus, underwent skin ultrasound using a Skinscanner DUB TPM device with a 75 MHz transducer, 4 mm penetration, 21 m resolution in the area of lesions and in adjacent areas of healthy skin, using their ratio coefficient (RC) for comparative evaluation. The thickness of the epidermis and dermis, their echogenicity were determined.&#x0D; With a linear form of scleroderma, an increase in the thickness of the epidermis in the area of the focus (RC 0.850.0125) and a decrease in its echogenicity (RC 1.580.46) were observed. The echogenicity of the dermis was significantly reduced in the lesion (RC 3.021.17). The dermis thickness was slightly less in the center of the lesion (RC 1.09), at the periphery of the lesion it was moderately increased (RC 0.86). In the plaque form of scleroderma, a decrease in the echogenicity of the epidermis was observed in the foci (RC 1.320.49); an increase in the thickness of the dermis (RC 0.790.16) and a decrease in its e echogenicity (RC 1.260.57). In 7 of 11 foci, a subepidermal hypoechoic band was visualized. With lichen sclerosis in the foci, an increase in the thickness of the epidermis (RC 0.420.12) and its acoustic density (RC 0.630.0793), a decrease in the thickness and echo density of the dermis (RC 1.320.00943 and RC 1.550.6, respectively).&#x0D; With different forms of LS, a different ultrasound picture was observed, depending on the stage and activity of the process. The changes identified during treatment reflect the effectiveness of the therapy and the rate of restoration of the skin structure during therapy.

Predictors of family impact of juvenile localized scleroderma.

To measure the impact juvenile localized scleroderma (jLS) has on family quality of life and to identify predictors of family impact in this population which may inform the development of tailored resources to enhance family functioning for patients with jLS. A retrospective cohort study of pediatric patients with jLS and their families was conducted. Five questionnaires were administered at each visit: Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM), PedsQL 4.0 Generic Core Scales (PedsQL-Generic), PedsQL Rheumatology Module (PedsQL-RM), Child Health Assessment Questionnaire (CHAQ), and Children's Dermatology Life Quality Index (CDLQI). Linear mixed models with random intercepts for each patient were used to find relationships between family impact scores and clinically relevant variables over time. Variables of interest included disease activity status, methotrexate use, jLS distribution, and scores for PedsQL-Generic and PedsQL-RM. The median baseline PedsQL-FIM total score was 80.9 (IQR=76.6-97.4). Adjusting for age and sex, the most significant predictors of family impact were PedsQL-Generic scores and four of five PedsQL-RM dimensions (all P<.001); methotrexate use had borderline significance (P=.06). Family impact increased more significantly over time in older patients. In multivariable modeling, PedsQL-Generic total score and jLS "other" distribution were significant for predicting an increased PedsQL-FIM score (P=.003 and P=.03, respectively). JLS has a moderate family impact. Family impact is predicted by patients' general and disease-specific health-related quality of life (HRQL) and their jLS subtype. There is a trend toward increased family impact with methotrexate treatment. This study emphasizes the importance of family-centered care in jLS.

Szisztémás szklerózis és lokalizált szkleroderma: Hol vagyunk most?

Systemic sclerosis is a collagen vascular disease which could lead to fibrosis of the skin and internal organs. It is characterized by a high disease burden and mortality. The 2013 classification criteria system helps to recognize the disease early, which allows prompt intervention and a better survival. In the past few year the recognition of the association between the presence of RNA polimerase III antibodies and malignancies was important. Treatment options of SSc have been improved. Early, intensive immunosuppressive treatment (cyclophosphamide, mycophenolate mofetil) of interstitial lung disease inhibits progression. There are several treatment modalities for the treatment of pulmonary arterial hypertension and digital ulcers (endothelin receptor antagonists, phosphodiesterase 5 inhibitors, prostaglandin analogues). Antifibrotic drugs (nintedanib, riociguate) are also available among former immunosuppressive and vasoactive agents. Lenabasum is a new promising selective cannabinoid receptor 2 agonist, which inhibits inflammation and fibrosis. Localized scleroderma presents a diverse clinical picture. The disease leads to fibrosis of the skin but it is not accompanied with serious inner organ involvement typically seen in systemic sclerosis. Capillaroscopy abnormalities, sclerodactyly and SSc specific antibodies are absent in localized scleroderma . The 2017 EDF guideline formulates a very useful classification, checkup and treatment recommendations.

Proliferative function of endothelium in local scleroderma, gender and age characteristics of the disease

Objective — to investigate the variability of vascular endothelial growth factor (VEGF) in localized scleroderma (LS), characteristics of the disease in different age groups. Materials and methods. The study included the clinical evaluation of 78 patients (27 men, 51 women) with localized scleroderma aged (43.2 ± 7.28) years. All patients underwent clinical, laboratory, and enzyme immunoassay investigation of VEGF. The criteria for inclusion in the study were: the presence of localized scleroderma and the absence of signs of a systemic process. Results and discussion. It has been proven that localized scleroderma is gender­related, more often recorded in women (65.4 %, p &lt; 0.05), with an attributive risk of 50.0 % compared to men. Late diagnosis of the disease was proven in 78.2 % of patients. The age and gender characteristics of this pathology were determined — men are more likely to get sick at a young age (up to 20 years; 22.2 % of the surveyed), however, women over the age of 55 prevail (p &lt; 0.05). Women sought dermatological help earlier compared to men (29.4 %; p &lt; 0.05), but had a higher risk of early progression (p &lt; 0.05). Among the clinical forms of localized scleroderma, most of the cases (70.5 %) were of the plaque form. In 15.4% of cases, a linear form was diagnosed, in 9.0% ­ lichen sclerosus, in 5.1 % — Pasini—Pierini idiopathic atrophoderma. The plaque form of LS was significantly more often detected in women (80.3 %), and the linear form and lichen sclerosus — in men (22.2 % each). The average number of lesions was 2.8 ± 1.12. Three lesions were found in almost half (43.6 %) of the patients, one lesion – in 23.1%, two lesions – in 16.7%, four lesions – in 11.5%. Five or more lesions were present in 4 (5.1 %) patients. It has been found that the highest content of VEGF was observed in classic plaque form (p &lt; 0.05), the lowest — in Pasini—Pierini idiopathic atrophoderma (p &lt; 0.05). U­shaped age dependence of the disease was determined: high content of VEGF­A in patients under the age of 20 (p &lt; 0.05), with a significant decrease of VEGF­A in patients aged 20—35 years (p &lt; 0.05) and further increase in those aged 35 to 55 years (p &lt; 0.05). It was established that VEGF­A level increased at patients with early progression of the disease — in the first 2 years after the start of clinical manifestations against the group of patients with slow progression — more than 6 years (p &lt; 0.05). In assessment of gender dependence, we found a higher content of VEGF­A in female patients compared to male patients (p &lt; 0.05). Conclusions. Localized scleroderma has gender and age­related characteristics and is 50.0 % more often recorded in women. Among men, young patients predominate. Studying the pathogenesis of LS and assessing the proliferative function of the endothelium of the disease will make it possible to predict the course of the disease, improve the diagnosis and treatment.

A new principle for the diagnosis morphea in the onset of the disease

BACKGROUND: Because of the low specificity morphea clinical manifestations in early stages, the differential diagnosis is difficult.&#x0D; AIMS: The purpose of the research is to propose a new diagnostic method for early stages of localized scleroderma.&#x0D; MATERIALS AND METHODS: During 20112020, 77 patients with clinical manifestations of morphea and 127 controls were examined and included in the study at the LenOblCenter. All participants were conducted a transcutaneous oximetry with the TCM-400 Radiometer apparatus. The tissue oxygen perfusion (tcpO2) level from 40 to 50 mm Hg was considered as a reversible decrease, from 30 to 40 mm hg was a borderline decline and the value below 30 mm hg was critical. The following diagnostic skin biopsy was conducted in all 77 patients&#x0D; RESULTS: Skin biopsy allowed to form 4 research groups: 40 patients with morphea, 12 patients with granuloma annulare, 15 patients with small plaque parapsoriasis and 10 individuals with large plaque parapsoriasis. 7 (17.5%) patients with morphea had normal tcpO2 values, 9 (22.5%) patients had significant decrease of tcpO2, 24 patients (60%) showed a reversible decrease of tcpO2. 3/12 (25%) patients with granuloma annulare and 1 patient (10%) with large plaque parapsoriasis had minor oxygen level decrease. Measurement on the healthy skin showed tcpO2 decrease in patients with comorbidities ― 3/77 (3.9%) in research group and 28/127 (22%) in controls.&#x0D; CONCLUSIONS: Transcutaneous oximetry is a new perspective direction in the diagnostic algorithm of the morphea based on the pathogenesis and morphological features of the disease.

Genetic Signatures From RNA Sequencing of Pediatric Localized Scleroderma Skin.

The purpose of this study was to explore the skin transcriptional profile in pediatric localized scleroderma (LS) to provide a better understanding of the altered immune and fibrotic pathways promoting disease. LS is a progressive disease of the skin and underlying tissue that causes significant functional disability and disfigurement, especially in developing children. RNA sequencing (RNAseq) technology allows for improved understanding of relevant cellular expression through transcriptome analysis of phases during LS disease progression (more active/inflammatory vs. inactive/fibrotic) and also permits the use of RNA extracted from existing paraffin-embedded skin tissue, which is important in pediatrics. A strong correlation was observed between the comparison of genes expressed between fresh (RNAlater) and paraffinized skin in healthy and LS subjects, supporting the use of paraffinized tissue. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ-, IFNα-, and TNFα-associated genes. GSEA© enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNγ itself, was more highly expressed in LS patients with more inflammatory lesions. The use of paraffinized skin for sequencing was proven to be an effective substitute for fresh skin by comparing gene expression profiles. The prevalence of the IFNγ signature in the lesion biopsies of active LS patients indicates that these genes reflect clinical activity parameters and may be the promoters of early, inflammatory disease.