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Competing Interests: The authors have no conflict of interest to declare.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM., (© 2024. The Author(s).)

Isolated cutaneous swelling can have varied etiologies. The clinical diagnosis is usually difficult, and a correct diagnosis always requires a pathological examination. Hereby, we report a case of linear keloidal morphea on the neck of an 18-year-old male who presented with an asymptomatic, firm lesion for 6 months. Histopathological examination was consistent with morphea. This case highlights the uncommon form of morphea in an unusual location, which can be misdiagnosed for numerous neoplastic conditions and for which simple histopathological evaluation can clinch the diagnosis., (© 2024 the International Society of Dermatology.)

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation and fibrosis, leading to severe cutaneous manifestations such as skin hardening, tightness, discoloration, and other textural changes that may result in disability. While LS shares similar histopathologic features and immune-fibroblast interactions with systemic sclerosis (SSc), its molecular mechanisms remain understudied. Endothelial cells (EC) are known to play a crucial role in SSc but have not been investigated in LS. Single-cell RNA sequencing (scRNA-seq) now allows for detailed examination of this cell type in the primary organ of interest for scleroderma, the skin. In this study, we analyzed skin-isolated cells from 27 LS patients (pediatric and adult) and 17 healthy controls using scRNA-seq. Given the known role of EC damage as an initial event in SSc and the histologic and clinical skin similarities to LS, we focused primarily on endothelial cells. Our analysis identified eight endothelial subclusters within the dataset, encompassing both disease and healthy samples. Interaction analysis revealed that signaling from diseased endothelial cells was predicted to promote fibrosis through SELE interaction with FGFBP1 and other target genes. We also observed high levels of JAG in arterial endothelial cells and NOTCH in capillary endothelial cells, indicating the activation of a signaling pathway potentially responsible for epidermal abnormalities and contributing to LS pathogenesis. In summary, our scRNA-seq analysis identified potential disease-propagating endothelial cell clusters with upregulated pathways in LS skin, highlighting their importance in disease progression.

Aim of the Study: to determine the frequency of joint lesions (JnL) in children with juvenile localized scleroderma and it's possible correlation with autoantibodies and markers of fibrosis., Materials and Methods: 500 children with JLS (370 girls and 130 boys) were studied retrospectively for the joint lesion, using standard physical examination, ultrasound examination (UlS) X-ray, MRI. In 190 patients we investigated antinuclear antibodies (antinuclear factor (ANF), rheumatoid factor (RF), antitopoisomerase 1 and anticentomere antibodies, antibodies to DNA, autoantibodies to collagen (Cab) types I-IV, cryoglobulins (CG), serum fibronectine (FN) and hyalyronic acid (HA) levels., Results: JLS patients were divided into 4 groups:124 patients with circumscribed morphea, 259- linear scleroderma, 93- generalized morphea, pansclerotic in 1 patient, mixed morphea - 23 patients. JnL were noticed in 175 patients (35%), among them the majority 151 patient (86%) with linear and unilateral forms of JLS. JnL were presented by joint pain in 47% of patients, limitation of joint movement in 60% of affected patients, mostly due to periarticular induration or tissue fibrosis. UlS showed joint effusions - in 16% of JnL, sinovitis and tenosinivitis in 45%. In 12 children joint space narrowing was detected by X ray, in 2-articular erosions. MRI was performed in 97 patients with limitation of joint movement, active synovitis, tenosynovitis found in 80 children. In 1 girl with unilateral scleroderma MRI with contrasting visualised avascular osteonecrosis of tibia. The absolute percentage of positive values detected autoantibodies and fibrosis markers was higher in children with JnL. ANF was detected in 56 % and RF in 28,4 % of patients with JnL, while sclerodermo specific antibodies and ds-DNA were detected in small percentage of JnL patients and in none without it. The levels of CG, FN, HA and Cab were elevated in patients with JnL. Cab of type I and type II were detected in most cases of JnL patients (71% and 62% correspondingly)., Conclusion: JnL occurs in 35% of JLS patients, predominantly in linear and unilateral forms of the disease. Detection of autoantibodies and fibrosis markers in 27-56% of JnL cases demonstrates the activity of autoimmune inflammation and justificates early systemic immunosuppressive therapy in JLS.

Background: Localized scleroderma (LoS) is an autoimmune disorder that primarily affects the skin, and is often treated with autologous fat grafting (AFG). Nevertheless, the retention rate of AFG in patients with LoS is typically low. We hypothesize that the low retention rate may be partially attributed to the inherent abnormalities of adipose-derived stem cells (ASCs) from nonlesional sites of patients with LoS., Methods: We performed a comparative analysis of the single-cell transcriptome of the SVF from nonlesional sites of patients with LoS and healthy donors, including cellular compositional analysis, differential expression analysis, and high-dimensional weighted gene coexpression network analysis. Experimental validation with fluorescence-activated cell sorting and bleomycin-induced skin fibrosis mice models were conducted., Results: We found a significant reduction in the relative proportion of CD55 high interstitial progenitors in ASCs under the condition of LoS. Differential expression analysis revealed inherent abnormalities of ASCs from patients with LoS, including enhanced fibrogenesis, reduced anti-inflammatory properties, and increased oxidative stress. Compared with CD55 low ASCs, CD55 high ASCs expressed significantly higher levels of secreted protein genes that had functions related to anti-inflammation and tissue regeneration (such as CD55, MFAP5, and METRNL). Meanwhile, CD55 high ASCs expressed significantly lower levels of secreted protein genes that promote inflammation, such as chemokine and complement protein genes. Furthermore, we provided in vivo experimental evidence that CD55 high ASCs had superior treatment efficacy compared with CD55 low ASCs in bleomycin-induced skin fibrosis mice models., Conclusions: We found that the low retention rate of AFG may be partially ascribed to the reduced pool of interstitial progenitor cells (CD55 high ) present within the ASC population in patients with LoS. We demonstrated the potential for improving the efficacy of AFG in the treatment of LoS by restoring the pool of interstitial progenitors within ASCs. Our study has significant implications for the field of translational regenerative medicine., (© 2024. The Author(s).)

Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist's annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist's assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.

Aims: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series., Methods and Results: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea., Conclusion: Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated., (© 2024 John Wiley & Sons Ltd.)

Linear scleroderma of head and face (LSH) in children is a severe disorder, that results in hemiatrophy of skin, subcutaneuse tissue, bones with functional disabilities, neurologic disorders and uveal involvement. The aim of the research was to establish uveal involvement in children with hemifacial scleroderma. Materials and methods: A retrospective analysis was done in a group of 110 children with hemifacial scleroderma. A comprehensive clinical, laboratory and instrumental examination was performed, including MRI of the brain, EEG, and an ophthalmologist's examination, which included visometry, biomicroscopy, and ophthalmoscopy. Results: 10 cases of uveal involvement were detected (9% of 110 pt). 9 patients had anterior segment inflammation (iridocyclitis), in 2 iridocyclitis was combined with retinal changes (in 1- peripheral focal chorioretinitis, in 1- iridocyclitis and central focal chorioretinitis). In one case, iridocyclitis was combined with optic neuropathy. In 3 children uveitis appeared at the disease debute, in the others 3-10 years later. Uveal inflammation in all cases was on the side of scleroderma skin involvement. In 3 children uveitis was bilateral. Seizures and concomittant foci in white matter of the brain were detected in 2 children with uveitis. 90% of the group had positive antinuclear factor. Persistent decrease in visual acuity developed in 3 patients. Соnclusion: Patients with LSH must undergo routine eye examination using basic ophthalmological techniques (visometry, biomicroscopy, ophthalmoscopy) every 6 months and highly necessary in case of relapse of scleroderma We assume that patients with UI in LSH must be defined as patients with JSS and treated intensively with systemicglucocorticoids, cytostatics and even biologics in case of resistance.

Background: To date, there are no accepted outcome measures to monitor morphea, and consensus on specific monitoring criteria for morphea remains elusive. A few studies have assessed the criterion validity of skin ultrasound in morphea. So, in this study, we approach ultrasound findings in morphea lesions., Material and Methods: This was a retrospective-analytical study conducted between December 2021 and May 2023. Patients were clinically evaluated at a dermatology outpatient clinic and then referred for high-frequency ultrasound (HF-US) evaluation and were selected to be included in this study. The lesions were confirmed by histopathology as well. Sonographic evaluations were performed on the lesion site and the symmetrical uninvolved other side. Dermal thickness and dermal echogenicities were recorded. Statistical analysis of group differences was performed by using the 2-tailed Student t-test. A p-value of less than 0.05 was considered statistically significant., Results: Forty-one morphea lesions in the inflammatory phase of 27 patients were included in the study. The mean dermal thickness of morphea lesions was 1107.97 ± 414.3 and the mean dermal thickness of the control side was 1094.65 ± 331.06, The difference between these two variables was not statistically significant. The mean dermal density of lesions was 49.13 ± 18.97 and the mean dermal density of the control side was 52.22 ± 25.33. The difference between these two variables was not statistically significant., Conclusion: This study shows that HF-US indicated increasing dermal thickness and reducing the dermal density of the morphea lesions in the inflammatory phase confirmed with the histopathology., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Multiple autoimmune syndrome is a manifestation of polyautoimmunity with the co-occurrence of three or more autoimmune diseases in a single patient. We report a unique case of a 55-year-old female patient that presented with four autoimmune diseases: autoimmune thyroid disease, vitiligo, morphea, and lichen sclerosus. She was evaluated for progression of morphea and lichen sclerosus, and we confirmed histopathological overlapping of these two diseases in the same lesion. We discuss the increasing prevalence of autoimmune diseases and similar case reports on dermatological polyautoimmunity.

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic disease characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermato-/polymyositis (DM/PM), and rheumatoid arthritis (RA). Naifold capillaroscopy (NFC) is a non-invasive test for evaluating the capillaries of the nail shaft used in the diagnosis of rheumatic diseases., Objectives: To determine whether there are characteristic abnormalities in NFC in MCTD patients, and whether the type of NFC lesions correlates with organ involvement in these patients., Methods: Clinical picture and NFC patterns were analyzed in 43 patients with MCTD. Capillaroscopic images were divided into scleroderma-like pattern (SD-like pattern) according to the Cutolo classification, non-specific lesions, and normal images. Relationships between the clinical aspects considered in the MCTD classification criteria and the changes in the capillaroscopic images were evaluated., Results: SD-like pattern was present in 20 MCTD patients (46.51%) with a predominance of the "early" pattern. Giant, branched, dilated capillaries and reduced capillary density were found more frequently in MCTD patients compared to the control group (p-values 0.0005, 0.005, 0.02, < 0.0001 respectively). There were associations found between the presence of a reduced number of vessels, avascular areas, and SD-like pattern with the presence of sclerodactyly in MCTD patients (p = 0.002, p = 0.006, p = 0.02, respectively), alongside an association between the presence of branched vessels and the subpapillary plexus with pulmonary arterial hypertension (PAH) (p = 0.04 and p = 0.005, respectively)., Conclusions: MCTD patients are significantly more likely to have abnormalities upon NFC. It is worthwhile to perform capillaroscopic examination in MCTD patients. Key Points • Scleroderma-like pattern was found in more than half of the MCTD patients. • Reduced capillary density was found to be a significant predictor of the diagnosis of MCTD. • There were relationships between the presence of reduced capillary density, avascular areas, and SD-like with the presence of sclerodactyly in the MCTD patients. • There was an association between the presence of branched vessels and the visibility of the subpapillary plexus and pulmonary arterial hypertension (PAH)., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Importance: Morphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy., Objective: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea., Design, Setting, and Participants: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect., Interventions: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up., Main Outcome and Measures: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated., Results: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF., Conclusions and Relevance: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment., Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.

Linear morphea, also known as linear scleroderma, is a localized form of scleroderma characterized by the presence of lesions that follow a linear distribution pattern. Apart from the typical inflammation and fibrosis of the skin, the linear subtype of morphea often affects underlying structures such as muscles and bones, which can lead to functional limitations. Lichen striatus, a linear inflammatory skin condition, primarily affects children aged 5 to 15 years. Interestingly, both diseases can exhibit lesions that follow the lines of Blaschko. Here we report a case with linear morphea following the lines of Blaschko mimicking lichen striatus in a 4-year-old child. This unique case represents the first documented instance of linear morphea exhibiting a precise Blaschko pattern and being successfully treated with baricitinib. The patient received oral baricitinib at a daily dosage of 2 mg for a duration of 1 year, resulting in remarkable improvement. The majority of the lesions softened, and there was no significant disease progression or occurrence of adverse events throughout the treatment period. Recognizing linear morphea at an early stage is of utmost importance in ensuring effective treatment and preventing disfiguring sequelae. Patients suspected of lichen striatus should also be closely followed and linear morphea should be excluded during the follow-up. The recent breakthrough in the application and the safety of baricitinib in scleroderma is also reviewed., (© 2023 Japanese Dermatological Association.)

Background: The Floating Sign is a histopathologic clue to the diagnosis of autoimmune sclerosing skin disorders such as morphea and interstitial granulomatous dermatitis (IGD). On the other hand, the "free-floating" sign has been associated with neoplasms, for example, dermatofibroma and interstitial mycosis fungoides. Herein, we report the Free Sign in sclerosing skin disorders., Methods: In a case-control study, we applied detailed histopathologic definitions of Floating Sign and Free Sign to assess their presence in morphea, IGD, and other sclerosing disorders., Results: Free Sign was present in most cases of morphea (46/55, 84%) and IGD (7/13, 54%) but not necrobiosis lipoidica (NL) (6/14, 42.8%) or sclerodermoid graft versus host disease (SGVHD) (2/7, 28.5%). The sensitivity and specificity of Free Sign for morphea versus other disorders was 84% and 56%, respectively. Floating Sign was not identified in most cases: NL (3/14, 21.4%), SGVHD (1/7, 14.2%), morphea (5/55, 9%), IGD (1/13, 7.7%). The diagnostic sensitivity of Floating Sign in morphea was 9%., Conclusions: The Free Sign was present in most cases of morphea in our series and may represent a clue to the presence of evolving sclerosis. Free Sign may be seen in other sclerosing disorders. Technical artifact is a potential cause of a false-positive Free Sign., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Among instrumental techniques, nailfold capillaroscopy plays a leading role in the assessment of Raynaud's phenomenon (RP) patients because it is the only method that provides opportunities for morphological assessment of capillaroscopic findings in the nailfold area, with proven diagnostic and prognostic significance in rheumatology. The discussion about updating the classification of RP in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. The presence of dilation of the "true" capillary diameters in primary RP could be observed. There are some cases of primary RP where the capillaroscopic pattern is completely normal and there are no dilated capillaries present, which could be related to the duration and severity of the symptoms. It is possible that longer duration and greater severity are associated with the appearance of capillary dilations, but more research is needed to confirm it. Rarely, pathological capillaroscpic features of microangiopathy could be observed in RP patients in whom clinical, laboratory and immunological findings are compatible with the diagnosis "primary RP". These cases should be defined as "suspected secondary RP" and require closer follow-up for the assessment of symptom evolution. Abnormal "scleroderma" type capillaroscopic pattern has been established as a new classification criterion for systemic sclerosis (SSc) in 2013. Similar changes ("scleroderma-like" pattern) could be observed in other rheumatic diseases, i.e., undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, including without evidence of overlap with scleroderma. The appearance of such microvascular abnormalities at disease presentation is less well studied in diseases different from SSc. However, "scleroderma-like" microangiopathy has also been reported as an initial sign in some systemic rheumatic diseases, such as UCTD and systemic lupus erythematosus. Thus, interpretation of capillaroscopic findings is performed in overall context, including clinical findings and laboratory and immunological test results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Discoid lupus erythematosus (DLE), a subtype of chronic cutaneous lupus may be observed in a linear pattern. A 21-year-old woman with history of chronic granulomatous disease state presented to our clinic for a chronic six-year skin eruption on her left eyebrow, left cheek, and left forehead. A punch biopsy of involved left forehead skin was performed and revealed perivascular and periadnexal lymphohistiocytic infiltrate without features of morphea or panniculitis, confirming the histopathologic changes of cutaneous lupus erythematous. The patient was diagnosed with linear DLE, mimicking en coup de sabre, within Blaschko lines. The pathogenesis for DLE in association with chronic granulomatous disease is ambiguous; however, X-linked lyonization is crucial for both conditions and may explain cooccurrence of disease states.

Introduction/objectives: systemic sclerosis (SSc) is an autoimmune disorder with multiple organs destruction. This study aimed to identify the ultrasonographic changes of major salivary glands in Egyptian scleroderma patients and to detect their association to different disease manifestations., Methods: Forty-seven SSc patients and 43 apparent healthy volunteers were enrolled. Demographics, inflammatory markers, and autoimmune status were recorded. Ultrasound evaluation of salivary glands was performed. Salivary gland changes' associations were statistically examined with SSc susceptibility and disease manifestations., Results: Thirty-one SSc patients exhibited glandular pathology (p < 0.0001), compared to controls. Of these abnormalities, SSc patients showed a total parotid gray scale of 2, total submandibular gray scale of 2, total glandular gray scale of 4, and total glandular Doppler signal of 1 at p < 0.0001, compared to the control group. Patients with SSc and glandular pathology had a higher prevalence of arthritis (p = 0.029) and ESR (p = 0.002) than those with normal glandular ultrasound. Significant associations were reported between gray scale ultrasound (GSUS) of total parotid (odds ratio "OR" = 0.4), total submandibular (OR = 0.36), and total glandular (OR = 0.53) with susceptibility to SSc at p < 0.0001. Total glandular GSUS (p = 0.039) and total submandibular power Doppler (p = 0.044) correlated with the SSc duration. Total parotid GSUS (p = 0.008) and total glandular GSUS (p < 0.0001) correlated with Schirmer's test., Conclusions: Major salivary glands are affected in SSc. Hence, scanning these glands with ultrasound is an additive tool besides the current practice. Key Points • Major salivary gland changes, observed by ultrasonography, are new findings in Egyptian SSc patients. • Ultrasound changes of major salivary glands are associated with inflammatory markers and clinical manifestations of SSc. • Scleroderma ultrasonography scans of the main salivary glands could be added to the routine work., (© 2023. The Author(s).)

Adipose tissue transplantation shows great therapeutic potential in reversing localized scleroderma-associated skin fibrosis. Brown adipose tissue (BAT) can specifically secrete various cytokines against fibrosis, but its therapeutic potential in improving skin fibrosis has not yet been demonstrated. In this study, we have demonstrated the superior therapeutic efficacy of BAT transplantation for sclerotic skin by transplanting two distinct types of adipose tissue. In comparison to the white adipose tissue (WAT) group, mice treated with BAT transplantation exhibited a significant reduction in dermal thickness. BAT transplantation effectively reverses skin sclerosis through mechanisms involving inflammation reduction, promotion of angiogenesis, inhibition of myofibroblast accumulation, and collagen deposition. This therapeutic effect can be attributed to its unique paracrine effects. Furthermore, transcriptome sequencing (RNA-Seq) revealed upregulation of pathways associated with lipogenesis and fatty acid metabolism in BAT while downregulating pathways are related to transforming growth factor β(TGF-β), epithelial-mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment., (© 2023 Federation of American Societies for Experimental Biology.)

En coup de sabre is a rare subtype of morphea. Only a few bilateral cases have been reported to date. We report a case of a 12-year-old male child with two linear brownish depressed asymptomatic lesions over the forehead with hair loss on the scalp. After thorough clinical, ultrasonography and brain imaging, a diagnosis of bilateral en coup de sabre morphea was made and the patient was treated with oral steroids and weekly methotrexate., (© 2023 Wiley Periodicals LLC.)

Objective: Systemic sclerosis (SSc) is a multifactorial autoimmune fibrotic disorder involving complex rewiring of cell-intrinsic and cell-extrinsic signaling coexpression networks involving a range of cell types. However, the rewired circuits as well as corresponding cell-cell interactions remain poorly understood. To address this, we used a predictive machine learning framework to analyze single-cell RNA-sequencing data from 24 SSc patients across the severity spectrum as quantified by the modified Rodnan skin score (MRSS)., Methods: We used a least absolute shrinkage and selection operator (LASSO)-based predictive machine learning approach on the single-cell RNA-sequencing data set to identify predictive biomarkers of SSc severity, both across and within cell types. The use of L1 regularization helps prevent overfitting on high-dimensional data. Correlation network analyses were coupled to the LASSO model to identify cell-intrinsic and cell-extrinsic co-correlates of the identified biomarkers of SSc severity., Results: We found that the uncovered cell type-specific predictive biomarkers of MRSS included previously implicated genes in fibroblast and myeloid cell subsets (e.g., SFPR2+ fibroblasts and monocytes), as well as novel gene biomarkers of MRSS, especially in keratinocytes. Correlation network analyses revealed novel cross-talk between immune pathways and implicated keratinocytes in addition to fibroblast and myeloid cells as key cell types involved in SSc pathogenesis. We then validated the uncovered association of key gene expression and protein markers in keratinocytes, KRT6A and S100A8, with SSc skin disease severity., Conclusion: Our global systems analyses reveal previously uncharacterized cell-intrinsic and cell-extrinsic signaling coexpression networks underlying SSc severity that involve keratinocytes, myeloid cells, and fibroblasts., (© 2023 American College of Rheumatology.)

Background: 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., Objectives: The study aimed to detect morphea's subclinical activity by Color Doppler ultrasound not identified with the clinical scorings., Materials & Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Although localised forms of scleroderma (morphoea) have very different clinical features and outcomes from systemic sclerosis the two conditions can occur together in some patients. In this study we have explored skin gene expression in a series of patients with keloidal morphoea, a distinct clinical variant, concurrently with systemic sclerosis., Methods: We compared skin gene expression from the keloidal lesions with that from skin elsewhere. We also examined a series of patients with diffuse or limited cutaneous SSc without morphoea and some healthy control skin biopsies., Results: Keloidal morphoea has a distinct gene expression signature that is mainly driven by differential expression of fibroblast-related genes compared with other cell types. Indeed, the signature reflects a profibrotic pattern seen in diffuse cutaneous SSc but is much more extreme. We propose that keloidal morphoea skin provides unique insight into the profibrotic population of cells driving dcSSc., Conclusions: Understanding the biology of keloidal morphoea may give valuable insight into the molecular and cellular pathology of systemic sclerosis. The discrete nature of keloidal lesions raises the possibility of haematogenous spread and we suggest that the driving cells could represent blood derived cells derived from circulating progenitors.

Background: Localized scleroderma, known as morphea, is a connective tissue disorder characterized by inflammation and fibrosis of the skin and the soft tissue. There exist no universally accepted validated outcome measures in order to monitor the disease activity. Besides clinical scores to evaluate outcome measures, imaging modalities are increasingly utilized in assessing patients with morphea, such as high-frequency ultrasonography (US), shear-wave elastography (SWE), and magnetic resonance imaging (MRI). However, the accuracy of these imaging modalities in monitoring morphea activity is not yet clear., Aims: To review the literature regarding the role of imaging modalities in assessing patients with morphea., Materials & Methods: In this study, we searched the PubMed/Medline database for articles published from inception until February 2023., Results: A total number of 23 original articles in three categories of US, elastography, and MRI were included., Discussion: Regarding US, criteria, including increased dermal thickness, increased echogenicity of the subcutaneous tissue, and decreased dermal echogenicity, were indicators of active morphea lesions when using high frequencies probe (18-20 MHz) color Doppler sonography. Moreover, studies evaluating SWE, a novel method to quantitatively assess tissue stiffness, demonstrated increased dermal stiffness in active lesions., Conclusion: Studies showed that MRI can help to determine the depth of disease, particularly as a first-line and follow-up diagnostic tool, especially in generalized and deep morphea. In addition, brain MRI may be useful for patients with localized craniofacial scleroderma experiencing new or worsening neurological symptoms., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Localized scleroderma (LS) is an autoimmune disease with both inflammatory and fibrotic components causing an abnormal deposition of collagen in the skin and underlying tissue, often leading to disfigurement and disability. Much of its pathophysiology is extrapolated from systemic sclerosis (SSc) since the histopathology findings in the skin are nearly identical. However, LS is critically understudied. Single-cell RNA sequencing (scRNA seq) technology provides a novel way to obtain detailed information at the individual cellular level, overcoming this barrier. Here, we analyzed the affected skin of 14 patients with LS (pediatric and adult) and 14 healthy controls. Fibroblast populations were the focus, since they are the main drivers of fibrosis in SSc. We identified 12 fibroblast subclusters in LS, which overall had an inflammatory gene expression (IFN and HLA-associated genes). A myofibroblast-like cluster (SFRP4/PRSS23) was more prevalent in LS subjects and shared many upregulated genes expressed in SSc-associated myofibroblasts, though it also had strong expression of CXCL9/10/11, known CXCR3 ligands. A CXCL2/IRF1 cluster identified was unique to LS, with a robust inflammatory gene signature, including IL-6, and according to cell communication analysis are influenced by macrophages. In summary, potential disease-propagating fibroblasts and associated gene signatures were identified in LS skin via scRNA seq.

Background: Ultraviolet (UV) A1 phototherapy is considered a beneficial treatment for various inflammatory, sclerotic, malignant, and other skin conditions. However, the available data regarding its efficacy for different indications, the potential side effects, and the recommended treatment protocols are sparse., Objectives: To assess the efficacy of UVA1 phototherapy and identify correlation between different indications and treatment protocols to response rates., Methods: We performed a retrospective study of a cohort of 335 patients treated with UVA1 phototherapy at the Department of Dermatology at Hadassah Medical Center, Jerusalem, Israel, between 2008 and 2018., Results: The study population included 163 patients with inflammatory diseases (mainly atopic dermatitis and other types of eczema), 67 patients with sclerotic diseases (morphea and graft versus host disease), nine patients with neoplastic diseases (cutaneous T cell lymphoma), and 188 patients with other cutaneous disorders. Response rates ranged between 85% and 89% across indications, without differences in response rates among the indication groups (p = .941). In a multivariant logistic regression model, increased number of treatments and higher maximal dosages were associated with response to treatment (p < .001). Using ROC analysis, a cut-off of 8 UVA1 phototherapy treatments was chosen as predictive for beneficial response (86.4% sensitivity, 78% specificity). A cut-off of 40 J/cm 2 was chosen as an optimal maximal dosage for differentiating between responders and non-responders (51.1% sensitivity, 83.1% specificity)., Conclusions: UVA1 phototherapy is an effective treatment for a variety of skin conditions. In most patients, at least eight treatments of a medium-high dosage are required for clinical response., (© 2022 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Lichen sclerosus (LS) is a cutaneous disease of unknown etiology that often involves the vulva or foreskin but also can affect extragenital sites. Regardless of the anatomic site, the histomorphology and presumably pathogenesis are similar. Perhaps a clue to the pathophysiology of LS lies in its frequent association with morphea, specifically, when occurring in an extragenital context. In our experience a striking feature evident in established lichen sclerosis (LS) is one of superficial vascular drop out whereby residual vessels exhibited endothelial cell necrosis and microvascular basement membrane zone thickening, the latter reflective of antecedent episodes of microvascular injury. We sought to understand the pathophysiology that underlies the distinct vascular changes and in doing so, shed light on the pathogenesis of LS. We examined 44 cases of LS over a period of 2019 to 2021. We were able to obtain past medical histories in 34 of the 44 cases. Regarding pathological assessment, the predominant focus was on microvascular changes. We assessed the role of C5b-9 mediated vascular injury in the pathogenesis of the vasculopathy and enhanced type I interferon signaling in vessels given the morphologic semblance to the select interferonopathy syndromes, namely fibrosing dermatomyositis and Kohlmeier Degos disease. We examined the expression of CMV DNA and protein based on prior observations in an earlier study that isolated early protein expression in the microvasculature in the setting of LS and scleroderma. From a clinical perspective, the most striking association was an older age at the time of diagnosis (mean age of 62 years and median age of 61.5 years) and the presence of vascular comorbidities of diabetes, hypertension, and hyperlipidemia in almost 80% of cases. All cases showed significant microvascular changes in the superficial corium with the most frequent findings being those of significant basement membrane zone reduplication and vascular drop out. A number of cases showed prominent microvascular deposits of C5b-9 in the zone of hyalinizing fibrosis or subjacent to the discernible table of fibroplasia in the absence of enhanced type I interferon signaling. In no case were there viral cytopathic changes associated with CMV affecting the endothelium. The studies that encode CMV DNA or protein did not show a significant role for CMV reactivation in endothelium in the majority of the studied cases. It is concluded that the pathophysiology of LS includes a microvascular injury syndrome within the papillary dermis. The mechanism of endothelial cell injury is complement mediated at least in part and could reflect an adaptive immune response targeting endothelium indicative of classic complement pathway activation when coexisting with morphea or occurring in younger individuals. A non-immune based endothelial dysfunction and complement mediated injury unrelated to antibody driven classic complement pathway activation are more likely pathogenetically in the setting of certain diseases like diabetes mellitus and hypertension. Vascular drop out can be explained by the diminished endothelial progenitor pool needed to repopulate the damaged microvessels in certain settings like hypertension and diabetes., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Inc.)

Morphea is an autoimmune disease characterized by skin sclerosis. According to the disease progression, morphea can be divided into inflammatory, sclerotic, and atrophic stages. Dermoscopy and high-frequency ultrasound (HF-US) have been applied in the noninvasive evaluation of many inflammatory diseases, but studies on the skin imaging features of the different stages of morphea are limited. To analyze the dermoscopic and HF-US features of the different stages of morphea and explore their auxiliary value in staging the disease, we followed 34 patients with histopathology-confirmed morphea between April 2018 and July 2021 who underwent dermoscopy and 50 and 20 MHz HF-US. Fisher's exact test was used to assess the differences in dermoscopic and HF-US features among patients with different stages of morphea. Seven patients were classified as the inflammatory stage, 20 as the sclerotic stage, and seven as the atrophic stage by histopathology. The most common dermoscopic features of inflammatory lesions were red structureless areas (100%) and linear curved vessels (85.7%). White clouds and shiny white streaks could be seen in 100% and 90% of sclerotic lesions, respectively. Among atrophic lesions, pigmentary structures (100%) and red structureless areas (85.7%) were the main features. In the HF-US examination, inflammatory lesions showed hypoechogenicity around the appendages (85.7%), a hypoechogenic dermis (71.4%), and an unclear boundary between the dermis and the subcutaneous fat (71.4%). Among lesions of the sclerotic stage, the main HF-US characteristics included a hyperechogenic dermis (85.0%), acoustic attenuation of the dermis (70.0%), and an unclear boundary between the dermis and the subcutaneous fat (85.0%). All atrophic lesions showed a hyperechogenic dermis, and 28.6% showed an unclear boundary between the dermis and the subcutaneous fat. Dermoscopy and HF-US can reveal the characteristic features of the different stages of morphea and show good correspondence with the histopathology. Dermoscopy and HF-US can provide important information for the staging of morphea., (© 2022 Japanese Dermatological Association.)

Importance: Morphea is an insidious inflammatory disorder of the skin and deeper tissues. Determining disease activity is challenging yet important to medical decision-making and patient outcomes., Objective: To develop and validate a scoring tool, the Morphea Activity Measure (MAM), to evaluate morphea disease activity of any type or severity that is easy to use in clinical and research settings., Design, Setting, and Participants: This pilot diagnostic study was conducted from September 9, 2019, to March 6, 2020, in 2 phases: development and validation. During the development phase, 14 morphea experts (dermatologists and pediatric dermatologists) used a Delphi consensus method to determine items that would be included in the MAM. The validation phase included 8 investigators who evaluated the tool in collaboration with 14 patients with pediatric morphea (recruited from a referral center [Medical College of Wisconsin]) during a 1-day in-person meeting on March 6, 2020., Main Outcomes and Measures: During the development phase, online survey items were evaluated by experts in morphea using a Likert scale (score range, 0-10, with 0 indicating not important and 10 indicating very important); agreement was defined as a median score of 7.0 or higher, disagreement as a median score of 3.9 or lower, and no consensus as a median score of 4.0 to 6.9. During the validation phase, reliability (interrater and intrarater agreement using intraclass correlation coefficients), validity (using the content validity index and κ statistics as well as correlations with the modified Localized Scleroderma Severity Index and the Physician Global Assessment of Activity using Spearman ρ coefficients), and viability (using qualitative interviews of investigators who used the MAM tool) were evaluated. Descriptive statistics were used for quantitative variables. Data on race and ethnicity categories were collected but not analyzed because skin color was more relevant for the purposes of this study., Results: Among 14 survey respondents during the development phase, 9 (64.3%) were pediatric dermatologists and 5 (35.7%) were dermatologists. After 2 rounds, a final tool was developed comprising 10 items that experts agreed were indicative of morphea activity (new lesion in the past 3 months, enlarging lesion in the past 3 months, linear lesion developing progressive atrophy in the past 3 months, erythema, violaceous rim or color, warmth to the touch, induration, white-yellow or waxy appearance, shiny white wrinkling, and body surface area). The validation phase was conducted with 14 patients (median age, 14.5 years [range, 8.0-18.0 years]; 8 [57.1%] female), 2 dermatologists, and 6 pediatric dermatologists. Interrater and intrarater agreement for MAM total scores was good, with intraclass correlation coefficients of 0.844 (95% CI, 0.681-0.942) for interrater agreement and 0.856 (95% CI, 0.791-0.901) for intrarater agreement. Correlations between the MAM and the modified Localized Scleroderma Severity Index (Spearman ρ = 0.747; P < .001) and the MAM and the Physician Global Assessment of Activity (Spearman ρ = 0.729; P < .001) were moderately strong. In qualitative interviews, evaluators agreed that the tool was easy to use, measured morphea disease activity at a single time point, and should be responsive to changes in morphea disease activity over multiple time points., Conclusions and Relevance: In this study, the MAM was found to be a reliable, valid, and viable tool to measure pediatric morphea activity. Further testing to assess validity in adults and responsiveness to change is needed.

Background: The treatment and curative effect evaluation of localized scleroderma (LS) still perplexes many clinical workers., Purpose: To investigate the efficiacy of methotrexate in the treatment of LS by the evaluation of ultrasonography., Methods: A prospective study enrolled 10 patients treated with MTX for at least 6 months was conducted. Treatment outcome was evaluated by a clinical score and 15-MHz ultrasonography. Safety assessment included the monitoring of adverse drug reactions and clinical laboratory examinations., Results: Eight of the 10 patients achieved clinical remission only with MTX. One patient was relieved after MTX combined with corticosteroids, while another one does not improve after the treatment of mycophenolate mofetil and corticosteroids. The effective rate of MTX is 80%. Nine patients were significantly improved with a decrease of the Localized Scleroderma Cutaneous Assessment Tool (the mean score of the LoSCAT cutaneous activity dropped from 5.2 to 1.0, p < 0.001, the mean score of the LS cutaneous damage dropped from 4.3 to 2.3, p = 0.002). The average difference of thickness between skin lesions and normal skin evaluated by ultrasonography decreased from 0.13 cm to 0.04 cm (p = 0.009) in eight patients. No serious adverse reactions occurred., Conclusion: Methotrexate is a safe and effective treatment for patients with LS. Ultrasonography can be considered as an efficient assessment tool for evaluation LS., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Systemic sclerosis is a rheumatoid disease best known for its fibrotic skin manifestations called scleroderma. Alternatively activated (M2-type) macrophages are normally involved in the resolution of inflammation and wound healing but also in fibrosing diseases such as scleroderma. TRPA1 is a non-selective cation channel, activation of which causes pain and neurogenic inflammation. In the present study, we investigated the role of TRPA1 in bleomycin-induced skin fibrosis mimicking scleroderma., Methods: Wild type and TRPA1-deficient mice were challenged with intradermal bleomycin injections to induce a scleroderma-mimicking disease. Macrophages were investigated in vitro to evaluate the underlying mechanisms., Results: Bleomycin induced dermal thickening and collagen accumulation in wild type mice and that was significantly attenuated in TRPA1-deficient animals. Accordingly, the expression of collagens 1A1, 1A2, and 3A1 as well as pro-fibrotic factors TGF-beta, CTGF, fibronectin-1 and YKL-40, and M2 macrophage markers Arg1 and MRC1 were lower in TRPA1-deficient than wild type mice. Furthermore, bleomycin was discovered to significantly enhance M2-marker expression particularly in the presence of IL-4 in wild type macrophages in vitro, but not in macrophages harvested from TRPA1-deficient mice. IL-4-induced PPARγ-expression in macrophages was increased by bleomycin, providing a possible mechanism behind the phenomenon., Conclusions: In conclusion, the results indicate that interfering TRPA1 attenuates fibrotic and inflammatory responses in bleomycin-induced scleroderma. Therefore, TRPA1-blocking treatment could potentially alleviate M2 macrophage driven diseases like systemic sclerosis and scleroderma., (© 2023. The Author(s).)

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role., (© 2022 Company of the International Journal of Experimental Pathology (CIJEP).)

Background: Infrared thermography (IRT) is a useful method to detect activity/inflammation in localized scleroderma (LoS); however, inactive skin lesions with a severe degree of dermal and subcutaneous atrophy may show false-positive results. Narrow-band reflectance spectrophotometry (NBRS) is an objective, non-invasive technique of measuring erythema and hyperpigmentation severity, yet has not been extensively studied in LoS., Objectives: The aim of this research was to compare the spectrophotometric results with thermographic examination of LoS lesions., Methods: The lesions were assessed using the Localized Scleroderma Assessment Tool (LoSCAT), Dyspigmentation, Induration, Erythema, and Telangiectasias (DIET) score, NBRS and IRT. The difference in the erythema index (ΔEI), melanin index (ΔMI) and average temperature Tavg (ΔTavg) were calculated between each lesion and its normal control., Results: Fifty-five patients with 49 active and 64 inactive LoS lesions were examined. The ΔEI strongly correlated with the erythema (r s  = 0.62, P < 0.0000002) and DIET score (r s  = 0.66, P < 0.0000001) and moderately correlated with the telangiectasias score (r s  = 0.58, P < 0.00001). ΔMI showed strong correlation with the dyspigmentation score (r s  = 0.65, P < 0.0000001). There was a strong correlation between the ΔTavg and the erythema score (r s  = 0.7, P < 0.000001). A moderate correlation between the Δ EI and ΔTavg was found in active LoS lesions (r s  = 0.53, P < 0.0001)., Conclusion: Narrow-band reflectance spectrophotometry may be a complementary method for determining erythema in LoS active lesions, although this technique remains inferior to IRT, because is unable to distinct between active and inactive lesions. However, NBRS enables to evaluate the severity of hyperpigmentation and telangiectasias, and it can be useful for the assessment of disease severity which is poorly evaluated by IRT., (© 2022 European Academy of Dermatology and Venereology.)

Objective: To evaluate the levels of periostin in patients with systemic sclerosis (SSc) and their association with features of systemic sclerosis., Methods: The levels of periostin were assessed in the serum of 106 SSc patients and 22 healthy controls and by immunofluorescence staining in cardiac tissue from 4 SSc patients and 4 controls. Serum periostin was measured via enzyme-linked immunosorbent assay. The results were analyzed using Mann-Whitney test or Kruskal-Wallis test followed by Dunn's multiple comparisons tests and Spearman's test for correlations. Cardiac tissue from SSc patients and controls was stained for periostin and co-stained for periostin and collagen type I using immunofluorescence., Results: Periostin levels were higher in patients with SSc compared to controls and directly correlated to modified Rodnan skin score and echocardiography parameters of left ventricular measurements. Immunofluorescence staining in SSc cardiac tissue showed patchy periostin expression in all SSc patients, but not in controls. Furthermore, there was extensive periostin expression even in areas without collagen deposition, while all established fibrotic areas showed colocalization of collagen and periostin. There was no association between periostin levels and interstitial lung disease, pulmonary hypertension or other vascular complications., Conclusion: Periostin is elevated in SSc cardiac tissue in vivo and circulating levels of periostin are increased in SSc, correlating with the extent of disease duration, degree of skin fibrosis, and left ventricular structural assessments. Periostin may be a potential biomarker that can provide further pathogenic insight into cardiac fibrosis in SSc., (© 2022. The Author(s).)

Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease of unknown aetiology. About 85% of total cases of LS are genital cases, while extragenital form is seen in only 15-20% of cases. Extragenital LS (EGLS) can occur simultaneously with genital form; however, in 6% of the cases, only extragenital form has been described. Genetic, autoimmune, infectious, environmental and hormonal factors are implicated in its aetiology. Extragenital LS presents as asymptomatic white opalescent papules, which cluster in plaques and slowly progress over time resulting in parchment-like skin usually involving upper trunk, neck and shoulders. Lesions are frequently accompanied by purpura/haemorrhagic spots. The relationship with morphoea has been a topic of debate. Association with several autoimmune diseases has been observed. Diagnosis is usually based on clinical and dermoscopic examination and further supported by histopathological findings. LS needs to be differentiated from several other dermatological conditions such as discoid lupus erythematosus, vitiligo, mycosis fungoides (hypopigmented variant), lichen planus, graft-versus-host disease and morphoea depending upon the stage of the disease. Generally, extragenital LS is believed to lack carcinogenic potential. However, case reports with possible malignant transformation have been described. In this article, the authors have described a concise review of the extragenital form of LS., (© 2022 Australasian College of Dermatologists.)

The role and potential molecular mechanism of inflammatory cells in pediatric localized scleroderma are poorly investigated. In this study, we first investigated the profiling of inflammatory cells in skin samples from pediatric localized scleroderma. Among them, CD4+ T-cells were up-regulated. Co-culture dermal fibroblasts with CD4+ T-cells promoted fibrosis of fibroblasts. Candidate lncRNAs were further explored by lncRNAs-seq between the normal skin tissues and pediatric localized scleroderma tissues, and the lncRNAs-seq between fibroblasts co-cultured with CD4+ T lymphocytes and control fibroblasts. By comparing the two datasets, we identified eight up-regulated and three down-regulated lncRNAs, which were the potential lncRNAs for the phenotype of pediatric localized scleroderma. Here, we identified the CD4+ T-cells infiltration in pediatric localized scleroderma and potential lncRNAs for the treatment of pediatric localized scleroderma., (© 2022 Wiley Periodicals LLC.)

A 21-year-old woman presented with a 13-year history of a linear lesion on the lip. She experienced no pain and only had an esthetic complaint. Her personal and family history was otherwise unremarkable. She had no history of photosensitivity, Raynaud's phenomenon, arthralgias, dry eyes, fever, trauma, or exposure to irradiation.