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There are several types of morphea with different levels of connective tissue involvement and morphological manifestations. In this mini review, it was pointed out the most important morphological and clinical aspects of localised scleroderma in the oral cavity. The case presented in this article supports the scientific information and is described with details. The morphea of mucous membrane which was clinically suspected, was proved by histopathological examination of the sample. The unusual location of the local findings posed a diagnostic challenge. The case history should be significant due to the low number of studies. The special attention should be taken to match the clinical with pathomorphological picture in localised scleroderma diagnosis and treatment when the involvement of skin and oral mucosa is.

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.

Drug-induced scleroderma-like lesion is a condition in which administration of a drug induces skin sclerotic lesions similar to systemic sclerosis or morphea. The clinical manifestations of drug-induced scleroderma-like lesion can be divided into two types: scleroderma-like lesions and morphea-like plaques. A wide variety of drugs can cause drug-induced scleroderma-like lesion. Bleomycin, L-tryptophan, vinyl chloride, and phytonadione (vitamin K1) have been reported, but in recent years, cases due to chemotherapeutic agents, such as taxane-based agents, gemcitabine, and tegafur-uracil, and immune checkpoint inhibitors have increased. Drug-induced scleroderma-like lesion differs from systemic sclerosis in that it does not include Raynaud's phenomenon, nail-fold capillary abnormality, organ involvement, such as reflux esophagitis, interstitial pneumonia, renal crisis, or anti-nuclear Abs. On the other hand, there are reports of cases in which Raynaud's phenomenon, positive conversion of anti-nuclear Abs, and development of skin sclerosis from the fingers developed after initiation of the drug. Whether the skin sclerosis improves after discontinuation of the drug depends on the patient. In patients with severe skin sclerosis, functional impairment, such as flexion contracture of the fingers, may occur, and systemic therapy, such as steroids, may be necessary. When treating patients with skin sclerosis, it is important to keep in mind the possibility that the sclerotic lesion may be induced by a drug.

Morphea profunda or subcutaneous (deep) morphea is a variant of localized morphea, characterized by one or more ill-defined, deep sclerotic plaque. Preferential sites are the abdomen, trunk, sacral area, or extremities. The presence of hyperplastic lymphoid follicles in the context of the sclerotic bands of morphea is rarely described. Localized scleroderma is sustained by a profibrotic inflammatory profile. Transforming growth factor-β (TGF-β), an imbalance between functional subclasses of T-lymphocytes (innate immune cells) has a role in activate collagen deposition. In this case report, we present two cases of morphea profunda with lymphoid follicular hyperplasia. A systematic review of the literature on the pathophysiology of localized scleroderma is also presented, with particular reference to the presence of lymphoid structures.

Morphea (localized scleroderma) is an inflammatory connective tissue disease, characterized by immune system dysfunction, vasculopathy and skin fibrosing. Phototherapy has been found to be effective in treating localized scleroderma. Psoralen + ultraviolet A (PUVA) and ultraviolet A1 (UVA1) phototherapy significantly enriched therapeutic possibilities.To compare the clinical effect of PUVA photochemotherapy and UVA1 phototherapy and to evaluate the treatment response rates.It was a retrospective one-centre research and observational study of all morphea patients treated with PUVA and UVA phototherapy. We reviewed phototherapy notes along with electronic and paper case records for all patients with morphea treated with PUVA and UVA1 phototherapy from January 2010 to December 2019.The study shows that patients in both groups experienced improvement based on clinical measures, resulting in a reduction in the clinical score in all groups. There is positive short- and long-term efficacy of UVA1 and PUVA phototherapy in patients with morphea. There were no statistical differences between the treatment response rates. Limitations: We had a relatively small study sample and it was a retrospective, observational study.Our data suggest that ultraviolet PUVA and UVA1 should be considered for the treatment of morphea with disseminated lesions or not responding to topical treatment. UVA1 is free of side effects linked to oral psoralens such as nausea, vomiting, photokeratosis, but we showed that there was no statistical advantage in the effectiveness of both. UVA1 phototherapy is, however, a less accessible form of treatment, available in the centres of higher quality.

Aim: To evaluate juvenile localized scleroderma, which is a disease with high rates of cosmetic and functional sequelae in children, from a pediatric rheumatology perspective. Materials and Methods: We retrospectively investigated the data of patients who were diagnosed with juvenile localized scleroderma (JLS) in our pediatric rheumatology clinic between 2015 and 2022, were aged Results: Among the 19 patients diagnosed with JLS, 12 (63.2%) were female, and 7 (36.8%) were male. The female-to-male ratio in the sample was 1.7. Eight (42.1%) patients had circumscribed JLS, 8 (42.1%) had linear JLS, 2 (10.6%) had mixed JLS, and 1 (5.3%) had generalized JLS. The patients' mean age of onset of symptoms was 8.2±5.5 years, while their mean age of diagnosis was 9.4±4.9 years. The most frequently involved anatomical regions were the extremities, whose involvement was found in 15 (78.9%) patients. The prevalence of lesions crossing joints was 57.9%, and joint damage was seen in 21.1% of the patients. The rate of cosmetic sequelae was 73.7%. There was antinuclear antibody positivity in 52.6% of the patients. Systemic involvement did not occur in any patients during their follow-ups. The most frequently used treatment agent was methotrexate. Complete remission was achieved in 2 (10.6%) patients. Conclusion: As it can lead to high degrees of cosmetic and functional sequelae, it is necessary to diagnose juvenile localized scleroderma early and start an aggressive treatment in the early period. To avoid wasting time, it is essential, especially for pediatricians, to immediately order biopsies from suspected lesions or refer these patients to pediatric rheumatology clinics.

Background: UVA1 phototherapy is a treatment used for multiple dermatological conditions. The optimal therapeutic regimens and dosing of UVA1 are a matter of debate. The dosages used vary widely between published studies and there are no evidence-based protocols that provide data on dosage, duration, or the role of maintenance therapy. The purpose of this study is to evaluate the experience in our medical center regarding treatment with UVA1, as well as the degree of patient satisfaction with the treatment according to their pathology. Methods: We present a retrospective evaluation of outcomes, treatment tolerability, and satisfaction in adult patients using a low dose of UVA1 phototherapy, administered in our dermatologic service between 2019 and 2022. Results: A total of 78 patients were treated with UVA1, of whom 46 patients (59%) were over 18 years old, completed treatment, and gave their consent. The overall objective clinical response rate was 91.30% (42/46), achieving a complete response in 17 (36.96%) patients, partial response in 25 (54.34%), and no response in 4 (8.70%). The complete response rates recorded were high in morphea, scleredema, or chronic hand eczema. In terms of the level of satisfaction objectively measured by TSQM-9 version 1.4, highlighting high scores obtained in mastocytosis, systemic sclerosis, morphea, scleredema, chronic hand eczema, or prurigo nodularis (over 65 points). Conclusions: We present a review of treatment with UVA1 phototherapy at low doses with good response in a wide variety of dermatological pathologies.

Connective tissue diseases share certain common traits such as skin inflammation, and joint and other structures rich in connective tissue, along with immune defects. They represent a heterogeneous group of diseases characterized by a wide variety of signs and symptoms. The autoimmune connective tissue diseases include lupus erythematous, dermatomyositis, and morphea, and are considered classic connective tissue diseases. In this chapter The Epidemiology, etiopathogenesis, clinical presentation, differential diagnosis, complementary examinations, and therapeutic approaches for connective tissue diseases are discussed.

Background Patients with chronic inflammatory skin disease (CISD) have potential risk factors for herpes zoster (HZ). However, little is known about HZ risk in CISD. Objective To determine whether CISD is associated with HZ. Methods Data were analyzed from the 2002 to 2012 Nationwide Inpatient Sample, a representative cohort of US hospitalizations (N = 68,088,221 children and adults). Results In multivariable logistic regression models including age, sex, race/ethnicity, insurance, household income, and long-term systemic corticosteroid use, hospitalization for HZ was associated with atopic dermatitis (adjusted odds ratio [95% confidence interval], 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Only lichen planus (crude odds ratio [95% confidence interval], 3.01 [1.36-6.67]), Sezary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) showed increased odds in bivariable models. Sensitivity analyses among those younger than 60 and younger than 50 years showed similar results. Predictors of HZ in CISD included female sex, fewer chronic conditions, and long-term systemic corticosteroid use. Limitations Cross-sectional study. Conclusions Many CISDs are associated with increased hospitalization for HZ, even below the ages recommended for HZ vaccination. Additional studies are needed to establish CISD-specific vaccination guidelines.

Children and adolescents with localized scleroderma (LS) are at high risk for extracutaneous-related functional impairment including hemiatrophy, arthropathy, seizures, and vision impairment. Compared with adult-onset LS, pediatric disease has a higher likelihood for poor outcome, with extracutaneous involvement twice as prevalent in linear scleroderma, disease relapses more common, and disease duration more than double. Consensus among pediatric rheumatologists on treating patients at risk for significant morbidity with systemic immunosuppressants has led to major improvements in outcome. This review discusses recent progress in assessment and treatment strategies and in our understanding of key disease pathways.

Morphea, a localized form of scleroderma, is a chronic inflammatory autoimmune disease of the skin. Color Doppler Ultrasound has been reported as a reliable tool to assess the activity of the disease. With histologically confirmed cases, this case series describes a new ultrasound sign consisting of a hyperechoic halo surrounding superficial subcutaneous veins of the extremities in transverse view, named the sun sign. This sign can help diagnose morphea in the inflammatory phase and correlate in pathology with perivascular infiltrates surrounding superficial subcutaneous veins.

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 ...

Localized scleroderma (LS, morphea, limited scleroderma, focal scleroderma) is a chronic autoimmune disease characterized by a progressive damage to the connective tissue with a predominance of fibrosclerotic disorders in the skin and the subcutaneous tissue. In addition surrounding structures may be affected: fascia, muscle, and bone tissues. This review reflects the current understanding about limited scleroderma, its pathogenesis, diagnosis, new biomarkers, and information about the possibilities of its transition to systemic scleroderma. The following new biomarkers have been identified: galactosylated IgG (Ig-Gal), progranulin (PGRN), chemokine CCXL 18, various types of microRNA (miRNA-let-7a, miRNA-7, miRNA-196a, miRNA-155, miRNA-483-5p), periostin, and myelin basic protein (MBP). Knowledge about new biomarkers of LS will help us to explore the patients' predisposition to the development of systemic scleroderma. In addition, by acting on these biomarkers, it is possible to prevent the progression of LS in the early stages and its transition to systemic scleroderma. The review also presents the current understanding of autoantibodies in LS and their correlation with clinical signs of the disease.

OBJECTIVE To study disease course and long-term outcome in children with linear scleroderma (SSc) treated with methotrexate (MTX) since diagnosis. METHODS 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. RESULTS 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. CONCLUSION 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.

Pediatric morphea is an inflammatory, fibrosing dermatologic disorder. Although morphea may be localized to the skin and subcutaneous tissues, differentiating it from systemic sclerosis, there is increasing evidence that morphea is a manifestation of a systemic inflammatory process, with the potential to involve many organ systems. Given the potential risk for irreversible sequelae, pediatric morphea should be treated early and aggressively. Long-term disease monitoring is essential.

Background The clinicopathologic correlations and prognostic risk factors for refractory disease in morphea (localized scleroderma) are poorly described. Objective To investigate the association between clinical characteristics and histopathologic features of morphea and identify risk factors for refractory disease. Methods We retrospectively reviewed the clinical and histopathologic features, treatment regimens, and clinical responses for 137 patients with biopsy-proven morphea from January 2008 to May 2019. Multivariate analysis was conducted to identify factors associated with poor treatment response. Results We detected associations between the pattern and degree of sclerosis and the anatomic site of the lesion, as well as between severe inflammation and concomitant autoimmune disease. Additionally, both bottom-heavy sclerosis and increased inflammation were associated with functional limitations/clinical symptoms. Based on our multivariate analysis, we found that increased risk of poor treatment response was correlated with tissue eosinophils and basal pigmentation. Limitations This was a single-center retrospective study. Conclusion Skin biopsy samples could show specific features of morphea, including eosinophil infiltration and basal pigmentation, which may indicate the need for aggressive treatment and frequent monitoring.

Demographic and clinical findings of patients with mucocutaneous morphea have not been well characterized, to our knowledge.To determine the demographic and clinical characteristics of morphea patients with mucocutaneous lesions who were enrolled in the Morphea in Adults and Children cohort.Cross-sectional study of 735 patients in the Morphea in Adults and Children cohort from 2007 to 2018.A total of 4.6% of linear morphea patients had oral involvement versus 2.4% among the entire cohort, whereas 10.3% of generalized morphea patients had genital involvement versus 3.7% among the entire cohort. Patients with genital lesions were older at disease onset than those with oral morphea (57 versus 11.5 years; P .001) and had more frequent extragenital lichen sclerosus et atrophicus (59.2% versus 5.6%; P = .004).Selection bias and limited number of affected subjects.Oral morphea lesions predominate in younger patients with facial linear morphea, whereas genital lesions predominate in postmenopausal women with overlying extragenital lichen sclerosus et atrophicus.

Background The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. Objective To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. Methods A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. Results A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). Limitations Retrospective nature and the inclusion of only patients with clinical photographs. Conclusion The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

Localized scleroderma (LS) is an autoimmune disease with sclerosis of the skin as the main manifestation. Currently, there is no specific treatment for LS. The effectiveness of ablative fractional laser (AFL) therapy for LS has been demonstrated in several studies. Combining ablative fractional Er:YAG laser therapy with topical methotrexate may yield therapeutic benefits for patients with LS. To compare the efficacy and safety of AFL-assisted delivery of methotrexate in adults with LS, we randomly divided patients into an AFL therapy group and an ablative fractional laser-assisted delivery of methotrexate (AFL+MTX) therapy group. Laser and assisted drug delivery treatment were given every four weeks for four months, and 22 patients completed the trial. Ultrasound measurements of dermal thickness and histological fibrosis degree and the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) score were used to assess therapeutic effects. Treatment results showed that both AFL and AFL-assisted methotrexate delivery were effective in treating LS, and the laser combined with methotrexate therapy was more effective in improving clinical appearance (p value = 0.042) and dermal thickness (p value = 0.016). No serious adverse reaction occurred in either group. In conclusion, AFL and assisted delivery of methotrexate are effective and safe treatments for LS.

Celiac disease is an immune-mediated disease, affecting multiple systems and organs including several dermatological conditions. Morphea, or localized scleroderma, is also an immune-mediated condition, in which an association with celiac disease has not thus far been recognized. We present an interesting case report of a 10-year-old child with a recent diagnosis of celiac disease presenting with morphea. Following treatment and adherence to a gluten-free diet, the morphea rapidly resolved. We suggest a possible relationship between the two entities and give a brief review of the relevant literature. We suggest that morphea might be one of the many dermatological manifestations of celiac disease, with possible implications for the need to screen patients with morphea for celiac disease.

Michal Szczepanek, Aleksandra Frątczak, Anna Lis-Święty Department of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, PolandCorrespondence: Anna Lis-ŚwiętyDepartment of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Francuska 20/24, Katowice, 40-027, PolandTel +48 602720948Email annadlis@neostrada.plBackground: Localized scleroderma (LoS) is an inflammatory fibrosing disease of the connective tissue, whose esthetic sequelae are atrophic skin lesions with hyperpigmentation. The key element of diagnostic and therapeutic procedures is the assessment of the disease’s severity and damage. The study objective was to analyze the usefulness of narrow-band reflectance spectrophotometry (NBRS) to assess erythema and hyperpigmentation in LoS lesions.Materials and Methods: Erythema indexes (EI) and melanin indexes (MI) were determined with the use of DermaLab Combo skin colour probe for LoS lesions and symmetrically located areas of normal skin. Then, relative percentage differences were determined for EI and MI, which were compared with the visual assessments of erythema and hyperpigmentation according to the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT).Results: A total of 84 LoS lesions were studied in 41 patients. The study showed a moderate correlations between the spectrophotometric measurements and clinical assessments of erythema as well as hyperpigmentation (Spearman correlation coefficient, r), r = 0.37; p = 0.00047 and r = 0.55; p=0.0000001, respectively.Conclusion: NBRS seems to be a useful tool to assess the severity of erythema and hyperpigmentation in LoS lesions. Further studies are required in order to compare the spectrophotometric results with other objective methods.Keywords: colour, erythema, morphea, postinflammatory hyperpigmentation

Michal Szczepanek, Aleksandra Frątczak, Anna Lis-Święty Department of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, PolandCorrespondence: Anna Lis-ŚwiętyDepartment of Dermatology, School of Medicine in Katowice, Medical University of Silesia, Francuska 20/24, Katowice, 40-027, PolandTel +48 602720948Email annadlis@neostrada.plBackground: Localized scleroderma (LoS) is an inflammatory fibrosing disease of the connective tissue, whose esthetic sequelae are atrophic skin lesions with hyperpigmentation. The key element of diagnostic and therapeutic procedures is the assessment of the disease’s severity and damage. The study objective was to analyze the usefulness of narrow-band reflectance spectrophotometry (NBRS) to assess erythema and hyperpigmentation in LoS lesions.Materials and Methods: Erythema indexes (EI) and melanin indexes (MI) were determined with the use of DermaLab Combo skin colour probe for LoS lesions and symmetrically located areas of normal skin. Then, relative percentage differences were determined for EI and MI, which were compared with the visual assessments of erythema and hyperpigmentation according to the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT).Results: A total of 84 LoS lesions were studied in 41 patients. The study showed a moderate correlations between the spectrophotometric measurements and clinical assessments of erythema as well as hyperpigmentation (Spearman correlation coefficient, r), r = 0.37; p = 0.00047 and r = 0.55; p=0.0000001, respectively.Conclusion: NBRS seems to be a useful tool to assess the severity of erythema and hyperpigmentation in LoS lesions. Further studies are required in order to compare the spectrophotometric results with other objective methods.Keywords: colour, erythema, morphea, postinflammatory hyperpigmentation

A nematode parasite, Dracunculus medinensis, causes dracunculiasis. Despite being non-fatal, this condition causes significant morbidity. Dracunculiasis is considered an eradicated disease in India since 1999. We report two cases that document the unusual linear morphea-like morphology of the calcified D. medinensis and the rare periorbital location of the worm. The cases presented here are rare and a diagnostic challenge, considering the eradicated status of dracunculiasis.

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI–73.7%, mLoSDI–43.9%, PGA-A–60.4%, PGA-D–40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration.

En coup de sabre form of morphea often affects the scalp with thickening, sclerosis, dyspigmentation, and scarring alopecia. Traditionally, it has been thought that the alopecia is not responsive to treatment and permanent. This report presents two cases with extensive, apparent scarring alopecia that improved with medical treatment.

Eosinophilic fasciitis is a rare disorder of unknown etiology and poorly understood pathogenesis. It may be triggered by excessive exercise, physical factors such as radiation therapy, exposure to certain medications, infections, the initiation of hemodialysis and some other medical conditions. Skin modifications appear with collagenous thickening of the subcutaneous fascia with typical aspect of “peau d’orange” and the “groove sign”. Arthritis, myalgia, myositis, neuropathies may occur. The majority of patients have peripheral blood eosinophilia. The diagnosis is confirmed with a full thickness incisional biopsy of skin and subcutaneous tissue down to the muscle surface and fascia. Systemic glucocorticoids are the mainstay of treatment, but some patients require additional immunosuppressive therapy. The long-term prognosis of this disease is unknown and in some cases the disease may releapse. We describe two patients with eosinophilic fasciitis, their evolution and complications, associating other pathologies: morphea and antiphospholipid syndrome, making the diagnosis and the treatment more challenging.

Objective The aim of this study was to evaluate factors associated with extracutaneous involvement (ECI) in juvenile localized scleroderma (jLS). Methods A prospective, multicentre, 6-month observational study was performed. The data collected included disease features, global assessments, and subject symptoms. Bivariate and linear multilevel regression analyses were performed. Results A total of 86 jLS subjects (80% female, 80% Caucasian), median age of disease onset 7.7 years, were evaluated. Most had linear scleroderma or mixed morphea. Of the 86 subjects, 49 (57%) had 125 extracutaneous problems {median 2 [interquartile range (IQR) 1, 3] per subject} from nine organ systems. Most of these subjects had multiple musculoskeletal problems. ECI was associated with more extensive cutaneous involvement, higher number of symptoms, family history of autoimmunity, and ANA and RF positivity. Subjects with ECI had higher scores for physician global assessment of damage (PGA-D), and parental global assessment of disease impact, but not baseline physician global assessment of disease activity (PGA-A). Although subjects with ECI received more MTX and glucocorticoid treatment, they had a slower reduction in PGA-A scores and symptoms over time, suggesting a poorer response to treatment. In logistic regression modelling, female sex had the largest effect on parental impact scores. Conclusion ECI occurred in the majority of subjects with jLS, and was associated with more medication use, longer treatment duration, higher PGA-D scores, and higher parental assessment of disease impact. Our findings suggest that jLS subjects with ECI have greater overall disease burden, both cutaneous and extracutaneous, and poorer response to treatment. More study of the treatment needs of this population is warranted.

Localized scleroderma (LS), also known as morphea, is a complex and poorly understood disorder in children. The various clinical subtypes of LS require different approaches to evaluation and treatment. Failure to recognize and appropriately treat the affected skin and underlying deep connective tissue can lead to long-term morbidity. We present a review of the current literature supporting treatment options for pediatric LS followed by a series of cases to highlight the complexity of treatment choices and identify clinical pearls. Increasing evidence has emerged for the utility of systemic immunomodulation in treating localized scleroderma. Multiple consensus-based treatment protocols are now available, though underlying evidence is moderate. There are emerging reports utilizing modern biologic and small molecules, but these remain relatively sparse. Therapeutic regimens for LS should be based upon a detailed physical examination augmented by the results of additional screening evaluations recommended for the subtype of LS. Close collaboration with multiple specialties may be needed to achieve optimal outcomes, including rheumatology, dermatology, physical therapy, and craniofacial plastic surgery. More study is needed to identify the efficacy of newer therapeutic options as well as the role for adjunctive therapies.

There are two major clinical subsets of scleroderma: (i) systemic sclerosis (SSc) is a complex systemic autoimmune disorder characterized by inflammation, vasculopathy, and excessive fibrosis of the skin and multiple internal organs and (ii) localized scleroderma (LoS), also known as morphea, is confined to the skin and/or subcutaneous tissues resulting in collagen deposition and subsequent fibrosis. SSc is rare but is associated with significant morbidity and mortality compared with other rheumatic diseases. Fatal outcomes in SSc often originate from organ complications of the disease, such as lung fibrosis, pulmonary artery hypertension (PAH), and scleroderma renal crisis (SRC). Current treatment modalities in SSc have focused on targeting vascular damage, fibrosis, and regulation of inflammation as well as autoimmune responses. Some drugs previously used in an attempt to suppress fibrosis, like D-penicillamine (D-Pen) or colchicine, have been disappointing in clinical practice despite anecdotal evidence of their advantages. Some canonical medications, including glucocorticoids, immunosuppressants, and vasodilators, have had some success in treating various manifestations in SSc patients. Increasing evidence suggests that some biologic agents targeting collagen, cytokines, and cell surface molecules might have promising therapeutic effects in SSc. In recent years, hematopoietic stem cell transplantation (HSCT), mostly autologous, has made great progress as a promising treatment option in severe and refractory SSc. Due to the complexity and heterogeneity of SSc, there are currently no optimal treatments for all aspects of the disease. As for LoS, local skin-targeted therapy is generally used, including topical application of glucocorticoids or other immunomodulatory ointments and ultraviolet (UV) irradiation. In addition, systemic immunosuppressants are also utilized in several forms of LoS. Here, we comprehensively discuss current treatment options for scleroderma, encompassing old, new, and future potential treatment options. In addition, we summarize data from new clinical trials that have the potential to modify the disease process and improve long-term outcomes in SSc.

Morphea, also known as localized scleroderma, is a chronic, autoimmune disease of connective tissue. It is characterized by a typical clinical feature. In morphea, there is no Raynaud’s phenomenon, no sclerodactyly or no ulcerations on the fingertips. Although morphea and systemic sclerosis have been perceived as separate disease entities for years, they are still confused both by patients (which is a source of unnecessary stress) and doctors. This may be due to, in part, misunderstood terminology. The controversy around morphea also concerns the division of this disease entity, including its less common subtypes, such as eosinophilic fasciitis. Discussions also revolve around the diagnostic aspects and possible treatment options. The paper attempts to present the debatable aspects regarding nomenclature, classification, diagnosis and treatment of morphea.

Cutaneous pseudolymphomas are a heterogeneous group of reactive lymphocytic infiltrates, which simulates cutaneous lymphomas clinically and histologically. Although in many cases the pathogenesis is not understood, a broad spectrum of different agents inducing pseudolymphomas has been reported. Cutaneous pseudolympomas are distinguished in four main groups: (a) nodular pseudolymphomas, (b) pseudo-mycosis fungoides (pseudo-MF) and simulators of other CTCLs, (c) other pseudolymphomas and (d) an intravascular pseudolymphoma. This article focuses on pseudolymphoma entities related to infections or inflammatory skin diseases. The integration of the clinical presentation and patients’ history is mandatory for the correct diagnosis.

Localized scleroderma is an inflammatory disease causing sclerosis of the skin. The aetiology and pathogenesis of localized scleroderma remain unclear. Localized scleroderma is considered a genetically driven disease. It is not well understood if genetic factors or environmental exposure individually can cause its development or if their interaction is needed to trigger the disease. Some authors postulate that familial clustering is evidence of a hereditary disease. Familial localized scleroderma has been rarely reported and is a case worth studying. We present the review of literature on this subject with 3 additional cases of familial localized scleroderma with paediatric onset.

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Sarcoidosis is a systemic granulomatous disorder of unknown etiology that can virtually involve any organ system. The most commonly affected sites include lungs, thoracic lymph nodes, eyes, heart, and central nervous system, with skin involvement in an estimated 20% to 35% of patients.1,2 The cutaneous manifestations of sarcoidosis are heterogeneous; however, these are broadly classified as “specific” if they contain noncaseating granulomas on histopathologic examination or as “nonspecific” if they lack this hallmark feature (Table I).1,2 Morpheaform sarcoidosis is a “specific” variant that can represent a particular diagnostic challenge.1 Due to its clinical resemblance to morphea, patients are often misdiagnosed as having localized scleroderma. Here, we describe a patient who was thought to have morphea but later diagnosed with skin-limited morpheaform sarcoidosis. Table I Examples of specific and nonspecific lesions of cutaneous sarcoidosis

The increase in the degree of fluctuation asymmetry is accompanied, among others, by diseases such as morphea en coup de sabre (morphea ECDS) or Parry‑Romberg syndrome (PHA). Patients suffering from them struggle not only with dermatological defects, but also with neurological, rheumatological, orthopedic, ophthalmological and dental symptoms. Morphological and functional disorders and craniofacial deformities related to them often generate psychosocial problems. The complexity of the issues to be solved proves the necessity of undertaking interdisciplinary actions aimed at developing objective diagnostic and therapeutic protocols, restoring (especially in pediatric patients) as close as possible to the correct developmental patterns, inhibiting the active phase of the disease and undertaking effective and aesthetically satisfying measures.

The care of breast cancer patients is important to dermatologists. Breast cancer's initial presentation, clinical progression, and its associated treatments can result in a variety of cutaneous complications. Dermatologists may be the first to identify a breast cancer diagnosis, as a subset of patients first present with direct extension of an underlying tumor or with a cutaneous metastasis. The surgical treatment of breast cancer also begets a variety of skin sequelae, including postoperative lymphedema, soft tissue infections, seromas, pyoderma gangrenosum, and scarring disorders. Moreover, breast cancer radiation treatment commonly results in skin changes, which can range from mild and temporary dermatoses to chronic and disfiguring skin ulceration, fibrosis, and necrosis. Radiation may also precipitate secondary malignancies, such as angiosarcoma, as well as rarer dermatologic diseases, such as radiation-induced morphea, lichen planus, and postirradiation pseudosclerodermatous panniculitis. Finally, breast cancer is also associated with an array of paraneoplastic phenomena, including Sweet's syndrome and the rarer intralymphatic histiocytosis. Herein, we review the dermatological manifestations of breast cancer, including conditions associated with its presentation, progression, and treatment sequelae. Chemotherapy-induced cutaneous side effects are beyond the scope of this review. This article provides a comprehensive review for dermatologist to be able to identify, diagnose, and manage breast cancer patients from initial presentation to treatment monitoring and subsequent follow-up.

Background The purpose of this study was to assess variability in cell composition and cell-specific gene expression in the skin of patients with localized scleroderma (LS) utilizing CryoStor® CS10 in comparison to RPMI to produce adequate preservation of tissue samples and cell types of interest for use in large-scale multi-institutional collaborations studying localized scleroderma and other skin disorders. Methods We performed single-cell RNA sequencing on paired skin biopsy specimens from 3 patients with LS. Each patient with one sample cryopreserved in CryoStor® CS10 and one fresh in RPMI media using 10× Genomics sequencing. Results Levels of cell viability and yield were comparable between CryoStor® CS10 (frozen) and RPMI (fresh) preserved cells. Furthermore, gene expression between preservation methods was collectively significantly correlated and conserved across all 18 identified cell cluster populations. Conclusion Comparable cell population and transcript expression yields between CryoStor® CS10 and RPMI preserved cells support the utilization of cryopreserved skin tissue in single-cell analysis. This suggests that employing standardized cryopreservation protocols for the skin tissue will help facilitate multi-site collaborations looking to identify mechanisms of disease in disorders characterized by cutaneous pathology.

Background: Linear morphea is a variant of scleroderma limited to the skin and underlying tissues secondary to an autoimmune inflammation leading to excess collagen deposition and fibrosis. Apart f...

Becker’s nevus (BN) is an acquired unilateral hyperpigmented hairy macule, whereas morphea is a chronic connective tissue disease of unknown etiology, characterized by skin thickening with increased quantities of collagen in the indurated lesion, usually involving the upper trunk and proximal extremity. The occurrence of both disease in the same anatomical site and individual was not reported previously. We report this rare case in a 17-year-old, Indian girl and was diagnosed after clinical histopathology and dermoscopic correlation. Morphea can be an interesting incidental occurrence within a large plaque of BN.

Besides the well-known use in supporting the non-invasive diagnosis of non-tumoral dermatoses (general dermatology), dermoscopy has been shown to be a promising tool also in predicting and monitoring therapeutic outcomes of such conditions, with the consequent improvement/optimization of their treatment. In the present paper, we sought to provide an up-to-date overview on the use of dermoscopy in highlighting response predictor factors and evaluating therapeutic results in the field of general dermatology according to the current literature data. Several dermatoses may somehow benefit from such applications, including inflammatory conditions (psoriasis, lichen planus, dermatitis, granulomatous conditions, erythro-telangiectatic rosacea, Zoon balanitis and vulvitis, cutaneous mastocytosis, morphea and extra-genital lichen sclerosus), pigmentary disorders (vitiligo and melasma) and infectious dermatoses (scabies, pediculosis, demodicosis and viral warts).

During the coronavirus disease 2019 (COVID-19) pandemic, individuals especially those with chronic diseases face various problems like psychological distress. To evaluate anxiety and depression among morphea patients taking immunosuppressants compared with controls during the COVID-19 pandemic. In this case-control study, electronic data of 42 eligible morphea patients and 42 age- and sex-matched healthy subjects were extracted. All participants were asked about adherence to the health protocols and the symptoms of COVID-19. To investigate anxiety and depression, we provided the participants with an online version of the Hospital Anxiety and Depression Scale (HADS) Questionnaire. In this standard questionnaire, a score ≥ 11 represents a significant psychological disorder. The two groups did not differ significantly in the mean HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) scores (p= .08 and p= .79, respectively). HADS-A and HADS-D scores were ≥ 11 in 16.67% and 11.90% of the patients, respectively. Among the morphea patients, those with sleeping problems during COVID-19 had a significantly higher mean HADS-D score (p= .048). Notably, 21.43% of patients discontinued their treatment due to fear of COVID-19 and experienced disease recurrence. Adherence to health protocols was higher in patients compared with controls. The rate of COVID-19 occurrence was not significantly different between the groups. Although there was no significant difference in anxiety and depression between the groups, it is recommended to provide psychiatric counseling opportunities to morphea patients to improve treatment outcomes during this pandemic.

Recombinant interferon beta‐1b is one of the treatment options of multiple sclerosis (MS). Insertional biologics that are used in the treatment of MS may lead to skin adverse effects, for example, morphea.

Scleroderma is a rare connective tissue disorder categorized into systemic sclerosis and localized scleroderma, also called morphea. Linear scleroderma of the scalp, also called en coup de sabre, is infrequently associated with neurologic symptoms. We describe a case of linear scleroderma en coup de sabre in a 28-year-old female presenting with seizures and characteristic cutaneous lesions. Imaging findings over a course of 7 years demonstrated waxing and waning signal changes. MR perfusion and spectroscopic imaging, demonstrating decreased cerebral blood volume, increased mean transit time, and decreased metabolites, was performed during a time of progressing radiological and clinical findings. Comparison with other reports in the literature supported several clinical and imaging findings that while not pathognomic, highly suggest the diagnosis of linear scleroderma en coup de sabre. Hyperintense signal on T2W magentic resonance imaging and contrast enhancement on computed tomography and magnetic resonance imaging have been the most commonly described imaging findings. To our knowledge, no previous description of spectroscopic or perfusion imaging of linear scleroderma en coup de sabre have been reported. It is our hope that this report may add MRS and magnetic resonance perfusion findings to a growing knowledge of this rare entity.

Since the field around morphea and systemic sclerosis (SSc) is evolving rapidly, this review approaches conventional as well as more recent clinical developments from a dermatological point of view. Skin manifestations are critical in sub-classifying these diseases ensuring a correct prognosis for these patients. They can be discretely present, and therefore, diagnosis can be challenging sometimes, implicating a thorough dermatological examination is mandatory. Furthermore, a growing amount of dermatologists perform nailfold videocapillaroscopy (NVC), a more recent reliable non-invasive imaging technique used for in vivo assessment of the microcirculation at the nailfold. After all, specific NVC-changes are present in a majority of patients with SSc. This way, dermatologists not only take part in the diagnosis process through clinical investigation but also through the use of a modern state of the art imaging technique that is becoming the golden standard in SSc multidisciplinary workup. In this review, current understandings for NVC in morphea and SSc are revised. So far, the role of NVC in the diagnosis/prognosis/classification of morphea patients has not been thoroughly investigated to make proper conclusions. As for SSc, it is well known that NVC contributes to the diagnosis and can make a fundamental difference especially when obvious clinical SSc signs are absent. This review emphasizes the (somewhat underestimated) role of dermatologists in the process of diagnosis and follow-up, and thus, the difference we can make for our patients and fellow colleagues in the multidisciplinary workup of SSc and morphea., SCOPUS: re.j, info:eu-repo/semantics/published

Morphea and systemic sclerosis are inflammatory, sclerosing disorders. Morphea primarily affects the dermis and subcutaneous fat, while systemic sclerosis typically involves the skin and internal organs. Functional impairment and cosmetic disfigurement are common in both diseases. Treatment options to mitigate disease progression remain limited. Both functional impairment and cosmetic deficits negatively impact quality of life and psychological well-being in this patient population. While the number of cosmetic procedures performed in the United States continues to rise each year, limited data exist regarding best practices for correcting aesthetic deficits caused by autoimmune conditions. There is scarce information to guide safety decisions regarding laser parameters, soft tissue augmentation, treatment intervals, and the concurrent use of immune-modifying or immune-suppressing medications. Given the fears of disease reactivation and exacerbation from postprocedural inflammation along with limited data, it is difficult for clinicians to provide evidence-based cosmetic treatment with realistic expectations with regard to short- and long-term outcomes. In the first article in this continuing medical education series, we attempt to address this practice gap.

Juvenile localized scleroderma (JLS) is a group of childhood diseases with the main symptom — skin and subcutaneous structures lesions, without any organ involvement. There is active (inflammatory) and fibrotic phase in development of JLS. The JLS treatment during active phase (when skin lesions are reversible) is the most effective. The management is determined by the area and depth of skin lesions, appearance and spread of new lesions, presence of extracutaneous signs of the disease. Topical and systemic immunosuppressants are the basic therapy for JLS. The use of antibiotics is not suggested. Clinical scores (LoSCAT), ultrasound, thermography and magnetic resonance imaging are recommended to estimate the treatment efficacy.

Objective: to assess the parameters of echocardiography, structure of cardiovascular pathology in patients suffering from morphea. Material and methods. The echocardiographic data and cardiovascular pathology were studied in 74 patients with morphea. Results. Diastolic dysfunction of the left ventricle was revealed in 37.5 % of the morphea patients, dilatation of the left atrium was found in 10.8% of the patients, pathological regurgitation on the aortic valve - in 21.62 %. 86.5 % of the patients had morphea combined with arterial hypertension. Conclusion: Such comorbid pathologies as arterial hypertension, dilatation of the left atrium, pathological regurgitation on the aortic valve and left ventricular diastolic dysfunction are common for patients with morphea.

The localized scleroderma (morphea) is the clinical option of the juvenile scleroderma, the third in prevalence rheumatic condition in pediatrics. The article summarizes all the data on the classification, diagnostics, and differential diagnosis of juvenile localized scleroderma. The recent international guidelines on the localized scleroderma in pediatrics (the European consensus of pediatric rheumatologists, the German and Japanese national guidelines) are presented in the article.