Morphea Research Articles

Novel multispectral imaging to predict disease progression in pediatric morphea.

Morphea, or localized scleroderma, is an inflammatory, fibrosing skin disorder that can be progressive and debilitating. Infrared thermography frequently has false positive results. The aim of this study was to assess the ability of multispectral imaging to predict disease progression in children with morphea. Children with morphea were recruited between 2016 and 2022. Multispectral images of affected and matched contralateral unaffected sites were obtained using the Antera™ 3D camera. Clinical assessment was performed using the Localized Scleroderma Assessment Tool (LoSCAT). Children were followed up every 3 months for imaging and clinical review. The main outcome measurement was correlation of hemoglobin gradient between affected and matched contralateral unaffected tissue and progression. Of 17 children, the average age was 12 years (range 6-18 years); most were female (76.5%) and white (94.1%). Nearly two-thirds (64.7%) had linear morphea, 35.2% had plaque morphea; 58.8% had been treated with systemic agents. The average LoSCAT score was 20.6 (range 5-73). The average hemoglobin gradient between affected and matched contralateral unaffected skin was four times higher in those who had progression (average differential 0.3, range 0.1-0.4) compared to those who did not (average differential 0.08, range 0.02-0.15). Using a cut off of a 0.18 hemoglobin gradient between affected and unaffected skin, the sensitivity of multispectral imaging for detecting progression in pediatric morphea is 90% with specificity of 100%. Multispectral imaging is a novel assessment tool with promising accuracy in predicting progression as an adjunct to clinical assessment in pediatric morphea. Further research should examine its performance against thermography.

Damage evaluation of craniofacial localized scleroderma using magnetic resonance imaging.

Localized scleroderma (LoS) is an autoimmune disease in which craniofacial lesions can cause severe facial deformities with brain involvement. Objective evaluation of craniofacial LoS is challenging. Magnetic resonance imaging (MRI) may be used as a damage assessment tool. This study aimed to analyze the tissue involvement of craniofacial LoS based on MRI and evaluate MRI for craniofacial LoS assessment. This cross-sectional study included patients with craniofacial LoS from September 2021 to August 2022 in Peking Union Medical College Hospital. Patients who were clinically assessed in a stable phase were enrolled; patients with previous surgical treatment or contraindications to MRI were excluded. Participants underwent clinical, MRI, and ultrasound assessments. MRI was compared with ultrasound by correlation analysis and Bland-Altman analysis. The involvement of different tissues and different facial subunits was compared. The accumulated soft tissue atrophy index (ASTAI) was compared with clinical scores by correlation analysis. A total of 28 patients were included (13 female; mean age, 18 years). MRI showed a good correlation and agreement with ultrasound (r=0.916, P<0.001). In different facial subunits, a significant negative correlation between the forehead and chin was found (r=-0.593, P=0.001). The ASTAI correlated well with the facial LoS damage index (r=0.580, P=0.001) and the Peking Union Medical College LoS facial aesthetic index (PUMC LoSFAI) (r=0.921, P<0.001). A total of 38.6% of clinical scores were inaccurate based on MRI. Neurological changes were found in one patient. MRI can reliably quantify damage in craniofacial LoS, and may serve as a useful and objective tool for overall craniofacial LoS evaluation.

A Comparison of Clinical, Demographic and Treatment Characteristics of Pediatric-Onset and Adult-Onset Patients Diagnosed With Localized Scleroderma.

Morphea localized scleroderma (LS) is a rare skin disease with unknown pathogenesis, which causes sclerosis of the dermis and subcutaneous tissue. It was aimed to compare the characteristics of patients with pediatric and adult-onset morphea. A retrospective analysis was performed on the records of 183 adult morphea patients. The demographics, clinical and laboratory characteristics, and treatment options of the patients were recorded. Adult patients with morphea over the age of 18 were divided into two groups according to the age of onset and compared. Twenty-two percent (N = 41) of the patients had pediatric-onset morphea (POLS) and 77.6% (n=142) had adult-onset morphea (AOLS). While POLS had a higher head-neck involvement, AOLS had a higher breast involvement (P < 0.001 and P = 0.043). Patients with linear morphea were younger, and more frequently had at least one laboratory anomaly (P = 0.016 versus 0.024). Anti-dsDNA positivity and low hemoglobin (Hb) were observed more frequently in patients with breast involvement. Patients with inguinal involvement, on the other hand, had lower Hb and a higher rate of diabetes, and those patients were older (P = 0.042, 0.040, and 0.012, respectively). Clinical characteristics and accompanying laboratory anomalies of the patients with morphea depend on the age of onset, involvement areas and the types of morphea, having such data readily available should guide the holistic approach for, and the monitoring process of, the disease.

Simultaneous occurrence of linear scleroderma and segmental vitiligo Ipsilateral: association with mosaicism?

O Vitiligo e a Esclerodermia são dermatoses distintas, que são marcadas por lesões cutâneas, de etiologia primariamente autoimune e patogênese incerta. Raros relatos descrevem a ocorrência simultânea de ambas afecções, sugerindo uma fisiopatologia comum provável, mas ainda indefinida. Acredita-se que a ocorrência de ambas as doenças pode resultar de mosaicismo genético, com apresentações unilaterais. Neste trabalho relatamos um caso raro e em criança do sexo feminino portadora de Vitiligo e Esclerodermia concomitantes e de acometimento ipsilateral e discutir uma possível associação entre as duas doenças.

Juvenile localized scleroderma

Juvenile scleroderma, often referred to as juvenile localized scleroderma or "morphea", is arare inflammatory disease of the skin and skin-related structures, accompanied by local sclerosis and tissue fibrosis. Depending on the clinical manifestation, four different subtypes can be defined: limited, generalized, linear, and mixed. To prevent possible sequelae of the disease, the diagnosis should be made as early as possible and therapy should be initiated at specialized centers in multiprofessional pediatric and dermatologic collaboration. In this review, we present the main clinical, laboratory, and therapeutic characteristics of juvenile localized scleroderma and summarize recommendations.

Biomarkers in skin autoimmunity-An update on localised scleroderma.

Human autoimmune diseases are complex and highly diverse conditions that can be of localised or systemic nature. Understanding the basic biology of autoimmune diseases goes hand in hand with providing the clinics with valuable biomarkers for managing these diseases. The focus of this review is paid to localised scleroderma, an autoimmune disease affecting skin and subcutaneous tissue. Localised scleroderma has very few serological biomarkers for clinical analyses distinguishing it from main differentials, and yet noneffective prognostic biomarkers. With this regard, the review covers well-established and new biomarkers such as cell surface proteins, autoantibodies and cytokines. In recent few years, several new biomarkers have been suggested, many provided with modern genomic studies. This includes epigenetic regulation of DNA, RNA transcriptomics and regulatory RNA such as microRNA and long non-coding RNA. These findings can for the first time shed light on the genetic mechanisms behind the disease and contribute to improved diagnosis and treatment.

Global research status of localised scleroderma reported over the period 1993-2022: A 30-year bibliometric analysis.

Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.

Navigating into the Dental Management of a Child with Morphea: A Case Report

Morphea, a morphological variant of Localised Scleroderma (LoS) that typically occurs in children, is an inflammatory disease of connective tissue leading to skin and underlying tissue sclerosis due to increased deposition of collagen. The aetiology of morphea is quite elusive. Morphea, along with other regions also affects oral and perioral tissues; the most common affected implication being facial skin and tongue rigidity. The author reports a case of a 10-year-old female who reported to the Department of Paediatric and Preventive Dentistry for retained maxillary anterior deciduous teeth. The patient also presented with scarring on her face, chest, and arms. Her lips were thin, rigid and partially fixed producing microstomia with decreased mouth opening. Clinical examination, blood tests, Contrast-Enhanced Computed Tomography/High-Resolution Computed Tomography (CECT/ HRCT) of thorax, Antinuclear Antibody (ANA) test, Antineutrophilic Cytoplasmic Antibody (ANCA) Test, Anti-dsDNA Test, systemic sclerosis/myositis profile, and histopathological evaluation confirmed the diagnosis of morphea. The management of morphea is multidisciplinary. Hence, the role of a paediatric dental surgeon in recognising the development of disease progression in a patient and avoiding any oral complications is very important.

Morphea caused by COVID-19 infection, first polish case report

Morphea, a localized scleroderma variant, is a rare dermatological condition characterized by fibrosis and thickening of the skin. While its etiology remains unclear, there have been reports of its association with viral infections, including COVID-19. We present a case of morphea in a 26-year-old female patient with a history of two episodes of COVID-19. The patient exhibited cutaneous lesions on her left forearm, bilateral axillae, and groin, accompanied by abdominal wall induration Laboratory investigations revealed no significant abnormalities, except for positive antinuclear antibodies (ANA) with various patterns. This case highlights the potential association between COVID-19 infection and the development of morphea, underscoring the importance of considering this relationship in patients presenting with dermatological manifestations following COVID-19. Further research is needed to elucidate the underlying mechanisms and optimize treatment strategies for such cases. Key words: COVID-19, Morphea, Post-COVID-19 Morphea, Skin diseases

Juvenile localized scleroderma: beyond our eyes can see

Juvenile localized scleroderma: beyond our eyes can see

Synthetic Nucleic Acid Antigens in Localized Scleroderma.

We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene BRAF, showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools.

Localized Scleroderma Causes Peripheral Neuropathies and Persistent Elevated Cerebrospinal Fluid Protein: A Case Report

We present a case of peripheral neuropathies and persistent elevated cerebrospinal fluid protein that is attributed to localized scleroderma. This patient’s has been miss diagnosed for more than 14 years, and the diagnosis of localized scleroderma was finally set up by skin biopsy, providing further evidence for the value of skin biopsy in the clinical practice in peripheral neuropathies.

Clinical characteristics of juvenile systemic sclerosis in Korea: 31-year single-center study.

To evaluate the clinical and laboratory characteristics, therapeutic drugs, and prognosis of juvenile systemic sclerosis (JSSc) at a single center in Korea. This study was a retrospective analysis of patients with JSSc aged <16 years at disease onset and who were treated at our hospital between January 1992 and April 2023. All patients met the Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc, and those with localized scleroderma (morphea) were excluded. Among the 13 patients, proximal skin sclerosis (100%), Raynaud's phenomenon (RP) (84.6%), and sclerodactyly (69.2%) were present at the time of diagnosis. The most common symptom before diagnosis was RP, which was present in 10 patients (76.9%), whereas proximal skin sclerosis was observed in only five patients (38.5%). Thirteen patients had positive anti-nuclear antibody (ANA). At the time of diagnosis, five individuals had findings suggestive of interstitial lung disease (ILD) on a pulmonary function test (PFT) or chest computed tomography (CT), two of whom were asymptomatic. During follow-up, three patients developed ILD, one developed renal dysfunction, one developed heart disease, and none died. This study was the first descriptive analysis of clinical features of JSSc in South Korea. Clinical suspicion is essential for diagnosing JSSc in patients with RP, especially if ANA is positive; however, proximal skin sclerosis, which is crucial for diagnosing JSSc, was unrecognized in the early phase of the disease. PFT should be considered even if a patient is asymptomatic or has normal chest CT.

Clinical features and therapeutic approaches of genital lichen sclerosus in children: results of an observational monocentric study

BackgroundLichen sclerosus is a chronic, progressive, inflammatory skin disease that presents unique challenges, particularly in the pediatric population, where limited data exist regarding its manifestation and optimal management. This retrospective observational monocentric study aims to provide insights into the clinical characteristics and therapeutic strategies employed, in a cohort of children and adolescents with genital lichen sclerosus.MethodsA comprehensive analysis was conducted involving a cohort of 60 pediatric patients ranging from 1 to 15 years old, all diagnosed with lichen sclerosus. These cases were referred to the Pediatric Dermatology Regional Center of the University of Padua, Italy, between January 2018 and January 2022. Moreover, we propose a treatment protocol that showed beneficial outcomes in all of our patients. Specifically, the initial use of mid-potency topical corticosteroids has proven effective in addressing severe acute flares. Following this acute phase, transitioning to long-term treatment with topical calcineurin inhibitors, such as tacrolimus or pimecrolimus, has demonstrated effectiveness in maintaining remission of the disease and also shown efficacy in treating mild cases. The therapeutic effectiveness was assessed by considering various clinical aspects, including erythema, paleness, skin erosions, and specific symptoms such as itching, burning, and pain.ResultsErythema emerged as the predominant clinical sign, reported in 43 (78.3%) patients, followed by paleness, reported in 17 (28.3%) patients. Pruritus was observed in 25 girls (58.1% of females) and 2 boys (11.8% of males), while pain and burning sensations were predominantly reported in female children. Among females, we observed a higher prevalence of cutaneous comorbidities, such as atopic dermatitis, psoriasis, alopecia areata, and linear scleroderma, as opposed to autoimmune systemic diseases, that were more prevalent in males. Regarding therapeutic approaches, 21 (35.0%) patients applied topical corticosteroids, 28 (46,7%) applied topical tacrolimus and 21 (35,0%) applied topical pimecrolimus. All treated patients experienced notable benefits following the initiation of treatment proposed by our protocol.ConclusionsThis study provides further insights into the clinical presentation and management of lichen sclerosus in the pediatric population, shedding light on potential therapeutic pathways for optimizing patient outcomes in this specific demographic. The proposed protocol appears to be a promising strategy, especially when the onset of the disease occurs during childhood.

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma.

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.

The effectiveness of photodynamic therapy using a nanocapsulated oligopeptide of 5-aminolevulinic acid in the complex treatment of the genital lichen sclerosus: A case report

Lichen sclerosus et atropicus is an autoimmune dermatosis belonging to the group of localized scleroderma, most often affecting the skin of the anogenital area. The disease is characterized by slow development with chronization, visualized as areas of atrophy and induration of the affected tissues, causes unbearable itching, pain, dysuria, as well as sexual dysfunction in men and women.&#x0D; The etiology of the disease has not yet been studied. However, genetic predisposition is becoming more likely, given that at least 10% of patients have a family history.&#x0D; Topical corticosteroids are currently the generally accepted method of treating lichen sclerosus. Other treatments include pharmaceuticals (for example, testosterone, progesterone, tacrolimus, 5-fluorouracil and retinoids), surgical excision, cryosurgery, laser therapy and ultraviolet radiation, but none of these treatments is satisfactory and does not lead to stabilization of the skinpathological process.&#x0D; A clinical case of complex effective treatment of genital lichen sclerosus et atrophicus by photodynamic photoporation using 5-aminolevulenic acid in a 19-year-old patient with a severe course of the disease, early manifestation in the neonatal period and a total vulvar skin lesion is presented.

Scleroderma: Difficulties in classification, diagnosis, treatment

Localized scleroderma (LoS) is an autoimmune connective tissue disease with a variety of clinical manifestations. The dermatologist faces the difficulties of establishing a diagnosis and choosing the most appropriate therapy due to the relatively rare prevalence. This review article explores the challenges of classification, diagnosis, and treatment, as well as the factors that contribute to their occurrence. The greatest difficulties in diagnosing LoS that affected the prognosis and progression of the illness are: a delay in diagnosis, including early detection; omission of the active stage of LoS; difficulties in differential diagnosis; lack of association with Lyme borreliosis; low diagnostic value of laboratory and histological tests; limited use of sensitive instrumental methods for diagnosis; and monitoring the activity of LoS in a doctor’s practice. The main difficulties in treatment are the delay in starting treatment; the use of therapy methods with low evidence-based effectiveness; the rare prescription of highly effective approaches; the insufficient effectiveness of systemic drugs and phototherapy; difficulties in determining the volume, timing, and regimen of therapy for each subtype of LoS; the difficulty of achieving a remission; dependence of treatment approach on the doctor’s specialization; the lack of targeted drugs with evidence-based effectiveness in LoS; the lack of high-level evidence-based effectiveness and safety of therapy in LoS; difficulties in the correction of complications of Lo S.

Linear alopecia in pediatrics: RCM and dermoscopy reveal diagnostic cues.

Alopecia areata (AA), trichotillomania (TM), nevus sebaceous (NS), and linear scleroderma en coup de sabre (LSCS) can all present with a patch of linear alopecia, making diagnosis challenging. The purpose of this study was to combine reflectance confocal microscopy (RCM) and dermoscopy in the diagnosis of these lesions in children. A total of 36 patients with linear alopecia were enrolled, of whom 14 had AA, seven had TM, nine had NS, and six had LSCS. We evaluated the characteristics and distinguishing features of the four conditions using RCM and dermoscopy. The key to differential diagnosis was the dermal Hair follicle density in the dermis was decreased in AA, and the size and density of the follicular openings were normal in TM. In NS, the major features were petal-like and frogspawn-like structures. In LSCS, dermal papillary rings, sebaceous glands, and follicles were partially or completely missing, and abundant fibrous material was distributed in the dermis. Dermoscopy revealed alopecia, and all four conditions resulted in decreased hair density. AA patients exhibited yellow dots, black dots, and exclamation mark hairs. TM patients presented with irregularly broken hairs and blood spots. Both NS and LSCS patients exhibited an absence of follicular openings; NS patients demonstrated whitish and yellowish round structures, while an atrophic area with white patches, linear vessels, and no yellow or black dots was observed in LSCS patients CONCLUSION: RCM combined with dermoscopy can provide additional information on disease states and differentiate between AA, TM, NS, and LSCS.

Skin involvement of juvenile scleroderma

Pediatric scleroderma is a rare chronic inflammatory disease in children. It includes two major clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). The two forms have a common mechanism but their clinical manifestations differ. Skin involvement occupies an important place in diagnostic classifications due to the richness of dermatological clinical manifestations and their suggestive aspect of the disease. If the vital prognosis is often not compromised, the functional prognosis is strongly affected, sometimes with deleterious aesthetic problems. Very few pediatric publications have been produced. In this article, we report the different skin manifestations inherent to this disease, and their management in children.

Disabling pansclerotic morphea in an adult Yemeni patient: a case report

Pansclerotic morphea is a highly rare, treatment-resistant, and debilitating variant of localized morphea that affects the entire thickness of the skin and sometimes involves muscles and bone. It manifests as expanding sclerotic plaques that eventually coalesce over the whole trunk or circumferentially extend into the extremities. It is also associated with an increased risk of cutaneous squamous cell carcinoma. Herein, we present the first case of a 30-year-old male patient with typical features of pansclerotic morphea in Yemen. Our patient’s case is unique because it presents a new sign not reported before, namely the boxer-jump sign, besides other previously reported typical signs.