Exploring the relationship between morphea and malignancy: a decade-long single-center study of 204 patients.

The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies in our cohort included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study suggests potential associations between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Further control studies are needed to explore these relationships more definitively.

Histopathologic spectrum of morphea: a single-center retrospective study.

Morphea is a rare autoimmune disease that often affects skin and subcutaneous tissues. The aim of this study was to determine the association between patient demographic parameters, lesion site, clinical subtype of morphea, and histological findings. Between 2016 and 2022, we investigated 78 patients with morphea at the Department of Pathology, Prof. Dr. Cemil Tascioglu City Hospital in Turkey. Case-specific hematoxylin and eosin stain slides were obtained from the pathology archive and assessed blindly by two pathologists. Flattening of rete ridges, location of inflammatory infiltrate, grade of inflammatory infiltrate, presence of plasma cells, presence of eosinophils, homogenization of dermal collagen, decrease of skin appendages, basal pigmentation and melanin incontinence were evaluated. Statistical analyses were performed using SPSS Statistics v.20 (IBM, Armonk, NY, USA). The most common clinical presentation was plaque type (87.5%), while histopathological findings included homogenization of dermal collagen (100%) and decrease of skin appendages (98.7%). Flattening of the rete ridges was observed in 46.2% of patients. Severity of the inflammatory infiltrate was found to be higher in these patients (p=0.028). Basal pigmentation was observed in 59% of patients. Line sign was more common in lower extremity lesions among all localizations (p=0.015). The histopathologic features of morphea are variable and confusing. Particularly, in cases with collagen homogenization, morphea should be considered in differential diagnosis with clinical correlation. In addition, the line sign could be helpful for identifying lesions located in the lower extremities.

Challenges and complications in juvenile localized scleroderma: A practical approach.

Juvenile localized scleroderma is characterised by inflammation which drives fibrosis in skin and soft tissues. The more severe subtypes of localized scleroderma such as linear and craniofacial are more common in children. Additionally, extracutaneous involvement is seen in half of all children and is associated with poorer treatment outcomes and health-related quality of life. Evidence for the management of craniofacial and extracutaneous involvement is lacking and therefore poses a challenge to clinicians. This review aims to provide a practical approach to management of these most challenging features of juvenile localized scleroderma through case studies where we present the available evidence, current recommendations and considerations for management.

Anti-synthetase and myelodysplastic syndromes with deep morphea: an example of shared immunopathogenesis? A case-based review.

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.

Interferon-Gamma-Inducible Protein-10 (IP-10) and Tumor Necrosis Factor-α (TNF-α) as Serological Predictors of Active Disease Status in Localized Scleroderma.

We investigated the ability of a panel of immune-related cytokines and chemokines to predict the disease activity state in localized scleroderma (LS) subjects followed longitudinally. A total of 194 sera samples were obtained from 45 LS subjects with diverse types of LS (40% linear, 20% mixed, 16% craniofacial, 13% generalized, and 11% circumscribed) in our cohort. Cytokines/chemokines that were significantly elevated at the baseline active disease visit compared to the inactive disease state at follow-up were Interferon-Gamma-Inducible Protein (IP)-10 (p < 0.021) and Tumor Necrosis Factor (TNF)-α (p < 0.033). Mixed effect logit modeling identified IP-10 (Odds Ratio (OR) [95% confidence interval] = 2.1 [1.4, 3.2], p < 0.001), TNF-α (OR = 1.8 [1.1, 3.0], p = 0.016), and Monocyte Chemoattractant Protein (MCP)-1 (OR = 2.0 [1.1, 3.9], p = 0.034) as significant predictors of active disease status. These findings support earlier correlations between IP-10 and TNF-α with disease activity parameters in a cross-sectional Luminex™ serological study and may enhance clinical decision-making when disease activity is challenging to assess by clinical examination alone.

Onset of Type I Diabetes Followed by Scleroderma Syndrome in a Child After the COVID-19: A Case Report.

Morphea, is a chronic inflammatory disease of the dermis and subcutaneous tissue. Research has indicated a connection between morphea and Type I Diabetes (T1D). COVID-19 can cause autoimmune diseases like scleroderma, T1D, systemic lupus erythematosus, and others. A 12-year-old girl with type 1 diabetes who was on insulin therapy was brought into the clinic for a metabolic evaluation. The patient had induration, skin hardness, and cutaneous erythema upon inspection. The onset of T1D was following a mild COVID-19 infection. Signs of morphea merged 3 months after the onset of T1D. Known as "long-term COVID," this sickness phase that follows the acute stage of COVID-19 is most likely the result of autoimmune activation. As this patient under evaluation reveals, COVID-19 has been demonstrated in the literature to cause the production of autoantibodies and to either cause or worsen autoimmune disorders in people who have a genetic susceptibility.

Case Report: Exacerbation after fat grafting in patients with active localized scleroderma.

Background: The application of autologous fat transplantation in facial lesions of patients with localized scleroderma (LoS) has been reported in recent years. Objective: The authors report a case of worsening of active localized scleroderma after autologous fat transplantation. Methods: A man presented with neck and facial skin atrophy and pigmentation with a history of LoS. Appearing 1.5 years ago, the lesion had progressively grown in size and shape. Consent was obtained after the patient was informed of the possible surgical risks during the active phase of the disease. He underwent autologous fat grafting into the right cheek with about 30 ml Coleman fat graft. Results: Skin dyspigmentation and atrophy progressively deteriorated 1 month into therapy, with slightly increased erythema and enlargement of the lesion. Six months after the therapy, the localized scleroderma-related score worsened. Limitations: There are different factors, such as that systemic medications could affect the treatment of localized scleroderma by autologous fat transplantation. Meanwhile, considering the limitation of the 6-month follow-up period, obtaining long-term follow-up data is necessary to evaluate sustained outcomes and potential complications. Conclusion: More clinical research is needed to determine the time interval between disease inactivity and the application of any surgical procedures to avoid reactivation.

Spatial Transcriptomics Identifies Cellular and Molecular Characteristics of Scleroderma Skin Lesions: Pilot Study in Juvenile Scleroderma.

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.

Magnetic Resonance Imaging in the Assessment and Management of Post-injection-Site Morphea.

Morphea, a form of localized scleroderma, can significantly affect individuals by causing skin tightening and discoloration. We describe the case of a 22-year-old woman who presented with progressive skin changes and discomfort in her right gluteal region following a history of an intramuscular injection in the right gluteal region. Clinical examination suggested morphea, prompting us to conduct an MRI to better understand the extent and nature of her condition. The MRI results revealed thickening of the skin layers and signs of inflammation, helping us differentiate between active inflammation and fibrosis. This case illustrates how MRI can provide crucial insights for managing morphea effectively.

Advances in the Management of Localized Scleroderma: A Systematic Review of Laser Therapy and Injectable Filler Approaches.

Localized scleroderma (LS), commonly known as morphea, presents a significant clinical challenge due to its chronic, inflammatory nature affecting the skin and potentially underlying tissues. This systematic review explores the innovative approach of combining laser therapy and injectable fillers, specifically hyaluronic acid, for the treatment of LS. We conducted a comprehensive literature review following PRISMA guidelines, examining articles from MEDLINE/PubMed to assess the combined efficacy of these treatments in improving both esthetic and functional outcomes for LS patients. The search yielded 64 articles, with six selected for in-depth analysis for a total of nine patients, covering a range of patient demographics and treatment types. Our review highlights cases where fractional CO2 laser therapy promoted long-term tissue remodeling and instances where hyaluronic acid fillers effectively addressed skin atrophy and volume loss, enhancing both immediate and long-lasting esthetic improvements. The synergy between these treatments suggests a promising dual approach, aiming to maximize esthetic outcomes and to improve the quality of life for LS patients. This review underscores the necessity of further research to establish a comprehensive, evidence-based clinical pathway integrating both treatments for managing LS, thereby enhancing patient satisfaction and addressing the multifaceted nature of this challenging dermatological condition.

Corrigendum: Scleroderma and Scleroderma-like syndromes.

[This corrects the article DOI: 10.3389/fimmu.2024.1351675.].

Linear morphea distributed along radial nerve with high incidence of neuromusculoskeletal disorders: A single-center case series.

Linear morphea is the most disabling subtype of morphea, which may cause a series of excutaneous manifestations and sequelae. To futher explore the clinical characteristics of linear morphea, we conducted a retrospective study of 22 patients diagnosed with linear morphea in our department during the past 2 years. Their baseline clinical information, skin manifestations, complications and therapeutic effect were analyzed. Here, we report six cases of a special linear morphea, usually occurring on the unilateral upper limbs of young women, spreading along the distribution of the radial nerve and frequently progressing across the joint, which increases the incidence of neuromusculoskeletal disorders. Instead of traditional topical drugs, a combination of systemic prednisone and methotrexate improved their skin lesions and complications. Recognition of this special type of linear morphea enables earlier diagnosis and active treatment plan, which contributes to ameliorate the symptoms and avoid functional sequelae.

Endpoints and outcomes for localized scleroderma/morphea: a scoping literature review.

BACKGROUND: Current treatment for localized scleroderma (LS) has been shown to halt disease activity, but little is still known about patient experiences with these treatments, nor is there consensus about optimal measurement strategies for future clinical trials. OBJECTIVE: Conduct a scoping review of the literature for the types of outcomes and measures (i.e. clinician-, patient-, and caregiver-reported) utilized in published treatment studies of LS. METHODS: Online databases were searched for articles related to the evaluation of treatment efficacy in LS with a special focus on pediatrics. RESULTS: Of the 168 studies, the most common outcomes used were cutaneous disease activity and damage measured via clinician-reported assessments. The most frequently cited measure was the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). Few patient-reported outcome measures (PROMs) were used. LIMITATIONS: Some studies only vaguely reported the measures utilized, and the review yielded a low number of clinical trials. CONCLUSION: In addition to evaluating disease activity with clinician-reported measures, the field could obtain critical knowledge on the patient experience by including high-quality PROMs of symptoms and functioning. More clinical trials using a variety of outcomes and measures are necessary to determine the most suitable course of treatment for LS patients.

A Rare Case of Bullous Morphea Associated with Autoimmune Hepatitis.

(1) Background: Bullous morphea is an extremely rare form of localized scleroderma, a condition that is marked by the presence of sporadic and intermittent blisters on sclerodermatous skin. This condition stands out due to its rarity and the unique manifestation of blistering, which sets it apart from other forms of localized scleroderma. Due to the infrequent presentation of bullous morphea, there is a significant gap in our understanding of its pathogenesis. The exact mechanisms that lead to the development of this condition remain largely unknown, which poses a challenge for medical professionals in terms of both diagnosis and treatment. The limited number of reported cases makes it difficult to establish a standardized approach to managing this condition, and as a result, treatment options are often limited and may vary from one patient to another. (2) Methods: In this case report, we present a rare case of bullous morphea that manifested before the onset of autoimmune hepatitis. When morphea presents unusually or is resistant to traditional immunosuppressive treatment, a comprehensive assessment of possible concurrent autoimmune illnesses provoking the rash must be conducted. (3) Results: We report a successful case of bullous morphea treated with systemic corticosteroids following a diagnosis of autoimmune hepatitis. (4) Conclusions: This case highlights the importance of considering overlapping autoimmune conditions in the management of bullous morphea and the potential efficacy of systemic corticosteroids in such scenarios. Collaborative efforts involving dermatologists, rheumatologists, and hepatologists are essential to enhance understanding and optimize treatment outcomes for patients affected by this rare and complex condition. Thus, further research is necessary to gain a deeper understanding of the pathogenesis of bullous morphea and to develop more effective and targeted treatment options for patients affected by this condition.

Seizure in Morphea: A Case Report of Parry-Romberg Syndrome.

Parry-Romberg syndrome is a rare neurocutaneous disease characterized by progressive hemifacial atrophy. We present the case of a 14-year-old, a known case of linear morphea, who presented with seizure and on evaluation was diagnosed with Parry-Romberg syndrome. It causes a profound impact on aesthetic well-being and has a significant psychosocial morbidity. This case report aims to highlight the effective multidisciplinary team approach involving a rheumatologist, dermatologist, neurologist, and ophthalmologist which ultimately culminated in the meticulous management of the disease in our patient.

Acral Folliculocentric Extragenital Lichen Sclerosus: A Case Report.

Introduction: Lichen sclerosus is a chronic inflammatory dermatological condition of unknown etiology, primarily impacting the genital epidermis in individuals of all genders, with a higher prevalence observed among postmenopausal women and prepubescent girls. Additionally, extragenital manifestations occur in approximately 20% of the patients diagnosed with genital lichen sclerosus. Notably, folliculocentric extragenital lichen sclerosus is rare and unusual, with only limited instances documented in existing literature. Case Description: We report a 33 years old lady presented with multiple asymptomatic lesions on the dorsal feet for 1 year and similar lesions on the left hand for 4 months. On examination: folliculocentric, shiny, atrophic papules coalescing into reticulated plaques over the dorsum of both feet and few shiny, flat-topped, pink papules over the dorsum of the left hand. A skin biopsy was performed and confirmed the diagnosis of extragenital lichen sclerosus. Conclusion: Acral folliculocentric extragenital lichen sclerosus is an unusual and rare clinical variant. Clinicopathologic correlation is necessary to establish the correct diagnosis. Contribution to the Literature: Herein, we present an unusual presentation of extragenital lichen sclerosus, and we highlight the importance of considering it in the differential diagnosis of guttate acral skin lesions. We also review and summarize relevant cases from the literature in hope to aid physicians, especially dermatologists, to consider and swiftly reach the diagnosis and offer appropriate management. We also hope to bring about new insights and broaden future research efforts regarding lichen sclerosus especially and atrophic skin disease in general.

Ultrasound Utility in the Management of Morphea: A Comprehensive Review.

Introduction: Morphea, an autoimmune progressive disorder, can significantly impact patient well-being, yet therapeutic options, though expanding, exhibit limited efficacy. A persistent challenge in disease management revolves around monitoring disease activity and gauging treatment effectiveness. To address this, various clinical assessment tools have been devised, each with its inherent limitations. The realm of imaging in morphea has undergone noteworthy expansion, with ultrasonography (US) emerging as an efficacious and cost-effective avenue for quantifying disease activity and evaluating therapeutic outcomes. However, the evidential support for its application remains equivocal. Our aim was to explore and analyze the existing evidence concerning the utility of ultrasound in the management of morphea. Materials and Methods: We conducted a comprehensive literature review using PubMed Medline to assess evidence concerning US utility in morphea management. Results: Sixteen total studies were included in our review. Discussion: Although the studies presented carry their own limitations, cumulative findings indicate the potential of ultrasound, particularly when coupled with Doppler, in facilitating staging, assessing disease activity, and longitudinal assessment of therapeutic efficacy in patients with morphea.

Scleroderma and scleroderma-like syndromes.

Systemic sclerosis is a systemic connective tissue disease whose main pathophysiological mechanism is a progressive fibrosis of internal organs and skin leading to thickening and induration. Blood vessels may also be involved. However, systemic scleroderma is not the only disease causing cutaneous sclerosis. There is a group of diseases that mimic scleroderma in their clinical presentation - these are scleroderma-like syndromes. A distinction can be made between syndromes of inflammatory/autoimmune, genetic, metabolic, toxic, drug-induced, occupational, paraneoplastic and syndromes caused by deposition disorders. In the following paper, we have reviewed the literature on scleroderma-like syndromes. We have outlined the factors predisposing to the development of each disease, its pathogenesis, clinical presentation, diagnostic and treatment process and the differences between each syndrome and systemic scleroderma.