Advancements in adipose-derived stem cell therapy for skin fibrosis.

Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.

Morfea en edad pediátrica / Morphea in childhood

La morfea es una rara enfermedad fibrosante de piel y tejidos subyacentes que aparece a cualquier edad, con más frecuencia en mujeres. Es de etiología autoinmune, benigna, con remisión espontánea o recidivante crónica; y se caracteriza por la aparición de áreas de piel esclerosadas, únicas o múltiples, redondeadas o lineales, asintomáticas, de evolución crónica y sin afección sistémica. Se presentó un paciente en edad pediátrica con esta enfermedad, cuya clínica, examen diagnóstico e histología fueron compatibles con la enfermedad de morfea lineal que, a pesar del retraso en su diagnóstico una vez iniciado el tratamiento inmunosupresor presentó una evolución favorable, simultáneamente se le realizó fisioterapia.

Morphea is a rare fibrosing disease of the skin and underlying tissues which is more common in women and can appear at any age. It is an autoimmune and benign disease with spontaneous remission or chronic relapsing course; it is characterized by the appearance of single or multiple, rounded or linear, asymptomatic, chronically evolving sclerosed skin areas without systemic involvement. We present a female pediatric patient with this disease, whose symptoms, diagnostic examination and histology were compatible with linear morphea that, despite the delay in its diagnosis, she had a favorable evolution once immunosuppressive treatment was started, and physiotherapy was simultaneously performed.

Reconstrução de hemiatrofia facial com hidroxiapatita de cálcio: relato de uma técnica segura e minimamente invasiva / Reconstruction of facial hemiatrophy using calcium hydroxylapatite filler: report of a safe and minimally invasive technique

Introdução: a hemiatrofia facial progressiva, também conhecida como síndrome de Parry Romberg, é uma forma rara de esclerodermia, cujo manejo de sequelas é desafiador. Objetivo: diante desse desafio, o objetivo deste estudo foi avaliar pela primeira vez na literatura a eficácia do preenchimento da hidroxiapatita de cálcio (CaHa) na reconstrução da mandíbula de um paciente com síndrome de Parry Romberg. Relato do caso: paciente do sexo feminino, 15 anos, com atrofia progressiva do lado direito da face por síndrome de Parry Romberg. Após o controle da doença, a principal queixa da paciente era assimetria facial, principalmente na região mandibular. Discussão: a CaHa é um preenchedor injetável biocompatível, que é gradualmente reabsorvido e substituído por estroma fibrovascular, formado principalmente por novo colágeno, em um processo que ocorre sem qualquer reação imunológica. Este perfil de segurança torna a CaHa uma boa escolha para a correção de sequelas de esclerodermia estável. Conclusão: este relato permite concluir que a biocompatibilidade do preenchimento de CaHa e a adequação para correção da mandíbula também são aplicáveis em procedimentos reconstrutivos para esclerodermia estável, de forma segura e minimamente invasiva, com ótimos resultados estéticos. O procedimento deve ser programado caso a caso, e um acompanhamento regular também é recomendado.

Introduction: Progressive Facial Hemiatrophy, also known as Parry Romberg Syndrome, is a rare form of linear scleroderma. The management of facial atrophy sequelae is challenging. Objective: This study aims to evaluate for the first time in literature the effectiveness of the calcium hydroxylapatite (CaHa) filler in the jawline reshaping of a patient with Parry Romberg Syndrome. Case report: A 15-year-old woman with progressive atrophy of the right side of the face due to Parry Romberg Syndrome. After disease control, the patient's main complaint was facial asymmetry, mainly in the jawline region. Discussion: CaHa is a biocompatible injectable filler that is gradually resorbed and replaced by fibrovascular stroma, mainly formed for new collagen, in a process that occurs without any immunological reaction. This safety profile makes CaHa a good choice for correcting stable scleroderma defects. Conclusion: This report concludes that CaHa filler biocompatibility and suitability for the jawline correction are also applicable in reconstructive procedures for stable scleroderma, safely and minimally invasively, with optimal aesthetic results. The method must be programmed case-by-case, and a regular follow-up is also recommended.

Clinical features and classification of 180 patients with morphea / 中华皮肤科杂志

Objective:To determine classification and clinical features of morphea.Methods:A retrospective analysis was conducted on epidemiological information about clinical manifestations of and laboratory data from 180 patients with morphea, who visited Zhongshan Hospital, Fudan University from January 2010 to July 2021. Two-independent-sample t test was used to compare the age at onset between genders, and chi-square test to analyze differences in clinical characteristics between different genders and subtypes. Results:Among the 180 patients, 123 were females and 57 were males, with a male-to-female ratio of 1∶2.16. The age at onset of morphea was 28.69 ± 17.97 years for female patients, and 29.90 ± 20.67 years for male patients. Among them, linear morphea was the most common type in this study (68 cases, 37.78%), followed by plaque morphea (63 cases, 35.00%), mixed morphea (28 cases, 15.56%) and deep morphea (21 cases, 11.67%). The disease occurred in all age groups, but the age at onset significantly varied among different clinical subtypes ( F = 5.95, P < 0.001). No significant difference was observed in the age at onset or proportion of clinical subtypes between genders ( F = 0.15, P = 0.696; χ2 =2.88, P = 0.410). Atrophoderma of Pasini and Pierini (APP) was very common (62 cases, 34.44%) in the 180 patients, which mainly manifested as plaques or linear lesions, and 26 out of 45 patients with plaque APP and 11 out of 17 with linear APP were both accompanied by other subtypes of morphea. Among the 75 patients tested for autoantibody profiles, 34 (45.33%) presented with positive results. More diverse types of autoantibodies were found in female patients compared with male patients, and antinuclear antibodies, anti-SSA and anti-SSB antibodies were the most common types. There were various types of comorbidities in female patients, but lichen sclerosus et atrophicus and vitiligo were the most common comorbidities in both genders. Conclusion:High incidence and frequent co-occurrence with other subtypes of APP may be the characteristics of Chinese patients with morphea, and it is recommended to classify morphea into plaque, linear, deep and mixed subtypes.

Taxane-induced scleroderma: report of two cases / Esclerodermia inducida por taxanos: informe de dos casos

ABSTRACT Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia and onycholysis. Taxane-induced scleroderma is rare. Few cases with skin findings resembling systemic sclerosis, have been reported after the administration of these agents. We report two cases with stage IV breast cancer, aged 66 and 71 years, who developed sclerodermic skin lesions in their extremities after starting treatment with placlitaxel and nabplaclitaxel respectively.

Los taxanos son agentes quimioterapéuticos cuyo uso se asocia a problemas dermatológicos tales como hiperpigmentación, síndrome manos-pies, paroniquia y onicolisis. La esclerodermia inducida por taxanos es rara, con pocos casos informados en la literatura. Informamos los casos de dos pacientes con cáncer de mama en estado IV, de 66 y 71 años, que desarrollaron lesiones esclerodérmicas en las extremidades después de ser tratadas con placlitaxel y nabplaclitaxel, respectivamente.

A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis, but a good prognosis,

Abstract Intravascular large B-cell lymphoma is a rare, non-mass-forming, extranodal large B-cell lymphoma subtype characterized by the presence of tumor cells in the lumens of vessels. It is divided into two major types: classical and Asian. Patients presenting only with skin involvement are mostly female, at a younger age than classical intravascular large B-cell lymphoma patients, and have a better prognosis. Since the diagnosis of cases with isolated skin involvement is difficult, keeping this entity in mind, performing a careful microscopic examination, and applying new, effective treatment regimens will make it possible to achieve better clinical outcomes in these cases.

A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis, but a good prognosis.

Intravascular large B-cell lymphoma is a rare, non-mass-forming, extranodal large B-cell lymphoma subtype characterized by the presence of tumor cells in the lumens of vessels. It is divided into two major types: classical and Asian. Patients presenting only with skin involvement are mostly female, at a younger age than classical intravascular large B-cell lymphoma patients, and have a better prognosis. Since the diagnosis of cases with isolated skin involvement is difficult, keeping this entity in mind, performing a careful microscopic examination, and applying new, effective treatment regimens will make it possible to achieve better clinical outcomes in these cases.

Treatment in Juvenile Scleroderma.

PURPOSE OF REVIEW: Treatment of scleroderma in children is challenging since little is known about its pathogenesis. Herein, we review the most recent evidence regarding the treatment of juvenile scleroderma. RECENT FINDINGS: According to the recent recommendations for Pediatric Rheumatology in Europe (SHARE), systemic treatment in localized scleroderma is needed when there is a risk for disability, such as in generalized or pansclerotic morphea and progressive linear scleroderma. In juvenile systemic sclerosis, the introduction of the severity score, J4S, has standardized the assessment of the patients in the daily practice and allowed a more tailored therapeutic approach. Since, to date, no clinical trial is available in JSSc, due to its rarity, the treatment is based on adults' experience. The recent recommendations for juvenile scleroderma represent an important instrument to standardize the treatment approach, confirm the role of methotrexate, and open new windows for effective experimental treatments, such as mycophenolate mofetil and biological agents, for severe or refractory cases.

Endothelial lesion and complement activation in patients with Scleroderma Renal Crisis / Lesão endotelial e ativação do complemento em pacientes com crise renal esclerodérmica

Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

Resumo Nas revisões de biópsias renais, a crise renal esclerodérmica (CRE) é caracterizada por lesões endoteliais vasculares, depósitos de C4d em vasos peritubulares e lesões agudas e crônicas que coexistem na mesma biópsia. Os sinais clínicos de microangiopatia trombótica (MAT) são descritos na esclerose sistêmica (ES); no entanto, não foram relacionados às lesões agudas descritas nas biópsias renais. Relatamos um caso de CRE em um paciente com síndrome de superposição de esclerodermia-dermatomiosite, que também apresentou dados clínicos e histopatológicos de MAT. No exame de fundo do olho, foi encontrada uma retinopatia hipertensiva aguda grave. A biópsia renal mostrou lesão endotelial grave com alargamento das células mucoides ao nível da íntima, proliferação concêntrica focal na maioria das pequenas arteríolas e depósitos de C3, C4d e IgM ao longo das paredes dos capilares. O estudo genético do complemento mostrou apenas a presença de haplótipos de risco da proteína cofator de membrana (PCM), sem outros distúrbios genéticos do complemento. Entendemos que em um paciente com MAT e ES, o dano renal seria fundamentalmente endotelial e do tipo agudo; além disso, observaríamos evidências claras de ativação do complemento. Uma vez que novos estudos correlacionam dados clínico-analíticos com estudos anatomopatológicos, é provável que sejamos forçados a redefinir o conceito de CRE, enfocando a relação entre dano endotelial agudo e ativação do complemento.

[The skin and rheumatism]. / Haut und Rheuma.

The skin is commonly affected in chronic inflammatory disorders and may act as a visual marker for internal or systemic inflammation. Frequent inflammatory skin diseases, like psoriasis and atopic dermatitis (AD), are associated with rheumatic and inflammatory bowel diseases. Metabolic, mental and cardiovascular comorbidity are frequent consequences of chronic inflammation. Further intersections between skin and joints are connective tissue diseases (collagenoses) and can be observed in complex diseases, e.g. systemic lupus erythematosus. Clinically, these diseases range from predominant cutaneous to severe systemic implication of several organs. Localized scleroderma should be clinically distinguished from systemic sclerosis and treated sufficiently to avoid long-term damage and disability. Thus, interdisciplinary disease management is of crucial importance.

Combined high-frequency and Doppler ultrasound in early diagnosis of atrophoderma of Pasini and Pierini

Abstract: Atrophoderma of Pasini and Pierini is a skin disorder affecting dermal collagen and is clinically characterized by well-defined plaques of depressed skin. Histopathological changes are subtle, and in most cases, the diagnosis requires a comparative study with healthy skin from the same anatomical site. High frequency ultrasound is a useful imaging method for diagnosis of atrophic skin changes. A case is presented in which ultrasound can support the clinical and the histopathological diagnosis of atrophoderma of Pasini and Pierini.

Case for diagnosis. Sclerodermiform manifestations of porphyria cutanea tarda secondary to hepatitis C

Abstract: A 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.

Coexistence of morphea and granuloma annulare: a rare case report

ABSTRACT CONTEXT: Localized scleroderma (morphea) is characterized by fibrosis of skin and subcutaneous tissue. Granuloma annulare is a relatively common disease that is characterized by dermal papules and arciform plaques. CASE REPORT: Here, we present the case of a 42-year-old woman who developed granuloma annulare on the dorsum of her feet and abdominal region, and morphea on the anterior side of her lower limbs. We also discuss the etiological and pathogenetic processes that may cause the rare coexistence of these two diseases. CONCLUSION: Only a few cases in the literature have described coexistence of morphea and granuloma annulare.

Radiation-induced morphea-a rare but severe late effect of adjuvant breast irradiation : Case report and review of the literature.

BACKGROUND: Radiation-induced morphea (RIM) is a circumscribed localized scleroderma that occurs most often in the breast. After an asymptomatic period of one month to several years, the symptoms (circumscribed inflammation, edema, sclerosis) often arise suddenly and cannot be clinically distinguished from a local recurrence in the form of inflammatory carcinoma. CASE: We present a case of a 74-year-old woman who developed this rare and serious local side-effect in connective tissue following neoadjuvant CDK 4/6 inhibitor abemaciclib (Verzenio®) and aromatase inhibitor anastrozole (Arimidex®) therapy and subsequent radiation therapy of the breast. CONCLUSIONS: Little is known about risk factors and pathogenesis of RIM. Here we describe the first case of RIM following immunotherapy. The diagnosis is based on clinical appearance and histopathological examination. Treatment should be initiated in the inflammatory stage in order to prevent or delay irreversible fibrosis and atrophy of the breast.

Clinicopathological analysis of six cases of disabling pansclerotic morphea / 中华皮肤科杂志

Objective To investigate clinical and pathological features of 6 cases of disabling pansclerotic morphea (DPM).Methods Clinical and pathological manifestations of and follow-up results in 6 patients,who were clinically and histopathologically diagnosed with DPM in the Department of Pathology,Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College from 2007 to 2017,were retrospectively analyzed.Results Among the 6 patients,4 were male and 2 were female.The age of onset ranged from 3 to 10 years,with an average age of 6.5 years.The average duration from the occurrence to the confirmation of the diagnosis was 6.2 years (range,2-10 years).At all the lesional sites,skin atrophy,thining and tightness occurred,and the limbs became thin.Additionally,there were muscular atrophy and visible deep thick veins on the surface of the limbs.The contracture,deformity and dysfunction of the adjacent joints occurred in 4 cases,and the lower limbs were obviously shortened in 2 cases.Peripheral blood examination showed no increase of eosinophils or hypergammaglobulinemia.Imaging examination revealed smooth cortical bone and clear trabecular bone,and no osseous abnormality was observed.Histopathological examination of contracted skin lesions of the lower limbs revealed atrophic and thinned epidermis,hyperpigmentation in the basal layer,hyperplastic,thickened,hardened and partly homogenized collagen fibers in the middle to deep dermis,subcutaneous adipose tissue region and deep tissue of the skin.Conclusions DPM usually does not affect viscera,but often involves deep tissue of the limbs.Histopathologically,DPM is mainly characterized by obviously hyperplastic and hardened collagen fibers in the dermis and subcutaneous tissue.

Evaluation of mean platelet volume in localized scleroderma

Abstract: Background: Localized scleroderma is a chronic inflammatory skin disease characterized by sclerosis of the dermis and subcutaneous tissue. Platelets play an important role in inflammation. Following activation, platelets rapidly release numerous mediators and cytokines, which contribute to inflammation. Objectives: To evaluate whether there was any relation between localized scleroderma and platelet parameters. Methods: Forty-one patients with localized scleroderma were enrolled in the study. The control group consisted of 30 healthy subjects. Results: The mean platelet volume level in the patient group was 9.9 ± 1.3 fl and in the control group was 7.6 ± 1.1 fl. This difference was statistically significant (p< 0.001). The plateletcrit values are minimally higher in the patient group as compared to the control group. It was statistically significant (p<0.001). There was no significant difference in the platelet counts between the two groups (p= 0.560) In the patient group, there was no significant relation between the mean platelet volume levels and clinical signs of disease (p=0.09). However, plateletcrit values are higher in generalized than localized forms of disease (p=0.01). Study Limitations: The limited number of patients and the retrospective nature of the study were our limitations. Conclusions: This study suggests that platelets might play a role in the pathogenesis of scleroderma. Platelet parameters may be used as markers for evaluating disease severity and inflammatory processes. Thus, there is a need for more detailed and prospective studies.

Morfea mamaria. Presentación de un caso / Breast Morphea. Case Presentation

La esclerodermia localizada es la forma localizada cutánea de esclerodermia, caracterizada por una fibrosis que se manifiesta en forma de placas o bandas cutáneas escleróticas infiltradas al tacto. La prevalencia se estima en aproximadamente 1-9/100.000, por tal razón se presenta el caso de una paciente con manifestaciones de una esclerodermia cutánea localizada cuya lesión apareció en una mama dos meses antes de asistir a consulta en su área de salud. La principal lesión que presentaba era una placa áspera, que no se dejaba pellizcar, de color carmelita, bordes irregulares, de aproximadamente seis centímetros de diámetro, localizada en mitad inferior de la mama derecha, incluyendo pezón y areola. Se detectaron las alteraciones histológicas propias de la enfermedad de base lo que corroboró el diagnóstico planteado y se descartó mediante otros exámenes cualquier presencia de proceso maligno.

Located scleroderma in the located for of cutaneous scleroderma, characterized by a fibrosis which shows in plaque form of cutaneous sclerotic bands infiltrated to touch. The prevalence is estimated in approximately 1-9/100.000, this is the reason why a case of a patient is presented with signs of a located cutaneous scleroderma. The lesion presented in a breast two months before visiting the doctor in her area. The main lesion was a tough plaque, which was not possible to pinch, brown colored, irregular edges, of approximately six centimeters, located in the mid-inferior right breast, including the nipple and areola. Histological changes which characterize the base disease were found, which corroborated the diagnosis and any malignant process was ruled out by other performed exams.

Consideraciones bucales en el tratamiento de pacientes con esclerodermia: reporte de dos casos / Bucal considerations in the treatment of patients with scleroderma: Report of two cases

La esclerodermia pertenece a un grupo de enfermedades autoinmunes del tejido conectivo, que produce: inflamación, disfunción vascular y fibrosis excesiva del tejido conectivo de soporte de la piel y los órganos viscerales. A nivel bucal se evidencian afecciones como xerostomía, microstomía, caries y enfermedad periodontal. El tratamiento odontológico requiere un manejo integral por parte de los profesionales, que comprenda las patologías orales presentes y los síntomas permanentes característicos de la enfermedad sistémica de base. El objetivo de este artículo es presentar dos casos de esclerodermia resaltando sus manifestaciones orales presentes.

Scleroderma belongs to a group of autoimmune connective tissue diseases that causes inflammation, vascular dysfunction and excessive fibrosis of the connective tissue supporting the skin and visceral organs. A level oral conditions such as xerostomia, microstomia, caries and periodontal disease are evident. Dental treatment requires a comprehensive management by professionals who understand oral pathologies and permanent characteristic symptoms of systemic disease. The aim of this paper is to present two cases of scleroderma highlighting present oral manifestations.

Do you know this syndrome? Werner syndrome

Abstract: Werner syndrome is a rare autosomal recessive disorder, caused by mutations in the WRN gene. Clinical findings include: senile appearance, short stature, grey hair, alopecia, bird-like face, scleroderma-like skin changes, skin ulcers, voice abnormalities, cataracts, osteoporosis, type 2 diabetes mellitus, ischemic heart disease and hypogonadism. The syndrome begins to become apparent in adolescence but it is usually diagnosed in the third or fourth decade of life. Since the patients usually die by the age of 40-50 years related to malignant neoplasms or atherosclerotic complications, they should be closely followed and treated for complications

A case of systemic sclerosis sine scleroderma and a literature review / 中华风湿病学杂志

Objective Systemic sclerosis sine scleroderma (ssSSc) is a rare type of systemic sclerosis,comparison between ssSSc and other types of systemic sclerosis (SSc),ssSSc is carried out in this study.Methods We reported a patient with Raynand's phenomenon,esophagus,intestine and lung involvement,positive ANA,anti-Scl-70 antibody,but had no skin sclerosis.Results For visceral involvement,ssSSc was not different from limited cutaneous systemic sclerosis (lcSSc),The incidence of pulmonary hypertension was higher in patients with ssSSc,lower with calcinosis,finger ulcer and acral dissolution,and the incidence of ssSSc and lcSSc interstitial lung disease was higher than that of diffuse cutaneous systemic sclerosis,(dcSSc).Conclusion Although ssSSc do not have skin sclerosis,however,visceral involvement is more extensive.Early diagnosis and treatmeat is extremely important.