Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea: A Nonrandomized Controlled Trial.

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

Management Options for Linear Scleroderma ("En Coup de Sabre").

BACKGROUND: En coup de sabre (ECDS) is a form of linear-scleroderma, primarily affecting the face. Despite effectiveness of pharmacological interventions in the management of lesions, sequelae of cutaneous deformities are common. OBJECTIVE: Review the existing surgical tools for the correction of "en coup de sabre" ECDS lesions and facial deformities. MATERIALS AND METHODS: The authors conducted a literature search for reports on surgical interventions for ECDS deformations, in the electronic databases of PubMed, Scopus, and Cochrane Library Databases. RESULTS: Twenty-six publications reporting 39 patients were found in the literature. The average age of patients was 25 ± 4.7 years. Thirty-one of the patients were females. Six methods were found in the literature for surgical correction of ECDS. Fat grafting was performed in 41% of patients, surgical reconstruction in 18%, injectable fillers in 15%, implants in 10%, botulinum toxin injections in 8%, and bone/cartilage grafts in 8%. Imaging studies of the skull and face were performed in 36% of patients. Bony defects were found in 64.3% of them. CONCLUSION: Different surgical and minimally invasive options exist in the armamentarium of clinicians correcting ECDS deformities. Tailoring the method of correction to patient's needs and expectation is crucial in ensuring patient satisfaction.

Fractional Ablative Carbon Dioxide Lasers for the Treatment of Morphea: A Case Series and Literature Review.

Morphea is an inflammatory, immune-mediated disease of unknown aetiology. It is characterised by excessive collagen deposition, which leads to the hardening of the dermis and subcutaneous tissues. The disease is associated with cosmetic and functional impairment, which can affect the patients' quality of life. Fractional ablative lasers (FALs) are currently used for the treatment of many skin diseases that are connected to tissue fibrosis due to the low risk of side effects and their great effectiveness. This study aimed to improve the aesthetic defects that are caused by morphea lesions and assess the efficacy and safety of FAL use in this indication. We also reviewed the literature on the subject. We present four women with biopsy-proven morphea, manifesting as hyperpigmented plaques and patches. One of the patients additionally had morphea-related knee joint contracture. Four fractional CO2 laser sessions, separated by one-month intervals, were performed and produced significant improvements in dyspigmentation and induration. An improved elasticity and a decrease in dermal thickness were also obtained, as proven by measurements using DermaLab Combo. No severe adverse effects occurred. Based on these cases presented by the authors, fractional CO2 lasers appear to be an effective, well-tolerated, and safe therapeutic option for patients suffering from morphea.

Combination of Autologous Fat Grafting and Negative-Pressure Wound Therapy for the Treatment of Scalp Linear Scleroderma.

ABSTRACT: Scalp linear scleroderma (LSc) is a subtype of localized scleroderma which typically affects young patients and which can be severely disfiguring. Traditional treatment options include bone grafting or tissue expansion. in this report, we present the case of a patient with scalp LSc successfully treated with scar release, autologous fat grafting, and negative-pressure wound therapy (NPWT). A 55-year-old female, with a history of craniectomy for a benign sellar tumor 10 years previously, developed LSc over the frontal scalp with exposure of titanium plates and screws. She was treated with removal of metalwork, scar release, autologous fat grafting from the abdominal wall and immediate application of NPWT. At 3-month postoperative follow-up, the appearance of the depressed lesion and of its margins had significantly improved. Our experience suggests that the combination of autologous fat grafting and NPWT is an effective treatment modality for scalp LSc.

Flap Reconstruction for Treatment of Pediatric Linear Scleroderma.

BACKGROUND: Linear scleroderma is a rare connective tissue disease characterized by thickening of the skin due to excess collagen deposit. It is the most frequent type of localized scleroderma in the pediatric population (40%-70%), and it usually affects the extremities and head. Linear scleroderma can cause growth disturbances, extremity length discrepancy, and debilitating joint contractures. The aim of this study was to describe the surgical outcomes of microsurgical flap reconstruction of linear scleroderma in the pediatric population. METHODS: A retrospective review of all children with linear scleroderma was performed at our institution. Patients less than 18 years of age with clinical diagnosis of linear scleroderma and who underwent microsurgical flap reconstruction for correction of their scleroderma were included. Fat grafting procedures were excluded. Patient demographics and surgical outcomes were collected. RESULTS: A total 7 patients underwent microsurgical flap reconstruction for treatment of their linear scleroderma producing debilitating soft tissue contractures and preventing ambulation or elbow extension. Six patients had scleroderma involving the lower extremity and 1 involving the upper extremity. Three anterolateral thigh and 4 latissimus dorsi flaps were performed. The median age at surgery was 7 years (Q1-Q3, 5-11), and the median body mass index was 21.3 kg/m2 (Q1-Q3, 16.5-22.1). The median follow-up was 121.1 months (Q1-Q3, 43.2-187.4). All flaps survived, and no donor site complications were reported. Perioperative complications included wound infection that required debridement (n = 1), immediate postoperative bleeding requiring surgical intervention (n = 1), intraoperative venous congestion (n = 1), and scleroderma recurrence outside the flap (n = 2). When comparing anterolateral thigh and latissimus dorsi flaps, there was no statistically significant difference in the development of surgical complications, number of surgical revisions per patient [median, 4 (Q1-Q3, 4-7) vs 2.5 (Q1-Q3, 1.3, 3), P = 0.0916], or unplanned surgical interventions [median, 0 (Q1-Q3, 0-1) vs 1 (Q1-Q3, 0-1), P = 0.7228]. The reconstruction was successful in improving range of motion in 6 patients, 5 of which reached full weight-bearing. However, all patients had residual limb deformity, and 4 had remaining extremity length discrepancy. CONCLUSIONS: Microsurgical flaps are a good option for functional improvement of severe pediatric linear scleroderma affecting the extremities. However, residual limb deformity is common, and patients are often required to undergo additional surgical revisions.

Treatment of En Coup de Sabre Deformity with Fat Grafting and Demineralized Bone Matrix: A Case Series.

En coup de sabre deformity (ECDS) is a form of localized scleroderma in the frontoparietal region caused by progressive subcutaneous tissue atrophy and bony defect. Although ECDS involves two layers, skin/subcutaneous tissue and bone, the existing literature mainly focuses only on treating the skin/subcutaneous tissue layer. In this case series, we aimed to propose a novel approach that includes the combined use of fat grafting and demineralized bone matrix (DBM). Four patients with ECDS deformity, operated between February 2016 and October 2018, were retrospectively evaluated. All the patients were treated with the novel approach. Patients were evaluated with localized scleroderma scale and computed tomography (CT) scan in the preoperative period and at the annual follow-up. We observed remarkable improvement in the localized scleroderma scale including appearance, palpation, and size scores in all patients at the annual follow-up. CT scans at the annual follow-up revealed new callus formation at the bony defect area in all patients. Reinforcing fat grafting with DBM could promote healing of the bony and skin/subcutaneous tissue defects associated with ECDS.

Treatment of linear scleroderma "En coup de Sabre" with single-stage autologous fat grafting: A case report and review of the literature.

BACKGROUND: Linear scleroderma "en coups de sabre" is a disease that causes scar-like lesions in the forehead and the scalp, and atrophy of the underlying structures. The result is an acute facial asymmetry that can be distressing to affected young adults. Several surgical treatments are available such as free tissue transfer and synthetic fillers. AIMS: In this report, we present a rare case of linear scleroderma "en coups de sabre," which was successfully managed with single-stage autologous fat grafting. PATIENTS/METHODS: The patient was a 17-year-old male who presented with a soft-tissue defect in the left forehead region. Treatment consisted of transferring autologous fat into the defect in a retrograde fashion, as described by Coleman, and overcorrecting the defect to account for fat resorption. RESULTS: At 6 mo postoperatively, the patient had maintained a satisfactory correction of his left forehead and scalp regions with minimal resorption of fat. CONCLUSION: Autologous fat grafting provides a safe and easy approach for the treatment of linear scleroderma "en coups de sabre". With minimal manipulation of the aspirated fat, combined with overcorrection of the defect, long-term clinically satisfactory results can be obtained.

Autologous fat grafting for the treatment of sclerotic lesions and scars.

INTRODUCTION: Microfat grafting is a well-known technique that is underutilized in dermatology. Instead of removing sclerotic tissue, microfat grafting preserves the tissue and uses stem cells for remodeling its structure into normal tissue. We performed a retrospective study of patients treated with microfat grafting for sclerotic and atrophic skin lesions and scars. PATIENTS AND METHODS: Seventy-two microfat grafts were performed using the Magalon technique under general anaesthesia for the treatment of sclerotic and atrophic skin lesions. We performed grafts for different indications, such as scars (n=55) and sclerotic and atrophic skin lesions (n=17: Parry-Romberg syndrome, morphea). The main outcome was assessed for satisfaction during follow-up. In addition, an independent committee judged the results based on photographs. RESULTS: Satisfaction levels (e.g. results were judged to be "good") were almost 91% (n=50/55) for scars and 100% (n=17/17) for atrophic and sclerotic skin lesions. Satisfaction levels according to the independent committee were 94.1% for sclerotic and atrophic lesions and nearly 51% for scars. CONCLUSION: Satisfaction was high after microfat grafting for atrophic and sclerotic skin lesions. Microfat grafting enabled restoration of the skin texture by exploiting stem cell properties. It is an efficient dermatological therapy for sclerotic and atrophic lesions, for which there are few alternative treatments.

Scleroderma of the Hand: Evaluation and Treatment.

Scleroderma is derived from Latin meaning hard skin. It is an uncommon, noninflammatory connective tissue disorder characterized by increased fibrosis of the skin and in certain variants, multiple other organ systems. Scleroderma involves a spectrum of pathologic changes and anatomic involvement. It can be divided into localized and systemic scleroderma. Hand involvement is common and can include calcium deposits within the soft tissues, digital ischemia, and joint contracture. Nonsurgical management consists of lifestyle modifications, biofeedback, therapy for digital stiffness/contracture, and various pharmacologic medications. When nonsurgical measures are unsuccessful, certain surgical options may be indicated, each with their inherent advantages and pitfalls. Patients with scleroderma who are undergoing surgical intervention pose unique difficulties because of their poorly vascularized tissue and deficient soft-tissue envelopes, thus increasing their susceptibility to wound healing complications and infection. Some subgroups of patients are frequently systemically ill, and specific perioperative measures should be considered to reduce their surgical risk. The spectrum of hand manifestations seen in patients with scleroderma will be reviewed with the focus on evaluation and management.

Huriez syndrome associated with basal cell carcinoma. A case report.

Huriez syndrome is a rare cancer-prone genodermatosis confined to the hands and feet connects with an increase in squamous cell carcinoma on affected skin. Its diagnosis is complex due to not well defined symptoms and since only few cases are described in literature. The differential diagnoses are many and the treatment is focused only on symptoms control and tumours eradication. Our case report is highly interesting because add new knowledge about this disease describing a new important feature of the syndrome. For the first time in literature we describe the arising of basal cell carcinoma from affected skin. KEY WORDS: H, Basal cell carcinoma, Huriez syndrome, Palmoplantar keratoderma.

Manejo ortopédico de la esclerodermia lineal localizada en niños: reporte de un caso / Orthopedic management of localized linear scleroderma in children: a case report

Resumen: Introducción: La esclerodermia localizada es la forma de presentación de esclerosis más frecuente en niños; tiene una incidencia de 2.7 por cada 100,000 habitantes, con predilección por la raza caucásica y el sexo femenino con relación de 2.4 a 4.1 por cada varón. El común denominador es la afección a nivel de tejido conectivo, genera una variedad de presentación clínica que va desde placas escleróticas localizadas circunscritas que afectan la piel hasta afecciones más profundas que atacan al tejido muscular y óseo, dejando secuelas estéticas y/o deformidades incapacitantes en el paciente. Objetivo: Presentación de caso y su manejo quirúrgico. Los datos expuestos se obtuvieron del expediente clínico físico y electrónico, entrevista directa con paciente y familiares y seguimiento y valoración de estudios radiográficos, desde Enero de 2012 hasta Noviembre de 2017. Discusión: El tratamiento quirúrgico está indicado cuando las deformidades y contracturas condicionan incapacidad en el paciente. Los mejores resultados se obtendrán una vez que la enfermedad haya dejado de progresar.

Abstract: Introduction: Localized scleroderma is the most common form of sclerosis in children; it has an incidence of 2.7 per 100,000 inhabitants, with a predilection for the Caucasian and female races of 2.4 to 4.1 per male. The common denominator is the connective tissue-level condition, causing a variety of clinical presentation ranging from localized sclerotic circumscribed plaques affecting the skin, to deeper conditions that attack muscle and bone tissue, leaving aesthetic consequences and/or disabling deformities in the patient. Objective: Case presentation and surgical management. The data presented were obtained from the physical and electronic clinical record, direct interview with patients and family members and monitoring and evaluation of radiographic studies, from January 2012 to November 2017. Discussion: Surgical treatment is indicated when deformities and contractures condition incapacity in the patient. The best results will be obtained once the disease has stopped progressing.

Juvenile sclerosing polycystic adenosis cytologically mimicking Warthin tumor.

Sclerosing polycystic adenosis (SPA) is a rare salivary gland disease. Histologically it resembles a low-grade ductal carcinoma in situ or sclerosing adenosis of the breast, characterized by lobular proliferation of ducts with apocrine cellular features surrounded by fibrosclerotic stroma. Although SPA is typically benign, recurrence is not uncommon, and cases with a malignant component have been documented. Thus, complete excision is desirable but preoperative diagnosis is challenging. A 12-year-old boy presented with a painless mass in the right neck. We identified a well-demarcated mass in the right parotid region measuring approximately 2 cm using cervical echography and magnetic resonance (MR) imaging. Fine-needle aspiration (FNA) revealed two cell types. There were loosely cohesive clusters of polymorphic epithelioid cells with irregular nuclei and abundant vacuolated cytoplasm containing zymogen granules. Some of these cells were binuclear. The other cell types represented normal ductal cells. The original cytological diagnosis was Warthin tumor. Right parotidectomy was performed. Histologically, we observed proliferation of ducts with granular, vacuolated, zymogen granules, and apocrine-like features in the cytoplasm with hyalinizing sclerotic stroma and some binuclear cells. Four years after parotidectomy, there has been no recurrence or malignant transformation.Cytological diagnosis of SPA is challenging on FNA specimens since SPA is a very rare entity of the salivary gland that can mimic other salivary gland neoplasms. A mixture of apocrine-like cells and sebaceous-like cells, nuclear pleomorphism, and zymogen granules can help to diagnose this rare lesion during the initial cytological diagnosis.

[Orthopedic management of localized linear scleroderma in children: a case report]. / Manejo ortopédico de la esclerodermia lineal localizada en niños: reporte de un caso.

INTRODUCTION: Localized scleroderma is the most common form of sclerosis in children; it has an incidence of 2.7 per 100,000 inhabitants, with a predilection for the Caucasian and female races of 2.4 to 4.1 per male. The common denominator is the connective tissue-level condition, causing a variety of clinical presentation ranging from localized sclerotic circumscribed plaques affecting the skin, to deeper conditions that attack muscle and bone tissue, leaving aesthetic consequences and/or disabling deformities in the patient. OBJECTIVE: Case presentation and surgical management. The data presented were obtained from the physical and electronic clinical record, direct interview with patients and family members and monitoring and evaluation of radiographic studies, from January 2012 to November 2017. DISCUSSION: Surgical treatment is indicated when deformities and contractures condition incapacity in the patient. The best results will be obtained once the disease has stopped progressing.

INTRODUCCIÓN: La esclerodermia localizada es la forma de presentación de esclerosis más frecuente en niños; tiene una incidencia de 2.7 por cada 100,000 habitantes, con predilección por la raza caucásica y el sexo femenino con relación de 2.4 a 4.1 por cada varón. El común denominador es la afección a nivel de tejido conectivo, genera una variedad de presentación clínica que va desde placas escleróticas localizadas circunscritas que afectan la piel hasta afecciones más profundas que atacan al tejido muscular y óseo, dejando secuelas estéticas y/o deformidades incapacitantes en el paciente. OBJETIVO: Presentación de caso y su manejo quirúrgico. Los datos expuestos se obtuvieron del expediente clínico físico y electrónico, entrevista directa con paciente y familiares y seguimiento y valoración de estudios radiográficos, desde Enero de 2012 hasta Noviembre de 2017. DISCUSIÓN: El tratamiento quirúrgico está indicado cuando las deformidades y contracturas condicionan incapacidad en el paciente. Los mejores resultados se obtendrán una vez que la enfermedad haya dejado de progresar.

A 26-Year Experience with Microsurgical Reconstruction of Hemifacial Atrophy and Linear Scleroderma.

BACKGROUND: Parry Romberg disease (hemifacial atrophy) and linear scleroderma (coup de sabre) are progressive, usually unilateral facial atrophies of unknown cause. The gold standard treatment for these patients has been microsurgical reconstruction following the "burning out" of the facial atrophy and stable contour for 2 years. METHODS: The authors report their experience treating patients with hemifacial atrophy and linear scleroderma with free tissue transfers between 1989 and 2016. A modified parascapular flap based on the circumflex scapular artery was most commonly used. RESULTS: A total of 177 patients were included. The most common complication was hematoma, occurring in 12 patients (7 percent). Follow-up ranged from 1 to 26 years. All patients subjectively experienced improved facial symmetry and aesthetics. No disease process has recurred to date, even in cases of severe, progressive disease. CONCLUSIONS: In the authors' experience, patients treated early in their disease course have immediate and sustained correction of their deformity, with slowing or in most cases cessation of the disease process following free tissue transfer. The authors now advocate for immediate reconstruction for active disease, especially in young children. CLINICAL QUESTIONS/LEVEL OF EVIDENCE: Therapeutic, IV.

Parry Romberg Syndrome and linear facial scleroderma: management in pediatric population.

Among all different types of cutaneous scleroderma, Parry Romberg syndrome and linear scleroderma "en coup de sabre" typically involve the visage. Gradual degeneration of the tissues, from the skin up to the bone, is the stigmata of the diseases and the range of clinical manifestations is wide. They typically start during childhood and slowly progress before stabilizing. Considering the gravity of the associated deformity and its impact on facial function and appearance, we strongly advocate a prompt intervention that however must be tailored on paediatric patients. There is not a general consensus on hemifacial atrophy treatment, but autologous fat grafting has been proved to be a suitable technique, due to its low morbidity, repeatability and efficacy in correcting volume defects and in improving skin texture. Following the same concept of safeness and non-invasiveness we propose 3D stereophotogrammetric acquisitions as a possible tool for the pre- and post-surgical follow up, indispensable to evaluate the surgical results. We present our case series composed of 8 paediatric patients, aged between 11 and 17 years, who underwent several lipofilling procedures, from 2012 to 2016. Starting from 2015, 3D stereophotgrammetric data has been obtained.