Overlapping Case of Advanced Systemic Sclerosis and IgG4-Related Disease after Autologous Hematopoietic Stem Cell Transplantation.

Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with a high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of a 44-year-old female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. After 11 years of ineffective SSc treatment, AHSCT was performed. The 63-month follow-up showed a regression of SSc symptoms. AHSCT was not intended as treatment in the case of IgG4RD, although the first symptoms of the disease developed before transplantation. The sinus lesions progressed after AHSCT and remained indolent only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy), which allowed histopathological confirmation of IgG4-RD.

Emerging diagnostic and therapeutic challenges for skin fibrosis in systemic sclerosis.

Systemic sclerosis (also called scleroderma, SSc) is a chronic autoimmune disorder characterized by excessive collagen deposition leading to skin fibrosis and various internal organ manifestations. The emergent diagnostics and therapeutic strategies for scleroderma focus on early detection and targeted interventions to improve patient outcomes and quality of life. Diagnostics for SSc have evolved significantly in recent years, driven by advancements in serological markers and imaging techniques. Autoantibody profiling, especially antinuclear antibodies (ANA) and specific scleroderma-associated autoantibodies, aids in identifying subsets of scleroderma and predicting disease progression. Furthermore, novel imaging modalities, such as high-frequency ultrasonography and optical coherence tomography, enable early detection of skin fibrosis and internal organ involvement, enhancing the diagnostic precision and allowing for tailored management. Therapeutic strategies for SSc are multifaceted, targeting immune dysregulation, vascular abnormalities, and fibrotic processes. Emerging biologic agents have shown promise in clinical trials, including monoclonal antibodies directed against key cytokines involved in fibrosis, such as transforming growth factor-ß (TGF-ß) and interleukin-6 (IL-6). Additionally, small-molecule inhibitors that disrupt fibrotic pathways, like tyrosine kinase inhibitors, have exhibited potential in limiting collagen deposition and preventing disease progression. Stem cell therapy, cell ablation and gene editing techniques hold great potential in regenerating damaged tissue and halting fibrotic processes. Early intervention remains crucial in managing SSc, as irreversible tissue damage often occurs in advanced stages. Novel diagnostic methods, such as biomarkers and gene expression profiling, are being explored to identify individuals at high risk for developing progressive severe disease and intervene proactively. Furthermore, patient-tailored therapeutic approaches, employing a combination of immunosuppressive agents and targeted anti-fibrotic therapies, are being investigated to improve treatment efficacy while minimizing adverse effects. The emergent diagnostics and therapeutic strategies in scleroderma are transforming the management of this challenging disease. Nevertheless, ongoing research and clinical trials are needed to optimize the efficacy and safety of these novel approaches in the complex and diverse spectrum of SSc manifestations.

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

[Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. / Atteinte sévère de l'intestin grêle et pseudo-obstruction intestinale chronique au cours de la sclérodermie systémique : bases physiopathologiques, diagnostiques et thérapeutiques, dont la nutrition parentérale.

Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.

Systemic scleroderma: Review and updated approach and case description to addressing pulmonary arterial hypertension and idiopathic pulmonary fibrosis: A dual challenge in treatment.

Pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and scleroderma (SSc) are three interrelated medical conditions that can result in significant morbidity and mortality. Pulmonary hypertension, a condition marked by high blood pressure in the lungs, can lead to heart failure and other complications. Idiopathic pulmonary fibrosis, a progressive lung disease characterised by scarring of lung tissue, can cause breathing difficulties and impaired oxygenation. Scleroderma, an autoimmune disease, can induce thickening and hardening of the skin and internal organs, including the lungs, leading to pulmonary fibrosis and hypertension. Currently, there is no cure for any of these conditions. However, early detection and proper management can improve the quality of life and prognosis of a patient. This review focusses on PH and IPF in patients with SSc, providing information on the causes, symptoms, and treatment of these conditions, together with illustrative images. It also provides an overview of interrelated medical conditions: PH, IPF, and SSc. It emphasises the importance of early detection and proper management to improve patient quality of life and prognosis.

French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.

[Autologous peripheral stem cell transplantation in systemic sclerosis: An important step forward, but we must temper our enthusiasm!] / Autogreffe de cellules souches périphériques dans la sclérodermie systémique : un progrès important, mais il faut tempérer notre enthousiasme !

Three prospective randomized studies have demonstrated the efficacy of autologous hematopoietic stem cell (HSC) transplantation in systemic sclerosis (SSc) on survival. These results encourage us to offer this therapy to patients who have a rapidly progressive disease and who have early symptoms but no advanced visceral involvement. HSC autograft can thus be discussed in patients with diffuse cutaneous SSc with a duration of the disease since the first visceral manifestations (cutaneous, cardiac, digestive, pulmonary, or renal) excluding Raynaud's phenomenon of less than 5 years. However, the indications for HSC autograft in SSc validated at European level and in the national diagnostic and care protocol (PNDS) are broader and some of these indications are debatable, in particular in patients with worsening diffuse interstitial lung disease. These indications are discussed in a reasoned way, taking into account the level of evidence and the toxicity of the HSC autograft.

Umbilical cord mesenchymal stem cells transplantation in patients with systemic sclerosis: a 5-year follow-up study.

OBJECTIVE: To assess the long-term safety and efficacy of umbilical cord mesenchymal stem cells transplantation (UMSCT) in patients with systemic sclerosis (SSc). METHODS: Forty-one patients with moderate to severe SSc underwent UMSCT at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2009 to 2017. In this study, we conducted a longitudinal and retrospective analysis and compared the clinical and laboratory manifestations before and after UMSCT. The main outcome of the study was overall survival. We evaluated changes in the modified Rodnan Skin Score (mRSS), as well as the changes in the pulmonary examination by using high-resolution computed tomography (HRCT) and ultrasound cardiogram (UCG). Additionally, we assessed the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the severity of peripheral vascular involvement during the first year after treatment. RESULTS: The overall 5-year survival rate was 92.7% (38 out of 41 patients). Following UMSCT, the mean mRSS significantly decreased from 18.68 (SD = 7.26, n = 41) at baseline to 13.95 (SD = 8.49, n = 41), 13.29 (SD = 7.67, n = 38), and 12.39 (SD = 8.49, n = 38) at 1, 3, and 5 years, respectively. Improvement or stability in HRCT images was observed in 72.0% of interstitial lung disease (ILD) patients. Pulmonary arterial hypertension (PAH) remained stable in 5 out of 8 patients at the 5-year follow-up. No adverse events related to UMSCT were observed in any of the patients during the follow-up period. CONCLUSION: UMSCT may provide a safe and feasible treatment option for patients with moderate to severe SSc based on long-term follow-up data. The randomized controlled study will further confirm the clinical efficacy of UMSCT in SSc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00962923. Key Point • UMSCT is safe and effective for SSc patients.

Effects of a Resilience-Building Energy Management Program on Fatigue and Other Symptoms in Systemic Sclerosis: A Randomized Controlled Trial.

OBJECTIVE: Supported self-management interventions for individuals with systemic sclerosis (SSc) are needed. We examined the effects of a 12-week resilience-building energy management program (called RENEW) for fatigue and other patient-reported outcomes. METHODS: Participants, who had physician-diagnosed SSc, moderate to severe fatigue, and were ≥18 years old, were randomly assigned to RENEW or waitlist control in a 2:1 ratio. The RENEW intervention included an educational website/application plus nine virtual peer-led health coaching sessions. The primary outcome was change in the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary outcomes were change in Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms and Connor-Davidson Resilience Scale. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. Multiple imputation was conducted; linear mixed models were used to assess group differences. A three-way interaction with group, time, and SSc duration was examined in each model. RESULTS: Among 173 participants (mean ± SD age 54.5 ± 11.7 years; 93% female, 85% White), 47% had diffuse cutaneous SSc; 57% were ≤5 years from diagnosis. At 12 weeks, compared to controls, RENEW participants had a clinically meaningful fatigue improvement (ß = -4.7; 95% confidence interval -6.7 to -2.7; P < 0.001) and improvement in all secondary outcomes. Among RENEW participants, individuals with shorter disease duration had greater improvements in fatigue at 12 weeks. CONCLUSION: An mHealth supported self-management intervention improved fatigue and other outcomes, particularly in newly diagnosed patients. This program may be broadly scalable for SSc symptom management.

Systemic sclerosis interstitial lung disease: unmet needs and potential solutions.

Systemic sclerosis (SSc), or scleroderma, is a rare, complex, systemic autoimmune disease of unknown aetiology, characterized by high morbidity and mortality often resulting from cardiopulmonary complications such as interstitial lung disease and pulmonary arterial hypertension. Despite substantial progress in unravelling the pathways involved in the pathogenesis of SSc and the increasing number of therapeutic targets tested in clinical trials, there is still no cure for this disease, although several proposed treatments might limit the involvement of specific organs, thereby slowing the natural history of the disease. A specific focus of recent research has been to address the plethora of unmet needs regarding the global management of SSc-related interstitial lung disease, including its pathogenesis, early diagnosis, risk stratification of patients, appropriate treatment regimens and monitoring of treatment response, as well as the definition of progression and predictors of progression and mortality. More refined stratification of patients on the basis of clinical features, molecular signatures, identification of subpopulations with distinct clinical trajectories and implementation of outcome measures for future clinical trials could also improve therapeutic management strategies, helping to avoid poor outcomes related to lung involvement.

A qualitative interview study exploring the psychological health impacts of the SPIN-CHAT program among people with systemic sclerosis at the onset of COVID-19: perceptions of trial participants and research team members.

PURPOSE: Explore trial participants' and research team members' perceptions of the impact of the videoconference-based, supportive care program (SPIN-CHAT Program) during early COVID-19 for individuals with systemic sclerosis (SSc). METHODS: Data were collected cross-sectionally. A social constructivist paradigm was adopted, and one-on-one videoconference-based, semi-structured interviews were conducted with SPIN-CHAT Trial participants and research team members. A hybrid inductive-deductive approach and reflexive thematic analysis were used. RESULTS: Of the 40 SPIN-CHAT Trial participants and 28 research team members approached, 30 trial participants (Mean age = 54.9; SD = 13.0 years) and 22 research team members agreed to participate. Those who took part in interviews had similar characteristics to those who declined. Five themes were identified: (1) The SPIN-CHAT Program conferred a range of positive psychological health outcomes, (2) People who don't have SSc don't get it: The importance of SSc-specific programming, (3) The group-based format of the SPIN-CHAT Program created a safe space to connect and meet similar others, (4) The structure and schedule of the SPIN-CHAT Program reduced feelings of boredom and contributed to enhanced psychological health, (5) The necessity of knowledge, skills, and tools to self-manage SSc and navigate COVID-19. CONCLUSION: Participants' and research team members' perspectives elucidated SPIN-CHAT Program benefits and how these benefits may have been realized. Results underscore the importance of social support from similar others, structure, and self-management to enhance psychological health during COVID-19. TRIAL REGISTRATION: clinicaltrials.gov (NCT04335279)IMPLICATIONS FOR REHABILITATIONThe videoconference-based, supportive care SPIN-CHAT Program enhanced psychological health amongst individuals affected by systemic sclerosis.SPIN-CHAT Program participants and research team members shared that being around similar others, program structure, and self-management support were important and may have contributed to enhanced psychological health.Further efforts are required to explore experiences within supportive care programs to better understand if and how psychological health is impacted.

Recent Advances in Treatment of Systemic Sclerosis and Morphea.

Systemic sclerosis (SSc) and morphea are autoimmune sclerosing diseases that cause significant morbidity, and in the case of SSc, mortality. The pathogenesis of both SSc and morphea share vascular dysfunction, auto-reactive T cells and Th2-associated cytokines, such as interleukin 4, and overproduction of transforming growth factor beta (TGFß). TGFß stimulates fibroblast collagen and extra-cellular matrix production. Although morphea and SSc have similar pathogenic pathways and histological findings, they are distinct diseases. Recent advances in treatment of morphea, skin sclerosis in SSc, and interstitial lung disease in SSc are focused on targeting known pathogenic pathways.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Case Report: Effectiveness of secukinumab in systemic sclerosis with early skin progress after autologous hematopoietic stem cell transplantation and end-stage kidney disease.

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment option in patients with severe forms of systemic sclerosis (SSc) by resetting the immune system. Nevertheless, secondary autoimmune disorders and progressive disease after aHSCT might necessitate renewed immunosuppressive treatments. This is particularly challenging when organ dysfunction, i.e., end-stage kidney failure, is present. In this case report, we present the unique case of a 43-year-old female patient with rapidly progressive diffuse systemic sclerosis who underwent aHSCT despite end-stage renal failure as consequence of SSc-renal crisis. Therefore, conditioning chemotherapy was performed with melphalan instead of cyclophosphamide with no occurrence of severe adverse events during the aplastic period and thereafter. After aHSCT, early disease progression of the skin occurred and was successfully treated with secukinumab. Thereby, to the best of our knowledge, we report the first case of successful aHSCT in a SSc-patient with end-stage kidney failure and also the first successful use of an IL-17 inhibitor to treat early disease progression after aHSCT.

Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

Investigation of the effects of upper extremity home exercises on grip strength, range of motion, activity performance, and functionality in individuals with systemic sclerosis: a randomized controlled trial.

OBJECTIVE: This study aimed to investigate the effects of upper extremity home exercises on grip strength, range of motion, activity performance, and functionality in individuals with systemic sclerosis and to compare with patient education. METHODS: A total of 46 individuals with systemic sclerosis (55.52±11.54 years) were included. Individuals were randomly assigned into intervention (n=23) and control (n=23) groups. Dynamometer, goniometer, Canadian Occupational Performance Measurement, Disabilities of the Arm, Shoulder, and Hand, Score for Assessment and Quantification of Chronic Rheumatic Affections of the Hands, and Duruoz Hand Index were used for evaluation. RESULTS: Post-treatment, in terms of delta (Δ) values, hand grip and pinch strengths (p: 0.000-0.016), active (p: 0.000-0.032) and passive (p: 0.000-0.043) total range of motions, Canadian Occupational Performance Measurement performance and satisfaction, Disabilities of the Arm, Shoulder, Score for Assessment and Quantification of Chronic Rheumatic Affections of the Hands, and Duruoz Hand Index (p: 0.000) were in favor of the intervention group. CONCLUSION: Upper extremity home exercises increase grip strength, range of motion, activity performance, and functionality in patients with systemic sclerosis. We recommend that rehabilitation programs include not only hand exercises but also upper extremity exercises.

Skin Gene Expression Profiles in Systemic Sclerosis: From Clinical Stratification to Precision Medicine.

Systemic sclerosis, also known as scleroderma or SSc, is a condition characterized by significant heterogeneity in clinical presentation, disease progression, and response to treatment. Consequently, the design of clinical trials to successfully identify effective therapeutic interventions poses a major challenge. Recent advancements in skin molecular profiling technologies and stratification techniques have enabled the identification of patient subgroups that may be relevant for personalized treatment approaches. This narrative review aims at providing an overview of the current status of skin gene expression analysis using computational biology approaches and highlights the benefits of stratifying patients upon their skin gene signatures. Such stratification has the potential to lead toward a precision medicine approach in the management of SSc.

Adipose derived stromal vascular fraction and fat graft for treating the hands of patients with systemic sclerosis. A randomized clinical trial.

BACKGROUND: Systemic Sclerosis in the hand is characteristically evidenced by Raynaud's phenomenon, fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment does not always cure these complications. Local adipose-derived stromal vascular fraction administration into the hands has been proposed as an emerging treatment due to its regenerative properties. The objective of this randomized controlled clinical trial was to evaluate the safety and clinical effects of fat micrografts plus adipose derived-stromal vascular fraction administration into the hands of patients with systemic sclerosis. METHODS: This was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with systemic sclerosis were assigned to the experimental or control group. Fat micrografts plus the adipose derived-stromal vascular fraction were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon, digital ulcers number, mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, serologic antibodies, hand function, and quality of life scores were evaluated in both groups. RESULTS: The results of the intervention were analyzed with the Wilcoxon rank test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann-Whitney U test. Adverse events were not observed in both groups. At the end of the study, statistically significant improvements were observed in pain levels (p<0.05) and number of digital ulcers (p<0.01) in the experimental vs control group. CONCLUSION: The injection of adipose derived-stromal vascular fraction plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with systemic sclerosis can be treated with this technique plus conventional medical treatment.