[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

[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 sclerosis, silica exposure and cellular therapies: The sand in the gears?

Systemic sclerosis (SSc) is a chronic orphan autoimmune disease with the highest mortality rate among rheumatic diseases. SSc-related interstitial-lung disease (ILD) remains among the leading causes of SSc-related mortality with still few therapeutic effective strategies. In patients with crystallin silica exposure, SSc is recognized as an occupational disease according to the French social security system (Table 25A of the general insurance regimen). Lympho-ablative or myeloablative immunosuppression followed by autologous hematopoietic stem-cell transplantation (aHSCT) is the only therapeutic approach with demonstrated efficacy, improved survival with disease modifying effects on SSc-fibrotic manifestations (skin disease and ILD) and quality of life. A documented past and/or present occupational silica exposure, with extensive exposure and/or silica-related ILD and/or with persistent silica content in the broncho-alveolar lavage fluid are contra-indications to aHSCT in SSc patients, due to the risk of silica-related malignancy or of SSc relapse. This article aims to discuss alternative options in SSc patients with a history of silica exposure, and how innovative cellular therapies (mesenchymal stromal cells, CAR cells) could represent new therapeutic options for these patients.

[The arguments favoring autologous haematopoietic stem cell transplantation in systemic scleroderma]. / Argumentaire « en faveur ¼ de la greffe de cellules souches hématopoïétiques autologues dans la sclérodermie systémique.

Autologous haematopoietic stem cell transplantation for systemic scleroderma, developed over more than 25 years, has shown in three randomised controlled clinical trials a significant impact not only in event-free survival, overall survival, cutaneous and pulmonary involvement, but also in the quality of life of patients living with recent severe diffuse cutaneous systemic scleroderma, compared with IV cyclophosphamid despite a transplant-related mortality between 2.4 and 10%. No immunosuppressants or biologics have shown such an impact on mortality in this disease. The risk of relapse is estimated between 9 and 24%, two years after transplant. On the basis of these results, French and international guidelines now position autologous haematopoietic stem cell transplantation as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma.

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.

[Update on targeted biopharmaceuticals in systemic sclerosis!] / Biothérapies ciblées : nouveautés dans la sclérodermie systémique !

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by inflammation, fibrosis, and autoimmunity. Despite few clinical trials when compared to other autoimmune diseases, SSc has benefited from renewed interest over the past ten years and a large number of clinical trials have been performed or are underway. We present here the results of the trials published in the last 5 years in ScS according to the chosen endpoint criteria and describe the trials in progress or expected in the years to come.

[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.

[Gastrointestinal tract involvement in systemic sclerosis]. / Atteinte digestive de la sclérodermie systémique.

Gastrointestinal tract involvement in systemic sclerosis concerns more than 90% of patients but is of heterogeneous clinical expression. It can involve the entire intestinal tract and be responsible for multifactorial malnutrition, which is frequent in this disease. It is a major source of deterioration in the quality of life and can even be life-threatening. Management is complex and multidisciplinary, ranging from simple hygienic and dietary measures, to specialized endoscopic or surgical interventional procedures, also including medical treatments, particularly proton pump inhibitors and prokinetics, with potential side effects. Ongoing research for new diagnostic and therapeutic tools promises to improve the management and prognosis of these patients.

[Autoimmune and inflammatory pathologies associated with systemic scleroderma: Clinical, serological and prognostic profiles. Bi-centric retrospective series in the PACA region]. / Pathologies auto-immunes et inflammatoires associées à la sclérodermie systémique : profils cliniques, sérologiques et pronostiques. Série rétrospective bi-centrique en région PACA.

INTRODUCTION: Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. METHODS: We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. RESULTS: The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. CONCLUSION: SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up.

Assessing the effect of PRP addition to facial micro-lipofilling for patients suffering from Scleroderma: A prospective routine care analysis.

BACKGROUND: Combining fat graft with platelet derived products is now common practice in regenerative surgery. We proposed to assess the safety and efficacy of Platelet-Rich Plasma (PRP) addition to a micro-lipofilling protocol for facial treatment of patients suffering from Systemic Sclerosis (SSc). OBJECTIVE: Main objective was to evaluate the improvement of the Mouth Handicap In Systemic Sclerosis (MHISS) scale score at 6 months post-therapy. METHOD: Included SSc patients had a MHISS score equal or up to 20. Surgery was performed under general anesthesia. Micro-fat and PRP (CCA-NA from DEPA Classification) were mixed in a 70/30 ratio, before injection in peri-oral sites according to a specific protocol. Efficacy criteria were recorded at baseline, 3 and 6 months. Moreover, we compared this cohort (current study) to a former (2015) non-enriched micro-lipofilling cohort in the same indication, using the same protocol. RESULTS: Thirteen women patients with mean age of 53.2 years (±14.3) have been included. At baseline, mean MHISS score was 29.5 (±8.7) and significantly decreased to 22.5 (±7.8) at 6 months (P=0.016), corresponding to a 22.0% of improvement from baseline, with a mean decrease of 6.5 points (±7.5) at 6 months. Patients received a mean volume of 30.8ml PRP-micro-fat (±8.1ml). CONCLUSION: PRP addition appeared beneficial, however, controlled studies are required to determine its superiority to facial micro-lipofilling.

[Cardiopulmonary exercise testing in the management of systemic sclerosis]. / La place de l'Exploration Fonctionnelle (cardio-)respiratoire d'eXercice (EFX) dans la prise en charge de la sclérodermie systémique.

Cardiopulmonary complications are the leading cause of mortality in patients with systemic sclerosis (SSc) requiring an early identification. A global and comprehensive approach is needed due to the complexity of the overlapping aetiologies of dyspnoea in SSc. Through its integrative approach of ventilatory, metabolic, cardiovascular, skeletal muscular and gas exchange findings, cardiopulmonary exercise testing (CPET) has been known to identify and sort competing mechanisms of exercise limitation in scleroderma patients presenting with dyspnoea. CPET may be used to screen for pulmonary arterial hypertension, suspect interstitial lung disease and guide therapeutic strategies including exercise rehabilitation. This review focuses on the clinical value of CPET in the decision-making processes for a more personalised diagnostic approach to SSc-related complications.

[Characteristics of patients with connective tissue disease-associated pulmonary arterial hypertension treated with prostanoids: A multicenter retrospective study]. / Caractéristiques des patients traités par prostanoïdes pour une hypertension artérielle pulmonaire associée à une connectivite : étude multicentrique rétrospective.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment. METHODS: In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment. RESULTS: Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment. CONCLUSION: This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

[Monocentric study on pharmaceuticals taken by patients to treat systemic sclerosis]. / Étude monocentrique sur les médicaments pris par les patients pour le traitement de la sclérodermie systémique.

INTRODUCTION: Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients. METHODS: This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance. RESULTS: The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009). CONCLUSION: This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.

[Development and validation of a questionnaire to assess facial handicap in systemic sclerosis]. / Création et validation d'un outil d'évaluation du handicap lié à l'atteinte du visage de la sclérodermie systémique.

BACKGROUND: Many studies have recorded significant impairment of health-related quality of life in systemic sclerosis patients using validated scales. However, these instruments are not specifically designed for facial signs. OBJECTIVES: To develop and validate a specific questionnaire to assess the burden on patients with facial signs of systemic sclerosis and which we have named "Burden of Face Affected" (BoFA). METHODS: BoFA was developed using standard methodology in 3 phases: exploration, development and validation. In all, 197 patients completed questionnaires. We analysed the degree of internal consistency (Cronbach's α) and external validity between BoFA and the 12-Item Short Form Healthy Survey (SF-12), the Mouth Handicap In Systemic Sclerosis Scale (MHISS), Rosenberg's self-esteem scale, and the Perceived Stress Scale (PSS). To assess reproducibility, a test-retest analysis was conducted. The original French version was translated into English and underwent cultural validation. RESULTS: The questionnaire comprises 20 items grouped into 4 dimensions. BoFA showed good internal consistency (Cronbach's α: 0.93). External validity was demonstrated in terms of good correlation between BoFA and other questionnaires, in particular MHISS (r=0.54). The test-retest analysis demonstrated good reproducibility (0.92). The BoFA score varied significantly according to the severity of facial scleroderma as assessed by the patients themselves. DISCUSSION: Facial involvement in systemic sclerosis may be considered by physicians to be a minor consequence of the disease and is often overlooked. Nevertheless, it is crucial for patients' quality of life. A number of studies have assessed the impact of facial signs on health-related quality of life using instruments such as DLQI (Dermatology Life Quality Index), SWAP (Satisfaction With Appearance Scale), Brief SWAP and SSPRO (Scleroderma Skin Patient-Reported Outcome). However, these are not specific for facial signs and focus on other sites. BoFA has good reliability and construct validity, and it assesses disability specifically involving the face in patients with systemic sclerosis. CONCLUSION: To our knowledge, BoFA is the first specific tool for assessing burden in patients with facial scleroderma. It is an easy-to-use tool for evaluating the burden of facial signs and may also be used to assess the degree of burden before and after treatment.

[Illnesses unrelated to systemic sclerosis (IUSS) diagnosed throughout the patient's follow-up in a referral center: A cohort of 200 patients]. / Affections non-directement attribuables à la sclérodermie systémique (ANDAS) diagnostiquées au cours du suivi dans un centre de compétence: à propos d'une cohorte de 200 patients.

INTRODUCTION: Our work aimed to investigate the illnesses unrelated to systemic sclerosis (IUSS), diagnosed among patients with systemic sclerosis (SSc) throughout their follow-up in a referral tertiary care center. METHODS: All the patients with SSc followed in the Internal Medicine Department of the University Hospital between October, 2014 and December, 2015, were included. We specifically reviewed the medical records of the patients who exhibited IUSS, defined as an illness that could not be considered as a typical clinical manifestation or as a usual complication of the disease. RESULTS: Two hundred patients were included, and 38 IUSS were diagnosed among 31 SSc patients, over a 4 years median follow-up period. These diagnoses included vascular diseases (26%), heart diseases (21%), neoplasia (8%), infectious diseases (6%), autoimmune diseases (5%), endocrinopathies (5%), and others (24%). The median follow-up time before IUSS diagnosis was two years. Seventeen (45%) of these diagnoses were considered in patients showing suggestive clinical signs. A specific therapy was delivered in 25 cases (66%). Group comparisons revealed that dyslipidemia was more frequent in patients with IUSS (OR = 2.6 [1.1-1.5]; p = 0.014), while no differences were found for the other characteristics. Especially, no association between auto-antibodies specificity and the occurrence of IUSS was found. CONCLUSION: This study focused on IUSS in SSc patients and highlights the need for a polyvalent clinical approach all along the follow up of SSc patients.

[A case of systemic sclerosis]. / U ne rémission « en peau de chagrin ¼.

In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10 year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3 antibodies in the context of ovarian cancer remission.

Characteristics of Systemic Sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review.

Among the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc.

[Pseudotumoral calcinosis of the wrist compressing the radial nerve in systemic sclerosis]. / Compression du nerf radial au poignet par une calcinose pseudo-tumorale au cours d'une sclérodermie systémique.

BACKGROUND: Pseudotumoral calcinosis, a rare complication of systemic scleroderma, is characterized by the presence in extra-articular tissue, but rarely intra-articular tissue, of large masses made up of hydroxyapatite crystals. PATIENTS AND METHODS: We report an original case of intra- and extra-articular pseudotumoral calcinosis of the wrist diagnosed in a patient followed for mild systemic scleroderma. The calcinosis was revealed in a highly unusual way via ductal syndrome secondary to compression of the radial nerve in the wrist. Surgical treatment resulted in marked clinical and functional improvement. COMMENT: Although subcutaneous calcinoses are a fairly common complication of systemic scleroderma, the pseudo-tumoral form remains extremely rare. It may be complicated by pain, recurrent infection, and functional restriction, but literature contains only very rare reports of its revelation via ductal syndrome.

[Systemic sclerosis and macrovascular involvement: Status of the issue in 2019]. / Atteintes macrovasculaires de la sclérodermie : état de la question en 2019.

Systemic sclerosis (SSc) is a rare immune disease leading to fibrosis of the skin and internal organs. Microvasculopathy is a hallmark of SSc. However, some patients have severe macrovascular complications as affecting cerebral, cardiac or peripheral vessels. To date, macrovascular involvement in SSc remains a matter of debate. Many studies have shown an increased prevalence of macrovascular involvement in SSc in comparison with controlled subjects with similar cardiovascular risk factors. Various methods were used: ankle brachial pressure index, intima media thickness, imagery, coronary calcium score, pulse wave velocity, or flow mediated dilation. The pathophysiology of macrovascular involvement remains unknown and is probably multifactorial: accelerated atherosclerosis, endothelial dysfunction, or reflected wave of microvessel obliteration. The aim of this study was to perform a comprehensible review of the literature, through the study of different types of involved vessels. Results of the main studies are summarized in tables according to the method of investigation used.