Sclerosis

Multiple sclerosis (MS) is a chronic and incurable neurological disease of the central nervous system. Three main forms of the disease have been distinguished: relapsing–remitting form (RRMS), secondary progressive form (SPMS), and primary progressive form (PPMS). Currently, in patients with MS, in addition to pharmacotherapy, neurorehabilitation is indicated to improve the motor function of the body and action in the most physiological movement patterns possible. In this therapy, work on lost or incorrect functions is used to provide the patient with self-sufficiency in everyday life. Kinesiotherapy is used as part of neurorehabilitation. This therapy for MS includes coordination exercises aimed at facilitating movement, strengthening exercises and resistance training, balance exercises, improving stability during everyday activities stretching and relaxation exercises, improving tissue elasticity, reducing tension, and breathing exercises. In this article, we present various possibilities for using kinesiotherapy in patients with MS at various stages of disease development. Moreover, we would like to draw attention to the benefits of physical activity leading to a significant improvement in the quality of life in MS patients. We believe that a regular exercise program should be part of the neurorehabilitation program in these patients in the future. Full article

Behavioral activation therapy (BAT) was initially developed to treat depression and was subsequently extended as a transdiagnostic therapy for other psychiatric and neurocognitive disorders. However, research on its impact in people with multiple sclerosis (MS) is lacking. We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living—key components of MS-related quality of life. Our proposed adaptation of the traditional therapy includes a focus on increasing engagement in cognitive, physical, or social activities (activity demand characteristics) to improve cognition and daily life function. In addition, these activities should be individually perceived as energizing, relaxing, or meaningful (subjective activity characteristics) to benefit neuropsychiatric symptoms and social connectedness. Finally, we propose that BAT in MS should specifically focus on reducing stressful activities (i.e., unenjoyable, high-arousal activities) and increasing relaxing activities (i.e., enjoyable, low-arousal activities), as this dimension might tackle the neuroinflammatory etiology of MS. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy, immune dysregulation, and progressive fibrosis affecting the skin and internal organs. Pulmonary complications, including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are major contributors to morbidity and mortality, while skin fibrosis remains a hallmark of disease heterogeneity. Despite advances in understanding SSc pathogenesis, early diagnosis and timely therapeutic intervention remain challenging due to the rapid progression of inflammation and the narrow window before irreversible fibrosis occurs. The identification of reliable biomarkers is crucial for improving diagnosis, monitoring disease activity, and guiding treatment decisions in SSc. While autoantibodies are well-established diagnostic tools, this review focused on non-autoantibody biomarkers, including soluble proteins, cytokines, chemokines, epigenetic modifiers, and oxidative stress indicators. These biomarkers reflect diverse pathogenic mechanisms such as endothelial injury, fibroblast activation, immune signaling, and extracellular matrix remodeling. By examining the available evidence across both clinical and preclinical studies, this review provides an updated overview of molecular markers involved in inflammation and fibrosis in SSc. Understanding their biological significance and therapeutic potential may improve risk stratification, guide targeted interventions, and ultimately contribute to the development of precision medicine strategies in systemic sclerosis. Full article

Background/Objectives: Health locus of control (LOC) refers to one’s perceptions of who or what controls one’s health. Recent evidence has found that chance LOC (CLOC) is associated with improved quality of life (QoL) in multiple sclerosis (MS). The purpose of the current study was to identify mediators and moderators of the LOC-QoL relationship in MS. Methods: For this study, 5266 participants with MS completed a questionnaire pack that included the Multidimensional Health Locus of Control Scale, the Unidimensional Self-Efficacy Scale for MS (USE-MS), and the World Health Organization Quality of Life Scale—BREF (WHOQoL-BREF). The relationship between LOC and QoL was examined within a structural equation model (SEM). Results: In the total sample, self-efficacy was found to fully mediate the relationship between LOC and QoL for both internal (ILOC) and CLOC orientations. Powerful others LOC (PLOC) had no association with QoL. The same results were found for the relationship of LOC to functioning. In the secondary progressive MS subgroup, the relationship between CLOC and QoL was only partially mediated by self-efficacy. Conclusions: LOC influences QoL through its impact on self-efficacy, one of several potentially mediating factors between LOC and QoL in MS. Disability did not moderate the associations of LOC, but moderation of the CLOC-QoL relationship by disease subtype was found. Psychological training to improve self-efficacy in MS may be particularly useful in those subgroups where LOC-QoL is largely mediated by self-efficacy. Full article

Introduction: Approximately 80% of individuals with multiple sclerosis (MS) have a positive response to autologous hematopoietic stem cell transplantation (aHSCT). Markers that may predict the transplant outcome are necessary. The objective of this work is to identify markers that may refine the selection of patients with multiple sclerosis who could benefit from aHSCT. Methods: We evaluated the levels of six biomarkers in the peripheral blood of patients with MS before aHSCT. The design of this study is cross-sectional; patients were divided into two transplant-responses-at-12-months groups, responders (ΔEDSS < 0) and non-responders (ΔEDSS > 0). Pre-transplant samples were used to assess the different markers. Results: Thirty-four patients were enrolled: fourteen were non-responders and twenty were responders to aHSCT. Among the evaluated biomarkers, a significant difference was only detected in miR-146a levels, with increased values in the non-responder group. Conclusions: The biomarker miR146a could be useful to evaluate the response to aHSCT in patients with MS. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The gut microbiota, a community of microorganisms in the digestive tract, has recently been implicated in ALS pathogenesis through its influence on neuroinflammation and metabolic pathways. This review explores the potential role of digestive microbiota and its metabolites in ALS progression and investigates therapeutic approaches targeting gut microbiota. Methods: A comprehensive review of the current literature was conducted to assess the relationship between gut microbiota composition, microbial metabolites, and ALS progression in patients. We searched for published reports on microbiota composition, microbial metabolites, and ALS, emphasizing the complex interplay between dysbiosis, neuroinflammation, and systemic metabolism. Special emphasis was placed on studies exploring short-chain fatty acids (SCFAs), bacterial amyloids (curli-like factors), and neurotoxins such as β-methylamino-L-alanine (BMAA). The role of the liver–gut axis was evaluated as well. The potential changes in microbiota would sustain the rationale for therapeutic strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions. Results: ALS patients exhibit gut dysbiosis, characterized by reduced SCFA-producing bacteria and an increase in potentially pathogenic genera. Of note, different studies do not agree on common patterns of microbiota being linked to ALS, supporting the need for further, more extensive studies. Dysbiosis sometimes correlates with systemic inflammation and disrupted liver function, amplifying neuroinflammatory responses. Key microbial metabolites, including SCFAs, bacterial amyloids, and BMAA, may exacerbate motor neuron degeneration by promoting protein misfolding, oxidative stress, and neuroinflammation. Emerging therapeutic strategies, including probiotics and FMT, show potential in restoring microbial balance, although clinical data in ALS patients remain limited. Conclusions: The gut microbiota could modulate neuroinflammation and systemic metabolism in ALS. Microbiota-targeted therapies, such as probiotics and dietary interventions, represent promising avenues for mitigating disease progression. Further research is required to validate these interventions through large-scale, longitudinal studies and to develop personalized microbiota-based treatments tailored to individual ALS phenotypes. Full article

Background: The 2011 Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria include both patients at risk of progression and those with mild non-progressive forms of SSc. Early diastolic and systolic dysfunction can indicate myocardial fibrosis in SSc patients, yet data on myocardial impairment in the VEDOSS population are limited. Objectives: This study aimed to identify subclinical echocardiographic changes and predictive markers of cardiac dysfunction in both very early and mild-longstanding forms of VEDOSS. Methods: We conducted a cross-sectional observational study involving 61 patients meeting VEDOSS criteria followed up regularly within our Scleroderma referral center. Patients were categorized as early VEDOSS (e-VEDOSS) or mild-longstanding VEDOSS (ml-VEDOSS) based on disease duration (≥10 years). We analyzed clinical and demographic data, focusing on echocardiographic parameters such as the E/A ratio and left ventricular (LV) thickness. Statistical analyses included chi-square, Fischer exact, and student’s t tests, with a significance threshold of p < 0.05. Results: ml-VEDOSS patients were older and reported a higher burden of comorbidities. Autoantibody-positive patients exhibited lower E/A ratios and increased left atrial size. Late nailfold videocapillaroscopic pattern patients exhibited increased PWED thickening and aortic valve insufficiency. Notably, patients undergoing vasodilators experienced larger right atrial volume, while patients receiving Renin-Angiotensin-Aldosterone System (RAAS) inhibitors reported reduced E/A ratio. Multivariable analysis confirmed DLCO% as the sole predictor of both diastolic and systolic impairment in VEDOSS population. Conclusions: Careful monitoring of cardiac function in VEDOSS patients is crucial as subclinical alterations may occur even in the absence of symptoms. DLCO% emerged as an important predictor of LV diastolic dysfunction. Full article

Apolipoprotein L1 (APOL1) genetic variations, notably the G1 and G2 alleles, have important roles in the pathophysiology of focal segmental glomerulosclerosis (FSGS) and other kidney problems, especially in people of African descent. This review summarizes current understanding about the genetic, molecular, and clinical features of APOL1-associated FSGS and investigates new therapeutic options. It reveals how APOL1 mutations generate kidney injury through mechanisms such as podocyte dysfunction, mitochondrial impairment, and dysregulated inflammatory networks. Recent treatment developments, such as small-molecule inhibitors like inaxaplin, antisense oligonucleotides, and novel interventions targeting lipid metabolism and inflammatory pathways, are being assessed for their capacity to address the specific issues presented by APOL1-associated nephropathy. We also address gaps in knowledge, such as the function of environmental triggers and the systemic consequences of APOL1 mutations, emphasizing the significance of targeted research. Full article

Background: Systemic sclerosis (SSc), also known as scleroderma, is a complex, chronic autoimmune disease characterized by fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The treatment of SSc has historically focused on symptom management and slowing down disease progression through conventional immune-suppressive agents. New therapeutic approaches have been emerging due to advances in understanding of the disease mechanisms, particularly in the areas of fibrosis, vascular involvement, and immune dysregulation. Methods: In this review of the literature, we discuss the current stage of development of B-cell-depleting immune therapies in SSc. Results: B-cell depletion therapy has become an area of growing interest in the treatment of SSc due to the role played by B cells in the pathogenesis of the disease. There is increasing evidence that B cells contribute to disease progression through multiple mechanisms. B cells in SSc are implicated in autoantibody production, cytokine production, and fibroblast activation. B cells are responsible for producing autoantibodies, such as anti-topoisomerase I (Scl-70) and anti-centromere antibodies, which are hallmarks of SSc. B cells release pro-inflammatory cytokines (such as interleukin-6 [IL-6] and transforming growth factor β [TGF-β]), which promote fibrosis and inflammation, they also contribute to the activation of fibroblasts, the cells responsible for excessive collagen production and fibrosis, a key feature of SSc. Conclusions: In light of these findings, therapies that target B cells are being investigated for their potential to modify the disease course in SSc, particularly by reducing autoantibody production, inflammation, and fibrosis. Full article

Background: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). Despite the availability of interventions for disease exacerbations and symptomatic management, EM remained without a cure. Oxidative stress has been implicated in the MS demyelination mechanism. Adjuvant therapies like α-lipoic acid (ALA) have garnered interest for their potential to mitigate oxidative damage and control MS symptoms. ALA is found naturally in vegetables and red meat and can also be synthesized in mitochondria through enzymatic reactions involving octanoic acid and cysteine. However, its bioavailability from dietary sources is limited, prompting an investigation into supplemental forms. We conducted a systematic review and meta-analysis to assess the effect of ALA on disability in randomized clinical trials (RCTs) for MS. Methods: Records were searched until June 2023 (CRD42023397760). Five RCTs evaluated ALA’s effect on MS progression using the Expanded Disability Status Scale (EDSS). The quality of evidence was assessed using GRADE, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Following the selection process, five studies were included involving 179 patients (87 placebo and 92 ALA). Oral administration of racemic ALA (R/S-ALA) at 600 mg twice daily reduced EDSS, indicating a potential for ALA supplementation to mitigate MS disability. The North American trials (SPMS patients) did not show heterogeneity, while Asian studies (RRMS patients) were moderated. The quality of evidence was high without publication bias. Conclusions: ALA treatment reduce EDSS scores. However, further studies are warranted to establish the role of ALA as an adjuvant in clinical practice in long-term follow-up (>2 years) RCTs. Full article

Background/Objectives: Footfall placement variability is associated with falls in older adults and neurological diseases. Thus, the study of dual-task gait impairment in middle-aged to older-aged adults with multiple sclerosis (MS) is clinically relevant, particularly in environments that mimic the obstacles experienced in daily ambulation. Methods: A total of 10 middle-aged to older-aged adults with MS (eight female, mean ± SD age = 56 ± 5 years), 12 healthy older adults (HOAs, nine female, age = 63 ± 4 years), and 10 healthy young adults (HYAs, five female, age = 22 ± 3) were asked to perform cued walking (CW) or obstacle walking (OW) tasks without or with a concurrent backward alphabet recitation task (CWT, OWT), or dual tasks. Gait performance and attentional demands were measured using hit rate, stride velocity, footfall placement bias and variance, and prefrontal cortex (PFC) oxygenated hemoglobin HbO levels. Results: A significant dual-task condition-by-cohort interaction was seen in footfall placement bias and variance as indicated by a higher footfall placement bias and variance in dual-task vs. single-task conditions seen in HOAs, in comparison to HYAs and adults with MS. Further, a significant walking condition-by-cohort interaction was seen in the HbO levels as indicated by the higher PFC HbO levels seen in OW vs. CW in adults with MS, compared to adults without MS. Conclusions: The decreased accuracy and increased attention in footfall placement to visual cues on the ground observed in adults with MS and HOAs, relative to HYAs, may provide a marker for gait impairment and fall risk in older adults with MS. Full article

Background/Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease marked by inflammatory demyelination in the central nervous system, leading to debilitating spasticity. Managing spasticity in MS remains a challenge, and intrathecal baclofen (ITB) therapy has emerged as a potential targeted treatment. This systematic review investigated the efficacy of ITB pumps in managing MS-related spasticity and explored their immunomodulatory effects. Methods: This review adhered to PRISMA guidelines and was submitted for registration retrospectively with the Open Science Foundation. A comprehensive literature search was conducted in PubMed, Embase, Scopus, and Web of Science from January 2013 to August 2024. Studies were included if they examined adult MS patients receiving ITB for spasticity, reporting outcomes related to spasticity and quality of life. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools, and findings were synthesized narratively. Results: Eight studies (n = 723 participants) met inclusion criteria. ITB was associated with significant reductions in spasticity severity and improvements in quality of life, with reduced reliance on oral antispasticity medications. Immunologically, ITB has demonstrated potential in modulating inflammatory pathways, downregulating pro-inflammatory cytokines, and shifting immune responses toward an anti-inflammatory profile. Common complications included catheter-related issues and infections, with low overall complication rates. Sensitivity analyses indicated robustness in outcomes across higher-quality studies. Conclusions: ITB pumps are effective in controlling spasticity and offer additional immunological benefits for MS patients. Further research should explore ITB’s long-term immunomodulatory effects and its potential in combined therapeutic strategies. The review was not financially supported, and no conflicts of interest were declared by the authors. Full article

Background: Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are, in essence, neurodegenerative disorders with significant individual, social, and economic burdens worldwide. Despite having different clinical onset and evolution, the two diseases share common risk factors and underlying pathophysiological mechanisms. Environmental risk factors are particularly interesting, considering the available effective counter strategies. High-fat diets remain a significant element that negatively impacts the onset and evolution of several disorders, including ALS and MS. Focusing on changeable disease-related aspects is increasingly appealing in the context of a lack of an effective treatment. Methods: This review aims to offer an updated overview of the influence of high-fat diets in modulating the risk of onset and progression of ALS and MS, based on the search of three relevant online databases. Results: In the first part, the shared pathophysiological mechanisms of ALS and MS are shown, and significant differences between the two disorders are highlighted. Subsequently, the most relevant research on this topic conducted in animal models and humans is presented, bringing additional proof of the critical role of high-fat diets in neurodegeneration. Finally, based on current knowledge, the authors offer potential therapeutic approaches and future relevant research directions to better control nutrition in ALS and MS patients, hoping to increase survival and quality of life. Conclusions: High-fat diets negatively impact the onset and evolution of ALS and MS. Full article

Background/Objectives: People with multiple sclerosis (MS) often experience sensory, psychomotor, and cognitive impairment, sphincter disturbances, and fatigue, which can affect their ability to perform work-related tasks, self-care, and daily activities. This study aimed to analyze the lifestyle changes, cognitive function, and disability outcomes over a seven-year follow-up period, exploring potential associations with predictive markers. Methods: At the end of the seven-year follow-up period, 32 participants returned for cognitive and clinical reassessment with the Twenty-Five-Foot Walk Test, Nine-Hole Peg Test, and Brief Repeatable Neuropsychological Battery. Lifestyle data were acquired via interviews regarding sleep quality, reading habits, technology use, physical activity levels, household responsibilities, and participation in leisure and cultural activities. Results: The occupational profile did not demonstrate significant changes, but 11 (34%) participants showed disability accumulation, and the number of relapses increased (p = 0.001). Over time, improvement was observed in verbal episodic memory and worsening in psychomotor speed. Better cognitive performance in mental agility was associated with higher levels of physical activity (p = 0.021) and technology use (p = 0.039). In addition, better cognition (verbal memory p = 0.038 and processing speed 0.015) and psychomotor speed (upper limbs p = 0.017 and lower limbs p = 0.003) and lower functional disability (p = 0.022) were associated with maintenance of household activities. Conclusions: The changes in verbal memory and psychomotor speed were more prominent over time, and verbal memory, psychomotor and processing speed, and mental agility were associated with good lifestyle habits, mainly household activities. The treatment strategies should include lifestyle changes and pharmacological interventions. Full article

Collagen export from the endoplasmic reticulum is required for normal tissue homeostasis, and yet, in fibrotic disorders, this process is significantly upregulated. In this review, we will focus on the signaling cascade from the inflammasome and how that promotes collagen via proinflammatory/profibrotic cytokines. Concordantly, these cytokines also induce the expression of TANGO1 to cope with the increased movement of collagen through the endoplasmic reticulum. In normal and fibrotic cells, this pathway is finely tuned to meet the necessary demand in collagen export. Currently, the role of TANGO1 in fibrotic disorders and how the inflammasome induces its expression is not well understood. In this review, we will assimilate the current information concerning inflammasome activation and how it induces TANGO1 expression, leading to fibrosis. Full article

Background/Objectives. Social cognition (SC), which implies the emotional and intellectual understanding of oneself and others, is an important facet of neuropsychological functioning concurrently to academic cognition (AC), which concerns non-social abilities (memory, language…). In relapsing-remitting multiple sclerosis (RRMS), it is not clear whether a cognitive decline occurs in both SC and AC nor whether a link exists between these two cognitive domains. The objective of the present longitudinal study was to conduct an extensive examination of both AC and SC in RRMS to document a 2-year evolution and to look for potential correlations between AC and SC. Methods. The neuropsychological results (AC and SC) of 48 RRMS patients obtained in clinical practice were retrospectively considered; 38 of the patients (30 females) were assessed again about 2 years later. Non-parametric tests were applied to test the intra-group cognitive evolution (Wilcoxon) and the link between AC and SC evolution (Spearman). Results. Whereas AC showed a stability or an improvement of performances during the retest, SC presented the reverse pattern, with a stability or a significant decline in facial emotion (recognition and discrimination) and humor perception. No significant statistical correlation was found between the significant modification of AC and SC during follow-up. Conclusions. The short-term deleterious evolution observed selectively for SC in the present study suggests that SC should be selected as a cognitive marker for RRMS follow-up, and that extensive examination may be preferred to investigate specific SC changes. Full article

The origins of multiple sclerosis (MS) have been a subject intriguing researchers and scholars for generations. The multifactorial etiological nature of the disease continues to be studied as a complex combination of genetic aspects and environmental or external risk elements contributing to the development of the disease. Descriptions of symptoms or clinical disorders suggestive of MS affecting historical figures or prominent individuals (i.e., Lidwina of Schiedam, Heinrich Heine, Augustus d’Este) did not provide clues on the origin of the disease, except for the observation that all these early possible cases were white European individuals. MS was initially framed as a neurological entity and named in the 19th century by the historical participation of the French masters Cruveilhier, Vulpian, and Charcot, among others, but the question of how the disease originated was not addressed until Charles Poser raised his conjecture on the origins of MS in two historical essays (1994 and 1995), raising the question if the Viking voyages and invasions from the 8th to the 11th century carried the Scandinavian MS genetic risk factor to Europe and the rest of the known world at that time. Poser did not have the benefit of access to ancient molecular DNA data and based his theoretical postulation on interesting historical and archeological observations. A series of studies and opinions published in 2024, utilizing sophisticated genetic analyses and genome identification, archeological DNA analysis, and other advanced techniques and biological computation, distinctly demonstrate the installation of HLA-DRB1*15:01 (class II allele) in Europe (with a higher prevalence in Scandinavia) following the massive Yamnaya pastoralists migration from the Pontic Steppe in Eurasia to western Europe (~5000 to 2500 BCE). The data suggest HLA-DRB1*15:01, the strongest genetic association with MS, underwent an evolutive switch (“thrifty drift”) from immune protector against novel zoonotic diseases appearing among the early pastoralists of the Yamnaya civilization to an autoimmune deleterious reactor to molecular mimicry and self-antigens, enabled by lifestyle changes and reduction of pastoralism once communities settled in Europe after the migration from the Pontic Steppe. This writer offers a new perspective on the origins of MS through a phase 1, the ancient east to west migration in the late Bronze Age, consolidating the HLA-DRB1*15:01 haplotype in Europe, and phase 2, the additional dissemination of the genetic MS risk through the Viking invasions, reinforcing inheritability by enabling a homozygous dominant inheritance. Full article

Introduction: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to features of multiple sclerosis (MS); yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N = 924) participated in an online survey through the National MS Society listserv. Structural equation modeling was used to examine the direct and indirect effects of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity, and interference) via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had an excellent fit (GFI = 0.998). Lifetime stressors had a direct relationship with MS severity (β = 0.27, p < 0.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of the mediation was significant (β = 0.45). Conclusions: This work provides foundational evidence to inform the conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate the effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve the disease course. Full article

Background: Systemic sclerosis (SSc) represents a multidimensional disease affecting various organs and systems, with the common denominator being the vascular pathology encountered in the micro- and macrocirculation of SSc patients. Recently, much progress has been made toward understanding the molecular basis of endothelial injury and subsequent fibroblast activation, thus paving the way for specific therapy that can target and counteract these processes. Aim: In this review, we examined the latest preclinical and clinical data on therapeutic options to address vascular abnormalities in SSc. Results: We discuss the efficacy of current treatments, including pharmacological agents and emerging therapies, in mitigating vascular damage and improving patient outcomes based on preclinical models and clinical trials that offer evidence of their safety and effectiveness. Conclusions: Although promising therapeutic strategies emerge, optimizing the management of vascular abnormalities in SSc requires further research. Full article