Sclerosis, Volume 3, Issue 3 (September 2025) – 6 articles

Background: Systemic sclerosis is a systemic autoimmune disease that also impacts women’s health in very different ways. Methods: This review summarises the most important data on sexuality, fertility, pregnancy, and menopause from the last 10 years. Findings: We identified nine articles with data on sexuality and a prevalence of sexual dysfunction varying between 46 and 90%. Fertility was examined in six studies, with evidence for a negative influence at least on ovarian reserve. With regard to menopause, only three studies are mentioned that show an increased risk for premature menopause in SSc women. Although pregnancies are rare in SSc women after disease onset, there is growing evidence that pregnancies are feasible but go along with a higher maternal and foetal risk compared to healthy controls. Interpretation: SSc is dominated by female gender, but aspects of women’s health influenced by the disease are still often ignored. The treating physician should be aware of the mostly negative impact on sexuality, fertility, and pregnancy and address these topics with the patients to adapt treatment and follow-up examinations to the patients’ complaints and life situation. Full article

Objectives: Systemic sclerosis-related interstitial lung disease (SSc-ILD) has high associated morbidity and mortality. With early diagnosis and treatment, we can improve clinical outcomes with immunosuppression. Some patients develop progressive pulmonary fibrosis (PPF) and are eligible for anti-fibrotic therapy. There are limited data on the incidence and prevalence of PPF in the SSc ILD cohort to guide case finding. We investigated this using data from UK tertiary Rheumatology and ILD centres. Methods: Patients with systemic sclerosis across two UK rheumatology units were identified using electronic records searched from 2021 to 2023 and were compared against established PPF diagnostic criteria. Results: 255 patients were identified. Prevalence of PPF was 5.49% and in those with established SSc-ILD, 23%. Median time to development of PPF was 5 years. In 64% of patients with PPF diagnosis, they had had systemic sclerosis for over 10 years. Incidence of PPF in patients with SSc was 3.9% and in those with known SSc-ILD 16.%. Only 50% of patients who met criteria for PPF had been referred to respiratory for consideration of antifibrotic initiation. Patients with a predominantly fibrotic baseline radiological pattern (UIP) had a trend towards development of PPF (p = 0.07). No patient with a predominantly inflammatory baseline pattern developed PPF (p = 0.021). Conclusions: Real world data have shown a prevalence of PPF in the SSc-ILD cohort of 23% with a median time of 5 years to development from diagnosis of SSc. Our data show active case finding may be incomplete and rheumatologists must be cognisant of PPF when evaluating patients with SSc. Full article

Focal and segmental glomerulosclerosis (FSGS) describes a histological pattern of injury seen by light microscopy in kidney biopsy specimens and is the end result of various injuries to the podocyte. Our understanding of this disease entity has evolved greatly since it was first described, with particular focus on changes in the classification of FSGS as a disease entity and expansion in our understanding of the underlying pathophysiology. The incidence and prevalence of FSGS and FSGS-associated end-stage kidney disease (ESKD) have increased globally, particularly in the United States; it is now the most common primary glomerular disorder in those with ESKD. APOL-1 is likely responsible for this epidemiological trend in kidney disease in the US and is an important focus of clinical trials and potential targeted therapies. Currently, the goal of treatment in FSGS is to achieve remission of proteinuria and to prevent progression to ESKD. Remission is achieved by using immunosuppressive therapies in primary FSGS, but treatment in secondary and genetic FSGS is largely supportive. Recurrent FSGS (rFSGS) post-transplantation remains a significant clinical challenge to nephrologists; current monitoring and treatment strategies are based on retrospective meta-analysis and observational studies with no clear consensus as to the optimum approach. Emerging therapies are focused on developing more targeted interventions in genetic and secondary FSGS. This review article aims to comprehensively explore this multifaceted disease entity. Full article

Introduction: Timed Twenty-Five Foot Walk (T25FW) and Patient-Determined Disease Steps (PDDSs) are measures commonly used for people with MS (PwMS). However, there is limited knowledge about the utility of using the measures to customize interventions. Aim: This exploratory study aimed to assess the correlation between T25FW and PDDS among PwMS enrolled in the Tele-Exercise and Multiple Sclerosis (TEAMS) study. Methods: The correlation was examined through a Spearman’s rho statistic for T25FW time and PDDS scores. Associations between TEAMS Intervention levels (T25FW baseline benchmarks: <6 s, 6–7.99 s, >8 s, unable to complete) and the PDDS-modified ranges (0–2, 3–4, 5–6, 7) were examined utilizing a chi-square test with Monte Carlo simulations. Results: The results showed a strong statistically significant positive correlation between the T25FW time and the PDDS scores (r_s = 0.72, p < 0.001). An additional Spearman’s correlation showed strong significant positive correlation between T25FW baseline benchmarks and PDDS-modified ranges used for intervention assignment (r_s = 0.73, p < 0.001). A chi-square with Monte Carlo simulations showed a significant association between the TEAMS Intervention Level and PDDS-modified ranges (p = 0.005). Conclusion: In conclusions, the findings suggest that T25FW, when considered with PDDSs, might offer some utility in supporting clinicians as they develop intervention strategies that consider both subjective and objective aspects. These findings also highlight the potential for integrated use of both tools in clinical decision-making, program design, and tailoring interventions to meet individual functional capabilities and self-reported disability in PwMS. Full article

Background: Falls are common among individuals with multiple sclerosis (MS), yet standard clinical mobility assessments—such as the Timed Up and Go (TUG)—may not fully capture the complexities of real-world ambulation, leading to suboptimal fall identification. There is a critical need to evaluate the ecological validity of these assessments and identify alternative tests that better reflect real-world mobility and more accurately detect falls. This study examined the ecological validity of the TUG and novel dual-task clinical assessments by comparing laboratory-based gait metrics to community ambulation in individuals with MS and evaluated their ability to identify fallers. Methods: Twenty-seven individuals with MS (age 59.11 ± 10.57) completed the TUG test and three novel dual-task mobility assessments (TUG-extended, 25-foot walk and turn, and Figure 8 walk), each performed concurrently with a phonemic verbal fluency task. After lab assessments, the participants wore accelerometers for three consecutive days. Gait speed and stride regularity data was collected during both the in-lab clinical assessments and identified walking bouts in the community. The participants were stratified as fallers or non-fallers based on self-reported fall history over the previous six months. Findings: Significant differences were observed between the TUG and real-world ambulation for both gait speed (p < 0.01) and stride regularity (p = 0.04). No significant differences were found in gait metrics between real-world ambulation and both the 25-foot walk and turn and TUG-extended. Intraclass correlation coefficient analysis demonstrated good agreement between the 25-foot walk and turn and real-world ambulation for both gait speed (ICC = 0.75) and stride regularity (ICC = 0.81). When comparing the TUG to real-world ambulation, moderate agreement was observed for gait speed (ICC = 0.56) and poor agreement for stride regularity (ICC = 0.41). The 25-foot walk and turn exhibited superior predictive ability of fall status (AUC = 0.76) compared to the TUG (AUC = 0.67). Conclusions: The 25-foot walk and turn demonstrated strong ecological validity. It also exhibited superior predictive ability of fall status compared to the TUG. These findings support the 25-foot walk and turn as a promising tool for assessing mobility and fall risk in MS, warranting further study. Full article

Introduction: Walking is perceived as the most important bodily function for persons with multiple sclerosis (pwMS) and is impaired in more than 70% of pwMS. In addition, the effect of multiple sclerosis (MS) on gait pattern increases in fast walking and during fatiguing exercises, altering the spatiotemporal gait parameters and walking reserve. Objectives: The objective of this study is to investigate the impact of a 12 min intermittent-walking protocol on spatiotemporal gait parameters and on the fatigability of pwMS, as well as the association with perceived exertion and reported symptoms of fatigue. Methods: Twenty-six persons with relapse-remitting MS and twenty-eight healthy controls (HCs) were included in this cross-sectional study. The Modified Fatigue Impact Scale and the Symbol Digit Modality Test were used to evaluate fatigue symptoms and cognitive function, respectively. Participants walked six times during an uninterrupted 2-min period. Before, during the rest periods and after the last 2 min walk, the rate of perceived exertion (RPE) was measured using the Borg Scale, and the spatiotemporal gait parameters were assessed with GaitRite. The cut-off value of 10% deceleration of the distance walked index classified pwMS into two groups: MS Fatigable (MS-F) and MS Non-Fatigable (MS-NF). One-way and two-way Analyses of variance (ANOVAs) were used to verify the effect of time and groups, respectively. Results: PwMS walked slower, travelled shorter distances, and presented shorter step lengths compared to HCs. No effects of the intermittent-walking protocol were found for all pwMS, but the MS-F group had deteriorated walking speed, step length, and cadence. Walking dysfunction was associated with perceived fatigability, reported symptoms of fatigue, cognitive function, and disability. Reported symptoms of fatigue was associated with perceived exertion but not with performance fatigability. Conclusions: Changes in gait parameters were weak to moderately associated with performance fatigability and the perception of effort and disability but not with reported fatigue symptoms, highlighting distinct constructs. The walking speed reserve and step length reserve also emerged as potential early markers of performance decline. Full article