Journal of Scleroderma and Related Disorders最新文献

Objective: The objective of the study is to explore the pathogenic relationship between vasculopathy and fibrosis in systemic sclerosis through expression of vascular biomarkers.

Methods: Plasma biomarkers including panVEGF-A, VEGF-A₁₆₅b and angiopoietins (Ang) and clinical parameters were investigated in 53 systemic sclerosis patients and 15 controls. Biopsies of affected skin from 10 systemic sclerosis patients and 5 controls were used to assess expression of hypoxia-inducible factor (HIF1α, -2α) and VEGF-A isoforms. Vasculopathy was assessed using nailfold capillaroscopy (qualitative pattern and intercapillary distance), reperfusion gradient after ischaemic challenge and ultrasound vascularity index (dorsovolar vascularity index). Skin fibrosis was assessed using skin scores and ultrasound (skin thickness, echogenicity and elastography).

Results: Plasma Ang-2 was increased (p = 0.012) and Ang-1/-2 ratio reduced (p = 0.018) in systemic sclerosis patients compared to controls. Ang-2 progressively increased across nailfold capillaroscopy patterns (p = 0.031) and weakly correlated with intercapillary distance (+0.284, p = 0.05) and reperfusion gradient (-0.356, p = 0.018). Plasma angiopoietins correlated with echogenicity (Ang-1 +0.381, p = 0.006; Ang-2 +0.330, p = 0.022) and elastography (Ang-2 +0.353, p = 0.014). Plasma VEGF-A₁₆₅b correlated with dorsovolar vascularity index (-0.289, p = 0.039). HIF1α and 2α were increased in skin (p = 0.008) with HIF2α predominance. Epidermal HIF2α correlated more strongly with VEGF-A₁₆₅b (+0.709, p = 0.022) than panVEGF-A (+0.552, p = 0.098). Epidermal HIF2α and fibroblast VEGF-A₁₆₅b tended to associate with early and diffuse cutaneous systemic sclerosis. Cutaneous expression of HIF1α (+0.489, p = 0.069) and HIF2α (+0.489, p = 0.064) correlated with intercapillary distance. Epidermal VEGF-A₁₆₅b correlated with skin thickness (-0.672, p = 0.006).

Conclusions: Increased expression of HIFα and antiangiogenic biomarkers associated with both vasculopathy and fibrosis in systemic sclerosis. Our data highlight the conceivable therapeutic targets of dual inhibitory biomarkers such as Ang-2.

Background: Systemic sclerosis (scleroderma) is associated with functional disability and poor quality of life. Patient-reported outcome measures provide valuable insights into patients' experiences, symptoms, and perceptions of their health. The Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Scleroderma Health Assessment Questionnaire (S-HAQ) are widely used patient-reported outcome measures in scleroderma research and clinical care. However, there is lack of data to (a) ensure and document patients with systemic sclerosis understand the concepts contained in these measure and (b) demonstrate face, item, and content validity for these items and measures.

Methods: We conducted cognitive debriefing of the S-HAQ in patients with diffuse cutaneous systemc sclerosis (dcSSc). The S-HAQ includes the HAQ-DI, a 20-item questionnaire that assesses functional ability for performing day-to-day activities, four systemic sclerosis-specific items that assess scleroderma symptoms, and one item on overall scleroderma-related limitations.

Results: The total sample of patients with dcSSc (N = 20) had a mean age of 57.6 years and average disease duration of 3.4 years. For the HAQ-DI, the participants understood the concepts and the items were clear. In addition, majority (60%-100%) of participants reported using aids and devices to perform activities of daily living and/or utilizing assistance from another person. The systemic sclerosis-specific items of the S-HAQ were relevant to participants but required revisions to item wording and response options, including a change from the visual analog scales to numerical rating scales.

Conclusion: The HAQ-DI and S-HAQ systemic sclerosis-specific items demonstrated content and item validity, respectively. Several minor modifications were made to the S-HAQ instructions, item wording, and rating scales.

Background: En coup de sabre (ECDS) is a rare variant of localized scleroderma which can be associated with neurologic symptoms including seizures, focal neurologic deficit, and movement disorders. Little is known about the disease course in ECDS. We describe two patients with a history of localized scleroderma ECDS of the scalp who developed worsening neurologic symptoms coincidental in timing with extension of preexisting skin and skull lesions and evidence of inflammatory pathology on brain biopsy.

Case report: Our first patient was diagnosed with localized scleroderma ECDS at the age of 12. He re-presented at age 34 with progression of his skin lesions, new indentation of the occipital bones, and new neurologic symptoms of ataxia, cranial nerve IV palsy, and cognitive decline. MRI brain revealed multiple lesions that were hyperintense on T2-weighted images, the largest of which was in the left temporal lobe. Brain biopsy pathology was consistent with a lymphocytic inflammatory process. He was treated with pulse steroids and mycophenolate with stabilization of his symptoms and brain lesions on imaging. Our second patient was initially diagnosed with localized scleroderma ECDS at age 46. Concurrently, neuroimaging showed right frontal and temporal lesions that were hyperintense on T2-weighted images in the context of neurologic symptoms of vertigo and headache. At age 50, he developed worsening of existing skin lesions followed by new generalized tonic-clonic seizures and behavioral changes. MRI brain revealed worsening of his brain lesions, and ultimately brain biopsy confirmed focal perivascular lymphocytic reaction consistent with immune-mediated vasculitis. He was treated with pulse steroids and cyclophosphamide with improvement in his symptoms.

Conclusion: Neurologic symptoms associated with localized scleroderma are a rare but well-documented association. These cases highlight the need to consider diffuse intracranial inflammatory pathology, rather than simply localized brain lesions, in ECDS, particularly in instances where skin lesions are progressive.

Objective: Hand functionality in systemic sclerosis is assessed using patient-reported measures. However, the Glittre-ADL test (TGlittre) provides an objective assessment of functional capacity using activities of daily living, including the hand shelf task. The aim of this study was to assess hand functional capacity in women with systemic sclerosis using the TGlittre-Shelf and to correlate it with demographics, body composition, hand function, physical function, digital dexterity, muscle strength, and lung function.

Methods: This was a cross-sectional study in which 41 women with systemic sclerosis and 41 healthy controls underwent the TGlittre-S. They also underwent the following assessments: Cochin Hand Functional Scale, modified Rodnan skin score, Health Assessment Questionnaire Disability Index, 9-hole peg test, handgrip strength, and pulmonary function tests.

Results: The mean age was 51.9 ± 13.7 and 45.9 ± 9.3 years in women with systemic sclerosis and healthy controls, respectively (p = 0.09). Body mass index was 24.4 ± 4.9 and 29.4 ± 5.3 kg/m² in women with systemic sclerosis and healthy controls, respectively (p < 0.0001). TGlittre-S time was higher in women with systemic sclerosis than in healthy controls [60 (55-74) vs 44 (41-49) sec, p < 0.0001]. In addition, 9-hole peg test was higher in women with systemic sclerosis than in healthy controls [24 (22-26) vs 20 (18-22) sec, p < 0.0001]. Similarly, Cochin Hand Functional Scale was higher in women with systemic sclerosis than in healthy controls [6 (0.5-25) vs 0 (0-0) points, p < 0.0001]. In women with systemic sclerosis, TGlittre-S time was significantly correlated with the following variables: handgrip strength (r_s  = -0.511, p = 0.0006), Health Assessment Questionnaire Disability Index (r_s  = 0.510, p = 0.0006), 9-hole peg test (r_s  = 0.398, p = 0.009), and Cochin Hand Functional Scale (r_s  = 0.351, p = 0.024).

Conclusion: In women with systemic sclerosis, there is a deterioration in impaired hand functional capacity as measured by TGlittre-S. In these patients, the longer the TGlittre-S time, the worse the handgrip strength, digital dexterity, and physical function. As TGlittre-S is easy to perform and does not require much space, its incorporation into clinical practice is promising and may be considered as an outcome measure for future studies in systemic sclerosis.

Objectives: The use of Janus kinase inhibitors is increasing in systemic sclerosis, a complex autoimmune disease characterized by fibrosis, vasculopathy, and immune dysregulation. In this review, we aimed to examine the studies in the literature reporting on patients with systemic sclerosis treated with Janus kinase inhibitors.

Methods: We performed a search on MEDLINE and Scopus for articles involving patients with systemic sclerosis treated with Janus kinase inhibitors from the inception of these databases through 1 August 2024.

Results: Our literature search revealed 18 articles describing 87 systemic sclerosis patients treated with Janus kinase inhibitors. The median (min-max) age of these patients was 48.5 (13-78) years (F/M = 4.9). The most commonly used Janus kinase inhibitors in systemic sclerosis were tofacitinib (82.8%), followed by baricitinib (13.8%). Janus kinase inhibitors were most commonly used to treat the combination of interstitial lung disease and skin involvement (44.9%), and the combination of gastrointestinal system and skin involvement (38.8%). Improvement rates with Janus kinase inhibitors were 87.5%, and 5.9% of patients on Janus kinase inhibitors relapsed. Adverse events were observed in 50% of systemic sclerosis patients treated with Janus kinase inhibitors. Various infections (21.1%) were the most common adverse event reported following Janus kinase inhibitor use.

Conclusion: Although Janus kinase inhibitors seem to be very effective, especially in patients with systemic sclerosis who have resistant/progressive skin disease, some side effects should not be ignored. Therefore, controlled clinical trials in larger populations are needed on Janus kinase inhibitors use in systemic sclerosis.

Objectives: To assess the frequency and determinants of immunosuppressant medication use in systemic sclerosis and changes in prescribing patterns over time.

Methods: The Australian Scleroderma Cohort Study participants meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for systemic sclerosis with recorded treatment data were included. The Chi-square, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Multivariable logistic regression models were used to establish the determinants of the use of immunosuppressants.

Results: Of 2019 participants, 60% received immunosuppressants, including 81% of those with diffuse systemic sclerosis and 52% of those with limited systemic sclerosis (p < 0.001). Forty-six percent of patients received prednisolone and 40% disease-modifying anti-rheumatic drugs. Immunosuppressant use was more common in those with severe or inflammatory systemic sclerosis features, including interstitial lung disease, synovitis or myositis. Comparing prescribing patterns early in incident systemic sclerosis from 2007-2014 to 2015-2024, disease-modifying anti-rheumatic drug use increased (35% vs 56%, p < 0.001), while prednisolone use decreased (24% vs 17%, p = 0.046). Immunosuppressants were commenced earlier in incident systemic sclerosis in 2015-2024 versus 2007-2014 (1.8 (interquartile range = 1.0-3.2) vs 2.4 (interquartile range = 1.2-4.0) years, p = 0.011). In multivariable modelling, prednisolone use was associated with diffuse systemic sclerosis (odds ratio = 1.8, 95% confidence interval = 1.4-2.2, p < 0.001), interstitial lung disease (odds ratio = 2.1, 95% confidence interval = 1.7-2.5, p < 0.001), myositis (odds ratio = 2.7, 95% confidence interval = 1.8-4.0, p < 0.001), synovitis (odds ratio = 2.2, 95% confidence interval = 1.8-2.6, p < 0.001) and systemic sclerosis heart involvement (odds ratio = 1.4, 95% confidence interval = 1.0-2.0, p = 0.044). Disease-modifying anti-rheumatic drug exposure was associated with diffuse systemic sclerosis (odds ratio = 2.7, 95% confidence interval = 2.1-3.4, p < 0.001), interstitial lung disease (odds ratio = 2.2, 95% confidence interval = 1.7-2.7, p < 0.001), myositis (odds ratio = 3.6, 95% confidence interval = 2.4-5.5, p < 0.001) and synovitis (odds ratio = 4.2, 95% confidence interval = 3.5-5.2, p < 0.001) and inversely associated with age (odds ratio = 0.7, 95% confidence interval = 0.5-0.8, p < 0.01) and pulmonary arterial hypertension (odds ratio = 0.5, 95% confidence interval = 0.4-0.7, p < 0.001). In subgroups with diffuse systemic sclerosis and limited systemic sclerosis and different autoantibody profiles, findings were generally similar, with interstitial lung disease, synovitis and myositis tending to be associated with prednisolone and/or disease-modifying anti-rheumatic drug use, as was systemic sclero

Background: The study was conducted to investigate the impact of systemic sclerosis (SSc) on hospitalized COVID-19 patients.

Method: This retrospective observational study analyzed data from the National Inpatient Survey (NIS) in 2021. Patients hospitalized with COVID-19 were categorized into SSc and non-SSc groups. Characteristics of patients and comorbidities were compared. The primary outcome was the mortality rate. Secondary outcomes included resource utilization and acute in-hospital complications of SSc. Multivariate logistic regression analyses were conducted, with p-values < 0.05 considered statistically significant.

Result: Of all, 1865 patients hospitalized with COVID-19 had SSc. Patients with SSc had a higher mortality risk (aOR = 1.37 [1.03-1.82]; p = 0.032). The average cost of hospitalization was significantly higher in the SSc group (p = 0.048), with no difference in LOS (9.4 ± 0.65 days vs 8.4 ± 0.03 days; p = 0.260). COVID-19 patients with SSc significantly had a higher risk for DIC (aOR 2.82 [1.06-7.53]; p = 0.038), left-sided HF (aOR 1.76 [1.16-2.67]; p = 0.008), ventricular arrhythmia (aOR 3.17 [1.01-9.89]; p = 0.047), oxygen dependence (aOR 2.41 [1.64-3.55]; p < 0.001), cardiac arrest (aOR 2.61 [1.63-4.18]; p < 0.001), and ileus (aOR 2.61 [1.45-4.69]; p = 0.001).

Conclusion: Hospitalized COVID-19 patients with SSc were more likely to develop in-hospital complications and had a higher mortality risk.

Digital ulcers are a major source of pain and disability in patients with systemic sclerosis. Current treatments are not ideal, yet drug development for digital ulcers is hampered by a lack of objective outcome measures to facilitate clinical trials. Advances in non-invasive imaging could provide a way forward. This review article first describes the rationale for non-invasive imaging of digital ulcers in both clinical practice and research. In clinical practice, magnetic resonance imaging allows early diagnosis of underlying osteomyelitis, and smartphone imaging allows early (remote) identification of digital ulcers. In research, non-invasive imaging provides new insights into pathophysiology, as well as the ability to measure precisely digital ulcer surface area and volume. The imaging techniques discussed include mobile phone photography, ultrasound, laser Doppler methods and emerging technologies (multispectral imaging and polarisation-sensitive optical coherence tomography). Between them, these methods hold promise as outcome measures for early and later phase trials, but first require full validation.

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by progressive fibrosis, vasculopathy, and immune dysregulation. The disease commonly presents with Raynaud's phenomenon and skin thickening, commonly of the upper limb. Isolated lower extremity presentation is uncommon and often misdiagnosed. This diagnostic uncertainty may lead to delayed recognition and increased morbidity, particularly when SSc mimics lymphedema in the early stages. We report a case of a 61-year-old female who initially presented with lower extremity swelling and was misdiagnosed with primary lymphedema. Despite treatment with diuretics and compression therapy, her symptoms progressed to involve her upper extremities, prompting further evaluation. Physical examination revealed non-pitting lower extremity scleroderma, sclerodactyly, puffy hands, and nailfold capillary abnormalities. Laboratory workup was positive for anti-RNA polymerase III antibodies, a marker associated with an increased risk of scleroderma renal crisis. The patient developed scleroderma renal crisis after a delayed diagnosis, necessitating hospital admission and initiation of angiotensin-converting enzyme inhibitors. This case highlights the challenges in distinguishing early lower extremity SSc from lymphedema. Early identification of atypical SSc presentations is critical to be cognizant of life-threatening complications such as scleroderma renal crisis. Clinicians should maintain a high index of suspicion for SSc in patients with persistent non-pitting lower extremity swelling, skin thickening, and abnormal capillaroscopy findings, even in the absence of initial upper limb involvement.

Systemic sclerosis is a rare autoimmune disease characterized by progressive fibrosis, microvascular dysfunction, and chronic inflammation, leading to significant functional and aesthetic impairments, particularly in the face and hands. Current therapeutic strategies are limited in their ability to reverse established skin fibrosis, prompting interest in regenerative approaches such as autologous fat grafting. Lipofilling and nanofat techniques, originally developed for volume restoration and skin rejuvenation, have demonstrated promising outcomes in improving skin texture, elasticity, and vascularization through mechanisms involving adipose-derived stem cells and stromal vascular fraction. This editorial reviews the available randomized controlled trials evaluating nanofat and lipofilling in the treatment of cutaneous manifestations of systemic sclerosis. A literature search identified four randomized controlled trials meeting inclusion criteria, primarily focused on facial fat grafting with or without platelet-rich plasma in corticosteroid-resistant patients. Although subjective improvements in skin quality were reported, methodological variability, small sample sizes, and non-standardized techniques limit the generalizability of findings. Given the autologous and minimally invasive nature of fat grafting, it represents a potentially valuable adjunct treatment for systemic sclerosis. However, further research, including multicenter registries and standardized protocols, is essential to better define its clinical utility and optimize outcomes in this complex disease.