Journal of Scleroderma and Related Disorders最新文献

Introduction: Digital ulcers (DUs) stand out as one of the most prevalent and clinically meaningful manifestations of systemic sclerosis (SSc) and are associated with significant morbidity. While systemic (pharmacological) therapy is currently established as the 'standard of care', effective local ulcer management remains crucial for all cases of DUs. This is particularly true for patients who cannot tolerate systemic treatments or in the case of refractory SSc-DUs. On this background, there is a pressing demand for the formulation of evidence-based guidelines to assist clinicians and patients in navigating the local treatment options for DUs.

Methods: A steering committee of international experts was established by the World Scleorderma Foundation (WSF) Digital Ulcer (DU) ad hoc committee. Two systematic literature reviews on local non-surgical and surgical treatments for the management of SSc-DUs were performed to inform the development of local treatment recommendations for SSc-DUs. Consensus methodology was used to develop the final treatment recommendations.

Results: Six overarching treatment principles and eight local treatment recommendations (five non-surgical and three surgical) were agreed upon for the management of SSc-DU. Among topical non-surgical options, botulin toxin can be conditionally recommended for refractory and/or severe DUs. Among surgical treatments, autologous adipose tissue grafting might be recommended for DU healing when combined with background systemic treatments.

Conclusion: These recommendations are specifically tailored to guide treatment decisions concerning both local and non-pharmacological approaches to managing SSc-related DUs. Our work has highlighted a notable quality gap in comparison to systemic treatments, underscoring the scarcity of high-quality studies concerning this topic.

Introduction: The objective of this investigation was to reveal abnormal musculoskeletal ultrasonographic (US) findings in the hand and wrist joints of systemic sclerosis (SSc) patients compared to healthy controls and to determine the severity of synovitis and tenosynovitis, as well as to disclose the demographic, clinical, and serologic characteristics of patients with SSc with synovitis.

Methods: The current study is a cross-sectional study comparing 50 SSc patients and 50 healthy controls between February and September 2023. Metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP), and wrist joints were evaluated with US.

Results: Synovitis (24 (48%) vs 6 (12%), p < .001), synovial hypertrophy (19 (38%) vs 1 (2%), p < .001), tenosynovitis (22 (44%) vs 5 (10%), p < .001), and calcinosis (7 (14%) vs 0, p = .012) were more common in SSc patients than in healthy controls. The presence of osteophytes was also more frequent in SSc patients but not statistically significant (36 (72%) vs 27 (54%), p = .062). The frequencies of moderate to severe synovitis and tenosynovitis were similar in the two groups, whereas mild synovitis (44% vs 12%, p < .001) and tenosynovitis (38% vs 8%, p < .001) were more common in SSc patients. The wrist was the most affected joint. Patients with synovitis had a higher mean age (p = .007) and erythrocyte sedimentation rate (ESR; p = .025). The presence of high c-reactive protein (CRP; p = .039) and hydroxychloroquine use (p = .024) were more common in these patients. There was no difference between the frequency of arthralgia in patients with and without synovitis.

Conclusions: Synovitis, tenosynovitis, and synovial hypertrophy seem to be quite common in SSc patients with or without arthralgia. Patients with synovitis are older, and acute phase markers may be higher in these patients.

Background: Hypogammaglobulinemia is a condition that can be related to both primary and secondary immunodeficiencies. While the role of primary immunodeficiency in immune-mediated diseases is well known, its occurrence in systemic sclerosis is not reported.

Objectives: This study aims to describe the clinical features associated with hypogammaglobulinemia in a cohort of limited cutaneous systemic sclerosis patients.

Methods: We retrospectively reviewed medical records of systemic sclerosis patients from two Italian referral centres (2010-2024). Included patients had limited cutaneous systemic sclerosis and presented reduced serum concentrations of one or more Ig isotypes (IgG < 700 mg/dL, IgA < 70 mg/dL or IgM < 50 mg/dL) in at least two separate measurements. Patients with secondary causes of hypogammaglobulinemia were excluded. Data collected included demographics, clinical features, Ig levels, infection history and comorbidities.

Results: We identified 30 systemic sclerosis patients (93% female, mean age 62 years) with limited cutaneous involvement and hypogammaglobulinemia. Most patients were positive for anti-centromere antibodies and received periodic intravenous infusions of prostaglandin analogues. No patient received immunosuppressive therapy. Median (interquartile range) serum IgG levels 519.5 (175) mg/dL, median IgA 65.5 (48) mg/dL and median IgM 71.5 (49) mg/dL. Four patients who met the European Society for Immunodeficiencies (ESID) criteria for common variable immunodeficiency experienced recurrent infections and had associated immune-mediated diseases. Five patients had selective IgA deficiency, with frequent immune-mediated comorbidities (thyroiditis, Sjögren's syndrome, arthritis, psoriasis). The other patients exhibited mild IgG deficiency without a significant infectious history.

Conclusions: This is the first study describing a cohort of patients with limited cutaneous systemic sclerosis and hypogammaglobulinemia. Our population presented a high prevalence of immune-mediated comorbidities but low infection rates. Further research is needed to explore the underlying mechanisms and clinical significance of hypogammaglobulinemia in these patients.

Objectives: Digital ulcers (DUs) are a major cause of pain and disability in systemic sclerosis (SSc) patients and remain a major treatment challenge. Our aim was to explore clinicians' perspectives towards treatment initiation and escalation, akin to a 'Treat to Target' (T2T) strategy.

Methods: SSc clinicians were invited to participate in an online survey.

Results: A total of 173 responses (75% rheumatologists) were obtained from 33 countries. When initiating a change in oral drug therapy for SSc-DUs, most (80%) respondents would consider adding new medication to existing treatment, and 50% would increase existing treatment dose. Time to assess the impact of treatment change varied considerably, with around half (43.6%) waiting 1 month. Endothelin receptor antagonists, phosphodiesterase type-5 inhibitors and prostanoids were considered most efficacious for DU prevention, with good perceived efficacy from calcium channel blockers and moderate benefit from anti-platelet agents and immunosuppression. Side effects (e.g. headache and peripheral oedema) are perceived to be a significant issue with oral vasodilatory/vasoactive therapies in many patients. The highest rated T2T targets were (1) complete absence of new/recurrent DUs (63%), (2) reduction >50% in the number of DU recurrence (52%) and (3) reduction in DU healing time (37%) and reduction in DU pain >50% (37%). The most frequent reasons for hospitalisation were to administer intravenous treatment (91%) and DU complications (87%). Surgery is reserved for the threatened digit (e.g. gangrene), underlying calcinosis and failure of medical therapy.

Conclusion: Significant heterogeneity currently exists concerning treatment initiation and escalation for SSc-DUs, potentially amenable to a T2T strategy.

Objective: Systemic sclerosis is characterized by vasculopathy at the microvascular level and less commonly the macrovascular level. The vasculopathy in systemic sclerosis, based on its functional and structural changes, leads to symptoms of vasospasm (Raynaud's phenomenon) and tissue injury. In most cases, preventive actions and pharmacotherapy provide beneficial treatment options; however, in severe cases, painful ulcerations, gangrene, and digital amputations may occur with treatment. In medication refractory cases, revascularization of medium and small vessels has been pursued. Other studies regarding long-term outcomes of revascularization of systemic sclerosis-Raynaud's patients are less reported. Methods: Patients at the University of Pennsylvania (2009-2022) were identified with International Classification of Diseases (ICD)-9 and ICD-10 diagnosis codes for systemic sclerosis (ACR/EULAR 2013 criteria), Raynaud's phenomenon, and vascular grafting. Retrospective assessment of preoperative and postoperative patient-reported symptoms (Raynaud's symptoms, pain, ulcers), exam findings, and imaging results were collected. Results: Twelve hands from 10 patients were identified. Nine patients had limited systemic sclerosis, and one patient had diffuse systemic sclerosis. Eight patients were female, and the average surgery age was 52.3 ± 17.7 years. Vessel occlusion and revascularization occurred in ulnar artery of 11 hands and radial artery of 1 hand. Patients were followed up for an average of 45.4 ± 38.7 months, with three patient deaths within 2 years. Unremitting digital ulcers, pain, and color change were noted in three patients, likely due to medication mal-adherence and graft occlusion. Most hands (9/12) had subjective and objective resolution, or improvement in digital ulcers, pain, and color changes. Conclusion: The retrospective study assessed the long-term benefits of arterial revascularization in medication refractory systemic sclerosis-Raynaud's patients.

Objective: This study evaluates assessment and prescription trends in systemic sclerosis across different Indian healthcare settings, with a focus on diagnostic practices such as screening for interstitial lung disease, pulmonary hypertension, and adherence to recommended treatment protocols. The goal is to identify disparities and areas for improvement in the management of systemic sclerosis.

Methods: A cross-sectional questionnaire-based survey was conducted among rheumatologists from teaching and non-teaching hospitals across India. Data collection focused on key diagnostic practices such as the modified Rodnan skin score, chest imaging, pulmonary function tests, and echocardiography. Organ-specific prescription trends were collected and compared between teaching and non-teaching centres.

Results: The response rate for the survey was 70.5%. Teaching centres demonstrated higher adherence to performing modified Rodnan skin score at baseline (72.2%) compared to non-teaching hospitals (38.4%). For interstitial lung disease screening, overall, 93.7% performed chest imaging, with only 31.4% utilizing a High-Resolution CT thorax as the screening tool. Teaching centres performed 6MWT (79.5%) more often than non-teaching centres (64.7%). Echocardiography was commonly used for screening pulmonary hypertension (96.4%), while 16.5% reported using right heart catheterization. Steroids were used by 79.9% of participants at low doses (<10 mg) for a duration of less than 3 months, commonly for myositis(68%). Methotrexate(49.8%) and mycophenolate (38.3%) were the most prescribed first-line agents for systemic sclerosis-skin involvement. For systemic sclerosis-interstitial lung disease, mycophenolate (95%) was the most commonly used immunosuppression. Sequential addition of antifibrotic(62.4%) to immunosuppression was preferred over an upfront combination in systemic sclerosis-interstitial lung disease. The majority treated uncomplicated Raynaud's phenomenon with calcium channel blockers, followed by PDE5 inhibitors (61.4%). An upfront combination of endothelin receptor antagonists and PDE5i for systemic sclerosis-pulmonary hypertension was reported by 42.2%.

Conclusion: The study highlights differences in systemic sclerosis management trends among Indian rheumatologists. Despite variations in disease-encounter and practice settings, adherence to international recommendations in key domains and areas for further improvement are brought to light.

Introduction/objectives: Raynaud's phenomenon is a common vasospastic disorder associated with reduced health-related quality of life and, occasionally, ischaemic tissue damage depending on aetiology. The effect of beta-1-adrenoceptor blockers (e.g. bisoprolol, atenolol) on Raynaud's phenomenon remains unclear. We aimed to assess the association between genetically mimicked beta-1-adrenoceptor blockade and the risk of Raynaud's phenomenon.

Methods: We used two protein-coding single nucleotide polymorphisms in the ADRB1 gene, rs1801252 (A > G; Ser49Gly) and rs1801253 (G > C; Arg389Gly), to derive an unweighted allele count as the instrumental variable, using individual-level UK Biobank data. Raynaud's phenomenon was defined using International Classification of Diseases or Read codes. We used the ratio method and analysis was performed separately using systolic and diastolic blood pressure as the biomarker. To examine the validity of this approach and the Raynaud's phenomenon case definition, we also tested the known association between phosphodiesterase-5 inhibition and Raynaud's phenomenon risk.

Results: Analysis included 4743 individuals with Raynaud's phenomenon (mean age 58 years, 68% female) and 403,762 controls. There was no evidence of an effect of genetically mimicked beta-1-adrenoreceptor blockade on the risk of Raynaud's phenomenon, using systolic blood pressure (odds ratio = 0.93 per mmHg reduction; 95% confidence interval = [0.83, 1.04]; p = 0.19) or diastolic blood pressure (odds ratio = 0.91 per mmHg reduction; 95% confidence interval = [0.78, 1.05]; p = 0.19). The positive control exposure phosphodiesterase-5 inhibition was associated with reduced Raynaud's phenomenon risk.

Conclusions: We found no genetic evidence to support a causal association between beta-1-adrenoceptor blockade and Raynaud's phenomenon risk in either direction. Randomised controlled trials are required to confirm the safety of beta-1-adrenoceptor blockers in people with Raynaud's phenomenon.

Objective: The Scleroderma Clinical Trials Consortium Damage Index is an index of global damage in systemic sclerosis. The objective of this study is to determine the minimal clinically important difference of the Scleroderma Clinical Trials Consortium Damage Index.

Methods: Patients in the Canadian Scleroderma Research Group registry and the Australian Scleroderma Cohort Study who completed Scleroderma Clinical Trials Consortium Damage Index scores and the SF36v2 at baseline and the first full follow-up visit were studied. To calculate the minimal clinically important difference, an anchor question came from SF36v2: "Compared to one year ago, how would you rate your health in general?." Options were: much better, somewhat better, about the same, somewhat worse and much worse. We use the "somewhat worse" or "much worse" categories to indicate those with any worsening. We used four anchor methods: receiver operating characteristic curve, change difference, regression analysis, and average change.

Results: We studied 1672 patients. Mean disease duration was 11.4 ± 10.0 years; 62.5% had diffuse cutaneous systemic sclerosis. Baseline mean Damage Index was 5.3 ± 4.2; mean change of Damage Index over 1 year was 0.9 ± 1.8 units. The calculated minimal clinically important difference values were 1 for receiver operating characteristic method, 0.625 for change difference, 0.1879 for regression analysis, and 1.37 for average change. Omitting the regression analysis method as an outlier, the mean of the other methods was 1.

Conclusion: The most appropriate minimal clinically important difference for the Scleroderma Clinical Trials Consortium Damage Index is a change of ⩾ 1.0 units in the Scleroderma Clinical Trials Consortium Damage Index as is already recognized by patients as a significant change after 1 year. This can be applied to group means as well as to individuals where an ordinal change is required.

Introduction/objective: Visible differences from medical conditions and injuries are associated with body image concerns, particularly among females and young adults. We compared dissatisfaction with appearance and social discomfort between people with systemic sclerosis and burn injury, since the extent and implications of appearance changes are well-established in burn injury.

Methods: We searched PubMed, PsycInfo, EMBASE, and CINAHL to 8 December 2024 for studies that used the Satisfaction with Appearance Scale among adults with burn injury or systemic sclerosis. We emailed study authors and requested Satisfaction with Appearance Scale Dissatisfaction with Appearance and Social Discomfort subscale means and standard deviations for subgroups defined by sex (female, male) and age (18-44 years, 45-64 years, ⩾ 65 years). For each subgroup, we conducted a random-effects meta-analysis to estimate the difference between mean scores for people with burn injury and systemic sclerosis.

Results: We identified 17 eligible studies from nine unique cohorts. We obtained subgroup results from two of three eligible burn cohorts (2658 participants, 98% of total eligible) and five of six eligible systemic sclerosis cohorts (3402 participants, 99% of total eligible participants). Dissatisfaction with Appearance subscale scores were higher among people with systemic sclerosis compared to burn injury by 2.2 to 5.7 points (standardized mean difference = 0.20 to 0.53) for females and males across all age groups (p < 0.05 for males aged 18-44 and 45-64 years). For social discomfort, differences were close to zero (standardized mean difference < 0.10) for females aged 18-44 and 45-64 years. For females aged ⩾ 65 years and all male age groups, scores were higher in systemic sclerosis than burn injury (standardized mean difference = 0.22 to 0.45), although none were statistically significant.

Conclusion: Dissatisfaction with appearance and social discomfort appear to be similar or greater among people with systemic sclerosis compared to people who have been hospitalized with a burn injury.