BACKGROUND AND AIMS: Systemic sclerosis (scleroderma; SSc) patients can develop pulmonary arterial hypertension (PAH), which is a leading cause of death. We sought to evaluate severity, therapeutic strategy and survival of SSc-PAH in the Australian Scleroderma Cohort Study (ASCS). METHODS: Among patients with 2013 American College of Rheumatology/European League Against Rheumatism-defined SSc, PAH was defined as mean pulmonary artery pressure (mPAP) ≥20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) >2 WU. Characteristics of those with and without PAH and those with incident PAH in 2014-2020 versus 2007-2013 were compared using descriptive statistics. Survival was evaluated using the Kaplan-Meier method and a multivariable Cox regression model. RESULTS: Among 1612 patients, 71 (4.4%) had incident PAH prior to censoring on 13 February 2024. Significantly more patients received PDE5i monotherapy in the first 12 months after PAH diagnosis in the later epoch (30 (63.8%) vs 6 (25.0%), P = 0.002). Dual therapy (any endothelin reception antagonist (ERA) and any PDE5i) was more common in the later epoch (26 (55.3%) vs 4 (16.7%), P = 0.002). Overall survival of those diagnosed with PAH between 2007 and 2013 was 91.67%, 87.50% and 56.88% at 1, 3 and 5 years. Overall survival of those diagnosed between 2014 and 2020 was 100.00%, 77.62% and 48.98% at 1, 3 and 5 years (P = 0.414). CONCLUSIONS: Despite increased use of dual therapy in the more recent epoch, we observed no significant improvement in overall survival in SSc-PAH in our cohort. Our cohort's 1-, 3- and 5-year mortality is comparable to those reported for other contemporary SSc-PAH cohorts.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy, inflammation, and fibrosis, in which pulmonary hypertension (PH) is a major cause of mortality. In SSc, the relationship between endothelial and platelet functions with echocardiographic findings have not been evaluated. Here, we evaluated the endothelial and platelet functions in SSc patients with different PH probability and tested their associations with echocardiographic parameters, including the maximal tricuspid regurgitant velocity (TRVmax). Endothelial function was assessed by flow-mediated dilation (FMD) of brachial artery and blood nitrite levels, measured by chemiluminescence method. Platelet activity was measured by light transmission aggregometry in response to stimulation by adenosine diphosphate (ADP) and thrombin receptor-activating peptide-6 (TRAP-6). PH probability was assessed by echocardiography, and PH diagnosis was confirmed by right heart catheterization. SSc patients with PH probability had lower FMD than age-matched controls: FMD decreased from 13.3 ± 3.9% in controls to 5.6 ± 1.7%, 4.6 ± 0.4%, and 3.8 ± 0.4% in SSc patients with low PH probability, intermediate PH probability, and confirmed PH, respectively. SSc patients with PH had higher blood nitrite levels than controls or the patients with low PH probability. TRVmax correlated inversely with FMD and positively with platelet aggregation. In multivariable regression analysis, TRAP-6-induced platelet aggregation and FMD were independently associated with TRVmax. Furthermore, we demonstrated in two patients that nebulized sodium nitrite transiently reduced TRVmax. In conclusion, SSc patients have endothelial dysfunction and increased platelet activity, which exhibits correlation with TRVmax.
Eosinophilic fasciitis (EF), also known as Shulman's disease, is a rare inflammatory and fibrosing disorder characterized by inflammation and eosinophilic infiltration of the fascia, leading to skin thickening and induration. It typically presents with limb edema progressing to induration and sclerosis and is frequently, but not invariably, associated with peripheral blood eosinophilia. Diagnosis relies on a combination of clinical, laboratory, imaging, and histopathological findings. We report the case of a 16-year-old female patient with a documented history of hypereosinophilic syndrome, moderate persistent asthma, and recurrent cutaneous abscesses, who presented with localized swelling of the left leg approximately one week after minor trauma. Clinical examination revealed a 3-cm fluctuant swelling with local inflammatory signs. Laboratory investigations showed a negative C-reactive protein level and an eosinophil count of 150/mm³, within the laboratory reference range. Soft-tissue ultrasonography demonstrated a subcutaneous collection measuring 24 × 17 mm. The patient received ceftriaxone for seven days without clinical improvement. Direct examination of purulent material showed no microorganisms, and culture was sterile. A deep skin and subcutaneous tissue biopsy revealed moderate fibrosis associated with a dense inflammatory infiltrate rich in eosinophils, with no evidence of malignancy. Based on the clinical and histopathological findings, EF was considered the most likely diagnosis. Systemic corticosteroid therapy was initiated at 1 mg/kg/day, resulting in progressive clinical improvement. This case highlights the diagnostic challenge of localized EF in the absence of peripheral blood eosinophilia and in a patient with a history of recurrent abscesses and hypereosinophilic syndrome. EF should therefore be considered in the differential diagnosis of persistent indurated limb swelling, even when the presentation is localized and mimics an infectious process.
Worldwide risk of autoimmune diseases, particularly multiple sclerosis (MS), varies between populations. One key factor is immune variation attributed to genetic variation. The human leukocyte antigen (HLA) system plays a central role in antigen presentation, immune regulation, and host-pathogen interactions. Variation across HLA genes has substantial clinical implications, influencing risk for autoimmune and neurodegenerative diseases. For instance, HLA-DRB1*15:01 remains the strongest and most consistently replicated genetic risk factor for MS, with similar HLA-associated patterns observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since HLA loci evolve under strong selective pressures, population-level HLA diversity reflects distinct histories of pathogen exposure, geography, climate, diet, and demographic isolation. Indigenous groups such as the First Nations, Métis, and Inuit therefore exhibit unique HLA distributions shaped by their ancestral environments. The variation in HLA genes as well as environmental factors have shaped the difference in MS prevalence and severity in these Indigenous populations compared to non-Indigenous groups.
OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is associated with substantial disease-specific mortality. Scleroderma-specific autoantibodies (SSc-Ab) may influence disease course, but their prognostic value in very early dcSSc remains unclear. We examined associations between autoantibody profiles and disease trajectories for clinical events in a prospective single-center cohort. METHODS: We retrospectively analyzed prospectively collected data from a subset of patients enrolled in an early SSc registry between October 2012 and July 2021, including those with early dcSSc or individuals at risk for dcSSc less than two years of their first non-Raynaud phenomenon (RP) symptom. Participants were classified as anti-RNA polymerase III antibody positive (RNAP3+), anti-topoisomerase I antibody positive (Scl70+), or triple-negative (negative for RNAP3, Scl70, and anticentromere antibody [ACA]). RESULTS: Among 115 patients with available SSc-Ab data (median follow-up, 5.5 years [interquartile range 2.1-7.2]), 42 were RNAP3+, 29 Scl70+, 6 ACA+, and 38 triple-negative. ACA+ patients were excluded from subgroup analyses because of the small sample size. Of the remaining 109 patients, 17 with prior clinical events at baseline were excluded from time-to-event analyses. Among the 92 included patients, 50 (54.3%) experienced one or more new clinical events during follow-up, including 59.4% of RNAP3+, 57.1% of Scl70+, and 46.9% of triple-negative patients. Among first new clinical events, RNAP3+ patients had higher frequencies of scleroderma renal crisis (6.3% vs 3.6% in Scl70+ and 0% in triple-negative), malignancy (35.7% vs 24.1% and 15.8%, respectively), mortality (9.4% vs 3.6% and 0%, respectively), and forced vital capacity decline (15.6% vs 10.7% and 12.5%, respectively), whereas modified Rodnan skin score worsening was most frequent in triple-negative patients (15.6% vs 10.7% in Scl70+ and 9.4% in RNAP3+). CONCLUSION: Scleroderma-specific autoantibodies in early SSc were associated with distinct baseline clinical phenotypes and showed numerical differences in longitudinal clinical outcomes in this single-center cohort.