Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study

Abstract

ObjectiveSystemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc.MethodsIn the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.ResultsOf the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.ConclusionIn SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

Systolic Dysfunction in Systemic Sclerosis: Prevalence and Prognostic Implications

“…Over a 3.3‐year observation period, we did not find any deterioration of LV function. This was surprising, yet results were consistent for EF, GLS, and FS, which may support the notion that most organ manifestations develop early in the course of SSc . One may further speculate whether this stabilization is due to the frequent administration of calcium channel blockers in SSc, which are shown to increase cardiovascular perfusion and function .…”

Cutaneous hardening in a patient with systemic sclerosis successfully treated with UVA‐1 phototherapy

“…Systemic sclerosis is a chronic autoimmune connective tissue disease of unknown etiology characterized by the deposition of collagen in skin and internal organs (Chaowattanapanit, Choonhakarn, Foocharoen, & Julanon, ). The lungs, kidneys, heart, gastrointestinal tract and musculoskeletal system may be affected (Jaeger et al, ). Treatment is focused on controlling organ involvement (Frech et al, ).…”

Clinical significance of rare serum autoantibodies in rheumatic diseases: a systematic literature review

“…This allowed the large scale and rapid identification of anti-RNApol antibodies in a clinical diagnostic laboratory setting to identify SSc patients who are at risk for developing SSc with these autoAbs (66,67). Anti-RNApol antibodies are found in 1.1% to 15% of SSc patients (33,36,37,40,41,45,47,49,52,54,68) and anti-RNA polymerase I/III positive patients are more likely to develop dcSSc with pulmonary involvement, joint and tendon involvement, myositis, and a significantly increased risk of scleroderma renal crisis (33,37,40,45,47,49,50,52,62). However, patients with anti-RNA polymerase III antibodies have lower risk of gastrointestinal (GI) manifestations and esophageal dysmotility compared to patients with anti-topo I/Scl70 (40,62), as well as a lower incidence of pulmonary disease (40).…”