Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement

Abstract

IntroductionWe investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.MethodsThirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.ResultsAt baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X2 = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04).ConclusionMost early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.

Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis

“…Furthermore, another study from a single centre showed that internal organ involvement may appear even before SSc patients fulfil the classification criteria of the American College of Rheumatology (ACR), formerly the American Rheumatism Association (ARA) 2–4. In this latter study, screening with sensitive tools for internal organ involvement in early SSc patients (defined as patients having Raynaud’s phenomenon (RP) with SSc marker autoantibodies and/or typical nailfold capillaroscopic (NC) findings and no manifestations other than puffy fingers (PuFi) or arthritis) identified at least one preclinical functional alteration in 42–48% of cases 3 4…”

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

“…By definition, patients with early SSc do not show any distinctive clinical manifestation of the disease (namely, sclerodactyly, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, electrocardiographic signs of myocardial fibrosis, or a serum creatinine increase suggestive of scleroderma renal crisis) except puffy fingers and/or arthritis [1-4]. …”

An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features

“…Similarly, the features of digital fissuring ("mechanic hands") ( figure 1) and a fixed rash on the digital extensor surfaces (Gottron's sign) (figure 2) are hallmarks of the anti-synthetase syndrome or systemic sclerosis-myositis overlap associated with PM-Scl antibody positivity [16,[25][26][27][28][29][30][31][32]. The use of nailfold microscopy in the evaluation of individuals with Raynaud's phenomenon is encouraged as capillary loop abnormalities can be predictive of developing a CTD such as systemic sclerosis or dermatomyositis [33][34][35][36]. Inflammatory arthropathy is included as an IPAF criterion and is characterised by symptoms or signs of peripheral joint synovitis, but joint pain alone is not included due to its lack of specificity.…”