Does early systemic sclerosis really exist?

Abstract

Systemic sclerosis (SSc) is an autoimmune systemic disease of unknown origin, characterized by sclerosis of the skin and internal organs associated with endothelial dysfunction, immune dysregulation, and autoantibody [1]. The most common manifestations are Raynaud's phenomenon (RP), digital ulcers, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), gastrointestinal disorders, scleroderma renal crisis (SRC), heart problems, and musculoskeletal symptoms. Nevertheless, SSc may be a clinically heterogeneous disease that ranges from a milder form to more rapid widespread internal organ involvement with different clinical features at onset. This entity is easy to diagnose in the advanced stages, but the vascular and fibrotic involvement may have started years previously. Prompt detection of the various manifestations benefits prognosis [2], but this is challenging in the early stages of the disease when most of the typical signs and symptoms are absent. Consequently, an SSc diagnosis may be delayed for years following the onset of RP, and even after the appearance of the first non-RP symptom. Thus, treatment and prognosis may be delayed until systemic involvement is evident or even irreversible [3]. Conventional classification criteria are limited in identifying early-stage SSc patients. The ACR/EULAR classification criteria specify that patients with pre-scleroderma, as defined by LeRoy and Koenig, do not have to be classified as definite SSc. However, autoimmunity can precede clinical manifestations by years [4], and efforts have been made to detect this situation before frank disease develops [5]. Nevertheless, diagnosis of early SSc can still be a challenge despite the wealth of published data and available information.