Evolving concepts of diagnosis and classification

Abstract

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by fibrosis of the skin and internal organs and a vasculopathy affecting the micro-and macro-vasculature. The pathogenesis of SSc involves the interplay between vascular injury and dysregulation of the immune response with resultant fibrosis of various target organs. More than 90% of patients with SSc suffer from Raynaud's phenomenon, a reversible vasospastic disorder induced by cold or stress, which results in typical white, blue, and red color changes of the distal extremities from decreased perfusion [1]. Other clinical features that are common in patients with SSc in addition to cutaneous sclerosis include pulmonary disease (interstitial lung disease and pulmonary hypertension), gastrointestinal dysmotility and malabsorption, digital ulcerations, inflammatory myositis and arthritis, cardiac and renal disease. There are two main subsets of SSc that are commonly recognized: limited cutaneous SSc and diffuse cutaneous SSc. The two subsets differ in manifestations and in prognosis, and presumably to some extent also in their pathogenesis. Although disease modifying therapies have demonstrated minimal efficacy in SSc [2-6], several organ-specific therapies have emerged over the past couple of decades resulting in improved survival and quality of life. These include angiotensin-converting enzyme (ACE) inhibitors for the treatment of scleroderma renal crisis (SRC) [7] and various agents for the treatment of pulmonary arterial hypertension (PAH), including prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors [8]. The development of successful disease-modifying therapies for SSc is hindered by the heterogeneous clinical manifestations of this disease, also making early diagnosis challenging. Patients with early disease are more likely to respond to targeted therapies, and irreversible organ damage may be prevented. For studying the effects of potential disease modifying drugs, and for more successful treatment in clinical practice, it is of paramount importance to recognize the presence of SSc early in the disease process. This is equally important for the diagnosis in clinical practice as well as for classification criteria used to include patients in clinical studies. If patients who are classified with SSc are similar to patients who are diagnosed with the disease, then it is straightforward to generalize evidence from clinical studies to those patients who have been diagnosed in practice. Therefore, classification and diagnosis in SSc should be developed toward recognition of SSc early in the disease process. This chapter will review the clinical subsets of SSc, the current American College of Rheumatology (ACR) classification criteria and its limitations, recently proposed classification criteria for SSc, and ongoing and future projects for revising and improving the ACR classification criteria.