Abstract

The spectrum of scleroderma spans Raynaud's phenomenon, localized forms of skin fibrosis and the clinically most important forms of systemic sclerosis that involve inflammatory, vascular and fibrotic pathology. A closer relationship between these disparate conditions is now appreciated, and skin sclerosis is no longer regarded as mandatory for the diagnosis of systemic sclerosis. There have been recent and substantial changes in disease classification, the appreciation of its natural history and the investigation and treatment of organ-based complications. Although scleroderma still has a high case-specific mortality, there have been major improvements in the management of renal and pulmonary disease, and areas such as gastrointestinal tract involvement can also often be improved. Each of these areas is reviewed, and progress in understanding pathogenesis also described. The management of organ-based complications has benefited from advances in other branches of medicine. Angiotensin-converting enzyme inhibitors for scleroderma renal crisis, proton pump inhibitors for reflux oesophagitis and advanced therapies for classes III and IV pulmonary arterial hypertension exemplify progress in the treatment of systemic sclerosis. There is also the prospect of targeted, cytokine-directed treatments that may for the first time offer the prospect of genuine disease-modifying intervention in early-stage disease. In parallel with these developments, there has been substantial progress in disease assessment with the construction and initial validation of tools to assess skin biomechanics, functional impairment and the severity and activity of systemic sclerosis. It is likely that clinical trials performed over the next few years will transform the management of systemic sclerosis and help to dispel its reputation as one of the least treatable of the autoimmune rheumatic diseases.