We searched PubMed using the key word “scleroderma” with the relevant topics—eg, “pathogenesis”, “CREST”, “genetic predisposition”, “transforming growth factor beta”, “autoimmunity”, “vascular damage”. Fields were restricted to publications in English. We also searched the citations from obtained papers. References were chosen based on the best evidence from clinical or laboratory studies. Review articles of scleroderma published in the past 5 years were also examined to ensure minimum
SeminarSystemic sclerosis: hypothesis-driven treatment strategies
Section snippets
Limited cutaneous scleroderma
Calcinosis and telangiectases, seen in the classic CREST variant, could take years or even decades to develop into limited cutaneous systemic sclerosis.7 Patients with the limited disorder generally have more favourable outcomes than patients with the diffuse form, and the 5-year survival rate has been reported to be as high as 86%.10 However, substantial morbidity and mortality can occur from occlusive digital vascular disease, gastrointestinal effects, interstitial lung fibrosis, and
Diffuse cutaneous scleroderma
Patients with diffuse cutaneous systemic sclerosis typically have a much more aggressive early disease course than those with the limited form.5, 7 Raynaud's phenomenon might not be present initially and could, in fact, follow the onset of skin swelling. Initial presentation can include diffusely swollen, oedematous, pruritic skin; fatigue; and non-specific joint and muscle pain. Skin thickening is typically rapid, extending proximally on the arms and legs, with or without truncal effects,
Pathogenesis
The clinical presentation of systemic sclerosis is typified by three cardinal features: excessive collagen production and deposition, vascular damage, and inflammation or autoimmunity (figure 1).6, 13 Although the causes of the disorder are not yet understood, a plausible hypothesis has been forwarded to explain the inter-relations and interactions among these three features (figure 1). The three major clinical features and their interactions can be seen as a pathophysiological triangle of
Evolution of trial design, study conduct, and outcome measures
Although drugs such as methotrexate, sulfasalazine, gold, and even cyclophosphamide have existed for decades to treat rheumatoid arthritis, the recent introduction of four new disease-modifying anti-rheumatic drugs (DMARDs; eg, leflunomide, etaneracept, inflixamab, and adalimamab) has given physicians and patients new alternatives to treat the symptoms of rheumatoid arthritis and to decrease the rate of joint destruction, deformity, and disability. These recent advances were made possible by
Search strategy and selection criteria
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