Systemic sclerosis

Abstract

Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition, research advancements have improved our understanding of its disease pathogenesis and clinical phenotypes and expanded our treatment armamentarium. Early and accurate diagnosis is essential, while ongoing efforts to risk stratify patients have a central role in predicting both organ involvement and disease progression. A holistic approach is required when choosing the optimal therapeutic strategy, balancing the side-effect profile with efficacy and tailoring the treatment according to the goals of care of the patient. This Seminar reviews the multiple clinical dimensions of systemic sclerosis, beginning at a precursor very early stage of disease, with a focus on timely early detection of organ involvement. This Seminar also summarises management considerations according to the pathological hallmarks of systemic sclerosis (eg, inflammation, fibrosis, and vasculopathy) and highlights unmet needs and opportunities for future research and discovery.

Figure 1:. Clinical features of (very) early systemic sclerosis

(A) The proportion of patients fulfilling the 2013 American College of Rheumatology and European Alliance of Associations for Rheumatology Classification Criteria for systemic sclerosis at 5 years was as follows for the following combinations of criteria: in patients with a scleroderma pattern on capillaroscopy plus systemic sclerosis-specific antibodies, 65·9% developed definite systemic sclerosis at 5 years;^, in patients with positive antinuclear antibodies and puffy fingers, 79·0% developed definite systemic sclerosis at 5 years; in patients with systemic sclerosis-specific autoantibodies and puffy fingers, 94·1% developed definite systemic sclerosis at 5 years; and in patients with capillaroscopic abnormalities (both systemic sclerosis specific as well as non-specific abnormalities) and systemic sclerosis-specific antibodies, 82·2% developed systemic sclerosis at 5 years. (B) 1·3% of patients with Raynaud phenomenon in the absence of scleroderma patterns on capillaroscopy and systemic sclerosis-specific antibodies developed systemic sclerosis at 5 years follow-up.

Figure 2:. The 2013 American College of Rheumatology and European Alliance of Associations for Rheumatology Classification Criteria for systemic sclerosis

A total score of 9 or higher is sufficient to classify a patient as having definite systemic sclerosis, in the absence of other causes for the individual criterion. These criteria were developed for research purposes and do not represent diagnostic criteria. *Maximum score of 2. †Maximum score of 3. MCP=metacarpophalangeal joint. PIP=proximal interphalangeal joint. VEDOSS=very early diagnosis of systemic sclerosis.