Systemic Sclerosis (Scleroderma)

Excerpt

Systemic sclerosis, also known as scleroderma, is a rare connective tissue disorder with an unknown and complex pathogenesis. Scleroderma can be divided into 2 primary forms—localized scleroderma (including morphea, linear scleroderma, and scleroderma en coup de sabre) and systemic sclerosis. Systemic sclerosis can be further classified as limited systemic sclerosis (formerly known as CREST syndrome, characterized by calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) or diffuse systemic sclerosis based on clinical and serological criteria. Although significant progress has been made in understanding the pathophysiology of scleroderma over the past centuries, the disease continues to pose significant morbidity and mortality in patients.

Localized scleroderma primarily affects the skin and subcutaneous tissue, leading to patches of thickened skin that, on biopsy, reveal dermal fibrosis similar to the histopathological changes seen in the thickened skin in systemic sclerosis. However, it is not associated with the Raynaud phenomenon, digital ischemic events, or internal organ involvement. Antinuclear antibodies may be present in up to 50% of cases of localized scleroderma; however, more specific autoantibodies such as anti-centromere, anti-Scl-70, and anti-RNA polymerase III are absent in this condition. Notably, localized scleroderma is not associated with increased mortality. On the other hand, systemic sclerosis is associated with several systemic manifestations and internal organ involvement, leading to increased mortality, and its classification is based on skin involvement.

Limited cutaneous systemic sclerosis, previously known as CREST syndrome, is characterized by skin thickening distal to the elbows and knees and/or on the face without trunk involvement. On the other hand, diffuse cutaneous systemic sclerosis involves skin thickening that may affect areas proximal to the elbows, knees, face, and/or trunk. Both limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis are associated with several systemic manifestations and positive autoantibodies. Antinuclear antibodies may be present in more than 90% of cases of systemic sclerosis, and up to 70% of cases exhibit at least one of the more specific autoantibodies (anti-centromere, anti-Scl-70, and anti-RNA polymerase III). Scleroderma most commonly affects the skin, gastrointestinal tract, lungs, kidneys, skeletal muscle, and pericardium among affected organs. The manifestations of scleroderma may overlap extensively with those of other rheumatological or immunological diseases. The severity of the presentation may also vary depending on the timing of the systemic sclerosis diagnosis.