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Content Update

Update May 22, 2017

New chapter on Systemic Sclerosis (Scleroderma) and Related Disorders from the forthcoming 20th edition of Harrison's.

The chapter on Systemic Sclerosis (Scleroderma) and Related Disorders from the forthcoming 20th edition of Harrison's is now available. This chapter features brand new images and an updated list of further readings that will be helpful to our readers. Click here to access the newly published chapter from the 20th edition.

 

Anthony S. Fauci, MD

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DEFINITION

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Systemic sclerosis (SSc) is an uncommon connective tissue disorder characterized by multisystem involvement, heterogeneous clinical manifestations, a chronic and often progressive course, and significant disability and mortality. Multiple genes contribute to disease susceptibility; however, environmental exposures are likely to play a major role in causing SSc. The early stage of the disease is associated with prominent inflammatory features. Over time, functional and structural alterations in multiple vascular beds and progressive visceral organ dysfunction due to fibrosis dominate the clinical picture. Although thickened skin (scleroderma) is the distinguishing hallmark of SSc, skin induration can occur in localized forms of scleroderma and other disorders (Table 382-1). Patients with SSc can be broadly grouped into diffuse cutaneous and limited cutaneous subsets defined by the pattern of skin involvement, as well as clinical and laboratory features (Table 382-2). Diffuse cutaneous SSc (dcSSc) is associated with extensive skin induration, starting in the fingers and ascending from distal to proximal limbs and the trunk. These patients often have early interstitial lung disease and acute renal involvement. In contrast, in patients with limited cutaneous SSc (lcSSc), Raynaud’s phenomenon may precede other manifestations of SSc by years. In these patients, skin involvement remains limited to the fingers (sclerodactyly), distal limbs, and face, and the trunk is not affected. The constellation of calcinosis cutis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia, seen in some lcSSc patients, is termed the CREST syndrome. Visceral organ involvement in lcSSc tends to show insidious progression, and pulmonary arterial hypertension (PAH), interstitial lung disease, hypothyroidism, and primary biliary cirrhosis may occur as late complications. In some patients, Raynaud’s phenomenon and other characteristic features of SSc occur in the absence of skin thickening. This syndrome has been termed SSc sine scleroderma.

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EPIDEMIOLOGY

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SSc is an acquired sporadic disease with a worldwide distribution and affecting all races. In the United States, the incidence is estimated at 9–19 cases per million per year. The only community-based survey of SSc yielded a prevalence of 286 cases per million. There are an estimated 100,000 cases in the United States, although this number may be significantly higher if patients who do not meet strict classification criteria are also included. Rates of SSc in England, Australia, and Japan appear to be lower. Age, gender, and ethnicity are important in disease susceptibility. In common with other connective tissue diseases, SSc shows a strong female predominance (4.6:1), which is most pronounced ...

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