The Differential Diagnosis of Systemic Sclerosis

Alan Tyndall; Susanna Fistarol


Curr Opin Rheumatol. 2013;25(6):692-699. 

In This Article

Abstract and Introduction


Purpose of review: The new American College of Rheumatology/European League Against Rheumatism classification criteria will enable earlier diagnosis and, therefore, the use of newer treatment modalities for systemic sclerosis (SSc). It is therefore critical to exclude non-SSc causes for diffuse skin thickening as early as possible.

Recent findings: The recently described gadolinium-induced nephrogenic systemic fibrosis may mimic SSc as may other conditions which require a different treatment strategy. Recently, treatment with immunoablation and autologous stem cell transplantation has been shown to significantly benefit some patients with conditions such as scleromyxoedema and SSc. The more accurate measurement of SSc-specific autoantibodies such as topoisomerase 1, centromere and RNA polymerase has recently allowed a more precise subclassification of SSc with implications for treatment and prognosis.

Summary: Skin thickening is a nonspecific manifestation of many different processes including (rarely) early scleroderma, which is mostly symmetrical and associated with Raynaud's phenomenon, nailfold capillaroscopic changes and antinuclear antibodies. If the latter three factors are absent, then other conditions must be excluded, the commonest being eosinophilic fasciitis. Skin biopsy (looking for eosinophil infiltration, increased mucin or amyloid deposition), SSc-specific autoantibodies or paraproteins in blood and a careful medical history and system screening will exclude nonscleroderma conditions.


Until recently, the diagnosis of systemic sclerosis (SSc) required either 'symmetrical proximal scleroderma, or two or more of the minor criteria, that is, sclerodactyly, digital pitting scars of fingertips or loss of substance of the distal finger pad and bilateral basilar pulmonary fibrosis'.[1] Intrinsic to the classification was exclusion of other conditions which may also result in proximal symmetrical skin thickening. Although new, more sensitive classification criteria have been recently developed,[2] exclusion of scleroderma mimics is still required.