Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review


Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud’s phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

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Systemic sclerosis


Localized scleroderma


Limited cutaneous systemic scleroderma


Diffuse cutaneous systemic scleroderma


anti-RNA polymerase III


Transforming growth factor-ß


Tumor necrosis factor


Friend leukemia integration factor 1


Platelet-derived growth factor


American College of Rheumatology


European League Against Rheumatism


European Scleroderma Trials and Research


Anti-nuclear antibody


Microangiopathy evolutiontion score


Nailfold videocapillaroscopy


Cutaneous telangectasias


Modified Rodnan skin score


Digital ulcers


Extractable nuclear antigens


Anti-centromere antibody


Anti-topoisomerase I




Progressive hemifacial atrophy


Localized scleroderma Skin Severity Index




Nephrogenic systemic fibrosis


Gadolinium-based contrast agents


Magnetic resonance imaging


Eosinophilic fasciitis


Human leukocyte antigens

IFN gamma:

Interferon gamma




Erythrocyte sedimentation rate


Positron emission tomography


Graft-versus-host disease


Anti-lupus anti-coagulant Sjögren’s syndrome-related antigen B


Psoralen plus ultraviolet A


Graft versus tumor


Porphyria cutanea tarda


Uroporphyrinogen decarboxylase




Human immunodeficiency virus






Aminolevulinic acid




Diabetes mellitus


Advanced glycosylation end-products


Werner syndrome


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Ferreli, C., Gasparini, G., Parodi, A. et al. Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review. Clinic Rev Allerg Immunol 53, 306–336 (2017).

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  • Scleroderma
  • Systemic sclerosis
  • Morphea
  • Scleroderma-like disorders
  • Cutaneous sclerosis