The Differential Diagnosis of Systemic Sclerosis

Alan Tyndall; Susanna Fistarol


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

In This Article

Nephrogenic Systemic Fibrosis

First recognized in San Diego in 1997 and published in 2000 in Lancet,[19] NSF evolved through several nomenclatures including scleromyxoedema-like illness of renal disease, scleromyxoedema-like illness of hemodialysis, scleromyxoedema-like fibromucinosis, dialysis-associated systemic fibrosis and nephrogenic fibrosing dermopathy.

It is now recognized as a gadolinium-induced fibrotic process mainly affecting not only the skin, but also the internal organs which only occurs in patients exposed to gadolinium in whom renal function is impaired, mostly stage 5 chronic kidney disease (CKD), that is, glomerular filtration rate less than 15 ml/min. In one series, NSF was detected in 13% of patients with stage 5 CKD who had been exposed to gadolinium.[20] The disease manifests itself with thickening and woody induration of the skin with yellowish or brownish discoloration often accompanied by burning and severe pruritus. Skin changes are usually limited to the extremities, but sometimes involve the trunk. NSF may result in severe contractions of joints and fatal internal organ involvement. In contrast to other cutaneous fibrosing disorders, the face is not involved. Cutaneous and conjunctival yellow plaques, pingueculae, may occur, but Raynaud's phenomenon, telangiectasiae and acroosteolysis are not present, nor autoantibodies typical of SSc.

Lesional biopsies show increased mucin and collagen deposition and a paucity of inflammatory cells, despite a general hypercellularity.[21] Some infiltrating cells have the phenotype of fibrocytes – cells of haematopoietic origin which migrate from the bone marrow to the sites of tissue injury and during the passage change their phenotype to one of a collagen-secreting myofibroblast.[22] Treatment is variable and not optimistic. Ineffective agents include glucocorticoids, cyclosporine, histamine-2 receptor antagonists and thalidomide. Variable responses to plasmapheresis, phototherapies and sirolimus have been reported, whereas imatinib remains a promising option.[23]