Quiz Page February 2008: A Hemodialysis Patient With Thickened Skin

What is your diagnosis based on the history and physical exam of the skin? 

Nephrogenic systemic fibrosis (NSF), or nephrogenic fibrosing dermopathy, was first identified in 1997 and has been reported in 215 patients worldwide.1 It is a severe, progressive, fibrotic disorder most commonly occurring in patients with end-stage renal disease requiring dialysis, but also found in advanced chronic kidney disease. Recent reports have correlated its development with exposure to gadolinium-based magnetic resonance imaging (MRI) contrast agents (GBCAs) and as of December 21, 2006, the US Food and Drug Administration (FDA) had received reports of 90 patients who developed NSF within 3 months following single or multiple administrations of a GBCA. Gadolinium has also been identified in skin biopsies of patients with NSF.2 In response, the FDA has asked manufacturers to include a new boxed warning on the product labeling of all GBCAs. Our patient received a GBCA 1 month before he started hemodialysis.

NSF affects men and women equally. Early signs typically include symmetric red or dark patches, papules, or plaques on the hands and feet progressing to skin thickening and brawny induration (days to weeks) with a peau d’orange appearance. Involvement of the trunk may ensue, but the head and neck are often spared. The skin tightening resembles scleroderma, and inhibits the flexion and extension of joints resulting in contractures. These limitations may render affected patients unable to walk or use their hands. Systemic involvement of the lungs, myocardium, striated muscles, and diaphragm has also been reported.3

How will you confirm the diagnosis? 

Despite a lack of specific laboratory findings, C-reactive protein and erythrocyte sedimentation rate are often elevated.4 Absence of paraproteinemia constitutes one of the most important differences between NSF and scleromyxedema. Histology of the cutaneous biopsies demonstrates marked thickening of the dermis with accumulation of thick collagen bundles separated by large clefts in the papillary and deep dermis.1 In addition, thick fibrous tissue tracts extend across the adipose tissue into the fascia, which are severely thickened. Mildly increased amounts of stromal mucin may also be noted but inflammation is typically absent. CD34+ dermal dendrocytes are abundant, and factor XIIIa+ and CD68+ monocytes and multinucleated cells are found in increased numbers.