Drs. Tammaro and Narcisi are from the Unit of Dermatology, Neurosciences, Mental Health, and Sense Organs Department, Sapienza University of Rome, Italy. Dr. Tuchinda is from the Department of Dermatology, University of Bangkok, Thailand. Dr. Sina is from the Department of Dermatology, University of Maryland, Baltimore.
The authors report no conflict of interest.
Correspondence: Alessandra Narcisi, MD, Unit of Dermatology, Neurosciences, Mental Health, and Sense Organs Department,Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa, 1039, 00189 Rome, Italy (123alexa@virgilio.it).
Circulating fibrocytes traffic to areas of chronic antigenic stimulation promoting wound repair and fibrotic reactions. Some authors have proposed that materials deposited in the skin might serve as targets for circulating fibrocytes.8 Circulating fibrocytes also are known to produce inflammatory cytokines including IL-1 and chemokines such as platelet-derived growth factor, transforming growth factor b, and others capable of propagating fibrotic responses. Increased expression of transforming growth factor has been reported in dendritic cells in NSF lesions and Parsons et al9 postulated that transglutaminase-2 activation of this protein may be responsible for inciting fibrosis in NSF. Transglutaminases also are known to be directly activated by Gd.10,11
Transmetalation has been proposed as a possible operative phenomenon responsible for NSF. Several cations including zinc, copper, iron, and carbon are known to compete with Gd and may displace it from the ligand, with anions such as OHe, PO4 3e, and CO3 2e binding the resultant free Gd. Some GBCAs contain excess ligand to diminish potential free Gd concentrations. In fact, substantial elevations of serum calcium and phosphorus in patients with NSF have been noted in a large series of patients with NSF. Calciphylaxis, an often catastrophic condition arising in patients with renal failure, has been described in association with NSF, and sodium thiosulfate has been used with success in treating both conditions.10 In addition, Sanyal et al12 noted a substantially higher serum calcium in NSF cases compared with controls.
Gadolinium plays an important role in the pathology of NSF and is confirmed by the presence of Gd in skin biopsies.
