%0 Journal Article
%T Understanding Nephrogenic Systemic Fibrosis
%A Tushar Chopra
%A Kiran Kandukurti
%A Silvi Shah
%A Raheel Ahmed
%A Mandip Panesar
%J International Journal of Nephrology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/912189
%X Nephrogenic systemic fibrosis (NSF) is a rare and a debilitating disease noted uncommonly in patients with impaired renal function when exposed to low-stability gadolinium-based contrast agents (Gd-CAs). According to experimental studies, cytokines released by the stimulation of effector cells such as skin macrophages and peripheral blood monocytes activate circulating fibroblasts which play a major role in the development of NSF lesions. The presence of permissive factors, presumably, provides an environment conducive to facilitate the process of fibrosis. Multiple treatment modalities have been tried with variable success rates. More research is necessary to elucidate the underlying pathophysiological mechanisms which could potentially target the initial steps of fibrosis in these patients. This paper attempts to collate the inferences from the in vivo and in vitro experiments to the clinical observations to understand the pathogenesis of NSF. Schematic representations of receptor-mediated molecular pathways of activation of macrophages and fibroblasts by gadolinium and the final pathway to fibrosis are incorporated in the discussion. 1. Introduction Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder which predominantly occurs in patients whose estimated glomerular filtration rate is below 30£¿mL/min/1.73£¿m2 or who are on dialysis [1, 2]. Clinically, these patients present with a thickening and hardening of skin which is often associated with pain, muscle weakness, bone pain, and joint contractures leading to severe disability [3]. These lesions can be found all over the body but typically occur on the lower extremities and the face is usually spared [4]. NSF, first described in 1997, can affect both children and the elderly and has an average age of onset of 46.8 years [5, 6]. No genetic or racial predisposition has been established. The most common presenting morphology is sharply demarcated plaques (58%) with irregular edges but papules (32%), nodules (17%), and rarely macules, vesicles, blisters, bullae, and ulcers have also been reported [1, 4, 5, 7]. The lesions are progressive and later can evolve into wrinkles and woody skin with a cobblestone or ¡°peau d¡¯orange¡± texture [8]. NSF skin lesions are usually hyperpigmented and erythematous (39%) but can vary from violaceous, brown, tan, yellow, pink, orange-red, and grey-brown [4, 9]. Although initially named, ¡°Nephrogenic Fibrosing Dermopathy,¡± since it was thought that the lesions were limited to the skin, it is now well documented that these lesions extend beyond the dermis and can
%U http://www.hindawi.com/journals/ijn/2012/912189/