Nephrogenic systemic fibrosis: time for the requiem?

Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing dermopathy (NFD), has had a checkered career. The index case was identified in 1997 by the group led by Shawn Cowper at Yale University. The entity was first described in 2000.[1] In 2001, the disease was formally named NFD.[2] Subsequent published case reports pointed towards systemic nature of the disease. In order to reflect this conceptual change, the nomenclature was changed to NSF.[3]

It was postulated, even before finding any incriminating factor, that NSF could be related to an agent not existing before 1997.[4] In 2006, gadolinium-based contrast agents (GBCAs) were suggested as the etiological link, when Grobner reported that five out of nine patients with end-stage renal disease (ESRD) developed cutaneous changes of NSF 2 to 4 weeks after exposure to these agents.[5] From then on, warnings and regulatory actions have been put in place, whereby renal function screening for magnetic resonance imaging (MRI) patients and using less or no GBCA when the glomerular filtration rate (GFR) is estimated to be less than 30 mL/min have become the norm. Since these new GBCA policies have come in force, NSF has nearly completely disappeared. As per the literature and the registry of the Yale-based International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR), that is the global repository of the biopsy-confirmed NSF cases (a little over 400 cases, both sources taken together), within the last 3 years, almost no new cases with symptom onset have been reported .

In India, the index case was found by us in 2004 from Kolkata.[6] It was an entirely fortuitous discovery as we stumbled upon the case while being engaged in a study on perforating dermatoses in patients with renal compromise. The credit for the histopathological diagnosis rests on Debabrata Bandyopadhyay. It was all the more remarkable because almost all the reports of NFD at that time were restricted to the US and Europe. We embarked on a formal study soon afterwards and reported a series that remains the largest one on this entity (n= 6) outside the western world.[7] Our report went a long way in dispelling notions that the condition has had geographical and racial predilections, a finding that was buttressed by quite a few case reports from different parts of the world, notably from Asia. We could add another case to our total[8] before the study had to be wound up, thanks to lack of infrastructural and logistic support. It is to be noted that since almost our entire study was conducted before the publication of the path-breaking study by Grobner,[5] we did not get to formally investigate the role of GBCA. Subsequently, a couple of cases have been reported from different parts of India, one of which provides a clear-cut evidence of the role of a GBCA (Omniscan),[9] while the other gives a negative history of such exposure.[10]

Judging from the epidemiological fallout of GBCA regulation on NSF, it seems that the disease has indeed reached its denouement. The uncertainties prevailing even 3 years back, when one could question the exact role of gadolinium in the jigsaw puzzle — whether it was really the pathogenic trigger or just an innocent bystander — seem passι.[11] The proof of the pudding has been in the eating. The disease has vanished, well, almost, with the stringent regulation of GBCAs; and, with its passing, we could rejoice.

I thank all the authors for their precious contributions for this symposium, the mood of which is distinctly celebratory, befitting the obituary of a dreaded condition that has hardly any effective cure barring prevention. The articles are testimony to the different vantage points of the authors: While Prasanta Basak and Stephen Jesmajian focus on the current concepts from the viewpoint of the internists, Rajesh Waikhom and Abhijit Taraphder review the condition from the nephrologic perspective. Zhitong Zou and Lin Ma have comprehensively reviewed all the biopsy-proven cases published hitherto and have given the radiological insight on minimizing NSF risk when performing GBCA-enhanced MRI or MR angiography.

It has been a great honour to be the Guest Editor of this Symposium and I am thankful to Dr Sandipan Dhar, the Editor, and the Editorial Board of the journal for this privilege. We sincerely hope that these contributions will be a valuable addition to NSF literature and that this symposium will be another landmark for the Indian Journal of Dermatology.