Localized nephrogenic fibrosing dermopathy: Aberrant dermal repairing?

doi:10.1016/j.jaad.2007.10.491

Journal of the American Academy of Dermatology

Volume 58, Issue 2, February 2008, Pages 336-339

https://doi.org/10.1016/j.jaad.2007.10.491 Get rights and content

Nephrogenic fibrosing dermopathy (NFD) has emerged as a clinicopathologic entity since 2000 and was recently renamed nephrogenic systemic fibrosis. The cause and pathogenesis remain uncertain. The classic clinical presentation is diffuse thickening and hardening of the skin that occurs in patients with renal insufficiency, with or without systemic involvement. We report a patient with renal failure who presented to our dermatology clinic with a localized plaque on the left forearm along the vein that was traumatized during the infusion of erythropoietin. Histologic examination revealed a dermal proliferation of CD34⁺ fibrocytes with collagen fibers and interstitial mucin accumulation, features characteristic for NFD. We conclude that NFD may present as a localized, scarlike plaque after trauma and exhibit overlapping histopathologic features resembling cicatrix and other dermal reparative/regenerative processes. NFD may, in fact, be a disorder of aberrant extracellular matrix remodeling in patients with renal insufficiency. This is a single case observation with discussion of literature and attempted hypothesis on pathogenesis. No experimental evidence is provided.

Section snippets

Case report

A 56-year-old African American man presented to our dermatology clinic in March 2005 with cordlike plaques along the veins on the left upper extremity and hand. The patient had a history of end-stage renal disease secondary to polycystic kidney disease requiring many years of dialysis and ultimately renal transplantation 1 year before presentation. He reported that the lesion developed immediately after intravenous catheterization and subsequent infusion of erythropoietin. On physical

Discussion

NFD, a fibrosing disorder in patients with renal insufficiencies, was first reported a few years ago¹ and was recently renamed NSF because of the systemic involvement in some patients. The most intriguing aspect of this disease has been the pathogenesis and pathophysiology. Because all reported cases appeared after the late 1990s, it is reasonable to speculate that patients may have been exposed to a novel agent that caused the disorder. However, the only known consistent association thus far

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Cited by (14)

Nephrogenic systemic fibrosis: Review of 370 biopsy-confirmed cases
2011, JACC: Cardiovascular Imaging
Discovery of an association between gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF) has led to less use of GBCA-enhanced magnetic resonance imaging in dialysis patients and patients with severe renal failure at risk of NSF, and the virtual elimination of new cases of NSF. But shifting patients with renal failure to alternative imaging methods may subject patients to other risks (e.g., ionizing radiation or iodinated contrast). This review paper examines 370 NSF cases reported in 98 articles to analyze NSF risk factors. Eliminating multiple risk factors by limiting GBCA dose to a maximum of 0.1 mmol/kg, dialyzing patients undergoing dialysis quickly following GBCA administration, delaying GBCA in acute renal failure until after renal function returns or dialysis is initiated, and avoiding nonionic linear GBCA in patients with renal failure especially when there are proinflammatory conditions may substantially reduce the risk of NSF.
Nephrogenic systemic fibrosis
2011, Revue de Medecine Interne
La fibrose systémique néphrogénique est une entité récente touchant l’insuffisant rénal, d’origine probablement toxique. Les malades souffrent d’une sclérose cutanée touchant de manière bilatérale et symétrique les membres et parfois le tronc, pouvant les confiner à l’immobilité du fait des contractures articulaires et d’une fibrose musculaire associée. Une atteinte systémique est décrite avec notamment cardiomyopathie, fibrose pulmonaire, paralysie diaphragmatique. L’examen histologique d’une biopsie cutanée confirme le diagnostic du fait de l’existence d’une sclérose avec de nombreux fibrocytes CD34+. Le pronostic est sévère avec de nombreux décès, rarement directement liés à la maladie. Une évolution favorable est possible, surtout en cas d’amélioration de la fonction rénale. Les traitements ont une efficacité limitée. La responsabilité des ions gadolinium toxiques (Gd⁺⁺⁺), libérés par certains produits de contraste utilisés en imagerie par résonance magnétique nucléaire, est étayée par des arguments épidémiologiques, biochimiques et expérimentaux. Des recommandations ont été faites en cas de nécessité d’examens de résonance magnétique nucléaire chez l’insuffisant rénal. Si elles sont suivies et efficaces, il est probable que cette affection disparaisse.
Nephrogenic systemic fibrosis is a recently described entity that occurs in patients with advanced renal failure. Its cause is probably toxic. The patients develop skin thickening, which is usually symmetrical on the limbs and sometimes extend to the trunk. Joint contractures and muscle sclerosis confine the patients to wheelchair. Systemic involvement may occur and includes cardiomyopathy, pulmonary fibrosis and diaphragmatic paralysis. The diagnosis is confirmed by the association of skin fibrosis and a cellular infiltration composed of CD34+ fibrocytes. Prognosis is severe with many deaths, rarely directly related to the disease. An improvement of lesions is possible, especially in case of resolution of the renal insufficiency. Several treatments have been evaluated, but none has shown consistent benefit. The toxic culprit is likely to be the gadolinium ions (Gd⁺⁺⁺), released from some contrast agents used in nuclear magnetic resonance imaging. Evidence of the responsibility of Gd⁺⁺⁺ is based on epidemiologic, biochemical and experimental data. Recommendations have been published for patients with renal insufficiency requiring a nuclear magnetic resonance imaging. If they are followed and efficient, it is likely that nephrogenic systemic sclerosis will disappear.
Quantitative assessment of dermal cellularity in nephrogenic systemic fibrosis: A diagnostic aid
2011, Journal of the American Academy of Dermatology
Nephrogenic systemic fibrosis (NSF) affects patients with impaired renal function who have received gadolinium-containing contrast agents (GCCAs). Increased dermal cellularity is a key diagnostic feature of NSF, however, the histologic findings can be subtle.
We sought to determine whether dermal cellularity in skin biopsy specimens from NSF cases: (1) differs significantly from that of controls; and (2) correlates with duration of the skin lesions, level of plasma creatinine, GCCA dose, or a combination of these.
Seventeen NSF skin biopsy specimens and age-, sex-, and site-matched controls were retrieved from the dermatopathology files of the Massachusetts General Hospital in Boston. Dermal cellularity was manually quantified on hematoxylin-eosin–stained sections and patient medical records were reviewed for demographic and clinical data.
NSF cases showed a mean dermal cellularity of 70.8/high-power field (control mean: 14.4/high-power field, P < .001) and a cut-off range of 19 to 26/high-power field was established. No significant correlation was identified between dermal cellularity and demographic and clinical data.
In this retrospective analysis, duration of skin lesion was defined as the interval from most recent prior GCCA study, rather than the actual clinical onset, to time of skin biopsy, and the cumulative GCCA dose may reflect a minimum if GCCA was received at an outside institution.
Enumeration of dermal cellularity on hematoxylin-eosin–stained sections can aid in the histologic diagnosis of NSF in the setting of chronic kidney disease and GCCA exposure and is independent of patient age, sex, plasma creatinine, time from last GCCA exposure, and GCCA dose.
Revisiting nephrogenic systemic fibrosis in 6 kidney transplant recipients: A single-center experience
2010, Journal of the American Academy of Dermatology
Citation Excerpt :
Numerous nonhematopoietic side effects of ESAs are recognized, including angiogenesis and enhancement of the fibrin-induced wound-healing response in rats via increased expression of inducible nitric oxide synthase protein within macrophages.32 A recent case report by Deng et al33 described the development of a localized scarlike plaque directly after intravenous infusion of erythropoietin. Considering these data, a potentially adverse effect of prolonged high doses of ESA in human beings, particularly in uremic patients with underlying inflammatory status, cannot be excluded as a possible contributory mechanism for some events observed in NSF.
Nephrogenic systemic fibrosis (NSF) is a fibrotic disorder occurring in patients with renal dysfunction. Exposure to gadolinium (Gd)-based contrast agents (GBCAs) during renal impairment is associated with development of NSF.
A cross-referenced search of kidney transplantation and radiology databases at a single institution revealed the prevalence of NSF in the transplant population. Clinical records and skin biopsy specimens from 6 patients with kidney transplant given a diagnosis of NSF were reviewed to identify contributing factors.
Between January 1999 and December 2006, NSF was diagnosed in 6 of 705 patients with kidney transplant (0.9%). Renal function was impaired in all patients. Of 33 patients with kidney transplant exposed to GBCAs, 5 (15.2%) developed NSF. Disease onset ranged from 7 days to 11 months after exposure to GBCAs. All 5 patients exposed to GBCAs who developed NSF were also treated with a β-blocker and clinical improvement was observed with discontinuation. The sixth case NSF appeared unrelated to Gd, without a known exposure, and testing of tissue via mass spectrometry revealed no Gd. Symptoms of NSF in this patient disappeared after administration of darbepoetin was switched from subcutaneous to intravenous injection. One patient with NSF who manifested the highest Gd level in tissue died 22 months after disease onset.
The study represents the retrospective experience of only a single center.
NSF can develop in kidney transplant recipients with altered graft function. In these patients, exposure to GBCAs appears associated with development of NSF. The role of β-blockers in the course of the disease merits further investigation.
Cutaneous mucinoses
2009, Weedon's Skin Pathology: Third Edition
Nephrogenic systemic fibrosis
2009, Annales de Dermatologie et de Venereologie

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Case reportLocalized nephrogenic fibrosing dermopathy: Aberrant dermal repairing?

Section snippets

Case report

Discussion

Lancet

Am J Kidney Dis

J Am Acad Dermatol

Am J Kidney Dis

Semin Arthritis Rheum

J Am Acad Dermatol

Am J Pathol

Case report
Localized nephrogenic fibrosing dermopathy: Aberrant dermal repairing?