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Dermatological Manifestations of Kidney Disease pp 119–136Cite as

Nephrogenic Systemic Fibrosis

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Abstract

Nephrogenic systemic fibrosis (NSF) emerged and virtually disappeared within a span of approximately 15 years. The story of the discovery, elucidation, and near extinction of this novel disease is fascinating—and the lessons learned are vitally important in our current complex and fragmented medical treatment climate. Physicians, pharmaceutical manufacturers and regulators were confounded by a series of circumstances and trends that laid the groundwork for the emergence of NSF: (1) the off-label use of gadolinium based contrast agents (GBCAs) that had not been approved for use in the renal population; (2) the ever-increasing doses and administrations of these agents as doctors and pharmaceutical companies quickly embraced the benefits of magnetic resonance angiography (MRA); (3) the clinical and pathological features of NSF that were unlike other medication toxicities; and (4) the span between disease cause and effect that was so prolonged, that merely tying these events together required the interdisciplinary collaboration of diverse medical specialties, each of which held a piece of the puzzle. While we may celebrate the departure of NSF, its future reemergence can be anticipated if certain currently available GBCAs are accidentally administered in the setting of renal disease, or if future GBCA formulations are not evaluated for toxicity in this setting. Lastly, the long-term effects of gadolinium retention are still unknown, and the possibility of renal or non-renal patients accumulating this rare metal and developing as-yet-unsuspected conditions should be considered. Physicians need to remain alert for the reemergence of this rare condition and for the appearance of potential new toxicities that may develop in the complex medical and treatment scenarios of the future.

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Abbreviations

AKI:

Acute kidney injury

ANA:

Antinuclear antibody

CDC:

Centers for disease control

CF:

Circulating fibrocyte

CKD:

Chronic kidney disease

eGFR:

estimated glomerular filtration rate

EMEA:

European Medicines Agency

EMG:

Electromyelogram

ESRD:

End-stage renal disease

FDA:

Food and Drug Administration

GBCA:

Gadolinium based contrast agent

Gd:

Gadolinium

GFR:

Glomerular filtration rate

H&E:

Hematoxylin and eosin

IEP:

Immunoelectrophoresis

IF:

Immunofixation

LDS:

Lipodermatosclerosis

MR:

Magnetic resonance

MRA:

Magnetic resonance angiography

MRI:

Magnetic resonance imaging

NFD:

Nephrogenic fibrosing dermopathy

NSF:

Nephrogenic systemic fibrosis

PHA:

Public health advisory

POC:

Point of care

SCX:

Scleromyxedema

SPEP:

Serum protein electrophoresis

SS:

Systemic sclerosis

TGFβ1:

Transforming growth factor beta-1

TIMP-1:

Tissue inhibitor of metalloproteinases-1

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Author information

Authors and Affiliations

  1. Harvard Combined Dermatology Residency, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Avery LaChance M.D., M.P.H.

  2. Division of Nephrology and Hypertension, Department of Internal Medicine, American University of Beirut, Cairo Street, 11-0236, Beirut, Riad El-Solh, 1107 2020, Lebanon

    Ali K. Abu-Alfa M.D.

  3. Section of Nephrology, Yale University School of Medicine, 330 Cedar Street, BB 114, 208029, New Haven, CT, 06520-8029, USA

    Ali K. Abu-Alfa M.D.

  4. Department of Dermatology, Yale University School of Medicine, Yale Dermatopathology Service, 15 York Street, LMP 5031, 208059, New Haven, CT, 06520-8059, USA

    Shawn E. Cowper M.D.

  5. Department of Pathology, Yale University School of Medicine, Yale Dermatopathology Service, 15 York Street, LMP 5031, 208059, New Haven, CT, 06520-8059, USA

    Shawn E. Cowper M.D.

Authors
  1. Avery LaChance M.D., M.P.H.
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  2. Ali K. Abu-Alfa M.D.
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  3. Shawn E. Cowper M.D.
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Corresponding author

Correspondence to Shawn E. Cowper M.D. .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Nelson Clinic, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA

    Julia R. Nunley

  2. Department of Medicine, Section of Nephrology, University of Illinois at Chicago / Advocate Christ Medical Center, Oak Lawn, Illinois, USA

    Edgar V. Lerma

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LaChance, A., Abu-Alfa, A.K., Cowper, S.E. (2015). Nephrogenic Systemic Fibrosis. In: Nunley, J., Lerma, E. (eds) Dermatological Manifestations of Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2395-3_12

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