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Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report

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Abstract

Background

Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function.

Objective

The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources.

Materials and methods

We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting.

Results

We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources.

Conclusion

Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

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References

  1. Cowper SE, Robin HS, Steinberg SM et al (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356:1000–1001

    Article  CAS  PubMed  Google Scholar 

  2. Ting WW, Stone MS, Madison KC et al (2003) Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 139:903–906

    Article  PubMed  Google Scholar 

  3. Cowper SE, Bucala R, Leboit PE (2006) Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis—setting the record straight. Semin Arthritis Rheum 35:208–210

    Article  PubMed  Google Scholar 

  4. Galan A, Cowper SE, Bucala R (2006) Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 18:614–617

    Article  PubMed  Google Scholar 

  5. Auron A, Shao L, Warady BA (2006) Nephrogenic fibrosing dermopathy in children. Pediatr Nephrol 21:1307–1311

    Article  PubMed  Google Scholar 

  6. Prince MR, Zhang HL, Prowda JC et al (2009) Nephrogenic systemic fibrosis and its impact on abdominal imaging. Radiographics 29:1565–1574

    Article  PubMed  Google Scholar 

  7. Morcos SK (2007) Nephrogenic systemic fibrosis following the administration of extracellular gadolinium based contrast agents: is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition? Br J Radiol 80:73–76

    Article  CAS  PubMed  Google Scholar 

  8. Dillman JR, Ellis JH, Cohan RH et al (2007) Frequency and severity of acute allergic-like reactions to gadolinium-containing i.v. contrast media in children and adults. AJR Am J Roentgenol 189:1533–1538

    Article  PubMed  Google Scholar 

  9. Halvorsen RA (2008) Which study when? Iodinated contrast-enhanced CT versus gadolinium-enhanced MR imaging. Radiology 249:9–15

    Article  PubMed  Google Scholar 

  10. Martin DR (2008) Nephrogenic systemic fibrosis. Pediatr Radiol 38:S125–S129

    Article  PubMed  Google Scholar 

  11. Saab G, Abu-Alfa A (2008) Nephrogenic systemic fibrosis—implications for nephrologists. Eur J Radiol 66:208–212

    Article  PubMed  Google Scholar 

  12. Joffe P, Thomsen HS, Meusel M (1998) Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 5:491–502

    Article  CAS  PubMed  Google Scholar 

  13. Abu-Alfa AK (2011) Nephrogenic systemic fibrosis and gadolinium-based contrast agents. Adv Chron Kidney Dis 18:188–198

    Article  Google Scholar 

  14. Grobner T, Prischl FC (2008) Patient characteristics and risk factors for nephrogenic systemic fibrosis following gadolinium exposure. Semin Dial 21:135–139

    Article  PubMed  Google Scholar 

  15. Dharnidharka VR, Wesson SK, Fennell RS (2007) Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 22:1395

    Article  PubMed  Google Scholar 

  16. DiCarlo JB, Gupta EA, Solomon AR (2006) A pediatric case of nephrogenic fibrosing dermopathy: improvement after combination therapy. J Am Acad Dermatol 54:914–916

    Article  PubMed  Google Scholar 

  17. Foss C, Smith JK, Ortiz L et al (2009) Gadolinium-associated nephrogenic systemic fibrosis in a 9-year-old boy. Pediatr Dermatol 26:579–582

    Article  PubMed  Google Scholar 

  18. Jain SM, Wesson S, Hassanein A et al (2004) Nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 19:467–470

    Article  PubMed  Google Scholar 

  19. Jan F, Segal JM, Dyer J et al (2003) Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr 143:678–681

    Article  PubMed  Google Scholar 

  20. Krous HF, Breisch E, Chadwick AE et al (2007) Nephrogenic systemic fibrosis with multiorgan involvement in a teenage male after lymphoma, Ewing’s sarcoma, end-stage renal disease, and hemodialysis. Pediatr Dev Pathol 10:395–402

    Article  PubMed  Google Scholar 

  21. Sanchez-Ross M, Snyder R, Colome-Grimmer MI et al (2007) Nephrogenic fibrosing dermopathy in a patient with systemic lupus erythematosus and acute lupus nephritis. Pediatr Dermatol 24:E36–E39

    Article  PubMed  Google Scholar 

  22. Sharma J, Mongia A, Schoenaman M et al (2008) Nephrogenic fibrosing dermatopathy, cardiac calcification and pulmonary hypertension in an adolescent on chronic hemodialysis. Indian J Nephrol 18:70–73

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Wiginton CD, Kelly B, Oto A et al (2008) Gadolinium-based contrast exposure, nephrogenic systemic fibrosis, and gadolinium detection in tissue. AJR Am J Roentgenol 190:1060–1068

    Article  PubMed  Google Scholar 

  24. McKoy JM, Fisher MJ, Courtney DM et al (2013) Results from the first decade of research conducted by the Research on Adverse Drug Events and Reports (RADAR) Project. Drug Saf 36:335–347

    Article  CAS  PubMed  Google Scholar 

  25. Bennett CL, Nebeker JR, Lyons EA et al (2005) The Research on Adverse Drug Events and Reports (RADAR) project. JAMA 293:2131–2140

    Article  CAS  PubMed  Google Scholar 

  26. Cowper S (2011) Nephrogenic systemic fibrosis (ICNSFR Website). Retrieved from http://www.icnsfr.org. Accessed Dec. 14, 2011

  27. Girardi M, Kay J, Elston DM et al (2011) Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 65:1095–1106

    Article  PubMed  Google Scholar 

  28. Matsumoto Y, Mitsuhashi Y, Monma F et al (2012) Nephrogenic systemic fibrosis: a case report and review on Japanese patients. J Dermatol 39:449–453

    Article  PubMed  Google Scholar 

  29. Nardone B, Laumann AE, Edwards BJ et al (2012) Advancing pharmacovigilance through analysis of gadolinium-based contrast agent (GBCA) exposure dataset for nephrogenic systemic fibrosis—a RADAR report. J Am Acad Dermatol 66:AB5

    Article  Google Scholar 

  30. Bongartz G (2007) Imaging in the time of NFD/NSF: do we have to change our routines concerning renal insufficiency? MAGMA 20:57–62

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Kanal E, Barkovich AJ, Bell C et al (2007) ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 188:1447–1474

    Article  PubMed  Google Scholar 

  32. U.S. Food and Drug Administration (2010) FDA Drug Safety Communication: New warnings for using gadolinium-based contrast agents in patients with kidney dysfunction. Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm223966.htm. Accessed March 17, 2011

  33. Morcos SK, Haylor J (2010) Pathophysiology of nephrogenic systemic fibrosis: a review of experimental data. World J Radiol 2:427–433

    Article  PubMed Central  PubMed  Google Scholar 

  34. Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108

    Article  CAS  PubMed  Google Scholar 

  35. ACR Committee on Drugs and Contrast Media (2013) ACR manual on contrast media. Retrieved from http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/Contrast%20Manual/2013_Contrast_Media.pdf. Accessed June 3, 2013

  36. European Medicines Agency (2010) Questions and answers on the review of gadolinium-containing contrast agents. Retrieved from http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/gadolinium_31/WC500015635.pdf. Accessed September 18, 2011

  37. Araya CE, Dharnidharka VR (2011) Use of contrast agents in children with chronic kidney disease. In: Warady BA, Schaefer F, Alexander SR (eds) Pediatric dialysis. Springer, New York, pp 629–644

    Google Scholar 

Download references

Acknowledgement

This project was supported by NIH grants 2 R01 CA102713-03A2 (DPW), 1 R01 CA125077-01A1 (DPW) and 1K01 CA134554-01 (JMM).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair St., Ste. 1600, Chicago, IL, 60611, USA

    Beatrice Nardone, Anne E. Laumann, Steven M. Belknap, Christian Bull, Victoria Godinez-Puig & Dennis P. West

  2. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Elise Saddleton & Frank H. Miller

  3. Department of Medicine, Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Beatrice J. Edwards & June M. McKoy

  4. VA Cooperative Studies Program Clinical Research Pharmacy, Albuquerque, NM, USA

    Dennis W. Raisch

  5. University of New Mexico College of Pharmacy, Albuquerque, NM, USA

    Dennis W. Raisch

  6. Department of Medicine, Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Steven M. Belknap

  7. Southern Illinois University School of Medicine, Springfield, IL, USA

    Anand Haryani

  8. Departments of Dermatology and Pathology, Yale School of Medicine, New Haven, CT, USA

    Shawn E. Cowper

  9. Division of Nephrology and Hypertension-American University of Beirut, Beirut, Lebanon

    Ali K. Abu-Alfa

  10. Section of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Ali K. Abu-Alfa

  11. Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO, USA

    Vikas R. Dharnidharka

  12. Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    June M. McKoy & Dennis P. West

Authors
  1. Beatrice Nardone
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  2. Elise Saddleton
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  3. Anne E. Laumann
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  4. Beatrice J. Edwards
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  5. Dennis W. Raisch
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  6. June M. McKoy
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  7. Steven M. Belknap
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  8. Christian Bull
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  9. Anand Haryani
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  10. Shawn E. Cowper
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  11. Ali K. Abu-Alfa
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  12. Frank H. Miller
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  13. Victoria Godinez-Puig
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  14. Vikas R. Dharnidharka
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  15. Dennis P. West
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Corresponding author

Correspondence to Dennis P. West.

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Nardone, B., Saddleton, E., Laumann, A.E. et al. Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report. Pediatr Radiol 44, 173–180 (2014). https://doi.org/10.1007/s00247-013-2795-x

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  • DOI: https://doi.org/10.1007/s00247-013-2795-x

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