Sections

Treatment

Medical Care

Nephrogenic systemic fibrosis (NSF) is usually a chronic, progressive condition. Rare cases of partial-to-complete spontaneous resolution have been reported in the absence of specific therapy, with the return of renal function. A favorable response to medical intervention is anecdotal. Of all treatments, extracorporeal photopheresis (ECP) seems to provide the best, albeit mild and extremely expensive, treatment modality for nephrogenic systemic fibrosis.

In one patient, ECP resulted in some improvement in skin texture.^[62]

In 2011, Elmholdt noted that low-dose oral imatinib mesylate slightly improved skin texture but not joint mobility in patients with nephrogenic systemic fibrosis.^[63]

In 2005, Schmook et al^[64]reported on successful treatment of nephrogenic systemic fibrosis with photodynamic therapy in a kidney transplant recipient.

In 2004, Kafi et al^[65]found that UV-A1 phototherapy improves nephrogenic systemic fibrosis.

Läuchli et al,^[66]in 2004, described the case of a 40-year-old woman with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of ECP.

Also in 2004, Chung and Chung^[67]found that nephrogenic systemic fibrosis responded to high-dose intravenous immunoglobulin.

Wahba et al^[68]suggest that UV light therapy has a role in the treatment of nephrogenic systemic fibrosis, based on 2 cases with which they were involved.

Another report noted that patients had no benefit from plasma exchange, intralesional triamcinolone, or intralesional methotrexate.

A trial of localized psoralen plus UV-A treatment in one patient produced no improvement. Oral prednisone (60 mg PO qd) has been effective in several cases, but it has been discontinued in some patients because of its adverse effects.

In 1 of 2 patients, intralesional alpha interferon (3 MU 3 times weekly) improved the skin, although in both patients, it had to be discontinued because of its adverse effects. In another patient, this therapy was associated with a worsening of lesions.

A small series of patients with dual liver/kidney transplants showed marked improvement with plasmapheresis. As renal function had improved posttransplant, the contribution of plasmapheresis to the improvement of cutaneous findings is not clear.

Cyclophosphamide has shown no efficacy in several patients.

Topical calcipotriene (Dovonex) under occlusion has resulted in subjective improvement in 2 patients. Calcipotriene plus betamethasone dipropionate (Taclonex) seemingly might have a role in topical treatment for nephrogenic systemic fibrosis.

Richmond et al^[69]noted 8 patients with nephrogenic systemic fibrosis, 5 of whom were treated with ECP for a mean number of 34 treatment sessions over a mean of 8.5 months. Mildly improved skin tightening, range of motion, and/or functional capacity were achieved.

Yerram et al^[70]reported on a patient who had nephrogenic systemic fibrosis and had multiple previous exposures to gadolinium (Gd3⁺)–based MRI studies and experienced a substantial decrease in pain and skin changes after a trial of intravenous sodium thiosulfate.

In 2008, Kreuter et al found limited effects of UV-A1 phototherapy in 3 patients with nephrogenic systemic fibrosis.^[71]

Inpatient care

Nephrogenic systemic fibrosis does not require inpatient care. No inpatient or outpatient treatment has been particularly successful in treating this condition. Plasmapheresis has shown some promise and is still being evaluated for its efficacy in persons who have not undergone transplantation.

Surgical Care

Surgical care has no role in the treatment of this condition. Although surgical care has no direct role in the treatment of nephrogenic systemic fibrosis, patients who have undergone successful kidney transplantation may show resolution of the lesions. Nephrogenic systemic fibrosis is not a contraindication to transplantation; however, because of reports of associated thrombotic events and early graft loss, evaluation for hypercoagulability should be performed.

Consultations

A dermatologist should assess the patient. The consultation is usually referred by a nephrologist. A dermatopathologist should be requested to review the biopsy material, and the suspicion of nephrogenic systemic fibrosis should be clearly indicated on the accession form.

Activity

This disease can result in limited movement. Although the role for physical therapy has not been studied, it would appear intuitive to be useful in patients who are affected.

Prevention

Guidelines have vastly decreased the number of cases of NSF. These guidelines include (1) limiting gadolinium-based contrast agents to a maximum dose of 0.1 mmol/kg, (2) dialyzing renally impaired patients undergoing dialysis rapidly following gadolinium-based contrast agents use, (3) delaying gadolinium-based contrast agents in acute renal failure by waiting until renal function improves or dialysis is started, and (4) not using nonionic linear GBCA in patients with renal failure, in particular when proinflammatory conditions are coincident.^{[72, 73, 74, 75, 76]}

Long-Term Monitoring

Because nephrogenic systemic fibrosis may restrict mobility, physical therapy might be helpful for some patients with this condition.

Medication

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Hubbard V, Davenport A, Jarmulowicz M, Rustin M. Scleromyxoedema-like changes in four renal dialysis patients. Br J Dermatol. 2003 Mar. 148(3):563-8. [Medline].
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Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001 Oct. 23(5):383-93. [Medline].
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Hancox JG, Mengesha YM, Sangueza OP, Yosipovitch G. Nephrogenic fibrosing dermopathy after five days of hemodialysis. J Drugs Dermatol. 2003 Oct. 2(5):550-3. [Medline].
Ruiz-Genao DP, Pascual-Lopez MP, Fraga S, Aragues M, Garcia-Diez A. Osseous metaplasia in the setting of nephrogenic fibrosing dermopathy. J Cutan Pathol. 2005 Feb. 32(2):172-5. [Medline].
Obermoser G, Emberger M, Wieser M, Zelger B. Nephrogenic fibrosing dermopathy in two patients with systemic lupus erythematosus. Lupus. 2004. 13(8):609-12. [Medline].
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Hauser C, Kaya G, Chizzolini C. Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis. Dermatology. 2004. 209(1):50-2. [Medline].
Glaich AS, Martinelli PT, Markus RF, Hsu S. Generalized elastolysis following nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2005 Jul. 53(1):174-6. [Medline].
Kucher C, Steere J, Elenitsas R, Siegel DL, Xu X. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure. J Am Acad Dermatol. 2006 Feb. 54(2 Suppl):S31-4. [Medline].
Edward M, Fitzgerald L, Thind C, Leman J, Burden AD. Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum. Br J Dermatol. 2007 Mar. 156(3):473-9. [Medline].
Saenz A, Mandal R, Kradin R, Hedley-Whyte ET. Nephrogenic fibrosing dermopathy with involvement of the dura mater. Virchows Arch. 2006 Sep. 449(3):389-91. [Medline].
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Ross C, De Rosa N, Marshman G, Astill D. Nephrogenic systemic fibrosis in a gadolinium-naïve patient: Successful treatment with oral sirolimus. Australas J Dermatol. 2014 Oct 21. [Medline].
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Kafi R, Fisher GJ, Quan T, et al. UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol. 2004 Nov. 140(11):1322-4. [Medline].
Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W. Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology. 2004. 208(3):278-80. [Medline].
Chung HJ, Chung KY. Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol. 2004 Mar. 150(3):596-7. [Medline].
Wahba IM, White K, Meyer M, Simpson EL. The case for ultraviolet light therapy in nephrogenic fibrosing dermopathy--report of two cases and review of the literature. Nephrol Dial Transplant. 2007 Feb. 22(2):631-6. [Medline].
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Kreuter A, Gambichler T, Weiner SM, Schieren G. Limited effects of UV-A1 phototherapy in 3 patients with nephrogenic systemic fibrosis. Arch Dermatol. 2008 Nov. 144(11):1527-9. [Medline].
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Lancelot E, Raynaud JS, Desché P. Current and Future MR Contrast Agents: Seeking a Better Chemical Stability and Relaxivity for Optimal Safety and Efficacy. Invest Radiol. 2020 Sep. 55 (9):578-588. [Medline].
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Marckmann P, Nielsen AH, Sloth JJ. Possibly enhanced Gd excretion in dialysate, but no major clinical benefit of 3-5 months of treatment with sodium thiosulfate in late stages of nephrogenic systemic fibrosis. Nephrol Dial Transplant. 2008 Oct. 23(10):3280-2. [Medline].

Media Gallery

Nephrogenic fibrosing dermopathy on the abdomen, demonstrating a peau d'orange appearance.
Nephrogenic systemic fibrosis on the abdomen, demonstrating a peau d'orange appearance. A keloid from a previous surgery is present.
Nephrogenic systemic fibrosis on the leg, demonstrating a bound-down and sclerotic appearance and texture.
Osteoid in dermis. Courtesy of Dirk M Elston, MD.
Hypercellular dermis. Courtesy of Dirk M Elston, MD.
Lollipop bodies (osteoid with protruding elastic fibers). Courtesy of Dirk M Elston, MD.

of 6

Author

Shawn Cowper, MD Director, NSF Registry Project, Associate Professor, Departments of Dermatology and Pathology, Yale University School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bracco pharmaceuticals; Ecron-Acunova.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, Association of Military Dermatologists, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Noah S Scheinfeld, JD, MD, FAAD † Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Carrie L Kovarik, MD Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine

Carrie L Kovarik, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

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