Nephrogenic Systemic Fibrosis Clinical Presentation

Updated: May 22, 2018
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

All patients with nephrogenic systemic fibrosis have a history of renal insufficiency of varying severity and duration and gadolinium exposure (with the exception of one report involving transplant recipients in which the donor exposure to gadolinium was not reported). A few have primarily liver disease. Most patients have had treatments that include hemodialysis, peritoneal dialysis, or renal transplantation. However, neither dialysis nor transplantation is a prerequisite for nephrogenic systemic fibrosis.

Thomsen et al [13] noted that more than 90% of proven nephrogenic systemic fibrosis cases are related to gadodiamide (Omniscan) and some to gadopentetate (Magnevist). [14]

Many patients with nephrogenic systemic fibrosis have calcium pathology. Traumatic calcinosis cutis in a dialysis patient with nephrogenic systemic fibrosis has been reported. Osseous metaplasia in the setting of nephrogenic systemic fibrosis has been noted. [42] A variant of nephrogenic systemic fibrosis with osteoclastlike giant cells, which has been termed a syndrome of dysregulated matrix remodeling, has been noted. Calciphylaxis and metastatic calcification associated with nephrogenic systemic fibrosis has also been reported. [34]

Patients may have a history of a tightening or a thickening of the skin. Stiffening of the hands and flexion contractures can also occur.

Some patients may have a history of preceding episodes of severe anasarca, recent vascular surgery, or hypercoagulability.

Some patients have known concurrent liver disease and/or neoplasia. A history of liver problems may be present. Some patients may have chronic hepatitis C.

The disease can develop days, months, or years after undergoing dialysis or after renal failure starts.

Patients may report that their skin is shiny.

This condition can develop slowly.

Pain or pruritus can be a prominent feature in many patients and can be a major component of their disability.

Some patients may have taken immunosuppressive medications.

Nephrogenic systemic fibrosis has been reported in 2 patients with systemic lupus erythematosus. [43]

Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic systemic fibrosis) has been noted. [44]

Nephrogenic systemic fibrosis has been described in a renal transplant recipient with tubulointerstitial nephritis and uveitis. [45]

Glaich et al [46] noted generalized elastolysis following nephrogenic systemic fibrosis.

Kucher et al [47] noted nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure.

Edward et al [48] noted cutaneous mucinosis associated with dermatomyositis and nephrogenic systemic fibrosis. They reported on fibroblast hyaluronan synthesis and the effect on patients' serum.

Saenz et al [49] noted nephrogenic systemic fibrosis with involvement of the dura mater.

Naylor et al [50] reported on a 65-year-old woman with nephrogenic systemic fibrosis with septal panniculitis whose biopsy specimen demonstrated unique histologic features of septal panniculitis with lymphocytic aggregates and Miescher radial granulomas mimicking erythema nodosum.

Neuromuscular involvement can occur in nephrogenic systemic fibrosis, and it can be documented by electromyography/nerve conduction studies. These findings may be difficult to appreciate clinically because of joint and skin fibrosis. [51]

Nephrogenic systemic fibrosis has been reported in a 14-year-old-girl with new-onset systemic lupus erythematosus and acute lupus nephritis after gadolinium exposure. [52]

Goddard et al [53] noted nephrogenic systemic fibrosis with recurrence after allograft failure.

Metformin use might influence nephrogenic systemic fibrosis, but this is not proven. [23]

Wahba et al [2] noted 2 organ transplant recipients who they stated had had no gadolinium exposure and yet developed nephrogenic systemic fibrosis. This report is of uncertain significance because (1) the nephrogenic systemic fibrosis tissue was not examined for gadolinium in the manner of High et al [54] and (2) the history of the apposite organ donors was not obtained; thus, gadolinium may have been present in the bodies of the patients reported by Wahba et al.

Gathings et al in 2014 noted that GAP appeared as erythematous plaques, with a diameter of 0.5-2.5 cm. One patient experience pruritus and the other did not. Histopathologically, these plaques demonstrated eosinophilic, collagenous, ovoid or round bodies (sclerotic bodies) in a variety of calcification. Previously, these sclerotic bodies were thought to be pathognomonic for nephrogenic systemic fibrosis, which required chronic renal insufficiency and imaging with gadolinium; this was not the case in these two patients. [55]

Ross in 2014 noted nephrogenic systemic fibrosis in a gadolinium-naïve woman that was treated successfully with oral sirolimus. [56]

It has been found that in patients with chronic liver disease, the incidence of nephrogenic systemic fibrosis after gadolinium exposure is roughly equal to controls. [57]

Perforating osteoma cutis has been noted in a patient with long-standing nephrogenic systemic fibrosis. [58]

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Physical Examination

Nephrogenic systemic fibrosis manifests with induration, thickening, and hardening of the skin with brawny hyperpigmentation. Distinct papules and subcutaneous nodules can also be seen. Cellulitis is commonly suspected. The skin can have a peau d'orange appearance, and plaques may have an amoeboid advancing edge. The skin is often shiny and hard to the touch. A woody consistency is typical.

The extremities are the most common areas of involvement, followed by the trunk. The face is almost never involved. Yellow palmar papules resembling cutaneous calcinosis have been reported. In addition, yellow scleral plaques have been reported in patients with nephrogenic systemic fibrosis. Solomon et al [59] noted nephrogenic systemic fibrosis mimicking inflammatory breast carcinoma.

Note the images below.

Nephrogenic fibrosing dermopathy on the abdomen, d Nephrogenic fibrosing dermopathy on the abdomen, demonstrating a peau d'orange appearance.
Nephrogenic systemic fibrosis on the abdomen, demo 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, demonstr Nephrogenic systemic fibrosis on the leg, demonstrating a bound-down and sclerotic appearance and texture.
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Complications

Nephrogenic systemic fibrosis can be disabling and restrict the patient's range of motion. Falls are not uncommon, and fractures frequently result.

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