Nephrogenic fibrosing dermopathy
What is nephrogenic fibrosing dermopathy?
Nephrogenic fibrosing dermopathy is a rare condition that results in tightened, swollen skin. It was first described in patients with kidney disease in 1997.
Nephrogenic fibrosing dermopathy predominantly affects the skin, but abnormal fibrosis of the internal organs may also occur, which is then often called nephrogenic systemic fibrosis.
Who is affected by nephrogenic fibrosing dermopathy?
Nephrogenic fibrosing dermopathy mainly affects patients with renal insufficiency (kidney disease).
It has no ethnicity or sex predilection. It has been reported in wide range of age groups from children to the elderly but most frequently seen in those of middle age. It is not associated with the duration of renal failure, can occur early or late in the disease, and affects patients treated with haemodialysis, peritoneal dialysis and renal transplantation.
Nearly all affected patients have had imaging studies with gadolinium, a contrast agent used in magnetic resonance imaging studies (MRIs and MRAs). Some have reported that the gadolinium exposure was up to 18 months before symptoms developed. Researchers have identified gadolinium in skin biopsies of nephrogenic fibrosing dermopathy. The precise mechanism of this causal relationship has not been established.
Nephrogenic fibrosing dermopathy has also been seen in patients with clotting problems or who have had recent surgery (particularly vascular surgery). It is very common for renal patients to have undergone a vascular procedure, such as AV fistula formation before starting haemodialysis.
What are the clinical features?
Nephrogenic fibrosing dermopathy is usually limited to the limbs, most often affecting ankles to thighs or wrists to upper arms.The trunk may also be involved.
- Tightening and swelling of the skin typically develops over days to weeks
- The skin is indurated, thickened, and woody in texture
- There may be papules (small bumps) and subcutaneous nodules (larger lumps under the skin)
- Yellow papules may appear around the eyes
- The skin surface may be shiny or have a peau d'orange appearance
- Brawny brown discolouration may occur
- The range of movement of affected joints may be reduced
- Muscle weakness and contractures may develop
About five percent will have a rapidly progressive course. Within weeks of disease onset, these patients become dependent on wheelchairs and may suffer from falls.
What is the cause?
The cause of nephrogenic fibrosing dermopathy is still unclear. Gadolinium based contrast agents are associated with varying risk of developing nephrogenic systemic fibrosis relating to their ability to release free gadolinium ions into the circulation. Gadodiamide and gadopentetic acid have the highest risk, and these agents should not be used in patients with severe kidney disease or acute renal insufficiency of any severity. Gadobenic acid has medium risk and gadobutrol and gadoteric acid appear to have low risk of causing the disease but all these agents should be used with caution in patients with severe renal insufficiency.
Recent studies have suggested that a circulating fibrocyte is responsible. This is a cell that causes fibrosis or scarring. For some unknown reason, it diffuses into the dermis of the skin, where it changes to look similar to normal dermal fibroblasts.
Why the circulating fibrocyte changes into terminal fibroblast-like cells in the skin and other organs is not known. It does seem however directly related to kidney function. Blood clotting may be part of the process as nephrogenic fibrosing dermopathy is frequently seen in association with surgery and thrombosis.
What investigations should be done?
Blood tests and imaging studies are unhelpful, except in ruling out other diseases.
A deep skin biopsy may be useful.
What treatment is available?
Nephrogenic fibrosing dermopathy is usually a chronic and progressive condition. Rarely, partial to complete spontaneous resolution has been reported in the absence of specific therapy, with improvement in renal function.
Physical therapies particularly swimming and massage are important to maintain muscle strength and joint function.
Anecdotal success has been reported with the following treatments.
- Extracorporeal photopheresis
- Photodynamic therapy
- Intravenous immunoglobulin
- UVB or UVA1 phototherapy
- Systemic steroids
- Intralesional interferon
- Vitamin D analogues such as calcipotriol in combination with potent topical steroids
- Sodium thiosulfate
Surgery has no role.
What is the prognosis?
Nephrogenic fibrosing dermopathy is rare and a relatively new disorder. Its natural history is not well understood. Some patients make a gradual recovery or gain improved mobility, but it is progressive in most.
Many patients die as a complication of their kidney disease or transplant surgery. A minority of patients, approximately 5%, have a fulminant course with rapid progression. Nephrogenic fibrosing dermopathy may contribute to death by restricting mobility leading to falls, fractures and the ensuing complications.