KOMO 4 |NSF - Nephrogenic Systemic Fibrosis or Nephrogenic Fibrosing Dermopathy – NFD

NSF - Nephrogenic Systemic Fibrosis or Nephrogenic Fibrosing Dermopathy – NFD

For the first time in 1997 Scientists identified Nephrogenic Systemic Fibrosis (NSF) also known as Nephrogenic Fibrosing Dermopathy (NFD).  Worldwide, approximately 200 cases of NSF/NFD. NSF/NFD is traced to the usage of gadolinium compounds as an injection to provide a brighter and better image on MRI (magnetic resonance imaging) and MRA (magnetic imaging angiography).

NSF was identified in patients with chronic severe renal insufficiency with a Glomerular filtration rate of 15 cc/min or less or a renal dysfunction due to the hepato-renal syndrome or in the perioperative liver transplantation period. It's established that patients with NSF develop fibrosis of the skin and connective tissues throughout their body.

25 cases of NSF/NFD were reported on May 29, 2006, by the Danish Medicines Agency. Out of the 25 cases, 20 occurred in Denmark and the remaining five in Austria.  These patients developed NSF/NFD within 3 months in a range of 2 weeks to 3 months after they had received the gadolinium-containing contrast agent.  The cases of the five patients from Austria are described in a publication titled:  Grobner T. Gadolinium - a specific trigger for the development of NFD and NSF Nephrol dial Transplant.

Causes of NSF/NSD

NSF/NFD is called as a signature disease as the only way to get it is through gadolinium injections given during MRI and MRA scans.  NSF/NFD occurs in patients with a history of kidney failure or liver dysfunction with high levels of acid in body fluids - a condition known as acidosis, which is common in patients with kidney failure.   

NSF/NFD is a skin condition that is often described as a swelling and tightening of the skin, usually limited to the extremities. NSF/NFD may take weeks to fully develop or even within a short period of days.  The impacts of this disease are manifold and diverse. A skin biopsy is necessary to make a definitive diagnosis about NSF/NSD as the disease is progressive and may prove to be fatal. 

Impact of NSF/NSD   

NSF/NFD in patients started from 2 days to 18 months after the MRI or MRA with the contrast agents.  Out of the 90 patients who reported NSF/NFD all hadn't received high does of a gadolinium contrast agent and some had received only one dose.  Here are possible impacts of NSF.

• Patients develop fibrosis of the skin and connective tissues throughout the body.
• Fibrosis or scarring of body organs may lead to damage to body organs that could even lead to death. 
• Inhibited flexion and extension of joints resulting in contractures due to thickening of skin. 
• Widespread fibrosis in other organs. 
• Patients may be unable to walk, or fully extend the joints if severly affected.

• Thick scar tissue may immobilize skin and joints.
• Internal organs may be paralyzed in serious cases eventually leading to fatal results.
• Weakness of muscles.

Signs and symptoms of NSF/NSD

• Burning, itching, swelling,
• Hardening and tightening of the skin, usually in the extremities
• Skin texture changes similar to an orange peel
• Red or dark patches on the skin
• Yellow spots on the white of the eyes
• Stiffness in joints & trouble moving or straightening the arms, hands, legs or feet
• Pain deep in the hip bones or ribs
• Calcification of muscle, skin, tendons
• Muscle weakness
• Symmetrical skin lesions, commonly on the ankles and thighs

Treatment for NSF/NFD

There is no consistently proven successful treatment for NSF/NFD since it is a rare disease with relatively recent diagnosis with the natural history not well understood.  However improving renal function seems to slow or arrest NSF and in many cases allows for gradual reversal of the process over time while some report a gradual improvement in mobility and slight softening of the skin over time. Complete spontaneous healing in a patient with ongoing kidney disease has not been reported.

Several kinds of treatments have been reported with investigations still underway.  The attempted treatment and improvised investigations include: oral steroids (prednisone), topical Dovonex (under occlusion), extracorporeal photopheresis (ECP), plasmapheresis, Cytoxan, Thalidomide, ultraviolet therapy, Physical therapy, Pentoxifyllin, high dose Intravenous Ig therapy, and renal transplantation.

NSF/NFD related prognosis

NSF/NFD by itself is not fatal but contributes to the death of a patient by restricting effective ventilation, restricting mobility to the point of causing an accidental fall that may be further exacerbated by fractures and clotting complications and by other means.  An estimated number of 5% or less have an exceedingly rapid and fulminant disease course that may result in death.   

Many patients with NSF have died due to the complications of their kidney disease or transplant surgery out of which was a patient who decided to discontinue dialysis despite widespread fibrosis involving the diaphragm, psoas muscles, proximal esophagus and intimal areas of vessels of the kidney and lungs.