Nephrogenic systemic fibrosis

Dr Daniel J Bell ◉ and A.Prof Frank Gaillard ◉ ◈ et al.

Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, is a complication of gadolinium-based contrast agents used in MRI.

It is characterized by "firm, erythematous, and indurated plaques of the skin associated with subcutaneous edema" ¹. Eventually, flexure contractures develop, with restriction to movement, pain and pruritus. Although the skin is primarily involved, many solid organs (e.g. lungs, heart, diaphragm, liver, and kidneys) can also be involved, eventually leading to death.

Screening

Patients should be screened for the possible risk of developing NSF by using institutional screening questionnaires and calculating the eGFR ²:

renal transplant (20% develop NSF): should have eGFR checked
liver failure patients: should have eGFR checked
outpatient screening (not on dialysis): eGFR use is controversial as they rarely develop NSF

Recommendations

Avoid gadolinium-containing contrast agents in patients whose:

eGFR is <30 mL/min/1.73 m²

Cautionary use of gadolinium-containing contrast agents in patients whose ^1,3:

eGFR is <60 mL/min/1.73 m²

"When contrast-enhanced MR imaging is requested for a patient with renal insufficiency who is hospitalised due to major surgery, major infection, or a thrombotic vascular event, alternative imaging is indicated to avoid the use of gadolinium-based contrast agents; this decision should be made after consultation with the referring service and the patient" ¹.

In cases where contrast still needs to be given ²:

if eGFR <30 mL/min
- take informed consent (risk of NSF <1/10,000 patients with eGFR <30 mL/min)
- the maximum dose of 0.1 mmol/kg
- adequate hydration must be provided
if the patient is on dialysis: (inpatient)
- MRI should be done just before dialysis as the contrast can be removed by subsequent dialysis
- some centers consider dialysis a strict contraindication

typically presents weeks to months after administration of Gd
typically involves the dermis in the extremities symmetrically, less commonly the trunk with the face spared, typically sparing the antecubital and popliteal fossae
presentation resembles scleromyxedema or eosinophilic fasciitis
skin lesions: hyperpigmented, thickened brawny induration
joint contractures
pain, pruritus, skin tightness or burning sensation

Pathology

The development of NSF with exposure to gadolinium-containing MRI contrast agents has been strongly reported in patients with moderate to end-stage renal impairment. This could be due to transmetallation, which is the replacement of the gadolinium from the chelate and forming a free gadolinium ion, free gadolinium ions may then deposit in different tissues and result in inflammation and fibrosis. Low stability gadolinium contrast media show the strongest association with NSF³.

Additional positive risk factors include:

concurrent infectious/inflammatory condition
concurrent infarcted/ischemic tissue (e.g. peripheral arterial thromboembolism)
recent surgery/trauma

Histology

deep dermal biopsy required
however findings are non-specific: thickened collagen bundle, mucin deposition, spindle cell proliferation, CD3 + fibroblasts

Contrast agents

The medical literature review has shown that ~78% of all unconfounded, single-agent cases of NSF have been associated with Omniscan^® (gadodiamide), while ~20% have been associated with Magnevist^® (gadopentetate dimeglumine), and less than 2%, with OptiMARK^® (gadoversetamide) ⁴.

Radiographic features

diffuse soft tissue tracer uptake on bone scans
skin thickening and subcutaneous stranding on multiple modalities
skin and muscle activity on PET

Treatment and prognosis

no consistently effective therapy
improved renal function: renal transplant, recovery from acute renal failure (ARF)
physical therapy
extracorporeal photopheresis, plasmapheresis, immunoglobulin therapy, steroids and other immunosuppressive agents