A 48-year-old black man, on hemodialysis since August 2002, presented to his primary care provider (PCP) in July 2006 with excruciating leg pain. According to the patient, the leg pain had worsened during the previous six months and was so severe that he was barely able to walk without pain. He was a full-time night security guard and reported walking three to five miles each night.
The man was undergoing hemodialysis three times per week, necessitated by nephritic range proteinuria. He had a questionable history of diabetes but a known diagnosis of hypertension. Definitive diagnosis through kidney biopsy was not obtained because of the associated risk, the patient's obesity, and his aversion to the procedure.
The patient had recently been hospitalized with shortness of breath and fluid overload. Intensive dialysis allowed a significant drop in his dialysis target weight. He was readmitted a few days later with chills, fever, cough, and shortness of breath. He was diagnosed with bilateral pulmonary emboli. The patient said his hypercoagulation work-up was negative, but he was started on warfarin before discharge.
On current presentation, he had swollen, tender legs and multiple excoriations over the calves, explained by the patient's admitted scratching. His skin was shiny and tight. He was still taking warfarin, with an international normalized ratio of 2.1. The patient denied shortness of breath, pruritus (any more than expected with renal disease), or increased fluid.
In addition to warfarin, he was taking esomeprazole 40 mg/d, extended-release metoprolol 25 mg bid, cinacalcet 90 mg/d, sevelamer 4,000 mg and lanthanum 5,000 mg before every meal, mometasone furoate as needed, hydroxyzine 25 mg every four hours as needed, miconazole powder applied to the feet as needed, and a daily prescription multivitamin complex.
Laboratory tests included normal findings (for a dialysis patient) on the complete blood count; blood urea nitrogen, 101 mg/dL (reference range, 7 to 20 mg/dL); serum creatinine, 16.6 mg/dL (0.8 to 1.4 mg/dL); Kt/V (a measure of adequacy of dialysis), 1.37 (acceptable); calcium, 9.6 mg/dL (8.2 to 10.2 mg/dL); serum phosphorus, 5.6 mg/dL (2.4 to 4.1 mg/dL); intact parathyroid hormone, 359 ng/L (10 to 65 ng/L).
The patient's PCP prescribed oxycodone for the pain and referred him to the vascular clinic for evaluation of his legs. A lower leg duplex scan with ankle/brachial indices performed on July 18 showed significant bilateral peripheral vascular disease. Subsequent magnetic resonance angiography (MRA) showed a questionable adrenal gland mass. Abdominal CT with and without contrast yielded negative results for the adrenal mass but showed a cyst in the right kidney. Although cysts are commonly found in dialysis patients, the vascular surgeon elected to evaluate the cyst with an MRI with gadolinium; the mass was found to be hemorrhagic.
Further vascular work-up continued, including MRI with gadolinium on September 26, 2006, which revealed two-vessel runoff in the right foot and three-vessel runoff in the left foot. According to the vascular consult, there was no area to bypass. The patient was sent back to his PCP. At this point, he was taking oxycodone four times per day and continuing to work full-time as a night security guard.
The patient was then sent to neurology for evaluation. By this time, the severity of his leg pain had increased 90%, with worsening swelling and persistent shininess (see figure). The neurologist was unable to obtain electromyograms due to the severity of the patient's pain and lower extremity swelling. No definitive diagnosis could be made.
About one year later, the man's attending nephrology group received copies of the work-up that the PCP sent to the dialysis center. It was apparent that neither the patient's PCP nor the vascular, radiology, or neurology consultants had seen the FDA warning released in June 20061 regarding the use of gadolinium in patients with renal disease. What had started out as a peripheral neuropathy (either renal or diabetic in etiology) was now a full-blown case of nephrogenic systemic fibrosis (NSF).
Open biopsy performed on October 29, 2007, confirmed the presence of gadolinium in the patient's epidermis. He became the first documented case of NSF in the Washington, DC area.
Discussion
In the late 1990s, several reports of an unknown sclerosing dermopathy in patients with chronic kidney disease began to emerge. In 2000, the new entity was named nephrogenic systemic fibrosis, with a disease course demonstrating systemic involvement that affected multiple organ systems and often resulted in severe joint limitations. A Web-based reporting system for this newly described disease, created by Shawn Cowper, MD, of Yale University,2 made it possible to investigate associated epidemiologic factors.