Superior Vena Cava Obstruction Associated With Nephrogenic Systemic Fibrosis
May 2014 | Volume 13 | Issue 5 | Case Reports | 615 | Copyright © May 2014
Kassandra E. Holzem MD,a Beatrice Nardone MD PhD,a Jon W. Lomasney MD,b Pedram Yazdan MD,a Pedram Gerami MD,a,c Dennis P. West PhD,a Anne E. Laumann MBChB MRCP (UK)a
aDepartment of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL bDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL cRobert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
A 56-year-old woman with hypertension-induced end stage renal disease presented with skin thickening and mottled discoloration. Cutaneous biopsy showed increased dermal fibroblasts embedded in fibromyxoid stroma with scattered perivascular and interstitial mononuclear cells. Immunohistochemistry revealed prominent CD34+ dendritic cells in septal spaces, consistent with Nephrogenic Systemic Fibrosis (NSF). Seven years and two years prior she had received a gadolinium-based contrast agent (GBCA). She died due to NSF. Gross autopsy revealed a thickened and stenotic superior vena cava (SVC). Extensive fibrosis of the SVC, dermis, and subcutaneous tissue was noted, together with hyalinized collagen fibers within the muscular wall of the intestines and dura mater. These findings support the importance of skin changes in the recognition of life threatening extracutaneous tissue involvement in NSF. J Drugs Dermatol.
Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder, affecting individuals with severe renal dysfunction. Patients develop progressively indurated skin plaques, confluent papules, visceral fibrosis, joint contractures, and the disorder typically causes significant disability and sometimes death. NSF is associated with systemic exposure to gadolinium-based contrast agents (GBCAs) used in magnetic-resonance imaging (MRI). The diagnosis is made on the basis of clinicopathologic correlation.1,2
NSF was initially thought to involve only the skin, subcutaneous tissue, and muscles, while sparing the internal organs.3 However, subsequent evidence demonstrated that fibrosis is also present in systemic tissues 4,5. This report illustrates the importance of systemic involvement with fibrosis of visceral organs and vascular tissues, with particular attention to superior vena cava obstruction secondary to fibrosis.
A 56-year-old woman with hypertension-induced end-stage renal disease, on hemodialysis for 20 years, presented with a six-year history of skin thickening and discoloration of both legs, associated with pain, swelling, and decreased range of motion in the knees and ankles. Her medical history included nephrolithiasis, urosepsis, septic arthritis, osteomyelitis, hepatitis C, as well as a cholecystectomy and a right nephrectomy 30 years prior. In 2004, she was admitted to hospital after a syncopal episode during dialysis. Throughout the course of the admission, she suffered severe pain in the hands and forearms.
At the time, this was attributed to peripheral neuropathy. Together with the increasing awareness of the condition, these symptoms were later recognized as being due to NSF; thus, documentation of previous GBCA (dose unavailable) exposure was obtained. During the work up for a renal hematoma in early 2004, she had received an unnamed GBCA, three months prior to the onset of her symptoms.
She was readmitted to hospital in early 2011 following recurrent syncopal episodes. On examination, the skin of the arms and legs was markedly thickened, and generalized violaceous patterned plaques were present (Figure1a). The upper extremities were firm to touch and swollen (Figure 1b). A cutaneous biopsy was performed and dermatopathology revealed increased dermal fibroblasts and thickened subcutaneous septa with CD34+ dendritic cells (Figures 2a-c). Additional investigation into her medical record revealed a further GBCA exposure during a spinal MRI two years prior to this admission.
Two months later, she was again hospitalized for syncopal episodes, dyspnea, and prolonged loss of consciousness. Her condition deteriorated rapidly with therapeutically refractory atrial fibrillation and hypotension and she died within one week with septic shock and multi-organ failure.
Autopsy revealed a stenotic superior vena cava (SVC) with extensive fibrosis of a thickened muscular wall, leading to an intra-luminal diameter of only 3 millimeters at the widest point (Figure 3a). There were pericardial adhesions, annular calcifi-