Nephrogenic systemic fibrosis (NSF): the role of tamoxifen

Dear Sir, Nephrogenic systemic fibrosis (NSF) is exclusively found in patients with marked renal impairment who have been exposed to gadolinium (Gd) through its use as a contrast agent in magnetic resonance imaging (MRI) studies [1]. The main clinical feature of NSF is thickening and hardening of the skin, and joint contractures are common. There is no confirmed effective treatment for NSF and no current evidence in the literature that spontaneous improvement occurs. Improvement in renal function, either by recovery after an acute kidney injury or through transplantation, is thought to be the most beneficial therapy [1–3], although relapses following re-exposure have been described [3]. We describe the case of a patient who we have successfully managed with tamoxifen. A 57-year-old male developed end-stage chronic renal failure (ESCRF) secondary to biopsy-proven IgA nephropathy and was commenced on haemodialysis. He was diagnosed with an epidural abscess and required surgical decompression, with good results. A cerebellar abscess was later noted, thought to have originated from the primary site. This was treated conservatively and monitored with regular MRI scans to assess progress. Overall, the patient underwent eight separate MRI examinations in a 12-month period, accumulating a total dose of 105 mL gadoteridol (ProHance). There are no records detailing the timing of post-MRI haemodialysis, but at that time, it was not a routine practice to reschedule haemodialysis sessions to minimize Gd exposure. Around a year later, he complained of progressive stiffness of his hands and feet. Examination revealed symmetrical thickening of the skin in his distal extremities with marked limitation of joint movement. NSF was confirmed on skin biopsy. Physiotherapy was commenced but proved ineffectual, and he refused any further input from services, including any formal assessment from the occupational therapy team. He required admission to hospital due to pain, severe enough to require opiate analgesia, and markedly deteriorating mobility resulting in his being virtually immobile. While an inpatient, he was commenced on oral steroids and tamoxifen, which lead to a dramatic improvement of his condition. He left hospital opiate-free and mobile using only a walking stick, and has successfully coped at home since then. To date, there are no validated treatments for NSF. The natural history of NSF is of progressive fibrosis, leading to contractures and immobility. In 5% of patients, the disease has an aggressive course that results in death—either directly due to respiratory compromise from pleural or diaphragmatic involvement, or by patients electing to discontinue dialysis due to deteriorating quality of life [4,5]. We suggest that this observation should prompt the need for further, randomized controlled trials into the potential benefit of tamoxifen in this situation.