The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

Abstract

Background: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency. Objectives: To describe the various presentations and identify predictive factors of death in patients with CPX. Methods: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days). Results: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes. Conclusions: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.

Perioperative Management of Calciphylaxis: Literature Review and Treatment Recommendations

“…A retrospective study of 71 patients with calciphylaxis undergoing sodium thiosulfate treatment showed that cerium nitrate-silver sulfadiazine therapy might be useful for vascular decalcification and infection prevention. 28 A study evaluating a biofilm of purified collagen matrix with polyhexamethylene biguanide showed complete ulcer healing and re-epithelization in a patient with calciphylaxis. 23 Use of the novel therapy SNF472, an intravenous formulation of myoinositol hexaphosphate, to inhibit hydroxyapatite crystal formation and prevent vascular calcification has shown potential therapeutic benefit.…”

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

“…Among these, 5 (9.6%) involved clinical studies that examined antioxidants for treatment of VC, while 47 (90.4%) involved experimental studies. For clinical therapeutic studies, four (80%) used parenteral sodium thiosulfate (STS), while one (20%) used topical cerium nitrate 13–17 . For experimental approaches, totally 36 compounds with antioxidant property have been tested against VC, including 12 natural dietary substances, 5 natural non-dietary substances, and 19 pharmaceuticals or synthetic chemicals (Fig.…”

“…We identified five clinical studies testing one parenteral and the other topical agent with an antioxidative ability regarding their efficacy in treating VC (Table 2) 13–17 . STS, which has been repeatedly tested in experimental models for inhibiting VC progression, is also used clinically to treat calcification involving arteries from different anatomical locations.…”

“…However, it is evident that these studies are anecdotal, enrolling few patients, and the results appear heterogeneous with some showing calcification regression 14,15 while others reporting no interval changes 13,16 . A topical chemical, cerium nitrate, has been shown to improve the overall outcome of patients with calciphylaxis when used for wound dressing, presumably through ROS scavenging and chelating local calcium 17 . Further studies are still needed to confirm these findings.…”

“…A topical chemical, cerium nitrate, has been shown to improve the overall outcome of patients with calciphylaxis when used for wound dressing, presumably through ROS scavenging and chelating local calcium 17 . Further studies are still needed to confirm these findings.…”