Acrocyanosis developed with amphotericin B deoxycholate but not with amphotericin B lipid complex

Amphotericin B deoxycholate (AmB-d), the main therapeutic agent for invasive fungal infections nearly for 50 years is associated with significant toxicities. Lipidbased formulations improve tolerability and may associate less side effects (Wong-Beringer A et al.,Clin Infect Dis 1998; 27: 603–18). We present a patient developed cyanosis under AmB-d treatment but not with amphotericin B lipid complex (ABLC). A 50-year-old man was admitted to our clinic with epistaxis and necrosis on the soft palate. He was under haemodialysis for chronic renal failure for 1 year. A magnetic resonance imaging revealed pansinusitis. The histopathological examination of the biopsied tissue showed fungal elements compatible with Mucormycetes. He was initiated ABLC in a dose of 5 mg kgday. Later this drug was switched to AmB-d for economical reasons on day 56 of the treatment. On the third day of the AmB-d treatment, he developed cyanosis on the fingers of hands (Fig. 1) and feet. AmB-d treatment was discontinued and cyanosis disappeared within 2 days. A repeated biopsy from the sinusal lesion showed persisting fungal elements and he was given AmB-d again. Fingers of hands and feet became cyanotic again within 2 days (Fig. 1). Discontinuation of the drug associated the improvement. He was given ABLC thereafter without any complication. Amphotericin B deoxycholate use is associated with significant toxicities limiting its use, including infusionrelated reactions, nephrotoxicity, hypokalemia and hepatotoxicity. Lipid formulations have been developed to improve tolerability while maintaining or even improving the efficacy profile of AmB-d by allowing higher doses. A systematic review demonstrated advantages with lipid-based formulations over AmB-d in terms of reduced risk of mortality and renal toxicity (Girois SB et al., Eur J Clin Microbiol Infect Dis 2006; 25: 138–49). However, the advantages with lipid-based formulations related with other side effects are not clear. Cyanotic Raynaud’s phenomenon is a rare known adverse effect of AmB-d: three previous cases have been published elsewhere (Zernikow B et al., Mycoses 1997; 40: 359–61). All the patients developed cyanosis after AmB-d but all were reported to tolerate liposomal amphotericin well. Spasm of peripheral vessels mediated by thromboxane A2 was suggested to be responsible for the cyanosis. Amphotericin B deoxycholate and its lipid-based formulations do not need adjustment for patients with decreased renal functions. However, as pharmacokinetics of these drugs are not the same (Ashley ESD et al., Clin Infect Dis 2006; 43(Suppl. 1): S28–39), renal failure may increase side effects of any drug without increasing those of another. Cyanotic Raynaud’s phenomenon is a rare side effect of AmB-d. Although the data are limited, a lipid-based formulation of it may be used instead. Correspondence: Resat Ozaras MD, Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical Faculty, Istanbul University, TR-34303 Cerrahpasa, Istanbul, Turkey. Tel./Fax: +90 212 414 3095. E-mail: rozaras@yahoo.com