Generalized exfoliative skin rash as an early predictor of supratherapeutic voriconazole trough levels in a leukemic child: A case report

Document Type : Case report

Authors

1 Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Medical Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Hematopathology, Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran

4 Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, USA

5 Persian Bayan Gene Research and Training Center, Shiraz, Iran

6 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

7 Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background and Purpose: Skin rashes, mostly seen in children and adolescents, are considered among the most common side effects of azole antifungals. Although therapeutic concentrations of voriconazole (VCZ) have been documented for infected skin, there is no evidence specifying whether specific dermatologic side effects could predict high VCZ serum concentration, especially in high-risk leukemic children.
Case report: Herein, we report a unique skin side effect of VCZ in a 5-year-old boy with T-cell acute lymphoblastic leukemia (ALL) referred to Amir Medical Oncology Center in Shiraz, Iran. The patient experienced erythroderma and macular rashes shortly after VCZ consumption, leading to generalized exfoliative skin rashes. Concurrent to these skin manifestations, VCZ serum concentration reached the supratherapeutic levels despite the recommended VCZ doses. As a result, VCZ was withheld, and the patient was treated with caspofungin. The lesions were resolved gradually within 2 weeks, and the patient successfully completed his treatment course with caspofungin.
Conclusion: The unique case presented in this study emphasizes the need for a high index of suspicion for VCZ toxicity in any patient with atypical dermatologic manifestations, especially generalized exfoliative skin rashes. Based on this report, VCZ supratherapeutic concentration could be predicted early in the course of treatment. Additional therapeutic dose monitoring should be considered to establish a confirmatory diagnosis. It is required to further investigate the toxic effect of high VCZ concentration on the skin epithelium.
 
 

Keywords


1. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002; 347(6):408-15.
2. Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis. 2014; 58(7):997-1002.
3. Vöhringer S, Schrum J, Ott H, Höger PH. Severe phototoxicity associated with long‐term voriconazole treatment. J Dtsch Dermatol Ges. 2011; 9(4):274-6.
4. Sahay P, Asif MI, Maharana PK, Titiyal JS. Periocular contact dermatitis with use of topical voriconazole 1% in mycotic keratitis. BMJ Case Rep. 2018; 2018:bcr2018226498.
5. McCarthy KL, Playford EG, Looke DF, Whitby M. Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy. Clin Infect Dis. 2007; 44(5):e55-6.
6. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012; 92(4):414-7.
7. Harris R, Jones H, Artis W. Orally administered ketoconazole: route of delivery to the human stratum corneum. Antimicrob Agents Chemother. 1983; 24(6):876-82.
8. Heykants J, Van Peer A, Van de Velde V, Van Rooy P, Meuldermans W, Lavrijsen K, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses. 1989; 32(Suppl 1):67-87.
9. Cauwenbergh G, Degreef H, Heykants J, Woestenborghs R, Van Rooy P, Haeverans K. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Acad Dermatol. 1988; 18(2):263-8.
10. Jeniel E, Nett DR. Itraconazole. In: Grayson ML, Crowe SM, McCarthy JS, Mills J, Mouton JW, Norrby SR, et al, editors. Kucers' the use of antibiotics seventh edition: a clinical review of antibacterial, antifungal and antiviral drugs. Florida: CRC Press; 2018. P. 2797.
11. Neely DN. Voriconazole. 6. Adverse reactions and toxicity. In: Grayson ML, Crowe SM, McCarthy JS, Mills J, Mouton JW, Norrby SR, et al, editors. Kucers' the use of antibiotics seventh edition: a clinical review of antibacterial, antifungal and antiviral drugs. Florida: CRC Press; 2018. P. 2832.
12. Epaulard O, Villier C, Ravaud P, Chosidow O, Blanche S, Mamzer-Bruneel MF, et al. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study. Clin Infect Dis. 2013; 57(12):e182-8.
13. Brown J, Van Manen RP. Voriconazole associated leukoencephalopathy: a review of the FDA AERS database. 51st Intersci Conf Antimicrob Agents Chemother, Chicago, IL, USA; 2011. P. 17-20.
14. Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver
function test abnormalities. J Clin Pharmacol. 2006; 46(2): 235-43.
15. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2019; 71(6):1367-76.
16. Grayson ML, Crowe SM, McCarthy JS, Mills J, Mouton JW, Norrby SR, et al. Newborn infants and children. Kucers' the use of antibiotics seventh edition: a clinical review of antibacterial, antifungal and antiviral drugs. Florida: CRC Press; 2018. P. 2826.
17. Badiee P, Hashemizadeh Z, Montaseri H. Therapeutic drug monitoring of voriconazole: comparison of bioassay with high-performance liquid chromatography. Jundishapur J Microbiol. 2017; 10(4):1.
18. Luong ML, Al-Dabbagh M, Groll AH, Racil Z, Nannya Y, Mitsani D, et al. Utility of voriconazole therapeutic drug monitoring: a meta-analysis. J Antimicrob Chemother. 2016; 71(7):1786-99.
19. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008; 46(2):201-11.
20. Badiee P, Alborzi A. Detection of Aspergillus species in bone marrow transplant patients. J Infect Dev Ctries. 2010; 4(8):511-6.
21. Kim SH, Yim DS, Choi SM, Kwon JC, Han S, Lee DG, et al. Voriconazole-related severe adverse events: clinical application of therapeutic drug monitoring in Korean patients. Int J Infect Dis. 2011; 15(11):e753-8.
22. Imhof A, Schaer DJ, Schwarz U, Schanz U. Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring. Swiss Med Wkly. 2006; 136(45-46):739-42.
23. Amanati A, Lotfi M, Manen RV, Faghihi MA, Yavarian M, Zekavat O, et al. Potential voriconazole associated posterior reversible leukoencephalopathy in children with malignancies: report of two cases. J Oncol Pharm Pract. 2020; 20:1078155220941590.
24. Miyakis S, Van Hal SJ, Ray J, Marriott D. Voriconazole concentrations and outcome of invasive fungal infections. Clin Microbiol Infect. 2010; 16(7):927-33.
25. Malani AN, Aronoff DM. Voriconazole-induced photosensitivity. Clin Med Res. 2008; 6(2):83-5.
26. Denning D, Griffiths C. Muco‐cutaneous retinoid‐effects and facial erythema related to the novel triazole antifungal agent voriconazole. Clin Exp Dermatol. 2001; 26(8):648-53.
27. Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis. 2003; 36(5):630-7.
28. Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis. 2002; 34(5):563-71.
29. Abdel-Haq N, Surapaneni V, Seth D, Pansare M, Asmar BI. Voriconazole-induced photosensitivity in children: a case report and literature review. Global Pediatr Health. 2014; 1:2333794X14562230.
30. El Rouby N, Lima JJ, Johnson JA. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018; 14(4):447-60.
31. Mihăilă RG. Voriconazole and the liver. World J Hepatol. 2015; 7(14):1828-33.
Volume 6, Issue 3
September 2020
Pages 73-78
  • Receive Date: 23 June 2020
  • Revise Date: 28 September 2020
  • Accept Date: 05 October 2020
  • First Publish Date: 05 October 2020