Invasive Rhino-Orbito-Cerebral Mucormycosis in Pediatric Patient with Acute Leukemia

Czech version

Authors: Eva Bačová ¹; Filip Chovanec ¹; Miroslava Makohusová ¹; Stanislava Hederová ¹; Martina Mikesková ¹; Andrea Hrašková ¹; Bruno Rudinský ²; Lukáš Plank ³; Pavlína Volfová ⁴; Alexandra Kolenová ¹
Authors‘ workplace: Klinika detskej hematológie a onkológie LF UK a Národný ústav detských chorôb, Bratislava, Slovenská republika 2 Neurocentrum, Klinika detskej chirurgie LF UK a Národný ústav detských chorôb, Bratislava, Slovenská republika 3 Ústav patologickej anatómie, ¹
Published in: Klin Onkol 2020; 33(2): 138-144
Category: Case Report
doi: https://doi.org/10.14735/amko2020138

Overview

Background: Invasive fungal infections are a life-threatening complication of cancer treatments, especially in hemato-oncological patients. Mucormycosis is the third leading cause of invasive fungal infections after Aspergillus and Candida infections. The first clinical symptoms are usually non-specific, which can lead to a late diagnosis and delayed therapy.

Purpose: The objective of this report is to summarize data in the literature about mucormycosis and to present a case report of a patient with acute lymphoblastic leukemia, who developed this infection at our center. Risk factors for the development of mucormycosis, clinical symptoms, radiology, laboratory results, and outcome were retrospectively evaluated.

Case: We describe a 6-years-old female patient with acute lymphoblastic leukemia. During the induction phase of therapy, the patient developed febrile neutropenia and did not respond to therapy with a combination of antibiotics and supportive treatment. Pansinusitis and orbitocellulitis developed. Examination of the biological material revealed that the etiological agent was a Rhizopus sp. The patient was treated with a combination of antimycotic drugs, but the infection disseminated to the central nervous system. She underwent radical surgical resection of the affected tissue. At this time, she is still under treatment with antimycotic and oncology agents, but is in remission of the main diagnosis and in good clinical condition.

Conclusion: Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and initiation of effective therapy using a combination of amphotericin B administration and surgery are necessary to obtain a favorable outcome.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Keywords:

mucormycosis – acute leukemia – Rhizopus

Sources

1. Hibbett DS, Binder M, Bischoff JF et al. A higher level phylogenetic classiﬁcation of the Fungi Mycol Res 2007; 111 (5): 509–547. doi: 10.1016/j.mycres.2007.03.004.

2. Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41 (5): 634–653. doi: 10.1086/432579.

3. Skiada A, Lass-Floerl C, Klimko N et al. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol 2018; 56 (Suppl1): S93–S101. doi: 10.1093/mmy/myx101.

4. Petrikkos G, Skiada A, Lortholary O et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 (Suppl 1): S23–S34. doi: 10.1093/cid/cir866.

5. Chakrabarti A, Singh R. Mucormycosis in India: uniquefeatures. Mycoses 2014; 57 (Suppl 3): 85–90. doi: 10.1111/myc.12243.

6. Chander J, Stchigel AM, Alastruey-Izquierdo A et al. Fungal necrotizing fasciitis, an emerging infectious disease caused by Apophysomyces (Mucorales). Rev Iberoam Micol 2015; 32 (2): 93–98. doi: 10.1016/j.riam.2014.06.005.

7. Pana ZD, Seidel D, Skiada A et al. Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries. BMC Infectious Diseases 2016; 16 (1): 667. doi: 10.1186/s12879-016-2005-1.

8. Skiada A, Pagano L, Groll A et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011; 17 (12): 1859–1867. doi: 10.1111/j.1469-0691.2010.03456.x.

9. Jeong W, Keighley C, Chen S et al. The epidemiology, management and outcomes of invasive mucormycosis in the 21st century: a systematic review. [online]. Available from: https: //www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=51958.

10. Klimko N, Khostelidi S, Volkova A et al. Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia. Mycoses 2014; 57 (Suppl 3): 91–96. doi: 10.1111/myc.12247.

11. Tissot F, Agrawal S, Pagano L et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017; 102 (3): 433–444. doi: 10.3324/haematol.2016.152900.

12. Cornely OA, Arikan-Akdagli S, Dannaoui E et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis. Clin Microbiol Infect 2014; 20 (Suppl 3): 5–26. doi: 10.1111/1469-0691.12371.

13. Katragkou A, Walsh TJ, Roilides E. Why is mucormycosis more difﬁcult to cure than more common mycoses? Clin Microbiol Infect 2014 (Suppl 6); 20: 74–81. doi: 10.1111/1469-0691.12466.

14. Lengerova M, Racil Z, Hrncirova K et al. Rapid detection and identification of mucormycetes in bronchoalveolar lavage samples from immunocompromised patients with pulmonary infiltrates by use of high-resolution melt analysis. J Clin Microbiol 2014; 52 (8): 2824–2828. doi: 10.1128/JCM.00637-14.

15. Funada H, Matsuda T. Pulmonary mucormycosis in a hematology ward. Intern Med 1996; 35 (7): 540–544. doi: 10.2169/internalmedicine.35.540.

16. Imhof A, Balajee SA, Fredericks DN et al. Breakthrough fungal infections in stem cell transplant recipiens receiving voriconazole. Clin Infect Dis 2004; 39 (5): 743–746. doi: 10.1086/423274.

17. Bitar D, Van Cauteren D, Lanternier F et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg Infect Dis 2009; 15 (9): 1395–1401. doi: 10.3201/eid1509.090334.

18. Rees JR, Pinner RW, Hajjeh RA et al. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992–1993: results of population-based laboratory active surveillance. Clin Infect Dis 1998; 27 (5): 1138–1147.

19. Farmakiotis D, Kontoyiannis DP. Mucormycosis. Infect Dis Clinf North Am 2016; 30 (1): 143–163. doi: 10.1016/j.idc.2015.10.011.

20. Walsh TJ, Gamaletsou MN. Treatment of fungal disease in the settings of neutropenia. Hematology Am Soc Hematol Educ Program 2013; 2013: 423–427. doi: 10.1182/asheducation-2013.1.423.

21. Pagano L, Offidani M, Fianchi L et al. Mucormycosis in hematologic patients. Haematologica 2004; 89 (2): 207–214.

22. Legouge C, Caillot D, Chrétien ML et al. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia? Clin Infect Dis 2014; 58 (5): 672–678. doi: 10.1093/cid/ cit929.

23. Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect 2009; 5 (Suppl 5): 60–65. doi: 10.1111/j.1469-0691.2009.02999.x.

24. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation and management. Clin Microbiol Rev 2005; 18 (3): 556–569. doi: 10.1128/CMR.18.3.556-569.2005.

25. Lackner M, Caramalho R, Lass-Flörl C. Laboratory diagnosis of mucormycosis: current status and future perspectives. Future Microbiol 2014; 9 (5): 683–695. doi: 10.2217/fmb.14.23.

26. Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy signiﬁcantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008; 47 (4): 503–509. doi: 10.1086/590004.

27. Lanternier F, Poiree S, Elie C et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-Amb) for the initial treatment of mucormycosis. J Antimicrob Chemother 2015; 70 (11): 3116–3123. doi: 10.1093/jac/dkv236.

28. Kyvernitakis A, Torres HA, Chamilos G et al. Initial use of combination treatment does not impact survival of 106 patients with hematologic malignancies and mucormycosis: a propensity score analysis. Clin Microbiol Infect 2016; 22 (9): e1–e8. doi: 10.1016/j.cmi.2016.03.029.

29. Reed C, Bryant R, Ibrahim AS et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008; 47 (3): 364–371. doi: 10.1086/589857.

30. Gil-Lamaignere C, Simitsopoulou M, Roilides E et al. Interferon-gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect Dis 2005; 191 (7): 1180–1187. doi: 10.1086/42 8503.

31. Roilides E, Antachopoulos C, Simitsopoulou M. Pathogenesis and host defence against Mucorales: the role of cytokines and interaction with antifungal drugs. Mycoses 2014; 57 (Suppl 3): 40–47. doi: 10.1111/myc.12236.

32. Gebremariam T, Alkhazraji S, Lin Lin et al. Prophylactic treatment with VT-1161 protects immunosuppressed mice from Rhizopus arrhizus var. arrhizus infection. Antimicrob Agents Chemother 2017; 61 (9): e00390– e0039017. doi: 10.1128/AAC.00390-17.