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CASE REPORT
Year : 2019  |  Volume : 22  |  Issue : 4  |  Page : 582-584

Invasive fungal consecutive infections in a patient with acute myeloid leukaemia


1 Department of Hematology and Medical Oncology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Infectious Diseases, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Clinical Pathology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Date of Acceptance22-Nov-2018
Date of Web Publication11-Apr-2019

Correspondence Address:
Dr. M Salehi
Imam Khomeini Hospital, Keshavarz Boulevard, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_359_17

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   Abstract 


A woman with AML who became febrile and neutropenic after chemotherapy. At the first, Aspergillus was isolated from a sinus biopsy. After 4 weeks, while she was taking voriconazole, another episode of fever combined with dry coughs was detected. Fungal culture and histopathology of sinus biopsy revealed mucormycosis.

Keywords: Hematologic malignancy, invasive fungal coinfections, invasive fungal consecutive infections


How to cite this article:
Safai Nodeh S R, Dehghan Manshadi S A, Jahanbin B, Khodaveisi S, Giasvand F, Seifi A, Salehi M. Invasive fungal consecutive infections in a patient with acute myeloid leukaemia. Niger J Clin Pract 2019;22:582-4

How to cite this URL:
Safai Nodeh S R, Dehghan Manshadi S A, Jahanbin B, Khodaveisi S, Giasvand F, Seifi A, Salehi M. Invasive fungal consecutive infections in a patient with acute myeloid leukaemia. Niger J Clin Pract [serial online] 2019 [cited 2019 Jul 24];22:582-4. Available from: http://www.njcponline.com/text.asp?2019/22/4/582/255923




   Introduction Top


Mucormycosis and aspergillosis are two serious opportunistic fungal infections in immunodeficient patients and both are associated with severe angioinvasion.[1] Epidemiology of fungal infections has changed with the introduction of antifungal chemoprophylaxis after 1990s.[2],[3] There is a significant decrease in the incidence of candidiasis in leukemic patients after introduction of fluconazole as prophylaxis and now aspergillosis is the most common invasive fungal infection in most centers.[2],[3] In addition, recently there have been reports of increasing incidence of mucormycosis among patients with hematologic malignancy in some centers.[2],[3] Invasive aspergillosis is the clinical infection that is caused usually by Aspergillus fumigatus and mucormycosis is also an invasive fungal infection which results from different kinds of fungi of the Phycomycetes family. The reports of coinfection or consecutive infections of invasive aspergillosis and mucormycosis are very rare and more have been seen in severe immunocompromised patients.[4],[5]

Case Report

A 34-year-old rural woman presented with a 2-month history of weakness, fatigue, anemia, and thrombocytopenia. Acute myeloid leukemia (AML-Non M3) was diagnosed through peripheral blood smear and bone marrow biopsy-aspiration. Chemotherapy was administered with 7 days of standard-dose cytarabine and 3 days of daunorubicin. On the 18th day of chemotherapy, while patient was taking fluconazole (400 mg/day) as prophylaxis, we detected fever (38.5°C) and severe neutropenia (ANC < 100). Antibiotic regimen with imipenem and vancomycin was started and sepsis workup was done. After 72 h, the woman's condition worsened. The results of primary sepsis workup were negative. The patient became dyspneic in addition to the fever. Physical reexamination revealed a necrotic black scar on the nasal septum and tachypnea (respiratory rate: 33/min). Amphotericin B was prescribed and the following investigations were ordered. The CT scan revealed pan sinusitis with bone destruction [Figure 1]. There were necrosis and black scar in sinusoscopy; so surgical debridement and tissue biopsy were done. Serum galactomannan was 2.5 and histopathology revealed septated narrow angles hyphae [Figure 2] and Aspergillus grew on tissue culture. After beginning of amphotericin B and surgical debridement, symptoms abated. Amphotericin B was changed to voriconazole, and despite profound neutropenia, fever and other complaints disappeared. Galactomannan level decreased to 1.1 after 2 weeks.
Figure 1: Paranasal CT scan, coronal view, revealed pan sinusitis with bone destruction

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Figure 2: Histologic examination: Septated narrow angels hyphae (hematoxylin and eosin staining)

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One month later, when she was being scheduled for the next chemotherapy cycle, another episode of fever was detected, with epistaxis and a dry cough. Amphotericin B was added to voriconazole and investigations were repeated. On a second CT scan, we detected new lesions in the PNS and multiple bilateral nodules with halo sign in both fields of her lungs [Figure 3]. Culture and histopathology of sinus biopsy revealed mucormycosis [Figure 4]. Antifungal combination therapy continued until 6 weeks. The complaints resolved and several sinusoscopy results were negative for fungal infections.
Figure 3: Chest CT scan; parenchymal and axial view, multiple bilateral nodules with halo sign in both lungs

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Figure 4: Histologic examination; nonseptate ribbon-like hyphae (hematoxylin and eosin staining)

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   Discussion Top


Sometimes, coinfection or consecutive infections with opportunistic microorganisms are detected in severe immunodeficient patients. These infections can be caused by fungal, mycobacterial, and even parasitic agents.[2],[3],[6],[7],[8] Coinfection or consecutive infections of invasive aspergillosis and mucormycosis have been usually reported in hematologic malignancy patients with severe neutropenia.[9] For example, in a patient with chronic lymphocytic leukemia treated with alemtuzumab reported by Henn and coworkers, there were three consecutive fungal infections (first cryptococcosis, and when the patient was taking amphotericin B and flucytosine, aspergillosis and mucormycosis were detected).[9]

In another report, an AML patient was infected with aspergillosis and mucormycosis during chemotherapy, took liposomal Amphotericin B, and was discharged after remission.[2] In addition, a case of Castleman's disease under chemotherapy developed aspergillosis and mucormycosis sinusitis and was cured after early surgical and medical treatment.[6]

There are several risk factors for aspergillosis and mucormycosis coinfection. These include hematological malignancy and intensive chemotherapy, hematopoietic stem-cell transplantation, severe graft-versus-host disease, and high-dose or long-term corticosteroid therapy.[3],[4],[5] Moreover, these coinfections or consecutive infections have been reported in patients with diabetes mellitus. In two available reports for aspergillosis and mucormycosis coinfection, two diabetic patients died during antifungal treatment.[4],[5]

Delay in diagnosis and beginning of treatment in fungal infections is usually associated with extensive vascular invasion and severe necrotic lesions. In other words, early diagnosis and treatment is the surest way to cure these infections.[1],[10]

Definitive diagnosis of fungal infections is very difficult and is feasible in only less than 40% of cases. The differential diagnosis between aspergillosis and mucormycosis is problematic because of the similar clinical and radiological findings. Evaluation of tissue biopsies is the preferred method.[3],[5]

Faster growth of mucorales compared to the Aspergillus family is an important point that emphasizes the need for earlier diagnosis and quicker treatment of mucormycosis compared with aspergillosis for preventing bad outcomes in mucormycosis cases.[10]

Early implementation of empiric antifungal treatment is the standard approach to manage hematologic malignancy patients with suspected fungal infections, especially in the neutropenic phase after chemotherapy.[2]

Voriconazole is the treatment of choice for patients with invasive aspergillosis but is not effective against mucorales. Different types of amphotericin B are effective against Mucorales, Aspergillus, and Candida.[3] As mentioned, differentiation between these three fungal infections is very important because the drug of choice is different.[3]

It seems now that there is only one drug for intravenous induction treatment of aspergillosis and mucormycosis coinfection and it is amphotericin B. But there is no accurate information about the duration and dosage of treatment in these cases. Posaconazole is only oral secure medication for treating aspergillosis–mucormycosis coinfection.[2]

In conclusion, in immunodeficient people, especially patients with hematologic malignancies with deep neutropenia, signs and symptoms of refractory infection or relapse of invasive fungal infections should prompt the clinicians to consider coinfection or consecutive fungal infections with two different types of molds.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

None.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Vaidya D, Shah P. Coinfection by Aspergillus and zygomycetes species in a case of acute rhinosinusitis. Case Rep Otolaryngol 2011;2011. doi: 10.1155/2011/382473.  Back to cited text no. 1
    
2.
Bergantim R, Elisabete R, Fernanda T, Guimarães JE. Invasive coinfection with Aspergillus and Mucor in a patient with acute myeloid leukemia. Clin Drug Investig 2013;33:S51-5.  Back to cited text no. 2
    
3.
Warpe BM. Pulmonary aspergillosis and mucormycosis in an Immunocompetent type 1 diabetic patient with past history of healed tuberculosis. J Diabetol 2015;2:4.  Back to cited text no. 3
    
4.
Rit K, Saha R, Dey R, Barik G. Rhino-oculo-cerebral Aspergillus and Mucor coinfections in an immunocompromised patient with type 2 diabetes mellitus. Med J DY Patil Univ 2014;7:486-8.  Back to cited text no. 4
  [Full text]  
5.
Mahadevaiah AH, Rajagopalan N, Patil M, Shivaprasad C. Coinfection of pulmonary mucormycosis and aspergillosis presenting as bilateral vocal cord palsy. BMJ Case Rep 2013;2013. doi: 10.1136/bcr-2013-009615.  Back to cited text no. 5
    
6.
Maiorano E, Favia G, Capodiferro S, Montagna MT, Lo Muzio L. Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient affected by Castleman disease. Virchows Arch 2005;446:28-33.  Back to cited text no. 6
    
7.
Aggarwal D, Chander J, Janmeja A, Katyal R. Pulmonary tuberculosis and mucormycosis co-infection in a diabetic patient. Lung India 2015;32:53-5.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Guo J, Sun Y, Man Y, Huang X, Qin Q, Zhou D, et al. Coinfection of Strongyloides stercoralis and Aspergillus found in bronchoalveolar lavage fluid from a patient with stubborn pulmonary symptoms. J Thorac Dis 2015;7:E43-6.  Back to cited text no. 8
    
9.
Henn A, Mellon G, Henry B, Roos-Weil D, Jauréguiberry S, Mordant P, et al. Disseminated cryptococcosis, invasive aspergillosis, and mucormycosis in a patient treated with alemtuzumab for chronic lymphocytic leukaemia. Scand J Infect Dis 2014;46:231-4.  Back to cited text no. 9
    
10.
Lewis RE, Lortholary R, Spellberg B, Roilides E, Kontoyiannis DP, Walsh TJ. How does antifungal pharmacology differ for mucormycosis versus aspergillosis. Clin Infect Dis 2012;54:67-72.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


This article has been cited by
1 Cytarabine/daunorubicin
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[Pubmed] | [DOI]



 

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