A case with acute myeloid leukemia and hepatosplenic Candida parapsilosis

Habip Gedik; Osman Yokus

doi:10.4103/1658-5127.171984

CASE REPORT

Year : 2015 | Volume : 6 | Issue : 4 | Page : 175-177

A case with acute myeloid leukemia and hepatosplenic Candida parapsilosis

Habip Gedik¹, Osman Yokus²
¹ Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey
² Department of Hematology, Ministry of Health Istanbul Training and Research Hospital, Istanbul, Turkey

Date of Web Publication

16-Dec-2015

Correspondence Address:
Habip Gedik
S.B. Bakırköy Sadi Konuk Eğitim ve Araştırma Hastanesi Bakırköy, İstanbul
Turkey

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/1658-5127.171984

Abstract

Hepatosplenic candidiasis (HSC) is a disseminated invasive fungal infection that develops commonly in patients with acute leukemia. The main symptom of HSC is a persistent fever in patients who have recovered from prolonged neutropenia subsequent to recent chemotherapy. Herein, a case is presented of a 32-year-old man who was followed up at hematology ward due to acute myeloid leukemia and febrile neutropenia related to cytarabine (ara-C) and daunorubicin chemotherapy. HSC was diagnosed and confirmed by ultrasonography, the culture of blood, and biopsy specimen.

Keywords: Hepatosplenic candidiasis, invasive fungal infection, leukemia

How to cite this article:
Gedik H, Yokus O. A case with acute myeloid leukemia and hepatosplenic Candida parapsilosis. J Appl Hematol 2015;6:175-7

How to cite this URL:
Gedik H, Yokus O. A case with acute myeloid leukemia and hepatosplenic Candida parapsilosis. J Appl Hematol [serial online] 2015 [cited 2023 Mar 27];6:175-7. Available from: https://www.jahjournal.org/text.asp?2015/6/4/175/171984

Introduction

In patients with acute leukemia, Candida infections are commonly seen and can exclusively affect liver and spleen subsequent to invading the blood from the gut or colonized sites. Hepatosplenic candidiasis (HSC) is a chronic, disseminated, invasive fungal infection that can affect patients with hematological malignancies. The principal clinical manifestation of HSC is a persistent fever in patients who have recovered from prolonged neutropenia subsequent to cancer chemotherapy.^[1] The diagnosis of HSC is mainly based on the presence of the following signs and symptoms including a prolonged fever, elevated serum bilirubin, and alkaline phosphatase levels, characteristic lesions that are occasionally seen with computed tomography (CT), nuclear magnetic resonance, and/or ultrasonography, and positive blood cultures. Positron emission tomography-CT is used for the diagnosis of HSC as well.^{[2],[3],[4],[5]}

In the presented case, HSC was diagnosed after the patient presented with protracted episodes of neutropenia induced by an extended chemotherapy regimen for acute leukemia.

Case Report

A 32-year-old man was admitted to our hematology department with acute myeloblastic leukemia (AML) and febrile neutropenia related to cytarabine (ara-C) and daunorubicin chemotherapy regimens. HSC was diagnosed and confirmed by ultrasonography and blood culture.

After diagnosis, the patient underwent treatment for AML. Neutropenia developed during chemotherapy and lasted 32 days. During neutropenia episode, the patient developed a fever that was treated with empirical antibacterial therapy (sulbactam cefoperazone 6 g/day, tid for 3 days followed by imipenem 2 g/day). However, fever persisted under antimicrobial treatment. The patient's fever was 38°C–39°C, and laboratory tests revealed an increase in his serum alkaline phosphatase and gamma-glutamyl transferase. An abdominal ultrasonography, CT scan, and magnetic resonance imaging (MRI) each showed multiple hypodense lesions that are consistent with hepatosplenic microabscesses in the liver and spleen and strongly suggest the HSC diagnosis. The disease continued to be present with persistent or recurrent fever after resolution of the neutropenia. A diagnostic fine needle biopsy was performed to obtain biopsy specimens of the hepatic lesions. The causative agent was identified by culture of blood and biopsy specimens as Candida parapsilosis. It was resistant to fluconazole. The patient was treated with caspofungin therapy for 1-month followed by voriconazole for 3 months. The patient's abnormal values, including body temperature and laboratory tests recovered. MRI revealed a decrease in the size and number of lesions in the liver and spleen after 2 months of therapy.

Discussion

Chronic disseminated candidiasis, commonly develop in patients with hematological malignancies as an invasive infection form of Candida spp.^[6],[7] Due to the increasing number of patients with hematologic malignancies receiving chemotherapy, severe candidal infections have emerged in patients who are followed up at onco-hematology departments due to the poor prognosis in neutropenia patients. Diagnosis of HSC depends on persistent fever in spite of broad spectrum antibiotics, thus needs investigations for secondary causation, such as cutaneous and invasive candidal infection. Improvement in the detection of yeast in blood culture bottles with the specific medium has been helpful, but the use of specific immunoserodiagnosis or polymerase chain reaction (PCR) methods is currently impractical. The availability of new antifungal drugs is often limited due to their high costs. Currently, fluconazole and amphotericin B are the most commonly used therapies; however, if antifungal resistance rate is higher or non-albican species is prevalent in cases of severe diseases, a combination of liposomal amphotericin B and caspofungin or voriconazole are recommended as monotherapy or combination therapies for treatment of cases with candidemia or HSC.^[8],[9],[10]

The timely diagnosis of invasive candidiasis (IC) is still a big challenge as the clinical presentation is unspecific and low sensitivity of blood cultures and prolonged incubation times. Thus, diagnosis of IC has been averted to antibody and PCR based methods. The mannan based antigen-antibody methods (antigen [Mn] and anti-mannan antibody [A-Mn]) have been reported to be promising.^[11] In our case report, the continuing high levels of alkaline phosphatase and gamma-glutamyl transferase prompted us to perform ultrasonography and abdominal MRI taking into consideration HSC in differential diagnosis due to hepatosplenic hypodense masses that might be related to liver and spleen candidiasis or other metastatic masses.

Hepatosplenic fungal (HSF) infections were reported in 37 (7.4%) of 500 adult patients with acute leukemia who received chemotherapy. There was no significant difference in the incidence of HSF infections among the patients with AML and those with acute lymphoblastic leukemia or between the patients treated with high dose chemotherapy and those with conventional or low dose chemotherapy. Candida tropicalis was the most common pathogen, followed by C. albicans. CT data revealed multiple hypodense lesions in the livers (89%), spleens (70%), and kidneys (27%) of those patients.^[12] Histologic confirmation may not be possible commonly due to complications of invasive procedures in patients with AML whom bleeding may occur related to thrombocytopenia.

Our case diagnosis was confirmed by non-invasive imaging techniques, culture based microbiological technique, and invasive techniques. Amphotericin B, caspofungin, micafungin, voriconazole, and posaconazole may achieve clinical and microbiological responses depend on antifungal sensitivity of fungal pathogens. Oral antifungal drugs may be chosen for prolonged treatment. Antifungal therapy is recommended to be chosen on the basis of local antifungal resistance status, severity of illness, duration of therapy, drug interactions, etc.^[10],[13]

Conclusion

HSC or IC should be taken into consideration and investigated in case a patient with acute leukemia has prolonged fever of unknown origin and hepatosplenic lesions in radiological imaginations. A diagnosis of HSC is commonly based on clinical presentation and imaging techniques, rarely biopsy specimen. Fungal cultures may not yield a diagnosis; in fact, an accurate diagnosis may depend on radiological findings. The antifungal treatment may last for more 3 months. The diagnosis of HSC is often difficult because of a nonspecific clinical presentation. In immunosuppressed patients, an unexplained fever that is unresponsive to antibiotic agents should prompt investigation of possible invasive fungal infection. Nevertheless, the diagnosis of HSC itself is not a contraindication for subsequent chemotherapy.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest

References

1.	Rajic Z, Colovic N, Sretenovic M, Plecic M, Jankovic S, Bakrac M, et al. Hepatosplenic candidiasis in acute leukaemia patients. Srp Arh Celok Lek 2008;136:414-8.
2.	Halkic N, Ksontini R. Images in clinical medicine. Hepatosplenic candidiasis. N Engl J Med 2007;356:e4.
3.	Elouennass M, Doghmi K, Fagot T, Soler C, Mac Nab C, Foissaud V, et al. Hepatosplenic and kidneys candidasis complicating an acute myeloblastic leukemia. A case treated with voriconazole and caspofungin. Ann Biol Clin (Paris) 2005;63:423-7.
4.	Altintas A, Ayyildiz O, Isikdogan A, Atay E, Kaplan MA. Successful initial treatment with caspofungin alone for hepatosplenic candidiasis in a patient with acute myeloblastic leukemia. Saudi Med J 2006;27:1423-4.
5.	Teyton P, Baillet G, Hindié E, Filmont JE, Sarandi F, Toubert ME, et al. Hepatosplenic candidiasis imaged with F-18 FDG PET/CT. Clin Nucl Med 2009;34:439-40.
6.	Larregina A, Bartoletti B, Romano H, Paniccia L, Polini NN. Hepatosplenic candidiasis in acute myeloid leukemia. Rev Argent Microbiol 2004;36:28-30.
7.	Festekjian A, Neely M. Incidence and predictors of invasive candidiasis associated with candidaemia in children. Mycoses 2011;54:146-53.
8.	Arda B, Soyer N, Sipahi OR, Hüdaverdi O, Tasbakan MI, Saydam G, et al. Possible hepatosplenic candidiasis treated with liposomal amphotericin B and caspofungin combination. J Infect 2006;52:387-8.
9.	Pellegrino B, Le Guyader N, Thien V, Fasola S, Auvrignon A, Leverger G. Severe candidosis infections in neutropenic patient in onco-hematologic department. Arch Pediatr 2003;10 Suppl 5:575s-81.
10.	Sorà F, Chiusolo P, Piccirillo N, Pagano L, Laurenti L, Farina G, et al. Successful treatment with caspofungin of hepatosplenic candidiasis resistant to liposomal amphotericin B. Clin Infect Dis 2002;35:1135-6.
11.	Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C; Third European Conference on Infections in Leukemia Group. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: Recommendations from the Third European Conference on Infections in Leukemia. Crit Care 2010;14:R222.
12.	Chen CY, Chen YC, Tang JL, Yao M, Huang SY, Tsai W, et al. Hepatosplenic fungal infection in patients with acute leukemia in Taiwan: Incidence, treatment, and prognosis. Ann Hematol 2003;82:93-7.
13.	Fenaux P, Lemaitre L, Ajana F, Colcher-Plantier I, Jouet JP, Bauters F. Hepatosplenic candidiasis: An overlooked cause of prolonged fever during recovery from an episode of neutropenia. Nouv Rev Fr Hematol 1989;31:45-9.