Chronic disseminated candidiasis (hepatosplenic candidiasis)
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
Chronic disseminated candidiasis (also called hepatosplenic candidiasis) is seen almost entirely in patients with hematologic malignancies who have just recovered from an episode of neutropenia [1,2]. Very few cases, some of which were not well documented, have been reported in patients who did not have leukemia or neutropenia .
Clinical issues related to chronic disseminated candidiasis will be reviewed here. An overview of Candida infections as well as the clinical manifestations, diagnosis, and treatment of candidemia are presented separately. (See "Overview of Candida infections" and "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults" and "Treatment of candidemia and invasive candidiasis in adults".)
The pathogenesis of chronic disseminated candidiasis is not well understood, but this entity is thought to result from invasion of Candida species from the gastrointestinal tract into the bloodstream as a result of prolonged neutropenia and a breach in mucosal integrity. The portal system may receive the largest inoculum and hence disease is prominent in the liver [2,4]. Evidence that the host inflammatory response plays an important role in the pathogenesis of this syndrome includes the histopathological picture of granulomatous (not suppurative) inflammation and the fact that symptoms and radiographic findings appear when the patient’s neutrophils return to normal .
Chronic disseminated candidiasis occurs almost exclusively in patients with acute leukemia but has been reported rarely in patients with lymphoma, aplastic anemia, and sarcoma [1,2].
Chronic disseminated candidiasis is now seen less frequently because of the widespread use of antifungal agents for prophylaxis and early initiation of empiric antifungal therapy for neutropenic fevers in high-risk leukemic and hematopoietic cell transplant patients [2,6]. The potential magnitude of this effect was illustrated in an autopsy study performed between 1990 and 1994 in 329 hematopoietic cell transplant recipients . Patients who received fluconazole prophylaxis had, when compared to those who were not treated with fluconazole, significantly lower rates of Candida infections (8 versus 27 percent) and hepatic candidiasis (3 versus 16 percent). (See "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prophylaxis of invasive fungal infections in adults with hematologic malignancies".)
- Thaler M, Pastakia B, Shawker TH, et al. Hepatic candidiasis in cancer patients: the evolving picture of the syndrome. Ann Intern Med 1988; 108:88.
- Kontoyiannis DP, Luna MA, Samuels BI, Bodey GP. Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am 2000; 14:721.
- Spindel SJ, Darouiche RO, Saeed ZA. Hepatosplenic candidiasis in non-neutropenic patients: a case report and literature survey. Int J Antimicrob Agents 1996; 7:149.
- Cole GT, Lynn KT, Seshan KR. Evaluation of a murine model of hepatic candidiasis. J Clin Microbiol 1990; 28:1828.
- Rammaert B, Desjardins A, Lortholary O. New insights into hepatosplenic candidosis, a manifestation of chronic disseminated candidosis. Mycoses 2012; 55:e74.
- van Burik JH, Leisenring W, Myerson D, et al. The effect of prophylactic fluconazole on the clinical spectrum of fungal diseases in bone marrow transplant recipients with special attention to hepatic candidiasis. An autopsy study of 355 patients. Medicine (Baltimore) 1998; 77:246.
- Anttila VJ, Elonen E, Nordling S, et al. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis 1997; 24:375.
- Anaissie E, Bodey GP, Kantarjian H, et al. Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med 1991; 91:142.
- Ratip S, Odabaşi Z, Karti S, et al. Clinical microbiological case: chronic disseminated candidiasis unresponsive to treatment. Clin Microbiol Infect 2002; 8:435.
- Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003; 37:634.
- Kauffman CA, Bradley SF, Ross SC, Weber DR. Hepatosplenic candidiasis: successful treatment with fluconazole. Am J Med 1991; 91:137.
- Pagano L, Mele L, Fianchi L, et al. Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes. Haematologica 2002; 87:535.
- Masood A, Sallah S. Chronic disseminated candidiasis in patients with acute leukemia: emphasis on diagnostic definition and treatment. Leuk Res 2005; 29:493.
- Samuels BI, Pagani JJ, Libshitz HI. Radiologic features of Candida infections. In: Candidiasis: Pathogenesis, Diagnosis and Treatment, Bodey GP (Ed), Raven Press, New York 1993. p.137.
- Anttila VJ, Lamminen AE, Bondestam S, et al. Magnetic resonance imaging is superior to computed tomography and ultrasonography in imaging infectious liver foci in acute leukaemia. Eur J Haematol 1996; 56:82.
- Pestalozzi BC, Krestin GP, Schanz U, et al. Hepatic lesions of chronic disseminated candidiasis may become invisible during neutropenia. Blood 1997; 90:3858.
- De Castro N, Mazoyer E, Porcher R, et al. Hepatosplenic candidiasis in the era of new antifungal drugs: a study in Paris 2000-2007. Clin Microbiol Infect 2012; 18:E185.
- Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503.
- Walsh TJ, Whitcomb PO, Revankar SG, Pizzo PA. Successful treatment of hepatosplenic candidiasis through repeated cycles of chemotherapy and neutropenia. Cancer 1995; 76:2357.
- Walsh TJ, Whitcomb P, Piscitelli S, et al. Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis. Antimicrob Agents Chemother 1997; 41:1944.
- Gokhale PC, Barapatre RJ, Advani SH, et al. Successful treatment of disseminated candidiasis resistant to amphotericin B by liposomal amphotericin B: a case report. J Cancer Res Clin Oncol 1993; 119:569.
- Sorà F, Chiusolo P, Piccirillo N, et al. Successful treatment with caspofungin of hepatosplenic candidiasis resistant to liposomal amphotericin B. Clin Infect Dis 2002; 35:1135.
- de Pauw BE, Raemaekers JM, Donnelly JP, et al. An open study on the safety and efficacy of fluconazole in the treatment of disseminated Candida infections in patients treated for hematological malignancy. Ann Hematol 1995; 70:83.
- Kontny U, Walsh TJ, Rossler J, et al. Successful treatment of refractory chronic disseminated candidiasis after prolonged administration of caspofungin in a child with acute myeloid leukemia. Pediatr Blood Cancer 2007; 49:360.
- Hübel K, Chemnitz J, Brochhagen HG, Cornely OA. Successful treatment of chronic disseminated candidiasis with caspofungin and itraconazole in a patient with progressive acute leukemia and prolonged neutropenia. Int J Hematol 2004; 79:289.
- Cornely OA, Lasso M, Betts R, et al. Caspofungin for the treatment of less common forms of invasive candidiasis. J Antimicrob Chemother 2007; 60:363.
- Vehreschild JJ, Krüger K, Kurzai O, et al. Salvage therapy of refractory chronic disseminated candidiasis in a patient with acute myeloid leukaemia and secondary prophylaxis during allogeneic stem cell transplantation. Mycoses 2006; 49 Suppl 1:42.
- Legrand F, Lecuit M, Dupont B, et al. Adjuvant corticosteroid therapy for chronic disseminated candidiasis. Clin Infect Dis 2008; 46:696.
- Chaussade H, Bastides F, Lissandre S, et al. Usefulness of corticosteroid therapy during chronic disseminated candidiasis: case reports and literature review. J Antimicrob Chemother 2012; 67:1493.