Fungal Infections in Patients with Leukemia

Abstract

Polymorphonuclear and mononuclear phagocytes are the leading host cells involved in the prevention and control of fungal infections’. Therefore fungal infection is a frequent complication of disease or chemotherapy-induced neutropenia in acute leukemia. Other predisposing factors include breaks in anatomical barriers such as mucositis, the administration of corticosteroids and antimicrobial treatments and the presence of indwelling catheters. The most common fungal agents encountered are Candida spp. and Aspergillus spp. while infections with Histoplasma, Coccidioides and Blastomyces are restricted to well-defined regions. These result in disseminated disease during neutropenia, after reactivation of long-dormant infection of the lungs. Another important infection, although less frequent than candidiasis and aspergillosis, is mucormycosis which involves mainly the lungs and the paranasal sinuses. Recently, an increasing number of unusual fungal infections have been reported in leukemia including Fusarium, Paecilomyces and Alternaria, Pseudoallescheria, Sporothrix, Trichosporon, and Geotrichum2. Over recent years candidemia and disseminated candidiasis are definitely increasing in leukemic patients. Most of the cases are due to Candida albicans, although in some institutions, it is being supplanted by C. tropicalis. C. krusei has emerged recently while C. parapsilosis is also common among patients receiving total parenteral nutrition. Other fungi, including C. guilliermondii, C. lusitaniae, and Torulopsis glabrata, may infrequently cause fungemia in leukemic patients. Clinical manifestations include fever refractory to antibacterial therapy, cutaneous lesions, myalgia, hypotension, and end~pthalmitis~. Blood cultures are positive in only 35% of the patients with autopsy-proven disseminated candidiasis and serological tests for antibodies are often negative. Detection of mannan antigen, and metabolites such as mannose or arabinitol have low sensitivity and are not reliable. In addition the positive predictive value of surveillance cultures during neutropenia are useful only for C. tropicalis but not for C. albicans4. Nevertheless mortality has decreased in recent years and this may be related to the increasing number of leukemic patients who achieve remission and survive Candida dissemination. This could also explain the recent emphasis on hepatosplenic candidiasis, which appears classically after recovery from neutropenia, with persisting fever, increase in serum alkaline phosphatase levels and hepatosplenic abscesses. Invasive aspergillosis is found in 25 to 40% of leukemic patients and at autopsy most of the cases are due to Aspergillus fumigatus and A. flaws. The risk of infection increases proportionally to the duration of neutropenia5 and the two primary sites of infection are the lungs and the paranasal sinuses. Clinical manifestations include persistent fever, pleuritic chest pain, and cough. Dyspnea and hypoxia appear late while rales are variably present on ausultation. Nasal discharge, epistaxis, facial swelling and tenderness are indicative of sinus infection. Chest and sinuses CT scans are superior to standard X-rays and should be performed on early suspicion. Dissemination to the central nervous system occurs in 10 to 15% of cases and this often results in fatal hemorrhage. The clinical picture of mucormycosis is very similar to that of aspergillosis, although less frequent and often fatal. Several fungi not previously associated with leukemia have recently been reported to cause disseminated infection. These include Fusarium spp., Pseudoallescheria boydii, and Trichosporon spp. The former two produce similar manifestations to aspergillosis and mucormycosis, however, maculopapular cutaneous lesions are more frequent and can produce necrotic ulcers. Another important difference is the isolation from blood.