Fungal infections in primary immunodeficiencies

Abstract

Patients with phagocytic, cellular, combined and other primary immunodeficiencies exhibit immune deficits that confer increased susceptibility to fungal infections. A number of yeasts and moulds, most commonly Candida and Aspergillus but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon, Penicillium and other, rarely isolated, fungal organisms, have been variably implicated in causing disease in patients with chronic granulomatous disease, severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency. Differences in the spectrum of fungal pathogens as well as in the incidence and clinical presentation of the infections may be observed among patients, depending upon different immune disorders. Fungal infections in these individuals may occasionally be the presenting clinical manifestation of a primary immunodeficiency and can cause significant morbidity and potentially fatal outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and establishment of diagnosis should actively be pursued using appropriate imaging, mycological and histological studies. A number of antifungal agents introduced over the last fifteen years, such as the lipid formulations of amphotericin B, the second-generation triazoles, and the echinocandins, increase the options for medical management of these infections. Surgery may also be needed in some cases, while the role of adjunctive immunotherapy has not been systematically evaluated. The low incidence of primary immunodeficiencies in the general population complicates single-center prospective or retrospective clinical studies aiming to address diagnostic or therapeutic issues pertaining to fungal infections in these patients.

Invasive Fungal Infections in Patients with Chronic Granulomatous Disease

“…Invasive mucormycosis has not been recognized in patients with CGD as frequently as IA [26,27]. A review of 929 pediatric and adult cases of mucormycosis revealed 81 % of the individuals having an impaired immune status, but none of these were associated with CGD [28].…”

Comparison of Inhibitory Mold Agar to Sabouraud Dextrose Agar as a Primary Medium for Isolation of Fungi

“…Fungal infections have become increasingly more common, especially in the setting of immunocompromised patients (1,5,6). In order to correctly diagnose and appropriately treat these infections, it is imperative first that the etiologic agent be grown and isolated on culture; only after that can the organism be identified and the most proper treatment be ensured.…”

Antifungal Activities of Natural and Synthetic Iron Chelators Alone and in Combination with Azole and Polyene Antibiotics against Aspergillus fumigatus

“…Antifungal synergy against conidia was observed for combinations of ketoconazole with ciclopirox or deferiprone, lactoferrin with amphotericin B, and fluconazole with deferiprone. Iron chelation alone or combined with antifungal drugs may be useful for prevention and treatment of mycosis.Invasive aspergillosis in neutropenic and immunocompromised patients is a serious therapeutic challenge (2,4,7,16). Prophylaxis using antifungal drugs has markedly reduced the occurrence of these infections (8,19,23,24); however, mortality for aspergillosis remains high (17).…”

“…Invasive aspergillosis in neutropenic and immunocompromised patients is a serious therapeutic challenge (2,4,7,16). Prophylaxis using antifungal drugs has markedly reduced the occurrence of these infections (8,19,23,24); however, mortality for aspergillosis remains high (17).…”