New clinical phenotypes of fungal infections in special hosts

Abstract

Incidence of invasive fungal infections increases over time with the rise in at-risk populations; in particular, patients with acquired immunodeficiencies due to immunosuppressive therapies such as anti-tumour necrosis factor-α (TNF-α) treatment, cirrhosis or burns. Some primary immunodeficiencies (PID) can also predispose selectively to invasive fungal diseases. Conversely, some atypical fungal diseases can reveal new PID. Deep dermatophytosis, Candida central nervous system infections or gastrointestinal disease, or disseminated phaeohyphomycosis-revealed CARD9 deficiency. Most patients with inherited chronic mucocutaneous candidiasis were found to carry STAT1 gain-of-function mutations. The spectrum of fungal susceptibility and clinical presentation varies according to the PID. Among acquired immunodeficiencies, immunosuppressive treatments such as TNF-α blocker therapy, which has revolutionized autoimmune disorder treatment, may be complicated by endemic mycosis, aspergillosis, pneumocystosis or cryptococcosis. Burn patients with damaged skin barrier protection are susceptible to severe Candida infections and filamentous fungal infections (such as Aspergillus spp., Mucorales). Moreover, patients with cirrhosis are at increased risk of fungal infections. Therefore, physicians should think of any potential underlying acquired or inherited immunodeficiency in a patient developing an atypical fungal infection, or of a potential fungal disease in the context of an atypical presentation in specific hosts.

The Role of Phagocytes in Immunity to Candida albicans

“…Patients with liver disease are at an increased risk of fungal infection. Those with cirrhosis have been found to have reduced complement levels and impaired monocyte activation and neutrophil mobilisation [106]. Patients with liver disease are at risk for infectious peritonitis, and C. albicans and C. neoformans were amongst the main species isolated in these cases.…”

“…Interestingly, unconjugated bilirubin in hyperbilirubinemia has also been linked to reduced phagocytic cell function; phagocytosis and killing of fungi [108,109]. Burns patients are at increased risk of fungal infection owing to a breached skin barrier and use of antimicrobial agents, with candidal infection in particular being associated with increased morbidity and mortality in these patients [106]. In addition to these disease states, other physical factors, alone or in combination, such as the use of intravenous catheters and mechanical ventilation also increase the risk of invasive fungal disease [98,104].…”

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child–Pugh B or C Liver Disease: A Case–Control Retrospective Study

“…Patients with end-stage liver disease (ESLD) are at high risk of acquiring invasive fungal infections (IFI) because of alterations in gut microbiota, gut permeability, and immune dysfunction [1,2]. The frequency of IFI in ESLD patients ranges from 1 to 10% [3,4], and development of IFI has a profound effect on the outcome of ESLD [5,6].…”

Emerging fungi causing human infection: new or better identified?

“…Pilmis et al summarize current knowledge on new clinical phenotypes of fungal infections in special hosts [4]. Incidence of invasive fungal infections is increasing over time with the rise of at-risk populations, in particular patients with acquired immunodeficiencies because of immunosuppressive therapies.…”

“…Conversely, some atypical fungal diseases can reveal new primary immunodeficiencies. Deep dermatophytosis, central nervous system candidiasis, or disseminated phaeohyphomycosis may result from newly discovered CARD9 deficiency [4]. Most patients with inherited chronic mucocutaneous candidiasis have been found to carry STAT1 gain-of-function mutations.…”