Immune Reconstitution Inflammatory Syndrome in Invasive Fungal Infections: What we know and what we need to know?

Invasive fungal infections (IFIs) cause significant mortality and morbidity in HIV-infected patients, patients with malignancy on chemotherapy, recipients of solid organ and haematological stem cell transplantation, patients with primary immunodeficiencies and those on immunomodulators such as steroids and tumour necrosis factor-alpha inhibitors. Immune reconstitution inflammatory syndrome (IRIS), an exaggerated, unexpected inflammatory phenomena occurring in temporal association with enhanced immune function in these conditions, is difficult to recognise and manage. Here, we detail what we have learnt from studies in cryptococcosis-associated IRIS and discuss other common fungal IRIS including histoplasmosis-IRIS, talaromycosis/penicilliosis-IRIS, pneumocystis-IRIS and a less well-recognised IRIS seen with invasive aspergillosis in the setting of neutrophil recovery. We also reflect on the enormity of what we are yet to understand about IRIS immunopathogenesis, diagnosis and management.