The impact of the host on fungal infections.

Outcomes of fungal infections in immunocompromised individuals depend on a complex interplay between host and pathogen factors, as well as treatment modalities. Problems occur when host responses to an infection are either too weak to effectively help eradicate the pathogen, or when they become too strong and are associated with host damage rather than protection. Immune reconstitution syndrome (IRS) can be generally defined as a restoration of host immunity in a previously immunosuppressed patient that becomes dysregulated and overly robust, resulting in host damage and sometimes death. IRS associated with opportunistic mycoses presents as new or worsening clinical symptoms or radiographic signs consistent with an inflammatory process that occur during receipt of an appropriate antifungal, and that cannot be explained by a newly acquired infection. Because there are currently no established tests or biomarkers for IRS, it can be difficult to distinguish from progression of the original infection, although culture and biomarkers for the fungal pathogen or infection are typically negative during diagnostic workup. IRS was originally characterized in human immunodeficiency virus-infected patients receiving antiretroviral therapy, but has subsequently been described in solid-organ transplant recipients, neutropenic patients, women in the postpartum period, and recipients of tumor necrosis factor-α inhibitor therapy. In each of these cases, recovery of the host's immunity during treatment of an initial infection results in a powerful proinflammatory environment that overshoots and leads to host damage. Optimal management of IRS has not been established at present, but often involves treatment with a corticosteroid or other anti-inflammatory compounds. This article uses a number of patient cases to explore the intricacies of diagnosing and managing a patient with IRS, as well as the other extreme, namely patients who are so immunocompromised without immune recovery that they essentially become breeding grounds for a wide range of opportunistic pathogens, often simultaneously.