Immune reconstitution inflammatory syndrome in non-HIV immunosuppressed patients

Immune reconstitution inflammatory syndrome (IRIS) represents a clinical phenomenon of immune-mediated inflammation against various antigens, including pathogenic microorganisms, drugs and unknown autoantigens, during recovery from immunosuppressed conditions. IRIS has become well recognized in HIV-infected populations. However, IRIS has seldom been recognized in HIV-negative immunocompromised patients. In the last 15 years, the immunopathogenesis of drug-induced hypersensitivity syndrome (DIHS) has been largely determined. Laboratory data and clinical observations support the idea that DIHS represents a prototype of non-HIV IRIS. Primary diseases in which non-HIV IRIS is secondary include severe cutaneous adverse drug reactions, such as DIHS, autoimmune diseases, collagen diseases, pregnancy and internal malignancies. Potential triggers of recovery from an immune deterioration state include a discontinuation or abrupt tapering of systemic steroids and/or immunosuppressants, withdrawal or reduced effects of anti-tumor necrosis factor-α antibodies, and the use of immune-checkpoint antagonists for the advanced stages of malignancies. Wide use of IRIS across large populations risks oversimplification but highlights a key unifying principle. Balanced sensitivity and specificity for its diagnostic criteria and classification are necessary for the establishment of clinical practice guidelines for non-HIV IRIS. Additionally, the development of a useful combination of biomarkers is currently an urgent issue.