Non-HIV
immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory disorders caused by
antigens, including drugs or pathogenic microorganisms present prior to immune recovery, or by the exacerbation of an inflammatory disorder that was already present. Drug-induced
hypersensitivity syndrome is a prototype of IRIS, and the pathophysiology of non-HIV IRIS can be recognized in several disorders treated with
corticosteroids,
immunosuppressants, molecular-targeted drugs, TNF-α antibody drugs,
immune checkpoint inhibitors, and dipeptidyl peptidase-4 inhibitors. This review focuses on the relationship between the immune mechanism of non-HIV IRIS and
drug allergies, especially severe
drug eruption. The
antigen recognition mechanism in
drug allergy varies depending on the clinical type and the causative drug. The p-i concept is the main mechanism in severe
drug eruption such as
Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug-induced
hypersensitivity syndrome/drug reaction with
eosinophilia and systemic symptoms. Lymphocytes activated by an
antigen other than a drug, such as a virus, can also develop
drug allergy by the loose binding of drugs with immune receptors of T cells or
human leukocyte antigen. Therefore, fluctuations in the immune environment affect the onset of severe
drug eruption. Novel agents that cause major changes in immunity have been marketed mainly for
autoimmune diseases and malignant
tumors; therefore, it is necessary to consider their effects when treating severe
drug eruptions. Moreover, although a list of diagnostic criteria for this syndrome has been drafted, predictive and diagnostic
biomarkers for this syndrome needs to be urgently developed.