Overimmunosuppression

Overimmunosuppression refers to an excessive reduction in immune function, typically resulting from medical therapy or, less commonly, underlying conditions. It leaves individuals highly vulnerable to infections, diminishes the body’s ability to clear pathogens, and can impair immune surveillance against malignancy or reactivation of latent infections.

Causes and mechanisms vary but commonly include iatrogenic immunosuppressive therapy used in organ transplantation, autoimmune diseases, hematologic disorders, or cancer. Drugs associated with overimmunosuppression include glucocorticoids, calcineurin inhibitors (tacrolimus, cyclosporine), antimetabolites (mycophenolate, azathioprine), mTOR inhibitors (sirolimus), and biologics (rituximab). Drug interactions, high-dose regimens, prolonged use, and organ dysfunction that alters drug metabolism can intensify suppression.

Clinical consequences are dominated by infections, especially opportunistic pathogens such as Pneumocystis jirovecii, cytomegalovirus, Candida and Aspergillus species, and bacteria or viruses that are normally controlled. Patients may experience slow or poor wound healing, reduced response to vaccines, and, with long-standing suppression, an increased risk of malignancies or relapse of underlying disease. Reactivation of latent infections (TB, HBV, CMV) is a particular concern.

Assessment involves clinical history, drug level monitoring, complete blood counts, immunoglobulin levels, and surveillance for infections. Prevention and management focus on optimizing the immunosuppressive regimen (dose reduction, agent changes), selective antimicrobial prophylaxis (eg, for PJP, CMV, fungal infections), vaccination when safe and appropriate, and prompt treatment of infections. Multidisciplinary care is often required to balance infection risk with control of the underlying disease.