Immune reconstitution inflammatory syndrome

Overview

Immune reconstitution inflammatory syndrome (IRIS) is a condition that occurs when the immune system begins to recover but responds to a previously acquired opportunistic infection with an overwhelming inflammatory reaction. This paradoxical worsening is most commonly seen in patients with HIV/AIDS who start antiretroviral therapy (ART), but it can also occur in other immunocompromised individuals after the initiation of immune-restoring treatments. IRIS can affect various organs and may present as a mild, self-limiting condition or a life-threatening syndrome depending on the underlying infection and immune response.

Causes

IRIS is caused by the rapid restoration of pathogen-specific immune responses to existing infections in the setting of recovering immunity. Common settings where IRIS may occur include:

• HIV/AIDS: Most frequently observed after initiating antiretroviral therapy in patients with low CD4 counts and high viral loads.

• Tuberculosis-associated IRIS (TB-IRIS): Occurs in HIV patients co-infected with tuberculosis when ART is started during TB treatment.

• Cryptococcal meningitis, cytomegalovirus, Mycobacterium avium complex, and hepatitis B or C: These infections are often implicated in IRIS.

• Post-transplantation and cancer treatment: Seen in patients undergoing immune recovery after bone marrow or organ transplants, or chemotherapy.

Symptoms

Symptoms of IRIS vary depending on the type and location of the underlying infection and the severity of immune activation. Common features include:

• Fever

• Lymphadenopathy

• Worsening of pre-existing infections

• Respiratory symptoms: Cough, shortness of breath, or new pulmonary infiltrates (especially in TB-IRIS)

• Neurological symptoms: Headache, altered mental status (especially in cryptococcal IRIS)

• Skin and soft tissue inflammation

• Weight loss and malaise

Diagnosis

IRIS is a clinical diagnosis based on the temporal relationship between immune recovery and the onset or worsening of symptoms. Diagnosis includes:

• History: Recent initiation of ART or other immune-restoring therapy.

• Clinical deterioration: New or worsening symptoms of a known or occult infection after starting treatment.

• Exclusion of new infections or drug resistance: It's critical to rule out new opportunistic infections or treatment failure due to resistance.

• Laboratory tests: May show elevated inflammatory markers; CD4 count and viral load monitoring may support the diagnosis in HIV patients.

• Imaging: Used to identify localized inflammatory responses, such as lymph node enlargement or pulmonary infiltrates.

Treatment

Treatment of IRIS is aimed at controlling inflammation while continuing treatment of the underlying infection and immune restoration:

• Continue ART or immune therapy: In most cases, immune restoration should not be stopped.

• Anti-inflammatory therapy: Corticosteroids are commonly used for moderate to severe IRIS to reduce inflammation.

• Treat underlying infection: Ensure that appropriate antimicrobial therapy is being administered for any known infection.

• Supportive care: Hospitalization may be needed in severe cases; oxygen, hydration, or other supportive measures should be provided as needed.

Prognosis

The prognosis of IRIS depends on the severity of the inflammatory reaction and the underlying infection. Mild cases often resolve spontaneously with continued treatment, while severe IRIS can lead to significant morbidity and mortality if not recognized and managed promptly. With early diagnosis, proper anti-infective therapy, and anti-inflammatory treatment, most patients recover fully. Long-term outcomes are generally favorable, especially in patients who achieve effective immune reconstitution.