Immune Reconstitution Inflammatory Syndrome (IRIS)

Causes of IRIS

IRIS occurs when the immune system rapidly recovers from a suppressed state, leading to an exaggerated inflammatory response against infections that were previously tolerated. Key contributing factors include:

• HIV/AIDS and ART Initiation – The most common scenario involves patients with advanced HIV/AIDS who begin ART, triggering an inflammatory response to opportunistic infections.

• Other Immunosuppressive Conditions – It can also be seen in patients recovering from chemotherapy, organ transplantation, or corticosteroid therapy.

• Latent or Subclinical Infections – The reactivating immune system may suddenly recognize and attack dormant infections, such as tuberculosis (TB) or cytomegalovirus (CMV).

Types of IRIS

There are two main types of IRIS:

1. Paradoxical IRIS – A worsening of an existing infection despite appropriate treatment, occurring after ART initiation.

2. Unmasking IRIS – A previously undiagnosed infection suddenly becomes apparent due to immune system recovery.

Common Infections Associated with IRIS

IRIS is most frequently associated with opportunistic infections such as:

• Tuberculosis (TB)

• Cryptococcal meningitis

• Cytomegalovirus (CMV) infections

• Mycobacterium avium complex (MAC)

• Progressive multifocal leukoencephalopathy (PML)

• Toxoplasmosis

Symptoms of IRIS

The symptoms of IRIS vary depending on the underlying infection but generally include:

• Fever

• Swelling and inflammation at the infection site

• Worsening respiratory symptoms (in TB cases)

• Neurological deterioration (in cryptococcal meningitis or CMV encephalitis)

• Skin lesions (seen in herpes or Kaposi’s sarcoma)

• Lymph node enlargement

Diagnosis of IRIS

Diagnosing IRIS is challenging, as its symptoms overlap with those of opportunistic infections and ART side effects. A diagnosis is typically based on:

• Medical History – Evaluating the timeline of ART initiation and symptom onset.

• Clinical Examination – Checking for signs of worsening infection.

• Laboratory Tests – Including CD4 count, viral load, and inflammatory markers like C-reactive protein (CRP).

• Imaging Studies – X-rays, CT scans, or MRIs to detect organ involvement.

Treatment of IRIS

The management of IRIS focuses on symptom control, treating the underlying infection, and balancing immune recovery. Key treatment strategies include:

• Continuing ART – In most cases, ART should not be stopped, as long-term benefits outweigh temporary inflammation.

• Targeted Antibiotics/Antivirals – Treating the specific opportunistic infection causing IRIS.

• Anti-inflammatory Medications – Corticosteroids like prednisone are sometimes used to manage severe inflammation.

• Supportive Care – Pain relief, fluid management, and respiratory support when necessary.

Prevention of IRIS

Preventing IRIS involves a proactive approach to managing opportunistic infections before immune recovery:

• Screening and Preemptive Treatment – Identifying and treating latent infections before starting ART.

• Gradual ART Initiation – In high-risk cases, a delayed ART approach can minimize severe IRIS reactions.

• Close Monitoring – Regular follow-ups during immune recovery help detect early signs of IRIS.

FAQs

1. What is the main cause of IRIS?

IRIS occurs due to an overactive immune response during recovery from immunosuppression, often triggered by ART in HIV/AIDS patients.

2. Can IRIS be fatal?

Severe cases of IRIS, especially those involving the central nervous system, can be life-threatening without proper treatment.

3. How long does IRIS last?

The duration varies, but symptoms typically resolve within weeks to months with appropriate treatment.

4. Should ART be stopped if IRIS develops?

In most cases, ART should be continued, with additional treatment provided for the underlying infection and inflammation.

5. Who is at highest risk for developing IRIS?

Patients with advanced HIV/AIDS, low CD4 counts, or untreated latent infections before starting ART are at the greatest risk of developing IRIS.