Immune Reconstitution Inflammatory Syndrome

Definition

Appropriate assessment to identify cause and severity of symptoms

Common causes of IRIS seen in southern Africa

Paradoxical TB IRIS

Paradoxical cryptococcal IRIS

Other manifestations of IRIS

Explanation to patient and family

Institute non-pharmacological interventions

Prescribe appropriate first line treatment

Review assessment and management

Definition 

IRIS results from a pathological inflammatory response, driven by the recovering immune system after ARV therapy is initiated, causing clinical deterioration. 

Appropriate assessment to identify cause and severity of symptoms 

• The immune reconstitution inflammatory syndrome [IRIS] is a frequent early complication of antiretroviral [ARV] therapy, especially in patients who start ARV therapy with low CD4 counts and established opportunistic infections. 
• Infective forms of IRIS may manifest either as an ‘unmasking’ of a previously untreated infection, or as a paradoxical clinical deterioration of an infective process for which the patient is on appropriate antimicrobial therapy. 
• Most cases occur within three months of ARV initiation during early rapid immune recovery. 
• IRIS may also occur when a failing ARV regimen is switched to a suppressive regimen or when ARV therapy is resumed after an interruption. 

Common infections manifest as a result of IRIS seen in Southern Africa 

• Tuberculosis 
• Cryptococcosis 
• Acne 
• Molluscum contagiosum 
• Warts 
• Herpes simplex and Zoster 
• Hepatitis B 
• Cytomegalovirus uveitis 
• Kaposi’s sarcoma
  

Paradoxical TB IRIS 

• Paradoxical TB IRIS occurs in 8-43% of patients who are started on ARV therapy while on TB treatment, typically one to four weeks after ARV therapy is initiated. 
• Common manifestations are the return of TB symptoms, fever, lymph node enlargement with inflammatory features, worsening radiographic pulmonary infiltrates, and the accumulation of serous effusions or sterile abscesses. A minority of patients may develop life-threatening meningitis. 
• Most cases are self limiting within a few weeks, but a minority can persist for many months, especially sterile abscesses. 

Paradoxical cryptococcal IRIS 

• Paradoxical cryptococcal IRIS occurs in patients who have had a diagnosis of cryptococcosis prior to starting ARV therapy, and are improving on antifungal therapy. 
• Typically after starting ARV therapy they develop recurrent meningitis symptoms that may be associated with raised intracranial pressure. 

Other manifestations of IRIS 

• A range of skin conditions can occur, recur or worsen with IRIS. These include; 
  • HSV 1 and 2, 
  • Herpes Zoster 
  • Warts 
  • Papular pruritic eruption 
  • Acne 
  • Molluscum contagiosum 
  • Patients with chronic hepatitis B & C may present with a flare of their hepatitis due to IRIS. 
  • A minority of Kaposi Sarcoma [KS] patients may develop KS IRIS after starting ARV therapy. 

Explanation to patient and family 

• This is probably the most important intervention. 
• The patient and family need to know that the deteriorating symptoms are not due to the ARV therapy. 
• An explanation needs to be given appropriate to the patient and family’s education and understanding, that the body is getting stronger because of the ARV therapy and that a battle is going on in the body, causing the symptoms. 
• They must be encouraged at all costs to continue with the ARV therapy and the TB therapy (for example). They must be encouraged to ‘ride the storm’ and be reassured that it will improve. 

Institute non-pharmacological interventions 

• A patient with severe symptoms of shortness of breath or high fever, or signs and symptoms of raised intracranial pressure may need to be admitted to an in patient unit. 
• All patients with recurrent meningitis should have a lumbar puncture to measure and if necessary, reduce raised intracranial pressure [serial lumber punctures may be needed to exclude alternate diagnoses]. 
• Patients may need tepid sponging or oxygen therapy to relieve symptoms. 

Prescribe appropriate first line treatment 

• Continue with ARV therapy. 
• Prescribe analgesics according to WHO ladder if needed. 
• In patients with unmasking IRIS, ARV therapy should be continued, and effective treatment for the condition started. For example, in the case of TB, not having been diagnosed prior to starting ARV therapy, TB treatment would now need to be started. 
• In paradoxical IRIS, ARV therapy and effective OI treatment should be continued. 
• In severe cases especially those with CNS involvement, corticosteroids [e.g. prednisone 2mg/kg, duration depending on response] should be considered in consultation with a specialist. 
• In rare cases when the reaction is life threatening and not responding to corticosteroids, it may be necessary to interrupt ARV therapy. 

Review assessment and management 

• Follow up the patient on a regular basis, monitoring all signs and symptoms. 
• It may be necessary to drain sterile TB abscesses repeatedly. 
• Serial lumber punctures may be necessary. 
• Continue to reassure the patient and family