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Author: Dr Anna Bota Llorca, Dermatology Registrar, Hospital Universitario Virgen Macarena, Sevilla, Spain. DermNet NZ Editor in Chief: Adjunct A/Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. January 2020.
Immune reconstitution inflammatory syndrome (IRIS) is an immune-mediated form of inflammation directed against antigens including various microorganisms and drugs, developing after recovery from a state immunosuppression . It is most commonly seen as a paradoxical worsening of pre-existing infectious processes after the initiation of antiretroviral therapy in patients with advanced human immunodeficiency virus (HIV) infection. Although it can also be caused by non-infectious disorders, IRIS is usually described in association with mycobacterial, fungal, and viral opportunistic infections.
It can be classified into two types :
There are multiple synonyms for IRIS: immune reconstitution syndrome, immune recovery disease, immune reconstitution disease, immune restoration disease, immune rebound illness, and immune response reactions.
In 10–20% of HIV-infected patients starting on antiretroviral therapy, rapid improvement of immune function is followed by its dysregulation. This results in an aberrant inflammation that is usually directed against an opportunistic infection.
Similar paradoxical reactions have also been described in patients who are not infected with HIV. This is thought to be due to sudden change in the T helper responses to inflammation with inadequate anti-inflammatory responses in the following cases [1,3].
The underlying mechanisms that cause IRIS are not yet fully understood .
HIV infection causes multiple deleterious effects on the immune system. It is characterised by a gradual drop in CD4+ lymphocytes, leading to opportunistic infections and specific neoplasms.
The viral load declines in the first 8 to 12 weeks after starting treatment with antiretroviral therapy before it stabilises. At the same time, there is an inverse proportional increase in the CD4+ lymphocyte count. IRIS usually occurs during the early, most rapid phase of immune recovery.
The likelihood and severity of IRIS in HIV mainly depend on the following risk factors [4,5]:
IRIS can occur a few weeks to several months after starting antiretroviral therapy for HIV. The clinical features closely relate to the type and location of pre-existing opportunistic infection, which can be previously diagnosed or unmasked after starting treatment . In most cases, the patient has systemic symptoms. The main opportunistic infections associated with IRIS are listed in the table below.
|Opportunistic infection||Onset of symptoms||Clinical manifestations|
|Mycobacterium tuberculosis||< 2 months||
|Mycobacterium avium complex||1–8 weeks||
|Cryptococcus neoformans||< 2 months||
|Pneumocystis jirovecii||1–3 weeks||
|Cytomegalovirus||4 weeks to 4 years||
|JC virus||3–4 weeks||
|Herpes zoster||1–4 months||
|Hepatitis B and C viruses (see viral hepatitis)||2–8 weeks||
|Kaposi sarcoma||< 12 weeks||
There is no confirmatory diagnostic test for IRIS, thus the diagnosis is based on clinical criteria.
It is generally accepted that most or all of the following criteria for IRIS in HIV should be present :
IRIS has a broad differential diagnosis and requires a careful clinical evaluation to exclude:
Most patients will require diagnostic tests and hospitalisation to minimise short-term morbidity and mortality. Antiretroviral therapy should not be stopped if IRIS is diagnosed. The treatment varies according to the severity of IRIS [7,8]:
In many cases, IRIS is a self-limited condition that only requires supportive treatment and specific treatment for the opportunistic infection.
The mortality rate associated with IRIS varies according to the underlying opportunistic infection and is high in patients with central nervous system symptoms.
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