Inflammatory immune reconstitution syndrome

What is immune reconstitution? inflammatory syndrome?

Inflammatory immune reconstitution syndrome (IRIS) generally describes the paradoxical worsening of pre-existing infectious processes after the initiation of antiretroviral therapy in patients with advanced human immunodeficiency virus (HIV) infection [one]. Although it can also be caused by noninfectious disorders, IRIS is generally described in association with opportunistic infections by mycobacteria, fungi, and viruses.

It can be classified into two types. [two]:

• Paradoxical IRIS: worsening of a previously diagnosed opportunistic infection after starting antiretroviral therapy
• Unmask IRIS: the presentation of a previously undiagnosed opportunistic infection with exaggerated inflammatory characteristics after starting antiretroviral therapy.

There are multiple synonyms for IRIS: immune recovery disease, immune reconstitution disease, immune restoration disease, immune rebound disease, and immune response reactions.

Who gets the immune reconstitution inflammatory syndrome?

In up to 10-20% of HIV-infected patients starting antiretroviral therapy, rapid improvement in immune function is followed by their deregulation. This results in an aberrant inflammation which is generally directed against an opportunistic infection.

Similar paradoxical reactions have also been described in patients who are not infected with HIV. This is believed to be due to a sudden change in T helper responses to impaired inflammation anti-inflammatory answers in the following cases [3,4].

• After starting treatment for tuberculosis (TB) or lepromatous leprosy
• In some patients with severe cutaneous Adverse drug reactions, autoimmune diseases, pregnancy, organ transplant receptors and internal neoplasms
• After stopping immunosuppressive medications, such as systemic corticosteroids tumor necrosis alpha factor (TNF-α) inhibitors, immune checkpoint antagonists (see objective Cancer therapies), or chemotherapy.

What causes inflammatory immune reconstitution syndrome?

The underlying mechanisms that cause IRIS are not yet fully understood [5].

HIV infection causes multiple ill effects on the immune system. It is characterized by a gradual drop in CD4 + lymphocytes, leading to opportunistic and specific infections neoplasms.

Viral load decreases in the first 8 to 12 weeks after starting treatment with antiretroviral therapy before stabilizing. At the same time, there is an inverse proportional increase in CD4 + lymphocyte tell. IRIS generally occurs during the earliest and fastest phase of immune recovery.

What are the risk factors for immune reconstitution inflammatory syndrome?

The probability and severity of IRIS depend mainly on the following risk factors [5,6]:

• CD4 severe lymphopenia (<100 células >
• The extent and severity of the opportunistic infection or infections.
• HIV viral load before starting antiretroviral therapy
• The timing of antiretroviral therapy and the initial response to treatment.

What are the clinical features of the immune reconstitution inflammatory syndrome?

IRIS can occur a few weeks or several months after starting antiretroviral therapy. Its clinical characteristics are closely related to the type and location of the pre-existing opportunistic infection, which can be previously diagnosed or unmasked after starting treatment. [1,2]. In most cases, the patient has systemic symptoms. The main opportunistic infections associated with IRIS are listed in the table below.

How is inflammatory immune reconstitution syndrome diagnosed?

There is no confirmatory diagnostic test for IRIS, therefore the diagnosis is based on clinical criteria.

• In paradoxical IRIS, the patient experiences clinical worsening despite being on effective treatment for opportunistic infection [5].
• The diagnosis of unmasking IRIS is based on the specific test for the underlying opportunistic infection.

In general, it is accepted that most or all of the following criteria for IRIS must be present [1]:

• Acquired immunodeficiency syndrome (AIDS) with low CD4 + cell count before starting treatment; the lower the CD4 + count, the greater the risk of IRIS
• A positive virological and immune response to antiretroviral therapy
• Absence of any other compatible cause of disease, such as drug-resistant infection, bacterial superinfection adverse drug reaction, pharmacological interaction or non-compliance of the patient with the treatment regimen
• Clinical manifestations of an inflammatory condition.
• Temporary association between the start of antiretroviral therapy and the start of symptoms.

Which is the differential diagnosis for immune reconstitution inflammatory syndrome?

IRIS has a wide differential diagnosis and requires careful clinical evaluation to exclude:

• Opportunistic infection progression.
• Adverse effects of treatment.
• Non-adherence to treatment.

What is the treatment for immune reconstitution inflammatory syndrome?

Most patients will require diagnostic tests and hospitalization to minimize in the short term. morbidity and mortality. Antiretroviral therapy should not be discontinued if IRIS is diagnosed. Treatment varies according to the severity of IRIS. [7.8]:

• Mild cases can be treated with supportive care and specific treatment for opportunistic infection.
• In severe cases or if neurological symptoms are present, corticosteroids (prednisone 1–2 mg / kg for 1–2 weeks) may be considered, with close monitoring; Corticosteroids should be avoided in viral infections.

What is the result of the immune reconstitution inflammatory syndrome?

In many cases, IRIS is a self-limiting condition that only requires supportive treatment and specific treatment for opportunistic infection.

The mortality rate associated with IRIS varies according to the underlying opportunistic infection and is high in patients with symptoms of the central nervous system.