Immune reconstitution inflammatory syndrome
Synonyms and keywords: Immune reconstitution syndrome; IRIS; IRS

# Overview
Immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution syndrome (IRS) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.
The suppression of CD4 T cells by HIV (or by immunosuppressive drugs) causes a decrease in the body's normal response to certain infections. Not only does this make it more difficult to fight the infection; it may mean that a level of infection that would normally produce symptoms is instead undetected (subclinical infection). If the CD4 count rapidly increases (due to effective treatment of HIV, or removal of other causes of immunosuppression), a sudden increase in the inflammatory response produces nonspecific symptoms such as fever, and in some cases a worsening of damage to the infected tissue.
Though these symptoms can be dangerous, they also indicate that the body may now have a better chance to defeat the infection. The most common treatment is to administer antibiotic or antiviral drugs against the infectious organism, and in some cases corticosteroids to suppress inflammation until the infection has been eliminated.
Infections most commonly associated with IRIS include cytomegalovirus, herpes zoster, Mycobacterium avium complex (MAC), Pneumocystis pneumonia, and tuberculosis. AIDS patients are more at risk for IRIS if they are starting HAART for the first time, or if they have recently been treated for an opportunistic infection. It is generally advised that when patients have low initial CD4 T cell count and opportunistic infection at the time of their HIV diagnosis, they receive treatment to control the opportunistic infections before HAART is initiated.
IRIS has been described in immunocompetent hosts who have meningitis caused by Cryptococcus gattii and Cryptococcus neoformans var. grubii, environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.

# Historical Perspective
-  was first discovered by , a , in  during/following .
- In ,  mutations were first identified in the pathogenesis of .
- In , the first  was developed by  to treat/diagnose .

# Classification
-  may be classified according to  into  subtypes/groups:
- Other variants of  include , , and .

# Pathophysiology
- The pathogenesis of  is characterized by , , and .
- The  gene/Mutation in  has been associated with the development of , involving the  pathway.
- On gross pathology, , , and  are characteristic findings of .
- On microscopic histopathological analysis, , , and  are characteristic findings of .

# Causes

## Drug Side Effect
- Dolutegravir
- Etravirine
- Lamivudine
- Rilpivirine
- Ritonavir
- Tipranavir
- Zidovudine

# Differentiating  from other Diseases
-  must be differentiated from other diseases that cause , , and , such as:

# Epidemiology and Demographics
- The prevalence of  is approximately  per 100,000 individuals worldwide.
- In , the incidence of  was estimated to be  cases per 100,000 individuals in .

## Age
- Patients of all age groups may develop .
-  is more commonly observed among patients aged  years old.
-  is more commonly observed among .

## Gender
-  affects men and women equally.
-  are more commonly affected with  than .
- The  to  ratio is approximately  to 1.

## Race
- There is no racial predilection for .
-  usually affects individuals of the  race.
-  individuals are less likely to develop .

# Risk Factors
- Common risk factors in the development of  are , , , and .

# Natural History, Complications and Prognosis
- The majority of patients with  remain asymptomatic for .
- Early clinical features include , , and .
- If left untreated,  of patients with  may progress to develop , , and .
- Common complications of  include , , and .
- Prognosis is generally , and the  of patients with  is approximately .

# Diagnosis

## Diagnostic Criteria
- The diagnosis of  is made when at least  of the following  diagnostic criteria are met:

## Symptoms
-  is usually asymptomatic.
- Symptoms of  may include the following:

## Physical Examination
- Patients with  usually appear .
- Physical examination may be remarkable for:

## Laboratory Findings
- There are no specific laboratory findings associated with .
- A    is diagnostic of .
- An  concentration of   is diagnostic of .
- Other laboratory findings consistent with the diagnosis of  include , , and .

## Imaging Findings
- There are no  findings associated with .
-  is the imaging modality of choice for .
- On ,  is characterized by , , and .
-  may demonstrate , , and .

## Other Diagnostic Studies
-  may also be diagnosed using .
- Findings on  include , , and .

# Treatment

## Medical Therapy
- There is no treatment for ; the mainstay of therapy is supportive care.
- The mainstay of therapy for  is  and .
-  acts by .
- Response to  can be monitored with  every .

## Surgery
- Surgery is the mainstay of therapy for .
-  in conjunction with  is the most common approach to the treatment of .
-  can only be performed for patients with  .

## Prevention
- There are no primary preventive measures available for .
- Effective measures for the primary prevention of  include , , and .
- Once diagnosed and successfully treated, patients with  are followed-up every . Follow-up testing includes , , and .

# Reference