What are the other Names for this Condition? (Also known as/Synonyms)

• NLRC4-AID (NLRC4-Associated Autoinflammatory Disease)
• NLRC4-Associated Macrophage Activation-like Syndrome (NLRC4-MAS)
• NLRC4-MAS (NLRC4-Associated Macrophage Activation-like Syndrome)

What is NLRC4-Associated Autoinflammatory Disease? (Definition/Background Information)

• NLRC4-Associated Autoinflammatory Disease (NLRC4-AID) is a rare disorder characterized by recurrent episodes of fever, rash, and inflammation of various organs, including the skin, joints, eyes, and gut. NLRC4-AID is mostly observed in children
• The condition is caused by mutations in the NLRC4 gene and is inherited in an autosomal dominant manner. The NLRC4 gene encodes a protein that helps regulate the immune system, and mutations in this gene can lead to an abnormal response of the immune system that results in inflammation
• The other signs and symptoms of NLRC4-Associated Autoinflammatory Disease may include abdominal pain, joint pain, and fatigue. NLRC4-AID is typically diagnosed based on a combination of clinical examination, laboratory tests, and genetic testing
• The treatment for NLRC4-Associated Autoinflammatory Disease typically involves oral or intravenous steroids to reduce inflammation and suppress the immune system, besides symptomatic treatment. Currently, it is not possible to prevent NLRC4-AID as it is a genetic disorder
• The prognosis of NLRC4-Associated Autoinflammatory Disease is generally good with proper treatment. However, the disorder is chronic and may require lifelong management. In rare cases, NLRC4-AID can lead to severe complications, especially if left untreated

Who gets NLRC4-Associated Autoinflammatory Disease? (Age and Sex Distribution)

• NLRC4-Associated Autoinflammatory Disease is a rare disorder that affects individuals of all ages but is most commonly diagnosed in childhood
• The disorder is more common in males than females.
• Ethnic group distribution and disease frequency are not yet known.

What are the Risk Factors for NLRC4-Associated Autoinflammatory Disease? (Predisposing Factors)

The risk factors for NLRC4-Associated Autoinflammatory Disease (NLRC4-AID) include:

• Having a family history of NLRC4-AID
• Mutation in the NLRC4 gene

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of NLRC4-Associated Autoinflammatory Disease? (Etiology)

NLRC4-Associated Autoinflammatory Disease is caused by mutations in the NLRC4 gene. The disorder is inherited in an autosomal dominant pattern.

• The NLRC4 gene encodes a protein that helps regulate the immune system. The NLRC4 gene is also known as SCAN4 nd CARD12 (the terminology may be confusing at times) 
• Mutations in this gene can lead to an abnormal response of the immune system, resulting in inflammation

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of NLRC4-Associated Autoinflammatory Disease?

The most common signs and symptoms of NLRC4-Associated Autoinflammatory Disease include:

• Recurrent episodes of fever
• Rash, which may be hive-like and can be induced by stroking or other skin friction
• Inflammation of various organs, including the skin, joints, eyes, and gut

Additional signs and symptoms may include

• Abdominal pain
• Joint pain
• Fatigue

Injury, surgery, physical or emotional stress can trigger flares in patients with this genetic defect.

How is NLRC4-Associated Autoinflammatory Disease Diagnosed?

NLRC4-Associated Autoinflammatory Disease is typically diagnosed based on a combination of 

• Clinical examination and medical history evaluation
• Assessment of the presenting signs and symptoms
• Laboratory tests
• Imaging studies
• Genetic testing

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of NLRC4-Associated Autoinflammatory Disease?

The complications of NLRC4-Associated Autoinflammatory Disease may include:

• Inflammation of various organs, leading to joint pain, eye problems, and gut issues
• Kidney inflammation and blood clots in rare cases
• With severe involvement, disseminated intravascular coagulation can occur

Macrophage activation syndrome (MAS) attacks can be triggered, leading to organ failure (involving the kidney, liver, and lung), including acute respiratory distress syndrome (ARDS).

How is NLRC4-Associated Autoinflammatory Disease Treated?

• Treatment for NLRC4-Associated Autoinflammatory Disease typically includes oral or intravenous steroids to reduce inflammation and suppress the immune system.
• In some cases, additional medications may be prescribed to manage the associated signs and symptoms

How can NLRC4-Associated Autoinflammatory Disease be Prevented?

• Presently, there is no known way to prevent NLRC4-Associated Autoinflammatory Disease as the cause is a genetic mutation
• Genetic counseling and testing may be recommended for individuals with a family history of the disorder

What is the Prognosis of NLRC4-Associated Autoinflammatory Disease? (Outcomes/Resolutions)

• The prognosis for NLRC4-Associated Autoinflammatory Disease is generally good with proper treatment
• However, NLRC4-AID is a chronic condition that may require lifelong management

Additional and Relevant Useful Information for NLRC4-Associated Autoinflammatory Disease:

The following link is a useful resource for further information on rare diseases and disorders:

https://www.dovemed.com/diseases-conditions/rare-disorders/