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

• Autoinflammation with Episodic Fever and Lymphadenopathy
• CRIAS (Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome)

What is Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome? (Definition/Background Information)

• Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome (CRIAS) is a rare genetic disorder that is characterized by skin rashes, joint pain, and chronic inflammation that can affect multiple organs and systems in the body
• The disorder is caused by mutations in the RIPK1 gene (that encodes the RIPK1 protein) and is inherited in an autosomal dominant manner. Thus, the risk factor for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome includes a positive family history of the disorder
• CRIAS is a congenital condition with onset during childhood. It is typically diagnosed based on a combination of clinical examination, blood tests, imaging studies, as needed, and genetic testing of the RIPK1 gene
• The treatment is typically symptomatic and supportive and may include medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and newer medications to decrease inflammation in a more specific manner
• Currently, there are no available measures to prevent Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of CRIAS and couples planning to have children
• The prognosis is generally good with adequate treatment. With effective treatment, most individuals with Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome can have a good quality of life, although severe cases of the disorder can cause significant discomfort and pain, particularly if left untreated

Who gets Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome? (Age and Sex Distribution)

• Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome (CRIAS) is a rare disorder with congenital manifestation (onset of symptoms occur during infancy and early childhood)
• It affects both males and females
• Because of the recent discovery of this disease, the frequency and racial/ethnic expression of CRIAS are currently unknown. As of early 2022, 12 individuals in three different European families have been reported

What are the Risk Factors for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome? (Predisposing Factors)

The risk factors for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome include:

• Having a family history of the disorder
• Inheriting a copy of the mutated RIPK1 gene from a parent to develop the disorder

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 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome? (Etiology)

Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome is a genetic disorder caused by mutations in the RIPK1 gene.

• The RIPK1 gene encodes a protein called the receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which plays a role in regulating inflammation
• These mutations lead to abnormal functioning of the RIPK1 protein, which can cause recurrent inflammation
• The disorder has an autosomal dominant pattern of transmission

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 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome?

The signs and symptoms of Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome (CRIAS) include:

• Recurrent episodes of fever
• Swollen lymph nodes (lymphadenopathy)
• Joint pain
• Muscle aches (myalgias)
• Headache
• Oral ulcers
• Pharyngitis (sore throat/tonsils)
• Abdominal pain

The onset and diagnosis of CRIAS usually take place during childhood.

How is Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome Diagnosed?

Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome is typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Imaging studies, as needed
• Lymph node biopsy, if possible
• Genetic testing for alterations in the MEFV gene

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 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome?

Complications of Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome may include

• Emotional stress
• Enlarged liver and/or spleen
• Reduced quality of life

How is Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome Treated?

Treatment for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome is typically symptomatic and supportive and may include medications to reduce inflammation and prevent recurrent episodes such as:

• Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids
• Anti-inflammatory drugs directed against Interleukin-6 (tocilizumab)
• Anti-inflammatory drugs directed against Interleukin-1 (canakinumab)
• Specific RIPK1 inhibitors are available on a research basis

How can Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome be Prevented?

Presently, it is not possible to prevent Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome as the cause is a genetic mutation.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome? (Outcomes/Resolutions)

The prognosis for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome is generally good with appropriate treatment.

• With suitable treatment, most patients can have a good quality of life
• However, the disorder can cause significant discomfort and pain if left untreated

Additional and Relevant Useful Information for Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome:

The following link is a useful resource for information on other rare conditions on DoveMed:

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