SAIDs (Formerly Known as Periodic Fever Syndromes)

SAIDs (systemic autoinflammatory diseases) are a group of disorders that cause frequent (recurring) fevers. These are fevers that keep coming back but aren’t caused by infections (like viruses or bacteria). An abnormality or regulation problem in your child’s natural (innate) immune system causes SAIDs. They used to be called periodic fever syndromes or recurrent fever syndromes.

Autoinflammatory diseases aren’t autoimmune diseases (like rheumatoid arthritis or lupus), in which your child’s acquired (adaptive) immune system malfunctions and mistakenly attacks healthy tissue.

SAIDs are much rarer than autoimmune disorders. Most are passed down (hereditary) and result from a genetic mutation (variant).

SAIDs typically (but not always) start when your child is a baby or toddler. Your child will experience episodes, or attacks, that cause fevers and other symptoms. They may not have symptoms between episodes. While there’s no cure for SAIDs, many periodic fever syndromes have treatments that can relieve your child’s symptoms.

Types of autoinflammatory disease

Researchers know of about 60 autoinflammatory diseases, and they’re continuing to discover more. Some of the most common SAIDs are:

• Familial Mediterranean fever (FMF). FMF is the most common genetically diagnosed recurrent fever syndrome. It causes painful inflammation in your child’s abdomen, chest and joints.
• Periodic fever, aphthous-stomatitis, pharyngitis, adenitis (PFAPA). PFAPA affects children in early childhood, usually starting before 4 years old. Episodes may resolve after age 10.
• Tumor necrosis factor receptor-associated periodic syndrome (TRAPS). TRAPS may first appear during early to late childhood or into adulthood.
• Mevalonate kinase deficiency (MKD). Formerly known as hyper-IgD syndrome, this type of periodic fever syndrome typically starts before 1 year of age.
• NLRP3-associated autoinflammatory diseases. Formerly known as cryopyrin-associated periodic syndromes (CAPS), this type consists of three different diseases (subtypes).
• Adult-onset Still’s disease (AOSD). AOSD starts in adulthood. It’s the adult counterpart of systemic juvenile idiopathic arthritis (JIA).
• NOD-2-associated granulomatous disease (Blau syndrome). This type typically begins before 4 years old. It primarily affects your child’s skin, eyes and joints.

Symptoms of SAIDs

SAIDs symptoms typically start during childhood. The most common symptom of the condition is a periodic (episodic) fever. People generally may feel well and have no symptoms between attacks. Each type of autoinflammatory disease may produce different symptoms:

• FMF may cause inflammation and severe pain in your child’s abdomen, chest and joints. A skin rash may develop in your child’s lower legs or ankles.
• PFAPA may cause a sore throat, mouth sores and swollen lymph nodes in your child’s neck.
• TRAPS may cause chills and muscle pain in your child’s trunk (torso) and arms. They may develop a painful red rash that moves from their arms and legs to their torso.
• MKD may cause chills, headaches, abdominal pain, loss of appetite and flu-like symptoms.
• NLRP3 diseases may cause rashes, headaches, malaise, joint pain and pink eye (conjunctivitis).
• AOSD may cause rashes, joint pain and muscle pain. Some also experience sore throat, abdominal pain, fatigue and malaise.
• Blau syndrome may cause a skin rash on your baby’s arms, legs or torso They may also experience joint pain and eye pain.

Autoinflammatory disease causes

Most SAIDs are genetic diseases. A variant in a certain gene causes each syndrome. The most common types of autoinflammatory diseases and their genetic causes are:

• FMF: MEFV gene, which provides instructions for how to make a protein called pyrin
• PFAPA: Unknown
• TRAPS: TNFRSF1A gene, which provides instructions for how to make a protein called tumor necrosis factor receptor (TNFR)
• MDK: MVK gene, which provides instructions for how to make a protein called mevalonic kinase
• NLRP3 diseases: NLRP3 gene, which provides instructions for how to make a protein called cryopyrin
• AOSD: Unknown
• Blau syndrome: NOD2 gene, which provides instructions for how to make a protein called NOD2

Complications of SAIDs

It’s important to get proper treatment because continued inflammation can cause amyloidosis (a buildup of protein in your kidneys), leading to permanent kidney damage.

How doctors diagnose SAIDs

Diagnosing autoinflammatory diseases can be a challenge. Their symptoms mimic those of other serious conditions, like lupus and lymphoma. To be sure your child’s condition is accurately diagnosed and managed, it’s important to find a physician trained in inflammatory diseases (rheumatologist).

Your child’s rheumatologist will use several factors to diagnose SAIDs. They’ll ask about your child’s symptoms and their biological family history. Your child’s provider may suspect period fever syndrome if your child:

• Frequently get fevers
• Has a biological family history of periodic fevers
• Comes from an ethnicity where periodic fevers are more common

Tests that are used

Your child’s rheumatologist may recommend several tests to make a diagnosis. These may include:

• Lab tests. Tests like C-reactive protein or complete blood count (CBC) can show signs of inflammation. These tests become positive during an attack and return to normal after an attack.
• Urine test. A urine protein test checks for high levels of protein in your urine. For MKD, a urine test for organic acid (acids that contain a carbon atom) will show high levels of mevalonic acid.
• Genetic testing. Genetic testing can look for genetic variants. But in some children with SAIDs, gene variants aren’t found, so test results may come back negative.

Autoinflammatory disease treatment

SAIDs treatment depends on the type and severity. The diseases aren’t curable, but you can typically manage your child’s symptoms with medication. If your child has episodes a few times a year, they can usually take nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve their symptoms. If the disease is more severe, your child’s provider may offer you other treatment options, including:

• FMF. You can manage FMF with a medication called colchicine, which helps reduce inflammation. If they can’t take colchicine, your child can try canakinumab, a biologic.
• PFAPA. You may shorten episodes of PFAPA with steroids (usually prednisone). In some children, a medicine used to treat stomach ulcers (cimetidine) may treat symptoms.
• TRAPS. Canakinumab is often an effective treatment for TRAPS. You can also help relieve symptoms with prescription anti-inflammatory drugs like glucocorticoids.
• MKD. Canakinumab is an effective option for treatment of MKD. During an episode, NSAIDs or steroids may also be helpful.
• NLRP3 diseases. Canakinumab and other immunomodulators like rilonacept and anakinra treat NLRP3-associated autoinflammatory diseases effectively.
• AOSD. Various anti-inflammatory drugs treat AOSD, including steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics.
• Blau syndrome. Depending on their symptoms, your child may try immunosuppressants, tumor necrosis factor (TNF) inhibitors and/or topical eye medications.

Does SAIDs go away?

Some autoinflammatory diseases are lifelong conditions. Others may last several years and then go away with age. Some conditions are lifelong disorders. But episodes may get milder and less frequent over time. Your child’s healthcare provider can provide specific details about your child’s disease.