Autoinflammatory diseases

SAIDs occur due to a defect in the immune system. This may be due to a genetic mutation, or there may not be a clear cause. Environmental factors may trigger the response in some people.

Your immune system protects you by detecting and fighting harmful substances in the body. These include bacteria, viruses, fungi, chemicals, toxins, and foreign particles (such as a splinter).

Your immune system involves:

• Innate immunity -- this is the protection you were born with. Innate immunity involves barriers that keep harmful materials from entering your body. Examples include your skin, stomach acid, and mucus. This is the first line of defense against invaders.
• Adaptive immunity -- this is the protection you gain as your body learns over time which substances are harmful. Your immune system builds a defense against that specific substance. Vaccines work by training your adaptive immunity to recognize harmful invaders, for example flu viruses, and attacking them.

SAIDs occur due to an abnormal reaction of innate immunity. Autoimmune diseases occur due to an abnormal reaction of adaptive immunity.

When innate immunity is activated, it triggers your immune response. Certain chemicals in the body are released at the infection or injury site causing signs of inflammation, including redness, heat, pain, and swelling. Inflammation is part of the body's self-healing process. As you recover from your illness or injury, inflammation goes away.

SAIDs occur when innate immunity is activated without a clear cause. This may cause inflammation to occur in excess or to last for long periods of time. Excess inflammation can damage healthy tissues in the skin, bones, eyes, liver, heart, or kidneys.

The defective MEFV gene responsible for the most common autoinflammatory disease, familial Mediterranean fever (FMF), was first identified in 1997. Since then, many SAIDs have been identified. Not all have a clear genetic cause.

There are more than 50 SAIDs, including:

• Familial Mediterranean fever (FMF)
• Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
• Cryopyrin-associated periodic syndromes (CAPS)
• Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
• Aicardi-Goutières syndrome
• Blau syndrome
• Adult Still disease
• Hereditary angioedema
• Behçet disease

Each SAID affects people differently. Some occur for a few years and never return. Some last a life-time and need ongoing management.

SAIDs can be passed down in families. So if your parent or siblings have an SAID, you are more at risk for also developing it.

People with SAIDs may show a wide range of symptoms, as inflammation can affect one or more organ or tissue types. Symptoms can come and go. When symptoms get worse, it is called a flare-up. There can be periods with no symptoms at all between flare-up events.

Common symptoms may include:

• Recurrent and unexplained fever
• Skin rash
• Joint or muscle pain
• Fatigue
• Headache
• Sore throat
• Mouth sores or genital sores
• Vomiting
• Swollen lymph nodes
• Chest pain
• Abdominal pain
• Conjunctivitis

SAIDs are diagnosed after other possible conditions such as infections, autoimmune diseases, and cancer are checked for and not found.

During a physical exam, the health care provider will ask about family and personal medical history.

Blood tests or urine tests can rule out any bacterial or viral infection as a cause of inflammation. These tests also help in finding the level of inflammation in the body.

• Complete blood count (CBC) with white blood cell differential (CBC with WBC differential)
• Comprehensive metabolic panel
• C-reactive protein (CRP)
• Erythrocyte sedimentation rate (ESR)
• Urinalysis
• Autoantibody tests (ANA tests) to check for any autoimmune disorder

Imaging and other tests check for damage or cancer in organs such as the skin, liver, spleen, or kidneys.

• Skin or tissue biopsy
• Ultrasound
• CT scan
• PET scan

Genetic testing may help diagnose certain SAIDs and help guide treatment.

Because these are complex conditions, it can take months and even years to diagnose SAIDs.

Most SAIDs can be treated. Your treatment will depend on the disease, the organs affected, and the severity of the inflammation. The main goals are to reduce flares, control inflammation, and prevent tissue and organ damage.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and celecoxib reduce fever, pain, and inflammation, but they can have long-term side effects. Therefore, they should be taken only for a short time and in low doses when possible.
• Corticosteroids are often prescribed to reduce inflammation.
• Colchicine can help control the severity of symptoms during disease flare-ups.
• Biologic agents, the medicines derived from living cells, have shown benefits against many SAIDs. These medicines reduce inflammation by suppressing the immune response. Biologic medicines are used if the disease is severe or continues for a long time (becomes chronic).

There are many different types of biologic agents. However, because they are expensive, they are often not first-line treatments. Also, advance approval is often needed for insurance coverage.

Stress and anxiety are known to be possible triggers of SAID flares. Work with your provider to help control stress and anxiety.

Many resources can help you understand more about SAIDs. You can also learn ways to manage your condition and prevent complications by joining such groups.

More information and support for people with SAIDs can be found at:

• Autoinflammatory Alliance -- autoinflammatory.org/
• National Organization for Rare Disorders -- rarediseases.org/organizations/autoinflammatory-alliance/

Most SAIDs are chronic, but symptoms can be controlled with treatment. The outcome depends on the type of disease and the organs affected. Most people with SAIDs need long-term treatment and regular monitoring to stay healthy. In some children, the SAID may go away on its own as they grow older.

If left untreated, many SAIDs can lead to serious complications such as:

• Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis
• Vision or hearing loss
• Meningitis
• Amyloidosis leading to kidney failure
• Organ damage
• Arthritis due to chronic inflammation in bones or joints

Long-term use of corticosteroids to treat chronic inflammation can cause severe side effects.

Contact your provider if you or your child has an unexplained fever that comes and goes, a skin rash, inflammation, or joint pain without a known cause.

There is no prevention for SAIDs as they are mainly caused by genetic mutations. Immediate attention to symptoms and regular follow-ups can prevent serious complications.

Systemic autoinflammatory diseases (SAIDs); Periodic fever syndromes

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Updated by: Diane M. Horowitz, MD, Rheumatology and Internal Medicine, Northwell Health, Great Neck, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.