Systemic Autoinflammatory Diseases (SAIDs)

Systemic autoinflammatory diseases (SAIDs) are a group of conditions in which the immune system inappropriately triggers episodes of inflammation. SAIDs are rare, although many cases are probably not diagnosed.

Children develop SAIDs at different ages, from infancy to mid-childhood, depending on the type of SAID a child has. While some children have chronic SAIDs that last throughout their lifetimes, others outgrow their condition in a few years.

Inflammation is the body’s natural response to many stressors, including infections, trauma, and surgery. Signs of inflammation include fever, swelling, and redness. For instance, when you cut yourself, the area becomes warm, swollen, and red. This helps your body’s tissues heal, and the inflammation stops after healing has occurred. However, inflammation without any cause can lead to autoinflammation.

Autoinflammatory diseases are a newly recognized group of conditions in which the body’s immune system causes frequent, self-limiting, spontaneous episodes of inflammation and fever.

In contrast to autoimmune diseases, the defect in autoinflammatory diseases is in the first responder arm of the immune system (the innate immune system), and there are no self-reacting antibodies in the majority of patients. The defect triggers inappropriate activation of the normal inflammatory response or disables the body’s capability to shut down the normal inflammatory response. 

It should be noted that some SAIDs can affect multiple branches of the immune system because of a broader inappropriate immune response. In that case, signs and symptoms of autoimmunity, allergy, and/or immunodeficiency can be present in one condition at the same time.

There are many types of SAIDs. Some are caused by specific genetic mutations that trigger episodes of inflammation. Every year, mutations are discovered that cause SAIDs. However, in over half of patients with a SAID, a genetic cause cannot be found. These patients are thought to have SAIDs because of how the environment interacts with their genetic makeup or because of genetic mutations that we cannot identify. 

In addition, other rheumatic and inflammatory diseases appear to behave very similarly to SAIDs. These diseases include systemic juvenile idiopathic arthritis (SJIA), Behcet’s disease, and chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis (CNO/CRMO).

The primary sign that your child might have a SAID is recurrent episodes of unexplained fever, with or without other signs of inflammation, that recur in a very similar pattern in an otherwise well-appearing child. 

Symptoms during flares may include:

• Fatigue
• Headache
• Sore throat
• Mouth sores
• Abdominal pain
• Chest pain
• Swollen glands
• Rash
• Joint and muscle pain

Most children with SAIDs don’t have any symptoms between episodes, and their symptoms will usually be similar from one episode to the next. Unlike most infectious diseases, when a child with a SAID is ill, the rest of the family is usually well.

Some SAIDs have a genetic basis, meaning they are inherited from one or both parents. Sometimes children acquire new genetic mutations that are not seen in either parent. In some children, the cause of SAIDs is unknown.

In general, episodes of inflammation occur when the immune system reacts to a perceived danger, creating the same reaction as when faced with an infection or injury, but in the absence of a cause.

In most patients, the first step of diagnosing a SAID is ruling out other conditions, such as recurrent viral infections, that could be causing your child’s recurring fevers. This process may include blood and urine testing, both when your child is well and when they have a disease flare. Genetic testing is available for some of these syndromes, although it is not helpful in diagnosing many cases. 

It will take a few months — sometimes a few years — of monitoring to diagnose a SAID. Even then, many patients remain under the category of “undifferentiated SAID,” meaning they do not fit within a specific diagnosis. Fortunately, it is still possible to manage these patients effectively.

The majority of SAIDs are treatable. Most of the time, SAIDs are managed with close monitoring and medications to minimize flares, control inflammation, and prevent long-term complications. 
A better understanding of the underlying cause of some SAIDs has brought about newer treatment options that get to the root cause of the problem. 

Your child’s treatment will depend on the type of SAID they have and the stage of the condition. Treatment may include:

• Medications such as steroids (prednisone, prednisolone), colchicine, biologics (drugs that block specific inflammatory molecules in the blood)
• Tonsillectomy
• Physical therapy, occupational therapy
• Mental health counseling, psychiatry 
• Referral to other specialists
   

Earlier recognition of SAIDs and the availability of new medications have made the long-term outlook of children with SAIDs bright. It’s possible your child’s SAID will eventually go away on its own, usually in three to five years, without long-term complications. However, SAID can be a life-long problem. If left untreated, it can cause health complications in the future. Complications can include kidney disease and meningitis. In our Autoinflammatory Disease Clinic, our goal is to rapidly diagnose and treat your child’s SAID in order to reduce or eliminate the chance of long-term complications.

Treatment options that aren’t part of conventional medicine are generally known as alternative or complementary medicine. They include treatments like acupuncture and special diets or dietary supplements. Although no diet or supplement has been clinically shown to help treat or prevent SAIDs, some people seem to benefit from these interventions.

For many children with SAIDs, some episodes may be triggered by emotional stress, for instance, the start of a new school year, birthday parties, trips, vacations, or holidays. Stress management such as breathing exercises, mindful meditation, acupuncture, biofeedback, and cognitive-behavioral therapy may help prevent episodes from occurring.

While some alternative techniques may help decrease the frequency or severity of flares, they often work best when combined with traditional treatments and medication. If you’re interested in exploring an alternative treatment for SAIDs, be sure to talk it over with your child’s doctor first. If they agree that it may have value and is not harmful, always keep your doctor informed of methods being used.

In 2014, Boston Children’s created the Autoinflammatory Diseases Clinic (AIDC), one of the country's oldest and largest SAID clinics. The AIDC is part of the Rheumatology Program at Boston Children's Hospital, which cares for more than 5,000 children in its outpatient clinic each year, including many children with SAIDs.

Our interdisciplinary team partners closely with families to understand and address any individual, family, or school issues that may arise as we work together to optimize your child’s adjustment to the challenges of living with SAIDs.

We are committed to supporting our patients’ and their families’ well-being. With specialized training in pediatric rheumatology, we understand the unique circumstances, challenges, and intricacies of living with unexplained fevers and inflammation. We offer many psychosocial supports and consultation services with Boston Children’s specialists according to our patients’ needs.

Our team is also actively involved in research as well as national, and international efforts to improve the recognition, management, and treatment of SAIDs. Our doctors are actively involved in educating patients, families, and physicians about this rare group of diseases.