Systemic Autoinflammatory Diseases (SAIDs) | Symptoms & Causes
What is inflammation?
Inflammation is the natural body’s 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 the body’s tissues heal, and the inflammation stops after healing has occurred. However, when inflammation occurs in the body without any cause, there is a possibility of autoinflammation.
What are the common signs and symptoms of SAIDs?
Recurrent unexplained fever episodes with or without other signs of inflammation that recur in a very similar pattern in an otherwise well-appearing child are the main clues that your child might have a SAID. Symptoms during flares may include fatigue, headache, sore throat, mouth sores, abdominal pain, chest pain, swollen glands, rash, and joint and muscle pain.
In most cases, your child won’t have any symptoms between episodes, and her symptoms will usually be similar from one episode to the next. When your child is ill, the rest of the family is usually well, unlike most infectious diseases.
What causes SAIDs?
Some SAIDs have a genetic basis, meaning they are inherited from one or both parents. Sometimes children acquire genetic mutations that are not seen in either parent. For other SAIDs, their cause remains unknown. In general, episodes of inflammation occur when the immune system reacts to a perceived danger, creating the same reaction it would do when faced with an infection or injury, but in the absence of a cause.
Are there other causes of recurrent fevers?
Yes. Recurrent fevers are most commonly caused by recurrent viral infections. However, many other conditions can cause recurrent fevers, including autoimmune disorders, cyclic neutropenia, tick-borne relapsing fever, inflammatory bowel disease, other chronic infections, and some types of cancers. Your doctor will direct you to the right specialist if there is a concern for any of these possibilities.
Systemic Autoinflammatory Diseases (SAIDs) | Diagnosis & Treatments
How are SAIDs diagnosed?
In most patients, we will first rule out other similar conditions which may cause your child’s recurring fevers, such as recurrent viral infections. We will consider blood and urine testing both when your child is doing well and when they have a disease flare. Genetic testing is available for some of these syndromes, although genetic testing is not helpful for diagnosis in many cases. It will take a few months of monitoring your child to make a diagnosis in many cases.
How are SAIDs treated?
If your child is being treated for a systemic autoinflammatory disease (SAID) at Boston Children’s Hospital, your entire family is involved. As an interdisciplinary team, we partner 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 tailor treatment for your child’s SAID to the type of syndrome we believe he has and the stage of his condition. This may include:
- medications such as steroids (prednisone, prednisolone), colchicine, biologics (drugs that block specific inflammatory molecules in the blood)
- tonsillectomy
- physical therapy or occupational therapy
- mental health counseling and psychiatry
What is the role of complementary and alternative medicine in the treatment of SAIDs?
When your child is facing a chronic illness, it’s understandable that you may want to explore all the treatment options, even those that aren’t part of conventional medicine. These methods, generally known as alternative or complementary medicine, encompass such treatments as 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 (e.g., beginning of the school year, birthday parties, trips, vacations, holidays). Therefore, working to help manage stress may be a valuable technique to prevent episodes from occurring. These techniques may include breathing exercises, mindful meditation, acupuncture, biofeedback, and cognitive-behavioral therapy.
While some of these techniques may help decrease the frequency or severity of flares, they often work best when combined with traditional treatments with medications. If you’re interested in exploring an alternative treatment for SAID, be sure to talk it over with your child’s doctor first and — if they agree that it may have value and is not harmful — always keep your doctor apprised of methods being used.
Systemic Autoinflammatory Diseases (SAIDs) | Frequently Asked Questions
SAIDs are rare, although they are likely underdiagnosed. There are no studies examining the incidence or prevalence of SAIDs in the United States. While some children may have a chronic disease that will affect them throughout their lifetime, others may outgrow their autoinflammation in a few years.
Autoinflammatory diseases are a group of conditions in which the immune system inappropriately triggers episodes of inflammation.
There are many types of SAIDs. Some are caused by specific genetic mutations that trigger episodes of inflammation. Every year, new mutations are being discovered that cause SAIDs. However, for half of the patients with SAIDs, 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, including Systemic Juvenile Idiopathic Arthritis (SJIA). Bechet’s Disease, and Chronic Nonbacterial Osteomyelitis/Chronic Recurrent Multifocal Osteomyelitis (CNO/CRMO).
- Familial Mediterranean Fever (FMF) is the most common genetic form of SAID. With FMF, your child’s fever may come on suddenly and last 12 to 72 hours, usually accompanied by severe abdominal pain. Attacks vary in frequency and usually begin mid-childhood. Untreated, patients with FMF may develop kidney problems later in life due to protein accumulation, called amyloidosis.
- Mevalonate Kinase Deficiency (MKD), also known as Hyper IgD Syndrome (HIDS): MKD usually presents in children around 6 months with recurrent episodes of fevers associated with tender swollen glands (lymph nodes), oral ulcers, abdominal pain, diarrhea, vomiting, and joint pain. Episodes typically recur every 1-2 months and last 4-7 days.
- Tumor necrosis factor receptor-associated periodic syndrome (TRAPS, formerly known as Hibernian fever) is characterized by fever lasting one to several weeks, accompanied by diffuse soreness in the arm or leg, abdominal pain, and rash. Symptoms usually begin in mid-childhood. If left untreated, amyloidosis may occur.
- Cryopyrin-Associated Periodic Syndromes (CAPS) (also known as NLRP3-Autoinflammatory Diseases): Three clinically similar autoinflammatory disorders make up CAPS; they’re all considered to be the same disorder with varying severity. Listed in order of severity from mild to severe:
- Familial Cold Autoinflammatory Syndrome 1(FCAS1): Also known as Familial Cold Induced Urticaria type 1, FCAS1 is characterized by childhood-onset fevers and a hive-like rash triggered by cold exposure. Symptoms typically last one to three days.
- Muckle-Wells Syndrome (MWS): Characterized by childhood-onset episodes of fevers, hives-like rash, typically associated with cold exposure, though they may also develop more chronic fevers and rash in the absence of cold exposure. If not treated, deafness and amyloidosis may occur.
- Neonatal Onset Multisystem Inflammatory Disorder (NOMID) or Chronic Infantile Neurological Cutaneous and Articular Syndrome (CINCA): Characterized by early-infancy-onset of prolonged fevers, continuous systemic inflammation, aseptic meningitis, joint deformities, and ear and eye problems. If untreated, it also affects growth and development.
- Periodic Fevers, cervical Adenitis, Pharyngitis, and Aphthous stomatitis (PFAPA): PFAPA is the most common SAID in children. It is characterized by fevers lasting four to five days, associated with lymph node swelling, sore throat, and oral ulcers. It typically recurs every 3-6 weeks on a predictable, periodic pattern. It usually begins in preschool-age children and resolves after three to five years.
Probably not. Most of the children with SAIDs are managed in our outpatient clinic.
Earlier recognition of SAIDs and the availability of new medications have made the long-term outlook of children with SAIDs very bright. In some cases, your child’s SAID will eventually go away on its own, usually in three to five years, without long-term complications. In others, SAID is a life-long problem with possible future complications if left untreated, including kidney disease and meningitis. In our Autoinflammatory Disease Clinic, our goal is to rapidly diagnose and treat your child’s SAID to reduce, or eliminate, the chance that they will have any long-term complications.
It’s possible. Some SAIDs have a genetic basis, meaning they’re inherited from parents. Many are multifactorial; that is, genes and the environment contribute to the disease process. However, the more we learn about these conditions, the more we realize that we can’t always predict who will become affected and how severe their disease will be.
None of the data suggests that SAID can be fixed or prevented with any sort of special diet—organic, gluten-free, or otherwise—or that a specific diet might alleviate your child’s symptoms. Nevertheless, we suggest that children with SAIDs follow a balanced, healthy diet.
Most children can participate in sports without limitations. However, for some, physical activity may trigger a disease flare, so patients will need to be mindful of whether this is happening and discuss with their doctors how they can participate in sports without triggering a flare.
Children should be able to go to school when they’re feeling well. During disease flares, they may have a fever and feel unwell, which may prevent them from attending school. Our ultimate goal is to prevent fever flares from occurring. If that is not possible, then we aim to make fever episodes occur less frequently, or we treat the episode as soon as it begins so that your child misses as little school as possible. We will provide you with a school note letting them know that your child’s fevers are not contagious.
Technically, there isn’t a cure for SAID, but in most cases, your child’s SAID may be treatable. For children with PFAPA, tonsillectomy may be curative. Sometimes SAIDs resolve on their own. For those for whom SAID is a chronic illness, doctors at Boston Children’s Hospital will work with you and your family to manage your child’s symptoms and reduce or prevent disease flares. We also work with adult rheumatologists who help transition your child to adult care when they are ready.
This is a question unique to each child. Our team welcomes the opportunity to discuss any of your concerns. We expect that your child will be able to live a full and active life, engaging in all (or most) childhood activities. Your child’s experiences should be much the same as those of any other kid her age.
Depending on where the defect is in the immune system, these conditions are grouped under different categories such as Inflammasomopathies (Familial Mediterranean Fever-FMF, Cryopyrin-Associated Periodic Syndromes-CAPS, Tumor necrosis factor receptor-associated periodic syndrome-TRAPS, Mevalonate Kinase Deficiency-MKD, Familial Cold Autoinflammatory Syndrome2-FCAS2/NLRP-12 related disease, Familial Cold Autoinflammatory Syndrome4-FCAS4/ NLRC-4 related disease), Interferonopathies (Aicardi-Goutier Syndrome-AGS, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature-CANDLE, Sting Associated Vasculopathy with onset in Infancy-SAVI), Relopathies (Haploinsufficiency of A20-HA20, RELA haploinsufficiency), among others.
Systemic Autoinflammatory Diseases (SAIDs) | Research & Innovations
At Boston Children’s Hospital, our care is informed by our research, and our discoveries in the laboratory strengthen the care we provide at each child's bedside. The scientific research program at Boston Children’s Hospital is one of the largest and most active of any pediatric hospital in the world.
In addition to providing expert care today, we’re searching for ways to improve the lives of children with SAID tomorrow by conducting research to understand the disease better and find new treatments.
Some of our recent studies
- In a recent study, we found that tonsillectomy is an effective treatment for curing patients with PFAPA. "I tell parents, 'I don't know why tonsillectomy works, but it has a good chance of ridding your child of fevers,'" says Greg Licameli, MD, FACS, of the Boston Children’s Department of Department of Otolaryngology and Communication Enhancement, whose own daughter underwent the procedure. Researchers in our Rheumatology Program continue to test the removed tonsils of these patients to understand better what might cause SAID and how best to treat children.
- We created a research app called Feverprints to collect temperatures from hundreds of participants from around the country. We found that average oral body temperatures are usually 97.7℉ and that fevers should be considered with temperatures 99.5℉ or higher. However, there was much variation of average temperatures during the day, with the lowest temperatures occurring around 4 a.m., and the highest temperatures occurring around 6 p.m.. Thus, a temperature of 99.5℉ in the afternoon may be within normal limits, whereas the same temperature occurring at 4 a.m. should be considered a fever.
- In another study, we described a gene defect (RELA) as the cause of the SAID in a family.
- We identified that patient’s polyarticular arthritis, vasculitis, and lung disease was caused by an SAID called SAVI after similar unexplained conditions in three generations of that family.
Clinical trials
Boston Children’s Hospital is known for pioneering some of the most effective diagnostic tools, therapies, and preventive approaches in matters relating to rheumatology. A significant part of our success comes from our commitment to research and advancing the frontiers of mental health care by conducting clinical trials.
Boston Children’s Hospital coordinates hundreds of clinical trials at any given time. Clinical trials are studies that may involve:
- evaluating the effectiveness of a new drug therapy
- testing a new diagnostic procedure or device
- examining a new treatment method for a particular condition
- taking a closer look at the causes and progression of specific diseases
Taking part in a clinical trial at Boston Children’s is entirely voluntary. Our team will be sure to fully address any questions you may have, and you may remove your child from the medical study at any time.
- search current and upcoming clinical trials at Boston Children’s
- search the National Institutes of Health’s list of clinical trials taking place around the world
Systemic Autoinflammatory Diseases (SAIDs) | Coping & Support
It’s normal for you to have many questions when your child is diagnosed with a SAID. Will it affect my child long-term? What do we do next? We’ve provided some answers on these pages, and our experts will explain your child’s condition in more detail if you would like.
When you’re at the hospital, we encourage you to visit our Hale Family Center for Families, dedicated to helping families locate the information and resources they need to better understand their child’s particular condition and take part in their care. All patients, families, and health professionals are welcome to use the center’s services at no extra cost. The center is open Monday through Friday from 8 a.m. to 7 p.m., and on Saturdays from 9 a.m. to 1 p.m. Please call 617-355-6279 for more information.
Visit our For Patients and Families site for all you need to know about:
- getting to Boston Children’s
- accommodations
- navigating the hospital experience
- other resources that are available for your family
Questions to ask your doctor
You and your family play an essential role in your child’s treatment. It’s essential that you share your observations and ideas with your child’s treating physician and that you have all the information you need to fully understand your child’s disease, as well as the treatment recommendations.
You’ve probably thought of many questions to ask about your child’s recurrent fevers. It’s often helpful to jot down your thoughts and questions ahead of time and bring them with you, along with a notebook, to your child’s appointment. That way, you will have all your questions in front of you when you meet with your child’s treating clinician and can take notes during the visit. If your child is old enough, you can also encourage them to write down questions.
Initial questions to ask your doctor might include:
- How did you arrive at the diagnosis of SAID?
- Are there any other conditions my child might have instead
- Does my child require further testing or procedures, such as blood, urine, or genetic testing?
- How should I care for the fevers at home?
- What activities should/shouldn’t my child participate in?
- Should my child’s diet change?
- How should I talk to my child about this condition?
- Will my child have kidney damage?
- Will my child grow out of SAID on her own without treatment?
- How can I tell if my child’s SAID is getting better or worse?
- When can I expect my child’s SAID to go away?
- Is my child’s SAID contagious?
- Can my child go to school?
- What treatments are you recommending and why?
List of abbreviations
- FMF: Familial Mediterranean Fever
- HIDS: Hyper IgD Syndrome
- TRAPS: TNF Receptor Associated with Periodic fever Syndrome
- CAPS: Cryopyrin-Associated Periodic Syndromes
- FCAS: Familial cold autoinflammatory syndrome
- MWS: Muckle Wells Syndrome
- NOMID: Neonatal Onset Multisystem Inflammatory Disorder
- CINCA: Chronic Infantile Neurological Cutaneous and Articular Syndrome
- PFAPA: Periodic Fevers, cervical Adenitis, Pharyngitis, Aphthous stomatitis
- AGS: Aicardi-Goutier Syndrome
- CANDLE: Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature
- SAVI: Sting Associated Vasculopathy with onset in Infancy
- HA20: Haploinsufficiency of A20
- CNO/CRMO: Chronic Nonbacterial Osteomyelitis/Chronic Recurrent Multifocal Osteomyelitis
- SJIA: Systemic Juvenile Idiopathic Arthritis
