Affecting less than 5 out of every 10,000 people1, recurrent autoinflammatory diseases (also known as Periodic Fever) syndromes are not common, and are classified as rare diseases. Although they involve the immune system, they are not autoimmune diseases. They can be caused by a change to the genetic recipe (DNA) of the non-specific innate immune system, which quite simply means the immune system activates to attack invaders that are not present in the body, causing damage to the body in the process.
Initial symptoms of these autoinflammatory diseases include recurrences of fevers lasting more than 24 hours, which are often accompanied by rashes and joint pain. Long-term, damage may occur due to the effects of continuous (chronic) inflammation.
Diagnosing a recurrent, periodic fever can be difficult and complicated, not only because they occur rarely, but because the symptoms are common to many other diseases. Successful diagnosis of a periodic fever may involve several diagnostic tests before the correct cause or condition is identified.
A healthy immune system is essential to fight off invading germs that can cause illnesses or disease – common viruses like the flu, or bacteria such as streptococcus. When germs enter the body, the immune system responds in two ways.
With autoinflammatory disease, the innate immune system activates “on its own” in response to germs that are not actually present in the body. This results in an inflammatory response that affects the entire body, causing a disease flare with typical symptoms including fever, rash, joint swelling, pain, and fatigue. These periodic flares can occur recurrently in some people or continuously (chronically) in others.
There are various causes of recurrent periodic fever syndromes and autoinflammatory diseases:
CAPS: Cryopyrin-associated periodic syndromes, FMF: Familial Mediterranean fever, TRAPS: Tumor necrosis factor receptor associated periodic syndrome, HIDS/MKD: Hyperimmunoglobulinemia D syndrome/Mevalonate kinase deficiency
Interleukin-1 beta (IL-1β) is a messenger of the nonspecific innate immune system. It plays a special role in many autoinflammatory diseases, promoting the inflammatory response and communicating to immune cells to come to where supposed invaders are in the body.
From a practical and emotional point of view, periodic fever syndromes can be quite overwhelming to live with for everyone, with lots of challenges to overcome. But with us understanding more and more about these recurrent diseases, improvements are being made to make diagnosis quicker and more accurate. As a result, there is more support and, indeed, more support groups for people affected by periodic fever syndromes and autoinflammatory diseases than ever before.
Because of the lack of knowledge and understanding around rare diseases, such as recurrent autoinflammatory conditions like SJIA, AOSD and Periodic Fever syndromes like FMF, TRAPS, HIDS/MKD, CAPS , more than 25% of people with rare diseases can wait anything from 5 to 30 years from when their symptoms first appear to when they receive an appropriate diagnosis. And up to 40% of people with rare diseases are initially diagnosed incorrectly. This has implications not only that person’s health, but on their social and personal lives.
Raising awareness and educating people about rare diseases is one of the most important things we can do to help people who affected by these conditions to help ensure they receive the right diagnosis at the right time and get the understanding and support they need.
Your help to spread the word about rare autoinflammatory conditions such as periodic fever syndromes and the challenges associated with diagnosing these diseases is vital. Follow us on Facebook and share the video above with the people around you.
This booklet will help you understand what hereditary recurrent fever syndromes are, their most common symptoms, how these autoinflammatory diseases work, how they are diagnosed, and how you or anyone affected by periodic fever syndromes learn to live with these life-changing conditions.
This helpful glossary should help explain all of terms, abbreviations and acronyms you will discover as you learn about periodic fever syndromes and autoinflammatory conditions.
Dr. Michaël Hofer is a pediatric immunologist and rheumatologist based at CHUV, the University of Lausanne, Switzerland. He is an expert in rheumatic diseases affecting children and teenagers, including autoinflammatory syndromes. Here, he outlines the difficulties as children transition from childhood to adulthood.
When it comes to autoinflammatory disease, a specialist doctor can provide you with all of the information, advice and care that you and your child need. Here are some things you’ll want to consider in choosing a specialist:
1) Specialist or primary care physician?
Your child’s regular doctor, pediatrician or primary care physician will always play an important role in their care, but it’s important to remember that they are not experts in every single disease, so may not have the deep understanding of your child’s specific rare autoinflammatory disease. A specialist will have that expert knowledge you need and be able to offer individual, tailored advice to you and your child.
2) What kind of specialist?
There are a number of different specialists that may be able to help, depending on your child’s condition. If your child has systemic juvenile idiopathic arthritis (SJIA) for example, a rheumatologist, who specializes in joints and arthritis, may be recommended. Genetic specialists or counsellors could also be important to consider as they can provide information on the cause of the disease and can help in understanding how other family members may be affected. The best thing to do is ask your child’s primary care physician, as they should have an idea of the kind of specialist care your child will benefit from most. If your child has multiple health needs, they may need multiple specialists. In this case, it will be important to put each specialist in touch with the other members of your child’s specialist team, so that they can make sure all suggested treatments are complementary and ensure your child is receiving safe, effective care.
3) What if you have to travel?
Travelling with an unwell child can be difficult, so it’s important to find a specialist not too far away. Some specialist centers provide transport, and some insurance policies may cover cost of travel too, so be sure to check before making your decision.
4) Does your insurance cover the care?
If you live in a country that requires health insurance, it’s important to create an open line of communication between you and your provider, as much as possible. Before you book an appointment with a specialist, check your policy will cover it and what information your provider requires. Talk to your provider if you have any doubts or questions.
Speak to your primary care physician first as they are likely to know about a number of different experts in your area and can use their connections to find out more.
Resources such as Orphanet can also help. Orphanet provides access to a directory of expert services and centers for rare diseases or groups of diseases. We would always recommend checking with your doctor once you’ve found a specialist through Orphanet, to make sure they agree with the choice. Your child is special and finding them a specialist doctor can help ensure they are receiving all the care they need.
Good communication with doctors and other healthcare professionals is important in helping you fully understand what your child’s diagnosis means, what treatment options are available, and how to care for your child. Here’s a step-by-step guide on what to do before, during and after medical appointments:
During your appointment:
Doctor’s appointments don’t have to be scary, stressful or negative experiences. Once you take the right steps to prepare, you can leave an appointment feeling well-informed and positive about you and your child’s next steps.
When you understand what all of the complicated sounding terms and medical language to do with autoinflammatory diseases mean, you will be able to have much better conversations with doctors about them.
Dr. Isabelle Koné-Paut, currently Head of the Department of Pediatric Rheumatology at the Paris SUD, Bicêtre University Hospital and coordinator of the National Reference Centre for Autoinflammatory Disorders answers them all here. If you don’t see the question you want to ask, please visit our Facebook page and post them there.
Marco Cattalini, Head of Pediatric Rheumatology at the Pediatric Clinic, Spedali Civili di Brescia and Assistant Professor of Pediatrics at the University of Brescia, Italy, shares his insights on the signs of periodic fever symptoms and how to find a specialist treatment center that fits your child’s needs.
The correct diagnosis of a periodic fever syndrome can be a challenge to doctors and physicians for three main reasons:
Start a "Fever Diary"
One of the main characteristics of periodic fever syndromes, from the mild to the more severe, is the recurrence of symptoms, such as high fever. It is our experience that the attention of the family first and the referring physicians thereafter are attracted by the recurrence of identical episodes. For this reason, if you suspect your child has an autoinflammatory disease, one of the best things you can do is to keep a “fever diary.” It’s not unusual that when we first see a child with “recurrent fevers” and we cannot come to a definitive diagnosis, we ask the parents to come back in a matter of months (depending on the severity of clinical manifestations) with the fever diary completed. In this diary you should note:
It is also very important that you ask your pediatrician to visit your child every time he/she has a fever and to help you fill in the diary with the precise signs associated with the fever.
Keep track of lab tests
During an attack, your physician may ask for laboratory tests (complete hemogram, ESR, CRP, urine analysis) that may be useful to see if inflammatory markers (an indication of inflammation in the body) are high during fever attacks and to rule out infections (i.e., pharyngeal swab, urine culture). If your pediatrician suspects an autoinflammatory disease, and there is a history of recurrent fever episodes with a high level of inflammatory markers during the attacks, it is also very important to take laboratory tests between the attacks, to see if the inflammatory markers normalize. One inflammatory marker that may be useful to check is Serum Amyloid A (SAA). Persistently elevated SAA levels may suggest a chronic inflammatory state, and it will be important to rule out a periodic fever syndrome.
If your diary shows recurrent episodes of systemic inflammation (i.e., fever, with elevated inflammatory markers and signs/symptoms of organ inflammation detected by your doctor) without evidence of bacterial origin, probably the most useful thing to do is to consult a physician with expertise on periodic fever syndromes for further work-up. (You can find a link to the Orphanet Directory of centers in the Links and Downloads section of this website)
If people live in remote regions where specialist treatment centers are not as accessible as they are for those who live in large cities, what are the three top tips you can give them, so they don’t miss a moment in their care?
Periodic fever syndromes are very rare diseases and many physicians are not familiar with them. As specialized centers are not always easily accessible, a few strategies may help to optimize the care of every child with autoinflammatory disease:
1. Ask for a medical letter:
The final diagnosis of periodic fever syndrome is usually done in a referral center. At that time, ask the medical team to provide you a detailed medical letter that includes the following:
2. Get contact details:
Ask the medical team for contacts (phone numbers, email addresses) where you or your primary care physician could contact the center in case of need and provide the referral center with the contacts of your primary care physician. Specialized centers can provide you and your primary care physician with all the information necessary to support you and your child. After a diagnosis is made:
1. Request patient association contact:
Ask for a patients’ association contact: patients’ associations for periodic fevers usually have their headquarters in referral centers, to be easily accessible, and are an invaluable help to manage your child’s needs. Referral centers may usually also suggest websites that provide verified information on periodic fever syndromes.
2. Call your doctor:
Promptly contact your primary care physician and share all the information gathered.
As with all rare diseases, the parents of children with periodic fever syndromes usually feel isolated and helpless, even after the diagnosis. It is very important you understand that, although rare, there are other families facing the same difficulties, and people working constantly to help you and your child to have the best possible lives. Keep in contact with them and help this community to grow stronger.
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