Determining the presence of periodic fever syndromes

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 insight on the signs of periodic fever symptoms and how to find the specialist treatment center that is fitting for your child’s needs.

What should you do if you suspect your child has a periodic fever syndrome?

This is a very good question on a relevant topic. The diagnosis of a periodic fever syndrome may be a challenge for physicians for three main reasons:

1. periodic fevers are very rare diseases in most countries and physicians –with the exception of those working in specialized centers- are often unfamiliar with their clinical presentation
 
2. since the diseases are very rare, the index of suspicion is usually low
 
3. clinical manifestations are usually not pathognomonic (distinctively characteristic of a particular disease or condition), but may overlap with much more common conditions (such as airway infections)

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 indeed attracted by the recurrence of episodes that are identical. 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:

• the exact date of each fever episode
• the exact duration of each fever episode
• If the child has symptoms associated with the fever (i.e., coughing, diarrhea). In the case of cutaneous manifestations (i.e., skin rashes) taking a photograph can be very useful
• what was the therapy prescribed?
• if laboratory or other tests have been prescribed, and what were the results

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 three top tips you can give them, so they don’t miss a moment in their care?

This is a relevant question: indeed, 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:
   • the main clinical characteristics of the disease your child suffers from, and the therapy needed (not only medical treatment but also other needs, such as physical therapy, etc.), explaining what the more common side effects could be and how they could be managed
   • how frequently the child has to be seen by a physician, and what tests should be run. This “follow/up plan” maybe individualized, according to on how difficult it is for you to reach a specialist center: in many cases, it is possible to agree on visiting the referral centers just once/twice a year and to refer to local hospital/primary physicians for more regular follow up. This plan, of course, depends on the final diagnosis, on the treatment regimen, and on how your child is doing under treatment
   • whether the disease or related treatment contraindicate normal life activity (i.e., school, sports, etc.) or universal medical procedure (i.e., vaccination)
   • what to do in case of common childhood diseases (i.e., upper respiratory tract infections, gastroenteritis) and, if relevant, what drugs should be avoided
   • when it is crucial to contact the medical team of the referral center
    

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 patient’s association contact: patients association 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 usually may 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 in 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 life. Keep in contact with them and help the community grow stronger.