Your child with frequent fevers: is it autoinflammatory?

When I was little, I used to get a lot of fevers.  With my fevers, I would develop pain in one or both of my ears, and I felt so drained that I just wanted to be left alone to watch TV (or play Atari).  If my fever spiked in the middle of the night, my parents would soak me in a tub of lukewarm water to lower my temperature (how I hated those baths!).  On the following day, I would visit my pediatrician, who would invariably diagnose me with an ear infection.  He prescribed a delicious bubble-gum flavored antibiotic that my parents kept at the top shelf in the refrigerator (out of my reach so I wouldn’t overdose).  I’m not sure if it was the taste or the active ingredient, but this antibiotic always made me feel better.  After what seemed like the millionth episode of fever, my pediatrician recommended that I get tubes in my ears, and the episodes of fever and ear pain subsided.

Recurrent infections, like those I had when I was a child, are the most common cause of frequent fevers in children.  Usually, these infections are due to viruses, such as the ones that cause the common cold.  Children with colds often develop symptoms attributable to the virus, including a runny nose, nasal congestion, or cough.  Multiple infections, one after the other, are especially common in children attending daycare or school, where they trade viruses like I used to trade baseball cards with my friends.  When I see these the worried parents of these children in my office, I have to remind them that it is normal for a child to have 9-12 colds every year.  Fortunately, these children continue to grow and gain weight without difficulty, and they are healthy between episodes. “As your child grows,” I tell the parents, “his immune system will become better at fighting infections, and the frequency and severity of fevers will diminish.”  Aside from stressing the importance of hand washing among all family members, there is not much that can (or needs) to be done about these episodes. 

However, if the episodes do not clearly match the above description, other diagnoses should be considered.  In this post, I will provide some tips that may help parents and physicians recognize a rare cause of fever in children: autoinflammatory diseases.  The most common autoinflammatory disease in children is called PFAPA, which stands for Periodic Fevers, Aphthous stomatitis (canker sores or oral ulcers), Pharyngitis (sore throat) and Adenitis (enlarged glands in the neck).   This disease usually presents in children less than 5 years of age, and causes episodes of fevers in addition to the features that make up the name of the disease (oral ulcers, sore throat, enlarged glands in the neck).  The fever usually lasts about 4 days, and it recurs at regular intervals, usually every month.  What is unique about PFAPA is that parents can usually predict when the child is “due” to get ill.  The episodes of fever are so regular as to be predictable.  This regularity is rare in most other diseases.  PFAPA is commonly misdiagnosed as frequent Strep infections, and testing for Strep throat is usually negative.  Patients do not readily respond to antibiotics, although their symptoms can disappear with one dose of steroids.

Another clue that the child may have an autoinflammatory disease is that all of the episodes of fever look alike.  For example, if the child always develops abdominal and joint pain with the fevers, then he may have familial Mediterranean fever (FMF).  If, in addition to fever, she always develops a painful rash, muscle pain, and red eyes, then she may have TNF-receptor associated periodic fever (TRAPS).  If he develops fevers, rashes, and joint pain after exposure to cold weather, then the child may have familial cold-induced autoinflammatory syndrome (FCAS).

The length and frequency of fever, associated symptoms, and age at which the fevers began can help differentiate between these (and other) autoinflammatory diseases.   Thus, it is very helpful to keep a fever diary,  specifying the characteristics of each episode.  Because many of these autoinflammatory diseases are inherited (genetic), there is often a history of other family members having similar symptoms.  In addition, it is important to note that some autoinflammatory diseases are more common in people of certain ethnic backgrounds, such as FMF in Sephardic Jews, Turks, and Armenians.

In addition to autoinflammatory diseases, there are some features of recurrent fevers that should warrant a closer look by a child’s  pediatrician.  These include prolonged episodes of fever (more than one week), recurrent fever without symptoms attributable to a viral infection, difficulty growing or gaining weight, or if the child does not return to his baseline between episodes.  Other causes of fever that should be considered in these instances include:

  • Immunodeficiencies: problems in the immune system that makes the child more susceptible to infections
  • Anatomic and metabolic abnormalities: abnormalities in certain organs that make them more prone to infections (like my ears), or diseases such as cystic fibrosis
  • Inflammatory bowel disease: inflammation of the intestines
  • Cancer: such as leukemia or lymphoma

With this knowledge, parents and pediatricians alike can help distinguish between the majority of children that develop recurrent fevers because of frequent viruses, from causes which may require additional workup or treatment.

28 thoughts on “Your child with frequent fevers: is it autoinflammatory?”

  1. This is a really helpful article. Thanks for all that you are doing to get more information and awareness out to the public about autoinflammatory diseases

  2. The only issue I have….yes, good information, but very simplified. My son’s PFAPA symptoms often sounds more like the other disorders, but bloodwork is negative, but as we all know, only a certain percentage of positives occur with bloodwork, leaving some kids with false negatives and often parents with more questions than answers. When I listen to others talk about their child’s symptoms, it’s never so simple and cut and dry. It really seems like there are some usual patterns but the actual symptoms vary. So much more research needs to continue on these disorders. I still have to wonder if at some point PFAPA will be found to be a spectrum of varying autoinflammatory conditions, which could explain the varying symptoms many of these kids get.

    1. Hi Wendy. You’re right that autoinflammatory diseases are more complex than what I’ve written here. In fact, they’re more complex than anyone knows! About 25-50% of patients that I see with autoinflammatory diseases have negative genetic workup, like your son. We still don’t know many of the genes that cause these diseases (new diseases are discovered every month!). In addition, some diseases like perhaps PFAPA and systemic arthritis (adult onset Still’s disease) do not seem to be completely genetic. There doesn’t seem to be one gene that causes the disease, like there is for Familial Mediterranean Fever, for example. Perhaps there are environmental triggers (such as infections) that, combined with a person’s genetic makeup, contribute to the disease. I hope that by continuing to study these diseases, we’ll be able to identify the causes of these illnesses, including your son’s. In the meantime, we are left to try different medicines to see if they work for a patient’s recurrent fevers.

      1. My grandson had recurrent high fevers for almost 5 weeks he has been on two different oral antibiotics and has had 3 rounds of Rocephin shots because they thought it was his ears his ears are still not well but they’re not as bad as they were he is having clammy sweats and still has a high fever today we went to the hospital for testing they are checking for Hepatitis C and several other things I just wondered if you had any ideas they said it may take for plus days for blood work to come back and that will be the longest for plus days probably of my life

        1. Yes, it can be quite stressful to care for a child with persistent fevers! It is a common challenge that doctors often face, one which does not have an easy solution. We are trying to better understand fevers with our Feverprints iPhone study (feverprints.com) to help doctors make faster, more accurate diagnoses for febrile patients.

  3. Hi Thankyou for raising awareness.
    As a doctor and dentist in the uk I had a fight to have my son diagnosed- he had fevers from 7 months but was not diagnosed until 27 months after we saw our 8th consultant (and had had immunology testing done privately). I was accused of being a hypochondriac to having munchausens by proxy!
    The fact that in between episodes PFAPA kids are completely well did not help.
    I have similar symptoms to my son with recurrent ulcers, swollen glands. Chills and fevers and we both get skin sores, arthralgia, abdominal pain, headache, dreadful fatigue and fevers but I have the label of probable Behçet’s disease which of course is another autoinflamatory disease.
    I am Sure behcets and PFAPA are on ends of a spectrum as I find that many children with PFAPA, once they pass puberty and still have it, are relabelled behcets!! The medical treatment here with colchicine is the same.
    Also many of the mothers of PFAPA I know have diagnoses of behcets!!
    The worst thing is my son and I often flare at the exactly the same time every month and then (because I am a single mum) it’s so hard as I feel dreadful and so does he!
    The plus is my geneticist enrolled him to have his entire genome studied in the Sanger institute DDD study which may help unravel things in the future!

    1. Thank you for your story! The challenges you and your son have faced in arriving at a diagnosis is unfortunately all too common. Many physicians still don’t recognize these diseases. Even those of us that do have many questions that are still unanswered. Research studies, like your son has recently participated in, will be incredibly helpful to learn more about autoinflammatory diseases. In the future, I hope to facilitate the study of patients with autoinflammatory diseases by creating an online registry for patients and their families. Thanks for reading my blog!

  4. My daughter has been having recurrent fevers since she was about 6 months old. She is now 22 months. We have been to several ERs, urgent cares. Primary care, and are being followed by infectious disease. She never has any symptoms besides not eating, high fever, stumbling more, crying as if in pain, and restless sleep. We’ve had labs run that show low igg and IGA along with no antibodies to some vaccines. We keep being v told to wait and see. No diagnosis. Its incredibly frustrating. She’s now getting them more frequently (every 22 days). As a mom, I know something is going on, but no one can give me answers.

    1. This is an interesting story. The frequency of fevers, regular timing, early onset of disease, and lack of other causes does raise the suspicion for an autoinflammatory disease. An appointment with a pediatric rheumatologist may help to clarify the cause, and perhaps provide a solution. Let me know if you need help finding a rheumatologist in your area.

    2. Omg!
      My 15 mth old son has been having recurrent very high fevers 103-104, poor growth,screaming out in pain, trouble with sleeping during the fevers and staggers like a drunk person during these episodes! We are at our wits ends. I don’t know where to turn!
      I feel like my baby is dying before my eyes!

  5. My 7 year old son has been having recurrent fevers (101.7) every few weeks now. He says he feels dizzy and complains of feeling like he will get sick but never actually does. He sleeps and in 24 hours feels fine. There are no other symptoms outside of this and no other children sick to cause it. His little brother and him go to the same daycare and eat/drink the same things and he is fine. There are no ulcers or rashes on him at all. It doesn’t seem to match what you are discussing except for the fever for no reason. What is this?

    1. The most common cause of recurrent fevers in children are recurrent viral infections, but I agree with you that it’s unusual that nobody else gets sick. a Good fever history, physical examination during an episode, consideration of bloodwork during and between fevers may be helpful to distinguish the underlying etiology. A good pediatrician can begin the appropriate workup.
      Good luck!

  6. My daughter is 7 years old and has gotten a fever every month since May of this year. They just come out of nowhere, and last about 3 days. She gets joint pain and abdominal pain with each one. She has been to the ER numerous times and has been worked up for appendicitis twice. I knew there was something going on but I didn’t know what, until we brought her to her Pediatrician during one of her fevers. The pediatrician checked her temp and it was 104.5 and felt her tummy which was really hurting. They gave her ibuprofen and consulted with the local ER. Her pediatrician suspects Familial Mediterranean Fever, and the local ER felt it was best to send her the Children’s hospital in Madera, CA. We drove the 2 hours and they evaluated her and kept her for over 6 hours. They ran a bunch of blood tests and her CRP level came back double than normal. So, they have referred her to an infectious disease doctor who she will see this Thursday. The one thing I have learned and is so important is to keep a fever diary. I had been keeping track of her fevers and showed the log to her doctor. She looked at it and was able to see a pattern and said that since there is a pattern, they have more information and can properly work her up and determine the cause. A couple of times she had a fever, they named it as a viral infection and sent her home. I am so glad now that we are being taken seriously and she is getting the tests and specialists she needs to figure out the cause of her symptoms.If you feel that something is wrong with your child, be persistent and don’t give up on getting a diagnosis. My daughter has missed several days of school and we the parents are being hounded by her school for her absences. So, in this case, once a diagnosis is confirmed, we will be discussing her medical condition with her school. Thanks for reading my post and for this very informative blog!

      1. Thanks for your comment and continued research Dr. Haussmann. I have a question about FMF. Does it cause kids not to grow? My daughter is very small and her height doesn’t even measure on the pediatricians growth chart, nor her weight. She has always been like this. Her doctor said she had constitutional growth delay. She will see an endocrinologist for her growth problems Sept 22nd, in which this appointment was made before we had suspicion about FMF. Could FMF be causing her growth delay and how does FMF affect growth?

        1. Hi. FMF can certainly affect growth. Many FMF patients have evidence of chronic inflammation in the blood, meaning that the body is spending energy causing inflammation rather than spending that same energy to grow bones, muscles, etc. In fact, any chronic illness that causes inflammation (juvenile arthritis, inflammatory bowel disease, systemic arthritis) can impair growth. Fortunately, treatment of FMF by controlling the inflammation can help to improve growth trajectory. However, most patients with FMF also will have the recurrent fevers with abdominal pain…it would be unusual for a child to have poor growth as the sole manifestation of FMF.

  7. My daughter has been diagnosed with FMF by the infectious disease specialist. She is on colchicine 6 mg daily. She has had recurrent fevers with abdominal pain since Fec. 2015 and is not growing properly too. I was just seeing if their was a connection between poor growth and FMF. She is waiting to see a ped. rheumatologist now. Any advice for me? This is all so new to me. Thanks!

  8. I have to say I am so excited that we have an appointment with you, coming up soon. My son has had recurrent revers every 3-5 weeks since he was 5 weeks old. Every test he has had done is normal or only mildly elevated, and no physicians seem to know what is causing these episodes that consist of fevers,lethargy, leg and lower back pain, sleeplessness, diarrhea with blood in his stools, and just over all feeling miserable. I have read many of your blog posts and I am hopeful you will lead us to the answers that I have been looking for for well over 2 years!

  9. Thank you for providing this information and feedback! Is there such thing as “incomplete PFAPA?” My daughter (4) has been having fevers every month for the last 8 months, lasting about a week, but without the mouth sores or abdominal pain that PFAPA and other diseases feature. She sometimes has lower leg pain a small rash, or sometimes has enlarged cervical lymph nodes, but in general only has fatigue before/during/after the fever strikes, lack of appetite, and irritability. She has a team of pediatricians, an infectious disease specialist, a fever specialist, and a rheumatologist, and we are kind of grasping at straws. The odd thing about the fevers are that they have a distinct daily pattern- 99s in the morning and often evening, while high in the afternoon (100.3-104 depending). Do PFAPA or any other autoimmune disease behave this way with incomplete symptoms and a daily fever pattern?

    1. PFAPA is the most common periodic fever syndrome in children, but certainly there are many other causes of recurrent fevers. Some children do not present with all of the features of PFAPA. A good history, physical exam, and selected blood tests may be able to help differentiate between the many causes of recurrent fevers.

  10. thank you
    i just made my parents confess …i actually don’t remember anything before i was 10 ..i remember everything …after when i was above 11 or 12 years ….and i get a UNUSUAL CHEST PAIN ..while i am running or …it gets occasionally ..when i am stressed out …RIGHT AT THE HEART …i haven’t told them yet ….but my parents say ..that when i was VERY YOUNG about 5-6 …..i used to get FEVER …and sometimes i even blacked out ..when i was diagnosed …..docs told ’em that i can be in come sort of danger ..so they would need to take care of me until i was 10 …..and my parents constantly KEEP MOVING …from place to place …2-3 times a year ……that explains everything ..cant i remember my child hood as others do !

  11. Can someone have a periodic autoinflammatory syndrome without fever? And what variation can there be in the length of the time period in any given individual (can it be something like, in weeks: 2, 2, 3, 2, 3, 4, 4, 5, 4, 3, 3, 2, 2, 2, 2, 5 )?

    (Please feel free to just answer the general questions above, for background here is my son’s info: The symptoms my son has are: behavior problems day 1 such as over-emotional, followed by scratchy throat day 2, sometimes sniffly (clear never green etc), aphthous ulcer on inside of cheek or roof of mouth, facial puffiness (“malar” or peri-orbital) and flushed cheeks and chin, continued poor behavior, slowed speech and exhaustion, lasting from 3 days to a week or so. He has a continuous chronic mild headache for 3 years now, which gets worse with these “colds”, the only headache free moments were during a prednisone trial (which helped amazingly giving him back energy he never otherwise has). He also improved markedly for a month or so one time when he had (we think it was) influenza. The other thing that helped was tonsillectomy, helped temporarily ceasing “colds” for 3-4 months. His overall health has declined, he is just sick so much, goes half days to school because so fatigued. A rheumatologist just gave us a pain syndrome handout and no tests (granted he has already had a mountain of tests including brain MRI and sequencing, all normal except he always has activated lymphocytes just hanging out for no good reason. He did have a mitochondrial variant of unknown significance (but I don’t know why getting the flu would help if it was that).).

  12. Sir,
    Whats the cure of this PFAPA? What test required for this in addition with sick history?

    My daughter gets fever and cold once in every month for the past 9 months. It is very regular without miss.
    Chest cold always..

  13. My 11 year old daughter has fever (temp range averaging between 99.6 and 101.7 since becoming sick) and constant headache (mostly mild, but always there.) Tons of blood work and everything coming back negative. We are in week 5 and she has only been near normal (for her) temp one day.
    When she gets sick she tends to hold a fever days longer than those around her, but that had not thrown red flags until I start recalling every detail from past illnesses and certain aspects start to become more obvious now.
    PCP and Specialists basically ignored my questions about possible autoimmune issues.
    I appreciate when i find postings like this one. Feel for all the parents dealing with anything negative with a childs health, but reassured seeing those that have found answers in time.
    Thank you all for sharing.

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