Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) Syndrome
What is Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) Syndrome?
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome is the most common recurrent fever syndrome in children. The disease is characterized by cyclic fever episodes, mouth ulcers (aphthous stomatitis), sore throat (pharyngitis) and swollen lymph nodes (adenitis). It is considered to be an autoinflammatory condition resulting from the non-specific dysregulation of the innate immune system. It is not contagious and does not have an infectious cause, which would be associated with a specific immune response. PFAPA typically presents in children 2-5 years of age with attacks lasting a few days and recurring in several weeks. Patients are seeming healthy between attacks.
Synonyms
- Marshall syndrome
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome is the most common recurrent fever syndrome in children. The disease is characterized by cyclic fever episodes, mouth ulcers (aphthous stomatitis), sore throat (pharyngitis) and swollen lymph nodes (adenitis). It is considered to be an autoinflammatory condition resulting from the non-specific dysregulation of the innate immune system. It is not contagious and does not have an infectious cause, which would be associated with a specific immune response. PFAPA typically presents in children 2-5 years of age with attacks lasting a few days and recurring in several weeks. Patients are seeming healthy between attacks.
Despite its characterization as the most frequent periodic fever syndrome in children, the exact prevalence is largely unknown due to the syndrome’s self-limiting nature and the lack of a definitive biomarker. Both sexes are affected, with males accounting for more than 60% of cases. Onset usually occurs before 5 years of age, although it can sometimes be found in adults possibly due to relapse.
| Name | Abbreviation |
|---|---|
| Marshall syndrome |
An exact cause for PFAPA is unknown although it is thought to be due to dysregulation of immune system autoinflammatory pathways. In particular, an intracellular protein complex known as the NLRP3 inflammasome is thought to be activated, triggering the release of inflammatory substances such as the cytokine interleukin 1 (IL-1), interferons and Th1 chemokines. The rapid appearance and resolution of symptoms suggests that the syndrome is driven by an intense, but time-limited, inflammatory cytokine burst. The fact that immunosuppressive drugs such as corticosteroids are effective in suppressing symptoms fits with this model.
Though PFAPA can sometimes be clustered in families, no specific gene has been identified. Patients with genetic susceptibility to Familial Mediterranean Fever with mutations in the MEFV gene may be at increased risk of developing PFAPA.
Typical episode features:
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High fever (abrupt onset, lasting 3–7 days)
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Aphthous stomatitis (painful mouth ulcers)
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Pharyngitis (red sore throat often with exudates, resembles strep throat)
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Cervical lymphadenitis (tender, swollen lymph nodes in the neck)
Additional characteristics:
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Recurrence every 3–8 weeks with predictable periodicity
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Well-being between episodes (child is asymptomatic, normal growth and development)
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No chronic organ involvement
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May have mild fatigue, headache, abdominal pain, joint pain, vomiting, diarrhea, or chills during attacks
A key criterion for PFAPA diagnosis is that patients are generally completely asymptomatic between episodes.
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Diagnosis of PFAPA is based mainly on clinical findings including recurring fevers with regular periodicity and accompanying pharyngitis, mouth ulcers and/or lymph node swelling in patients under 5 years old. At least three episodes with symptom-free intervals in between are required for diagnosis.
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Laboratory findings may include elevated C-reactive protein, erythrocyte sedimentation rate and leukocytes (white blood cell levels) during episodes. Blood counts, strep cultures, imaging or genetic tests may be performed to rule out other conditions such as recurrent infections, cyclic neutropenia, Familial Mediterranean Fever (FMF), Mavalonate Kinase Deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS).
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A positive response to corticosteroid treatment may support the diagnosis.
Variations of these criteria can be applied to diagnose adult onset PFAPA.
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Corticosteroids (prednisone or prednisolone): May rapidly abort attacks, but may shorten the interval to next episode.
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Colchicine or cimetidine: May reduce frequency in some patients.
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Tonsillectomy ± adenoidectomy: Effective in many cases, may result in permanent remission.
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IL-1 inhibitors (anakinra, canakinumab): Considered in severe/refractory cases, though rarely needed.
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Supportive care: Analgesics, hydration, reassurance.
The long-term prognosis for PFAPA syndrome is excellent. The disease is usually benign and does not cause severe symptoms, long-term complications, or permanent physical damage. Children diagnosed with PFAPA maintain normal physical and neurological development. This strong prognostic reassurance is essential for mitigating the high anxiety frequently observed in caregivers confronted with severe, recurrent febrile episodes. Treatments are often initiated for quality of life considerations such as missed school, social activities or managing parental stress.
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Rigante D, Gentileschi S, Vitale A, Tarantino G, Cantarini L. 2017. “Evolving Frontiers in the Treatment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis (PFAPA) Syndrome.” Isr Med Assoc J. 19(7):444-447. PMID: 28786261.
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Wang A, Manthiram K, Dedeoglu F, Licameli GR. 2021. “Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: A review.” World J Otorhinolaryngol Head Neck Surg. 7(3):166-173. doi: 10.1016/j.wjorl.2021.05.004. PMID: 34430824; PMCID: PMC8356195.
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Orphanet: PFAPA syndrome.
Last updated 20 Nov 2012, 10:55 PM
20 Nov 2012, 10:55 PM
The pfapa facebook page is attempting to gather location information on PFAPA patients to look at spatial distribution. I have attached a link to the survey here for those not on the facebook page. The survey asks for where you are located, how many children you have affected, and how many children you have total. There is also a couple questions on treatment that has been used, these are all western medicine options but there is a spot to enter in other treatments. The survey does not collect any other information than what you provide to the form. Please take a moment to complete the survey. I will make sure the results are posted here. "SURVEY":https://docs.google.com/spreadsheet/viewform?fromEmail=true&formkey=dGI0c0pLNGc2VlY4Y3RWbzJ3U0h3Y2c6MQ
Last updated 20 Nov 2012, 09:34 PM
20 Nov 2012, 09:34 PM
Hi Rinne. We went through the same thing with my now 4 year old. When she was about 2 1/2 she started getting high fevers (103-104) that lasted 3-4 days every 2 weeks. She was miserable, wouldn't eat, couldn't sleep and would complain that her throat was hurting. The lymp nodes on her neck would also get very swollen. Every time we would take her to the doctor and they would check for strep throat (always negative) and could never find anything wrong with her. They always said it was just a virus and to give her fluids and alternate Motrin and Tylenol. I too was worried about her having all the meds in her system but the doctor told me that as long as it wasn't daily for months it was safe. After months I finally got them to do some bloodwork and they found her white blood counts were a little high. Eventually they referred her to an immunologist. He actually diagnosed her with PFAPA. We started giving her oral steroids when she started having an episode and it usually stopped the fever but not the symptoms. He also started her on Colchicine which was supposed to stop the episodes. I was very uncomfortable with her taking the medicine and had read a lot about kids having success with T&A. So this past August she had her tonsils and adenoids taken out. Since then she hasn't had any episodes. She is finally healthy and actually gaining weight. Having the T&A was the best decision we made! I'm not sure if this helps at all but if you have any other questions let me know.
20 Nov 2012, 03:17 AM
Hi everyone, I'm not sure if anyone actually uses this but I am looking for any information possible. My 15 month old daughter has had fevers every three weeks since she was 9 months old. They last 3 days and go up to 104 degrees. She is absolutely miserable during these fever episodes and I am looking for advice on how to bring the fevers down. As right now we alternate Advil and tempra and I'm worried about her system having to much of these. How do you cope? What symptoms do your little ones have? And what medications are they on? What treatments are their doctors prescribing? Sorry so many questions but I am feeling really alone in this and nobody seems to have any answers.
Last updated 3 Mar 2011, 04:20 AM
3 Mar 2011, 04:20 AM
If anyone is interested in sharing your child's photo or story please email me at StopCAIDnow@aol.com Mike Quick(5x pro bowler for the NFL) and I are producing a video for the Foundations homepage. We welcome your VOICE and pictures to be added to the video. We will also use the pictures or videos at the Gala. The Gala will be covered by the media, so if you do not want the exposure please do not send your picture. We will not list any names or personal information on either the video for the homepage or the Gala. If you send in a video of yourself talking and choose to say who you are and what your child has, that will be the only way we will share your personal information. We want to share your story, your pictures the way you want it to be shared with the world. Thank you, StopCAIDnow,Inc.
Last updated 12 Feb 2011, 05:42 AM
12 Feb 2011, 05:42 AM
If anyone has pictures they would like to share on the Foundation website or share their story please email me @ stopcaidnow.com Lisa Moreno-Dickinson CEO/President for Stop Childhood Auto Inflammatory Diseases www.stopcaidnow.com
Last updated 10 Jun 2009, 10:56 PM
10 Jun 2009, 10:56 PM
Thank you SO MUCH, your words are so comforting, I really appreciate you sharing with me. Best wishes to you and your family always.
8 Jun 2009, 02:00 PM
My son has done very well despite all the seizures. he did (and still does) receive speech therapy for some delays in communication processing ability. He has successfully completed kindergarten and first grade and is an amazing little boy. Because I was aware that there might be some issues i began working with a speech therapist with him at the first signs of delay - my pediatrician was more than happy to make a referral for the evaluation to begin the process. The most important thing is that you advocate for your child - you know her best and your mother's intuition will guide you. There is no harm in having evals and getting the good news that she is on target - that helps you rest easier and enjoy the moment with her. if there is a need for intervention early is better! My son is an avid sports player - both soccer and baseball and very active in scouting. Folks who did not know him as an infant and toddler are completely unaware that he has had such struggles in the past. You and your daughter are in my thoughts and prayers - let me know if you have any other questions.
8 Jun 2009, 01:16 AM
Thank you for your info. My baby was recently diagnosed with this, and she has had seizures. Did your son develop fine with all the seizures? This is my concern for my baby.
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PFAPA location map
Created by jgardner1 | Last updated 20 Nov 2012, 10:55 PM
Anyone here?
Created by Rinne | Last updated 20 Nov 2012, 09:34 PM
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Created by stopcaidnow | Last updated 3 Mar 2011, 04:20 AM
Interested in sharing
Created by stopcaidnow | Last updated 12 Feb 2011, 05:42 AM
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