ConditionChildren's health
Periodic Fever Syndromes
Periodic fever syndromes are conditions that cause repeated episodes of fever, separated by weeks of feeling completely well, without any infection. They are autoinflammatory: the innate immune system switches on inflammation by itself. The most common is PFAPA, which affects young children and usually fades by adolescence. Inherited types include familial Mediterranean fever (FMF), TRAPS, HIDS (mevalonate kinase deficiency) and CAPS. Diagnosis rests on the pattern of attacks, blood tests during and between them, and genetic testing. Most are well controlled with treatment.
Also called: Autoinflammatory syndromes, recurrent fever syndromes, hereditary periodic fevers, autoinflammatory diseases
At a glance
- What they are
- Repeated fever attacks without infection, with full health in between.
- Most common type
- PFAPA in children under 5; it usually goes away by the teens.
- Inherited types
- FMF, TRAPS, HIDS/MKD, CAPS, each linked to a specific gene.
- Diagnosis
- Fever diary, CRP during and between attacks, exclusion of infection, genetic tests.
- Treatment
- Steroid dose for PFAPA; colchicine for FMF; IL-1 blockers for TRAPS, HIDS and CAPS.
- Main long-term risk
- AA amyloidosis in untreated inherited types.
When to get help
Call 911 or go to the ER
- A baby under 3 months with a temperature of 38 °C (100.4 °F) or more
- Fever with a stiff neck, a rash that does not fade when pressed, confusion or difficulty breathing
- Fever with severe abdominal pain and a rigid belly, or a child who is floppy and hard to wake
See a doctor within a day or two
- Fever lasting 5 days or more, especially with red eyes, red lips, a rash and swollen hands (possible Kawasaki disease)
- Recurrent fevers with weight loss, night sweats, bruising or bone pain
- Fever attacks with swelling of the legs or foamy urine (possible amyloid kidney disease)
Book a routine appointment
- Fevers that recur every few weeks with the child well in between
- A diary showing a regular cycle of fever with mouth ulcers or sore throat
- Recurrent fever with a family history of FMF or similar illness
- Hearing loss, red eyes or a hives-like rash that comes with fevers
What makes a fever "periodic"
Fever is a normal part of childhood infection. Periodic fever syndromes are suspected when:
- fever episodes recur for at least 6 months
- they look similar each time, often on a regular schedule
- the child or adult is entirely well between episodes, with normal growth
- no infection is found, and antibiotics do not change the course
These conditions are driven by the innate immune system, mostly through a signaling molecule called interleukin-1 (IL-1). Unlike autoimmune diseases, there are usually no autoantibodies.
Main types compared
| Syndrome | Typical onset | Attack length | Distinctive features | Gene |
|---|---|---|---|---|
| PFAPA | Ages 2 to 5 | 3 to 6 days, every 3 to 8 weeks, clock-like | Mouth ulcers, sore throat, swollen neck glands | None identified |
| Familial Mediterranean fever | Childhood, before 20 | 12 to 72 hours | Belly or chest pain (serositis), joint pain, red rash on lower leg | MEFV |
| TRAPS | Any age, often childhood | 1 to 3 weeks or longer | Migrating muscle pain with overlying rash, swelling around the eyes | TNFRSF1A |
| HIDS / mevalonate kinase deficiency | Infancy, under 1 year | 3 to 7 days | Swollen glands, diarrhea, vomiting, rash; attacks after vaccines | MVK |
| CAPS | Birth or infancy | Daily or episodic | Hives-like rash, cold-triggered attacks, red eyes, hearing loss | NLRP3 |
| Cyclic neutropenia (not autoinflammatory) | Childhood | 3 to 6 days every 21 days | Mouth ulcers, infections, very low neutrophils during attacks | ELANE |
PFAPA
PFAPA stands for Periodic Fever, Aphthous stomatitis (mouth ulcers), Pharyngitis and cervical Adenitis (swollen neck glands). It is the most common periodic fever in children. Fevers often reach 39 to 40.5 °C (102 to 105 °F) and arrive so regularly that parents can predict them on a calendar. Children grow normally and have no long-term complications. Most outgrow it within 4 to 8 years, typically by age 10 to 12.
Familial Mediterranean fever
FMF is the most common inherited periodic fever worldwide, frequent in people of Armenian, Turkish, Arab, Sephardic and Ashkenazi Jewish and other Eastern Mediterranean ancestry. Attacks cause intense abdominal pain that can mimic appendicitis. Untreated, it can lead to amyloidosis, which damages the kidneys.
TRAPS, HIDS and CAPS
These are rare and usually need specialist care. CAPS ranges from mild familial cold autoinflammatory syndrome to severe neonatal-onset disease with meningitis and joint damage.
What attacks feel like
Besides fever, attacks commonly include:
- mouth ulcers, sore throat and swollen neck glands
- abdominal pain, sometimes with vomiting or diarrhea
- chest pain from inflamed lining of the lungs
- joint or muscle pain
- rashes, red eyes, headaches and tiredness
How they are diagnosed
- Fever diary: record the date, highest temperature, duration and every symptom for each attack. Photos of rashes help. This is the most useful diagnostic tool.
- Blood tests during an attack: high CRP, ESR and white cell count show inflammation.
- Blood tests between attacks: markers return to normal in PFAPA; persistent raised inflammation suggests another condition.
- Exclude infection and other causes: throat swabs, urine tests, and tests for blood disorders, Behçet's disease, inflammatory bowel disease and lymphoma when relevant.
- Serial blood counts 2 to 3 times a week for 6 weeks if cyclic neutropenia is possible.
- Urine mevalonic acid during an attack for HIDS.
- Genetic testing: a gene panel for inherited fever syndromes.
- Response to treatment: dramatic improvement of PFAPA with one dose of steroid, or of FMF with colchicine, supports the diagnosis.
Diagnosis is often led by a pediatric rheumatologist or immunologist.
Treatment
PFAPA
- One dose of oral steroid (prednisone or prednisolone) at the start of an attack usually stops the fever within hours. It may shorten the time until the next attack.
- Colchicine can lengthen the gap between attacks in some children.
- Tonsillectomy cures or improves PFAPA in many children and is an option when attacks are frequent and disruptive.
- Fever medicines such as acetaminophen (paracetamol) or ibuprofen ease discomfort but do not stop attacks; follow the label dose. Do not give aspirin to children or teenagers.
Inherited syndromes
- FMF: daily colchicine for life prevents attacks and amyloidosis. IL-1 blockers are used if colchicine fails.
- TRAPS: steroids for attacks; IL-1 blockers (such as canakinumab) for frequent attacks.
- HIDS/MKD: NSAIDs or steroids for attacks; IL-1 blockers for severe disease.
- CAPS: IL-1 blockers (anakinra, canakinumab, rilonacept) are highly effective and prevent hearing loss and organ damage.
Complications and outlook
PFAPA has no lasting effects and usually resolves on its own. In untreated FMF, TRAPS and CAPS, chronic inflammation can cause AA amyloidosis, mainly affecting the kidneys, as well as hearing and vision loss in CAPS. With modern treatment, most people with inherited periodic fevers live normal lives. Monitoring of urine protein and inflammation markers is part of long-term care.
Frequently asked questions
What is the most common periodic fever syndrome?
PFAPA is the most common periodic fever syndrome in children. It causes fever every 3 to 8 weeks, with mouth ulcers, sore throat and swollen neck glands. Familial Mediterranean fever is the most common inherited type worldwide.
Why does my child get a fever every month?
Frequent infections at nursery are the most common reason. If the fevers come on a regular schedule, the child is completely well between them, and tests show no infection, a periodic fever syndrome such as PFAPA is possible. Keep a fever diary and share it with your pediatrician.
Does PFAPA go away?
Yes. PFAPA usually resolves on its own, typically after 4 to 8 years and often by age 10 to 12. Attacks tend to become less frequent and milder over time. It does not cause long-term damage.
Are periodic fever syndromes genetic?
Some are. FMF, TRAPS, HIDS and CAPS are caused by changes in specific genes and can run in families. PFAPA is not linked to a single gene, although it is somewhat more common when a parent or sibling had recurrent fevers or tonsillitis in childhood.
Can adults have periodic fever syndromes?
Yes. FMF and TRAPS can start or be diagnosed in adulthood, and adult-onset PFAPA has been described. Adults with recurrent, unexplained fevers and normal health in between should be evaluated by a rheumatologist.
Sources
This guide was written from current patient and clinical guidance, including:
- American College of Rheumatology: Periodic fever syndromes patient information
- Eurofever/PRINTO: Classification criteria for autoinflammatory recurrent fevers
- Genetic and Rare Diseases Information Center (GARD): Periodic fever syndromes
- American Academy of Pediatrics (HealthyChildren.org): Periodic fever syndromes and PFAPA
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): Autoinflammatory diseases