Synopsis
Recognise stereotyped sterile inflammatory attacks, distinguish PFAPA from monogenic autoinflammatory disease and recurrent infection, capture objective evidence during flares and refer early enough to prevent amyloidosis and organ damage.
- Periodic fever means recurrent stereotyped inflammatory attacks with objective wellness or a stable baseline between them after infection, malignancy, immune deficiency and autoimmune disease are considered.
- Ask families to record measured temperature, duration, interval, rash, mouth, throat, nodes, serositis, joints, eyes, hearing, triggers and complete recovery in a fever diary.
- PFAPA usually begins before age five with three- to seven-day fevers every few weeks, aphthous ulcers, pharyngitis or cervical adenitis and normal growth between attacks.
- PFAPA is clinical: throat cultures are negative during typical attacks and corticosteroid response supports but does not prove the diagnosis; inherited periodic fever must be reconsidered when atypical.
- FMF attacks usually last one to three days with peritonitis-like abdominal pain, pleurisy, arthritis or erysipelas-like leg rash; colchicine prevents attacks and AA amyloidosis.
- Mevalonate kinase deficiency causes three- to seven-day attacks with cervical nodes, abdominal symptoms, rash and aphthae, often triggered by vaccination or infection.
- TRAPS often produces attacks longer than a week with migratory myalgia or rash and periorbital oedema; CAPS can cause cold-triggered urticaria-like rash, red eyes, meningitic symptoms and hearing loss.
- Obtain FBC, CRP or ESR, ferritin, renal and liver profile, urinalysis and serum amyloid A when available both during an attack and when well to document the inflammatory pattern.
- Genetic testing is phenotype-led through an autoinflammatory service; broad unsupervised panels create uncertain variants and do not replace clinical assessment.
- Refer suspected monogenic disease, persistent interval inflammation, proteinuria, hearing or neurological features, or colchicine-resistant FMF for specialist IL-1-directed treatment.
Key red flags
Poor growth, persistent symptoms between attacks, organ enlargement, lymphadenopathy, clubbing or fixed rash argues against uncomplicated PFAPA and needs broader investigation.
Neutropenia during predictable roughly three-week episodes suggests cyclic neutropenia and requires serial FBC rather than clinical PFAPA diagnosis.
Travel, exposure, immunodeficiency, central lines or immunosuppression maintains a high infection probability even when fever has recurred previously.
Proteinuria, oedema or persistently raised serum amyloid A between attacks raises AA amyloidosis from uncontrolled monogenic autoinflammation.
Prolonged attacks, serositis, migratory myalgia, periorbital oedema, cold-triggered urticaria-like rash, hearing loss or family history suggests monogenic periodic fever.
Very high ferritin with cytopenia, hepatitis, coagulopathy or neurological deterioration suggests macrophage activation rather than a routine periodic attack.
Investigation priorities
Demonstrate stereotyped duration, interval, associated features, treatment response and complete inter-episode recovery.
Management branches
A child with recurrent fever presents unwell or with atypical features.
- Use ABCDE and assess sepsis, meningism, macrophage activation, abdomen and immune status.
- Obtain cultures and give antimicrobials when clinical probability warrants them.
- Compare the episode with the established pattern but never let the label override current physiology.