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Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.

Familial Mediterranean fever and periodic-fever syndromes

Rheumatology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull
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Fever with a surgical, septic or macrophage-activation mimic

Periodic-fever diagnoses do not protect against sepsis, meningitis, peritonitis, appendicitis, ectopic pregnancy, testicular torsion or macrophage activation; immunomodulated patients may deteriorate with muted signs.

Action: Assess physiology and localise the acute syndrome, obtain cultures and imaging or surgical review before attributing it to a familiar attack, withhold cytokine inhibitor during serious infection, and treat the emergency while the autoinflammatory history is verified in parallel.

Synopsis

Recognise stereotyped autoinflammatory attacks, distinguish familial Mediterranean fever from other monogenic and acquired fever syndromes, use genetic evidence proportionately, and prevent persistent inflammation and AA amyloidosis with colchicine or cytokine-directed therapy.

  • Familial Mediterranean fever causes stereotyped attacks lasting about 12–72 hours with fever, peritonitic abdominal pain, pleurisy, monoarthritis or erysipelas-like erythema and complete or near-complete recovery between attacks.
  • Clinical phenotype and response matter; MEFV testing supports diagnosis but one variant, a variant of uncertain significance or a negative panel neither proves nor excludes FMF by itself.
  • Longer TRAPS attacks often include migratory myalgia or rash and periorbital oedema; MKD adds cervical nodes, aphthae, diarrhoea and vaccine-triggered fever; CAPS adds urticaria-like rash, conjunctivitis, hearing and CNS disease.
  • During an attack obtain FBC, CRP or ESR, serum amyloid A where available, renal and liver profiles and urine; use cultures and imaging when infection or surgery remains plausible.
  • First-line FMF prevention is daily colchicine, started as soon as the clinical diagnosis is made; it prevents attacks and AA amyloidosis but is not reliable rescue for pain already established.
  • An adult commonly starts colchicine 1–1.5 mg daily in one or two doses and increases by 0.5 mg steps to a maximum of 3 mg daily when attacks or inflammation persist and tolerance permits.
  • Confirm adherence, diagnosis, dose and persistent inflammation before calling colchicine resistance; one or more attacks monthly despite the maximum tolerated dose for at least six months is a common threshold.
  • Add IL-1 inhibition for colchicine-resistant or intolerant FMF and as targeted treatment for CAPS, TRAPS and MKD, using syndrome-specific licensed and commissioned pathways.
  • Monitor attacks, serum amyloid A or CRP between attacks, urine protein and eGFR; the aim is suppression of subclinical inflammation as well as fewer fevers.
  • Continue colchicine through conception, pregnancy and breastfeeding when indicated. Avoid dangerous combinations with clarithromycin and other potent CYP3A4 or P-gp inhibitors, especially in kidney disease.

Key red flags

Shock, altered consciousness, meningism, persistent focal peritonism, gastrointestinal bleeding or hypoxaemia requires emergency infection and surgical assessment rather than attack treatment alone.

A new fever pattern lasting longer, localising differently or failing the usual treatment should reopen infection, malignancy, inflammatory bowel and macrophage-activation differentials.

Proteinuria, oedema, hypertension or falling eGFR suggests AA amyloidosis and requires urgent renal and National Amyloidosis Centre assessment.

Sensorineural hearing loss, chronic aseptic meningitis, papilloedema or destructive bony overgrowth in a periodic-fever phenotype suggests severe CAPS and threatened irreversible damage.

Severe colchicine-related diarrhoea, proximal weakness, neuropathy, cytopenia or multiorgan illness after clarithromycin or another CYP3A4 or P-gp inhibitor requires urgent toxicity care.

Persistent fever with falling platelets or fibrinogen, liver injury, coagulopathy, neurological change or rapidly increasing ferritin raises MAS or secondary HLH.

CAPS spectrum

Cold-triggered or persistent fever with neutrophilic urticaria-like rash, red eyes, sensorineural deafness, meningitic symptoms or bony overgrowth suggests NLRP3 activation.

Investigation priorities

01
First-line attack diary and objective temperatureFirst stepFirst line

Establish stereotypy, duration, interval, triggers and organ pattern before selecting molecular tests.

Management branches

First diagnostic stepCapture an untreated attack and the interval

Recurrent unexplained fever has a stereotyped history but no secure diagnosis.

  1. Record age at onset, family and ancestry, duration, interval, serosal, skin, eye, ear, ulcer, node, joint and neurological features and response to prior medicines.
  2. Obtain inflammatory, blood, renal, liver and urine tests during an early attack and repeat SAA or CRP and urine when clinically well.
  3. Refer to a specialist autoinflammatory service for phenotype-led MEFV or panel testing, biochemical tests and genetic counselling.
FMF first-line managementStart daily colchicine and suppress SAA

The clinical phenotype supports familial Mediterranean fever with or without confirmatory MEFV variants.

  1. Start colchicine 1–1.5 mg daily in one or two doses and counsel that continuous adherence prevents attacks and AA amyloid.
  2. Increase by 0.5 mg steps when attacks or SAA persist, to a maximum of 3 mg daily in an adult if organ function and tolerability permit.
  3. Monitor attack diary, interval SAA or CRP, urine protein, FBC, kidney, liver and muscle toxicity and continue treatment during pregnancy planning.

Key medicines

ColchicineStart 1–1.5 mg orally each day in one or two divided doses; increase by 0.5 mg steps for attacks or persistent SAA to a maximum of 3 mg daily in adults when tolerated.Adjust for renal or liver impairment and monitor FBC, liver, kidney and muscle symptoms; avoid potent CYP3A4 or P-gp inhibitors such as clarithromycin where exposure can become fatal.
CanakinumabFor adults and patients weighing at least 40 kg with FMF, TRAPS, MKD or CAPS, give 150 mg subcutaneously every four weeks; an inadequate response may permit escalation to 300 mg every four weeks under the product pathway.Exclude active serious infection, screen TB, update vaccines and avoid live vaccines; monitor neutropenia, liver, injection reactions and the product-specific pregnancy plan.
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Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • EULAR/PReS 2024 FMF management updateCurrent colchicine initiation, dose escalation, resistance, IL-1 treatment and monitoring.
  • EULAR/ACR IL-1 autoinflammatory disease guidanceCAPS, TRAPS and MKD diagnosis, organ surveillance and targeted treatment.
  • Ilaris European product informationCanakinumab licensed periodic-fever indications, dose and infection safety.
  • Kineret European product informationAnakinra CAPS dose, renal adjustment, infection and reproductive safety.
  • National Amyloidosis CentreUK expert referral, fibril typing and systemic assessment for suspected AA amyloidosis.
  • NICE NG203 chronic kidney disease recommendationsProteinuria, CKD monitoring and renal referral context.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateRapid draftClinical stateAwaiting review
AA amyloid signal

New albuminuria, nephrotic oedema, hypertension or falling filtration in any persistent autoinflammatory syndrome requires urgent amyloid investigation.

JurisdictionUnited Kingdom