Familial Mediterranean Fever Flashcards
Define FMF.
Auto-inflammatory disorder with self-limiting attacks of fever, severe abdominal pain, arthralgias or monoarthritis, pleurisy, or an erysipeloid rash on one ankle or foot, typically lasting 24-72 hours.
What is the genetic inheritance of FMF? Are carriers asymptomatic? Is it recessive?
Mendelian-recessive inheritance mutation in MEFV gene encoding marenostrin/pyrin.
MEFV gene analysis confirms FMF.
What is the epidemiology of FMF?
Mainly affects populations from the Mediterranean basin, especially Arab, Trkish, Sephardic Jewish, and Armenian ancestry where it is common.
When do first symptoms appear?
For the majority of patients, the first clinical signs appear during childhood.
What are the signs and symptoms of FMF?
- periodic fever - >38°C, usually for 12 - 72 hours
- abdominal pain(95%) - varies from mild to peritonitic
- altered bowel habit - usually constipation but children may have diarrhoea
- acute joint pain/swelling - usually one large joint at a time and may present with effusions in 75%
- unilateral pleuritic chest pain
- acute myalgia - lasts around 2 days
Other:
- Pericarditis pleural run (0.5-1%)
- Abdominal scars from multiple exploratory procedures
- Hepatosplenomegaly (15-20%) - transient elevation of liver enzymes of unknown significance
Which simple diagnostic test can be used for FMF?
Genetic testing - presence of 2 mutations on different alleles confirms diagnosis
Diagnostic test with colchicine is positive if symptoms disappear with colchicine treatment and reappear after colchicine withdrawal.
What investigations would you do for FMF?
- FBC - leukocytosis and/or thrombocytosis
- ESR - raised (may also be raised between attacks)
- CRP - ^
- Serum fibrinogen - ^
- Serum amyloid A - ^
- LFTs - elevated during attacks only (ALT and AST)
- Urinalysis - may have proteinuria during attacks
What is the treatment for attacks and between attacks of FMF?
Acute attack - analgesic/NSAID + colchicine
Between attacks - colchicine = 1.2 to 2.4 mg/day orally given once daily or in 2 divided doses. Patients usually require lifelong treatment. Dose adjusted based on response, ESR, serum amyloid A, CRP, and fibrinogen.
What was the cause of death in FMF before colchicine was used?
Amyloid nephropathy from AA amyloid in long standing inflammation
What is the management of FMF?
Colchicine - lifelong prophylaxis. The only established tx for FMF and prevents renal amyloidosis; 95% effective. Only used for symptomatic patients, not those with genetic mutations alone.
Other:
ADD NSAIDs - in acute attacks; increasing colchicine doses is not encouraged. Also used for myalgias.
Prednisolone - for prolonged myalgias
IL-1 inhibitors - new tx for those resistant to colchicine
What are the complications of FMF?
Amyloidosis
Arthritis
Spondyloarthropathy
Infertility
Failure to thrive
Appendectomies and exploratory abdo procedures before correct diagnosis
Low risk:
Protracted febrile myalgia syndrome - Severe muscle pain and tenderness that lasts for weeks and responds only to high-dose corticosteroids
Vasculitis
Behcet’s
Acute hepatitis and hyperbilirubinaemia
Cryptogenic liver cirrhosis
What is the prognosis with FMF?
Colchicine use reduces risk of most complications
A few may not respond to colchicine
