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Familial Autoinflammatory Syndromes (FAS)

Familial autoinflammatory syndromes (FAS) are characterized by recurrent episodes of antigen-independent inflammation, involvement of the innate immune system mediated primarily by IL-1β and absence of infection or autoimmunity (no autoantibodies).

Typically, acute unprovoked attacks are characterized by fever and elevated inflammatory markers associated with additional symptoms involving joints, abdomen, skin, and eyes. Acute attacks resolve spontaneously, and between acute attacks patients are usually asymptomatic with normal laboratory values.

  • Autoinflammatory syndromes present as recurrent episodes of inflammation without evidence of infection or autoantibodies.
  • Autoinflammatory syndromes are characterized by episodes of fever, rash, arthritis, peritonitis, eye inflammation, and elevated acute phase reactants in various combinations that normalize between flares.
  • Familial Mediterranean fever (FMF) is the only autoinflammatory syndrome responsive to colchicine.
  • In the cryopyrin-associated periodic syndromes (CAPS), nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) mutations cause dysfunction of the inflammasome leading to abnormal interleukin-1β (IL-1β) production.
  • Amyloidosis (AA) can lead to renal failure in untreated patients.
  • IL-1β inhibitors are the most effective therapy for many of these diseases.

The most common FAS is the Familial Mediterranean fever (FMF).

There are two presentations of FMF. Type 1 is characterized by recurrent episodes of inflammation and serositis. Patients can develop AA and renal failure. Type 2, where there is no previous history of inflammatory episodes, is characterized by AA (especially renal) as the first manifestation of FMF. Both types of FMF respond to colchicine therapy

Clinical features characteristic of acute FMF episode:

  • Children <20 years of age (90% of cases) of Eastern Mediterranean ancestry (Armenian, Jewish, Arabian, and Turkish origin)
  • Fever lasting 12 to 72 hours (100%)
  • Serositis: generalized peritonitis (85% to 95%), unilateral pleuritis (33% to 66%),
  • Typically nondestructive large joint monoarticular arthritis (hip, knee, ankle, wrist) (50% to 77%): severe pain out of proportion to swelling; absence of erythema and warmth; poorly responsive to prednisone, Erysipelas-like rash (30%)
  • Attacks responsive to colchicine
  • Recurrence of attacks: average every 2 to 4 weeks
  • Uncommon manifestations: polyarthritis, prolonged arthritis, severe lower extremity myalgias, aseptic meningitis, pericarditis, scrotal swelling, lymphadenopathy, Henoch–Schönlein purpura, infertility as a result of peritoneal adhesions

DD: FMF, Still Disease, Collagenoses, RA, JIA, SpA, Vasculitits, Tumors, Infections

DD: FMF, Still Disease, Collagenoses, RA, JIA, SpA, Vasculitits, Tumors, Infections Fever + Autoinflammatory Syndromes, DD: FMF, TRAPS, HIDS, CAPS (FCAS; WMS; NOMID; CINCA), VEXAS; PFAPA; ZN




Medscape Hereditary Periodic Fever Syndromes

American College of Rheumatology CAPS-Juvenile


Familial Mediterranean Fever