Comparison of the Most Common Monogenetic Autoinflammatory Syndromes
Syndrome | Inheritance | Age at Onset (years) | High-Risk Ethnic Populations | Duration of Attack (days) | Clinical Features | Amyloid Risk | Gene | Protein |
---|---|---|---|---|---|---|---|---|
FMF | Autosomal recessive | <20 (90% of patients) | Jewish, Arab, Turkish, Armenian, Italian | 1–3 | Erysipelas-like rash, sterile peritonitis, monoarthritis, pleuritis | +++ | MEFV | Pyrin |
TRAPS | Autosomal dominant or de novo | <20 (middle-age onset reported) | Any ethnic group | >7 | Myalgias with overlying rash, conjunctivitis or periorbital edema, peritonitis, large joint arthritis | ++ | TNFRSF1A | TNF receptor Type I |
HIDS | Autosomal recessive | <1 (90% of patients) | Dutch, French, other European | 3–7 | Maculopapular rash, abdominal pain, polyarthritis, splenomegaly, cervical adenopathy, aphthous ulcers | – | MVK | Mevalonate kinase |
FCAS | Autosomal dominant | <1 (95% of patients) | Mostly European | <2 | Cold-induced urticaria, arthralgia, conjunctivitis | – | CIAS1 (NLRP3) | Cryopyrin |
MWS | Autosomal dominant | <20 | Northern European | 2–3 | Urticarial rash, arthralgia/arthritis, conjunctivitis/episcleritis, sensorineural hearing loss | ++ | CIAS1 (NLRP3) | Cryopyrin |
NOMID | Autosomal dominant or de novo | <1 (birth or early infancy) | Any ethnic group | Continuous | Urticaria-like rash, epiphyseal overgrowth, arthritis, contractures, conjunctivitis, uveitis, vision loss, hearing loss, hoarseness, chronic aseptic meningitis, hepatosplenomegaly | + | CIAS1 (NLRP3) | Cryopyrin |
PAPA | Autosomal dominant | <10 | Any ethnic group | Variable | Pyogenic sterile arthritis, pyoderma gangrenosum, cystic acne | – | CD2BP1/PSTPIP1 | CD2-binding protein |
Blau | Autosomal dominant | <3–5 | Any ethnic group | Variable | Polyarthritis, tenosynovitis, anterior or panuveitis, granulomatous dermatitis | + | NOD2/ CARD15 | NOD2 |
DIRA | Autosomal recessive | <4 weeks | Newfoundland, Puerto Rico, Netherlands, Lebanon | Almost continuous | Pustulosis, pathergy, sterile osteomyelitis, periostitis at ends of ribs/long bones, respiratory distress. Fever typically absent | – | IL-1RN | IL-1ra |
DITRA | Autosomal recessive | Variable (neonate to adult) | Any ethnic group | Variable, days to weeks | Generalized pustular psoriasis (including palms, soles), high fever, arthralgia, glossitis, nail dystrophy | – | IL36RN | IL-36ra |
CANDLE | Autosomal recessive | Birth or infancy | Various ethnicities reported | Variable, frequent, or continuous | Fever, annular rash, lipodystrophy, lip swelling, aseptic meningitis, growth delay, episcleritis, conjunctivitis, cardiomyopathy, diarrhea, hepatomegaly, arthropathy | – | PSMB8, and others | Proteosome subunit B8 |
DADA2 | Autosomal recessive | Variable; childhood | Unknown | Variable | Fever, livedo reticularis, early-onset vasculopathy (stroke and/or polyarteritis nodosa presentation), mild immunodeficiency | – | CECR1 | ADA2 |
CANDLE, Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; DADA2, deficiency of adenosine deaminase 2; DIRA, deficiency of IL-1 receptor antagonist; DITRA, deficiency of IL-36 receptor antagonist; FCAS, familial cold autoinflammatory syndrome; FMF, familial Mediterranean fever; HIDS, hyperimmunoglobulin-D syndrome; MWS, Muckle Wells syndrome; NOMID, neonatal onset multisystem inflammatory disease (sometimes referred to as chronic infantile neurologic, cutaneous and articular syndrome, or CINCA); PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome; TRAP, TNF-receptor-associated periodic syndrome.