AA amyloidosis in the four historical monogenic autoinflammatory diseases: Clinical burden and insights from a retrospective referral-centre study.

BACKGROUND: AA amyloidosis (AAA) remains a life-threatening yet largely preventable complication of monogenic autoinflammatory diseases (AIDs). METHODS: We retrospectively described patients with AAA secondary to one of the four historical monogenic AIDs (familial Mediterranean fever [FMF], cryopyrin-associated periodic syndrome [CAPS], mevalonate kinase deficiency [MKD] and tumour necrosis factor receptor-associated periodic syndrome [TRAPS]) followed at the French National Referral Centre for Monogenic AIDs and Inflammatory Amyloidosis (2012-2025). RESULTS: Among 181 patients followed for AAA, 50 (28%) had one of the four monogenic AIDs (FMF n = 41, CAPS n = 4, MKD n = 3, TRAPS n = 2), corresponding to an overall prevalence of 5% among all patients with monogenic AIDs. AAA preceded the diagnosis of the underlying AID in 40% of patients, particularly those with non-FMF diseases. Disease burden remained high, with 46% of patients requiring kidney transplantation, whereas mortality reached 26% during follow-up. CONCLUSION: AAA continues to reflect delayed diagnosis, highlighting the need for increased awareness among adult healthcare providers, systematic genetic evaluation of unexplained AAA and early inflammatory control.