Archive | 2021
Clinical Presentation and Genetic Variants in Autoinflammatory Diseases: Results From the German anti-IL1 Registry for Orphan Diseases (GARROD)
Abstract
\n Background: To investigate the clinical presentation and genetic variants in patients of the German anti-IL1 registry for autoinflammatory orphan diseases (GARROD) between 2013-2019.Methods: Multicenter, retrospective analysis of demographic, clinical and genetic data of 231 patients with autoinflammatory diseases (AID) who received anti-IL1 targeted therapy.Results: Inflammatory attacks started before the age of 18 years in 44% of the patients. Symptom onset was on average 17.8 years prior to the initiation of anti-IL1 targeted therapy. AID spectrum comprised familial Mediterranean fever (FMF; n=71; 30.7%), cryopyrin-associated periodic syndromes (CAPS; n=43; 18.6%), adult-onset Still’s disease (AOSD, n=32; 13.8%) or other AID (n=85; 36.8%). Monogenetic AID were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 65% of patients with FMF, 14% with CAPS and 47% with TNF receptor-associated periodic syndrome (TRAPS). Heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 23% of patients with FMF, 51% with CAPS and 47% with TRAPS. Patients with VUS were older at disease onset, indicating a milder phenotype.Twenty-nine patients (12.5%) had secondary AA amyloidosis at initiation of anti-IL1 therapy. Primary Diseases were FMF (n=22), TRAPS (n=1) and idiopathic AA amyloidosis (n=6).Conclusions: Molecular genetic analyses might substantiate the clinical diagnosis of a monogenetic AID. In the absence of a known pathogenic variant, the functional role of VUS can be discussed. Our data support the concept of a variable penetrance of VUS, leading to late-onset AID.Anti-IL1 targeted drugs are used to control systemic inflammation, prevent disease flares and AA amyloidosis.