Caution Should be Used in the Recognition of Adult-Onset Autoinflammatory Disorders: Facts or Fiction?

inheritance patterns, and the most peculiar clinical manifestations. The recognition of AIDs derives from the combination of clinical data, evaluation of acute phase reactants, clinical efficacy in response to specific drugs, and identification of specific mutations in the causative genes (Federici et al., 2006; Gattorno et al., 2008; Cantarini et al., 2010a, 2011, 2012a,b; Muscari et al., 2012). Genetic testing remains a feasible tool to corroborate the clinical diagnosis of AIDs. Most of these disorders are manifest in childhood, but a certain number of patients may experience disease onset during adulthood. To date, among monogenic AIDs a late disease onset has been described in FMF (Sohar et al., 1967; Sayarlioglu et al., 2005; Cantarini et al., 2010b), TRAPS (Aksentijevich et al., 2001; Dodé et al., 2002; Aganna et al., 2003; Cantarini et al., 2012c), CAPS (Vitale et al., 2012), and NLRP12AD (Borghini et al., 2011). Adult-onset FMF is fairly rare, however it has been reported as late as age 65 (Cantarini et al., 2010b), and advanced age is not an exclusion criterion (Livneh et al., 1997): this picture is mainly related to low-penetrance mutations, giving rise to a milder disease, generally similar to that of younger patients (Sayarlioglu et al., 2005). On the contrary, a more significant variability in terms of clinical phenotype may be observed in TRAPS (Aksentijevich et al., 2001; Dodé et al., 2002; Aganna et al., 2003; Ravet et al., 2006; Cantarini et al., 2009, 2010c,d,e,f,g; Rigante et al., 2011; Brizi et al., 2012): this heterogeneity is largely related to the wide spectrum of known TNFRSF1A mutations, which can be distinguished into high-penetrance and low-penetrance variants (Touitou et al., 2004). As in FMF, adult-onset of symptoms is usually Caution should be used in the recognition of adult-onset autoinflammatory disorders: facts or fiction?