Systemic autoinflammatory diseases (
SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known
SAIDs are
familial Mediterranean fever (FMF);
cryopyrin-associated periodic syndrome (CAPS);
mevalonate kinase deficiency (MKD); and periodic
fever, aphthosis,
pharyngitis, and
adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of
vaccines for all individuals with
SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of
vaccines in patients with
SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with
SAIDs on treatment with
biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with
colchicine alone than in those treated with both
colchicine and
canakinumab. Conversely, a decreased risk of
SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the
mRNA-based
BNT162b2 vaccine.
Canakinumab did not appear to affect the ability to produce
antibodies against non-live
vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the
pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either
anakinra or
canakinumab. PFAPA patients seem to be less responsive to
measles,
mumps, and
rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against
hepatitis A. In consideration of the clinical
frailty of both children and adults with
SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.