Autoinflammatory Diseases

  • Donato Rigante
  • Antonio Vitale
  • Luca Cantarini


Autoinflammatory diseases (AIDs) represent a relatively new group of rare disorders determined by deregulation of specific components of innate immunity. They are currently subdivided into monogenic and multifactorial diseases with the former strictly related to specific gene mutations and the latter characterized by a deregulation of innate immunity in the absence of Mendelian inheritance. Familial Mediterranean fever (FMF), tumor necrosis factor-associated periodic syndrome, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, and Blau syndrome are the most frequently identified monogenic AIDs. On the other hand, Behçet’s disease, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, Schnitzler’s disease, and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome are all recognized multifactorial AIDs encountered in the rheumatologic practice.

A few data are currently available on the role of microbiome in AIDs. However, the interaction between innate immunity and microbial agents is well known, and great interest has been recently directed to the role of microbiome in the development of “sterile” inflammation. In particular, the disruption of intestinal milieu and the impairment of gut homeostasis have proved to affect FMF and inflammasome-mediated osteomyelitis. Particularly, the total number of gut bacteria, intestinal bacterial diversity, and the shift toward specific microbes have been related to the occurrence of inflammatory bouts in FMF patients. Accordingly, the curative role of tonsillectomy in patients with PFAPA syndrome and the intriguing findings on the role of diet-induced microbial changes in gut’s patients further support the role of microbiome in the hyperactivation of innate immunity in AIDs.


FMF CAPS CRMO Hereditary periodic fevers Innate immunity Interleukin (IL)-1 Multifactorial autoinflammatory diseases MKD, PFAPA TRAPS 

List of Abbreviations


Amyloid A


Autosomal dominant


Autoinflammatory diseases


Autosomal recessive


Cryopyrin-associated periodic syndrome


Chronic infantile neurological cutaneous articular syndrome


Chronic recurrent multifocal osteomyelitis


Damage-associated molecular patterns


Familial cold autoinflammatory syndrome


Familial Mediterranean fever




Mediterranean fever


Mevalonate kinase deficiency


Mevalonate kinase


Muckle-Wells syndrome


NOD-like receptor-related protein 3


Nucleotide-binding and oligomerization domain


Nucleotide-binding and oligomerization domain-containing protein 2


Neonatal-onset multisystem inflammatory disease


Pathogen-associated molecular patterns


Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis


Pattern recognition receptors


Synovitis, acne, pustulosis, hyperostosis, and osteitis


Systemic juvenile idiopathic arthritis


Toll-like receptors


Tumor necrosis factor


Tumor necrosis factor receptor superfamily member 1A


Tumor necrosis factor receptor-associated periodic fever syndrome


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Donato Rigante
    • 1
  • Antonio Vitale
    • 2
  • Luca Cantarini
    • 2
  1. 1.Institute of Pediatrics, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli”RomeItaly
  2. 2.Research Center of Systemic Autoinflammatory Diseases, Behçet’s Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences Surgery and NeurosciencesUniversity of SienaSienaItaly

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