Periodic Syndromes

  • John G. Ryan
  • Daniel L. Kastner


  • Hereditary periodic fever syndromes are autoinflammatory diseases characterized by episodes of fever with serosal, synovial, and/or skin inflammation.

  • Familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) are inherited in an autosomal recessive manner and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID) are dominantly inherited.

  • ■ Colchicine and biologic therapies such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) receptor agonists are successful in the treatment of some of these inherited diseases.


Familial Mediterranean Fever Familial Mediterranean Fever Patient MEFV Mutation Periodic Syndrome Periodic Fever Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    McDermott MF, Aksentijevich I, Galon J, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999;97:133–144.PubMedCrossRefGoogle Scholar
  2. 2.
    Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999;135: 15–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Aksentijevich I, Torosyan Y, Samuels J, et al. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet 1999;64:949–962.PubMedCrossRefGoogle Scholar
  4. 4.
    Kastner DL, Aksentijevich I. Intermittent and periodic arthritis syndromes. In: Koopman WJ, Moreland LW, eds. Arthritis and allied conditions. 15th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:1411–1461.Google Scholar
  5. 5.
    International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997;90:797–807.CrossRefGoogle Scholar
  6. 6.
    French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25–31.CrossRefGoogle Scholar
  7. 7.
    Chae JJ, Komarow HD, Cheng J, et al. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol Cell 2003;11:591–604.PubMedCrossRefGoogle Scholar
  8. 8.
    Cazeneuve C, Sarkisian T, Pecheux C, et al. MEFV-gene analysis in Armenian patients with familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications. Am J Hum Genet 1999;65:88–97.PubMedCrossRefGoogle Scholar
  9. 9.
    Drenth JP, Haagsma CJ, van der Meer JW. Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Baltimore) 1994;73: 133–144.Google Scholar
  10. 10.
    Drenth JP, Cuisset L, Grateau G, et al. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 1999;22:178–181.PubMedCrossRefGoogle Scholar
  11. 11.
    Houten SM, Kuis W, Duran M, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet 1999; 22:175–177.PubMedCrossRefGoogle Scholar
  12. 12.
    Simon A, Drewe E, van der Meer JW, et al. Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Clin Pharmacol Ther 2004;75:476–483.PubMedCrossRefGoogle Scholar
  13. 13.
    McDermott EM, Smillie DM, Powell RJ. Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family. Mayo Clin Proc 1997;72:806–817.PubMedCrossRefGoogle Scholar
  14. 14.
    Hull KM, Drewe E, Aksentijevich I, et al. The TNF receptor-associated periodic syndrome: emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 2002;81:349–368.CrossRefGoogle Scholar
  15. 15.
    Wanderer AA, Hoffman HM. The spectrum of acquired and familial cold-induced urticaria/urticaria-like syn dromes. Immunol Allergy Clin North Am 2004;24:259–286.PubMedCrossRefGoogle Scholar
  16. 16.
    Muckle TJ, Wells M. Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. Q J Med 1962;31:235–248.PubMedGoogle Scholar
  17. 17.
    Prieur AM, Griscelli C, Lampert F, et al. A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J Rheumatol Suppl 1987;66:57–68.PubMedCrossRefGoogle Scholar
  18. 18.
    Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 2001;29:301–305.PubMedCrossRefGoogle Scholar
  19. 19.
    Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002;46:3340–3348.PubMedCrossRefGoogle Scholar
  20. 20.
    Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1b inhibition. N Engl J Med 2006;355: 581–592.PubMedCrossRefGoogle Scholar
  21. 21.
    Maksymowych WP, Suarez-Almazor ME, Buenviaje H, et al. HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis. J Rheumatol 2002;29:2319–2326.PubMedGoogle Scholar
  22. 22.
    Guerne PA, Weisman MH. Palindromic rheumatism: part of or apart from the spectrum of rheumatoid arthritis. Am J Med 1992;93:451–460.PubMedCrossRefGoogle Scholar
  23. 23.
    Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, Ramos-Remus C, Russell AS, Suarez-Almazor ME. Prognostic factors for the development of rheumatoid arthritis and other connective tissue diseases in patients with palindromic rheumatism. J Rheumatol 1999;26:540–545.PubMedGoogle Scholar
  24. 24.
    Ghormley RK, Weiner AD. Periodic benign synovitis; idiopathic intermittent hydrarthrosis. J Bone Joint Surg Am 1956;38A:1039–1055.Google Scholar
  25. 25.
    Brown JP, Rola-Pleszczynski M, Menard HA. Eosinophilic synovitis: clinical observations on a newly recognized subset of patients with dermatographism. Arthritis Rheum 1986;29:1147–1151.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • John G. Ryan
    • 1
    • 2
  • Daniel L. Kastner
    • 3
  1. 1.Genetics and Genomics BranchBethesdaUSA
  2. 2.Genetics and Genomics BranchNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthBethesdaUSA
  3. 3.National Institute of Arthritis and Musculoskeletal and Skin DiseasesBethesdaUSA

Personalised recommendations