Skip to main content

Advertisement

SpringerLink
Log in

The labyrinth of autoinflammatory disorders: a snapshot on the activity of a third-level center in Italy

  • Review Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Autoinflammatory disorders (AIDs) are a novel class of diseases elicited by mutations in genes regulating the homeostasis of innate immune complexes, named inflammasomes, which lead to uncontrolled oversecretion of the proinflammatory cytokine interleukin-1β. Protean inflammatory symptoms are variably associated with periodic fever, depicting multiple specific conditions. Childhood is usually the lifetime in which most hereditary AIDs start, though still a relevant number of patients may experience a delayed disease onset and receive a definite diagnosis during adulthood. As a major referral laboratory for patients with recurrent fevers, we have tested samples from 787 patients in the period September 2007–March 2014, with a total of 1,328 AID-related genes evaluated and a gene/patient ratio of 1.69. In this report, we describe our experience in the clinical approach to AIDs, highlight the most striking differences between child and adult-onset AIDs, and shed an eye-opening insight into their diagnostic process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Rigante D, Frediani B, Galeazzi M, Cantarini L (2013) From the Mediterranean to the sea of Japan: the transcontinental odyssey of autoinflammatory diseases. Biomed Res Int 2013:485103

    PubMed Central  PubMed  Google Scholar 

  2. Joost PH, van der Meer JW (2006) The inflammasome: a linebacker of innate defense. N Engl J Med 355:730–732

    Google Scholar 

  3. Cantarini L, Rigante D, Brizi MG, Lucherini OM, Sebastiani GD, Vitale A, Gianneramo V, Galeazzi M (2012) Clinical and biochemical landmarks in systemic autoinflammatory diseases. Ann Med 44:664–673

    PubMed  Google Scholar 

  4. Dinarello CA (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:3720–3732

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Rigante D (2012) The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmun Rev 11:348–356

    PubMed  Google Scholar 

  6. Lamkanfi M, Dixit VM (2009) Inflammasomes: guardians of cytosolic sanctity. Immunol Rev 227:95–105

    CAS  PubMed  Google Scholar 

  7. Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, Lesage S, Waterham H, Wise C, Sarrauste de Menthiere C, Touitou I (2008) The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat 29:803–808

    PubMed  Google Scholar 

  8. French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17:25–31

    Google Scholar 

  9. Berger R, Smit GP, Schierbeek H, Bijsterveld K, le Coultre R (1985) Mevalonic aciduria: an inborn error of cholesterol biosynthesis? Clin Chim Acta 152:219–222

    CAS  PubMed  Google Scholar 

  10. Houten SM, Wanders RJ, Waterham HR (2000) Biochemical and genetic aspects of mevalonate kinase and its deficiency. Biochim Biophys Acta 1529:19–32

    CAS  PubMed  Google Scholar 

  11. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O'Shea JJ, Kastner DL et al (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–144

    CAS  PubMed  Google Scholar 

  12. Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354

    CAS  PubMed  Google Scholar 

  13. Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A 103:9982–9987

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint BG (2002) Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 71:198–203

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J (2004) NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20:319–325

    CAS  PubMed  Google Scholar 

  16. Jéru I, Duquesnoy P, Fernandes-Alnemri T, Cochet E, Yu JW, Lackmy-Port-Lis M, Grimprel E, Landman-Parker J, Hentgen V, Marlin S, McElreavey K, Sarkisian T, Grateau G, Alnemri ES, Amselem S (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci U S A 105:1614–1619

    PubMed Central  PubMed  Google Scholar 

  17. Blau EB (1985) Familial granulomatous arthritis, iritis, and rash. J Pediatr 107:689–693

    CAS  PubMed  Google Scholar 

  18. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Häfner R, Chamaillard M, Zouali H, Thomas G, Hugot JP (2001) CARD15 mutations in Blau syndrome. Nat Genet 29:19–20

    CAS  PubMed  Google Scholar 

  19. Masters SL, Simon A, Aksentijevich I, Kastner DL (2009) Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 27:621–668

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Obici L, Merlini G (2012) Amyloidosis in autoinflammatory syndromes. Autoimmun Rev 12:14–17

    CAS  PubMed  Google Scholar 

  21. Ben-Chetrit E, Touitou I (2009) Familial mediterranean Fever in the world. Arthritis Rheum 61:1447–1453

    CAS  PubMed  Google Scholar 

  22. Lidar M, Yaqubov M, Zaks N, Ben-Horin S, Langevitz P, Livneh A (2006) The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol 33:1089–1092

    PubMed  Google Scholar 

  23. Lidar M, Livneh A (2007) Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med 65:318–324

    CAS  PubMed  Google Scholar 

  24. Radakovic S, Holzer G, Tanew A (2013) Erysipelas-like erythema as a cutaneous sign of familial Mediterranean fever: a case report and review of the histopathologic findings. J Am Acad Dermatol 68:e61–e63

    PubMed  Google Scholar 

  25. Ozen S, Demirkaya E, Amaryan G, Koné-Paut I, Polat A, Woo P, Uziel Y, Modesto C, Finetti M, Quartier P, Papadopoulou-Alataki E, Al-Mayouf SM, Fabio G, Gallizzi R, Cantarini L, Frenkel J, Nielsen S, Hofer M, Insalaco A, Acikel C, Ozdogan H, Martini A, Ruperto N, Gattorno M, Paediatric Rheumatology International Trials Organisation; Eurofever Project (2014) Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis 73:662–667

    PubMed  Google Scholar 

  26. Senel K, Melikoglu MA, Baykal T, Melikoglu M, Erdal A, Ugur M (2010) Protracted febrile myalgia syndrome in familial Mediterranean fever. Mod Rheumatol 20:410–412

    PubMed  Google Scholar 

  27. Ben-Chetrit E, Levy M (1998) Familial Mediterranean fever. Lancet 351:659–664

    CAS  PubMed  Google Scholar 

  28. Ben-Chetrit E, Bergmann S, Sood R (2006) Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford) 45:274–282

    CAS  Google Scholar 

  29. Touitou I, Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D, Yalçinkaya F, Ozen S, Majeed H, Ozdogan H, Kastner D, Booth D, Ben-Chetrit E, Pugnère D, Michelon C, Séguret F, Gershoni-Baruch R, International Study Group for Phenotype-Genotype Correlation in Familial Mediterranean Fever (2007) Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum 56:1706–1712

    PubMed  Google Scholar 

  30. Cantarini L, Volpi N, Galeazzi M, Giani T, Fanti F, Lucherini OM, Aglianò M, Alessandrini C, Giannini F, Magi S, Greco G, Baldari CT, Cimaz R (2010) Colchicine myopathy and neuromyopathy: two cases with different characteristics. J Clin Rheumatol 16:229–232

    PubMed  Google Scholar 

  31. Cantarini L, Volpi N, Lucherini OM, Giannini F, Galeazzi M (2009) A case of amyloid myopathy in a patient with familial Mediterranean fever. Clin Exp Rheumatol 27:S106–S107

    CAS  PubMed  Google Scholar 

  32. Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W (2001) Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford) 40:579–584

    CAS  Google Scholar 

  33. Steichen O, van der Hilst J, Simon A, Cuisset L, Grateau G (2009) A clinical criterion to exclude the hyperimmunoglobulin D syndrome (mild mevalonate kinase deficiency) in patients with recurrent fever. J Rheumatol 36:1677–1681

    PubMed  Google Scholar 

  34. Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Kimpen JL, Duran R, Poll-The BT, Kuis W (2000) Mevalonate kinase deficiency and Dutch type periodic fever. Clin Exp Rheumatol 18:525–532

    CAS  PubMed  Google Scholar 

  35. Stabile A, Compagnone A, Napodano S, Raffaele CG, Patti M, Rigante D (2013) Mevalonate kinase genotype in children with recurrent fevers and high serum IgD level. Rheumatol Int 33:3039–3042

    CAS  PubMed  Google Scholar 

  36. Cantarini L, Vitale A, Magnotti F, Lucherini OM, Caso F, Frediani B, Galeazzi M, Rigante D (2013) Weekly oral alendronate in mevalonate kinase deficiency. Orphanet J Rare Dis 8:196

    PubMed Central  PubMed  Google Scholar 

  37. Aksentijevich I, Galon J, Soares M, Mansfield E, Hull K, Oh HH, Goldbach-Mansky R, Dean J, Athreya B, Reginato AJ, Henrickson M, Pons-Estel B, O'Shea JJ, Kastner DL (2001) The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype–phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet 69:301–314

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Rebelo SL, Bainbridge SE, Amel-Kashipaz MR, Radford PM, Powell RJ, Todd I, Tighe PJ (2006) Modeling of tumor necrosis factor receptor superfamily 1A mutants associated with tumor necrosis factor receptor-associated periodic syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum 54:2674–2687

    CAS  PubMed  Google Scholar 

  39. Kimberley FC, Lobito AA, Siegel RM, Screaton GR (2007) Falling into TRAPS-receptor misfolding in the TNF receptor 1-associated periodic fever syndrome. Arthritis Res Ther 9:217

    PubMed Central  PubMed  Google Scholar 

  40. Dodé C, André M, Bienvenu T, Hausfater P, Pêcheux C, Bienvenu J, Lecron JC, Reinert P, Cattan D, Piette JC, Szajnert MF, Delpech M, Grateau G, French Hereditary Recurrent Inflammatory Disorder Study Group (2002) The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 46:2181–2188

    PubMed  Google Scholar 

  41. Cantarini L, Rigante D, Merlini G, Vitale A, Caso F, Lucherini OM, Sfriso P, Frediani B, Punzi L, Galeazzi M, Cimaz R, Obici L (2013) The expanding spectrum of low-penetrance TNFRSF1A gene variants in adults presenting with recurrent inflammatory attacks: Clinical manifestations and long-term follow-up. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2013.12.002

    PubMed  Google Scholar 

  42. Cantarini L, Imazio M, Brucato A, Lucherini OM, Galeazzi M (2010) Innate versus acquired immune response in the pathogenesis of recurrent idiopathic pericarditis. Autoimmun Rev 9:436–440

    PubMed  Google Scholar 

  43. Cantarini L, Lucherini OM, Baldari CT, Laghi Pasini F, Galeazzi M (2010) Familial clustering of recurrent pericarditis may disclose tumour necrosis factor receptor-associated periodic syndrome. Clin Exp Rheumatol 28:405–407

    PubMed  Google Scholar 

  44. Cantarini L, Lucherini OM, Cimaz R, Baldari CT, Bellisai F, Rossi Paccani S, Laghi Pasini F, Capecchi PL, Sebastiani GD, Galeazzi M (2009) Idiopathic recurrent pericarditis refractory to colchicine treatment can reveal tumor necrosis factor receptor-associated periodic syndrome. Int J Immunopathol Pharmacol 22:1051–1058

    CAS  PubMed  Google Scholar 

  45. Cantarini L, Lucherini OM, Cimaz R, Baldari CT, Laghi Pasini F, Galeazzi M (2010) Sacroileitis and pericarditis: atypical presentation of tumor necrosis factor receptor-associated periodic syndrome and response to etanercept therapy. Clin Exp Rheumatol 28:290–291

    CAS  PubMed  Google Scholar 

  46. Cantarini L, Lucherini OM, Cimaz R, Galeazzi M (2010) Recurrent pericarditis caused by a rare mutation in the TNFRSF1A gene and with excellent response to anakinra treatment. Clin Exp Rheumatol 28:802

    CAS  PubMed  Google Scholar 

  47. Cantarini L, Lucherini OM, Brucato A, Barone L, Cumetti D, Iacoponi F, Rigante D, Brambilla G, Penco S, Brizi MG, Patrosso MC, Valesini G, Frediani B, Galeazzi M, Cimaz R, Paolazzi G, Vitale A, Imazio M (2012) Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study. Clin Res Cardiol 101:525–531

    CAS  PubMed  Google Scholar 

  48. Hull KM, Drewe E, Aksentijevich I, Singh HK, Wong K, McDermott EM, Dean J, Powell RJ, Kastner DL (2002) The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 81:349–368

    CAS  Google Scholar 

  49. Simon A, Park H, Maddipati R, Lobito AA, Bulua AC, Jackson AJ, Chae JJ, Ettinger R, de Koning HD, Cruz AC, Kastner DL, Komarow H, Siegel RM (2010) Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome. Proc Natl Acad Sci U S A 107:9801–9806

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM (2011) Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 208:519–533

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Dickie LJ, Aziz AM, Savic S, Lucherini OM, Cantarini L, Geiler J, Wong CH, Coughlan R, Lane T, Lachmann HJ, Hawkins PN, Robinson PA, Emery P, McGonagle D, McDermott MF (2012) Involvement of X-box binding protein 1 and reactive oxygen species pathways in the pathogenesis of tumour necrosis factor receptor-associated periodic syndrome. Ann Rheum Dis 71:2035–2043

    CAS  PubMed  Google Scholar 

  52. Hoffman HM, Wanderer AA, Bride DH (2001) Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 108:615–620

    CAS  PubMed  Google Scholar 

  53. Muckle TJ, Wells M (1962) Urticaria, deafness and amyloidosis: a new heredo-familial syndrome. Q J Med 31:235–248

    CAS  PubMed  Google Scholar 

  54. Prieur AM (2001) A recently recognised chronic inflammatory disease of early onset characterised by the triad of rash, central nervous system involvement and arthropathy. Clin Exp Rheumatol 19:103–106

    CAS  PubMed  Google Scholar 

  55. Cantarini L, Lucherini OM, Frediani B, Brizi MG, Bartolomei B, Cimaz R, Galeazzi M, Rigante D (2011) Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 24:827–836

    CAS  PubMed  Google Scholar 

  56. Rigante D, Ansuini V, Caldarelli M, Bertoni B, La Torraca I, Stabile A (2006) Hydrocephalus in CINCA syndrome treated with anakinra. Childs Nerv Syst 22:334–337

    CAS  PubMed  Google Scholar 

  57. Kitley JL, Lachmann HJ, Pinto A, Ginsberg L (2010) Neurologic manifestations of the cryopyrin-associated periodic syndrome. Neurology 74:1267–1270

    CAS  PubMed  Google Scholar 

  58. Lepore L, Paloni G, Caorsi R, Alessio M, Rigante D, Ruperto N, Cattalini M, Tommasini A, Zulian F, Ventura A, Martini A, Gattorno M (2010) Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with anakinra. J Pediatr 157:310–315

    PubMed  Google Scholar 

  59. Ebrahimi-Fakhari D, Wahlster L, Mackensen F, Blank N (2010) Clinical manifestations and longterm followup of a patient with CINCA/NOMID syndrome. J Rheumatol 37:2196–2197

    PubMed  Google Scholar 

  60. Jéru I, Le Borgne G, Cochet E, Hayrapetyan H, Duquesnoy P, Grateau G, Morali A, Sarkisian T, Amselem S (2011) Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis Rheum 63:1459–1464

    PubMed  Google Scholar 

  61. Jéru I, Hentgen V, Normand S, Duquesnoy P, Cochet E, Delwail A, Grateau G, Marlin S, Amselem S, Lecron JC (2011) Role of interleukin-1β in NLRP12-associated autoinflammatory disorders and resistance to anti-interleukin-1 therapy. Arthritis Rheum 63:2142–2148

    PubMed  Google Scholar 

  62. Rose CD, Martin TM, Wouters CH (2011) Blau syndrome revisited. Curr Opin Rheumatol 23:411–418

    CAS  PubMed  Google Scholar 

  63. Sfriso P, Caso F, Tognon S, Galozzi P, Gava A, Punzi L (2012) Blau syndrome, clinical and genetic aspects. Autoimmun Rev 12:44–51

    CAS  PubMed  Google Scholar 

  64. Ter Haar N, Lachmann H, Uzen S, Woo P, Uziel Y, Modesto C, Koné-Paut I, Cantarini L, Insalaco A, Neven B, Hofer M, Rigante D, Al-Mayouf S, Touitou I, Gallizzi R, Papadopoulou-Alataki E, Martino S, Kuemmerle-Deschner J, Obici L, Iagaru N, Simon A, Nielsen S, Martini A, Ruperto N, Gattorno M, Frenkel J, Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever/Eurotraps Projects (2013) Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis 72:678–685

    PubMed  Google Scholar 

  65. Vitale A, Rigante D, Lucherini OM, Caso F, Muscari I, Magnotti F, Brizi MG, Guerrini S, Patti M, Punzi L, Galeazzi M, Cantarini L (2013) Biological treatments: new weapons in the management of monogenic autoinflammatory disorders. Mediat Inflamm 2013:939847

    Google Scholar 

  66. Seyahi E, Ozdogan H, Celik S, Ugurlu S, Yazici H (2006) Treatment options in colchicine resistant familial Mediterranean fever patients: thalidomide and etanercept as adjunctive agents. Clin Exp Rheumatol 24:S99–S103

    CAS  PubMed  Google Scholar 

  67. Rigante D, La Torraca I, Avallone L, Pugliese AL, Gaspari S, Stabile A (2006) The pharmacologic basis of treatment with colchicine in children with familial Mediterranean fever. Eur Rev Med Pharmacol Sci 10:173–178

    CAS  PubMed  Google Scholar 

  68. Savic S, Dickie LJ, Wittmann M, McDermott MF (2012) Autoinflammatory syndromes and cellular responses to stress: pathophysiology, diagnosis and new treatment perspectives. Best Pract Res Clin Rheumatol 26:505–533

    CAS  PubMed  Google Scholar 

  69. Cantarini L, Lucherini OM, Iacoponi F, Cimaz R, Simonini G, Rigante D, Laghi Pasini F, Baldari CT, Capecchi PL, Brizi MG, Galeazzi M (2010) Development and preliminary validation of a diagnostic score for identifying patients affected with adult-onset autoinflammatory disorders. Int J Immunopathol Pharmacol 23:1133–1141

    CAS  PubMed  Google Scholar 

  70. Cantarini L, Iacoponi F, Lucherini OM, Obici L, Brizi MG, Cimaz R, Rigante D, Benucci M, Sebastiani GD, Brucato A, Sabadini L, Simonini G, Giani T, Laghi Pasini F, Baldari CT, Bellisai F, Valentini G, Bombardieri S, Paolazzi G, Galeazzi M (2011) Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. Int J Immunopathol Pharmacol 24:695–702

    PubMed  Google Scholar 

  71. Muscari I, Iacoponi F, Cantarini L, Lucherini OM, Simonini G, Brizi MG, Vitale A, Frediani B, Cimaz R, Galeazzi M (2012) The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders: our experience and review of the literature. Autoimmun Rev 12:10–13

    PubMed  Google Scholar 

  72. Cantarini L, Vitale A, Lucherini OM, Muscari I, Magnotti F, Brizi G, Frediani B, Sebastiani GD, Galeazzi M, Rigante D (2013) Childhood versus adulthood-onset autoinflammatory disorders: myths and truths intertwined. Reumatismo 65:55–62

    CAS  PubMed  Google Scholar 

  73. Cantarini L, Rigante D, Lucherini OM, Cimaz R, Laghi Pasini F, Baldari CT, Benucci M, Simonini G, Di Sabatino V, Brizi MG, Galeazzi M (2010) Role of etanercept in the treatment of tumor necrosis factor receptor-associated periodic syndrome: personal experience and review of the literature. Int J Immunopathol Pharmacol 23:701–707

    CAS  PubMed  Google Scholar 

  74. Trost S, Rosé CD (2005) Myocarditis and sacroiliitis: 2 previously unrecognized manifestations of tumor necrosis factor receptor associated periodic syndrome. J Rheumatol 32:175–177

    PubMed  Google Scholar 

  75. Sayarlioglu M, Cefle A, Inanc M, Kamali S, Dalkilic E, Gul A, Ocal L, Aral O, Konice M (2005) Characteristics of patients with adult-onset familial Mediterranean fever in Turkey: analysis of 401 cases. Int J Clin Pract 59:202–205

    CAS  PubMed  Google Scholar 

  76. Okutur K, Seber S, Oztekin E, Bes C, Borlu F (2008) Recurrent pericarditis as the initial manifestation of Familial Mediterranean fever. Med Sci Monit 14:CS139–CS141

    PubMed  Google Scholar 

  77. Tutar HE, Imamoglu A, Kendirli T, Akar E, Atalay S, Akar N (2001) Isolated recurrent pericarditis in a patient with familial Mediterranean fever. Eur J Pediatr 160:264–265

    CAS  PubMed  Google Scholar 

  78. Federici L, Rittore-Domingo C, Koné-Paut I, Jorgensen C, Rodière M, Le Quellec A, Touitou I (2006) A decision tree for genetic diagnosis of hereditary periodic fever in unselected patients. Ann Rheum Dis 65:1427–1432

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Gattorno M, Sormani MP, D'Osualdo A, Pelagatti MA, Caroli F, Federici S, Cecconi M, Solari N, Meini A, Zulian F, Obici L, Breda L, Martino S, Tommasini A, Bossi G, Govers A, Touitou I, Woo P, Frenkel J, Koné-Paut I, Baldi M, Ceccherini I, Martini A (2008) A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children. Arthritis Rheum 58:1823–1832

    CAS  PubMed  Google Scholar 

  80. Marshall GS, Edwards KM, Butler J, Lawton AR (1987) Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 110:43–46

    CAS  PubMed  Google Scholar 

  81. Marshall GS, Edwards KM, Lawton AR (1989) PFAPA syndrome. Pediatr Infect Dis J 8:658–659

    CAS  PubMed  Google Scholar 

  82. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM (1999) Periodic fever syndrome in children. J Pediatr 135:15–21

    CAS  PubMed  Google Scholar 

  83. Cavuoto M, Bonagura VR (2008) Adult-onset periodic fever, aphthous stomatitis, pharyngitis, and adenitis. Ann Allergy Asthma Immunol 100:170

    PubMed  Google Scholar 

  84. Padeh S, Stoffman N, Berkun Y (2008) Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults. Isr Med Assoc J 10:358–360

    PubMed  Google Scholar 

  85. Cazzato M, Neri R, Possemato N, Puccini R, Bombardieri S (2013) A case of adult periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome associated with endocapillary proliferative glomerulonephritis. Clin Rheumatol 32:S33–S36

    PubMed  Google Scholar 

  86. Colotto M, Maranghi M, Durante C, Rossetti M, Renzi A, Anatra MG (2011) PFAPA syndrome in a young adult with a history of tonsillectomy. Intern Med 50:223–225

    PubMed  Google Scholar 

  87. Cantarini L, Vitale A, Galeazzi M, Frediani B (2012) A case of resistant adult-onset periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome responsive to anakinra. Clin Exp Rheumatol 30:593

    PubMed  Google Scholar 

  88. Cantarini L, Vitale A, Bartolomei B, Galeazzi M, Rigante D (2012) Diagnosis of PFAPA syndrome applied to a cohort of 17 adults with unexplained recurrent fevers. Clin Exp Rheumatol 30:269–271

    PubMed  Google Scholar 

  89. Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43:227–253

    CAS  PubMed  Google Scholar 

  90. Cantarini L, Capecchi PL, Lucherini OM, Laghi Pasini F, Galeazzi M (2010) Familial Mediterranean fever diagnosed in an elderly patient. Clin Exp Rheumatol 28:S91

    PubMed  Google Scholar 

  91. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879–1885

    CAS  PubMed  Google Scholar 

  92. Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castañer JL, Whiteford ML, Janssens-Korpola PL, Manna R, Powell RJ, Woo P, Solis P, Minden K, Frenkel J, Yagüe J, Mirakian RM, Hitman GA, McDermott MF (2003) Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum 48:2632–2644

    CAS  PubMed  Google Scholar 

  93. Lucherini OM, Obici L, Ferracin M, Fulci V, McDermott MF, Merlini G, Muscari I, Magnotti F, Dickie LJ, Galeazzi M, Negrini M, Baldari CT, Cimaz R, Cantarini L (2013) First report of circulating microRNAs in tumour necrosis factor receptor-associated periodic syndrome (TRAPS). PLoS ONE 8:e73443

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Vitale A, Lucherini OM, Galeazzi M, Frediani B, Cantarini L (2012) Long term clinical course of patients carrying the Q703K mutation in the NLRP3 gene: a case series. Clin Exp Rheumatol 30:943–946

    PubMed  Google Scholar 

  95. Goldbach-Mansky R (2012) Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol 167:391–404

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Borghini S, Tassi S, Chiesa S, Caroli F, Carta S, Caorsi R, Fiore M, Delfino L, Lasigliè D, Ferraris C, Traggiai E, Di Duca M, Santamaria G, D'Osualdo A, Tosca M, Martini A, Ceccherini I, Rubartelli A, Gattorno M (2011) Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum 63:830–839

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Vitale A, Rigante D, Maggio MC, Emmi G, Romano M, Silvestri E, Lucherini OM, Emmi L, Gerloni V, Cantarini L (2013) Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series. Clin Exp Rheumatol 31:155–156

    PubMed  Google Scholar 

  98. Martin J, Kodjikian L, Duquesne A, Le Scanff J, Sève P (2009) Blau syndrome. QJM 104:997–998

    Google Scholar 

  99. Aksentijevich I, D'Putnam C, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL (2007) The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 56:1273–1285

    CAS  PubMed  Google Scholar 

  100. Aróstegui JI, Aldea A, Modesto C, Rua MJ, Argüelles F, González-Enseñat MA, Ramos E, Rius J, Plaza S, Vives J, Yagüe J (2004) Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene. Arthritis Rheum 50:4045–4050

    PubMed  Google Scholar 

  101. Ravet N, Rouaghe S, Dodé C, Bienvenu J, Stirnemann J, Lévy P, Delpech M, Grateau G (2006) Clinical significance of P46L and R92Q substitutions in the tumor necrosis factor superfamily 1A gene. Ann Rheum Dis 65:1158–1162

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Tchernitchko D, Chiminqgi M, Galactéros F, Préhu C, Segbena Y, Coulibaly H, Rebaya N, Loric S (2005) Unexpected high frequency of P46L TNFRSF1A allele in sub-Saharan West African populations. Eur J Hum Genet 13:513–515

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

  1. Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy

    Luca Cantarini, Antonio Vitale, Orso Maria Lucherini, Caterina De Clemente, Francesco Caso, Flora Magnotti, Bruno Frediani & Mauro Galeazzi

  2. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy

    Francesco Caso

  3. Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

    Luisa Costa

  4. Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    Giacomo Emmi & Elena Silvestri

  5. Maternal and Child Health Department, University of Palermo, Palermo, Italy

    Maria Cristina Maggio

  6. Univeritary Department Pro.Sa.M.I. “G. D’Alessandro”, University of Palermo, Palermo, Italy

    Eugenia Prinzi

  7. Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Bari, Italy

    Giuseppe Lopalco

  8. Department of Pediatrics, Rheumatology Unit, Anna Meyer Children’s Hospital and University of Florence, Florence, Italy

    Rolando Cimaz

  9. Institute of Pediatrics, Policlinico A. Gemelli, Università Cattolica Sacro Cuore, Rome, Italy

    Donato Rigante

Authors
  1. Luca Cantarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Vitale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Orso Maria Lucherini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Caterina De Clemente
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Caso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luisa Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giacomo Emmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elena Silvestri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Flora Magnotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Cristina Maggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eugenia Prinzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giuseppe Lopalco
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Bruno Frediani
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Rolando Cimaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mauro Galeazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Donato Rigante
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luca Cantarini.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cantarini, L., Vitale, A., Lucherini, O.M. et al. The labyrinth of autoinflammatory disorders: a snapshot on the activity of a third-level center in Italy. Clin Rheumatol 34, 17–28 (2015). https://doi.org/10.1007/s10067-014-2721-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-014-2721-0

Keywords

Search

Navigation