MRI  Vol.3 No.1 , February 2014
Autoinflammatory diseases in childhood

Autoinflammatory diseases are defined as recurrent attacks of systemic inflammation that are often unprovoked (or triggered by a minor event) related to a lack of adequate regulation of the innate immune system. Within the past decade, the list of autoinflammatory diseases has included cryopyrin-associated periodic syndromes, familial Mediterranean fever, mevalonate kinase deficiency, tumor necrosis factor receptor-associated periodic syndrome, hereditary pyogenic disorders, pediatric granulomatous autoinflammatory diseases, idiopathic febrile syndromes (systemic-onset juvenile idiopathic arthritis, PFAPA syndrome), complement dysregulation syndromes and Behcet’s disease. The hereditary autoinflammatory diseases are a group of Mendelian disorders characterized by seemingly unprovoked fever and localized inflammation. Autoinflammatory diseases can activate NOD-like receptors and inflammasome products including especially interleukin 1β. In this review, it focuses on how recent advances have impacted hereditary autoinflammatory diseases.

Cite this paper
Sozeri, B. and Kasapcopur, O. (2014) Autoinflammatory diseases in childhood. Modern Research in Inflammation, 3, 7-18. doi: 10.4236/mri.2014.31002.
[1]   Hashkes, P.J. and Toker, O. (2012) Autoinflammatory syndromes. Pediatric Clinics of North America, 59, 447-470.

[2]   Savic, S., Dickie, L.J., Wittmann, M. and McDermott, M.F. (2012) Autoinflammatory syndromes and cellular responses to stress: Pathophysiology, diagnosis and new treatment perspectives. Best Practice & Research Clinical Rheumatology, 26, 505-533. 07.009

[3]   Masters, S.L., Simon, A., Aksentijevich, I. and Kastner, D.L. (2009) Horror autoinflammaticus: The molecular pathophysiology of autoinflammatory disease. Annual Review of Immunology, 27, 621-668.

[4]   Ben-Chetrit, E. and Levy, M. (1998) Familial Mediterranean fever. Lancet, 351, 659-664.

[5]   Konstantopoulos, K., Kanta, A., Deltas, C., Atamian, V., Mavrogianni, D., Tzioufas, A.G., et al. (2003) Familial Mediterranean fever associated pyrin mutations in Greece. Annals of the Rheumatic Diseases, 62, 479-481.

[6]   La Regina, M., Nucera, G., Diaco, M., Procopio, A., Gasbarrini, G., Notarnicola, C., et al. (2003) Familial Mediterranean fever is no longer a rare disease in Italy. European Journal of Human Genetics, 11, 50-56.

[7]   Tunca, M., Akar, S., Onen, F., Ozdogan, H., Kasapcopur, O., Yalcinkaya, F., et al. (2005) Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore), 84, 1-11.

[8]   Gedalia, A., Adar, A. and Gorodischer, R. (1992) Familial Mediterranean fever in children. The Journal of Rheumatology, 35, 1-9.

[9]   Ben-Chetrit, E. and Ben-Chetrit, A. (2001) Familial Mediterranean fever and menstruation. BJOG, 108, 403-407.

[10]   Rigante, D. (2012) The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmunity Reviews, 11, 348-356.

[11]   Brik, R., Shinawi, M., Kasinetz, L. and Gershoni-Baruch, R. (2001) The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis & Rheumatology, 44, 14161419.<1416::AID-ART 236>3.0.CO;2-6

[12]   Lidar, M., Kedem, R., Mor, A., Levartovsky, D., Langevitz, P. and Livneh, A. (2005) Arthritis as the sole episodic manifestation of familial Mediterranean fever. The Journal of Rheumatology, 32, 859-862.

[13]   Okutur, K., Seber, S., Oztekin, E., Bes, C. and Borlu, F. (2008) Recurrent pericarditis as the initial manifestation of Familial Mediterranean fever. Medical Science Monitor, 14, CS139-CS141.

[14]   Tufan, G. and Demir, S. (2010) Uncommon clinical pattern of FMF: Protracted febrile myalgia syndrome. Rheumatology International, 30, 1089-1090.

[15]   Aksu, K. and Keser, G. (2011) Coexistence of vasculitides with familial Mediterranean fever. Rheumatology International, 31, 1263-1274.

[16]   Livneh, A., Langevitz, P., Zemer, D., Zaks, N., Kees, S., Lidar, T., et al. (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis & Rheumatology, 40, 1879-1885.

[17]   Yalcinkaya, F., Ozen, S., Ozcakar, Z.B., Aktay, N., Cakar, N., Duzova, A., et al. (2009) A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford), 48, 395-398.

[18]   Kondi, A., Hentgen, V., Piram, M., Letierce, A., Guillame-Czitrom, S. and Koné-Paut, I. (2010) Validation of the new pediatric criteria for the diagnosis of familial Mediterranean fever: Data from a mixed population of 100 children from the French reference centre for auto-inflammatory disorders. Rheumatology (Oxford), 49, 2200-2203.

[19]   Ozcakar, Z.B., Yalcinkaya, F., Cakar, N., Acar, B., Bilgic, A.E., Uncu, N., et al. (2011) Application of the new pediatric criteria and Tel Hashomer criteria in heterozygous patients with clinical features of FMF. European Journal of Pediatrics, 170, 1055-1057.

[20]   The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell, 90, 797-807.

[21]   (1997) A candidate gene for familial mediterranean fever. French FMF Consortium. Nature Genetics, 17, 25-31.

[22]   Chae JJ, Aksentijevich I and Kastner DL. (2009) Advances in the understanding of familial mediterranean fever and possibilities for targeted therapy. British Journal of Haematology, 146, 467-478.

[23]   Milhavet, F., Cuisset, L., Hoffman, H.M., Slim, R., ElShanti, H., Aksentijevich, I., et al. (2008) The infevers autoinflammatory mutation online registry: Update with new genes and functions. Human Mutation, 29, 803-880.

[24]   Shinawi, M., Brik, R., Berant, M., et al. (2000) Familial Mediterranean fever: High gene frequency and heterogeneous disease among an Israeli-Arab population. The Journal of Rheumatology, 27, 1492-1495.

[25]   Gershoni-Baruch, R., Shinawi, M., Leah, K., et al. (2001) Familial Mediterranean fever: Prevalence, penetrance and genetic drift. European Journal of Human Genetics, 9, 634-637.

[26]   Touitou, I. (2001) The spectrum of familial Mediterranean fever (FMF) mutations. European Journal of Human Genetics, 9, 473-483.

[27]   Mattit, H., Joma, M., Al-Cheikh, S., et al. (2006) Familial Mediterranean fever in the Syrian population: Gene mutation frequencies, carrier rates and phenotype genotype correlation. European Journal of Medical Genetics, 49, 481-486.

[28]   Brik, R., Shinawi, M., Kepten, I., Berant, M. and Gershoni-Baruch, R. (1999) Familial Mediterranean fever: Clinical and genetic characterization in amixed pediatric population of Jewish and Arab patients. Pediatrics, 103, 70-73.

[29]   Yilmaz, E., Ozen, S., Balci, B., Duzova, A., Topaloglu, R., Besbas, N., et al. (2001) Mutation frequency of Familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. European Journal of Human Genetics, 9, 553-555.

[30]   Majeed, H.A., El-Shanti, H., Al-Khateeb, M.S. and Rabaiha, Z.A. (2002) Genotype/phenotype correlations in Arab patients with familial Mediterranean fever. Seminars in Arthritis and Rheumatism, 31, 371-376.

[31]   Daniels, M., Shohat, T., Brenner-Ullman, A. and Shohat, M. (1995) Familial Mediterranean fever: High gene frequency among the non-Ashkenazic and Ashkenazic Jewish populations in Israel. American Journal of Medical Genetics, 55, 311-314.

[32]   Yuval, Y., Hemo-Zisser, M., Zemer, D., Sohar, E. and Pras, M. (1995) Dominant inheritance in two families with familial Mediterranean fever (FMF). American Journal of Medical Genetics, 57, 455-457.

[33]   Booty, M.G., Chae, J.J., Masters, S.L., Remmers, E.F., Barham, B., Le, J.M., Barron, K.S., Holland, S.M., Kastner, D.L. and Aksentijevich, I. (2009) Familial Mediterranean fever with a single MEFV mutation: Where is the second hit? Arthritis & Rheumatism, 60, 1851-1861. 24569

[34]   Ozen, S. (2009) Changing concepts in familial Mediterranean fever: Is it possible to have an autosomal-recessive disease with only one mutation? Arthritis & Rheumatism, 60, 1575-1577.

[35]   Singh-Grewal, D., Chaitow, J., Aksentijevich, I. and Christodoulou, J. (2007) Coexistent MEFV and CIAS1 mutations manifesting as familial Mediterranean fever plus deafness [letter]. Annals of the Rheumatic Diseases, 66, 1541.

[36]   Fonnesu, C., Cerquaglia, C., Giovinale, M., Curigliano, V., Verrecchia, E., de Socio, G., La Regina, M., Gasbarrini, G. and Manna, R. (2009) Familial Mediterranean fever: A review for clinical management. Joint Bone Spine, 76, 227-233.

[37]   Onen, F. (2006) Familial mediterranean fever. Rheumatology International, 26, 489-496.

[38]   Dinarello, C.A., Wolff, S.M., Goldfinger, S.E., Dale, D.C. and Alling, D.W. (1974) Colchicine therapy for familial mediterranean fever. A double-blind trial. New England Journal of Medicine, 291, 934-937.

[39]   Ozturk, M.A., Kanbay, M., Kasapoglu, B., Onat, A.M., Guz, G., Furst, D.E. and Ben-Chetrit, E. (2011) Therapeutic approach to familial Mediterranean fever: A review update. Clinical and Experimental Rheumatology, 29, S77-S86.

[40]   Cronstein, B.N. and Terkeltaub, R. (2006) The inflammatory process of gout and its treatment. Arthritis Research & Therapy, 8, S3.

[41]   Nuki, G. (2008) Colchicine: A critical appraisal of its mechanism of action and efficacy in crystal-induced inflammation. Current Rheumatology Reports, 10, 218-227. s11926-008-0036-3

[42]   Ben-Chetrit, E., Bergmann, S. and Sood, R. (2006) Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: A possible new outlook through microarray analysis. Rheumatology, 45, 274-282.

[43]   Kallinich, T., Haffner, D., Niehues, T., Huss, K., Lainka, E., Neudorf, U., Schaefer, C., Stojanov, S., Timmann, C., Keitzer, R., Ozdogan, H. and Ozen, S. (2007) Colchicine use in children and adolescents with familial Mediterranean fever: Literature review and consensus statement. Pediatrics, 119, e474-e483.

[44]   Padeh, S., Gerstein, M. and Berkun, Y. (2012) Colchicine is a safe drug in children with familial Mediterranean fever. Journal of Pediatrics, 161, 1142-1146. 05.047

[45]   Cerquaglia, C., Diaco, M., Nucera, G., La Regina, M., Montalto, M. and Manna, R. (2005) Pharmacological and clinical basis of treatment of familial Mediterranean fever (FMF) with colchicine or analogues: An update. Current Drug Target-Inflammation & Allergy, 4, 117-124.

[46]   Meinzer, U., Quartier, P., Alexandra, J.F., Hentgen, V., Retornaz, F. and Koné-Paut, I. (2011) Interleukin-1 targeting drugs in familial Mediterranean fever: A case series and a review of the literature. Seminars in Arthritis and Rheumatism, 41, 265-271. 2010.11.003

[47]   Marek-Yagel, D., Berkun, Y., Padeh, S., Abu, A., Reznik-Wolf, H., Livneh, A., Pras, M. and Pras, E. (2009) Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis and Rheumatism, 60, 1862-1866.

[48]   Frenkel, J., Houten, S.M., Waterham, H.R., Wanders, R.J., Rijkers, G.T., Kimpen, J.L.L., Duran, R., Poll-The, B.T. and Kuis, W. (2000) Mevalonate kinase deficiency and Dutch type periodic fever. Clinical and Experimental Rheumatology, 18, 525-532.

[49]   Drenth, J.P., van Deuren, M., van der Ven-Jongekrijg, J., Schalkwijk, C.G. and van der Meer, J.W. (1995) Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Blood, 85, 3586-3593.

[50]   Mandey, S.H., Kuijk, L.M., Frenkel, J. and Waterham, H.R. (2006) A role for geranylgeranylation in interleukin-1beta secretion. Arthritis and Rheumatism, 54, 3690-3695. 22194

[51]   van der Hilst, J.C., Bodar, E.J., Barron, K.S., Frenkel, J., Drenth, J.P., van der Meer, J.W., Simon, A. and the International HIDS Study Group. (2008) Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine, 87, 301-310.

[52]   Simon, A., Kremer, H.P., Wevers, R.A., Scheffer, H., De Jong, J.G., van der Meer, J.W. and Drenth, J.P. (2004) Mevalonate kinase deficiency: Evidence for a phenotypic continuum. Neurology, 62, 994-997.

[53]   D’Osualdo, A., Picco, P., Caroli, F., Gattorno, M., Giacchino, R., Fortini, P., Corona, F., Tommasini, A., Salvi, G., Specchia, F., Obici, L., Meini, A., Ricci, A., Seri, M., Ravazzolo, R., Martini, A. and Ceccherini, I. (2005) MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever. European Journal of Human Genetics, 13, 314-320.

[54]   Ammouri, W., Cuisset, L., Rouaghe, S., Rolland, M.O., Delpech, M., Grateau, G. and Ravet, N. (2007) Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. Rheumatology, 46, 1597-1600.

[55]   Siewert, R., Ferber, J., Horstmann, R.D., Specker, C., Heering, P.J. and Timmann, C. (2006) Hereditary periodic fever with systemic amyloidosis: Is hyper-IgD syndrome really a benign disease? American Journal of Kidney Diseases, 48, e41-e45.

[56]   Touitou, I., Lesage, S., McDermott, M., Cuisset, L., Hoffman, H., Dode, C., Shoham, N., Aganna, E., Hugot, J.P., Wise, C., Waterham, H., Pugnere, D., Demaille, J. and de Menthiere, C.S. (2004) Infevers: An evolving mutation database for auto-inflammatory syndromes. Human Mutation, 24, 194-198.

[57]   Houten, S.M., Kuis, W., Duran, M., De Koning, T.J., van Royen-Kerkhof, A., Romeijn, G.J., Frenkel, J., Dorland, L., de Barse, M.M.J., Huijbers, W.A.R., Rijkers, G.T., Waterham, H.R., Wanders, R.J.A. and Poll-The, B.T. (1999) Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nature Genetics, 22, 175-177.

[58]   Mandey, S.H., Schneiders, M.S., Koster, J. and Waterham, H.R. (2006) Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency. Human Mutation, 27, 796-802.

[59]   Takada, K., Aksentijevich, I., Mahadevan, V., Dean, J.A., Kelley, R.I. and Kastner, D.L. (2003) Favorable preliminary experience with etanercept in two patients with the hyperimunoglobulinemia D and periodic fever syndrome. Arthritis & Rheumatism, 48, 2645-2651. 11218

[60]   Rigante, D., Ansuini, V., Bertoni, B., Pugliese, A.L., Avallone, L., Federico, G. and Stabile, A. (2006) Treatment with anakinra in the hyperimmunoglobulinemia D/periodic fever syndrome. Rheumatology International, 27, 97-100.

[61]   McDermott, M.F., Aksentijevich, I., Galon, J., McDermott, E.M., Ogunkolade, B.W., Centola, M., 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.

[62]   Nedjai, B., Hitman, G.A., Church, L.D., Minden, K., Whiteford, M.L., McKee, S., Stjernberg, S., Pettersson, T., Ranki, A., Hawkins, P.N., P Arkwright, D., McDermott, M.F. and Turner, M.D. (2011) Differential cytokine secretion results from p65 and c-Rel NF-κB subunit signaling in peripheral bloodmononuclear cells of TNF receptorassociated periodic syndrome patients. Cellular Immunology, 268, 55-59.

[63]   Aganna, E., Hammond, L., Hawkins, P.N., Aldea, A., Mc-Kee, S.A., van Amstel, H.K., et al. (2003) Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis and Rheumatism, 48, 2632-2644.

[64]   D’Osualdo, A., Ferlito, F., Prigione, I., Obici, L., Meini, A., Zulian, F., Pontillo, A., Corona, F., Barcellona, R., Di Duca, M., Santamaria, G., Traverso, F., Picco, P., Baldi, M., Plebani, A., Ravazzolo, R., Ceccherini, I., Martini, A. and Gattorno, M. (2006) Neutrophils from patients with TNFRSF1A mutations display resistance to tumor necrosis factor-induced apoptosis: Pathogenetic and clinical implications. Arthritis and Rheumatism, 54, 998-1008.

[65]   Ravet, N., Rouaghe, S., Dode, C., Bienvenu, J., Stirnemann, J., Levy, P., Delpech, M. and Grateau, G. (2006) Clinical significance of P46L and R92Q substitutions in the tumour necrosis factor superfamily 1A gene. Annals of the Rheumatic Diseases, 65, 1158-1162. 2005.048611

[66]   Federici, S., Caorsi, R. and Gattorno, M. (2012) The autoinflammatory diseases. Swiss Medical Weekly, 142, Article ID: w13602.

[67]   Pelagatti, M.A., Meini, A., Caorsi, R., Cattalini, M., Federici, S., Zulian, F., Calcagno, G., Tommasini, A., Bossi, G., Sormani, M.P., Caroli1, F., Plebani, A., Ceccherini, I., Martini, A. and Gattorno, M. (2011) Long-term clinical profile of children with the low-penetrance R92Q mutation of the TNFRSF1A gene. Arthritis and Rheumatism, 63, 1141-1150.

[68]   Stojanov, S. and McDermott, M.F. (2005) The tumour necrosis factor receptor-associated periodic syndrome: Current concepts. Expert Reviews in Molecular Medicine, 7, 1-18. 1017/S1462399405009749

[69]   Hull, K.M., Drewe, E., Aksentijevich, I., Singh, H.K., Wong, K., McDermott, E.M., Dean, J., Powell, R.J. and Kastner, D.L. (2002) The TNF receptor-associated periodic syndrome (TRAPS): Emerging concepts of an autoinflammatory disorder. Medicine, 81, 349-368. 00005792-200209000-00002

[70]   Drewe, E., McDermott, E.M., Powell, P.T., Isaacs, J.D. and Powell, R.J. (2003) Prospective study of anti-tumour necrosis factor receptor superfamily 1B fusion protein, and case study of anti-tumour necrosis factor receptor superfamily 1A fusion protein, in tumour necrosis factor receptor associated periodic syndrome (TRAPS): Clinical and laboratory findings in a series of seven patients. Rheumatology, 42, 235-239.

[71]   Kallinich, T., Briese, S., Roesler, J., Rudolph, B., Sarioglu, N., Blankenstein, O., Keitzer, R., Querfeld, U. and Haffner, D. (2004) Two familial cases with tumor necrosis factor receptor-associated periodic syndrome caused by a noncysteine mutation (T50M) in the TNFRSF1A gene associated with severe multiorganic amyloidosis. Journal of Rheumatology, 31, 2519-2522.

[72]   Gattorno, M., Pelagatti, M.A., Meini, A., Obici, L., Barcellona, R., Federici, S., Buoncompagni, A., Plebani, A., Merlini, G. and Martini, A. (2008) Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis & Rheumatism, 58, 1516-1520.

[73]   Hoffman, H., Mueller, J., Brodie, D., Wanderer, A.A. and Kolodner, R.D. (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature Genetics, 29, 301-305.

[74]   Feldmann, J., Prieur, A.M., Quartier, P., Berquin, P., Certain, S., Cortis, E., Teillac-Hamel, D., Fischer, A. and de Saint Basile, G. (2002) Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. American Society of Human Genetics, 71, 198-203.

[75]   Aksentijevich, I., Putnam, C.D., Remmers, E.F., Mueller, J.L., Le, J., Kolodner, R.D., Moak, Z., Chuang, M., Austin, F., Goldbach-Mansky, R., Hoffman, H.M. and Kastner, D.L. (2007) The clinical continuum of cryopyrinopathies: Novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis & Rheumatism, 56, 1273-1285.

[76]   Henderson, C. and Goldbach-Mansky, R. (2010) Monogenic autoinflammatory diseases: New insights into clinical aspects and pathogenesis. Current Opinion in Rheumatology, 22, 567-578.

[77]   Hoffman, H.M., Wanderer, A.A. and Broide, D.H. (2001) Familial cold autoinflammatory syndrome: Phenotype and genotype of an autosomal dominant periodic fever. Journal of Allergy and Clinical Immunology, 108, 615-620.

[78]   Maksimovic, L., Stirnemann, J., Caux, F., Ravet, N., Rouaghe, S., Cuisset, L., Letellier, E., Grateau, G., Morin, A.S. and Fain, O. (2008) New CIAS1 mutation and anakinra efficacy in overlapping of Muckle-Wells and familial cold autoinflammatory syndromes. Rheumatology, 47, 309-310.

[79]   Muckle, T.J. and Wells, M. (1962) Urticaria, deafness, and amyloidosis: A new heredo-familial syndrome. Quarterly Journal of Medicine, 31, 235-248.

[80]   Nazzari, G., Desirello, G. and Crovato, F. (1995) Recurrent urticarial skin eruption since infancy. Muckle-Wells syndrome (MWS). Archives of Dermatology, 131, 81-85. archderm.131.1.81

[81]   Leslie, K.S., Lachmann, H.J., Bruning, E., McGrath, J.A., Bybee, A., Gallimore, J.R., Roberts, P.F., Woo, P., Grattan, C.E. and Hawkins, P.N. (2006) Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations. Archives of Dermatology, 142, 1591-1517.

[82]   Prieur, A.M. (2001) A recently recognised chronic inflammatory disease of early onset characterised by the triad of rash, central nervous systeminvolvement and arthropathy. Clinical and Experimental Rheumatology, 19, 103-106.

[83]   Prieur, A.M. and Griscelli, C. (1981) Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation. Journal of Pediatrics, 99, 79-83.

[84]   Prieur, A.M., Griscelli, C., Lampert, F., Truckenbrodt, H., Guggenheim, M.A., Lovell, D.J., Pelkonnen, P., Chevrant-Breton, J. and Ansell, B.M. (1987) A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scandinavian Journal of Rheumatology, 66, 57-68.

[85]   Aksentijevich, I., Nowak, M., Mallah, M., Chae, J.J., Watford, W.T., Hofmann, S.R., et al. (2002) 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 and Rheumatism, 46, 3340-3348.

[86]   Caroli, F., Pontillo, A., D’Osualdo, A., Travan, L., Ceccherini, I., Crovella, S., Alessio, M., Stabile, A., Gattorno, M., Tommasini, A., Martini, A. and Lepore, L. (2007) Clinical and genetic characterization of Italian patients affected by CINCA yndrome. Rheumatology, 46, 473-478. rheumatology/kel269

[87]   Bilginer, Y., Akpolat, T. and Ozen, S. (2011) Renal amyloidosis in children. Pediatric Nephrology, 26, 1215-1227.

[88]   Neven, B., Marvillet, I., Terrada, C., Ferster, A., Boddaert, N., Couloignier, V., Pinto, G., Pagnier, A., Bodemer, C., Bodaghi, B., Tardieu, M., Prieur, A.M. and Quartier, P. (2010) Longterm efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis and Rheumatism, 62, 258-267.

[89]   Goldbach-Mansky, R., Shroff, S.D., Wilson, M., Snyder, C., Plehn, S., Barham, B., Pham, T.H., Pucino, F., Wesley, R.A., Papadopoulos, J.H., Weinstein, S.P., Mellis, S.J. and Kastner, D.L. (2008) A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis and Rheumatism, 58, 2432-2442.

[90]   Lachmann, H.J., Kone-Paut, I., Kuemmerle-Deschner, J.B., Leslie, K.S., Hachulla, E., Quartier, P., Gitton, X., Widmer, A., Patel, N. and Hawkins, P.N. (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. New England Journal of Medicine, 360, 2416-2425.

[91]   Jeru, I., Duquesnoy, P., Fernandes-Alnemri, T., Cochet, E., Yu, J.W., Lackmy-Port-Lis, M., Grimprel, E., Landman-Parker, J., Hentgen, V., Marlin, S., McElreavey, K., Sarkisian, T., Grateau, G., Alnemri, E.S. and Amselem, S. (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proceedings of the National Academy of Sciences of the United States of America, 105, 1614-1619.

[92]   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. and Gattorno, M. (2010) Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of a NLRP12 mutation. Arthritis and Rheumatism, 63, 830-839.

[93]   Aksentijevich, I., Masters, S.L., Ferguson, P.J., Dancey, P., Frenkel, J., van Royen-Kerkhoff, A., et al. (2009) An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. New England Journal of Medicine, 360, 2426-2437.

[94]   Lindor, N.M., Arsenault, T.M., Solomon, H., Seidman, C.E. and McEvoy, M.T. (1997) A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clinic proceedings, 72, 611-615.

[95]   Shoham, N.G., Centola, M., Mansfield, E., Hull, K.M., Wood, G., Wise, C.A. and Kastner, D.L. (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proceedings of the National Academy of Sciences of the United States of America, 100, 13501-13506.

[96]   Wise, C.A., Gillum, J.D., Seidman, C.E., Lindor, N.M., Veile, R., Bashiardes, S. and Lovett, M. (2002) Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Human Molecular Genetics, 11, 961-969. hmg/11.8.961

[97]   Yeon, H.B., Lindor, N.M., Seidman, J.G. and Seidman, C.E. (2000) Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. American Journal of Human Genetics, 66, 1443-1448.

[98]   Ferrero-Miliani, L., Nielsen, O.H., Andersen, P.S. and Girardin, S.E. (2007) Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1beta generation. Clinical and Experimental Immunology, 147, 227-235.

[99]   Blau, E.B. (1985) Familial granulomatous arthritis, iritis, and rash. Journal of Pediatrics, 107, 689-693.

[100]   Miceli-Richard, C., Lesage, S., Rybojad, M., Prieur, A.M., Manouvrier-Hanu, S., Hafner, R., Chamaillard, M., Zouali, H., Thomas, G. and Hugot, J.P. (2001) CARD15 mutations in Blau syndrome. Nature Genetics, 29, 19-20.

[101]   Kanazawa, N., Okafuji, I., Kambe, N., Nishikomori, R., Nakata-Hizume, M., Nagai, S., et al. (2005) Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: Common genetic etiology with Blau syndrome. Blood, 105, 1195-1197. blood-2004-07-2972

[102]   van Duist, M.M., Albrecht, M., Podswiadek, M., Giachino, D., Lengauer, T., Punzi, L. and De Marchi, M. (2005) A new CARD15 mutation in Blau syndrome. European Journal of Human Genetics, 13, 742-747.

[103]   Fink, C.W. and Cimaz, R. (1997) Early onset sarcoidosis: Not a benign disease. Journal of Rheumatology, 24, 174-177.

[104]   Caorsi, R., Pelagatti, M.A., Federici, S., Finetti, M., Martini, A. and Gattorno, M. (2010) Periodic fever, apthous stomatitis, pharyngitis and adenitis syndrome. Current Opinion in Rheumatology, 22, 579-584.

[105]   Cochard, M., Clet, J., Le, L., Pillet, P., Onrubia, X., Guéron, T., Faouzi, M. and Hofer, M. (2010) PFAPA syndrome is not a sporadic disease. Rheumatology, 49, 1984-1987. matology/keq187

[106]   Berkun, Y., Levy, R., Hurwitz, A., Meir-Harel, M., Lidar, M., Livneh, A. and Padeh, S. (2011) The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Seminars in Arthritis and Rheumatism, 40, 467-472. 1016/j.semarthrit.2010.06.009