THE BROAD-RANGING PANORAMA OF SYSTEMIC AUTOINFLAMMATORY DISORDERS WITH SPECIFIC FOCUS ON ACUTE PAINFUL SYMPTOMS AND HEMATOLOGIC MANIFESTATIONS IN CHILDREN
Main Article Content
Keywords
Autoinflammatory disorder, autoinflammation, interleukin-1, innovative biotechnologies, recurrent fever, personalized medicine, child
Abstract
Systemic autoinflammatory disorders (SAIDs) are inherited defects of innate immunity characterized by recurrent sterile inflammatory attacks involving skin, joints, serosal membranes, gastrointestinal tube and other tissues, which recur with variable rhythmicity and display reactive amyloidosis as a potential long-term complication. Dysregulated inflammasome activity leading to overproduction of many proinflammatory cytokines, such as interleukin-1 (IL-1), and delayed shutdown of inflammation are considered crucial pathogenic keys in the vast majority of SAIDs. Progresses of cellular biology have partially clarified the mechanisms behind monogenic SAIDs, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, hereditary pyogenic diseases, idiopathic granulomatous diseases and defects of the ubiquitin-proteasome pathway, whereas little is clarified for the polygenic SAIDs, such as periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) syndrome. The puzzle of symptomatic febrile attacks recurring over time in children requires evaluating the mixture of clinical data, inflammatory parameters in different disease phases, therapeutic efficacy of specific drugs such as colchicine, corticosteroids or IL-1 antagonists, and genotype analysis in selected cases. Long-term history of periodic fevers should also need to rule out chronic infections and malignancies. This review is conceived as a practical template for a proper classification of children with recurring fevers and includes tips useful for the diagnostic approach to SAIDs, focusing on the specific acute painful symptoms and blood manifestations encountered in childhood.
Downloads
Download data is not yet available.
Abstract 1543
PDF Downloads 973
HTML Downloads 252
References
1. Minasyan H. Phagocytosis and oxycytosis: two arms of human innate immunity. Immunol Res 2018;66:271-80. doi: 10.1007/s12026-018-8988-5 PMid: 29633843
2. Lamkanfi M, Dixit VM. Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 2012;28:137-61. doi: 10.1146/annurev-cellbio-101011-155745 PMid: 22974247
3. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediators Inflamm 2015;2015:194864. doi: 10.1155/2015/194864 PMid: 25784780
4. Bodar EJ, Drenth JP, van der Meer JW, et al. Dysregulation of innate immunity: hereditary periodic fever syndromes. Br J Haematol 2009;144:279-302. doi: 10.1111/j.1365-2141.2008.07036.x PMid: 19120372
5. Rigante D. New mosaic tiles in childhood hereditary autoinflammatory disorders. Immunol Lett 2018;193:67-76. doi: 10.1016/j.imlet.2017.11.013 PMid: 29198619
6. Gentileschi S, Vitale A, Frediani B, et al. Challenges and new horizons in the periodic fever, aphthous stomatitis, pharingitis and adenitis (PFAPA) syndrome. Expert Opin Orphan Drugs 2017;5:165-71. https://doi.org/10.1080/21678707.2017.1279049
7. Caso F, Cantarini L, Lucherini OM, et al. Working the endless puzzle of hereditary autoinflammatory disorders. Mod Rheumatol 2014;24:381-9. doi: 10.3109/14397595.2013.843755 PMid: 24251993
8. Vanaja SK, Rathinam VA, Fitzgerald KA. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol 2015;25:308-15. doi: 10.1016/j.tcb.2014.12.009 PMid: 25639489
9. Rigante D, Frediani B, Galeazzi M, et al. From the Mediterranean to the sea of Japan: the transcontinental odyssey of autoinflammatory diseases. Biomed Res Int 2013;2013:485103. doi: 10.1155/2013/485103 PMid: 23971037
10. Rigante D, La Torraca I, Avallone L, et al. The pharmacological basis of treatment with colchicine in children with familial Mediterranean fever. Eur Rev Med Pharmacol Sci 2006;10:173-8. PMid: 16910346
11. Park YH, Wood G, Kastner DL, et al. Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat Immunol 2016;17:914-21. doi: 10.1038/ni.3457 PMid: 27270401
12. Varan Ö, Kucuk H, Babaoglu H, et al. Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis. Mod Rheumatol 2018 Apr 27:1-4. doi: 10.1080/14397595.2018.1457469 PMid: 29578360
13. Rigante D, Lopalco G, Tarantino G, et al. Non-canonical manifestations of familial Mediterranean fever: a changing paradigm. Clin Rheumatol 2015;34:1503-11. doi: 10.1007/s10067-015-2916-z PMid: 25761640
14. Sohar E, Gafni J, Pras M, et al. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227-53. PMid: 5340644
15. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997;40:1879-85. doi: 10.1002/1529-0131(199710)40 PMid: 9336425
16. Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet 2007; 15: 911-6. doi: 10.1038/sj.ejhg.5201869 PMid: 17568393
17. Rigante D. The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmun Rev 2012;11:348-56. doi: 10.1016/j.autrev.2011.10.008 PMid: 22024500
18. Hull KM, Drewe E, Aksentijevich I, et al. The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 2002;81:349-68. PMid: 12352631
19. Cantarini L, Rigante D, Merlini G, et al. 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 2014;43:818-23. doi: 10.1016/j.semarthrit.2013.12.002 PMid: 24393624
20. Rigante D, Lopalco G, Vitale A, et al. Key facts and hot spots on tumor necrosis factor receptor-associated periodic syndrome. Clin Rheumatol 2014;33:1197-207. doi: 10.1007/s10067-014-2722-z PMid: 24935411
21. Rigante D, Cantarini L, Imazio M, et al. Autoinflammatory diseases and cardiovascular manifestations. Ann Med 2011;43:341-6. doi: 10.3109/07853890.2010.547212 PMid: 21284530
22. Ozen S, Demir S. Monogenic periodic fever syndromes: treatment options for the pediatric patient. Paediatr Drugs 2017;19:303-1. doi: 10.1007/s40272-017-0232-6 PMid: 28497352
23. Cantarini L, Lucherini OM, Frediani B, et al. Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 2011;24:827-36. doi: 10.1177/039463201102400402 PMid: 22230390
24. Li C, Tan X, Zhang J, et al. Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome (CAPS). Sci China Life Sci 2017;60:1436-44. doi: 10.1007/s11427-017-9246-4 PMid: 29285715
25. Rigante D. A developing portrait of hereditary periodic fevers in childhood. Expert Opin Orphan Drugs 2018;6:47-55. https://doi.org/10.1080/21678707.2018.1406797
26. Rigante D, Cipolla C, Rossodivita A. Recombinant human growth hormone in neonatal-onset multisystem inflammatory disease. Clin Pediatr Endocrinol 2018;27:101-5. doi: 10.1297/cpe.27.101 PMid: 29662270
27. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associate periodic syndrome (CAPS). Ann Rheum Dis 2017;76:942-7. doi: 10.1136/annrheumdis-2016-209686 PMid: 27707729
28. Federico G, Rigante D, Pugliese AL, et al. Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome. Scand J Rheumatol 2003;32:312-4. PMid: 14690147
29. Lucherini OM, Rigante D, Sota J, et al. Updated overview of molecular pathways involved in the most common monogenic autoinflammatory diseases. Clin Exp Rheumatol 2018;36 Suppl 110(1):3-9. PMid: 29742053
30. Landmann EC, Walker UA. Pharmacological treatment options for cryopyrin-associated periodic syndromes. Expert Rev Clin Pharmacol 2017;10:855-64. doi: 10.1080/17512433.2017.1338946 PMid: 28586272
31. Rigante D, Ansuini V, Caldarelli M, et al. Hydrocephalus in CINCA syndrome treated with anakinra. Childs Nerv Syst 2006;22:334-7. doi: 10.1007/s00381-006-1280-3 PMid: 16525848
32. Rigante D, Manna R, Verrecchia E, et al. Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. Clin Rheumatol 2018;37:2007-9. doi: 10.1007/s10067-018-4145-8 PMid: 29766377
33. Ebrahimi-Fakhari D, Wahlster L, Mackensen F, et al. Clinical manifestations and longterm follow-up of a patient with CINCA/NOMID syndrome. J Rheumatol 2010; 37: 2196-7. doi: 10.3899/jrheum.100290 PMid: 20889617
34. Vitale A, Rigante D, Maggio MC, et al. Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series. Clin Exp Rheumatol. 2013;31(3 Suppl 77):155-6. PMid: 24064030
35. Gusdorf L, Lipsker D. Schnitzler syndrome: a review. Curr Rheumatol Rep 2017;19:46. doi: 10.1007/s11926-017-0673-5 PMid: 28718061
36. Esposito S, Ascolese B, Senatore L, et al. Current advances in the understanding and treatment of mevalonate kinase deficiency. Int J Immunopathol Pharmacol 2014;27:491-8. doi: 10.1177/039463201402700404 PMid: 25572728
37. Frenkel J, Houten SM, Waterham HR, et al. Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford) 2001;40:579-84. PMid: 11371670
38. Rigante D. Autoinflammatory syndromes behind the scenes of recurrent fevers in children. Med Sci Monit 2009;15:RA179-87. PMid: 19644432
39. Ter Haar NM, Jeyaratnam J, Lachmann HJ, et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever Registry. Arthritis Rheumatol 2016;68:2795-805. doi: 10.1002/art.39763 PMid: 27213830
40. van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore) 2008;87:301-10. doi: 10.1097/MD.0b013e318190cfb7 PMid: 19011501
41. Rigante D, Frediani B, Cantarini L. A comprehensive overview of the hereditary periodic fever syndromes. Clin Rev Allergy Immunol 2018;54:446-53. doi: 10.1007/s12016-016-8537-8 PMid: 27068928
42. Tallon B, Corkill M. Peculiarities of PAPA syndrome. Rheumatology 2006;45:1140-3. doi: 10.1093/rheumatology/kei178 PMid: 16527883
43. Ferguson PJ, Chen S, Tayeh MK, et al. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J Med Genet 2005;42:551-7. doi: 10.1136/jmg.2005.030759 PMid: 15994876
44. Jesus AA, Osman M, Silva CA, et al. A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheumatol 2011;63:4007-17. doi: 10.1002/art.30588 PMid: 22127713
45. Rigante D, Vitale A, Lucherini OM, et al. The hereditary autoinflammatory disorders uncovered. Autoimmun Rev 2014;13:892-900. doi: 10.1016/j.autrev.2014.08.001 PMid: 25149390
46. Vinkel C, Thomsen SF. Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne. Int J Dermatol 2017;56:811-8. doi: 10.1111/ijd.13603 PMid: 28345207
47. Wollina U. Emerging treatments for pyoderma gangrenosum. Expert Opin Orphan Drugs 2017;5:827-32. https://doi.org/10.1080/21678707.2017.1375404
48. Rigante D, Cantarini L. Monogenic autoinflammatory syndromes at a dermatological level. Arch Dermatol Res 2011;303:375-80. doi: 10.1007/s00403-011-1134-z PMid: 21340744
49. Rigante D. A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner. Expert Rev Clin Immunol 2017;13:571-97. doi: 10.1080/1744666X.2017.1280396 PMid: 28064547
50. Caso F, Costa L, Rigante D, et al. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev 2014;13:1220-9. doi: 10.1016/j.autrev.2014.08.010 PMid: 25182201
51. Janssen CE, Rose CD, De Hertogh G, et al. Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2-related disorders Blau syndrome and Crohn disease. J Allergy Clin Immunol 2012;129:1076-84. doi: 10.1016/j.jaci.2012.02.004 PMid: 22464675
52. Al Nabhani Z, Dietrich G, Hugot JP, et al. Nod2: The intestinal gate keeper. PLoS Pathog 2017;13:e1006177. doi: 10.1371/journal.ppat.1006177 PMid: 28253332
53. Engelhardt KR, Shah N, Faizura-Yeop I, et al. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J Allergy Clin Immunol 2013;131:825-30. doi: 10.1016/j.jaci.2012.09.025 PMid: 23158016
54. Zhou Q, Yu X, Demirkaya E, et al. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A 2016;113:10127-32. doi: 10.1073/pnas.1612594113 PMid: 27559085
55. Damgaard RB, Walker JA, Marco-Casanova P, et al. The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell 2016;166:1215-30. doi: 10.1016/j.cell.2016.07.019 PMid: 27523608
56. McDermott A, Jacks J, Kessler M, et al. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015;54:121-9. doi: 10.1111/ijd.12695 PMid: 25521013
57. Bienias M, Brück N, Griep C, et al. Therapeutic approaches to type I interferonopathies. Curr Rheumatol Rep 2018;20:32. doi: 10.1007/s11926-018-0743-3 PMid: 29679241
58. Aicardi J, Goutières F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 1984;15:49-54. doi:10.1002/ana.410150109 PMid: 6712192
59. Crow YJ, Chase DS, Lowenstein Schmidt J, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 2015;167A:296-312. doi: 10.1002/ajmg.a.36887 PMid: 25604658
60. Crow YJ, Vanderver A, Orcesi S, et al. Therapies in Aicardi-Goutieres syndrome. Clin Exp Immunol 2014;175:1-8. doi: 10.1111/cei.12115 PMid: 23607857
61. Kvaerner KJ, Nafstad P, Jaakkola JJ. Upper respiratory morbidity in preschool children: a cross-sectional study. Arch Otolaryngol Head Neck Surg 2000;126:1201-6. PMid: 11031406
62. Esposito S, Bianchini S, Fattizzo M, et al. The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Pediatr Infect Dis J 2014;33:650-2. doi: 10.1097/INF.0000000000000346 PMid: 24642520
63. Rigante D, Gentileschi S, Vitale A, et al. Evolving frontiers in the treatment of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Isr Med Ass J 2017;19:444-7. PMid: 28786261
64. Cantarini L, Vitale A, Bartolomei B, et al. Diagnosis of PFAPA syndrome applied to a cohort of 17 adults with unexplained recurrent fevers. Clin Exp Rheumatol 2012;30:269-71. PMid: 22325152
65. Cantarini L, Vitale A, Sicignano LL, et al. Diagnostic criteria for adult-onset Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome. Front Immunol 2017;8:1018. doi: 10.3389/fimmu.2017.01018 PMid: 28970828
66. Rigante D, Vitale A, Natale MF, et al. A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. Clin Rheumatol 2017;36:463-8. doi: 10.1007/s10067-016-3317-7 PMid: 27251674
67. Koné-Paut I. Behçet's disease in children, an overview. Pediatr Rheumatol Online J 2016;14(1):10. doi: 10.1186/s12969-016-0070-z PMid: 26887984
68. Cantarini L, Vitale A, Bersani G, et al. PFAPA syndrome and Behçet’s disease: a comparison of two medical entities based on the clinical interviews performed by three different specialists. Clin Rheumatol 2016;35:501-5. doi: 10.1007/s10067-015-2890-5 PMid: 25665824
69. Caso F, Costa L, Rigante D, et al. Biological treatments in Behçet’s disease: beyond anti-TNF-therapy. Mediators Inflamm 2014;2014:107421. doi: 10.1155/2014/107421 PMid: 25061259
70. Vitale A, Rigante D, Lopalco G, et al. Interleukin-1 inhibition in Behçet's disease. Isr Med Assoc J 2016;18:171-6. PMid: 27228638
71. Grevich S, Shenoi S. Update on the management of systemic juvenile idiopathic arthritis and role of IL-1 and IL-6 inhibition. Adolesc Health Med Ther 2017;8:125-35. doi: 10.2147/AHMT.S109495 PMid: 29184458
72. Deuteraiou K, Kitas G, Garyfallos A, et al. Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseases. Rheumatol Int 2018;38:1345-54. doi: 10.1007/s00296-018-4074-5 PMid: 29869008
73. Vitale A, Cantarini L, Rigante D, et al. Anakinra treatment in patients with gout and diabetes type 2. Clin Rheumatol 2015;34:981-4. doi: 10.1007/s10067-014-2601-7 PMid: 24733251
74. Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis. Autoimmun Rev 2015;14:90-7. doi: 10.1016/j.autrev.2014.10.005 PMid: 25308531
75. Rigante D, La Torraca I, Ansuini V, et al. The multi-face expression of familial Mediterranean fever in the child. Eur Rev Med Pharmacol Sci 2006;10:163-71. PMid: 16910345
76. Soriano A, Manna R. Familial Mediterranean fever: new phenotypes. Autoimmun Rev 2012;12:31-7. doi: 10.1016/j.autrev.2012.07.019 PMid: 22878273
77. Tufan G, Demir S. Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome. Rheumatol Int 2010;30:1089-90. doi: 10.1007/s00296-009-1024-2 PMid: 19590876
78. Lachmann HJ, Papa R, Gerhold K, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis 2014;73:2160-7. doi: 10.1136/annrheumdis-2013-204184 PMid: 23965844
79. Harada Y, Fukiage K, Nishikomori R, et al. CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: a case report. Mod Rheumatol 2017;27:1098-100. doi: 10.3109/14397595.2015.1040609 PMid: 25867226
80. Vitale A, Insalaco A, Sfriso P, et al. A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists: a nationwide multi-center retrospective observational study. Front Pharmacol 2016;7:380. doi: 10.3389/fphar.2016.00380 PMid: 27822185
81. Prietsch V, Mayatepek E, Krastel H., et al. Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum. Pediatrics 2003;111:258-61. PMid: 12563048
82. Löffler W, Lohse P, Weihmayr T, et al. Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts. Infection 2017;45:395-402. doi: 10.1007/s15010-017-0996-1 PMid: 28251506
83. Wouters CH, Maes A, Foley KP, et al. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J 2014;12:33. doi: 10.1186/1546-0096-12-33 PMid: 25136265
84. Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol 2017;8:927. doi: 10.3389/fimmu.2017.00927 PMid: 28848544
85. Celkan T, Celik M, Kasapçopur O, et al. The anemia of familial Mediterranean fever disease. Pediatr Hematol Oncol 2005;22:657-65. doi: 10.1080/08880010500278681 PMid: 16251171
86. Kucuk A, Erol MF, Senel S, et al. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. Korean J Intern Med 2016;31:386-91. doi: 10.3904/kjim.2015.039 PMid: 26864298
87. Sakall? H, Kal O. Mean platelet volume as a potential predictor of proteinuria and amyloidosis in familial Mediterranean fever. Clin Rheumatol 2013;32:1185-90. doi: 10.1007/s10067-013-2257-8 PMid: 23592230
88. Ar?ca S, Ozer C, Ar?ca V, et al. Evaluation of the mean platelet volume in children with familial Mediterranean fever. Rheumatol Int 2012;32:3559-63. doi: 10.1007/s00296-011-2251-x PMid: 22086472
89. Erden A, Batu ED, Armagan B, et al. Blood group 'A' may have a possible modifier effect on familial Mediterranean fever and blood group '0' may be associated with colchicine resistance. Biomark Med 2018;12:565-72. doi: 10.2217/bmm-2017-0344 PMid: 29873519
90. Lepore L, Paloni G, Caorsi R, et al. Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with anakinra. J Pediatr 2010;157:310-5. doi: 10.1016/j.jpeds.2010.02.040 PMid: 20472245
91. Lipsker D, Veran Y, Grunenberger F, et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore) 2001;80:37-44. PMid: 11204501
92. Steiner LA, Ehrenkranz RA, Peterec SM, et al. Perinatal onset mevalonate kinase deficiency. Pediatr Dev Pathol 2011;14:301-6. doi: 10.2350/11-02-0985-OA.1 PMid: 21425920
93. Majeed HA, Kalaawi M, Mohanty D, et al. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. J Pediatr 1989;115:730-4. PMid: 2809904
94. McDermott A, Jacks J, Kessler M, et al. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015;54:121-9. doi: 10.1111/ijd.12695 PMid: 25521013
95. Stabile A, Bertoni B, Ansuini V, et al. The clinical spectrum and treatment options of macrophage activation syndrome in the pediatric age. Eur Rev Med Pharmacol Sci 2006;10:53-9. PMid: 16705949
96. Rigante D, Emmi G, Fastiggi M, et al. Macrophage activation syndrome in the course of monogenic autoinflammatory disorders. Clin Rheumatol 2015;34:1333-9. doi: 10.1007/s10067-015-2923-0 PMid: 25846831
97. Minoia F, Bovis F, Davì S, et al. Development and initial validation of the macrophage activation syndrome/primary hemophagocytic lymphohistiocytosis score, a diagnostic tool that differentiates primary hemophagocytic lymphohistiocytosis from macrophage activation syndrome. J Pediatr 2017;189:72-8. doi: 10.1016/j.jpeds.2017.06.005 PMid: 28807357
98. Larroche C, Mouthon L. Pathogenesis of hemophagocytic syndrome. Autoimmunity Rev 2004;3:69-75. doi: 10.1016/S1568-9972(03)00091-0 PMid: 15003190
99. Rigante D, Esposito S. A roadmap for fever of unknown origin in children. Int J Immunopathol Pharmacol 2013;26:315-26. doi: 10.1177/039463201302600205 PMid: 23755747
100. Cantarini L, Lopalco G, Cattalini M, et al. Interleukin-1: Ariadne's thread in autoinflammatory and autoimmune disorders. Isr Med Assoc J 2015;17:93-7. PMid: 26223084
101. Pras E, Livneh A, Balow JE Jr, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 1998;75:216-9. PMid: 9450890
102. Cantarini L, Lucherini OM, Iacoponi F, et al. Development and preliminary validation of a diagnostic score for identifying patients affected with adult-onset autoinflammatory disorders. Int J Immunopathol Pharmacol 2010;23:1133-4. doi: 10.1177/039463201002300417 PMid: 21244762
103. Cantarini L, Iacoponi F, Lucherini OM, et al. Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. Int J Immunopathol Pharmacol 2011;24:695-702. doi: 10.1177/039463201102400315 PMid: 21978701
104. Piram M, Koné Paut I, Lachmann H, et al. Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis 2014;73:2168-73. doi: 10.1136/annrheumdis-2013-203666 PMid: 24026675
105. Ter Haar NM, Annink KV, Al-Mayouf SM, et al. Development of the autoinflammatory disease damage index (ADDI). Ann Rheum Dis 2017;76:821-30. doi: 10.1136/annrheumdis-2016-210092 PMid: 27811147
2. Lamkanfi M, Dixit VM. Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 2012;28:137-61. doi: 10.1146/annurev-cellbio-101011-155745 PMid: 22974247
3. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediators Inflamm 2015;2015:194864. doi: 10.1155/2015/194864 PMid: 25784780
4. Bodar EJ, Drenth JP, van der Meer JW, et al. Dysregulation of innate immunity: hereditary periodic fever syndromes. Br J Haematol 2009;144:279-302. doi: 10.1111/j.1365-2141.2008.07036.x PMid: 19120372
5. Rigante D. New mosaic tiles in childhood hereditary autoinflammatory disorders. Immunol Lett 2018;193:67-76. doi: 10.1016/j.imlet.2017.11.013 PMid: 29198619
6. Gentileschi S, Vitale A, Frediani B, et al. Challenges and new horizons in the periodic fever, aphthous stomatitis, pharingitis and adenitis (PFAPA) syndrome. Expert Opin Orphan Drugs 2017;5:165-71. https://doi.org/10.1080/21678707.2017.1279049
7. Caso F, Cantarini L, Lucherini OM, et al. Working the endless puzzle of hereditary autoinflammatory disorders. Mod Rheumatol 2014;24:381-9. doi: 10.3109/14397595.2013.843755 PMid: 24251993
8. Vanaja SK, Rathinam VA, Fitzgerald KA. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol 2015;25:308-15. doi: 10.1016/j.tcb.2014.12.009 PMid: 25639489
9. Rigante D, Frediani B, Galeazzi M, et al. From the Mediterranean to the sea of Japan: the transcontinental odyssey of autoinflammatory diseases. Biomed Res Int 2013;2013:485103. doi: 10.1155/2013/485103 PMid: 23971037
10. Rigante D, La Torraca I, Avallone L, et al. The pharmacological basis of treatment with colchicine in children with familial Mediterranean fever. Eur Rev Med Pharmacol Sci 2006;10:173-8. PMid: 16910346
11. Park YH, Wood G, Kastner DL, et al. Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat Immunol 2016;17:914-21. doi: 10.1038/ni.3457 PMid: 27270401
12. Varan Ö, Kucuk H, Babaoglu H, et al. Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis. Mod Rheumatol 2018 Apr 27:1-4. doi: 10.1080/14397595.2018.1457469 PMid: 29578360
13. Rigante D, Lopalco G, Tarantino G, et al. Non-canonical manifestations of familial Mediterranean fever: a changing paradigm. Clin Rheumatol 2015;34:1503-11. doi: 10.1007/s10067-015-2916-z PMid: 25761640
14. Sohar E, Gafni J, Pras M, et al. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227-53. PMid: 5340644
15. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997;40:1879-85. doi: 10.1002/1529-0131(199710)40 PMid: 9336425
16. Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet 2007; 15: 911-6. doi: 10.1038/sj.ejhg.5201869 PMid: 17568393
17. Rigante D. The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmun Rev 2012;11:348-56. doi: 10.1016/j.autrev.2011.10.008 PMid: 22024500
18. Hull KM, Drewe E, Aksentijevich I, et al. The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 2002;81:349-68. PMid: 12352631
19. Cantarini L, Rigante D, Merlini G, et al. 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 2014;43:818-23. doi: 10.1016/j.semarthrit.2013.12.002 PMid: 24393624
20. Rigante D, Lopalco G, Vitale A, et al. Key facts and hot spots on tumor necrosis factor receptor-associated periodic syndrome. Clin Rheumatol 2014;33:1197-207. doi: 10.1007/s10067-014-2722-z PMid: 24935411
21. Rigante D, Cantarini L, Imazio M, et al. Autoinflammatory diseases and cardiovascular manifestations. Ann Med 2011;43:341-6. doi: 10.3109/07853890.2010.547212 PMid: 21284530
22. Ozen S, Demir S. Monogenic periodic fever syndromes: treatment options for the pediatric patient. Paediatr Drugs 2017;19:303-1. doi: 10.1007/s40272-017-0232-6 PMid: 28497352
23. Cantarini L, Lucherini OM, Frediani B, et al. Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 2011;24:827-36. doi: 10.1177/039463201102400402 PMid: 22230390
24. Li C, Tan X, Zhang J, et al. Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome (CAPS). Sci China Life Sci 2017;60:1436-44. doi: 10.1007/s11427-017-9246-4 PMid: 29285715
25. Rigante D. A developing portrait of hereditary periodic fevers in childhood. Expert Opin Orphan Drugs 2018;6:47-55. https://doi.org/10.1080/21678707.2018.1406797
26. Rigante D, Cipolla C, Rossodivita A. Recombinant human growth hormone in neonatal-onset multisystem inflammatory disease. Clin Pediatr Endocrinol 2018;27:101-5. doi: 10.1297/cpe.27.101 PMid: 29662270
27. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associate periodic syndrome (CAPS). Ann Rheum Dis 2017;76:942-7. doi: 10.1136/annrheumdis-2016-209686 PMid: 27707729
28. Federico G, Rigante D, Pugliese AL, et al. Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome. Scand J Rheumatol 2003;32:312-4. PMid: 14690147
29. Lucherini OM, Rigante D, Sota J, et al. Updated overview of molecular pathways involved in the most common monogenic autoinflammatory diseases. Clin Exp Rheumatol 2018;36 Suppl 110(1):3-9. PMid: 29742053
30. Landmann EC, Walker UA. Pharmacological treatment options for cryopyrin-associated periodic syndromes. Expert Rev Clin Pharmacol 2017;10:855-64. doi: 10.1080/17512433.2017.1338946 PMid: 28586272
31. Rigante D, Ansuini V, Caldarelli M, et al. Hydrocephalus in CINCA syndrome treated with anakinra. Childs Nerv Syst 2006;22:334-7. doi: 10.1007/s00381-006-1280-3 PMid: 16525848
32. Rigante D, Manna R, Verrecchia E, et al. Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. Clin Rheumatol 2018;37:2007-9. doi: 10.1007/s10067-018-4145-8 PMid: 29766377
33. Ebrahimi-Fakhari D, Wahlster L, Mackensen F, et al. Clinical manifestations and longterm follow-up of a patient with CINCA/NOMID syndrome. J Rheumatol 2010; 37: 2196-7. doi: 10.3899/jrheum.100290 PMid: 20889617
34. Vitale A, Rigante D, Maggio MC, et al. Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series. Clin Exp Rheumatol. 2013;31(3 Suppl 77):155-6. PMid: 24064030
35. Gusdorf L, Lipsker D. Schnitzler syndrome: a review. Curr Rheumatol Rep 2017;19:46. doi: 10.1007/s11926-017-0673-5 PMid: 28718061
36. Esposito S, Ascolese B, Senatore L, et al. Current advances in the understanding and treatment of mevalonate kinase deficiency. Int J Immunopathol Pharmacol 2014;27:491-8. doi: 10.1177/039463201402700404 PMid: 25572728
37. Frenkel J, Houten SM, Waterham HR, et al. Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford) 2001;40:579-84. PMid: 11371670
38. Rigante D. Autoinflammatory syndromes behind the scenes of recurrent fevers in children. Med Sci Monit 2009;15:RA179-87. PMid: 19644432
39. Ter Haar NM, Jeyaratnam J, Lachmann HJ, et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever Registry. Arthritis Rheumatol 2016;68:2795-805. doi: 10.1002/art.39763 PMid: 27213830
40. van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore) 2008;87:301-10. doi: 10.1097/MD.0b013e318190cfb7 PMid: 19011501
41. Rigante D, Frediani B, Cantarini L. A comprehensive overview of the hereditary periodic fever syndromes. Clin Rev Allergy Immunol 2018;54:446-53. doi: 10.1007/s12016-016-8537-8 PMid: 27068928
42. Tallon B, Corkill M. Peculiarities of PAPA syndrome. Rheumatology 2006;45:1140-3. doi: 10.1093/rheumatology/kei178 PMid: 16527883
43. Ferguson PJ, Chen S, Tayeh MK, et al. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). J Med Genet 2005;42:551-7. doi: 10.1136/jmg.2005.030759 PMid: 15994876
44. Jesus AA, Osman M, Silva CA, et al. A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheumatol 2011;63:4007-17. doi: 10.1002/art.30588 PMid: 22127713
45. Rigante D, Vitale A, Lucherini OM, et al. The hereditary autoinflammatory disorders uncovered. Autoimmun Rev 2014;13:892-900. doi: 10.1016/j.autrev.2014.08.001 PMid: 25149390
46. Vinkel C, Thomsen SF. Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne. Int J Dermatol 2017;56:811-8. doi: 10.1111/ijd.13603 PMid: 28345207
47. Wollina U. Emerging treatments for pyoderma gangrenosum. Expert Opin Orphan Drugs 2017;5:827-32. https://doi.org/10.1080/21678707.2017.1375404
48. Rigante D, Cantarini L. Monogenic autoinflammatory syndromes at a dermatological level. Arch Dermatol Res 2011;303:375-80. doi: 10.1007/s00403-011-1134-z PMid: 21340744
49. Rigante D. A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner. Expert Rev Clin Immunol 2017;13:571-97. doi: 10.1080/1744666X.2017.1280396 PMid: 28064547
50. Caso F, Costa L, Rigante D, et al. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev 2014;13:1220-9. doi: 10.1016/j.autrev.2014.08.010 PMid: 25182201
51. Janssen CE, Rose CD, De Hertogh G, et al. Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2-related disorders Blau syndrome and Crohn disease. J Allergy Clin Immunol 2012;129:1076-84. doi: 10.1016/j.jaci.2012.02.004 PMid: 22464675
52. Al Nabhani Z, Dietrich G, Hugot JP, et al. Nod2: The intestinal gate keeper. PLoS Pathog 2017;13:e1006177. doi: 10.1371/journal.ppat.1006177 PMid: 28253332
53. Engelhardt KR, Shah N, Faizura-Yeop I, et al. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J Allergy Clin Immunol 2013;131:825-30. doi: 10.1016/j.jaci.2012.09.025 PMid: 23158016
54. Zhou Q, Yu X, Demirkaya E, et al. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A 2016;113:10127-32. doi: 10.1073/pnas.1612594113 PMid: 27559085
55. Damgaard RB, Walker JA, Marco-Casanova P, et al. The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell 2016;166:1215-30. doi: 10.1016/j.cell.2016.07.019 PMid: 27523608
56. McDermott A, Jacks J, Kessler M, et al. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015;54:121-9. doi: 10.1111/ijd.12695 PMid: 25521013
57. Bienias M, Brück N, Griep C, et al. Therapeutic approaches to type I interferonopathies. Curr Rheumatol Rep 2018;20:32. doi: 10.1007/s11926-018-0743-3 PMid: 29679241
58. Aicardi J, Goutières F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 1984;15:49-54. doi:10.1002/ana.410150109 PMid: 6712192
59. Crow YJ, Chase DS, Lowenstein Schmidt J, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 2015;167A:296-312. doi: 10.1002/ajmg.a.36887 PMid: 25604658
60. Crow YJ, Vanderver A, Orcesi S, et al. Therapies in Aicardi-Goutieres syndrome. Clin Exp Immunol 2014;175:1-8. doi: 10.1111/cei.12115 PMid: 23607857
61. Kvaerner KJ, Nafstad P, Jaakkola JJ. Upper respiratory morbidity in preschool children: a cross-sectional study. Arch Otolaryngol Head Neck Surg 2000;126:1201-6. PMid: 11031406
62. Esposito S, Bianchini S, Fattizzo M, et al. The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Pediatr Infect Dis J 2014;33:650-2. doi: 10.1097/INF.0000000000000346 PMid: 24642520
63. Rigante D, Gentileschi S, Vitale A, et al. Evolving frontiers in the treatment of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Isr Med Ass J 2017;19:444-7. PMid: 28786261
64. Cantarini L, Vitale A, Bartolomei B, et al. Diagnosis of PFAPA syndrome applied to a cohort of 17 adults with unexplained recurrent fevers. Clin Exp Rheumatol 2012;30:269-71. PMid: 22325152
65. Cantarini L, Vitale A, Sicignano LL, et al. Diagnostic criteria for adult-onset Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome. Front Immunol 2017;8:1018. doi: 10.3389/fimmu.2017.01018 PMid: 28970828
66. Rigante D, Vitale A, Natale MF, et al. A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. Clin Rheumatol 2017;36:463-8. doi: 10.1007/s10067-016-3317-7 PMid: 27251674
67. Koné-Paut I. Behçet's disease in children, an overview. Pediatr Rheumatol Online J 2016;14(1):10. doi: 10.1186/s12969-016-0070-z PMid: 26887984
68. Cantarini L, Vitale A, Bersani G, et al. PFAPA syndrome and Behçet’s disease: a comparison of two medical entities based on the clinical interviews performed by three different specialists. Clin Rheumatol 2016;35:501-5. doi: 10.1007/s10067-015-2890-5 PMid: 25665824
69. Caso F, Costa L, Rigante D, et al. Biological treatments in Behçet’s disease: beyond anti-TNF-therapy. Mediators Inflamm 2014;2014:107421. doi: 10.1155/2014/107421 PMid: 25061259
70. Vitale A, Rigante D, Lopalco G, et al. Interleukin-1 inhibition in Behçet's disease. Isr Med Assoc J 2016;18:171-6. PMid: 27228638
71. Grevich S, Shenoi S. Update on the management of systemic juvenile idiopathic arthritis and role of IL-1 and IL-6 inhibition. Adolesc Health Med Ther 2017;8:125-35. doi: 10.2147/AHMT.S109495 PMid: 29184458
72. Deuteraiou K, Kitas G, Garyfallos A, et al. Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseases. Rheumatol Int 2018;38:1345-54. doi: 10.1007/s00296-018-4074-5 PMid: 29869008
73. Vitale A, Cantarini L, Rigante D, et al. Anakinra treatment in patients with gout and diabetes type 2. Clin Rheumatol 2015;34:981-4. doi: 10.1007/s10067-014-2601-7 PMid: 24733251
74. Cantarini L, Lopalco G, Selmi C, et al. Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis. Autoimmun Rev 2015;14:90-7. doi: 10.1016/j.autrev.2014.10.005 PMid: 25308531
75. Rigante D, La Torraca I, Ansuini V, et al. The multi-face expression of familial Mediterranean fever in the child. Eur Rev Med Pharmacol Sci 2006;10:163-71. PMid: 16910345
76. Soriano A, Manna R. Familial Mediterranean fever: new phenotypes. Autoimmun Rev 2012;12:31-7. doi: 10.1016/j.autrev.2012.07.019 PMid: 22878273
77. Tufan G, Demir S. Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome. Rheumatol Int 2010;30:1089-90. doi: 10.1007/s00296-009-1024-2 PMid: 19590876
78. Lachmann HJ, Papa R, Gerhold K, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis 2014;73:2160-7. doi: 10.1136/annrheumdis-2013-204184 PMid: 23965844
79. Harada Y, Fukiage K, Nishikomori R, et al. CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: a case report. Mod Rheumatol 2017;27:1098-100. doi: 10.3109/14397595.2015.1040609 PMid: 25867226
80. Vitale A, Insalaco A, Sfriso P, et al. A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists: a nationwide multi-center retrospective observational study. Front Pharmacol 2016;7:380. doi: 10.3389/fphar.2016.00380 PMid: 27822185
81. Prietsch V, Mayatepek E, Krastel H., et al. Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum. Pediatrics 2003;111:258-61. PMid: 12563048
82. Löffler W, Lohse P, Weihmayr T, et al. Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts. Infection 2017;45:395-402. doi: 10.1007/s15010-017-0996-1 PMid: 28251506
83. Wouters CH, Maes A, Foley KP, et al. Blau syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatr Rheumatol Online J 2014;12:33. doi: 10.1186/1546-0096-12-33 PMid: 25136265
84. Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol 2017;8:927. doi: 10.3389/fimmu.2017.00927 PMid: 28848544
85. Celkan T, Celik M, Kasapçopur O, et al. The anemia of familial Mediterranean fever disease. Pediatr Hematol Oncol 2005;22:657-65. doi: 10.1080/08880010500278681 PMid: 16251171
86. Kucuk A, Erol MF, Senel S, et al. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. Korean J Intern Med 2016;31:386-91. doi: 10.3904/kjim.2015.039 PMid: 26864298
87. Sakall? H, Kal O. Mean platelet volume as a potential predictor of proteinuria and amyloidosis in familial Mediterranean fever. Clin Rheumatol 2013;32:1185-90. doi: 10.1007/s10067-013-2257-8 PMid: 23592230
88. Ar?ca S, Ozer C, Ar?ca V, et al. Evaluation of the mean platelet volume in children with familial Mediterranean fever. Rheumatol Int 2012;32:3559-63. doi: 10.1007/s00296-011-2251-x PMid: 22086472
89. Erden A, Batu ED, Armagan B, et al. Blood group 'A' may have a possible modifier effect on familial Mediterranean fever and blood group '0' may be associated with colchicine resistance. Biomark Med 2018;12:565-72. doi: 10.2217/bmm-2017-0344 PMid: 29873519
90. Lepore L, Paloni G, Caorsi R, et al. Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with anakinra. J Pediatr 2010;157:310-5. doi: 10.1016/j.jpeds.2010.02.040 PMid: 20472245
91. Lipsker D, Veran Y, Grunenberger F, et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore) 2001;80:37-44. PMid: 11204501
92. Steiner LA, Ehrenkranz RA, Peterec SM, et al. Perinatal onset mevalonate kinase deficiency. Pediatr Dev Pathol 2011;14:301-6. doi: 10.2350/11-02-0985-OA.1 PMid: 21425920
93. Majeed HA, Kalaawi M, Mohanty D, et al. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. J Pediatr 1989;115:730-4. PMid: 2809904
94. McDermott A, Jacks J, Kessler M, et al. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015;54:121-9. doi: 10.1111/ijd.12695 PMid: 25521013
95. Stabile A, Bertoni B, Ansuini V, et al. The clinical spectrum and treatment options of macrophage activation syndrome in the pediatric age. Eur Rev Med Pharmacol Sci 2006;10:53-9. PMid: 16705949
96. Rigante D, Emmi G, Fastiggi M, et al. Macrophage activation syndrome in the course of monogenic autoinflammatory disorders. Clin Rheumatol 2015;34:1333-9. doi: 10.1007/s10067-015-2923-0 PMid: 25846831
97. Minoia F, Bovis F, Davì S, et al. Development and initial validation of the macrophage activation syndrome/primary hemophagocytic lymphohistiocytosis score, a diagnostic tool that differentiates primary hemophagocytic lymphohistiocytosis from macrophage activation syndrome. J Pediatr 2017;189:72-8. doi: 10.1016/j.jpeds.2017.06.005 PMid: 28807357
98. Larroche C, Mouthon L. Pathogenesis of hemophagocytic syndrome. Autoimmunity Rev 2004;3:69-75. doi: 10.1016/S1568-9972(03)00091-0 PMid: 15003190
99. Rigante D, Esposito S. A roadmap for fever of unknown origin in children. Int J Immunopathol Pharmacol 2013;26:315-26. doi: 10.1177/039463201302600205 PMid: 23755747
100. Cantarini L, Lopalco G, Cattalini M, et al. Interleukin-1: Ariadne's thread in autoinflammatory and autoimmune disorders. Isr Med Assoc J 2015;17:93-7. PMid: 26223084
101. Pras E, Livneh A, Balow JE Jr, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 1998;75:216-9. PMid: 9450890
102. Cantarini L, Lucherini OM, Iacoponi F, et al. Development and preliminary validation of a diagnostic score for identifying patients affected with adult-onset autoinflammatory disorders. Int J Immunopathol Pharmacol 2010;23:1133-4. doi: 10.1177/039463201002300417 PMid: 21244762
103. Cantarini L, Iacoponi F, Lucherini OM, et al. Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. Int J Immunopathol Pharmacol 2011;24:695-702. doi: 10.1177/039463201102400315 PMid: 21978701
104. Piram M, Koné Paut I, Lachmann H, et al. Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis 2014;73:2168-73. doi: 10.1136/annrheumdis-2013-203666 PMid: 24026675
105. Ter Haar NM, Annink KV, Al-Mayouf SM, et al. Development of the autoinflammatory disease damage index (ADDI). Ann Rheum Dis 2017;76:821-30. doi: 10.1136/annrheumdis-2016-210092 PMid: 27811147