Autoinflammatory Diseases (AID)

Abstract

Most of the autoinflammatory diseases (AID) are orphan diseases with recurrent episodes of systemic inflammation. Fever and exanthema are leading features. Given the ongoing elucidation of pathogenic causes and hence therapeutic approaches, we provided a review of the current literature of AID.

Zusammenfassung

Die meisten autoinflammatorischen Erkrankungen sind seltene Erkrankungen mit wiederk­eh­renden Episoden systemischer Inflammation. Fieber und Exanthem sind führende Merkmale. In Anbetracht der fortlaufenden Aufklärung pathogenetischer Ursachen und der daraus resultierenden Therapieansätze, stellen wir die gegenwärtige Literatur über AID zusammenfassend dar.

Key words

autoinflammatory diseases - monogenetic - inflammasome - interleukin 1

Schlüsselwörter

Autoinflammation - monogenetische Erkrankungen - Inflammasom - Interleukin 1

• References

• 1 The AGREE Collaboration Appraisal of Guidelines for Research & Evaluation (AGREE) instrument www.agreecollaboration.org
• 2 Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever . The International FMF Consortium. Cell 1997; 90: 797-807
• 3 A candidate gene for familial Mediterranean fever . Nature genetics. 1997; 17: 25-31
• 4 Infevers an online database for autoinflammatory mutations [online]. In: Institut de genetique humaine 2013
• 5 Agarwal AK, Xing C, DeMartino GN et al. PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet 2010; 87: 866-872
• 6 Akash MS, Shen Q, Rehman K et al. Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus. J Pharm Sci 2012; 101: 1647-1658
• 7 Aksentijevich I, DP C, Remmers EF et al. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 2007; 56: 1273-1285
• 8 Aksentijevich I, Kastner DL. Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat Rev Rheumatol 2011; 7: 469-478
• 9 Aksentijevich I, Masters SL, Ferguson PJ et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Eng J Med 2009; 360: 2426-2437
• 10 Aksentijevich I, Nowak M, Mallah M et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002; 46: 3340-3348
• 11 Aksu K, Keser G. Coexistence of vasculitides with familial Mediterranean fever. Rheumatol Int 2011; 31: 1263-1274
• 12 Allen IC, McElvania-TeKippe E, Wilson JE et al. Characterization of NLRP12 during the in vivo host immune response to Klebsiella pneumoniae and Mycobacterium tuberculosis. PloS one 2013; 8: e60842
• 13 Almeida de Jesus A, Goldbach-Mansky R. Monogenic autoinflammatory diseases: Concept and clinical manifestations. Clin Immunol 2013; 147: 155-174
• 14 Ammouri W, Cuisset L, Rouaghe S et al. Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. Rheumatology (Oxford) 2007; 46: 1597-1600
• 15 Andres M, Pascual E. Anakinra for a refractory case of intermittent hydrarthrosis with a TRAPS-related gene mutation. Ann rheum dis 2013; 72: 155
• 16 Arad U, Niv E, Caspi D et al. “Trap” the diagnosis: a man with recurrent episodes of febrile peritonitis, not just familial Mediterranean fever. IMAJ 2012; 14: 229-231
• 17 Bachetti T, Chiesa S, Castagnola P et al. Autophagy contributes to inflammation in patients with TNFR-associated periodic syndrome (TRAPS). Ann rheum dis 2013; 72: 1044-1052
• 18 Bader-Meunier B, Florkin B, Sibilia J et al. Mevalonate kinase deficiency: a survey of 50 patients. Pediatrics 2011; 128: e152-e159
• 19 Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet 1998; 351: 659-664
• 20 Berkun Y, Eisenstein E, Ben-Chetrit E. FMF – clinical features, new treatments and the role of genetic modifiers: a critical digest of the 2010–2012 literature. Clin Exp Rheumatol 2012; 30: S90-S95
• 21 Bernot A, da Silva C, Petit JL et al. Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Human molecular genetics 1998; 7: 1317-1325
• 22 Berthold LD, Steiner D, Scholz D et al. Imaging of chronic inflammatory bowel disease with 18 F-FDG PET in children and adolescents. Klin Padiatr 2013; 225: 212-217
• 23 Boisson B, Laplantine E, Prando C et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol 2012; 13: 1178-1186
• 24 Brenner M, Ruzicka T, Plewig G et al. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol 2009; 161: 1199-1201
• 25 Bulua AC, Mogul DB, Aksentijevich I et al. Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study. Arthritis Rheum 2012; 64: 908-913
• 26 Canoui E, Maigné G, Jeru I et al. Atypical presentation of a cryopyrin-associated periodic syndrome, revealing a novel NLRP3 mutation. Clin Immunology. 2013 DOI: 10.1016/j.clim.2013.1005.1020
• 27 Cowen EW, Goldbach-Mansky R. DIRA, DITRA, and new insights into pathways of skin inflammation: what’s in a name?. Arch Dermatol 2012; 148: 381-384
• 28 Cremers JP, Drent M, Bast A et al. Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide. Curr Opin Pulm Med 2013; 19: 545-561
• 29 Delves PJ, Roitt IM. The immune system. First of two parts. N Eng J Med 2000; 343: 37-49
• 30 Delves PJ, Roitt IM. The immune system. Second of two parts. N Eng J Med 2000; 343: 108-117
• 31 Dewalle M, Domingo C, Rozenbaum M et al. Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF). Eur J Hum Genet 1998; 6: 95-97
• 32 Dogan CS, Akman S, Koyun M et al. Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schonlein purpura without FMF symptoms. Rheumatol Int 2013; 33: 377-380
• 33 Drenth JP, Haagsma CJ, van der Meer JW. Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Baltimore) 1994; 73: 133-144
• 34 Federici S, Caorsi R, Gattorno M. The autoinflammatory diseases. Swiss Med Wkly 2012; 142: w13602
• 35 Feldmann J, Prieur AM, Quartier P et al. 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 2002; 71: 198-203
• 36 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: 551-557
• 37 Fuchs-Telem D, Sarig O, van Steensel MA et al. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet 2012; 91: 163-170
• 38 Galeotti C, Meinzer U, Quartier P et al. Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency. Rheumatology (Oxford) 2012; 51: 1855-1859
• 39 Garavello W, Romagnoli M, Gaini RM. Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study. J Pediatr 2009; 155: 250-253
• 40 Garg A, Hernandez MD, Sousa AB et al. An autosomal recessive syndrome of joint contractures, muscular atrophy, microcytic anemia, and panniculitis-associated lipodystrophy. J clin endocrinol metabol 2010; 95: E58-E63
• 41 Glocker EO, Kotlarz D, Boztug K et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Eng J Med 2009; 361: 2033-2045
• 42 Goldfinger SE. Colchicine for familial Mediterranean fever. N Eng J Med 1972; 287: 1302
• 43 Goldstein RC, Schwabe AD. Prophylactic colchicine therapy in familial Mediterranean fever. A controlled, double-blind study. Ann Intern Med 1974; 81: 792-794
• 44 Hashkes PJ, Spalding SJ, Giannini EH et al. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med 2012; 157: 533-541
• 45 Heller H, Gafni J, Michaeli D et al. The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 1966; 9: 1-17
• 46 Hoffman HM, Mueller JL, Broide DH et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature genetics 2001; 29: 301-305
• 47 Houten SM, Kuis W, Duran M et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nature genetics 1999; 22: 175-177
• 48 Houten SM, van Woerden CS, Wijburg FA et al. Carrier frequency of the V377I (1129 G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet 2003; 11: 96-200
• 49 Janka G. Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr 2009; 221: 278-285
• 50 Jeru I, Duquesnoy P, Fernandes-Alnemri T et al. Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci USA 2008; 105: 1614-1619
• 51 Jeske M, Lohse P, Kallinich T et al. Genotype-Phenotype and Genotype-Origin Correlations in Children with Mediterranean Fever in Germany – an AID-Net Study. Klin Padiatr 2013; 225: 325-330
• 52 Jordan CT, Cao L, Roberson ED et al. PSORS2 is due to mutations in CARD14. Am J Hum Genet 2012; 90: 784-795
• 53 Kallinich T, Haffner D, Niehues T et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics 2007; 119: e474-e483
• 54 Kanariou M, Dracou C, Spanou K et al. Twenty year follow-up of a patient with a new de-novo NLRP3 mutation (S595G) and CINCA syndrome. Klin Padiatr 2009; 221: 379-381
• 55 Kanazawa N. Nakajo-Nishimura syndrome: an autoinflammatory disorder showing pernio-like rashes and progressive partial lipodystrophy. Allergol int 2012; 61: 197-206
• 56 Klein AK, Horneff G. Improvement of sensoneurinal hearing loss in a patient with Muckle-Wells syndrome treated with anakinra. Klin Padiatr 2010; 222: 266-268
• 57 Kluk J, Rustin M, Brogan PA et al. CANDLE Syndrome: a report of a novel mutation and review of the literature. Br J Dermatol. 2013 DOI:
• 58 Kolly L, Busso N, von Scheven-Gete A et al. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1beta production. J Allergy Clin Immunol 2013; 131: 1635-1643
• 59 Kone-Paut I, Piram M. Targeting interleukin-1beta in CAPS (cryopyrin-associated periodic) syndromes: what did we learn?. Autoimmun Rev 2012; 12: 77-80
• 60 Krudewig J, Baumann U, Bernuth von H et al. Interdisciplinary AWMF guideline for the treatment of primary antibody deficiencies. Klin Padiatrie 2012; 224: 404-415
• 61 Lachmann HJ, Goodman HJ, Gilbertson JA et al. Natural history and outcome in systemic AA amyloidosis. N Eng J Med 2007; 356: 2361-2371
• 62 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. 2013 DOI: 10.1136/annrheumdis-2013-204184
• 63 Lainka E, Bielak M, Lohse P et al. Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population. Eur J Pediatr 2012; 171: 1775-1785
• 64 Lainka E, Neudorf U, Lohse P et al. Analysis of cryopyrin-associated periodic syndromes (CAPS) in German children: epidemiological, clinical and genetic characteristics. Klin Padiatr 2010; 222: 356-361
• 65 Lainka E, Neudorf U, Lohse P et al. Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children. Rheumatol Int 2012; 32: 3253-3260
• 66 Lainka E, Neudorf U, Lohse P et al. Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics. Rheumatology (Oxford) 2009; 48: 987-991
• 67 Larsen CM, Faulenbach M, Vaag A et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 2009; 32: 1663-1668
• 68 Lindor NM, Arsenault TM, Solomon H et al. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc 1997; 72: 611-615
• 69 Liu Y, Ramot Y, Torrelo A et al. Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum 2012; 64: 895-907
• 70 Lucherini OM, Obici L, Ferracin M et al. First Report of Circulating MicroRNAs in Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS). PloS one 2013; 8: e73443
• 71 Majeed HA, Al-Tarawna M, El-Shanti H et al. The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. Report of a new family and a review. Eur J Pediatr 2001; 160: 705-710
• 72 Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Eng J Med 2011; 365: 620-628
• 73 Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol 2009; 27: 229-265
• 74 Masters SL, Simon A, Aksentijevich I et al. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol 2009; 27: 621-668
• 75 McDermott MF, Aksentijevich I, Galon J et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999; 97: 133-144
• 76 Meinzer U, Quartier P, Alexandra JF et al. Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature. Sem arthr rheum 2011; 41: 265-271
• 77 Moser C, Pohl G, Haslinger I et al. Successful treatment of familial Mediterranean fever with Anakinra and outcome after renal transplantation. Nephrol Dial Transplant 2009; 24: 676-678
• 78 Obici L, Meini A, Cattalini M et al. Favourable and sustained response to anakinra in tumour necrosis factor receptor-associated periodic syndrome (TRAPS) with or without AA amyloidosis. Ann Rheum Dis 2011; 70: 1511-1512
• 79 Ombrello MJ, Remmers EF, Sun G et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Eng J Med 2012; 366: 330-338
• 80 Omenetti A, Carta S, Delfino L et al. Increased NLRP3-dependent interleukin 1beta secretion in patients with familial Mediterranean fever: correlation with MEFV genotype. Ann Rheum Dis 2014; 73: 462-469
• 81 Ozcakar ZB, Yalcinkaya F. Vascular comorbidities in familial Mediterranean fever. Rheumatol Int 2011; 31: 1275-1281
• 82 Ozen S, Bilginer Y, Aktay Ayaz N et al. Anti-interleukin 1 treatment for patients with familial Mediterranean fever resistant to colchicine. J rheumatol 2011; 38: 516-518
• 83 Pachlopnik Schmid J, de Saint Basile G. Angeborene hamophagozytische Lymphohistiozytose (HLH). Klin Padiatr 2010; 222: 345-350
• 84 Pelagatti MA, Meini A, Caorsi R et al. Long-term clinical profile of children with the low-penetrance R92Q mutation of the TNFRSF1A gene. Arthritis Rheum 2011; 63: 1141-1150
• 85 Peridis S, Pilgrim G, Koudoumnakis E et al. PFAPA syndrome in children: A meta-analysis on surgical vs. medical treatment. Int J Pediatr Otorhinolaryngol 2010; 74: 1203-1208
• 86 Reddy S, Jia S, Geoffrey R et al. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Eng J Med 2009; 360: 2438-2444
• 87 Renko M, Salo E, Putto-Laurila A et al. A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr 2007; 151: 289-292
• 88 Rittore C, Sanchez E, Soler S et al. Identification of a new exon 2-skipped TNFR1 transcript: regulation by three functional polymorphisms of the TNFR-associated periodic syndrome (TRAPS) gene. Ann Rheum Dis. 2013 DOI: 10.1136/annrheumdis-2012-203023
• 89 Rose CD, Martin TM, Wouters CH. Blau syndrome revisited. Curr Opin Rheumatol 2011; 23: 411-418
• 90 Salai M, Langevitz P, Blankstein A et al. Total hip replacement in familial Mediterranean fever. Bull Hosp Jt Dis 1993; 53: 25-28
• 91 Sander O, Westenfeld R, Hetzel G. Therapie der Amyloidose bei Familiärem Mittelmeerfieber – eine Kasuistik und Literaturrecherche. Z Rheumatol 2012; 71: S55
• 92 Schlesinger N, Alten RE, Bardin T et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012; 71: 1839-1848
• 93 Schwartz T, Langevitz P, Zemer D et al. Increased incidence of Behcet disease (BD) in familial Mediterranean fever. In: Sohar E, Gafni J, Pras M. Hrsg Familial Mediterranean fever. Tel Aviv: 1997: 148-150
• 94 Sfriso P, Caso F, Tognon S et al. Blau syndrome, clinical and genetic aspects. Autoimmun Rev 2012; 12: 44-51
• 95 Simon A, Drenth JP, Matern D et al. Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable periodic fevers. Mol gen metabol 2013; 108: 166-171
• 96 Simon A, Drewe E, van der Meer JW et al. Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Clin pharmacol ther 2004; 75: 476-483
• 97 Simon A, van der Meer JW, Drenth JP. Familial Mediterranean fever – a not so unusual cause of abdominal pain. Best Pract Res Clin Gastroenterol 2005; 19: 199-213
• 98 Simonini G, Xu Z, Caputo R et al. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum 2012; 65: 513-518
• 99 Stankovic Stojanovic K, Delmas Y, Torres PU et al. Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure. Nephrol Dial Transplant 2011; 27: 1898-1901
• 100 Stoffels M, Szperl A, Simon A et al. MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease. Ann Rheum Dis 2014; 73: 455-461
• 101 Stojanov S, McDermott MF. The tumour necrosis factor receptor-associated periodic syndrome: current concepts. Expert Rev Mol Med 2005; 7: 1-18
• 102 Tanaka N, Izawa K, Saito MK et al. High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 2011; 63: 3625-3632
• 103 Tasliyurt T, Yigit S, Rustemoglu A et al. Common MEFV gene mutations in Turkish patients with Behcet’s disease. Gene 2013; 530: 100-103
• 104 Ter Haar N, Lachmann H, Ozen S et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis 2013; 72: 678-685
• 105 Torrelo A, Patel S, Colmenero I et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol 2010; 62: 489-495
• 106 Tran AP, Edelman J. Interleukin-1 inhibition by anakinra in refractory chronic tophaceous gout. Int J Rheum Dis 2011; 14: e33-e37
• 107 Tsitsami E, Papadopoulou C, Speletas M. A case of hyperimmunoglobulinemia d syndrome successfully treated with canakinumab. Case rep rheumatol 2013; 2013 795027
• 108 Tunca M, Akar S, Onen F et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11
• 109 Turner MD, Chaudhry A, Nedjai B. Tumour necrosis factor receptor trafficking dysfunction opens the TRAPS door to pro-inflammatory cytokine secretion. Biosci Rep 2012; 32: 105-112
• 110 Valenzuela PM, Araya A, Perez CI et al. Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Clin Rheumatol. 2013 DOI:
• 111 Vigo G, Zulian F. Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA). Autoimmun Rev 2012; 12: 52-55
• 112 Wise CA, Bennett LB, Pascual V et al. Localization of a gene for familial recurrent arthritis. Arthritis Rheum 2000; 43: 2041-2045
• 113 Yalcinkaya F, Cakar N, Misirlioglu M et al. Genotype-phenotype correlation in a large group of Turkish patients with familial mediterranean fever: evidence for mutation-independent amyloidosis. Rheumatology (Oxford) 2000; 39: 67-72
• 114 Yalcinkaya F, Ozen S, Ozcakar ZB et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford) 2009; 48: 395-398
• 115 Yazgan H, Gultekin E, Yazicilar O et al. Comparison of conventional and low dose steroid in the treatment of PFAPA syndrome: preliminary study. Int J Pediatr Otorhinolaryngol 2012; 76: 1588-1590
• 116 Zhou Q, Lee GS, Brady J et al. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet 2012; 91: 713-720