Abstract
Background: In the last decade, we have come to better understand and manage the vasculitides. The classification of vasculitides has been revised. Genome- wide association studies and linkage analyses have been undertaken in hope of better understanding the pathogenesis of vasculitides. Comprehensive genetic studies have highlighted new pathways that may guide us in more targeted therapies. Description of the monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), Haploinsufficiency of A20 (HA20), have introduced a new perspective to vasculopathies, and introduced alternative treatments for these diseases.
Conclusion: In this review, the important discoveries in pathogenesis and consensus treatment recommendations from the past decade will be summarized.
Keywords: Systemic vasculitis, treatment, pathogenesis, DADA2, genetic studies, pathways.
Graphical Abstract
[1]
Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 2010; 69(5): 798-806.
[2]
Ruperto N, Ozen S, Pistorio A, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis 2010; 69(5): 790-7.
[3]
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65(1): 1-11.
[4]
Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev 2017; 16(12): 1246-53.
[5]
Novak J, Rizk D, Takahashi K, et al. New Insights into the Pathogenesis of IgA Nephropathy. Kidney Dis (Basel) 2015; 1(1): 8-18.
[6]
Yang YH, Huang YH, Lin YL, et al. Circulating IgA from acute stage of childhood Henoch-Schönlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway. Clin Exp Immunol 2006; 144(2): 247-53.
[7]
Gülhan B, Orhan D, Kale G, Besbas N, Özen S. Studying cytokines of T helper cells in the kidney disease of IgA vasculitis (Henoch-Schönlein purpura). Pediatr Nephrol 2015; 30(8): 1269-77.
[8]
Goldstein AR, White RH, Akuse R, Chantler C. Long-term follow-up of childhood Henoch-Schönlein nephritis. Lancet 1992; 339(8788): 280-2.
[9]
Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schönlein Purpura in adults: outcome and prognostic factors. J Am Soc Nephrol 2002; 13(5): 1271-8.
[10]
Shrestha S, Sumingan N, Tan J, Alhous H, McWilliam L, Ballardie F. Henoch Schönlein purpura with nephritis in adults: adverse prognostic indicators in a UK population. QJM 2006; 99(4): 253-65.
[11]
Uppal SS, Hussain MA, Al-Raqum HA, et al. Henoch-Schönlein’s purpura in adults versus children/adolescents: A comparative study. Clin Exp Rheumatol 2006; 24(2)(Suppl. 41): S26-30.
[12]
Eleftheriou D, Batu ED, Ozen S, Brogan PA. Vasculitis in children. Nephrol Dial Transplant 2015; 30(Suppl. 1): i94-i103.
[14]
Ozen S. The spectrum of vasculitis in children. Best Pract Res Clin Rheumatol 2002; 16(3): 411-25.
[15]
Chartapisak W, Opastiraku S, Willis NS, Craig JC, Hodson EM. Prevention and treatment of renal disease in Henoch-Schönlein purpura: A systematic review. Arch Dis Child 2009; 94(2): 132-7.
[16]
Langford C. Clinical features and diagnosis of small-vessel vasculitis. Cleve Clin J Med 2012; 79(Suppl. 3): S3-7.
[17]
Guillevin L, Durand-Gasselin B, Cevallos R, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 1999; 42(3): 421-30.
[18]
Iudici M, et al. Childhood- versus adult-onset ANCA-associated vasculitides: A nested, matched case-control study from the French Vasculitis Study Group Registry. Autoimmun Rev 2017.
[19]
Zwerina J, Eger G, Englbrecht M, Manger B, Schett G. Churg-Strauss syndrome in childhood: A systematic literature review and clinical comparison with adult patients. Semin Arthritis Rheum 2009; 39(2): 108-15.
[20]
Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 2012; 367(3): 214-23.
[21]
Carr EJ, Niederer HA, Williams J, et al. Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis. BMC Med Genet 2009; 10: 121.
[22]
Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 1994; 120(1): 12-7.
[23]
Laudien M, Gadola SD, Podschun R, et al. Nasal carriage of Staphylococcus aureus and endonasal activity in Wegener s granulomatosis as compared to rheumatoid arthritis and chronic Rhinosinusitis with nasal polyps. Clin Exp Rheumatol 2010; 28(1)(Suppl. 57): 51-5.
[24]
Kain R, Exner M, Brandes R, et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 2008; 14(10): 1088-96.
[25]
Miller FW, Alfredsson L, Costenbader KH, et al. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun 2012; 39(4): 259-71.
[26]
Sangaletti S, Tripodo C, Chiodoni C, et al. Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity. Blood 2012; 120(15): 3007-18.
[27]
Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75(9): 1583-94.
[28]
Detoraki A, Di Capua L, Varricchi G, Genovese A, Marone G, Spadaro G. Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: A 36-month follow-up study. J Asthma 2016; 53(2): 201-6.
[29]
Jachiet M, Samson M, Cottin V, et al. Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients. Arthritis Rheumatol 2016; 68(9): 2274-82.
[30]
Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 2017; 376(20): 1921-32.
[31]
Shimojima Y, Ishii W, Kishida D, Fukushima K, Ikeda SI. Imbalanced expression of dysfunctional regulatory T cells and T-helper cells relates to immunopathogenesis in polyarteritis nodosa. Mod Rheumatol 2017; 27(1): 102-9.
[32]
Ozen S, Anton J, Arisoy N, et al. Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr 2004; 145(4): 517-22.
[33]
Alibaz-Oner F, Koster MJ, Crowson CS, et al. Clinical Spectrum of Medium-Sized Vessel Vasculitis. Arthritis Care Res (Hoboken) 2017; 69(6): 884-91.
[34]
Ozen S. The changing face of polyarteritis nodosa and necrotizing vasculitis. Nat Rev Rheumatol 2017; 13(6): 381-6.
[35]
Erden A, Batu ED, Sönmez HE, et al. Comparing polyarteritis nodosa in children and adults: a single center study. Int J Rheum Dis 2017; 20(8): 1016-22.
[36]
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): 1-11.
[37]
Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014; 370(10): 921-31.
[38]
Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014; 370(10): 911-20.
[39]
Batu ED, Karadag O, Taskiran EZ, et al. A Case Series of Adenosine Deaminase 2-deficient Patients Emphasizing Treatment and Genotype-phenotype Correlations. J Rheumatol 2015; 42(8): 1532-4.
[40]
Van Eyck L Jr, et al. Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency J Allergy Clin Immunol 2015; 135(1): 283-7 e5.
[41]
Caorsi R, Penco F, Grossi A, et al. ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: A multicentre national study. Ann Rheum Dis 2017; 76(10): 1648-56.
[42]
Caorsi R, Penco F, Schena F, Gattorno M. Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatr Rheumatol Online J 2016; 14(1): 51.
[43]
Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009; 68(3): 310-7.
[44]
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation 2017; 135(17): e927-99.
[45]
Burns JC, Herzog L, Fabri O, et al. Seasonality of Kawasaki disease: a global perspective. PLoS One 2013; 8(9): e74529.
[46]
Lee YC, Kuo HC, Chang JS, et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 2012; 44(5): 522-5.
[47]
Onouchi Y, Ozaki K, Burns JC, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 2012; 44(5): 517-21.
[48]
Kuo HC, Yang KD, Juo SH, et al. ITPKC single nucleotide polymorphism associated with the Kawasaki disease in a Taiwanese population. PLoS One 2011; 6(4): e17370.
[49]
Kuo HC, Yu HR, Juo SH, et al. CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children. J Hum Genet 2011; 56(2): 161-5.
[50]
Khor CC, Davila S, Breunis WB, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet 2011; 43(12): 1241-6.
[51]
Alphonse MP, Duong TT, Shumitzu C, et al. Inositol-Triphosphate 3-Kinase C Mediates Inflammasome Activation and Treatment Response in Kawasaki Disease. J Immunol 2016; 197(9): 3481-9.
[52]
Egami K, Muta H, Ishii M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr 2006; 149(2): 237-40.
[53]
Sano T, Kurotobi S, Matsuzaki K, et al. Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr 2007; 166(2): 131-7.
[54]
Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 2006; 113(22): 2606-12.
[55]
Davies S, Sutton N, Blackstock S, et al. Predicting IVIG resistance in UK Kawasaki disease. Arch Dis Child 2015; 100(4): 366-8.
[56]
Berdej-Szczot E, Małecka-Tendera E, Gawlik T, Firek-Pędras M, Szydłowski L, Gawlik A. Risk factors of immunoglobulin resistance and coronary complications in children with Kawasaki disease. Kardiol Pol 2017; 75(3): 261-6.
[57]
Renauer P, Sawalha AH. The genetics of Takayasu arteritis. Presse Med 2017; 46(7-8 Pt 2): e179-87.
[58]
Arnaud L, Haroche J, Mathian A, Gorochov G, Amoura Z. Pathogenesis of Takayasu’s arteritis: A 2011 update. Autoimmun Rev 2011; 11(1): 61-7.
[59]
Park MC, Lee SW, Park YB, Lee SK. Serum cytokine profiles and their correlations with disease activity in Takayasu’s arteritis. Rheumatology (Oxford) 2006; 45(5): 545-8.
[60]
Terao C, et al. Ustekinumab as a therapeutic option for Takayasu arteritis: from genetic findings to clinical application. Scand J Rheumatol 2015; 1-3.
[61]
Terao C, Yoshifuji H, Kimura A, et al. Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population. Am J Hum Genet 2013; 93(2): 289-97.
[62]
Brunner J, Feldman BM, Tyrrell PN, et al. Takayasu arteritis in children and adolescents. Rheumatology (Oxford) 2010; 49(10): 1806-14.
[63]
Morales E, Pineda C, Martínez-Lavín M. Takayasu’s arteritis in children. J Rheumatol 1991; 18(7): 1081-4.
[64]
Watson L, Brogan P, Peart I, Landes C, Barnes N, Cleary G. Diagnosis and assessment of disease activity in takayasu arteritis: a childhood case illustrating the challenge. Case Rep Rheumatol 2014; 2014: 603171.
[65]
Chun YS, Park SJ, Park IK, Chung H, Lee J. The clinical and ocular manifestations of Takayasu arteritis. Retina 2001; 21(2): 132-40.
[66]
Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2009; 68(3): 318-23.
[67]
Eleftheriou D, Varnier G, Dolezalova P, McMahon AM, Al-Obaidi M, Brogan PA. Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom. Arthritis Res Ther 2015; 17: 36.
[68]
Ozen S, Duzova A, Bakkaloglu A, et al. Takayasu arteritis in children: preliminary experience with cyclophosphamide induction and corticosteroids followed by methotrexate. J Pediatr 2007; 150(1): 72-6.
[69]
Tanaka F, Kawakami A, Iwanaga N, et al. Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med 2006; 45(5): 313-6.
[70]
Nakaoka Y, Higuchi K, Arita Y, et al. Tocilizumab for the treatment of patients with refractory Takayasu arteritis. Int Heart J 2013; 54(6): 405-11.
[71]
Batu ED, Sönmez HE, Hazırolan T, Özaltın F, Bilginer Y, Özen S. Tocilizumab treatment in childhood Takayasu arteritis: Case series of four patients and systematic review of the literature. Semin Arthritis Rheum 2017; 46(4): 529-35.
[72]
Keser G, Aksu K. What is new in management of Takayasu arteritis? Presse Med 2017; 46(7-8 Pt 2): e229-35.
[73]
Davatchi F, Sadeghi Abdollahi B, Chams-Davatchi C, et al. The saga of diagnostic/classification criteria in Behcet’s disease. Int J Rheum Dis 2015; 18(6): 594-605.
[74]
Disease, I.T.f.t.R.o.t.I.C.f.B.s., Evaluation of the international criteria for Behçet’s disease (ICBD). Clin Exp Immunol 2006; 24(Suppl. 42): S13.
[75]
Disease, I.T.f.t.R.o.t.I.C.f.B.s., Revision of the international criteria for Behçet’s disease (ICBD). Clin Exp Rheumatol 2006; 24(Suppl. 42): S14-5.
[76]
The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014; 28(3): 338-47.
[77]
Kone-Paut I, et al. Consensus classification criteria for paediatric Behcet's disease from a prospective observational cohort: PEDBD. Ann Rheum Dis An important international collaborative study that led to devised a clasiffiation criteria for Behçet's Disease 2015.
[78]
Batu ED, Sönmez HE, Sözeri B, Butbul Aviel Y, Bilginer Y, Özen S. The performance of different classification criteria in paediatric Behçet’s disease. Clin Exp Rheumatol 2017; 35(6)(Suppl. 108): 119-23.
[79]
Kim DK, Chang SN, Bang D, Lee ES, Lee S. Clinical analysis of 40 cases of childhood-onset Behçet’s disease. Pediatr Dermatol 1994; 11(2): 95-101.
[80]
Koné-Paut I, Darce-Bello M, Shahram F, et al. Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet’s disease: an international cohort study of 110 patients. One-year follow-up data. Rheumatology (Oxford) 2011; 50(1): 184-8.
[81]
Koné-Paut I, Yurdakul S, Bahabri SA, et al. Clinical features of Behçet’s disease in children: An international collaborative study of 86 cases. J Pediatr 1998; 132(4): 721-5.
[82]
Krause I, Uziel Y, Guedj D, et al. Childhood Behçet’s disease: clinical features and comparison with adult-onset disease. Rheumatology (Oxford) 1999; 38(5): 457-62.
[83]
Pivetti-Pezzi P, Accorinti M, Abdulaziz MA, La Cava M, Torella M, Riso D. Behçets disease in children. Jpn J Ophthalmol 1995; 39(3): 309-14.
[84]
Nanthapisal S, Klein NJ, Ambrose N, Eleftheriou D, Brogan PA. Paediatric Behçet’s disease: A UK tertiary centre experience. Clin Rheumatol 2016; 35(10): 2509-16.
[85]
de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behçet’s disease: a systematic review and meta-analysis of case-control genetic association studies. Arthritis Rheum 2009; 61(10): 1287-96.
[86]
Remmers EF, Cosan F, Kirino Y, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease. Nat Genet 2010; 42(8): 698-702.
[87]
Mizuki N, Meguro A, Ota M, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat Genet 2010; 42(8): 703-6.
[88]
Fei Y, Webb R, Cobb BL, Direskeneli H, Saruhan-Direskeneli G, Sawalha AH. Identification of novel genetic susceptibility loci for Behçet’s disease using a genome-wide association study. Arthritis Res Ther 2009; 11(3): R66.
[89]
Kirino Y, Bertsias G, Ishigatsubo Y, et al. Genome-wide association analysis identifies new susceptibility loci for Behçet’s disease and epistasis between HLA-B*51 and ERAP1. Nat Genet 2013; 45(2): 202-7.
[90]
Lee YJ, Horie Y, Wallace GR, et al. Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet’s disease. Ann Rheum Dis 2013; 72(9): 1510-6.
[91]
Hou S, Yang Z, Du L, et al. Identification of a susceptibility locus in STAT4 for Behçet’s disease in Han Chinese in a genome-wide association study. Arthritis Rheum 2012; 64(12): 4104-13.
[93]
Takeuchi M, Ombrello MJ, Kirino Y, et al. A single endoplasmic reticulum aminopeptidase-1 protein allotype is a strong risk factor for Behçet’s disease in HLA-B*51 carriers. Ann Rheum Dis 2016; 75(12): 2208-11.
[94]
Takeuchi M, Mizuki N, Meguro A, et al. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet’s disease susceptibility. Nat Genet 2017; 49(3): 438-43.
[96]
Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet’s syndrome--a phase 2, placebo-controlled study. N Engl J Med 2015; 372(16): 1510-8.
[97]
Gül A, Tugal-Tutkun I, Dinarello CA, et al. Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis 2012; 71(4): 563-6.
[98]
Grayson PC, Yazici Y, Merideth M, et al. Treatment of mucocutaneous manifestations in Behçet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther 2017; 19(1): 69.
[99]
Mirouse A, Barete S, Monfort JB, et al. Ustekinumab for Behçet’s disease. J Autoimmun 2017; 82: 41-6.
[100]
Caso F, Costa L, Rigante D, et al. Biological treatments in Behçet’s disease: Beyond anti-TNF therapy. Mediators Inflamm 2014; 2014: 107421.
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