Skip to main content

Advertisement

Log in

Sex Differences in Pediatric Rheumatology

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Autoimmune diseases affect up to 10% of the world's population and, as a whole, they are far more common in females, although differences exist according to the single disease and also in different age groups. In childhood-onset autoimmune diseases, the sex bias is generally less evident than in adults, probably for the different hormonal milieau, being estrogens strongly implicated in the development of autoimmunity. Still, some rheumatic conditions, such as juvenile idiopathic arthritis (JIA), show a strong predilection for girls (F:M = 3–6.6:1), and differences may coexist between males and females regarding disease outcome. For example, chronic anterior uveitis associated with JIA affects more commonly girls but boys tend to have a more severe course. Systemic lupus erythematosus predominantly affects girls and women (F:M = 3–5:1 in children, F:M = 10–15:1 in adults). Behςet’s disease has been reported to be more prevalent in adult males (F:M = 1:1–4); in children, there are no differences. The sex ratio is equal in children and adults for Henoch-Schönlein purpura (F:M = 1:1). A higher male-to-female ratio exists for Kawasaki disease (F:M = 1:1.1–1.6 in children, F:M = 1:1,5 in adults). Juvenile dermatomyositis (F:M = 2–5:1), systemic sclerosis (F:M = 4:1 in children, F:M = 6:1 in adults), and Takayasu arteritis (F:M = 2:1 in children, F:M = 7–9:1 in adults) are more common in girls and women then in boys and men. There is no gender bias for acute rheumatic fever in children, while in adults, the F:M ratio is 2:1. Given that estrogen levels are not different between genders during childhood, pediatric rheumatic diseases could represent good models to study other mechanisms related to the development of autoimmunity. Recently, the levels of miRNA expression, and their variation according to sex chromosomes, have been linked to the development of autoimmune diseases, with different impact among sexes. This review will focus not only on the sex bias reported in the more common rheumatic conditions of childhood, focusing on differences in incidence, but also on outcome and trying to depict the mechanisms underlying those differences.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brickman CM, Shoenfeld Y (2001) The mosaic of autoimmunity. Scand J Clin Lab Invest Suppl 235:3–15

    CAS  PubMed  Google Scholar 

  2. Xie X, Miao L, Yao J et al (2013) Role of multiple microRNAs in the sexually dimorphic expression of Cyp2b9 in mouse liver. Drug Metab Dispos 41:1732–1737. https://doi.org/10.1124/dmd.113.052217

    Article  CAS  PubMed  Google Scholar 

  3. Dai R, Ahmed SA (2011) MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res 157:163–179. https://doi.org/10.1016/j.trsl.2011.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Guo X, Su B, Zhou Z, Sha J (2009) Rapid evolution of mammalian X-linked testis microRNAs. BMC Genomics 10:97. https://doi.org/10.1186/1471-2164-10-97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pinheiro I, Dejager L, Libert C (2011) X-chromosome-located microRNAs in immunity: might they explain male/female differences? BioEssays 33:791–802. https://doi.org/10.1002/bies.201100047

    Article  CAS  PubMed  Google Scholar 

  6. Selmi C, Brunetta E, Raimondo MG, Meroni PL (2012) The X chromosome and the sex ratio of autoimmunity. Autoimmun Rev 11:A531–A537. https://doi.org/10.1016/j.autrev.2011.11.024

    Article  CAS  PubMed  Google Scholar 

  7. Takeno M, Nagafuchi H, Kaneko S et al (1997) Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production. J Immunol 158:3529–3538

    CAS  PubMed  Google Scholar 

  8. Menasha J, Levy B, Hirschhorn K, Kardon NB (2005) Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med 7:251–263. https://doi.org/10.1097/01.GIM.0000160075.96707.04

  9. Germain EL, Plotnick LP (1986) Age-related anti-thyroid antibodies and thyroid abnormalities in Turner syndrome. Acta Paediatr Scand 75:750–755

    Article  CAS  PubMed  Google Scholar 

  10. Price WH (1979) A high incidence of chronic inflammatory bowel disease in patients with Turner’s syndrome. J Med Genet 16:263–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jørgensen KT, Rostgaard K, Bache I et al (2010) Autoimmune diseases in women with Turner’s syndrome. Arthritis Rheum 62:658–666. https://doi.org/10.1002/art.27270

    Article  CAS  PubMed  Google Scholar 

  12. Arslan D, Kuyucu T, Kendirci M, Kurtoglu S (2000) Celiac disease and Turner’s syndrome: patient report. J Pediatr Endocrinol Metab 13:1629–1631

    CAS  PubMed  Google Scholar 

  13. Rujner J, Wisniewski A, Gregorek H et al (2001) Coeliac disease and HLA-DQ 2 (DQA1* 0501 and DQB1* 0201) in patients with Turner syndrome. J Pediatr Gastroenterol Nutr 32:114–115

    Article  CAS  PubMed  Google Scholar 

  14. Scarpa R, Lubrano E, Castiglione F et al (1996) Juvenile rheumatoid arthritis, Crohn’s disease and Turner’s syndrome: a novel association. Clin Exp Rheumatol 14:449–450

    CAS  PubMed  Google Scholar 

  15. Zulian F, Schumacher HR, Calore A et al (1999) Juvenile arthritis in Turner’s syndrome: a multicenter study. Clin Exp Rheumatol 16:489–494

    Google Scholar 

  16. Accorinti M, La Cava M, Speranza S, Pivetti-Pezzi P (2002) Uveitis in Turner’s syndrome. Graefes Arch Clin Exp Ophthalmol 240:529–532. https://doi.org/10.1007/s00417-002-0481-z

    Article  PubMed  Google Scholar 

  17. Tsunekawa H, Ohno-Jinno A, Zako M (2007) Uveitis in 2 cases of Turner’s syndrome. Can J Ophthalmol 42:756–757. https://doi.org/10.3129/i07-120

    Article  PubMed  Google Scholar 

  18. Ober C, Loisel DA, Gilad Y (2008) Sex-specific genetic architecture of human disease. Nat Rev Genet 9:911–922. https://doi.org/10.1038/nrg2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pauklin S, Sernández IV, Bachmann G et al (2009) Estrogen directly activates AID transcription and function. J Exp Med 206:99–111. https://doi.org/10.1084/jem.20080521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Smith-Bouvier DL, Divekar AA, Sasidhar M et al (2008) A role for sex chromosome complement in the female bias in autoimmune disease. J Exp Med 205:1099–1108. https://doi.org/10.1084/jem.20070850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tucker LB, Uribe AG, Fernández M et al (2008) Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus 17:314–322. https://doi.org/10.1177/0961203307087875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lleo A, Battezzati PM, Selmi C et al (2008) Is autoimmunity a matter of sex? Autoimmun Rev 7:626–630. https://doi.org/10.1016/j.autrev.2008.06.009

    Article  CAS  PubMed  Google Scholar 

  23. Maloney KC, Ferguson TS, Stewart HD et al (2017) Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis. Lupus 96120331770782. https://doi.org/10.1177/0961203317707828

  24. Rider V, Li X, Peterson G et al (2006) Differential expression of estrogen receptors in women with systemic lupus erythematosus. J Rheumatol 33:1093–1101

    CAS  PubMed  Google Scholar 

  25. Gourdy P, Araujo LM, Zhu R et al (2005) Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN-gamma production by invariant natural killer T cells. Blood 105:2415–2420. https://doi.org/10.1182/blood-2004-07-2819

    Article  CAS  PubMed  Google Scholar 

  26. Shen H, Panchanathan R, Rajavelu P et al (2010) Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity. J Mol Cell Biol 2:284–290. https://doi.org/10.1093/jmcb/mjq023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dai R, Phillips RA, Zhang Y et al (2008) Suppression of LPS-induced interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood 112:4591–4597. https://doi.org/10.1182/blood-2008-04-152488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dong G, Fan H, Yang Y et al (2015) 17β-estradiol enhances the activation of IFN-α signaling in B cells by down-regulating the expression of let-7e-5p, miR-98-5p and miR-145a-5p that target IKKε. Biochim Biophys Acta 1852:1585–1598. https://doi.org/10.1016/j.bbadis.2015.04.019

    Article  CAS  PubMed  Google Scholar 

  29. Pan W, Zhu S, Yuan M et al (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781. https://doi.org/10.4049/jimmunol.0904060

    Article  CAS  PubMed  Google Scholar 

  30. Sawalha AH, Webb R, Han S et al (2008) Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS One 3:e1727. https://doi.org/10.1371/journal.pone.0001727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lu L-J, Wallace D, Ishimori M et al (2010) Review: male systemic lupus erythematosus: a review of sex disparities in this disease. Lupus 19:119–129. https://doi.org/10.1177/0961203309350755

    Article  PubMed  Google Scholar 

  32. Li J, McMurray RW (2007) Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model. Clin Immunol 123:219–226. https://doi.org/10.1016/j.clim.2007.01.008

    Article  CAS  PubMed  Google Scholar 

  33. Scofield RH, Bruner GR, Namjou B et al (2008) Klinefelter’s syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58:2511–2517. https://doi.org/10.1002/art.23701

    Article  PubMed  PubMed Central  Google Scholar 

  34. Young NA, Wu L-C, Burd CJ et al (2014) Estrogen modulation of endosome-associated toll-like receptor 8: an IFNα-independent mechanism of sex-bias in systemic lupus erythematosus. Clin Immunol 151:66–77. https://doi.org/10.1016/j.clim.2014.01.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sthoeger ZM, Geltner D, Rider A, Bentwich Z (1987) Systemic lupus erythematosus in 49 Israeli males: a retrospective study. Clin Exp Rheumatol 5:233–240

    CAS  PubMed  Google Scholar 

  36. Liang Y, Leng R-X, Pan H-F, Ye D-Q (2017) The prevalence and risk factors for serositis in patients with systemic lupus erythematosus: a cross-sectional study. Rheumatol Int 37:305–311. https://doi.org/10.1007/s00296-016-3630-0

    Article  CAS  PubMed  Google Scholar 

  37. Specker C, Becker A, Lakomek HJ et al (1994) Systemic lupus erythematosus in men—a different prognosis? Z Rheumatol 53:339–345

    CAS  PubMed  Google Scholar 

  38. Font J, Cervera R, Navarro M et al (1992) Systemic lupus erythematosus in men: clinical and immunological characteristics. Ann Rheum Dis 51:1050–1052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. López P, Mozo L, Gutiérrez C, Suárez A (2003) Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features. Lupus 12:860–865. https://doi.org/10.1191/0961203303lu469xx

    Article  PubMed  Google Scholar 

  40. Lo JT, Tsai MJ, Wang LH et al (1999) Sex differences in pediatric systemic lupus erythematosus: a retrospective analysis of 135 cases. J Microbiol Immunol Infect 32:173–178

    CAS  PubMed  Google Scholar 

  41. Hui-Yuen JS, Christiano AM, Askanase A (2016) Sex differences in genomics in lupus: girls with systemic lupus have high interferon gene expression while boys have high levels of tumour necrosis factor-related gene expression. Scand J Rheumatol 45:394–396. https://doi.org/10.3109/03009742.2015.1132760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Voulgari PV, Katsimbri P, Alamanos Y, Drosos AA (2002) Gender and age differences in systemic lupus erythematosus. A study of 489 Greek patients with a review of the literature. Lupus 11:722–729. https://doi.org/10.1191/0961203302lu253oa

    Article  CAS  PubMed  Google Scholar 

  43. Medina G, Vera-Lastra O, Barile L et al (2004) Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: a comparative study of 73 patients. Lupus 13:11–16. https://doi.org/10.1191/0961203304lu482oa

    Article  CAS  PubMed  Google Scholar 

  44. Riveros Frutos A, Casas I, Rúa-Figueroa I et al (2017) Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort. Lupus 26:698–706. https://doi.org/10.1177/0961203316673728

    Article  CAS  PubMed  Google Scholar 

  45. Chiaroni-Clarke RC, Li YR, Munro JE et al (2015) The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes Immun 16:495–498. https://doi.org/10.1038/gene.2015.32

    Article  CAS  PubMed  Google Scholar 

  46. Sullivan DB, Cassidy JT, Petty RE (1975) Pathogenic implications of age of onset in juvenile rheumatoid arthritis. Arthritis Rheum 18:251–255

    Article  CAS  PubMed  Google Scholar 

  47. Adib N, Hyrich K, Thornton J et al (2008) Association between duration of symptoms and severity of disease at first presentation to paediatric rheumatology: results from the childhood arthritis prospective study. Rheumatology (Oxford) 47:991–995. https://doi.org/10.1093/rheumatology/ken085

    Article  CAS  Google Scholar 

  48. Li YR, Li J, Zhao SD et al (2015) Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nat Med 21:1018–1027. https://doi.org/10.1038/nm.3933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Uz E, Mustafa C, Topaloglu R et al (2009) Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritis. Arthritis Rheum 60:3410–3412. https://doi.org/10.1002/art.24956

    Article  PubMed  Google Scholar 

  50. Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

    PubMed  Google Scholar 

  51. Ladd JR, Cassidy JT, Martel W (1971) Juvenile ankylosing spondylitis. Arthritis Rheum 14:579–590

    Article  CAS  PubMed  Google Scholar 

  52. Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet (London, England) 369:767–778. https://doi.org/10.1016/S0140-6736(07)60363-8

    Article  CAS  Google Scholar 

  53. Giltay EJ, Popp-Snijders C, van Schaardenburg D et al (1998) Serum testosterone levels are not elevated in patients with ankylosing spondylitis. J Rheumatol 25:2389–2394

    CAS  PubMed  Google Scholar 

  54. Ravelli A, Felici E, Magni-Manzoni S et al (2005) Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis Rheum 52:826–832. https://doi.org/10.1002/art.20945

    Article  PubMed  Google Scholar 

  55. Tay-Kearney ML, Schwam BL, Lowder C et al (1996) Clinical features and associated systemic diseases of HLA-B27 uveitis. Am J Ophthalmol 121:47–56

    Article  CAS  PubMed  Google Scholar 

  56. Saurenmann RK, Levin AV, Feldman BM et al (2010) Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis. Arthritis Rheum 62:1824–1828. https://doi.org/10.1002/art.27416

    Article  CAS  PubMed  Google Scholar 

  57. Woreta F, Thorne JE, Jabs DA et al (2007) Risk factors for ocular complications and poor visual acuity at presentation among patients with uveitis associated with juvenile idiopathic arthritis. Am J Ophthalmol 143:647–655. https://doi.org/10.1016/j.ajo.2006.11.025

    Article  PubMed  Google Scholar 

  58. Thorne JE, Woreta F, Kedhar SR et al (2007) Juvenile idiopathic arthritis-associated uveitis: incidence of ocular complications and visual acuity loss. Am J Ophthalmol 143:840–846.e2. https://doi.org/10.1016/j.ajo.2007.01.033

    Article  PubMed  Google Scholar 

  59. Hoeve M, Kalinina Ayuso V, Schalij-Delfos NE et al (2012) The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty. Br J Ophthalmol 96:852–856. https://doi.org/10.1136/bjophthalmol-2011-301023

    Article  PubMed  Google Scholar 

  60. Shah M, Mamyrova G, Targoff IN et al (2013) The clinical phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine (Baltimore) 92:25–41. https://doi.org/10.1097/MD.0b013e31827f264d

    Article  CAS  Google Scholar 

  61. Ravelli A, Trail L, Ferrari C et al (2010) Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients. Arthritis Care Res (Hoboken) 62:63–72. https://doi.org/10.1002/acr.20015

    Article  Google Scholar 

  62. Sanner H, Gran J-T, Sjaastad I, Flato B (2009) Cumulative organ damage and prognostic factors in juvenile dermatomyositis: a cross-sectional study median 16.8 years after symptom onset. Rheumatology 48:1541–1547. https://doi.org/10.1093/rheumatology/kep302

    Article  PubMed  Google Scholar 

  63. Tansley SL, Betteridge ZE, Shaddick G et al (2014) Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset. Rheumatology (Oxford) 53:2204–2208. https://doi.org/10.1093/rheumatology/keu259

    Article  Google Scholar 

  64. Stübgen J-P (2017) Juvenile dermatomyositis/polymyositis and lymphoma. J Neurol Sci 377:19–24. https://doi.org/10.1016/j.jns.2017.03.033

    Article  PubMed  Google Scholar 

  65. Symmons DP, Sills JA, Davis SM (1995) The incidence of juvenile dermatomyositis: results from a nation-wide study. Br J Rheumatol 34:732–736

    Article  CAS  PubMed  Google Scholar 

  66. Miller FW, Cooper RG, Vencovský J et al (2013) Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum 65:3239–3247. https://doi.org/10.1002/art.38137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Miller FW, Chen W, O’Hanlon TP et al (2015) Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes. Genes Immun 16:470–480. https://doi.org/10.1038/gene.2015.28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lintner KE, Patwardhan A, Rider LG et al (2016) Gene copy-number variations (CNVs) of complement C4 and C4A deficiency in genetic risk and pathogenesis of juvenile dermatomyositis. Ann Rheum Dis 75:1599–1606. https://doi.org/10.1136/annrheumdis-2015-207762

    Article  CAS  PubMed  Google Scholar 

  69. Niewold TB, Kariuki SN, Morgan GA et al (2010) Gene-gene-sex interaction in cytokine gene polymorphisms revealed by serum interferon alpha phenotype in juvenile dermatomyositis. J Pediatr 157:653–657. https://doi.org/10.1016/j.jpeds.2010.04.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Dourmishev L, Kamenarska Z, Kaneva R et al (2014) Association between estrogen receptor-α gene polymorphisms and dermatomyositis in Bulgarian patients. Int J Dermatol 53:e363–e364. https://doi.org/10.1111/ijd.12322

    Article  CAS  PubMed  Google Scholar 

  71. Vacca A, Cormier C, Mathieu A et al (2011) Vitamin D levels and potential impact in systemic sclerosis. Clin Exp Rheumatol 29:1024–1031

    PubMed  Google Scholar 

  72. Elhai M, Avouac J, Walker UA et al (2016) A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 75:163–169. https://doi.org/10.1136/annrheumdis-2014-206386

    Article  PubMed  Google Scholar 

  73. Chifflot H, Fautrel B, Sordet C et al (2008) Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum 37:223–235. https://doi.org/10.1016/j.semarthrit.2007.05.003

    Article  PubMed  Google Scholar 

  74. LeRoy EC, Black C, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205

    CAS  PubMed  Google Scholar 

  75. Meier FMP, Frommer KW, Dinser R et al (2012) Update on the profile of the EUSTAR cohort: an analysis of the EULAR scleroderma trials and research group database. Ann Rheum Dis 71:1355–1360. https://doi.org/10.1136/annrheumdis-2011-200742

    Article  PubMed  Google Scholar 

  76. Jacobsen S, Halberg P, Ullman S (1998) Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma). Br J Rheumatol 37:750–755

    Article  CAS  PubMed  Google Scholar 

  77. Barnes J, Mayes MD (2012) Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol 24:165–170. https://doi.org/10.1097/BOR.0b013e32834ff2e8

    Article  PubMed  Google Scholar 

  78. Berdeli A, Ozyürek AR, Ulger Z et al (2006) Association of macrophage migration inhibitory factor gene -173 G/C polymorphism with prognosis in Turkish children with juvenile rheumatoid arthritis. Rheumatol Int 26:726–731. https://doi.org/10.1007/s00296-005-0062-7

    Article  CAS  PubMed  Google Scholar 

  79. Donn R, Alourfi Z, Zeggini E et al (2004) A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis. Arthritis Rheum 50:1604–1610. https://doi.org/10.1002/art.20178

    Article  PubMed  Google Scholar 

  80. Albers HM, Kurreeman FAS, Houwing-Duistermaat JJ et al (2008) The TRAF1/C5 region is a risk factor for polyarthritis in juvenile idiopathic arthritis. Ann Rheum Dis 67:1578–1580. https://doi.org/10.1136/ard.2008.089060

    Article  CAS  PubMed  Google Scholar 

  81. Prahalad S, Hansen S, Whiting A et al (2009) Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis. Arthritis Rheum 60:2124–2130. https://doi.org/10.1002/art.24618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hinks A, Ke X, Barton A et al (2009) Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis Rheum 60:251–257. https://doi.org/10.1002/art.24187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lamb R, Thomson W, Ogilvie E et al (2005) Wnt-1-inducible signaling pathway protein 3 and susceptibility to juvenile idiopathic arthritis. Arthritis Rheum 52:3548–3553. https://doi.org/10.1002/art.21392

    Article  CAS  PubMed  Google Scholar 

  84. Chiaroni-Clarke RC, Li YR, Munro JE et al (2015) The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes Immun 16:495–498. https://doi.org/10.1038/gene.2015.32

    Article  CAS  PubMed  Google Scholar 

  85. Goulielmos GN, Chiaroni-Clarke RC, Dimopoulou DG et al (2016) Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population. Pediatr Rheumatol Online J 14:25. https://doi.org/10.1186/s12969-016-0087-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sanjeevi CB, Miller EN, Dabadghao P et al (2000) Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis. Arthritis Rheum 43:1397–1404. https://doi.org/10.1002/1529-0131(200006)43:6<1397::AID-ANR25>3.0.CO;2-6

    Article  CAS  PubMed  Google Scholar 

  87. Zhou Q, Wang H, Schwartz DM et al (2016) Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet 48:67–73. https://doi.org/10.1038/ng.3459

    Article  CAS  PubMed  Google Scholar 

  88. Zeggini E, Thomson W, Kwiatkowski D et al (2002) Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. Arthritis Rheum 46:3304–3311. https://doi.org/10.1002/art.10698

    Article  CAS  PubMed  Google Scholar 

  89. Reinards THCM, Albers HM, Brinkman DMC et al (2015) CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis. Ann Rheum Dis 74:2193–2198. https://doi.org/10.1136/annrheumdis-2013-205138

    Article  CAS  PubMed  Google Scholar 

  90. Hinks A, Eyre S, Ke X et al (2010) Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis. Genes Immun 11:194–198. https://doi.org/10.1038/gene.2009.105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ellis JA, Chavez RA, Pezic A et al (2013) Independent replication analysis of genetic loci with previous evidence of association with juvenile idiopathic arthritis. Pediatr Rheumatol 11:12. https://doi.org/10.1186/1546-0096-11-12

    Article  Google Scholar 

  92. Scussel-Lonzetti L, Joyal F, Raynauld J-P et al (2002) Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore) 81:154–167

    Article  Google Scholar 

  93. Kucharz EJ, Jarczyk R, Jonderko G et al (1996) High serum level of prolactin in patients with systemic sclerosis. Clin Rheumatol 15:314

    Article  CAS  PubMed  Google Scholar 

  94. Straub RH, Zeuner M, Lock G et al (1997) High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis. Br J Rheumatol 36:426–432

    Article  CAS  PubMed  Google Scholar 

  95. Tiniakou E, Costenbader KH, Kriegel MA (2013) Sex-specific environmental influences on the development of autoimmune diseases. Clin Immunol 149:182–191. https://doi.org/10.1016/j.clim.2013.02.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mayes MD, Lacey JV, Beebe-Dimmer J et al (2003) Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum 48:2246–2255. https://doi.org/10.1002/art.11073

    Article  PubMed  Google Scholar 

  97. Scalapino K, Arkachaisri T, Lucas M et al (2006) Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. J Rheumatol 33:1004–1013

    PubMed  Google Scholar 

  98. Zulian F, Athreya BH, Laxer R et al (2006) Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford) 45:614–620. https://doi.org/10.1093/rheumatology/kei251

    Article  CAS  Google Scholar 

  99. Gül A (2001) Behçet’s disease: an update on the pathogenesis. Clin Exp Rheumatol 19:S6–12

    PubMed  Google Scholar 

  100. Remmers EF, Cosan F, Kirino Y et al (2010) Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease. Nat Genet 42:698–702. https://doi.org/10.1038/ng.625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Maldini C, LaValley MP, Cheminant M et al (2012) Relationships of HLA-B51 or B5 genotype with Behçet’s disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatology 51:887–900. https://doi.org/10.1093/rheumatology/ker428

    Article  PubMed  Google Scholar 

  102. Koné-Paut I, Shahram F, Darce-Bello M et al (2016) Consensus classification criteria for paediatric Behçet’s disease from a prospective observational cohort: PEDBD. Ann Rheum Dis 75:958–964. https://doi.org/10.1136/annrheumdis-2015-208491

    Article  PubMed  Google Scholar 

  103. Davatchi F, Shahram F, Chams-Davatchi C et al (2010) Behcet’s disease: from east to west. Clin Rheumatol 29:823–833. https://doi.org/10.1007/s10067-010-1430-6

    Article  PubMed  Google Scholar 

  104. Ucar-Comlekoglu D, Fox A, Sen HN (2014) Gender differences in Behçet’s disease associated uveitis. J Ophthalmol 2014:1–8. https://doi.org/10.1155/2014/820710

    Article  Google Scholar 

  105. Calin A, Fries JF (1975) Striking prevalence of ankylosing spondylitis in “healthy” w27 positive males and females. N Engl J Med 293:835–839. https://doi.org/10.1056/NEJM197510232931701

    Article  CAS  PubMed  Google Scholar 

  106. Saylan T, Ozarmagan G, Azizlerli G et al (1986) Behçet disease in Turkey. Z Hautkr 61:1120–1122

    CAS  PubMed  Google Scholar 

  107. Kural-Seyahi E, Fresko I, Seyahi N et al (2003) The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore) 82:60–76

    Article  Google Scholar 

  108. Saadoun D, Wechsler B, Desseaux K et al (2010) Mortality in Behçet’s disease. Arthritis Rheum 62:2806–2812. https://doi.org/10.1002/art.27568

    Article  CAS  PubMed  Google Scholar 

  109. See L-C, Kuo C-F, Chou I-J et al (2013) Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: a Taiwan population-based study. Semin Arthritis Rheum 43:381–386. https://doi.org/10.1016/j.semarthrit.2013.06.001

    Article  PubMed  Google Scholar 

  110. Oh SH, Han EC, Lee JH, Bang D (2009) Comparison of the clinical features of recurrent aphthous stomatitis and Behçet’s disease. Clin Exp Dermatol 34:e208–e212. https://doi.org/10.1111/j.1365-2230.2009.03384.x

    Article  CAS  PubMed  Google Scholar 

  111. Davatchi F, Shahram F, Chams-Davatchi C et al (2010) Behcet’s disease in Iran: analysis of 6500 cases. Int J Rheum Dis 13:367–373. https://doi.org/10.1111/j.1756-185X.2010.01549.x

    Article  PubMed  Google Scholar 

  112. Wang L-Y, Zhao D-B, Gu J, Dai S-M (2010) Clinical characteristics of Behçet’s disease in China. Rheumatol Int 30:1191–1196. https://doi.org/10.1007/s00296-009-1127-9

    Article  CAS  PubMed  Google Scholar 

  113. Shahram F, Davatchi F, Nadji A et al (2003) Recent epidemiological data on Behçet’s disease in Iran. In: Adamantiades-Behçet’s disease. Kluwer Academic Publishers, Boston, pp 31–36

    Google Scholar 

  114. Letsinger JA, McCarty MA, Jorizzo JL (2005) Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol 52:500–508. https://doi.org/10.1016/j.jaad.2004.10.863

    Article  PubMed  Google Scholar 

  115. Bang D, Hur W, Lee ES, Lee S (1995) Prognosis and clinical relevance of recurrent oral ulceration in Behçet’s disease. J Dermatol 22:926–929

    Article  CAS  PubMed  Google Scholar 

  116. Saurenmann RK, Levin AV, Feldman BM et al (2007) Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis Rheum 56:647–657. https://doi.org/10.1002/art.22381

    Article  CAS  PubMed  Google Scholar 

  117. Metreau-Vastel J, Mikaeloff Y, Tardieu M et al (2010) Neurological involvement in Paediatric Behçet’s disease. Neuropediatrics 41:228–234. https://doi.org/10.1055/s-0030-1269909

    Article  CAS  PubMed  Google Scholar 

  118. Mat C, Yurdakul S, Uysal S et al (2006) A double-blind trial of depot corticosteroids in Behçet’s syndrome. Rheumatology (Oxford) 45:348–352. https://doi.org/10.1093/rheumatology/kei165

    Article  CAS  Google Scholar 

  119. Yurdakul S, Mat C, Tüzün Y et al (2001) A double-blind trial of colchicine in Behçet’s syndrome. Arthritis Rheum 44:2686–2692

    Article  CAS  PubMed  Google Scholar 

  120. Hamuryudan V, Mat C, Saip S et al (1998) Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128:443–450

    Article  CAS  PubMed  Google Scholar 

  121. Gregory AC, Kempen JH, Daniel E et al (2013) Risk factors for loss of visual acuity among patients with uveitis associated with juvenile idiopathic arthritis: the systemic immunosuppressive therapy for eye diseases study. Ophthalmology 120:186–192. https://doi.org/10.1016/j.ophtha.2012.07.052

    Article  PubMed  Google Scholar 

  122. Masuda K, Nakajima A, Urayama A et al (1989) Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’s disease. Lancet (London, England) 1:1093–1096

    Article  CAS  Google Scholar 

  123. Martini G, Foeldvari I, Russo R et al (2006) Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database. Arthritis Rheum 54:3971–3978. https://doi.org/10.1002/art.22207

    Article  CAS  PubMed  Google Scholar 

  124. Gürler A, Boyvat A, Türsen U (1997) Clinical manifestations of Behçet’s disease: an analysis of 2147 patients. Yonsei Med J 38:423–427. https://doi.org/10.3349/ymj.1997.38.6.423

    Article  PubMed  Google Scholar 

  125. Ideguchi H, Suda A, Takeno M et al (2011) Behçet disease. Medicine (Baltimore) 90:125–132. https://doi.org/10.1097/MD.0b013e318211bf28

    Article  Google Scholar 

  126. Koné-Paut I, Yurdakul S, Bahabri SA et al (1998) Clinical features of Behçet’s disease in children: an international collaborative study of 86 cases. J Pediatr 132:721–725

    Article  PubMed  Google Scholar 

  127. Koné-Paut I, Darce-Bello M, Shahram F et al (2011) Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet’s disease: an international cohort study of 110 patients. One-year follow-up data. Rheumatology (Oxford) 50:184–188. https://doi.org/10.1093/rheumatology/keq324

    Article  Google Scholar 

  128. Yazici H, Pazarli H, Barnes CG et al (1990) A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 322:281–285. https://doi.org/10.1056/NEJM199002013220501

    Article  CAS  PubMed  Google Scholar 

  129. Akman-Demir G, Ayranci O, Kurtuncu M et al (2008) Cyclosporine for Behçet’s uveitis: is it associated with an increased risk of neurological involvement? Clin Exp Rheumatol 26:S84–S90

    CAS  PubMed  Google Scholar 

  130. Tursen U, Gurler A, Boyvat A (2003) Evaluation of clinical findings according to sex in 2313 Turkish patients with Behçet’s disease. Int J Dermatol 42:346–351

    Article  PubMed  Google Scholar 

  131. Bonitsis NG, Luong Nguyen LB, LaValley MP et al (2015) Gender-specific differences in Adamantiades-Behçet’s disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. Rheumatology (Oxford) 54:121–133. https://doi.org/10.1093/rheumatology/keu247

    Article  CAS  Google Scholar 

  132. Yazici H, Ugurlu S, Seyahi E (2012) Behçet syndrome: is it one condition? Clin Rev Allergy Immunol 43:275–280. https://doi.org/10.1007/s12016-012-8319-x

    Article  CAS  PubMed  Google Scholar 

  133. Özer HTE, Günesaçar R, Dinkçi S et al (2012) The impact of smoking on clinical features of Behçet’s disease patients with glutathione S-transferase polymorphisms. Clin Exp Rheumatol 30:S14–S17

    PubMed  Google Scholar 

  134. Rizvi SW, McGrath H (2001) The therapeutic effect of cigarette smoking on oral/genital aphthosis and other manifestations of Behçet’s disease. Clin Exp Rheumatol 19:S77–S78

    CAS  PubMed  Google Scholar 

  135. Aramaki K, Kikuchi H, Hirohata S (2007) HLA-B51 and cigarette smoking as risk factors for chronic progressive neurological manifestations in Behçet’s disease. Mod Rheumatol 17:81–82. https://doi.org/10.1007/s10165-006-0541-z

    Article  PubMed  Google Scholar 

  136. Can M, Gunes M, Haliloglu OA et al (2012) Effect of vitamin D deficiency and replacement on endothelial functions in Behçet’s disease. Clin Exp Rheumatol 30:S57–S61

    CAS  PubMed  Google Scholar 

  137. Hamzaoui K, Ben Dhifallah I, Karray E et al (2010) Vitamin D modulates peripheral immunity in patients with Behçet’s disease. Clin Exp Rheumatol 28:S50–S57

    PubMed  Google Scholar 

  138. Kane A, Mirabel M, Touré K et al (2013) Echocardiographic screening for rheumatic heart disease: age matters. Int J Cardiol 168:888–891. https://doi.org/10.1016/j.ijcard.2012.10.090

    Article  PubMed  Google Scholar 

  139. Carapetis JR, Steer AC, Mulholland EK, Weber M (2005) The global burden of group a streptococcal diseases. Lancet Infect Dis 5:685–694. https://doi.org/10.1016/S1473-3099(05)70267-X

    Article  PubMed  Google Scholar 

  140. Marijon E, Ou P, Celermajer DS et al (2007) Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med 357:470–476. https://doi.org/10.1056/NEJMoa065085

    Article  CAS  PubMed  Google Scholar 

  141. Rothenbühler M, O’Sullivan CJ, Stortecky S et al (2014) Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents. Lancet Glob Heal 2:e717–e726. https://doi.org/10.1016/S2214-109X(14)70310-9

    Article  Google Scholar 

  142. Baroux N, Rouchon B, Huon B et al (2013) High prevalence of rheumatic heart disease in schoolchildren detected by echocardiography screening in New Caledonia. J Paediatr Child Health 49:109–114. https://doi.org/10.1111/jpc.12087

    Article  PubMed  Google Scholar 

  143. Ba-Saddik IA, Munibari AA, Al-Naqeeb MS et al (2011) Prevalence of rheumatic heart disease among school-children in Aden, Yemen. Ann Trop Paediatr 31:37–46. https://doi.org/10.1179/1465328110Y.0000000007

    Article  CAS  PubMed  Google Scholar 

  144. Beaton A, Okello E, Lwabi P et al (2012) Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren. Circulation 125:3127–3132. https://doi.org/10.1161/CIRCULATIONAHA.112.092312

    Article  PubMed  Google Scholar 

  145. Longo-Mbenza B, Bayekula M, Ngiyulu R et al (1998) Survey of rheumatic heart disease in school children of Kinshasa town. Int J Cardiol 63:287–294

    Article  CAS  PubMed  Google Scholar 

  146. Oli K, Porteous J (1999) Rheumatic heart disease among school children in Addis Ababa City: awareness and adequacy of its prophylaxis. Ethiop Med J 37:155–161

    CAS  PubMed  Google Scholar 

  147. Periwal KL, Gupta BK, Panwar RB et al (2006) Prevalence of rheumatic heart disease in school children in Bikaner: an echocardiographic study. J Assoc Physicians India 54:279–282

    CAS  PubMed  Google Scholar 

  148. Regmi PR, Pandey MR (1997) Prevalence of rheumatic fever and rheumatic heart disease in school children of Kathmandu city. Indian Heart J 49:518–520

    CAS  PubMed  Google Scholar 

  149. Sadiq M, Islam K, Abid R et al (2009) Prevalence of rheumatic heart disease in school children of urban Lahore. Heart 95:353–357. https://doi.org/10.1136/hrt.2008.143982

    Article  CAS  PubMed  Google Scholar 

  150. Saxena A, Ramakrishnan S, Roy A et al (2011) Prevalence and outcome of subclinical rheumatic heart disease in India: the RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study. Heart 97:2018–2022. https://doi.org/10.1136/heartjnl-2011-300792

    Article  PubMed  Google Scholar 

  151. Steer AC, Kado J, Wilson N et al (2009) High prevalence of rheumatic heart disease by clinical and echocardiographic screening among children in Fiji. J Heart Valve Dis 18:327–335 discussion 336

    PubMed  Google Scholar 

  152. Thakur JS, Negi PC, Ahluwalia SK, Vaidya NK (1996) Epidemiological survey of rheumatic heart disease among school children in the Shimla Hills of northern India: prevalence and risk factors. J Epidemiol Community Health 50:62–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Fenoglio D, Battaglia F, Parodi A et al (2011) Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis. Clin Immunol 139:249–257. https://doi.org/10.1016/j.clim.2011.01.013

    Article  CAS  PubMed  Google Scholar 

  154. Sani MU, Karaye KM, Borodo MM (2007) Prevalence and pattern of rheumatic heart disease in the Nigerian savannah: an echocardiographic study. Cardiovasc J Afr 18:295–299

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Carapetis JR, Wolff DR, Currie BJ (1996) Acute rheumatic fever and rheumatic heart disease in the top end of Australia’s Northern Territory. Med J Aust 164:146–149

    CAS  PubMed  Google Scholar 

  156. Ozer O, Davutoglu V, Sari I et al (2009) The spectrum of rheumatic heart disease in the southeastern Anatolia endemic region: results from 1900 patients. J Heart Valve Dis 18:68–72

    PubMed  Google Scholar 

  157. Sliwa K, Carrington M, Mayosi BM et al (2010) Incidence and characteristics of newly diagnosed rheumatic heart disease in Urban African adults: insights from the Heart of Soweto Study. Eur Heart J 31:719–727. https://doi.org/10.1093/eurheartj/ehp530

    Article  PubMed  Google Scholar 

  158. Shrestha NR, Pilgrim T, Karki P et al (2012) Rheumatic heart disease revisited: patterns of valvular involvement from a consecutive cohort in eastern Nepal. J Cardiovasc Med (Hagerstown) 13:755–759. https://doi.org/10.2459/JCM.0b013e32835854b6

    Article  Google Scholar 

  159. Roberts K, Maguire G, Brown A et al (2014) Echocardiographic screening for rheumatic heart disease in high and low risk Australian children. Circulation 129:1953–1961. https://doi.org/10.1161/CIRCULATIONAHA.113.003495

    Article  PubMed  Google Scholar 

  160. Gardner-Medwin JMM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet (London, England) 360:1197–1202. https://doi.org/10.1016/S0140-6736(02)11279-7

    Article  Google Scholar 

  161. Piram M, Maldini C, Biscardi S et al (2017) Incidence of IgA vasculitis in children estimated by four-source capture-recapture analysis: a population-based study. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/kex158

  162. Ronkainen J, Nuutinen M, Koskimies O (2002) The adult kidney 24 years after childhood Henoch-Schönlein purpura: a retrospective cohort study. Lancet (London, England) 360:666–670. https://doi.org/10.1016/S0140-6736(02)09835-5

    Article  Google Scholar 

  163. Ramelli V, Lava SAG, Simonetti GD et al (2017) Blistering eruptions in childhood Henoch-Schönlein syndrome: systematic review of the literature. Eur J Pediatr 176:487–492. https://doi.org/10.1007/s00431-017-2858-3

    Article  PubMed  Google Scholar 

  164. Kano Y, Mitsuyama Y, Hirahara K, Shiohara T (2007) Mycoplasma pneumoniae infection-induced erythema nodosum, anaphylactoid purpura, and acute urticaria in 3 people in a single family. J Am Acad Dermatol 57:S33–S35. https://doi.org/10.1016/j.jaad.2005.08.027

    Article  PubMed  Google Scholar 

  165. Ostini A, Simonetti GD, Pellanda G et al (2016) Familial Henoch-Schönlein Syndrome. JCR J Clin Rheumatol 22:80–81. https://doi.org/10.1097/RHU.0000000000000360

    Article  PubMed  Google Scholar 

  166. Chen T, Lu Y, Wang W et al (2014) Elevated urinary levels of cystatin C and neutrophil gelatinase-associated lipocalin in Henoch-Schönlein purpura patients with renal involvement. PLoS One 9:e101026. https://doi.org/10.1371/journal.pone.0101026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Chan H, Tang Y-L, Lv X-H et al (2016) Risk factors associated with renal involvement in childhood Henoch-Schönlein purpura: a meta-analysis. PLoS One 11:e0167346. https://doi.org/10.1371/journal.pone.0167346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Stefek B, Beck M, Ioffreda M et al (2015) Henoch–Schönlein purpura with posterior reversible encephalopathy syndrome. J Pediatr 167:1152–1154. https://doi.org/10.1016/j.jpeds.2015.07.066

    Article  PubMed  Google Scholar 

  169. dos Santos D, Langer FW, dos Santos T et al (2017) Posterior reversible encephalopathy syndrome as a complication of Henoch–Schönlein purpura in a seven-year-old girl. Scott Med J 62:34–37. https://doi.org/10.1177/0036933017690467

    Article  PubMed  Google Scholar 

  170. Kato H, Sugimura T, Akagi T et al (1996) Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 94:1379–1385

    Article  CAS  PubMed  Google Scholar 

  171. Newburger JW, Takahashi M, Gerber MA et al (2004) Diagnosis, treatment, and long-term Management of Kawasaki Disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation 110:2747–2771. https://doi.org/10.1161/01.CIR.0000145143.19711.78

    Article  PubMed  Google Scholar 

  172. Nakamura Y, Yashiro M, Uehara R et al (2012) Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey. J Epidemiol 22:216–221

    Article  PubMed  PubMed Central  Google Scholar 

  173. Hall GC, Tulloh LE, Tulloh RMR (2016) Kawasaki disease incidence in children and adolescents: an observational study in primary care. Br J Gen Pract 66:e271–e276. https://doi.org/10.3399/bjgp16X684325

    Article  PubMed  PubMed Central  Google Scholar 

  174. Onouchi Y, Gunji T, Burns JC et al (2008) ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 40:35–42. https://doi.org/10.1038/ng.2007.59

    Article  CAS  PubMed  Google Scholar 

  175. Onouchi Y, Ozaki K, Buns JC et al (2010) Common variants in CASP3 confer susceptibility to Kawasaki disease. Hum Mol Genet 19:2898–2906. https://doi.org/10.1093/hmg/ddq176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Lee Y-C, Kuo H-C, Chang J-S et al (2012) Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 44:522–525. https://doi.org/10.1038/ng.2227

    Article  CAS  PubMed  Google Scholar 

  177. Burns JC, Herzog L, Fabri O et al (2013) Seasonality of Kawasaki disease: a global perspective. PLoS One 8:e74529. https://doi.org/10.1371/journal.pone.0074529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Yoshioka T, Matsutani T, Toyosaki-Maeda T et al (2003) Relation of streptococcal pyrogenic exotoxin C as a causative superantigen for Kawasaki disease. Pediatr Res 53:403–410. https://doi.org/10.1203/01.PDR.0000049668.54870.50

    Article  CAS  PubMed  Google Scholar 

  179. Matsubara K, Fukaya T, Miwa K et al (2006) Development of serum IgM antibodies against superantigens of Staphylococcus Aureus and streptococcus pyogenes in Kawasaki disease. Clin Exp Immunol 143:427–434. https://doi.org/10.1111/j.1365-2249.2006.03015.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Saeki Y, Ishihara K (2014) Infection-immunity liaison: pathogen-driven autoimmune-mimicry (PDAIM). Autoimmun Rev 13:1064–1069. https://doi.org/10.1016/j.autrev.2014.08.024

    Article  PubMed  Google Scholar 

  181. Kato T, Numaguchi A, Ando H et al (2012) Coronary arterial ectasia in a 2-year-old boy showing two symptoms of Kawasaki disease without manifesting fever. Rheumatol Int 32:1101–1103. https://doi.org/10.1007/s00296-011-1860-8

    Article  PubMed  Google Scholar 

  182. Smith LB, Newburger JW, Burns JC (1989) Kawasaki syndrome and the eye. Pediatr Infect Dis J 8:116–118

    CAS  PubMed  Google Scholar 

  183. Kawasaki T (1967) Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 16:178–222

    CAS  PubMed  Google Scholar 

  184. Newburger JW, Takahashi M, Gerber MA et al (2004) Diagnosis, treatment, and long-term Management of Kawasaki Disease: a statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Pediatrics 114:1708–1733. https://doi.org/10.1542/peds.2004-2182

    Article  PubMed  Google Scholar 

  185. Yamashita M, Ae R, Yashiro M et al (2017) Difference in risk factors for subtypes of acute cardiac lesions resulting from Kawasaki disease. Pediatr Cardiol 38:375–380. https://doi.org/10.1007/s00246-016-1525-1

    Article  PubMed  Google Scholar 

  186. Brunner J, Feldman BM, Tyrrell PN et al (2010) Takayasu arteritis in children and adolescents. Rheumatology (Oxford) 49:1806–1814. https://doi.org/10.1093/rheumatology/keq167

    Article  Google Scholar 

  187. Shrivastava S, Srivastava RN, Tandon R (1986) Idiopathic obstructive aortoarteritis in children. Indian Pediatr 23:403–410

    CAS  PubMed  Google Scholar 

  188. Hahn D, Thomson PD, Kala U et al (1998) A review of Takayasu’s arteritis in children in Gauteng, South Africa. Pediatr Nephrol 12:668–675

    Article  CAS  PubMed  Google Scholar 

  189. Vanoli M, Daina E, Salvarani C et al (2005) Takayasu’s arteritis: a study of 104 Italian patients. Arthritis Rheum 53:100–107. https://doi.org/10.1002/art.20922

    Article  CAS  PubMed  Google Scholar 

  190. Gudbrandsson B, Molberg Ø, Garen T, Palm Ø (2017) Prevalence, incidence, and disease characteristics of Takayasu arteritis by ethnic background: data from a large, population-based cohort resident in southern Norway. Arthritis Care Res (Hoboken) 69:278–285. https://doi.org/10.1002/acr.22931

    Article  Google Scholar 

  191. Soto ME, Del Carmen Á-CM, Huesca-Gómez C et al (2012) Detection of IS6110 and HupB gene sequences of mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu’s arteritis. BMC Infect Dis 12:194. https://doi.org/10.1186/1471-2334-12-194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Lupi-Herrera E, Sánchez-Torres G, Marcushamer J et al (1977) Takayasu’s arteritis. Clinical study of 107 cases. Am Heart J 93:94–103

    Article  CAS  PubMed  Google Scholar 

  193. Numano F (2000) Vasa vasoritis, vasculitis and atherosclerosis. Int J Cardiol 75(Suppl 1):S1–S8 discussion S17–9

    Article  PubMed  Google Scholar 

  194. Sahin Z, Bıcakcıgil M, Aksu K et al (2012) Takayasu’s arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. Arthritis Res Ther 14:R27. https://doi.org/10.1186/ar3730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Kasuya K, Hashimoto Y, Numano F (1992) Left ventricular dysfunction and HLA Bw52 antigen in Takayasu arteritis. Heart Vessels Suppl 7:116–119

    Article  CAS  PubMed  Google Scholar 

  196. Saruhan-Direskeneli G, Hughes T, Aksu K et al (2013) Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet 93:298–305. https://doi.org/10.1016/j.ajhg.2013.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Renauer PA, Saruhan-Direskeneli G, Coit P et al (2015) Identification of susceptibility loci in IL6, RPS9 / LILRB3, and an intergenic locus on chromosome 21q22 in Takayasu arteritis in a genome-wide association study. Arthritis Rheumatol 67:1361–1368. https://doi.org/10.1002/art.39035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Alibaz-Oner F, Yentür SP, Saruhan-Direskeneli G, Direskeneli H (2015) Serum cytokine profiles in Takayasu’s arteritis: search for biomarkers. Clin Exp Rheumatol 33:S-32–S-35

    Google Scholar 

  199. Goel R, Kumar TS, Danda D et al (2014) Childhood-onset Takayasu arteritis—experience from a tertiary care center in South India. J Rheumatol 41:1183–1189. https://doi.org/10.3899/jrheum.131117

    Article  PubMed  Google Scholar 

  200. Misra DP, Aggarwal A, Lawrence A et al (2015) Pediatric-onset Takayasu’s arteritis: clinical features and short-term outcome. Rheumatol Int 35:1701–1706. https://doi.org/10.1007/s00296-015-3272-7

    Article  CAS  PubMed  Google Scholar 

  201. Peter J, David S, Danda D et al (2011) Ocular manifestations of Takayasu arteritis. Retina 31:1170–1178. https://doi.org/10.1097/IAE.0b013e3181fe540b

    Article  PubMed  Google Scholar 

  202. Sharma BK, Jain S (1998) A possible role of sex in determining distribution of lesions in Takayasu arteritis. Int J Cardiol 66(Suppl 1):S81–S84

    Article  PubMed  Google Scholar 

  203. Clemente G, Hilário MO, Len C et al (2016) Brazilian multicenter study of 71 patients with juvenile-onset Takayasu’s arteritis: clinical and angiographic features. Rev Bras Reumatol 56:145–151. https://doi.org/10.1016/j.rbre.2016.01.004

    Article  Google Scholar 

  204. Lim AY, Lee GY, Jang SY et al (2015) Gender differences in clinical and angiographic findings of patients with Takayasu arteritis. Clin Exp Rheumatol 33:S-132–S-137

    Google Scholar 

Download references

Funding

No funding was dedicated to this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rolando Cimaz.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This type of work (review) does not require ethical approval, since it did not involve human participants.

Informed Consent

This type of work (review) does not require informed consent, since it did not involve human participants.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cattalini, M., Soliani, M., Caparello, M.C. et al. Sex Differences in Pediatric Rheumatology. Clinic Rev Allerg Immunol 56, 293–307 (2019). https://doi.org/10.1007/s12016-017-8642-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-017-8642-3

Keywords

Navigation