nach oben

Erschienen in:

29.06.2022 | Autoinflammation

Autoinflammation – Unterschiede bei Kindern und Erwachsenen

verfasst von: Martin Krusche, PD Dr. Tilmann Kallinich

Erschienen in: rheuma plus | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Zusammenfassung

Autoinflammatorische Erkrankungen präsentieren sich als multisystemische Entzündungen und werden häufig bereits im frühen Kindesalter manifest. Bei wenigen Erkrankungen, wie z. B. dem kürzlich beschriebenen VEXAS-Syndrom (Vakuolen, E1-Enzym, X‑chromosomal, autoinflammatorisch, somatisch) treten die ersten Krankheitssymptome dagegen ausschließlich im Erwachsenenalter auf. Dieser Beitrag beschreibt, inwiefern sich die phänotypische Ausprägung und Schwere einzelner autoinflammatorischer Erkrankungen in Abhängigkeit vom Lebensalter unterscheiden. Zudem werden altersabhängige Differenzen in der Ausbildung von vorliegenden Organschäden aufgezeigt. Neben den hereditären periodischen Fiebersyndromen werden auch das Krankheitsbild der Adenosindesaminase-2-Defizienz, die Interferonopathien, das PFAPA-Syndrom mit periodischem Fieber, aphthöser Stomatitis, Pharyngitis und zervikaler Adenitis sowie das VEXAS- und das Schnitzler-Syndrom beleuchtet.

Vorheriger Artikel Diagnose und Therapie des nichtspezifischen Kreuzschmerzes

Nächster Artikel Die chronisch inflammatorisch demyelinisierende Polyneuropathie als Differenzialdiagnose zur Polymyalgia rheumatica

Kallinich T, Hinze C, Wittkowski H (2020) Classification of autoinflammatory diseases based on pathophysiological mechanisms. Z Rheumatol 79:624–638. https://doi.org/10.1007/s00393-020-00794-3CrossRefPubMed

Gattorno M et al (2019) Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 78:1025–1032. https://doi.org/10.1136/annrheumdis-2019-215048CrossRefPubMed

Kallinich T, Orak B, Wittkowski H (2017) Role of genetics in familial Mediterranean fever. Z Rheumatol 76:303–312. https://doi.org/10.1007/s00393-017-0265-9CrossRefPubMed

Park YH et al (2020) Ancient familial Mediterranean fever mutations in human pyrin and resistance to Yersinia pestis. Nat Immunol 21:857–867. https://doi.org/10.1038/s41590-020-0705-6CrossRefPubMedPubMedCentral

Langevitz P et al (1999) Familial Mediterranean fever: new aspects and prospects at the end of the millenium. Isr Med Assoc J 1:31–36PubMed

Yalcinkaya F et al (2009) A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford) 48:395–398. https://doi.org/10.1093/rheumatology/ken509CrossRef

Demirkaya E et al (2016) Performance of different diagnostic criteria for familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. J Rheumatol 43:154–160. https://doi.org/10.3899/jrheum.141249CrossRefPubMed

Kondi A et al (2010) Validation of the new paediatric criteria for the diagnosis of familial Mediterranean fever: data from a mixed population of 100 children from the French reference centre for auto-inflammatory disorders. Rheumatology (Oxford) 49:2200–2203. https://doi.org/10.1093/rheumatology/keq252CrossRef

Padeh S et al (2010) Familial Mediterranean fever in the first two years of life: a unique phenotype of disease in evolution. J Pediatr 156:985–989. https://doi.org/10.1016/j.jpeds.2009.12.010CrossRefPubMed

10.

Padeh S et al (2010) Familial Mediterranean fever in children presenting with attacks of fever alone. J Rheumatol 37:865–869. https://doi.org/10.3899/jrheum.090687CrossRefPubMed

11.

Hentgen V, Grateau G, Stankovic-Stojanovic K, Amselem S, Jeru I (2013) Familial Mediterranean fever in heterozygotes: are we able to accurately diagnose the disease in very young children? Arthritis Rheum 65:1654–1662. https://doi.org/10.1002/art.37935CrossRefPubMed

12.

Butbul Aviel Y et al (2019) Familial Mediterranean fever is commonly diagnosed in children in Israel with periodic fever aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr 204:270–274. https://doi.org/10.1016/j.jpeds.2018.08.080CrossRefPubMed

13.

Sonmez HE, Batu ED, Bilginer Y, Ozen S (2017) Discontinuing colchicine in symptomatic carriers for MEFV (Mediterranean FeVer) variants. Clin Rheumatol 36:421–425. https://doi.org/10.1007/s10067-016-3421-8CrossRefPubMed

14.

Tanatar A, Karadag SG, Sonmez HE, Cakan M, Aktay Ayaz N (2019) Short-term follow-up results of children with familial Mediterranean fever after cessation of colchicine: is it possible to quit? Rheumatology (Oxford) 58:1818–1821. https://doi.org/10.1093/rheumatology/kez156CrossRef

15.

Ricci P et al (2020) The grandfather’s fever. Clin Rheumatol 39:585–594. https://doi.org/10.1007/s10067-019-04741-9CrossRefPubMed

16.

Yasar Bilge NS et al (2018) Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis 21:880–884. https://doi.org/10.1111/1756-185X.13259CrossRefPubMed

17.

Brenner R et al (2018) Familial Mediterranean fever and incidence of cancer: an analysis of 8,534 Israeli patients with 258,803 person-years. Arthritis Rheumatol 70:127–133. https://doi.org/10.1002/art.40344CrossRefPubMed

18.

Altunoglu A et al (2013) Phenotype 2 familial mediterranean fever: evaluation of 22 case series and review of the literature on phenotype 2 FMF. Ren Fail 35:226–230. https://doi.org/10.3109/0886022X.2012.745115CrossRefPubMed

19.

Lainka E et al (2009) Incidence of TNFRSF1A mutations in German children: epidemiological, clinical and genetic characteristics. Rheumatology (Oxford) 48:987–991. https://doi.org/10.1093/rheumatology/kep140CrossRef

20.

Cudrici C, Deuitch N, Aksentijevich I (2020) Revisiting TNF receptor-associated periodic syndrome (TRAPS): current perspectives. Int J Mol Sci. https://doi.org/10.3390/ijms21093263CrossRefPubMedPubMedCentral

21.

Lachmann HJ et al (2014) 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 73:2160–2167. https://doi.org/10.1136/annrheumdis-2013-204184CrossRefPubMed

22.

Pelagatti MA et al (2011) Long-term clinical profile of children with the low-penetrance R92Q mutation of the TNFRSF1A gene. Arthritis Rheum 63:1141–1150. https://doi.org/10.1002/art.30237CrossRefPubMedPubMedCentral

23.

Ruiz-Ortiz E et al (2017) Disease phenotype and outcome depending on the age at disease onset in patients carrying the R92Q low-penetrance variant in TNFRSF1A gene. Front Immunol 8:299. https://doi.org/10.3389/fimmu.2017.00299CrossRefPubMedPubMedCentral

24.

Poirier O et al (2004) Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness—the ECTIM, AXA, EVA and GENIC studies. Eur J Hum Genet 12:213–219. https://doi.org/10.1038/sj.ejhg.5201143CrossRefPubMed

25.

Caminero A, Comabella M, Montalban X (2011) Role of tumour necrosis factor (TNF)-alpha and TNFRSF1A R92Q mutation in the pathogenesis of TNF receptor-associated periodic syndrome and multiple sclerosis. Clin Exp Immunol 166:338–345. https://doi.org/10.1111/j.1365-2249.2011.04484.xCrossRefPubMedPubMedCentral

26.

Levy R et al (2015) Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever registry. Ann Rheum Dis 74:2043–2049. https://doi.org/10.1136/annrheumdis-2013-204991CrossRefPubMed

27.

Vitale A, Lucherini OM, Galeazzi M, Frediani B, Cantarini L (2012) Long-term clinical course of patients carrying the Q703K mutation in the NLRP3 gene: a case series. Clin Exp Rheumatol 30:943–946PubMed

28.

Mensa-Vilaro A et al (2016) Brief report: late-onset cryopyrin-associated periodic syndrome due to myeloid-restricted somatic NLRP3 mosaicism. Arthritis Rheumatol 68:3035–3041. https://doi.org/10.1002/art.39770CrossRefPubMed

29.

Rowczenio DM et al (2017) Late-onset cryopyrin-associated periodic syndromes caused by somatic NLRP3 mosaicism-UK single center experience. Front Immunol 8:1410. https://doi.org/10.3389/fimmu.2017.01410CrossRefPubMedPubMedCentral

30.

Brennenstuhl H et al (2021) Phenotypic diversity, disease progression, and pathogenicity of MVK missense variants in mevalonic aciduria. J Inherit Metab Dis. https://doi.org/10.1002/jimd.12412CrossRefPubMed

31.

Drenth JP et al (1999) Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International hyper-IgD study group. Nat Genet 22:178–181. https://doi.org/10.1038/9696CrossRefPubMed

32.

Ter Haar NM et al (2016) The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever registry. Arthritis Rheumatol 68:2795–2805. https://doi.org/10.1002/art.39763CrossRefPubMed

33.

Ozen S et al (2017) International retrospective chart review of treatment patterns in severe familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, and mevalonate kinase deficiency/hyperimmunoglobulinemia D syndrome. Arthritis Care Res (Hoboken) 69:578–586. https://doi.org/10.1002/acr.23120CrossRef

34.

Zhang S (2016) Natural history of mevalonate kinase deficiency: a literature review. Pediatr Rheumatol Online J 14:30. https://doi.org/10.1186/s12969-016-0091-7CrossRefPubMedPubMedCentral

35.

Navon Elkan P et al (2014) Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 370:921–931. https://doi.org/10.1056/NEJMoa1307362CrossRefPubMed

36.

Zhou Q et al (2014) Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 370:911–920. https://doi.org/10.1056/NEJMoa1307361CrossRefPubMedPubMedCentral

37.

Lee PY (2018) Vasculopathy, immunodeficiency, and bone marrow failure: the intriguing syndrome caused by deficiency of adenosine deaminase 2. Front Pediatr 6:282. https://doi.org/10.3389/fped.2018.00282CrossRefPubMedPubMedCentral

38.

Zhang B et al (2021) Adult-onset deficiency of adenosine deaminase 2‑a case report and literature review. Clin Rheumatol. https://doi.org/10.1007/s10067-021-05587-wCrossRefPubMedPubMedCentral

39.

Pinto B, Deo P, Sharma S, Syal A, Sharma A (2021) Expanding spectrum of DADA2: a review of phenotypes, genetics, pathogenesis and treatment. Clin Rheumatol. https://doi.org/10.1007/s10067-021-05711-wCrossRefPubMed

40.

Ombrello AK et al (2019) Treatment strategies for deficiency of adenosine deaminase 2. N Engl J Med 380:1582–1584. https://doi.org/10.1056/NEJMc1801927CrossRefPubMedPubMedCentral

41.

Caorsi R, Penco F, Schena F, Gattorno M (2016) Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatr Rheumatol Online J 14:51. https://doi.org/10.1186/s12969-016-0111-7CrossRefPubMedPubMedCentral

42.

Rama M et al (2018) A decision tree for the genetic diagnosis of deficiency of adenosine deaminase 2 (DADA2): a French reference centres experience. Eur J Hum Genet 26:960–971. https://doi.org/10.1038/s41431-018-0130-6CrossRefPubMedPubMedCentral

43.

Schepp J et al (2017) Screening of 181 patients with antibody deficiency for deficiency of adenosine deaminase 2 sheds new light on the disease in adulthood. Arthritis Rheumatol 69:1689–1700. https://doi.org/10.1002/art.40147CrossRefPubMed

44.

Crow YJ (2011) Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 1238:91–98. https://doi.org/10.1111/j.1749-6632.2011.06220.xCrossRefPubMed

45.

Rodero MP, Crow YJ (2016) Type I interferon-mediated monogenic autoinflammation: the type I interferonopathies, a conceptual overview. J Exp Med 213:2527–2538. https://doi.org/10.1084/jem.20161596CrossRefPubMedPubMedCentral

46.

de Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R (2015) Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol 33:823–874. https://doi.org/10.1146/annurev-immunol-032414-112227CrossRefPubMedPubMedCentral

47.

Feist E, Brehm A, Kallinich T, Kruger E (2017) Clinical aspects and genetics of proteasome-associated autoinflammatory syndromes (PRAAS). Z Rheumatol 76:328–334. https://doi.org/10.1007/s00393-017-0264-xCrossRefPubMed

48.

Zhang X et al (2015) Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation. Nature 517:89–93. https://doi.org/10.1038/nature13801CrossRefPubMed

49.

Watkin LB et al (2015) COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet 47:654–660. https://doi.org/10.1038/ng.3279CrossRefPubMedPubMedCentral

50.

Liu Y et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507–518. https://doi.org/10.1056/NEJMoa1312625CrossRefPubMedPubMedCentral

51.

Dai Y, Liu X, Zhao Z, He J, Yin Q (2020) Stimulator of interferon genes-associated vasculopathy with onset in infancy: a systematic review of case reports. Front Pediatr 8:577918. https://doi.org/10.3389/fped.2020.577918CrossRefPubMedPubMedCentral

52.

Aicardi J, Goutieres F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 15:49–54. https://doi.org/10.1002/ana.410150109CrossRefPubMed

53.

Crow YJ et al (2015) Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 167A:296–312. https://doi.org/10.1002/ajmg.a.36887CrossRefPubMed

54.

Staels F et al (2020) Adult-onset ANCA-associated vasculitis in SAVI: extension of the phenotypic spectrum, case report and review of the literature. Front Immunol 11:575219. https://doi.org/10.3389/fimmu.2020.575219CrossRefPubMedPubMedCentral

55.

Jeremiah N et al (2014) Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 124:5516–5520. https://doi.org/10.1172/JCI79100CrossRefPubMedPubMedCentral

56.

Picard C et al (2016) Severe pulmonary fibrosis as the first manifestation of interferonopathy (TMEM173 mutation). Chest 150:e65–71. https://doi.org/10.1016/j.chest.2016.02.682CrossRefPubMed

57.

Rice GI et al (2017) Genetic, phenotypic, and interferon biomarker status in ADAR1-related neurological disease. Neuropediatrics 48:166–184. https://doi.org/10.1055/s-0037-1601449CrossRefPubMedPubMedCentral

58.

Namjou B et al (2011) Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort. Genes Immun 12:270–279. https://doi.org/10.1038/gene.2010.73CrossRefPubMedPubMedCentral

59.

Cantarini L, Vitale A, Bartolomei B, Galeazzi M, Rigante D (2012) Diagnosis of PFAPA syndrome applied to a cohort of 17 adults with unexplained recurrent fevers. Clin Exp Rheumatol 30:269–271PubMed

60.

Cantarini L et al (2017) Diagnostic criteria for adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Front Immunol 8:1018. https://doi.org/10.3389/fimmu.2017.01018CrossRefPubMedPubMedCentral

61.

Sicignano LL et al (2021) Children and adults with PFAPA syndrome: similarities and divergences in a real-life clinical setting. Adv Ther 38:1078–1093. https://doi.org/10.1007/s12325-020-01576-8CrossRefPubMed

62.

Hofer M et al (2014) International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatology (Oxford) 53:1125–1129. https://doi.org/10.1093/rheumatology/ket460CrossRef

63.

Beck DB et al (2020) Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 383:2628–2638. https://doi.org/10.1056/NEJMoa2026834CrossRefPubMedPubMedCentral

64.

Ferrada MA et al (2021) Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS syndrome. Arthritis Rheumatol. https://doi.org/10.1002/art.41743CrossRefPubMed

65.

Tsuchida N et al (2021) Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220089CrossRefPubMed

66.

Arlet JB, Terrier B, Kosmider O (2021) Mutant UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 384:2163. https://doi.org/10.1056/NEJMc2102124CrossRefPubMed

67.

Simon A et al (2013) Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy 68:562–568. https://doi.org/10.1111/all.12129CrossRefPubMed

68.

Kacar M, Pathak S, Savic S (2019) Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome. Rheumatology (Oxford) 58:vi31–vi43. https://doi.org/10.1093/rheumatology/kez448CrossRef

Titel: Autoinflammation – Unterschiede bei Kindern und Erwachsenen
verfasst von: Martin Krusche
PD Dr. Tilmann Kallinich
Publikationsdatum: 29.06.2022
Verlag: Springer Vienna
Erschienen in: rheuma plus / Ausgabe 4/2022
Print ISSN: 1868-260X
Elektronische ISSN: 2191-2610
DOI: https://doi.org/10.1007/s12688-022-00534-2

Geht’s Ihnen noch gut?

Interview

„Refraktäre Gicht sollte nicht existieren“

aktuell

Nach Hüft- und Knie-OP: wann wieder ans Steuer?

aktuell

Die chronisch inflammatorisch demyelinisierende Polyneuropathie als Differenzialdiagnose zur Polymyalgia rheumatica

Aus der Praxis

Schmerzen im Kunstgelenk – Lag’s an der Grippeimpfung?

Rheumatologie
aktuell

Erneute Updates der EULAR-Empfehlungen

Editorial

Springer Medizin Österreich

Autoinflammation – Unterschiede bei Kindern und Erwachsenen

Zusammenfassung

Weitere Artikel der Ausgabe 4/2022

Geht’s Ihnen noch gut?

„Refraktäre Gicht sollte nicht existieren“

Nach Hüft- und Knie-OP: wann wieder ans Steuer?

Die chronisch inflammatorisch demyelinisierende Polyneuropathie als Differenzialdiagnose zur Polymyalgia rheumatica

Schmerzen im Kunstgelenk – Lag’s an der Grippeimpfung?

Erneute Updates der EULAR-Empfehlungen

Springer Medizin Österreich

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Geht’s Ihnen noch gut?

„Refraktäre Gicht sollte nicht existieren“

Nach Hüft- und Knie-OP: wann wieder ans Steuer?

Die chronisch inflammatorisch demyelinisierende Polyneuropathie als Differenzialdiagnose zur Polymyalgia rheumatica

Schmerzen im Kunstgelenk – Lag’s an der Grippeimpfung?

Erneute Updates der EULAR-Empfehlungen