Cryopyrin-assoziierte periodische Syndrome

Zusammenfassung

Autoinflammatorische Erkrankungen zeichnen sich durch abnorme systemische Entzündungsreaktionen aus, die vorwiegend durch Störungen des angeborenen Immunsystems vermittelt werden. Als Prototypen dieser Erkrankungen gelten die seltenen Cryopyrin-assoziierten periodischen Syndrome (CAPS), denen ursächlich eine Mutation des NLRP3-Gens mit konsekutiver Aktivierung von Interleukin-1β (IL-1β) zugrunde liegt. Die drei Vertreter dieser Gruppe, die multisystemische entzündliche Erkrankung mit Beginn im Neugeborenenalter (NOMID/CINCA), das Muckle-Wells-Syndrom (MWS) und das familiäre autoinflammatorische Kältesyndrom (FCAS) sind durch rezidivierende Fieberschübe und Entzündungsreaktionen an verschiedenen Organen, u. a. charakteristische urtikarielle Exantheme, gekennzeichnet. Die Diagnose CAPS wird anhand des klinischen Bildes, der Familienanamnese und Mutationsanalyse sowie unter Abgrenzung weiterer dermatologischer und rheumatologischer Krankheitsbilder gestellt. Therapeutisch kommen IL-1β-Antagonisten zum Einsatz, die bei allen drei Entitäten eine sehr gute Wirksamkeit und Verträglichkeit zeigen.

Summary

Autoinflammatory diseases are characterized by abnormal systemic inflammatory responses primarily mediated by a dysfunction of the innate immunity. Disease prototypes are the rare cryopyrin-associated periodic syndromes (CAPS), which are caused by mutations of the NLRP3 gene leading to subsequent interleukin-1β activation. CAPS consist of the neonatal onset multi-system inflammatory disease (NOMID/CINCA), Muckle-Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS). Clinical symptoms are recurrent episodes of fever and inflammatory reactions of various organs, including urticarial skin rashes. The diagnosis of CAPS is made on the basis of clinical presentation, family history, mutation analysis and by separation from other dermatologic and rheumatologic disorders. The treatment of choice is the use of IL-1β antagonists, which have been shown to be very effective and well tolerated in all three subgroups.

Schlüsselwörter

CAPS - NOMID/CINCA - MWS - FCAS - Auto-inflammation - Interleukin-1β

Keywords

CAPS - NOMID/CINCA - MWS - FCAS - autoinflammation - interleukin-1β

• Literatur

• 1 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 19992 (097) 133-44.
• 2 Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell 2010; 140: 784-790.
• 3 Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002; 10: 417-426.
• 4 Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol 2009; 27: 229-265.
• 5 McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 3: e297
• 6 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.
• 7 Neven B, Callebaut I, Prieur AM. et al Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU. Blood 2004; 103: 2809-2815.
• 8 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. Nat Genet 2001; 29: 301-305.
• 9 Ting JP, Kastner DL, Hoffman HM. CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 2006; 6: 183-195.
• 10 Agostini L, Martinon F, Burns K. et al NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 2004; 20 (03) 319-325.
• 11 Dowds TA, Masumoto J, Zhu L. et al Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem 2004; 279: 21924-21928.
• 12 Prieur AM, Griscelli C, Lampert F. et al A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J Rheumatol Suppl 1987; 66: 57-68.
• 13 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.
• 14 Dollfus H, Hafner R, Hofmann HM. et al Chronic infantile neurological cutaneous and articular/ neonatal onset multisystem inflammatory disease syndrome: ocular manifestations in a recently recognized chronic inflammatory disease of childhood. Arch Ophthalmol 2000; 118: 1386-1392.
• 15 van der Hilst JC, Simon A, Drenth JP. Hereditary periodic fever and reactive amyloidosis. Clin Exp Med 2005; 5: 87-98.
• 16 Muckle TJ. Wellsm. Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. Q J Med 1962; 31: 235-248.
• 17 Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol 2008; 144: 392-402.
• 18 Stych B, Dobrovolny D. Familial cold auto-inflammatory syndrome (FCAS): characterization of symptomatology and impact on patients' lives. Curr Med Res Opin 2008; 24: 1577-1582.
• 19 Lachmann HJ, Hawkins PN. Developments in the scientific and clinical understanding of autoinflammatory disorders. Arthritis Res Ther 2009; 11: 212
• 20 Alexander T, Klotz O, Feist E. et al Successful treatment of acute visual loss in Muckle-Wells syndrome with interleukin 1 receptor antagonist. Ann Rheum Dis 2005; 64: 1245-1246.
• 21 Kile RL, Rusk HA. A case of cold urticaria with an unusual family history. JAMA 1940; 114: 1067-1068.
• 22 Johnstone RF, Dolen WK, Hoffman HM. A large kindred with familial cold autoinflammatory syndrome. Ann Allergy Asthma Immunol 2003; 90: 233-237.
• 23 Krause K, Zuberbier T, Maurer M. Modern approaches to the diagnosis and treatment of cold contact urticaria. Curr Allergy Asthma Rep 2010; 10: 243-249.
• 24 Hoffman HM, Wanderer AA, Broide DH. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol 2001; 108: 615-620.
• 25 Goldbach-Mansky R, Shroff SD, Wilson M. et al A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin- 1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum 2008; 58: 2432-2442.
• 26 Thornton BD, Hoffman HM, Bhat A, Don BR. Successful treatment of renal amyloidosis due to familial cold autoinflammatory syndrome using an interleukin 1 receptor antagonist. Am J Kidney Dis 2007; 49: 477-481.
• 27 Aksentijevich I, DP C, Remmers EF, Mueller JL. 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.
• 28 Kieffer C, Cribier B, Lipsker D. Neutrophilic urticarial dermatosis: a variant of neutrophilic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature. Medicine (Baltimore) 2009; 88: 23-31.
• 29 Peroni A, Colato C, Zanoni G, Girolomoni G. Urticarial lesions: if not urticaria, what else? The differential diagnosis of urticaria: part II. Systemic diseases. J Am Acad Dermatol 2010; 62: 557-570. quiz 71-72
• 30 de Koning HD, Bodar EJ, van der Meer JW, Simon A. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum 2007; 37: 137-148.
• 31 Goldbach-Mansky R, Dailey NJ, Canna SW. et al Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 2006; 355: 581-592.
• 32 Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB. et al Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 2009; 360: 2416-2425.
• 33 Hoffman HM, Throne ML, Amar NJ. et al Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum 2008; 58: 2443-2452.
• 34 Rynne M, Maclean C, Bybee A. et al Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism. Ann Rheum Dis 2006; 65: 533-534.
• 35 Leslie KS, Lachmann HJ, Bruning E. et al Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations. Arch Dermatol 2006; 142: 1591-1597.
• 36 Hawkins PN, Lachmann HJ, McDermott MF. Interleukin- 1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med 2003; 348: 2583-2584.
• 37 Church LD, McDermott MF. Canakinumab, a fullyhuman mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther 2009; 11: 81-89.
• 38 Geyer M, Muller-Ladner U. Actual status of antiinterleukin- 1 therapies in rheumatic diseases. Curr Opin Rheumatol 2010; 22: 246-251.
• 39 Feist E, Burmester GR. Canakinumab for treatment of cryopyrin-associated periodic syndrome. Expert Opin Biol Ther 2010; 10: 1631-1636.