67:
39:
268:
Because CAPS is extremely rare and has a broad clinical presentation, it is difficult to diagnose, and a significant delay exists between symptom onset and definitive diagnosis. There are currently no clinical or diagnostic criteria for CAPS based solely on clinical presentation. Instead, diagnosis
259:
have been identified. Some reports suggest rare mutations are more frequently associated with a severe phenotype, and some mutations are associated with distinct phenotypes, probably reflecting the differential impact of the mutation on the activity of the inflammasome in the context of individual
1016:
Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, Weinstein SP, Belomestnov P, Yancopoulos GD (August 1, 2008). "Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies".
202:
Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these
115:
The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients with systemic involvement from 16 countries, the most prevalent clinical features were fever (84% of cases, often with concurrent constitutional
373:
Levy R, Gérard L, Kuemmerle-Deschner J, Lachmann HJ, Koné-Paut I, Cantarini L, Woo P, Naselli A, Bader-Meunier B (November 1, 2015). "Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the
Eurofever Registry".
1413:
1060:
Ross JB, Finlayson LA, Klotz PJ, Langley RG, Gaudet R, Thompson K, Churchman SM, McDermott MF, Hawkins PN (February 1, 2017). "Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up".
1336:
Matsubara T, Hasegawa M, Shiraishi M, Hoffman HM, Ichiyama T, Tanaka T, Ueda H, Ishihara T, Furukawa S (July 1, 2006). "A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agents".
103:(NOMID, also called chronic infantile neurologic cutaneous and articular syndrome or CINCA) that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway, and
442:"Keratoendotheliitis Fugax Hereditaria: A Novel Cryopyrin-Associated Periodic Syndrome Caused by a Mutation in the Nucleotide-Binding Domain, Leucine-Rich Repeat Family, Pyrin Domain-Containing 3 (NLRP3) Gene"
703:
Molina-LĂłpez C, Hurtado-Navarro L, GarcĂa CJ, Angosto-Bazarra D, Vallejo F, Tapia-Abellán A, Marques-Soares JR, Vargas C, Bujan-Rivas S, Tomás-Barberán FA, Arostegui JI, Pelegrin P (February 6, 2024).
1230:"Therapeutic interleukin (IL) 1 blockade normalises increased IL1 beta and decreased tumour necrosis factor alpha and IL10 production in blood mononuclear cells of a patient with CINCA syndrome"
1285:
Kallinich T, Hoffman HM, Roth J, Keitzer R (June 1, 2016). "The clinical course of a child with CINCA/NOMID syndrome improved during and after treatment with thalidomide".
87:-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping
354:
100:
232:, the mutation occurs in exon 1. Intracellular formation of the interleukin 1 inflammasome leads to the activation of the potent pro-inflammatory cytokines
760:
Tapia-Abellán A, Angosto-Bazarra D, MartĂnez-Banaclocha H, de Torre-Minguela C, CerĂłn-Carrasco JP, PĂ©rez-Sánchez H, Arostegui JI, Pelegrin P (June 2019).
303:). These therapies are generally effective in alleviating symptoms and substantially reducing levels of inflammatory indices. Case reports suggest that
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92:
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plays a central role in the pathogenesis of the disease, therapy typically targets this cytokine in the form of monoclonal antibodies (such as
229:
192:
104:
199:
and stroma, leading to short term blurring of vision and, after repeated attacks, to central corneal stromal opacities in some patients.
1492:
597:"Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome"
440:
Turunen JA, Wedenoja J, Repo P, Järvinen RS, Jäntti JE, Mörtenhumer S, Riikonen AS, Lehesjoki AE, Majander A, Kivelä TT (January 2018).
244:. The IL-1 inflammasome may also be released from activated macrophages, amplifying the cytokine production cascade. The mutation in
1116:"Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist"
902:
Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N (June 4, 2009).
705:"Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1β production"
279:
mutations. Acute phase reactants and white blood cell count are usually persistently elevated, but this is aspecific for CAPS.
1114:
Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL, Anderson JP, Wanderer AA, Firestein GS (November 13, 2016).
959:
Sibley CH, Chioato A, Felix S, Colin L, Chakraborty A, Plass N, Rodriguez-Smith J, Brewer C, King K (September 1, 2015).
652:
Neven B, Prieur AM, Quartier dit Maire P (September 1, 2008). "Cryopyrinopathies: update on pathogenesis and treatment".
1171:
Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C (August 10, 2006).
817:
481:
Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA, Scott DG, Nicholls A, Pavek S (October 1, 1999).
96:
88:
1425:
847:
Toplak N, Frenkel J, Ozen S, Lachmann HJ, Woo P, Koné-Paut I, De
Benedetti F, Neven B, Hofer M (July 1, 2012).
211:
Cryopyrin-associated periodic syndromes are associated with a gain-of-function missense mutation in exon 3 of
195:, systemic symptoms are not reported whereas the patients experience periodical transient inflammation of the
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137:
1465:
329:
66:
538:
Darisipudi MN, Thomasova D, Mulay SR, Brech D, Noessner E, Liapis H, Anders HJ (October 21, 2016).
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genetic background. Inheritance of these disorders is autosomal dominant with variable penetrance.
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884:
685:
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233:
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84:
961:"A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease"
136:, or less commonly joint contracture, patellar overgrowth, bone deformity, bone erosion and/or
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1173:"Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition"
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symptoms such as fatigue, malaise, mood disorders or failure to thrive), skin rash (either
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in which the autoinflammatory symptoms affect only the anterior segment of the eye.
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849:"An international registry on autoinflammatory diseases: the Eurofever experience"
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124:; 97% of cases) especially after cold exposure, and musculoskeletal involvement (
1385:
595:
Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (November 1, 2001).
540:"Uromodulin Triggers IL-1β–Dependent Innate Immunity via the NLRP3 Inflammasome"
308:
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83:) is a group of rare, heterogeneous autoinflammatory disease characterized by
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140:; 86% of cases). Less common features included ophthalmological involvement (
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Cryopyrin-associated periodic syndrome is autosomal dominant in inheritance
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Cryopyrin-associated periodic syndromes: background and therapeutics.
762:"MCC950 closes the active conformation of NLRP3 to an inactive state"
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904:"Use of canakinumab in the cryopyrin-associated periodic syndrome"
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275:
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483:"Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44"
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Seitz M, Kamgang RK, Simon HU, Villiger PM (December 1, 2005).
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leads to aberrant constitutive formation of this inflammasome.
95:(FCAS, formerly termed familial cold-induced urticaria), the
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23:
330:"Orphanet: Cryopyrin associated periodic syndrome"
299:), or interleukin 1 receptor antagonists (such as
203:symptoms, although the exact reported rates vary.
164:(42% of cases), neurological involvement (morning
184:or intellectual disability; 40% of cases), and
101:neonatal-onset multisystem inflammatory disease
544:Journal of the American Society of Nephrology
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353:: CS1 maint: numeric names: authors list (
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1386:Autoinflammatory Alliance CAPS Guidebook
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93:familial cold autoinflammatory syndrome
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77:Cryopyrin-associated periodic syndrome
24:Cryopyrin-associated periodic syndrome
654:Nature Clinical Practice Rheumatology
230:keratoendotheliitis fugax hereditaria
193:keratoendotheliitis fugax hereditaria
105:keratoendotheliitis fugax hereditaria
7:
1382:Mod Rheumatol. 2010 Jun;20(3):213-21
1287:Scandinavian Journal of Rheumatology
368:
366:
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307:and the anti-IL-6 receptor antibody
253:Up to 170 heterogenous mutations in
1177:The New England Journal of Medicine
908:The New England Journal of Medicine
295:), binding proteins/traps (such as
160:or impaired vision; 71% of cases),
487:American Journal of Human Genetics
14:
446:American Journal of Ophthalmology
1234:Annals of the Rheumatic Diseases
965:Annals of the Rheumatic Diseases
853:Annals of the Rheumatic Diseases
376:Annals of the Rheumatic Diseases
977:10.1136/annrheumdis-2013-204877
865:10.1136/annrheumdis-2011-200549
388:10.1136/annrheumdis-2013-204991
1:
1132:10.1016/S0140-6736(04)17401-1
240:through a cascade involving
221:, a major component of the
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1493:Autoinflammatory syndromes
721:10.1038/s41467-024-44990-0
89:autoinflammatory syndromes
1299:10.1080/03009740410010236
778:10.1038/s41589-019-0278-6
459:10.1016/j.ajo.2018.01.017
162:neurosensory hearing loss
45:
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1339:Arthritis and Rheumatism
1019:Arthritis and Rheumatism
1246:10.1136/ard.2005.036749
1077:10.2310/7750.2008.07050
766:Nature Chemical Biology
311:may also be effective.
556:10.1681/ASN.2012040338
921:10.1056/NEJMoa0810787
709:Nature Communications
97:Muckle–Wells syndrome
1189:10.1056/NEJMoa055137
666:10.1038/ncprheum0874
217:, the gene encoding
1378:Kubota T, Koike R.
1126:(9447): 1779–1785.
828:on October 21, 2016
197:corneal endothelium
176:, or less commonly
150:optic nerve atrophy
148:, or less commonly
1452:External resources
122:maculopapular rash
111:Signs and symptoms
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1351:10.1002/art.21965
1240:(12): 1802–1803.
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914:(23): 2416–2425.
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382:(11): 2043–2049.
138:osteolytic lesion
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18:Medical condition
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188:(4% of cases).
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226:inflammasome
212:
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207:Pathogenesis
201:
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170:papilloedema
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76:
75:
15:
1071:(1): 8–16.
832:October 21,
715:(1): 1096.
309:tocilizumab
305:thalidomide
293:canakinumab
269:is made by
99:(MWS), and
57:Dermatology
29:Other names
1482:Categories
818:"Infevers"
315:References
297:rilonacept
174:meningitis
130:arthralgia
118:urticarial
91:including
1442:430079001
1437:SNOMED CT
1359:0004-3591
1307:0300-9742
1254:0003-4967
1197:1533-4406
1140:1474-547X
1085:1203-4754
1039:0004-3591
985:1468-2060
930:1533-4406
873:1468-2060
786:1552-4450
729:2041-1723
674:1745-8390
621:1061-4036
564:1046-6673
507:0002-9297
452:: 41–50.
422:206850668
406:1468-2060
339:April 27,
283:Treatment
264:Diagnosis
242:caspase 1
219:cryopyrin
172:, and/or
134:arthritis
132:, and/or
52:Specialty
1461:Orphanet
1367:16802372
1323:30354429
1315:16134734
1272:16284353
1215:16899778
1158:15541451
1101:34516905
1093:18258152
1047:18668535
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