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Familial cold autoinflammatory syndrome 4(FCAS4)

MedGen UID:
863713
Concept ID:
C4015276
Disease or Syndrome
Synonym: FCAS4
SNOMED CT: FCAS4 - familial cold autoinflammatory syndrome 4 (1264006004); NLRC4-related familial cold autoinflammatory syndrome (1264006004); NLR family caspase recruitment domain-containing 4-related familial cold autoinflammatory syndrome (1264006004); NLRC4-related familial cold urticaria (1264006004)
 
Gene (location): NLRC4 (2p22.3)
 
Monarch Initiative: MONDO:0014498
OMIM®: 616115
Orphanet: ORPHA576349

Definition

A rare hereditary periodic fever syndrome with characteristics of infantile or childhood onset of episodes of fever and cold-induced urticaria-like rash and arthralgia. Ocular features such as conjunctivitis and uveitis may also be present. Presentation is typically mild and symptoms resolve without treatment in most cases. [from SNOMEDCT_US]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Urticaria
MedGen UID:
22587
Concept ID:
C0042109
Disease or Syndrome
Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Marzano AV, Maronese CA, Genovese G, Ferrucci S, Moltrasio C, Asero R, Cugno M
J Allergy Clin Immunol 2022 Apr;149(4):1137-1149. doi: 10.1016/j.jaci.2022.02.007. PMID: 35396080
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA
Nat Med 2015 Mar;21(3):248-55. Epub 2015 Feb 16 doi: 10.1038/nm.3806. PMID: 25686105Free PMC Article

Recent clinical studies

Etiology

Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Zhuang L, Chen J, Yu J, Marathe A, Sahajwalla C, Borigini M, Maynard J, Burckart GJ, Wang Y
Clin Pharmacol Ther 2019 Sep;106(3):557-567. Epub 2019 Jan 28 doi: 10.1002/cpt.1302. PMID: 30447083
Peleg H, Ben-Chetrit E
Curr Opin Rheumatol 2017 Jan;29(1):4-11. doi: 10.1097/BOR.0000000000000347. PMID: 27755121
So A, Ives A, Joosten LA, Busso N
Nat Rev Rheumatol 2013 Jul;9(7):391-9. Epub 2013 May 14 doi: 10.1038/nrrheum.2013.61. PMID: 23670136
Neven B, Prieur AM, Quartier dit Maire P
Nat Clin Pract Rheumatol 2008 Sep;4(9):481-9. Epub 2008 Jul 29 doi: 10.1038/ncprheum0874. PMID: 18665151

Diagnosis

Marzano AV, Maronese CA, Genovese G, Ferrucci S, Moltrasio C, Asero R, Cugno M
J Allergy Clin Immunol 2022 Apr;149(4):1137-1149. doi: 10.1016/j.jaci.2022.02.007. PMID: 35396080
Maltseva N, Borzova E, Fomina D, Bizjak M, Terhorst-Molawi D, Košnik M, Kulthanan K, Meshkova R, Thomsen SF, Maurer M; COLD-CE Steering Committee
Allergy 2021 Apr;76(4):1077-1094. Epub 2020 Dec 24 doi: 10.1111/all.14674. PMID: 33249577
Georgin-Lavialle S, Ducharme-Benard S, Sarrabay G, Savey L, Grateau G, Hentgen V
Best Pract Res Clin Rheumatol 2020 Aug;34(4):101529. Epub 2020 Jun 13 doi: 10.1016/j.berh.2020.101529. PMID: 32546426
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Lachmann HJ
Best Pract Res Clin Rheumatol 2017 Aug;31(4):596-609. Epub 2018 Jan 11 doi: 10.1016/j.berh.2017.12.001. PMID: 29773275

Therapy

Maltseva N, Borzova E, Fomina D, Bizjak M, Terhorst-Molawi D, Košnik M, Kulthanan K, Meshkova R, Thomsen SF, Maurer M; COLD-CE Steering Committee
Allergy 2021 Apr;76(4):1077-1094. Epub 2020 Dec 24 doi: 10.1111/all.14674. PMID: 33249577
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Lachmann HJ
Best Pract Res Clin Rheumatol 2017 Aug;31(4):596-609. Epub 2018 Jan 11 doi: 10.1016/j.berh.2017.12.001. PMID: 29773275
Ozen S, Demir S
Paediatr Drugs 2017 Aug;19(4):303-311. doi: 10.1007/s40272-017-0232-6. PMID: 28497352
Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA
Nat Med 2015 Mar;21(3):248-55. Epub 2015 Feb 16 doi: 10.1038/nm.3806. PMID: 25686105Free PMC Article

Prognosis

Shangguan Y, Ding X, Ma L, Cai YX, Xiang S, Huang XF, Shen Y, Yu HG, Zheng W
J Immunol Res 2024;2024:5722548. Epub 2024 Mar 6 doi: 10.1155/2024/5722548. PMID: 38481988Free PMC Article
Miyamoto T, Izawa K, Masui S, Yamazaki A, Yamasaki Y, Matsubayashi T, Shiraki M, Ohnishi H, Yasumura J, Kawabe T, Miyamae T, Matsubara T, Arakawa N, Ishige T, Takizawa T, Shimbo A, Shimizu M, Kimura N, Maeda Y, Maruyama Y, Shigemura T, Furuta J, Sato S, Tanaka H, Izumikawa M, Yamamura M, Hasegawa T, Kaneko H, Nakagishi Y, Nakano N, Iida Y, Nakamura T, Wakiguchi H, Hoshina T, Kawai T, Murakami K, Akizuki S, Morinobu A, Ohmura K, Eguchi K, Sonoda M, Ishimura M, Furuno K, Kashiwado M, Mori M, Kawahata K, Hayama K, Shimoyama K, Sasaki N, Ito T, Umebayashi H, Omori T, Nakamichi S, Dohmoto T, Hasegawa Y, Kawashima H, Watanabe S, Taguchi Y, Nakaseko H, Iwata N, Kohno H, Ando T, Ito Y, Kataoka Y, Saeki T, Kaneko U, Murase A, Hattori S, Nozawa T, Nishimura K, Nakano R, Watanabe M, Yashiro M, Nakamura T, Komai T, Kato K, Honda Y, Hiejima E, Yonezawa A, Bessho K, Okada S, Ohara O, Takita J, Yasumi T, Nishikomori R; Japan CAPS Working Group
Arthritis Rheumatol 2024 Jun;76(6):949-962. Epub 2024 Mar 7 doi: 10.1002/art.42808. PMID: 38268504
Fonollosa A, Pelegrín L, García-Morillo S, Buján-Rivas S, Distefano L, Robles-Maruenda A, Fernández-Martín J, González-García A, Garcia-Aparicio Á, Ortego-Centeno N, Llorenç V, Sainz de la Maza M, Pinedo C, Sopeña B, Cocho L, Carreño E, Blanco R, Antón J, Pérez-Quintana M, Marques-Soares JR, Artaraz J, Ruiz-Arruza I, Soto-Peleteiro A, Gómez-Caverzaschi V, Araújo O, Espinosa G, Adan A, Fabiani C, Cantarini L, Hernández-Rodríguez J; Spanish Society of Ocular Inflammation (SEIOC) and the AutoInflammatory Diseases Alliance (AIDA) Network
Clin Exp Rheumatol 2023 Oct;41(10):2105-2114. Epub 2023 Sep 28 doi: 10.55563/clinexprheumatol/ukegcc. PMID: 37812477
Kuemmerle-Deschner JB
Semin Immunopathol 2015 Jul;37(4):377-85. Epub 2015 May 12 doi: 10.1007/s00281-015-0491-7. PMID: 25963520
Ross JB, Finlayson LA, Klotz PJ, Langley RG, Gaudet R, Thompson K, Churchman SM, McDermott MF, Hawkins PN
J Cutan Med Surg 2008 Jan-Feb;12(1):8-16. doi: 10.2310/7750.2008.07050. PMID: 18258152

Clinical prediction guides

Zhang C, Yu Z, Gao S, Ma M, Gou L, Wang C, Wang L, Li J, Zhong L, Zhou Y, Wang W, Song H
Pediatr Rheumatol Online J 2023 Oct 17;21(1):124. doi: 10.1186/s12969-023-00881-0. PMID: 37848905Free PMC Article
Fonollosa A, Pelegrín L, García-Morillo S, Buján-Rivas S, Distefano L, Robles-Maruenda A, Fernández-Martín J, González-García A, Garcia-Aparicio Á, Ortego-Centeno N, Llorenç V, Sainz de la Maza M, Pinedo C, Sopeña B, Cocho L, Carreño E, Blanco R, Antón J, Pérez-Quintana M, Marques-Soares JR, Artaraz J, Ruiz-Arruza I, Soto-Peleteiro A, Gómez-Caverzaschi V, Araújo O, Espinosa G, Adan A, Fabiani C, Cantarini L, Hernández-Rodríguez J; Spanish Society of Ocular Inflammation (SEIOC) and the AutoInflammatory Diseases Alliance (AIDA) Network
Clin Exp Rheumatol 2023 Oct;41(10):2105-2114. Epub 2023 Sep 28 doi: 10.55563/clinexprheumatol/ukegcc. PMID: 37812477
Wu N, Wu D, Miao J, Zhao M, Wang Y, Yu W, Shen M
Clin Rheumatol 2023 Oct;42(10):2841-2848. Epub 2023 Jun 27 doi: 10.1007/s10067-023-06679-5. PMID: 37368056
Kuemmerle-Deschner JB, Koitschev A, Ummenhofer K, Hansmann S, Plontke SK, Koitschev C, Koetter I, Angermair E, Benseler SM
Arthritis Rheum 2013 Mar;65(3):824-31. doi: 10.1002/art.37810. PMID: 23440695
Rosengren S, Mueller JL, Anderson JP, Niehaus BL, Misaghi A, Anderson S, Boyle DL, Hoffman HM
J Allergy Clin Immunol 2007 Apr;119(4):991-6. Epub 2007 Feb 22 doi: 10.1016/j.jaci.2006.12.649. PMID: 17320940Free PMC Article

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