Variability of clinical symptoms of cryopyrin-associated periodic syndrome within the family

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Cryopyrin-associated periodic syndrome is a group of autoinflammatory diseases caused by mutations in the NLRP3 gene, which lead to uncontrolled inflammasome activation and, consequently, excessive production of the proinflammatory cytokine interleukin 1β. Diagnosis is challenging, since many patients have a heterogeneous multisystem clinical picture. This publication presents a familial case of the disease with variability of manifestations from “blurred” and asymptomatic to a detailed clinical picture with multisystem involvement (persistent inflammatory activity, fever and urticaria associated with cold exposure, erythema nodosum, poly- and monoarthritis, uveitis, aphthous stomatitis, scrotal ulcers, and headache). Two patients had an atypical presentation of symptoms with predominant involvement of the joints, eyes, and oral mucosa, due to which one of them was initially given an alternative diagnosis of Behcet’s disease (syndrome). Genetic testing made it possible to identify a pathogenic mutation in the NLRP3 gene, verify the diagnosis, and promptly prescribe pathogenetic therapy with an interleukin 1 inhibitor, which is necessary to prevent irreversible organ damage (amyloidosis, sensorineural hearing loss, vision loss, etc.) and reduce the burden of the disease.

About the authors

Ulyana A. Markina

Moscow Clinical Science and Research Center Hospital No. 52

Email: itcher.md@bk.ru
ORCID iD: 0000-0002-6646-4233
SPIN-code: 6424-0012
Russian Federation, Moscow

Anna A. Roppelt

Moscow Clinical Science and Research Center Hospital No. 52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-5132-1267
SPIN-code: 7249-4423

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Viktoria V. Zakharova

Moscow Clinical Science and Research Center Hospital No. 52; Endocrinology Research Centre

Email: neskvikk@mail.ru
ORCID iD: 0000-0001-5949-5317
SPIN-code: 1491-2770
Russian Federation, Moscow; Moscow

Oksana A. Golovina

Moscow Clinical Science and Research Center Hospital No. 52

Email: ksan7ch@mail.ru
ORCID iD: 0000-0001-7247-545X
SPIN-code: 1538-3632
Russian Federation, Moscow

Zinaida Yu. Mutovina

Moscow Clinical Science and Research Center Hospital No. 52; Central State Medical Academy

Email: zmutovina@mail.ru
ORCID iD: 0000-0001-5809-6015
SPIN-code: 3943-7930

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow

Alеna Igorevna Zagrebneva

Moscow Clinical Science and Research Center Hospital No. 52; North-Western State Medical University named after I.I. Mechnikov

Email: alrheumo@mail.ru
ORCID iD: 0000-0002-3235-1425
SPIN-code: 6351-4980

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Saint Petersburg

Yunna S. Petrusenko

Biotek Campus

Email: ypetrusenko@biotc.ru
ORCID iD: 0009-0002-8318-5241
SPIN-code: 6632-2260
Russian Federation, Moscow

Elina V. Gazieva

Russian University of Medicine

Email: elinagazieva23@yandex.ru
ORCID iD: 0009-0004-5425-584X
Russian Federation, Moscow

Alexander V. Karaulov

I.M. Sechenov First Moscow State Medical University (Sechenovskiy University); LIFT Center

Email: drkaraulov@mail.ru
ORCID iD: 0000-0002-1930-5424
SPIN-code: 4122-5565

MD, Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow

Maryana A. Lysenko

Moscow Clinical Science and Research Center Hospital No. 52; The Russian National Research Medical University named after N.I. Pirogov

Email: gkb52@zdrav.mos.ru
ORCID iD: 0000-0001-6010-7975
SPIN-code: 3887-6250

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; Moscow

Darya S. Fomina

Moscow Clinical Science and Research Center Hospital No. 52; I.M. Sechenov First Moscow State Medical University (Sechenovskiy University); Astana Medical University

Author for correspondence.
Email: daria_fomina@mail.ru
ORCID iD: 0000-0002-5083-6637
SPIN-code: 3023-4538

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow; Astana, Kazakhstan

References

  1. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942–947. doi: 10.1136/annrheumdis-2016-209686 EDN: YESOUZ
  2. Welzel T, Kuemmerle-Deschner JB. Diagnosis and management of the cryopyrin-associated periodic syndromes (CAPS): what do we know today? J Clin Med. 2021;10(1):128. doi: 10.3390/jcm10010128 EDN: DVJJHI
  3. Nakanishi H, Prakash P, Ito T, et al. Genetic hearing loss associated with autoinflammation. Front Neurol. 2020;11:141. doi: 10.3389/fneur.2020.00141 EDN: LRQELN
  4. Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145(2):295–302. doi: 10.1177/0194599811402296
  5. Diprose WK, Jordan A, Anderson NE. Autoinflammatory syndromes in neurology: when our first line of defence misbehaves. Pract Neurol. 2022;22(2):145–153. doi: 10.1136/practneurol-2021-003031 EDN: GZFFPU
  6. Rodrigues F, Cuisset L, Cador-Rousseau B, et al. AA amyloidosis complicating cryopyrin-associated periodic syndrome: a study of 86 cases including 23 French patients and systematic review. Rheumatology (Oxford). 2022;61(12):4827–4834. doi: 10.1093/rheumatology/keac145 EDN: KOWUUP
  7. Rigante D, Emmi G, Fastiggi M, et al. Macrophage activation syndrome in the course of monogenic autoinflammatory disorders. Clin Rheumatol. 2015;34(8):1333–1339. doi: 10.1007/s10067-015-2923-0
  8. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child. 2001;85(5):421–426. doi: 10.1136/adc.85.5.421
  9. Eroglu FK, Kasapcopur O, Beşbaş N, et al. Genetic and clinical features of cryopyrin-associated periodic syndromes in Turkish children. Clin Exp Rheumatol. 2016;34(6 Suppl 102):S115–S120.
  10. Yıldız M, Haşlak F, Adrovic A, et al. Autoinflammatory diseases in childhood. Balkan Med J. 2020;37(5):236–246. doi: 10.4274/balkanmedj.galenos.2020.2020.4.82 EDN: BMKIBL
  11. 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(7):2809–2815. doi: 10.1182/blood-2003-07-2531
  12. Kozlova AL, Pershin BS, Varlamova TV, Shcherbina AYu. Diagnosis and treatment of patients with cryopyrin-associated periodic syndrome. Current Pediatrics. 2015;14(2):292–297. (In Russ.) doi: 10.15690/vsp.v14i2.1301 EDN: RURJDZ
  13. Kozlova AL, Burlakov VI, Nesterenko ZA, et al. Cryopyrin-associated periodic syndrome assess the efficacy and safety of anakinra therapy: a single center experience. Pediatric Hematology/Oncology and Immunopathology. 2022;21(1):88–92. (In Russ.) doi: 10.24287/1726-1708-2022-21-1-88-92 EDN: FDLUTI
  14. Orphanet: NLRP3-associated autoinflammatory disease. Available from: https://www.orpha.net/en/disease/detail/208650
  15. Liu J, Yu X, Li C, et al., Behçet’s syndrome in a Chinese pedigree of NLRP3-associated autoinflammatory disease: a coexistence or novel presentation? Front Med (Lausanne). 2021;8:695197. doi: 10.3389/fmed.2021.695197 EDN: ZJFUUA
  16. International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD). The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014;28(3):338–347. doi: 10.1111/jdv.12107 EDN: SKMXXD
  17. Romano M, Arici ZS, Piskin D, et al. The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist. Ann Rheum Dis. 2022;74(7):1102–1121. doi: 10.1136/annrheumdis-2021-221801 EDN: EUROWW
  18. Mori T, Saburi M, Hagihara M, et al. Long-term remission of cryopyrin-associated periodic syndrome after allogeneic haematopoietic stem cell transplantation. Ann Rheum Dis. 2021;80(4):542–543. doi: 10.1136/annrheumdis-2020-218695 EDN: PYNXER
  19. Gao Y, Zhong Z, Yang P. Genetics in Behcet’s disease: an update review. Front Ophthalmol (Lausanne). 2022;2:916887. doi: 10.3389/fopht.2022.916887 EDN: WWRXHZ

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright © ABV-press, 2026

License URL: https://rusalljournal.ru/raj/about/submissions#copyrightNotice
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-42773 от  21.07.2009.