Autoinflammation is a new concept, new nosologies. How to recognize it and what to do?
https://doi.org/10.21508/1027-4065-2025-70-6-116-126
Abstract
Autoinflammatory diseases are grouped into a large group of pathologies of a genetic or multifactorial nature, characterized by early onset, repeated episodes of systemic inflammation (fever, rash, increased levels of acute phase proteins), unrelated to infections or other more common causes in children. Patients often have a family history that is burdened: there are similar cases among family members. The polymorphism of clinical manifestations of autoinflammatory diseases necessitates a multidisciplinary approach; They are studied all over the world by doctors of various specialties: pediatricians, immunologists, allergologists, rheumatologists, hematologists, etc. The article highlights the issues of diagnosis and differential diagnosis, clinical and laboratory manifestations, genetic diagnosis, complications, therapeutic approaches, algorithms for faster diagnosis, early and timely therapy. The issues raised relate mainly to the most studied and most common recurrent fevers in children in real clinical practice: familial Mediterranean fever, cryopyrin-associated recurrent syndromes, recurrent febrile syndrome associated with mutation of the tumor necrosis factor alpha receptor gene, mevalonate kinase deficiency syndrome.
About the Authors
S. O. Salugina
Nasonova Research Institute of Rheumatology
Russian Federation
Russian Federation
15522, Moscow
Е. S. Fedorov
Nasonova Research Institute of Rheumatology
Russian Federation
Russian Federation
15522, Moscow
References
1. Kastner D.L., Aksentuevich I., Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell 2010; 140: 784–790. DOI: 10.1016/j.cell.2010.03.002
2. Kuzmina N.N., Salugina S.O., Fedorov E.S. Autoinflammatory diseases and syndromes in children. Moscow: IMA-press. 2012
3. Hashkes P.J., Laxer R.M., Simon A. Textbook of autoinflammation. Springer, 2019; 820
4. Rameev V.V., Lysenko (Kozlovskaya) L.V., Bogdanova M.V., Moiseev S.V. Autoinflammatory diseases. Kliniches kaya farmakologiya i terapiya 2020; 29(4): 49–60 (in Russ.). DOI 10.32756/0869-5490–2020–4–49–60
5. Fietta P. Autoinflammatory disease: the hereditary periodic fever syndromes. Acta Biol. Ateneo Parmense 2004; 75: 92–99
6. McDermott M.F., Aksentijevich I., Galon J., McDermott E.M., Ogunkolade B.W., Centola M., et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999; 97(1): 133–144
7. Federici S., Martini A., Gattorno M. The central role of anti-- IL-1 blockade in the treatment of monogenic and multi-- factorial autoinflammatory diseases. Frontiers un Immunology. 2013; 4: 351. DOI: 10.3389/fimmu.2013.00351
8. Toplak N., Frenkel J., Ozen S., Lachmann H.J., Woo P., Koné-- Paut I., et al. An international registry on autoinflammatory diseases: the Eurofever experience. Ann Rheum Dis. 2012; 71(7): 1177–1182. DOI: 10.1136/annrheumdis-2011-200549
9. Clinical guidelines — Familial Mediterranean fever (Hereditary familial amyloidosis) — 2023–2024–2025 (03/14/2023) — Approved by the Ministry of Health of the Russian Federation (in Russ) http://disuria.ru/_ld/13/1345_kr23E85p0MZ.pdf Ссылка активна на 8.10.2025
10. Clinical guidelines — Cryopyrin-associated periodic syndromes (Other specified disorders involving the immune mechanism, not elsewhere classified) — 2023–2024–2025 (03/15/2023) — Approved by theMinistry ofHealth oftheRussian Federation (inRuss) http://disuria.ru/_ld/14/1431_kr23E85p0M08p2M.pdf Ссылкпа активна на 8.10.2025
11. Clinical guidelines — Tumor necrosis factor receptor gene mutation-associated periodic syndrome (TRAPS) (Other specified disorders involving the immune mechanism, not elsewhere classified) — 2023–2024–2025 (03/16/2023) — Approved by the Ministry of Health of the Russian Federation (in Russ) http://disuria.ru/_ld/13/1339_kr23D89p8MZ.pdf Ссылка активна на 8.10.2025
12. Simon A., van der Meer J.W.S. Patogenesis of familial periodic fever syndromes or hereditary inflammatory syndromes. Am J Physiol Regul Integr Comp Physiol 2007; 292: 86–98. DOI: 10.1152/ajpregu.00504.2006
13. Janeway T.C., Mosental H. Unusual paroxysmal syndrome probably allied to recurrent vomiting, with a study of nitrogen metabolism. Trans Assoc Am Physicians. 1908; 504–518. DOI: 10.1001/ARCHINTE.1908.00050080016002
14. Siegal S. Benign paroxysmal peritonitis. Ann. Intern. Med. 1945; 23: 1–21
15. Reimann H.A. “Periodic disease A probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. JAMA 1948; 136: 239–244
16. Fedorov E.S., Salugina S.O. Familial Mediterranean fever (periodic disease): history or a real problem. Sovremennaya Revmatologiya 2018; 12(3): 61–69. (in Russ.) DOI: 10.14412/1996-7012-2018-3-61-69
17. Lachmann H.J., Papa R., Gerhold K., Obici L., Touitou I., Cantarini L., et al. The phenotype of TNF receptor-- associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registryAnn Rheum Dis 2014; 73: 2160–2167. DOI: 10.1136/annrheumdis-2013-204184
18. Salugina S.O., Fedorov E.S., Kaleda M.I., Kamenets E.A., Zakharova E.Y. Clinical and genetic characteristics of patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) according to the data from the V.A. Nasonova Research Institute of Rheumatology. Pediatria n.a. G.N. Speransky. 2022; 101 (4): 64–71. DOI: 10.24110/0031-403X-2022-101-4-64-71
19. Ter Haar N.M., Jeyaratnam J., Lachmann H.J., Simon A., Brogan P.A., Doglio M., et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the eurofever registry Arthritis Rheumatol, 2016; 68(11): 2795–2805. DOI: 10.1002/art.39763
20. Kozlova A.L., Bludova V.O., Burlakov V.I., Raykina E.V., Varlamova T.V., Kurnikova M.A., et al. Mevalonate kinase deficiency syndrome: Single center experience. NauchcnoPrakticheskaya Revmatologia 2021; 59(3): 326–334 (in Russ.) DOI: 10.47360/1995-4484-2021-326-334
21. Levy R., Gérard L., Kuemmerle-Deschner J., Lachmann H.J., Koné-Paut I., Cantarini L., et al. Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry AnnRheum Dis 2015; 74: 2043–2049 DOI: 10.1136/annrheumdis-2013-20499
22. Monfort B., Desbayes S., Dusser P., Bourguiba R., Savey L., Vinit C., et al. Cutaneous manifestations of monogenic auto-inflammatory diseases: An international cohort study from the Juvenile Inflammatory Rheumatism cohort J Am Acad Dermatol. 2022; 87(6): 1391–1394. DOI: 10.1016/j.jaad.2022.08.015
23. Salugina S.O., Fedorov E.S., Torgashina A.V. CINCA/NOMID is a rare autoinflammatory syndrome in rheumatological practice Experience of diagnosis, management and therapy with interleukin-1 inhibitors. Sovremennaya Revmatologiya 2024; 18(2): 25–32. (in Russ) DOI: 10.14412/1996-7012-2024-2-25-32
24. The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet. 1997; 17(1): 25–31
25. The International FMF Consortium. Ancient missense mutation in a new member of the RoRet gene family are likely to cause familial Mediterrnean fever. Cell. 1997; 90(4): 797–807
26. Drenth J.P., Cuisset L., Grateau G., Vasseur C., van de Velde-- Visser S.D., de Jong J.G. et al. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat. Genet. 1999; 22 (2): 178–181. DOI: 10.1038/9696
27. Hoffman H.M., Mueller J.L., Broide D.H., Wanderer A.A., Kolodner R.D. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001; 29(3): 301–305. DOI: 10.1038/ng756
28. Aksentijevich I., Nowak M., Mallah M., Chae J.J., Watford W.T., Hofmann S.R. 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(12): 3340–3348. DOI: 10.1002/art.10688
29. The registry of Hereditary Auto-inflammatory Disorders Mutations. https://infevers.umai-montpellier.fr/web/ Ссылка активна на 8.10.2025
30. Gattorno M., Hofer M., Federici S., Vanoni F., Bovis F., Aksentijevich I., et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 2019; 78: 1025 –1032. DOI: 10.1136/annrheumdis-2019-215048
31. Obici L.,Merlini G. Amyloidosis in autoinflammatory syndromes. Autoimmunity Reviews 2012; 12: 14–17 DOI: 10.1016/j.autrev.2012.07.016
32. Rameev V.V., Moiseev S.V., Kozlovskaya L.V. AA amyloidosis in autoinflammatory diseases. Klinicheskaya farmakologiya i terapiya 2021; 30(4): 52–61 (in Russ.). DOI: 10.32756/0869-5490-2021–4–52–61
33. Ter Haar N.M., Oswald M., Jeyaratnam J., Anton J., Barron K.S., Brogan P.A. et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis. 2015; 74(9): 1636–1644. DOI: 10.1136/annrheumdis-2015-207546
34. Soriano A., Soriano M., Espinosa G. Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide. Front Immunol. 2020; 11: 865. DOI: 10.3389/fimmu.2020.00865
35. Hansman S., Lainka E., Horneff G., Holzinger D., Rieber N., Jansson A.F., et al. Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/ HIDS: a German PRO-KIND initiative. Pediatr Rheumatol Online J. 2020; 18(1): 17. DOI: 10.1186/s12969-020-0409-3
36. Ter Haar N., Lachmann H., Ozen S., Woo P., Uziel Y., Modesto C., et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis. 2013; 72(5): 678–685. DOI: 10.1136/annrheumdis2011-201268
37. Romano M., Arici Z.S., Piskin D., Alehashemi S. 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 ntcrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist Ann Rheum Dis 2022; 81: 907–921. DOI: 10.1136/annrheumdis-2021-221801
38. Ozen S., Demirkaya E., Erer B., Livneh A., Ben-Chetrit E., Giancane G., et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016 Apr; 75(4): 644–651. DOI: 10.1136/annrheumdis-2015-208690. Epub 2016 Jan 22
39. Ozen S., Sağ E., Oton T,. Gül A., Sieiro Santos C., Bayraktar D., et al. EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update. Ann Rheum Dis. 2025; 84(6): 899–909. DOI: 10.1016/j.ard.2025.01.028
40. Kuemmerle-Deschner J., Gautam R., George A., Raza S., Lomax K.G., Hur P. Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome. RMD Open. 2020; 6(2): e001227. DOI: 10.1136/rmdopen-2020–001227
41. Neven B., Marvillet I., Terrada C., Ferster A., Boddaert N., Couloignier V., et al. Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-- onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 2010; 62: 258–267. DOI: 10.1002/art.25057
42. Walker U.A., Tilson H.H., Hawkins P.N., Poll T.V., Noviello S., Levy J., et al. Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-- associated periodic syndrome: results from the β-Confident Registy. RMD Open. 2021; 7(2): e001663. DOI: 10.1136/rmdopen-2021–001663
43. Benedetti F., Gattorno M., Anton J., Ben-Chetrit E., Frenkel J., Hoffman H., et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med. 2018; 378(20): 1908–1919. DOI: 10.1056/NEJMoa1706314
44. Salugina S.O., Fedorov E.S. Biologic disease-modifying antirheumatic drugs in the treatment of major monogenic autoinflammatory diseases: literature review and clinical observation. Sovremennaya Revmatologiya 2021; 15(6): 95– 100 (in Russ) DOI: 10.14412/1996-7012-2021-6-95-100
Review
For citations:
Salugina S.O., Fedorov Е.S. Autoinflammation is a new concept, new nosologies. How to recognize it and what to do? Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2025;70(6):116-126. (In Russ.) https://doi.org/10.21508/1027-4065-2025-70-6-116-126
Views:
30
JATS XML
Email this article 