Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies
Cryopyrin-associated periodic syndromes (CAPS) are a group of rare, genetically determined autoinflammatory diseases resulting from gain-of-function mutations in the NLRP3 gene. These mutations lead to constitutive activation of the inflammasome and overproduction of interleukin-1β and interleukin-...
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Kazimierz Wielki University
2025-07-01
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| Series: | Journal of Education, Health and Sport |
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| Online Access: | https://apcz.umk.pl/JEHS/article/view/61828 |
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| author | Joanna Nadaj Bartosz Czyżewski Anna Mariankowska Anna Dróżdż Weronika Posuniak Michał Dorota Karol Kozłowski Oliwia Kawa Wojciech Żywiec Cezary Milczarek |
| author_facet | Joanna Nadaj Bartosz Czyżewski Anna Mariankowska Anna Dróżdż Weronika Posuniak Michał Dorota Karol Kozłowski Oliwia Kawa Wojciech Żywiec Cezary Milczarek |
| author_sort | Joanna Nadaj |
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Cryopyrin-associated periodic syndromes (CAPS) are a group of rare, genetically determined autoinflammatory diseases resulting from gain-of-function mutations in the NLRP3 gene. These mutations lead to constitutive activation of the inflammasome and overproduction of interleukin-1β and interleukin-18, driving chronic systemic inflammation. CAPS encompasses three distinct clinical phenotypes—familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and chronic infantile neurologic cutaneous and articular syndrome (CINCA/NOMID)—which vary in severity and organ involvement. FCAS presents the mildest course with cold-induced symptoms, while CINCA/NOMID is the most severe form, often associated with CNS involvement and progressive sensorineural deficits.
Recent advances in understanding CAPS pathophysiology have led to the development of targeted biological therapies aimed at IL-1 inhibition. Anakinra, canakinumab, and rilonacept have demonstrated significant clinical efficacy in reducing systemic inflammation, alleviating symptoms, and improving long-term outcomes, including prevention of organ damage. Early intervention is crucial, especially in severe forms such as CINCA/NOMID, to avoid irreversible complications. The diagnosis of CAPS is based on clinical criteria supported by elevated inflammatory markers and confirmed by genetic testing.
This review presents a comprehensive overview of CAPS, covering its molecular mechanisms, clinical manifestations, diagnostic criteria, and current therapeutic strategies, with a focus on IL-1 targeted treatments as the mainstay of care.
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| format | Article |
| id | doaj-art-64aa7a0ff1a345128db0a25dafd5ecc4 |
| institution | DOAJ |
| issn | 2391-8306 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Kazimierz Wielki University |
| record_format | Article |
| series | Journal of Education, Health and Sport |
| spelling | doaj-art-64aa7a0ff1a345128db0a25dafd5ecc42025-08-20T02:40:05ZengKazimierz Wielki UniversityJournal of Education, Health and Sport2391-83062025-07-018310.12775/JEHS.2025.83.61828Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies Joanna Nadaj0https://orcid.org/0009-0005-5991-7993Bartosz Czyżewski1https://orcid.org/0009-0005-1665-8573Anna Mariankowska2https://orcid.org/0009-0003-0714-404XAnna Dróżdż3https://orcid.org/0009-0006-4822-3643Weronika Posuniak4https://orcid.org/0009-0006-6923-8377Michał Dorota5https://orcid.org/0009-0008-7481-0045Karol Kozłowski6https://orcid.org/0009-0006-8249-1908Oliwia Kawa7https://orcid.org/0009-0007-2342-8236Wojciech Żywiec8https://orcid.org/0009-0009-5505-5168Cezary Milczarek9https://orcid.org/0009-0003-2041-8324Medical University of LodzCentral Clinical Hospital of Medical University of Lodz, Pomorska 251, 92-213 LodzProvincial Hospital of St. Luke in Tarnow, ul Lwowska 178A, 33-100 TarnowCentral Clinical Hospital of Medical University of Lodz, ul Pomorska 251, 92-213 LodzHospital of the Ministry of Interior and Administration in Lodz. ul. Polnocna 42, 91-425 LodzCentral Clinical Hospital of Medical University of Lodz, ul Pomorska 251, 92-213 LodzProvincial Integrated Hospital in Kielce, Grunwaldzka 45, 25-736 KielceProvincial Hospital of St. Luke in Tarnow, ul Lwowska 178A, 33-100 TarnowProvincial Hospital of St. Luke in Tarnow, ul Lwowska 178A, 33-100 TarnowMedical University of Lodz, al. Tadeusza Kosciuszki 4, 90-419 Lodz Cryopyrin-associated periodic syndromes (CAPS) are a group of rare, genetically determined autoinflammatory diseases resulting from gain-of-function mutations in the NLRP3 gene. These mutations lead to constitutive activation of the inflammasome and overproduction of interleukin-1β and interleukin-18, driving chronic systemic inflammation. CAPS encompasses three distinct clinical phenotypes—familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and chronic infantile neurologic cutaneous and articular syndrome (CINCA/NOMID)—which vary in severity and organ involvement. FCAS presents the mildest course with cold-induced symptoms, while CINCA/NOMID is the most severe form, often associated with CNS involvement and progressive sensorineural deficits. Recent advances in understanding CAPS pathophysiology have led to the development of targeted biological therapies aimed at IL-1 inhibition. Anakinra, canakinumab, and rilonacept have demonstrated significant clinical efficacy in reducing systemic inflammation, alleviating symptoms, and improving long-term outcomes, including prevention of organ damage. Early intervention is crucial, especially in severe forms such as CINCA/NOMID, to avoid irreversible complications. The diagnosis of CAPS is based on clinical criteria supported by elevated inflammatory markers and confirmed by genetic testing. This review presents a comprehensive overview of CAPS, covering its molecular mechanisms, clinical manifestations, diagnostic criteria, and current therapeutic strategies, with a focus on IL-1 targeted treatments as the mainstay of care. https://apcz.umk.pl/JEHS/article/view/61828Cryopyrin-Associated Periodic SyndromesNLRP3AnakinraCINCA/NOMIDMuckle-Wells syndromeFamilial Cold Autoinflammatory Syndrome |
| spellingShingle | Joanna Nadaj Bartosz Czyżewski Anna Mariankowska Anna Dróżdż Weronika Posuniak Michał Dorota Karol Kozłowski Oliwia Kawa Wojciech Żywiec Cezary Milczarek Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies Journal of Education, Health and Sport Cryopyrin-Associated Periodic Syndromes NLRP3 Anakinra CINCA/NOMID Muckle-Wells syndrome Familial Cold Autoinflammatory Syndrome |
| title | Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies |
| title_full | Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies |
| title_fullStr | Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies |
| title_full_unstemmed | Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies |
| title_short | Cryopyrin-Associated Periodic Syndromes (CAPS): Pathogenesis, Clinical Manifestations, and IL-1-Targeted Therapeutic Strategies |
| title_sort | cryopyrin associated periodic syndromes caps pathogenesis clinical manifestations and il 1 targeted therapeutic strategies |
| topic | Cryopyrin-Associated Periodic Syndromes NLRP3 Anakinra CINCA/NOMID Muckle-Wells syndrome Familial Cold Autoinflammatory Syndrome |
| url | https://apcz.umk.pl/JEHS/article/view/61828 |
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