Open Access Maced J Med Sci. 2020 Sep 03; 8(F):241-245. 241 Scientifc Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Sep 03; 8(F):241-245. https://doi.org/10.3889/oamjms.2020.5024 eISSN: 1857-9655 Category: F - Review Articles Section: Narrative Review Article Cryopyrin-Associated Periodic Syndromes and Treatment Options Lidija Kareva*, Katarina Stavrik, Kristina Mironska Department of Immunology, University Pediatric Clinic, University “Ss. Cyril and Methodius”, Skopje, Republic of Macedonia Abstract Cryopyrin-associated periodic syndromes (CAPSs) are a growing family of autoinfammatory diseases, also known as periodic fever syndromes. There are three forms of CAPS: (1) Familial Cold autoinfammatory syndrome or familial cold urticaria, (2) Muckle-wells syndrome, and (3) neonatal-onset multisystem infammatory disease or chronic infantile neurological cutaneous articular syndrome. Genetic mutations in the NLRP3 gene were found to be present in most patients. The foremost common fndings between all the CAPS disorders are rash, fever which is sometimes present at birth or in early childhood, joint problems, and conjunctivitis. More extreme forms of CAPS include more persistent infammation that can cause hearing loss and meningitis and can lead to mental and developmental delays. Drugs for CAPS target the source of infammation – which is the over-production of interleukin 1ß by modifed cryopyrin infammasomes. Three drugs are used to treat CAPS: Rilonacept, canakinumab, and anakirna. With these drugs, the prognosis is greatly improved, with most patients having less frequent episodes, decreased buildup of amyloid in the body, and extended life of severe cases up to adulthood. Edited by: Slavica Hristomanova-Mitkovska Citation: Kareva L, Stavrik K, Mironska K. Cryopyrin- Associated Periodic Syndromes and Treatment Options. Open Access Maced J Med Sci. 2020 Sep 03; 8(F):241-245. https://doi.org/10.3889/oamjms.2020.5024 Keywords: Cryopyrin-associated periodic syndrome; Familial cold autoinfammatory syndrome; Muckle-Wells syndrome; Neonatal-onset multisystem infammatory disease; Anakinra; Rilonacept; Canakinumab *Correspondence: Lidija Kareva, Department of Immunology, University Pediatric Clinic, “Ss. Cyril and Methodius University,” Vodnjanska 17, 1000 Skopje, Republic of Macedonia. Phone: +389075215613. E-mail: kvlidija@yahoo.com Received: 30-May-2020 Revised: 25-Jul-2020 Accepted: 29-Jul-2020 Copyright: © 2020 Lidija Kareva, Katarina Stavrik, Kristina Mironska Funding: This research did not receive any fnancial support Competing Interest: The authors have declared that no competing interest exists Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC 4.0) Introduction Cryopyrin-associated periodic syndromes (CAPSs) are a growing family of autoinfammatory diseases, also known as periodic fever syndromes. Autoinfammatory diseases are a group of disorders characterized by repetitive episodes of systemic and organ-specifc infammation. Unlike autoimmune diseases which are caused by activation of the specifc immune system, people with autoinfammatory diseases do not produce autoantibodies or antigen- specifc lymphocytes, instead, these diseases are caused by genetic mutations in molecules that regulate the innate immune response [1], [2]. There are three forms of CAPS: (1) Familial cold autoinfammatory syndrome (FCAS) or familial cold urticaria, (2) Muckle- Wells Syndrome (MWS), and (3) Neonatal-onset multisystem infammatory disease (NOMID) or chronic infantile neurological cutaneous articular syndrome (CINCA). Genetic mutations in the NLRP3 gene were found to be present in most patients [3], [4], [5], [6]. These three syndromes represent varying degrees of infammation caused by the same condition with diferent levels of severity. The NLRP3 gene gives instructions for making a protein called cryopyrin which is one of the regulators of the process of infammation. Cryopyrin is included within the get together of a molecular complex called an infammasome that mediates activation of caspase-1. Caspase-1 regulates the production of interleukin-1 (IL-1) beta. NLRP3 mutations result in an abnormal cryopyrin structure, leading to abnormally high infammasome activity response, resulting to overproduction of proinfamatory cytokine IL-1ß [3], [4], [5], [6], [7], [8], [9]. These results are connected with the episodes of fever and damage to the body’s cells and tissues. The foremost common fndings between all the CAPS disorders are rash, fever which is sometimes present at birth or in early childhood, joint problems, and conjunctivitis. More extreme forms of CAPS include more persistent infammation that can cause hearing loss and meningitis and can lead to mental and development delays. Epidemiology CAPS is very rare diseases. The incidence in Germany is 0.34 per 10 6 persons-years [10]. Based on that, research in Republic of Macedonia should be 1–2 new patients every 2 years.