{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:00:11Z","timestamp":1777950011320,"version":"3.51.4"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Schnitzler syndrome (SchS) is a rare, late-onset, acquired autoinflammatory disorder characterized by recurrent urticarial lesions, monoclonal gammopathy and systemic inflammation. Although interleukin-1 (IL-1) blockade with anakinra is considered as a standard of care, real-world data on long-term outcomes, biomarker utility and dose reduction remain limited. To evaluate the long-term efficacy and safety of anakinra, the utility of inflammatory biomarkers for disease monitoring, the feasibility of dose reduction and diagnostic delay in a cohort of Polish patients with SchS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study of 13 adults with SchS treated with anakinra at two Polish tertiary referral centers between 2018 and 2025. Clinical manifestations, laboratory parameters, treatment response, adverse events and longitudinal follow-up data were analyzed. Receiver operating characteristic (ROC) analyses were used to compare biomarkers of disease activity, including serum amyloid A (SAA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, D-dimers and complete blood count (CBC)-derived inflammatory indices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 13 patients achieved rapid complete clinical remission within 48 hours of starting anakinra, accompanied by significant reductions in CRP and SAA. Remission was sustained over a median follow-up of 38.2 months (maximum 92.5 months), with no treatment discontinuations. In 3 patients (23%), dosing intervals were successfully extended to every 48\u201372 hours without loss of disease control. ROC analyses revealed that SAA showed the highest discriminatory power for distinguishing active disease from remission (AUC 0.974), outperforming ESR, fibrinogen and D-dimers. CBC-derived inflammatory indices declined markedly after treatment initiation but served mainly as adjunctive rather than primary monitoring tools. The therapy was well tolerated with no serious adverse events. The most frequent events were injection-site reactions, mild paradoxical psoriasis, transient neutropenia and consistent weight gain. Median diagnostic delay was 49 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Anakinra provides highly effective and safe long-term disease control in SchS. SAA appears to be the most reliable biomarker for monitoring disease activity, while cautious interval prolongation may be feasible in selected patients in sustained remission. Furthermore, treatment-associated weight gain is a consistent clinical observation requiring attention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1830866","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:32:51Z","timestamp":1777872771000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term anakinra therapy in Schnitzler syndrome: real-world evidence on remission of neutrophilic dermatitis and systemic inflammation, safety, biomarker insights and dose optimization"],"prefix":"10.3389","volume":"17","author":[{"given":"Mariusz","family":"Sikora","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Pneumonology, Allergology, Clinical Immunology and Rare Diseases, Military Institute of Medicine - National Research Institute","place":["Warsaw, Poland"]},{"name":"National Institute of Geriatrics, Rheumatology and Rehabilitation","place":["Warsaw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Zi\u0119tkiewicz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdansk","place":["Gdansk, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Jahnz-R\u00f3\u017cyk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pneumonology, Allergology, Clinical Immunology and Rare Diseases, Military Institute of Medicine - National Research Institute","place":["Warsaw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Wi\u0119sik-Szewczyk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pneumonology, Allergology, Clinical Immunology and Rare Diseases, Military Institute of Medicine - National Research Institute","place":["Warsaw, Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14060646","article-title":"Schnitzler syndrome: Insights into its pathogenesis, clinical manifestations, and current management","volume":"14","author":"Braud","year":"2024","journal-title":"Biomolecules"},{"key":"B2","first-page":"363","article-title":"Urticaire chronique, l\u00e9sions osseuses, macroglobulin\u00e9mie IgM: maladie de Waldenstrom","volume":"81","author":"Schnitzler","year":"1974","journal-title":"Bull Soc Fr Dermatol Syphiligr"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/2045-7022-4-41","article-title":"Schnitzler\u2019s syndrome: Lessons from 281 cases","volume":"4","author":"De Koning","year":"2014","journal-title":"Clin Trans All"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.084830","article-title":"Schnitzler syndrome: An under-diagnosed clinical entity","volume":"98","author":"Jain","year":"2013","journal-title":"Haematologica"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/all.13035","article-title":"Schnitzler syndrome: Validation and applicability of diagnostic criteria in real-life patients","volume":"72","author":"Gusdorf","year":"2017","journal-title":"Allergy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s13555-016-0108-7","article-title":"Schnitzler syndrome: A dramatic response to anakinra","volume":"6","author":"Gouveia","year":"2016","journal-title":"Dermatol Ther (Heidelb)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/10428190210181","article-title":"Malignant evolution of Schnitzler\u2019s syndrome--chronic urticaria and IgM monoclonal gammopathy: Report of a new case and review of the literature","volume":"43","author":"Lim","year":"2002","journal-title":"Leukemia Lymphoma"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08251.x","article-title":"Another devastating complication of the Schnitzler syndrome: AA amyloidosis","volume":"158","author":"Claes","year":"2008","journal-title":"Br J Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.5603\/Hem.2018.0023","article-title":"Amyloidoza AA \u2014 przyczyny, diagnostyka, opcje terapeutyczne","volume":"9","author":"Wi\u0119sik-Szewczyk","year":"2018","journal-title":"Hematologia"},{"key":"B10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13075-015-0696-0","article-title":"The role of interleukin-1 beta in the pathophysiology of Schnitzler\u2019s syndrome","volume":"17","author":"De Koning","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13023-019-1117-2","article-title":"Schnitzler\u2019s syndrome - a novel hypothesis of a shared pathophysiologic mechanism with Waldenstr\u00f6m\u2019s disease","volume":"14","author":"Van Leersum","year":"2019","journal-title":"Orphanet J Rare Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-38","article-title":"The schnitzler syndrome","volume":"5","author":"Lipsker","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/i9hsfr","article-title":"IL-1 targeting agents in Schnitzler syndrome: A multicentre, real-world study from the international AIDA Network Schnitzler Registry","volume":"43","author":"Calabrese","year":"2025","journal-title":"Clin Exp Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2024.10.001","article-title":"Investigator-initiated, multi-center, single-arm, open-label study of the effectiveness of canakinumab in Japanese patients with Schnitzler syndrome","volume":"74","author":"Kambe","year":"2025","journal-title":"Allergology Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02843.x","article-title":"Efficacy and safety of the interleukin\u20101 antagonist rilonacept in S chnitzler syndrome: An open\u2010label study","volume":"67","author":"Krause","year":"2012","journal-title":"Allergy"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/205833","article-title":"An underrated clinical tool: CBC-derived inflammation indices as a highly sensitive measure of systemic immune response and inflammation","volume":"34","author":"Geller","year":"2025","journal-title":"Adv Clin Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S265482","article-title":"Schnitzler syndrome in a 27-year-old man: Diagnostic and therapeutic dilemma in adult auto-inflammatory syndromes a case report and literature review","volume":"13","author":"Wi\u0119sik-Szewczyk","year":"2020","journal-title":"IJGM"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.5114\/reum.2019.91298","article-title":"Monogenic autoinflammatory diseases in adults \u2013 a challenge to rheumatologic practice at the onset of the Polish national programme of interleukin 1 inhibitor treatment","volume":"57","author":"Milchert","year":"2019","journal-title":"Reumatologia"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86336","article-title":"Anakinra as a diagnostic challenge and treatment option for systemic autoinflammatory disorders of Undefined etiology","author":"Harrison","year":"2016","journal-title":"JCI Insight"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.08.031","article-title":"Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler\u2019s syndrome: A french multicenter study","volume":"13","author":"N\u00e9el","year":"2014","journal-title":"Autoimmun Rev"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-810366","article-title":"Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome","volume":"131","author":"Rowczenio","year":"2018","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.10.031","article-title":"Complete remission in 3 of 3 anti-IL-6\u2013treated patients with Schnitzler syndrome","volume":"129","author":"Krause","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/14hu2k","article-title":"Retention rate of IL-1 inhibitors in Schnitzler\u2019s syndrome","volume":"40","author":"Crisafulli","year":"2022","journal-title":"Clin Exp Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2023.2242705","article-title":"Schnitzler syndrome refractory to anakinra: Successful treatment with canakinumab","volume":"34","author":"Salcedo-Mingoarranz","year":"2023","journal-title":"J Dermatol Treat"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61050792","article-title":"Efficacy and safety of anakinra in colchicine-resistant or -intolerant familial Mediterranean fever: A single-center real-life experience","volume":"61","author":"Ocak","year":"2025","journal-title":"Med (Kaunas)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12969-022-00725-3","article-title":"Tapering of biological treatment in autoinflammatory diseases: A scoping review","volume":"20","author":"Welzel","year":"2022","journal-title":"Pediatr Rheumatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-010-1375-9","article-title":"Dramatic response to IL1-RA treatment in longstanding multidrug resistant Schnitzler\u2019s syndrome: A case report and literature review","volume":"29","author":"Besada","year":"2010","journal-title":"Clin Rheumatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1483669","article-title":"Post-marketing safety of anakinra and canakinumab: A real-world pharmacovigilance study based on FDA adverse event reporting system","volume":"16","author":"Liu","year":"2025","journal-title":"Front Pharmacol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-011-2096-3","article-title":"Injection-site reactions upon Kineret (anakinra) administration: Experiences and explanations","volume":"32","author":"Kaiser","year":"2012","journal-title":"Rheumatol Int"},{"key":"B30","unstructured":"Kineret, INN-anakinra [Summary of product characteristic]\n          \n          2026"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08470.x","article-title":"New-onset psoriasis following treatment with the interleukin-1 receptor antagonist anakinra","volume":"158","author":"Gonz\u00e1lez-L\u00f3pez","year":"2008","journal-title":"Br J Dermatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/mjt9x1","article-title":"Anakinra-induced psoriasis in a patient with Schnitzler\u2019s syndrome","volume":"40","author":"Bauer-Alonso","year":"2022","journal-title":"Clin Exp Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4274\/qrheumatol.galenos.2023.44153","article-title":"Anakinra-induced paradoxical psoriasis and a case report and review of literature","volume":"1","author":"Ibramhkhalilova","year":"2024","journal-title":"Rheumatol Q"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2021.4056","article-title":"Psoriasis as an adverse reaction to biologic agents beyond anti-TNF-\u03b1 therapy","volume":"31","author":"Karamanakos","year":"2021","journal-title":"Eur J Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2611461","article-title":"The molecular mechanism of the adverse effects of the biological and small molecular drugs in the therapy of inflammatory skin diseases \u2013 psoriasis and atopic dermatitis","volume":"58","author":"Lemiesz","year":"2026","journal-title":"Ann Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.adengl.2018.09.012","article-title":"Paradoxical reactions to biologic therapy in psoriasis: A review of the literature","volume":"109","author":"Munera-Campos","year":"2018","journal-title":"Actas Dermo-Sifiliogr\u00e1ficas (English Edition)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2024.05.015","article-title":"Paradoxical psoriasis: An updated review of clinical features, pathogenesis, and treatment options","volume":"144","author":"Maronese","year":"2024","journal-title":"J Invest Dermatol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.6.2955","article-title":"The IL-1 system in psoriatic skin: IL-1 antagonist sphere of influence in lesional psoriatic epidermis","volume":"158","author":"Debets","year":"1997","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115896","article-title":"Interleukin-1 receptor antagonist in normal and psoriatic epidermis","volume":"90","author":"Hammerberg","year":"1992","journal-title":"J Clin Invest"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-021-01429-8","article-title":"The emerging role of interleukin 1\u03b2 (IL-1\u03b2) in cancer cachexia","volume":"44","author":"Laird","year":"2021","journal-title":"Inflammation"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.36469\/9860","article-title":"A retrospective patient chart review and survey in patients with cryopyrin-associated periodic syndromes treated with anakinra","volume":"1","author":"Lachmann","year":"2013","journal-title":"JHEOR"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/815tdt","article-title":"Long-term safety and efficacy of anakinra and canakinumab in patients with familial Mediterranean fever: A single-centre real-life study with 101 patients","volume":"39","author":"Atas","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15141","DOI":"10.1038\/s41598-021-94565-y","article-title":"The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia","volume":"11","author":"Cheung","year":"2021","journal-title":"Sci Rep"},{"key":"B44","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41574-024-01047-y","article-title":"Inflammation and resolution in obesity","volume":"21","author":"Sot\u00e1k","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12622","article-title":"Pharmacokinetics of anakinra in subjects of heavier vs. lighter body weights","volume":"12","author":"Yang","year":"2019","journal-title":"Clin Trans Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12969-022-00757-9","article-title":"The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases","volume":"20","author":"Legger","year":"2022","journal-title":"Pediatr Rheumatol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s42358-025-00491-2","article-title":"Comparative analysis of conventional and novel inflammatory biomarkers in familial Mediterranean fever during attack-free periods","volume":"65","author":"Klisic","year":"2025","journal-title":"Adv Rheumatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-024-01413-0","article-title":"The potential role of serum amyloid A as biomarker of rheumatic diseases: A systematic review and meta-analysis","volume":"24","author":"Zinellu","year":"2024","journal-title":"Clin Exp Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.631299","article-title":"Serum amyloid A in inflammatory rheumatic diseases: A compendious review of a renowned biomarker","volume":"11","author":"Sori\u0107 Hosman","year":"2021","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.ard.2025.01.028","article-title":"EULAR\/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update","volume":"84","author":"Ozen","year":"2025","journal-title":"Ann Rheumatic Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1425168","article-title":"C-reactive protein: structure, function, regulation, and role in clinical diseases","volume":"15","author":"Zhou","year":"2024","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s10020-018-0047-0","article-title":"Serum amyloid A \u2013 a review","volume":"24","author":"Sack","year":"2018","journal-title":"Mol Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2011.607189","article-title":"Kinetics of c-reactive protein (CRP) and serum amyloid A protein (SAA) in patients with community-acquired pneumonia (CAP), as presented with biologic half-life times","volume":"16","author":"Takata","year":"2011","journal-title":"Biomarkers"},{"key":"B54","doi-asserted-by":"publisher","first-page":"4705","DOI":"10.1038\/s41467-022-32222-2","article-title":"Human acute inflammatory recovery is defined by co-regulatory dynamics of white blood cell and platelet populations","volume":"13","author":"Foy","year":"2022","journal-title":"Nat Commun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/hemato6040042","article-title":"Hematological inflammatory markers and chronic diseases: current evidence and future perspectives","volume":"6","author":"Dug\u0103e\u015fescu","year":"2025","journal-title":"Hemato"},{"key":"B56","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41598-025-21188-y","article-title":"Elevated neutrophil-to-lymphocyte ratio and the incidence of autoimmune diseases: evidence from a large prospective cohort study","volume":"16","author":"Yoon","year":"2026","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1830866\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:32:53Z","timestamp":1777872773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1830866\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":56,"alternative-id":["10.3389\/fimmu.2026.1830866"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1830866","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"article-number":"1830866"}}