---
title: "From Idiopathic Recurrent Pericarditis to Behçet’s Disease: IL-1–Driven Autoinflammatory Case Repo"
id: "frontiers-in-immunology-12-case-report-from-idiopathic-recurrent-pericarditis-to-systemic-beh-et-s-disease"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-12-case-report-from-idiopathic-recurrent-pericarditis-to-systemic-beh-et-s-disease"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1900526"
published_at: "2026-08-14T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# From Idiopathic Recurrent Pericarditis to Behçet’s Disease: IL-1–Driven Autoinflammatory Case Repo
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-12-case-report-from-idiopathic-recurrent-pericarditis-to-systemic-beh-et-s-disease
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1900526)
- **Published At:** 2026-08-14T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Source article: case report published in Frontiers in Immunology (title provided by user). The article title links **idiopathic recurrent pericarditis** and **Behçet’s Disease** under an **IL-1**–driven autoinflammatory phenotype. - The available source text provided here contains only website navigation and metadata; the main article body and clinical content were not included in the source provided to this task. - Because the article full text and abstract were not present in the supplied source, specific clinical details such as patient demographics, history, diagnostic testing, genetic or biomarker data, treatment interventions, outcomes, and follow-up were not reported in the source. - The title implies a clinical progression or diagnostic unmasking from isolated recurrent pericarditis to a systemic autoinflammatory disorder recognized as Behçet’s Disease, with a central role attributed to **IL-1** signaling; however, the source did not provide supporting data or evidence. - No data on therapeutic response to IL-1 blockade, specific biologic agents, steroid-sparing strategies, or adverse events were reported in the provided source material. - No imaging, laboratory values, histopathology, immunologic assays, or timelines were available in the supplied content. - For clinicians or researchers seeking actionable details (diagnostic criteria used, case timeline, response to therapy, or genetic testing), the source here is incomplete; the full article at Frontiers in Immunology should be consulted for complete clinical information and evidence. - This rewrite therefore summarizes what is explicitly present (title and journal) and documents absent information, and lists follow-up steps clinicians might take to obtain the primary report and related evidence (not derived from the source).
## Clinical Analysis & Structured Key Points
Frontiers | Case Report: From idiopathic recurrent pericarditis to systemic Behçet’s Disease: unmasking a unified IL-1-driven autoinflammatory phenotype CASE REPORT article Front. Immunol. , 14 August 2026 Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1900526 Published in Frontiers in Immunology Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders 7 impact factor 11.3 citescore Part of a Research Topic Behçet’s Syndrome: from pathophysiology to personalized therapeutics Submission open 9432 views 7 articles Editor & Reviewers Edited by A B Alessandra Bettiol Reviewed by A P Aleksandra Plavsic O D Omar Dhrif Outline Figures and Tables Figure 1 View in article CASE REPORT article Front. Immunol. , 14 August 2026 Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1900526 Case Report: From idiopathic recurrent pericarditis to systemic Behçet’s Disease: unmasking a unified IL-1-driven autoinflammatory phenotype B E Bizzi Emanuele 1 * M A Mauro Angela 2 C G Cristiano Germinario 3 C F Casarin Francesca 1 B S Berra Silvia 1 M S Ministrini Stefano 4 G A Gidaro Antonio 5 M G Manzotti Giuseppina 6 M A Marra Alessandro Maria 7 R S Rotunno Sara 8 G E Greco Elisabetta 9 M S Modica Stella 9 P F Paciullo Francesco 10 S M Sculco Martina 10 D S Damanti Sarah 10 A G Abatianni Giulia 10 G C Gagliardi Caterina 10 R Q Rovere Querini Patrizia 10 +10 more B A Brucato Antonio 1 1. Department of Internal Medicine, Fatebenefratelli Hospital, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli and Sacco Hospitals, Milan, Italy 2. Department of Pediatrics, Fatebenefratelli Hospital, Milan, Italy 3. Farmacia Marsico, Acquaviva Delle Fonti, Bari, Italy 4. Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland 5. Department of Internal Medicine, Sacco Hospital, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli and Sacco Hospitals, Milan, Italy 6. Allergology Service, Casa di Cura Beato Palazzolo, Bergamo, Italy 7. Pulmonology Unit, Azienda Socio-Sanitaria Territoriale (ASST) Rhodense, Garbagnate Milanese Hospital, Milan, Italy 8. Internal Medicine, S.Pietro Fatebenefratelli Hospital, Rome, Italy 9. Rheumatology, Allergology and Clinical Immunology, Department of “Medicina dei Sistemi”, University of Rome Tor Vergata, Rome, Italy 10. Department of Internal Medicine, Vita-Salute San Raffaele Hospital, Milan, Italy See more Article metrics View details Abstract Background: Recurrent idiopathic recurrent pericarditis (RP) is increasingly recognized as an organ-specific autoinflammatory syndrome driven by the interleukin-1 (IL-1) axis. Behçet’s Disease (BD), a systemic vasculitis, exhibits significant pathogenetic overlap with RP through IL-1 mediated hyperinflammation, particularly in phenotypes dominated by serositis. The clinical evolution of prolonged, seemingly idiopathic RP into overt, systemic BD upon the tapering of targeted therapy remains a critical, yet underreported, observation. Case presentation: A 42 years old female with corticosteroid-dependent, colchicine-resistant RP achieved complete and sustained clinical and biochemical remission using the IL-1 receptor antagonist, Anakinra, for almost 30 months, despite the tapering started after 18 months of continuous therapy with Anakinra, associated to colchicine and a quick tapering and withdrawal of corticosteroids. Following the elective tapering of Anakinra, the patient remained stable for three months with a dose of an injection of 100mg of Anakinra three times per week, before suffering a severe pericardial relapse concurrent with the systemic onset of systemic BD. The clinical condition observed fulfilled the International Criteria for Behçet’s Disease (ICBD), featuring recurrent oral and genital ulcerations, erythema nodosum and a positive pathergy test. The immediate reinitiation of Anakinra (100mg daily) led to the rapid and complete resolution of both the pericardial inflammation and all systemic mucocutaneous manifestations. Conclusions: This case highlights a potential pathogenetic overlap between refractory RP and serositis-dominant BD phenotypes, suggesting that isolated RP may, in select cases, represent an early mono-organ precursor of a systemic autoinflammatory propensity. Furthermore, it provides clinical rationale for considering IL-1 blockade in serositis-dominant BD, though larger prospective studies are needed to confirm these findings. Introduction Behçet’s Disease (BD) is a multifaceted systemic inflammatory disorder classically characterized by recurrent oral ulcers, genital ulcers, and uveitis, but its clinical spectrum encompasses a wide range of mucocutaneous, ocular, vascular, neurological, and musculoskeletal manifestations ( 1 – 6 ). While historically categorized as a systemic vasculitis, contemporary immunological insights view BD as a bridge between autoimmunity and autoinflammation ( 7 , 8 ). At the molecular level, its pathogenesis involves an intricate interaction between genetic factors, notably the HLA-B51 allele, and environmental triggers that spark inflammasome activation and the overproduction of proinflammatory cytokines, particularly interleukin-1 (IL-1) and TNF-alpha ( 8 , 9 ). Managing refractory BD phenotypes remains a significant clinical challenge ( 10 ). Pericardial involvement represents a less common manifestation, but emerging evidence suggests that certain mono-organ presentations may actually serve as the initial phase of a broader systemic autoinflammatory propensity, which fully declares itself only upon the tapering of targeted immunosuppression ( 1 , 6 ). In parallel, recurrent pericarditis (RP) is a debilitating autoinflammatory condition characterized by repeated flares of pericardial inflammation. Once labeled as idiopathic, contemporary molecular research has redefined a major subset of RP as a prototypical organ-specific autoinflammatory syndrome ( 11 – 16 ). This paradigm shift relies on the pivotal role played by the NLRP3 inflammasome ( 17 – 23 ), which processes and releases bioactive IL-1beta in response to cellular danger signals ( 17 , 18 ). Dysregulation of this axis leads to a self-perpetuating inflammatory loop refractory to conventional therapies such as NSAIDs and colchicine, often resulting in corticosteroid dependence ( 24 – 31 ). The clinical success of targeted IL-1 blockers like Anakinra and Rilonacept has not only transformed RP management but has also acted as a diagnostic ex juvantibus confirmation of its autoinflammatory nature. The diagnostic boundaries between isolated RP and systemic vasculitides like BD are increasingly blurred, as both conditions share a reliance on the IL-1 axis, particularly in cases where serositis is a dominant feature ( 6 , 9 , 10 , 32 – 38 ). Cardiac involvement in BD, termed cardio-Behçet, occurs in 1% to 6% of patients ( 36 – 43 ). Pericarditis is among the most frequent cardiac findings, often presenting in association with other cardiac lesions or as part of a broader autoinflammatory cluster involving serosal, mucocutaneous, and articular manifestations ( 11 , 12 , 44 – 46 ). Crucially, pericarditis can act as the inaugural or sentinel sign of BD, preceding classic diagnostic features by months or years ( 47 – 55 ). In these scenarios, extensive clinical series highlight that diagnostic latency often leads to an initial classification of idiopathic RP ( 49 – 52 , 54 – 60 ). Pericarditis can occur concurrently with severe vascular or intracardiac complications, including intracardiac thrombi, valvular sequelae, aortic aneurysms, or coronary involvement ( 48 , 61 – 63 ). Recognizing specific autoinflammatory clusters driven by innate immunity activation is therefore essential for guiding personalized therapy ( 34 – 40 , 43 , 64 , 65 ). Recent evidence underlines that this autoinflammatory phenotype is primarily driven by IL-1 dysregulation, explaining why serositis-dominant presentations show a distinct therapeutic response to IL-1 antagonists ( 66 ). The molecular connection between RP and BD lies in shared innate immune pathways ( 6 – 8 , 32 , 67 – 69 ), where NLRP3 assembly and IL-1beta release orchestrate localized or systemic hyperinflammation ( 33 , 70 – 74 ). In RP, danger signals trigger localized pericardial neutrophil recruitment ( 29 – 31 , 75 – 77 ), whereas in BD, systemic NLRP3 overexpression drives widespread tissue involvement ( 6 , 7 , 32 , 78 ). While international consensus and ESC guidelines provide structured protocols for biological dose reduction ( 16 , 79 ), tapering IL-1 blockade can unmask latent systemic drive. Here, we present a case where elective Anakinra tapering unmasked systemic BD in a patient long managed for refractory RP, illustrating the shared autoinflammatory spectrum underlying these conditions. Case presentation Patient information: a 42 years old caucasian female presented to our immunology clinic with a longstanding history of RP. Her medical history was otherwise unremarkable, with no family history of autoimmune or autoinflammatory diseases. Prior to the current episode, she had experienced multiple flares of pericarditis (9 episodes) over a seven years period, characterized by pleuritic chest pain, pericardial friction rubs and diffuse ST-segment elevation on electrocardiogram (ECG). Most of the previous episodes of RP had occurred when she had attempted tapering of prednisone below 15 mg/day, while maintaining the background therapy of indomethacin 50 mg three times daily and colchicine 0.5 mg daily. During the initial 7-year pre-referral period, the patient was managed at primary/secondary centers for isolated recurrent pericarditis. Systemic autoinflammatory screening and pathergy testing were not performed during those early flares, and while no major extra-cardiac events were reported, the presence of minor, unrecorded mucocutaneous symptoms during that period cannot be definitively ruled out. Upon referral to our immunology clinic (Month 1), a detailed systemic review was negative for ocular, vascular, articular, or persistent mucocutaneous lesions; however, formal pathergy testing was deferred until the acute multi-system flare at Month 33. Clinical findings At the time of her initial referral to our center, the patient was corticosteroid dependent (requiring 15mg/day of prednisone to suppress symptoms) and colchicine resistant, and presented a new RP flare after stopping NSAID therapy for approximately one week, without tapering NSAID dose. Physical examination typically revealed slight tachycardia and muffled heart sounds, with laboratory findings showing markedly elevated C-reactive protein (CRP) (85 mg/L) and an increased white blood cell count with marked neutrophilia, while extensive infectious (blood cultures for aerobic and anaerobic bacteria, Interferon-Gamma Release Assay for Mycobacterium tuberculosis , HIV-1/2 serology, hepatitis B and C serology and serology for cardiotropic viruses such as Coxsackievirus, Echovirus, Adenovirus, Parvovirus B19, EBV, CMV, HSV, Borrelia burgdorferi , Coxiella burnetii , Mycoplasma pneumoniae , Syphilis screening), neoplastic (chest X-ray and complete abdominal ultrasound examination) and autoimmune workups (including ANA, ANCA and ENA panels) were consistently negative, leading to a diagnosis of idiopathic recurrent pericarditis. Comprehensive biochemical evaluation confirmed normal renal function (serum creatinine 0.72 mg/dL, estimated glomerular filtration rate >90 mL/min/1.73 m²) and normal urinalysis without microscopic hematuria, active urinary sediments, or proteinuria (24-hour urine protein <0.15 g/24h), ruling out renal involvement or secondary amyloidosis. Pericardiocentesis was withheld as the effusion remained non-tamponading (30 mm max, without echocardiographic signs of hemodynamic compromise) in accordance with current guidelines. However, the presence of concurrent pleural and peritoneal effusions during acute inflammatory flares was consistent with an autoinflammatory exudative polyserositis phenotype. To rule out underlying monogenic autoinflammatory syndromes, Next-Generation Sequencing (NGS) panel screening for targeted genes (including MEFV, TNFRSF1A, NLRP3, MVK, and PSTPIP1) was performed during the initial evaluation of refractory pericarditis, showing no pathogenic or likely pathogenic variants. Along with ultrasound confirmation of pericarditis, which showed thickened pericardial sheets and non-tamponading pericardial effusion approximately 20mm thick, the patient also showed signs of minimal pleural and peritoneal effusion. Therapeutic interventions (Phase I) Given the refractory nature of her condition and the side effects of chronic steroid use, treatment with the IL-1 receptor antagonist Anakinra (100mg daily, subcutaneously) was initiated. The clinical response was immediate and dramatic: CRP levels normalized within two weeks and she achieved complete symptomatic remission in less than a week; over the following 30 months, despite the slow tapering of Anakinra, she remained asymptomatic, allowing for the successful tapering and discontinuation of corticosteroids, while colchicine therapy (0,5mg/day) was still ongoing. Timeline and the systemic event After 18 months of sustained daily administration of Anakinra and clinical stability, followed by a slow tapering performed by interruption of one of the weekly doses every 3 months (6 times/week for three months, then 5 times/week for another 3 months, then 4 times/week for three months, then 3 times/week for three months) a slight increase of CRP was observed after two months of Anakinra administration 3 times a week (8mg/L) without clinical consequences, and the administration of Anakinra was stabilized to three times a week. However, in the third month, she suffered a systemic relapse. Diagnostic assessment Upon arrival at the Emergency Department, the patient presented with acute, severe retrosternal chest pain and dyspnea. Simultaneously, she exhibited multiple painful oral aphthous ulcers consisting of more than three lesions, deep scarred genital ulcerations and tender erythematous nodules on her lower shins, clinically consistent with erythema nodosum. A pathergy test performed via needle prick also yielded a positive result within 24 hours. Transthoracic echocardiography showed a 30mm pericardial effusion without signs of incipient tamponade, while laboratory investigations revealed a significant CRP spike of 120 mg/L. Genetic testing for HLA-B51 was performed during the acute multi-system flare and returned negative. While HLA-B51 is a recognized genetic susceptibility marker for BD, its absence does not preclude the diagnosis, particularly in non-ocular, serositis-dominant phenotypes. Based on the concurrent presence of oral and genital ulcers, erythema nodosum and the positive pathergy test, the patient achieved a score of 7 points on the International Criteria for Behçet’s Disease (ICBD), with this total far exceeding the diagnostic threshold of 4, effectively confirming a transition from seemingly isolated recurrent pericarditis to systemic Behçet’s Disease. Therapeutic interventions (Phase II) and outcomes After a telephone consultation regarding the case, and also in accordance with the patient’s decision, instead of increasing the dosage of prednisone, it was decided to restart therapy with Anakinra at 100 mg/day with one administration per day. The clinical response was swift, with the patient’s chest pain gradually and completely resolving within 72 hours. Within one week, the mucocutaneous lesions showed significant healing and a followup echocardiography performed at 10 days confirmed the substantial resolution of the pericardial effusion (20mm). Following this intervention, the patient has remained in complete clinical and biochemical remission for over 12 months on continuous Anakinra therapy, with no further flares reported to date. A subsequent cardiac MRI, performed 1 month after Anakinra full dose restart, revealed a condition of chronic pericarditis, with thickening of the pericardial layers, without the characteristics of constrictive pericarditis and without further signs of cardiac involvement typical of BD, while a repeat of the same examination after 9 months highlighted a stable cardiac and pericardial condition with only a reduction in the effusion, detectable only posteriorly and less than 10 mm thick. A cautious tapering of the prednisone dosage was started 3 months after the clinical condition stabilized, mainly at the patient’s request, reaching 12 months of followup with a maintenance dose of approximately 5 mg of prednisone per day ( Figure 1 ). Figure 1 Detailed disease course. During the pre-referral period (Years 1–7), the patient experienced 9 recurrent pericarditis flares. These episodes were characterized by corticosteroid dependence and colchicine resistance. A severe flare occurred following NSAID cessation. Upon referral (Months 1–18), daily Anakinra (100 mg) was initiated. This led to immediate clinical and biochemical remission. Corticosteroids were tapered over 12 months. During the Anakinra tapering phase (Months 19–30), the Anakinra dose was gradually reduced. Background colchicine therapy (0.5 mg/day) remained ongoing. At three injections per week (Months 31–33), a slight asymptomatic CRP rise (8 mg/L) was noted. A systemic relapse occurred at Month 33. This event unmasked systemic Behçet’s Disease, including a 30 mm pericardial effusion, oral/genital ulcers and a positive pathergy test. The patient achieved an ICBD score of 7. Intensive follow-up (Months 34–46) involved restarting daily Anakinra and 12.5 mg/day of prednisone. Complete remission was maintained as prednisone was tapered to 5 mg/day by month 12 of follow-up. BD, Behçet’s Disease; CRP, C-reactive protein; ICBD, International Criteria for Behçet’s Disease; IL-1, Interleukin-1; NSAIDs, Non-steroidal anti-inflammatory drugs; RP, Recurrent pericarditis. Patient perspective The patient reported a significant improvement in her quality of life following the definitive diagnosis and the subsequent stabilization of her therapy. She emphasized that while the long standing recurrent pericarditis had been physically and mentally exhausting, the sudden onset of systemic mucocutaneous symptoms was particularly distressing. The rapid resolution of both the cardiac and systemic manifestations upon the reinitiation of full dose of IL-1 blockade provided the patient with a renewed sense of security and she expressed high treatment satisfaction and a strong commitment to long term adherence to the daily subcutaneous injection regimen. Furthermore, given her stable clinical status and significant concerns regarding potential long term side effects, the patient strongly requested a tapering of her prednisone dosage. Literature review and discussion Pericardial involvement in BD is a recognized, albeit relatively infrequent, manifestation of the cardio-Behçet spectrum ( 49 – 52 , 54 – 60 ). Large scale cohort studies and systemic reviews have estimated the prevalence of cardiac involvement to range between 1% and 6% of patients, with significant geographical variations, often appearing more frequently in cohorts from the Mediterranean basin and the Middle East. Among these cardiac manifestations, pericarditis is frequently identified as the most common clinical finding, often occurring in association with other cardiac lesions such as intracardiac thrombi, endomyocardial fibrosis or coronary vasculitis ( 48 , 61 – 63 ). A critical observation in the current literature is the temporal relationship between pericardial inflammation and the full expression of BD. While pericarditis often occurs during the established course of the disease, it has been increasingly documented as a se
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