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Recurrent pericarditis (RP) has been traditionally regarded as a "nightmare" for both clinicians and patients. Until approximately a decade ago, available treatments were thin on the ground with non-steroidal anti-inflammatory medications, glucocorticoids, colchicine, and classical immunosuppressants being the only options. The first important step in the tale of RP was the advent of colchicine in clinical practice, which has been shown to halve the rate of first and subsequent pericarditis recurrences. The second major breakthrough advance in this setting was the introduction of interleukin-1 inhibitors based on the recently unveiled autoinflammatory nature of pericarditis. At present, anti-interleukin-1 inhibitors available for clinical use in patients with refractory RP include anakinra and rilonacept, with the latter having obtained FDA approval for this indication. Apart from the remarkable efficacy and good safety profile which is a common feature of all anti-interleukin-1 compounds, rilonacept has the advantage of weekly administration (instead of daily compared to anakinra) which is important in terms of adherence to treatment and improved quality of life albeit at the expense of a higher cost. This review aims to summarize the available evidence on the role of rilonacept in the treatment of RP and the reduction of the recurrences risk.

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BACKGROUND: Recurrent pericarditis (RP) is a complex condition associated with significant morbidity. Prior studies have evaluated which variables are associated with clinical remission. However, there is currently no established risk-stratification model for predicting outcomes in these patients. OBJECTIVES: We developed a risk stratification model that can predict long-term outcomes in patients with RP and enable identification of patients with characteristics that portend poor outcomes. METHODS: We retrospectively studied a total of 365 consecutive patients with RP from 2012 to 2019. The primary outcome was clinical remission (CR), defined as cessation of all anti-inflammatory therapy with complete resolution of symptoms. Five machine learning survival models were used to calculate the likelihood of CR within 5 years and stratify patients into high-risk, intermediate-risk, and low-risk groups. RESULTS: Among the cohort, the mean age was 46 ± 15 years, and 205 (56%) were women. CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial late gadolinium enhancement, age, etiology, sex, ejection fraction, and heart rate as the most important parameters. The model predicted the outcome with a C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (log-rank test; P < 0.0001). CONCLUSIONS: We developed a novel risk-stratification model for predicting CR in RP. Our model can also aid in stratifying patients, with high discriminative ability. The use of an explainable machine learning model can aid physicians in making individualized treatment decision in RP patients.

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PURPOSE OF REVIEW: To outline recent advances in imaging and treatment for recurrent pericarditis (RP). RECENT FINDINGS: Greater understanding of NLRP3 inflammasome activation in the pathogenesis of RP has led to the development of several anti-interleukin (IL-1) agents, and technological advancements have increased the utility of multimodality imaging in RP. Multimodality imaging plays a crucial role in the assessment of RP, with echocardiography serving as the initial imaging modality; cardiac magnetic resonance (CMR) as a pivotal test for diagnosis, grading severity, and surveillance; and cardiac computed tomography (CT) providing complimentary information and assisting operative assessment. Anti-IL-1 agents are now well-established as second line therapy for RP, with recent clinical trials demonstrating their efficacy.

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Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.

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Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed.

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Purulent pericarditis secondary to bacterial infections is rarely seen in the current era of broad-spectrum antibiotics. Complications tend to be higher in comparison to viral or idiopathic etiologies in cases of bacterial pericarditis. Staphylococcal aureus, Streptococcus pneumoniae, or Haemophilus influenza are the more commonly identified pathogens in cases of bacterial pericarditis. We report a case of purulent pericarditis from Bacteroides thetaiotaomicron and Streptococcus milleri occurring in conjunction in a 56-year-old male. To our knowledge, there are no published case reports describing purulent pericarditis from B. thetaiotaomicron and S. milleri occurring simultaneously in the literature.

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Remarkable advances have occurred in the understanding of the pathophysiology of pericardial diseases and the role of multimodality imaging in this field. Medical therapy and surgical options for pericardial diseases have also evolved substantially. Pericardiectomy is indicated for chronic or irreversible constrictive pericarditis, refractory recurrent pericarditis despite optimal medical therapy, or partial agenesis of the pericardium with a complication (eg, herniation). A multidisciplinary evaluation before pericardiectomy is essential for optimal patient outcomes. Overall, given the good outcomes reported, radical pericardiectomy on cardiopulmonary bypass, if feasible, is the preferred approach. Due to patient complexity, as well as the technical aspects of the surgery, pericardiectomy should be performed at high-volume centers that have the required expertise. The current review highlights the essential features of this multidisciplinary approach from diagnosis to recovery in patients undergoing pericardiectomy.

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Aims: To determine the utility of serial cardiac magnetic resonance (CMR) imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis (RP), compared with C-reactive protein (CRP) assay alone. Methods and results: In 2018-21, we enrolled 18 (14.5 ± 1.8 years old, 72% males) consecutive RP patients treated with anakinra (100 mg/day in patients ≥ 18 years old; 2 mg/kg/day < 18 years old) due to RP corticosteroid-dependent or not responsive to colchicine or non-steroidal anti-inflammatory drugs. After hospitalization, they were 1:1 randomized to CMR [no pericardial oedema and/or late gadolinium enchantment (LGE)] or CRP (<0.6 mg/dL). Tests were repeated every 3 months until negative to halve the anakinra dosage and cessation. The idiopathic aetiology was the most prevalent (n = 8, 44%), followed by post-pericardiotomy (n = 6, 33%). After a median treatment period of 8.7 ± 3.6 months, CRP-guided RP patients experienced more recurrences than CMR-guided ones (6 vs. 1, P = 0.016), with the worst prognosis in terms of recurrences (log-rank, P = 0.025) and significantly increased time of treatment (12.7 ± 2 vs. 16.1 ± 3.4 months, P = 0.019). In a multivariable exploratory Cox regression model, the number of previous recurrences and the idiopathic aetiology were independent predictors of RP during the anakinra treatment. New recurrences were subsequently directed to CMR imaging, and therapy was modified according to the LGE/oedema trend. After 1-year follow-up, no further recurrence was detected. Conclusion: Among patients with RP and treated with anakinra, serial CMR imaging of the pericardium can be utilized as an imaging biomarker, more informative for therapy duration than the solely CRP assessment. ClinicalTrialsgov Identifier: NCT06071156.

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Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

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BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

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Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

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Undifferentiated connective tissue disease (UCTD) is a condition characterized by symptoms and laboratory findings related to various systematic autoimmune diseases. Severe symptoms like chest pain in patients with UCTD could suggest an underlying secondary condition, such as pericarditis. Our case involves a 36-year-old woman with a history of UCTD and recently diagnosed rheumatoid arthritis (RA) who presented with persistent sub-sternal chest pain and pressure that began three weeks ago. Over the past year, she experienced six similar episodes of chest pain, diagnosed as idiopathic pericarditis. She promptly underwent treatment with oral prednisone and was instructed to continue her current medications (colchicine, methotrexate, and Plaquenil). Subsequent laboratory results, obtained several days posttreatment, revealed an elevated C-reactive protein (CRP), normal erythrocyte sedimentation rate (ESR), an elevated rheumatoid factor, and a normal echocardiogram, suggesting resolution of the acute flare. Despite having a comprehensive treatment regimen, the patient continues to experience recurrent pericarditis episodes. The cause of the recurrence remains uncertain, potentially associated with repeated use of high-dose steroids and a recent diagnosis of RA. Consequently, her rheumatologist opted to initiate treatment with intravenous Golimumab to better manage the RA and potentially address recurrent pericarditis. Physicians should maintain a heightened clinical suspicion of pericarditis in UCTD patients experiencing chest pain, as initiating prompt treatment helps prevent long-term complications and can be lifesaving in certain instances.

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Recurrent pericarditis poses a significant challenge to clinicians, particularly when patients are unresponsive or intolerant to conventional treatments. Accurate diagnosis of recurrent pericarditis, potentially facilitated by collaboration with other medical specialties, is crucial for ensuring timely and appropriate treatment of symptoms and prevention of further episodes. We present a case of a 52-year-old male patient with a history of multiple episodes of pericarditis, who was admitted to the Cardiology Department due to another recurrence. The first episode of pericarditis was diagnosed nearly a year before his current hospitalization. Initially, the patient received high doses of Ibuprofen and colchicine, but there was no favorable response to this treatment regimen. At that point, intravenous prednisolone was initiated, which led to clinical and laboratory improvement. Since then, the patient had experienced two more recurrences while tapering off prednisolone. Immunological tests, Mantoux tuberculin skin test, and chest and abdominal computed tomography (CT) had revealed no evidence of an underlying cause. On admission the patient was febrile and the electrocardiogram showed diffuse ST elevation and PR depression in leads I, II, aVF, V2-V6. Bedside echocardiogram revealed a small pericardial effusion and since the chest X-ray was normal and no other potential infection sites were identified, the diagnosis of recurrent pericarditis was established. During his current hospitalization, intravenous prednisolone was initiated, colchicine was continued and a more detailed history was taken, raising the suspicion upon the presence of an auto-inflammatory disease. Genetic investigation identified an uncommon heterozygous mutation in the familial Mediterranean fever gene (MEFV) and after consideration of patient's history, familial Mediterranean fever was diagnosed. Anakinra was initiated on top of colchicine and gradual tapering of corticosteroids and the patient showed significant improvement, with no other recurrence during the two-year follow-up.

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Pericarditis in pregnancy is uncommon, and there is a paucity of data regarding the safety and efficacy of conventional therapy. We describe a complex case of recurrent pericarditis in the setting of pregnancy and newly diagnosed systemic lupus erythematosus and discuss the challenges in managing this subset of patients.

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Idiopathic recurrent pericarditis (IRP) can be the hallmark of an autoinflammatory syndrome with recurrent attacks of chest pain and symptom-free intervals following an acute episode. The recurrence rate may be 35% in the pediatric population, frequently with less severe manifestations than at the first episode. Pericarditis can be the sole clinical manifestation or may be part of a systemic autoinflammatory disease (SAID), especially in the case of a recurrence. Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate-Kinase Deficiency (MKD), nucleotide-binding oligomerization domain 2 (NOD2)-associated autoinflammatory syndrome, and others are closely related to IRP based on similar clinical manifestations and treatment responses to anti-interleukin 1 (IL-1) agents, such as anakinra, and should therefore be excluded in patients with IRP. A newly described SAID, an autosomal dominant disorder known as NLRP12-AID (nucleotide-binding leucine-rich repeat-containing receptor 12-related autoinflammatory disease) is caused by heterozygous mutations in the NLRP12 gene and most commonly affects children. Fewer than 40 pediatric patients with NLRP12-AID have been described in the medical literature, with none presenting with RP. We report a case of relapsing pericarditis responsive to anti-IL-1 therapy in a male adolescent who carried a missense mutation in the NLRP12 gene potentially causative of the excessive activation of inflammatory pathways. This is a unique case in the medical literature that associates recurrent pericarditis in an adolescent presumed to be related to the missense mutation in the NLRP12 gene. The role of the NLRP12 inflammasome in generating and maintaining recurrent pericardial inflammation should be considered.

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PURPOSE OF THE REVIEW: We review the pathophysiology, diagnosis, and contemporary treatment for recurrent pericarditis, with focus on interleukin-1 (IL-1) inhibitors. RECENT FINDINGS: Recurrent pericarditis occurs in about 15-30% of patients who have acute pericarditis. With increased understanding of the autoinflammatory pathophysiology of recurrent pericarditis, IL-1 inhibitors including anakinra, canakinumab, and rilonacept have been applied to this condition with great promise. In particular, the RHAPSODY trial found rilonacept significantly improves pain and inflammation, while also reducing recurrence with few adverse events. The next IL-1 inhibitor on the block for pericarditis, goflikicept, is also discussed. Understanding the role of the inflammasome via the autoinflammatory pathway in pericarditis has led to incorporation of IL-1 inhibitors in the treatment of recurrent pericarditis, with proven efficacy and safety and randomized trials. This will lead to increase uptake of this agent which demonstrated lower rates of recurrence and faster time to resolution.

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A 16-year-old male with past medical history of congenital atrial septal defect surgical repair, presented with recurrent pericarditis secondary to post-cardiotomy injury syndrome (PCIS), After failing medical therapy, he ultimately underwent pericardiectomy for symptom resolution, PCIS is underdiagnosed in children and should be considered in patients with recurrent chest, pain.

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Background: Primary pericardial mesothelioma is an extremely rare disease. Prognosis is poor, with little effects of chemo- or radio-therapy. The majority of cases is diagnosed at autopsy. Case summary: A 22-year-old man, who presented with recurrent pericarditis and large pericardial effusion 2 months after a second BNT162b2 COVID-19 vaccine, underwent pericardiocentesis and pericardial window. Pathology specimen of pericardium revealed benign mesothelial inflammation, consistent with acute pericarditis. Four months later, he presented with a large pericardial mass manifesting in heart failure and underwent urgent pericardiectomy. A new pathology specimen immunostaining and fluorescence in situ hybridization analysis revealed pericardial mesothelioma. Despite intensive care, the patient died 3 weeks later. Discussion: Primary pericardial mesothelial should be considered in the differential diagnosis of refractory recurrent pericarditis, even with prior biopsy-proven pericarditis or when a putative trigger (COVID-19 mRNA prior vaccination) is suspected, as was the case in this patient. Tumour diagnosis and identification consist of multimodal imaging and laboratory tests. A multidisciplinary, individualized care approach should be performed.