Pericarditis: Comprehensive Disease Characteristics Research Report

1. Disease Information

Overview. Pericarditis is inflammation of the pericardium — the fibroserous sac (visceral + parietal layers separated by a potential space normally containing 15–50 mL of fluid) surrounding the heart. It is the most common disease of the pericardium and presents across a clinical spectrum: acute pericarditis, incessant pericarditis (>4–6 weeks but <3 months, continuous), recurrent pericarditis (relapse after a symptom-free interval of ≥4–6 weeks), chronic pericarditis (>3 months), and, as a downstream sequela, constrictive pericarditis (fibrotic, calcified, non-compliant pericardium impairing diastolic filling). The 2025 ESC Guidelines for the management of myocarditis and pericarditis (the first integrated ESC guideline covering both conditions) introduce the umbrella concept of "inflammatory myopericardial syndrome" (IMPS) reflecting shared etiopathogenesis and frequent myopericardial overlap (myopericarditis/perimyocarditis) (Eur Heart J 2025; https://academic.oup.com/eurheartj/article/46/40/3952/8234483).

Key identifiers (to be OAK-verified before KB entry, per dismech policy): - MONDO: MONDO:0004770 (pericarditis) — suggested; a specific-form request would need e.g. constrictive pericarditis, tuberculous pericarditis, uremic pericarditis as related/child terms - OMIM: No single-gene OMIM disease entry for idiopathic/common pericarditis; monogenic periodic-fever syndromes that present with recurrent pericarditis have their own OMIM numbers (TRAPS: OMIM #142680; FMF: OMIM #249100) - ICD-10-CM: I30 (Acute pericarditis) — I30.0 (Acute nonspecific idiopathic pericarditis), I30.1 (Infective pericarditis), I30.8/I30.9; I31 (Other diseases of pericardium) — I31.0 (Chronic adhesive pericarditis), I31.1 (Chronic constrictive pericarditis), I31.3 (Pericardial effusion, noninflammatory), I31.4 (Cardiac tamponade); I32 (Pericarditis in diseases classified elsewhere, e.g., uremic, TB) - ICD-11: BB21 (Pericarditis), BB21.0 (Acute pericarditis), BB21.1 (Chronic pericarditis), BB23 (Constrictive pericarditis) - MeSH: D010493 (Pericarditis); D010496 (Pericarditis, Constrictive); D010494 (Pericarditis, Tuberculous) - Orphanet: ORPHA:98915 (Recurrent pericarditis) is a listed rare-disease entity for the recurrent/autoinflammatory form

Synonyms/alternative names: inflammation of the pericardium; pericardial inflammation; acute idiopathic pericarditis; Dressler syndrome (post-myocardial-infarction pericarditis, a subtype); postpericardiotomy syndrome; post-cardiac injury syndrome (umbrella term for post-MI, post-surgical, and post-traumatic pericarditis); tuberculous pericarditis; uremic/dialysis-associated pericarditis; effusive-constrictive pericarditis; transient constrictive pericarditis.

Evidence basis: This entry synthesizes aggregated disease-level clinical, epidemiological, genetic, and mechanistic literature (cohort studies, RCTs, systematic reviews, guideline documents) rather than a single-patient/EHR source.

2. Etiology

Disease causal factors — pericarditis is fundamentally a stereotypical inflammatory response of the pericardium to injury, regardless of trigger. Recognized categories:

• Infectious
• Viral (most common identifiable cause in high-income settings): enteroviruses (coxsackievirus, echovirus), adenovirus, parvovirus B19, herpesviruses (EBV, CMV, HHV-6), influenza, and SARS-CoV-2 (both from infection and, rarely, post-mRNA-vaccination myopericarditis).
• Bacterial: Mycobacterium tuberculosis — the dominant cause of pericarditis and constrictive pericarditis in Africa/Asia, especially with HIV co-infection (JACC Adv 2024; https://www.jacc.org/doi/10.1016/j.jacadv.2024.101427); purulent bacterial pericarditis (Staphylococcus, Streptococcus, Pneumococcus) — rare but high mortality.
• Fungal/parasitic: rare, seen in immunocompromised hosts.
• Idiopathic — the largest single category in immunocompetent patients in developed countries (up to 80–90% of ambulatory cases), presumed largely post-viral/autoimmune but without an identified trigger.
• Autoimmune/systemic inflammatory disease: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, sarcoidosis, IBD, vasculitides (e.g., polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis).
• Autoinflammatory (monogenic): TNF receptor-associated periodic syndrome (TRAPS, TNFRSF1A), familial Mediterranean fever (FMF, MEFV) — see Section 4.
• Post-cardiac injury syndrome (PCIS) — umbrella for:
• Post-myocardial infarction pericarditis — early peri-infarction pericarditis (direct extension of necrosis, days) vs. Dressler syndrome (delayed, immune-mediated, weeks–months post-MI) (PMC9681686).
• Postpericardiotomy syndrome — after cardiac surgery.
• Post-traumatic/post-procedural — after PCI, pacemaker/device implantation, catheter ablation, thoracic trauma (PMC8887692).
• Mechanism: anti-actin/anti-myosin autoantibodies following mesothelial/myocardial injury with immune-complex deposition in pericardium/pleura/lung, producing a delayed hypersensitivity-like polyserositis (ScienceDirect 2024, PMID:38559602).
• Neoplastic: primary pericardial tumors (rare, e.g., mesothelioma) or, far more commonly, metastatic disease (lung, breast cancer, lymphoma, melanoma) causing malignant pericardial effusion/pericarditis via direct invasion, lymphatic dissemination, or hematogenous spread (5–20% of patients with metastatic cancer have pericardial involvement; tamponade in up to 50% of malignant effusions).
• Metabolic: uremic pericarditis (pre-dialysis or early-dialysis ESRD, from toxic metabolite accumulation and increased microvascular permeability) and dialysis-associated pericarditis (from underdialysis in patients on chronic renal replacement) — occurring in up to 14% (range 2–21%) of ESRD patients (PMID:28873222).
• Radiation-induced: mediastinal radiotherapy (e.g., for lymphoma, breast cancer) — acute or delayed (years later) fibrosing pericarditis/constriction with particularly poor pericardiectomy outcomes (PMID:34547827).
• Drug-induced: procainamide, hydralazine, isoniazid (lupus-like), anticoagulants (hemopericardium), immune checkpoint inhibitors (irAE pericarditis/myopericarditis).
• Traumatic: blunt or penetrating chest trauma.

Genetic risk factors: - TNFRSF1A (HGNC:11916) pathogenic/likely-pathogenic and low-penetrance variants — found in ~6% of idiopathic recurrent pericarditis (IRP) cohorts (PMID:23745996); TRAPS patients have pericarditis in ~30% of cases (JACC Case Rep 2024). - MEFV (HGNC:6998) — rare deleterious variants (including the low-penetrance R202Q) enriched in IRP cohorts vs. ancestry-matched controls (~3.9–5%) (PMC11508427; PMID:35658515). - Family history/familial clustering of recurrent pericarditis can unmask TRAPS (PMID:20497634). - No common-variant GWAS signal specific to idiopathic pericarditis is well established in the literature to date (a genuine gap — see Section 4).

Environmental risk factors: male sex (2-fold higher incidence), age (bimodal — viral/idiopathic peaks in younger adults; malignant/uremic causes skew older), recent viral respiratory/GI illness, cardiac surgery/PCI/device implantation (procedural exposure), thoracic radiotherapy, tuberculosis exposure/endemicity and HIV co-infection (Africa/Asia), chronic kidney disease/dialysis dependence, autoimmune disease diagnosis, malignancy, and (rare) mRNA COVID-19 vaccination (myopericarditis, predominantly young males, self-limited).

Protective factors: Colchicine as secondary chemoprophylaxis after a first episode substantially reduces recurrence (see Section 12) — a pharmacologic rather than a constitutional protective factor. No robust genetic protective variant is established. Adequate/intensified dialysis reduces uremic pericarditis risk. Complete TB treatment reduces progression to constriction. No specific dietary/lifestyle protective factor is well characterized in the primary literature.

Gene–environment interactions: The clearest example is autoinflammatory-gene-primed inflammasome hyperresponsiveness (TNFRSF1A/MEFV variant carriers) interacting with a nonspecific inflammatory trigger (viral illness, minor injury, cold exposure — classic "stress trigger" reported by TRAPS patients) to precipitate a pericarditis flare, rather than a single environmental agent being sufficient on its own.

3. Phenotypes

*HP term suggestions are drawn from domain knowledge and should be OAK-verified (runoak -i sqlite:obo:hp info <ID> -O obo) against canonical labels before KB entry, per this repository's anti-hallucination protocol — several (friction rub, tamponade, constriction) I could not confirm exist as exact HPO leaf terms without direct OAK lookup and are flagged for curator verification rather than asserted.

Onset: Acute pericarditis can occur at any age but idiopathic/viral forms peak in young-to-middle-aged adults; malignant and uremic forms skew older; autoinflammatory-gene-associated recurrent pericarditis often begins in childhood/adolescence.

Severity/progression/course: Most acute idiopathic/viral pericarditis is self-limited (days to a few weeks) with NSAID/colchicine therapy. ~15–30% of a first episode recur; of those, further relapses are common, and a subset become colchicine-resistant/corticosteroid-dependent, driving IL-1-blockade candidacy. Recurrence overall approaches ~30% after a first episode. Progression to constrictive pericarditis is course-dependent: low risk (<1%) after viral/idiopathic pericarditis, intermediate (2–5%) after autoimmune/neoplastic, and high (20–30%) after bacterial/purulent or tuberculous pericarditis (Imazio et al., summarized in AFP 2024 review).

Quality-of-life impact: Recurrent pericarditis is associated with substantial QoL impairment — chronic pain, fatigue, activity limitation, anxiety about recurrence, and school/work absenteeism; IL-1-blockade trials (RHAPSODY, AIRTRIP) used patient-reported QoL instruments as secondary endpoints and demonstrated meaningful improvement with anti-IL-1 therapy (NEJM 2021, PMID:33200890).

4. Genetic/Molecular Information

Pericarditis is overwhelmingly a non-Mendelian, acquired inflammatory condition; monogenic contribution is confined to a minority of recurrent/idiopathic cases explained by autoinflammatory-disease genes.

Causal/associated genes: - TNFRSF1A (HGNC:11916; OMIM 191190) — encodes TNF receptor superfamily member 1A (p55 TNF receptor). Missense variants (e.g., cysteine-disrupting variants affecting extracellular disulfide bonds, and low-penetrance variants such as R92Q) impair receptor shedding/protein folding, causing TRAPS (OMIM #142680). Found in ~6% of idiopathic recurrent pericarditis cohorts (PMID:23745996); low-penetrance variants specifically implicated in adult-onset recurrent inflammatory attacks including pericarditis. - MEFV (HGNC:6998; OMIM 608107) — encodes pyrin. Pathogenic/likely-pathogenic variants cause FMF (OMIM #249100, AR); the low-penetrance R202Q variant has been specifically linked to anakinra-dependent recurrent pericarditis (PMC11508427). Rare deleterious MEFV variants enriched (~3.9%) in idiopathic recurrent pericarditis vs. ancestry-matched controls (PMID:35658515). - Other periodic-fever-syndrome genes (NLRP3/CAPS, MVK/hyper-IgD syndrome) are plausible but less specifically documented for pericarditis as the dominant phenotype; extrapolate cautiously.

Pathogenic variant characteristics: - Classification: predominantly missense (TNFRSF1A cysteine and non-cysteine variants; MEFV exon 10 and low-penetrance variants); ACMG/AMP tiers range from pathogenic (classic TRAPS-causing cysteine variants) to VUS/low-penetrance risk alleles (R92Q in TNFRSF1A, R202Q/E148Q in MEFV) — these lower-penetrance alleles act more as susceptibility/modifier variants than fully deterministic Mendelian causes, consistent with variable expressivity in adult-onset presentations. - Population allele frequency: low-penetrance variants (e.g., MEFV E148Q, R202Q) are relatively common polymorphisms in general population databases (gnomAD) with much lower penetrance than classic exon-10 FMF variants — curators should check gnomAD allele frequency directly per variant. - Origin: germline (autoinflammatory-gene variants); somatic variants are not a recognized mechanism in pericarditis. - Functional consequence: TNFRSF1A variants are broadly considered dominant-negative/gain-of-function for inflammatory signaling (impaired receptor shedding → sustained TNF signaling; also intracellular receptor misfolding triggering an unfolded-protein-response-linked pro-inflammatory state) rather than simple loss-of-function. MEFV pathogenic variants cause gain-of-function pyrin inflammasome activation.

Modifier genes: Not well characterized specifically for pericarditis; in the broader autoinflammatory-disease literature, additional NLRP3-pathway and cytokine-gene variants are proposed modifiers of clinical severity/penetrance, but pericarditis-specific modifier data are sparse — a knowledge gap.

Epigenetic information: No disease-specific pericarditis epigenetic dataset was identified in this search; broadly, inflammatory-disease epigenomic resources (ENCODE, Roadmap Epigenomics) have not to our knowledge been applied specifically to pericardial tissue in pericarditis.

Chromosomal abnormalities: Not a recognized feature of pericarditis; no aneuploidy/translocation association identified.

Suggested GO/molecular annotations for curation: GO:0043123 (positive regulation of canonical NF-kappaB signal transduction) for TNFRSF1A/pyrin-driven signaling; GO:0002218 (activation of innate immune response); NLRP3 inflammasome activation (GO:0043123-adjacent; consider GO term for "NLRP3 inflammasome complex assembly" if present in the ontology) — verify exact GO IDs via OAK before use.

5. Environmental Information

• Environmental/toxic factors: thoracic irradiation (mediastinal RT for lymphoma/breast cancer) is the best-documented environmental trigger outside infection, causing both acute pericarditis and delayed (sometimes decades-later) fibrosing constrictive pericarditis with disproportionately poor surgical outcomes (PMID:34547827). No specific chemical toxin/pollutant is robustly linked in CTD/TOXNET-style evidence at the level of a primary etiologic driver (distinct from generalized cardiovascular risk).
• Lifestyle factors: No strong dedicated lifestyle-modification literature (diet, exercise) for primary prevention of idiopathic pericarditis; post-diagnosis, strenuous physical activity is specifically discouraged during the acute/active phase until symptom and CRP normalization (guideline-level recommendation, ESC 2025) because of a theoretical/observed association with recurrence and to reduce arrhythmia risk in concurrent myocarditis.
• Infectious agents: the best-characterized "environmental" driver class.
• Viral: coxsackievirus B (classic), echovirus, adenovirus, parvovirus B19, EBV, CMV, HHV-6, influenza, SARS-CoV-2.
• Bacterial: Mycobacterium tuberculosis (leading global cause of pericarditis/constriction, especially sub-Saharan Africa with HIV co-infection — mortality 8–34%, rising to ~40% in untreated HIV co-infection) (JACC Adv 2024); Staphylococcus aureus, Streptococcus pneumoniae, and other pyogenic bacteria (purulent pericarditis, high mortality if untreated); Coxiella burnetii, Borrelia burgdorferi (rare).
• Fungal: Histoplasma, Aspergillus, Candida — rare, immunocompromised hosts.
• Parasitic: Echinococcus, Entamoeba histolytica — rare, endemic-region case reports.

6. Mechanism / Pathophysiology

Causal chain overview (general/idiopathic-viral pericarditis): 1. Trigger (viral infection, cardiac injury, autoimmune activation, uremic toxin accumulation, or malignant infiltration) → 2. Pericardial mesothelial cell injury/stress → 3. Innate immune sensing and NLRP3 inflammasome activation in pericardial (and epicardial) tissue — central, converging mechanistic node across etiologies (JACC Basic Transl Sci 2020; https://www.jacc.org/doi/10.1016/j.jacbts.2020.11.016) → 4. IL-1β (and IL-1α) release → downstream NF-κB-driven cytokine cascade (IL-6, TNF, chemokines) → 5. Local vascular/mesothelial inflammatory response: increased microvascular permeability, leukocyte (neutrophil, then lymphocyte/macrophage) infiltration, fibrin deposition on pericardial surfaces → 6. Clinical phase: pericardial friction rub (fibrin-roughened surfaces), pericardial effusion (increased permeability + reduced lymphatic clearance), pleuritic chest pain (irritation of pain-sensitive parietal pericardium/pleura), diffuse ST-elevation (subepicardial inflammation) → 7. Resolution or chronicity: in most cases inflammation resolves; in a subset, recurrent inflammatory cycling occurs (IL-1-driven, explaining efficacy of IL-1 blockade), or fibrotic organization and calcification of the pericardium develop over months–years → constrictive pericarditis (loss of pericardial compliance → equalization of diastolic pressures across chambers → ventricular interdependence → right-heart-failure phenotype).

Etiology-specific mechanistic branches: - Autoimmune/post-cardiac-injury syndrome: mesothelial/myocardial injury exposes normally sequestered cardiac antigens → anti-actin/anti-myosin (anti-heart) autoantibody formation → immune-complex deposition in pericardium/pleura/lung → delayed (weeks-months) hypersensitivity-type serositis, classically Dressler syndrome post-MI (PMC10978175, PMID:38559602). - Autoinflammatory (monogenic): TNFRSF1A misfolded-receptor retention/impaired shedding or MEFV pyrin gain-of-function → constitutively primed innate immune cells (monocytes/macrophages) → recurrent, stereotyped IL-1β-driven flares independent of adaptive immunity, explaining corticosteroid- or colchicine-refractory but IL-1-blockade-responsive disease. - Tuberculous pericarditis: classic four-stage pathogenesis (fibrinous exudation → serosanguinous effusion with high lymphocyte/monocyte content → organization with granuloma/caseation → constrictive scarring) driven by delayed-type (Th1) hypersensitivity to mycobacterial antigens, worsened by HIV-associated immune dysregulation; fibrocalcific encasement impedes diastolic filling (Circulation 2005; ScienceDirect immunopathogenesis review). - Uremic/dialysis-associated pericarditis: accumulation of uremic toxins (urea, other nitrogenous solutes) causes direct pericardial inflammation and increased microvascular permeability; underdialysis is the proposed proximate mechanism for the dialysis-associated form; intensified dialysis often resolves it, supporting a toxin-clearance-dependent mechanism (PMID:28873222). - Neoplastic: tumor cells reach the pericardium by direct invasion, lymphatic dissemination, or hematogenous spread; disrupt capillary/venule integrity → exudative or hemorrhagic effusion; separately, neoplastic infiltration causes pericardial scarring/loss of elasticity that can mimic constriction.

Cell types involved: pericardial mesothelial cells (primary site of injury/inflammasome activation), monocytes/macrophages, neutrophils (early), T lymphocytes (delayed/autoimmune phase), fibroblasts (fibrotic/constrictive phase), and — in myopericarditis overlap — cardiomyocytes.

Suggested ontology terms for curation (verify via OAK before use): - GO biological processes: "NLRP3 inflammasome complex assembly," "positive regulation of interleukin-1 beta production," "positive regulation of canonical NF-kappaB signal transduction," "fibrosis"/extracellular matrix remodeling terms for the constrictive-progression node. - CL cell types: mesothelial cell (relevant pericardial mesothelium term), macrophage, neutrophil, fibroblast, CD4-positive T cell. - UBERON: pericardium, pericardial cavity/space, epicardium, parietal pericardium, visceral pericardium.

Molecular/omics profiling: Dedicated transcriptomic/proteomic/single-cell atlases of human pericarditis tissue are sparse in the literature relative to myocarditis; most mechanistic insight instead derives from (a) pericardial/pleural fluid cytokine profiling (elevated IL-1β, IL-6, TNF in inflammatory effusions) and (b) the interferon-γ-knockout mouse model (Section 15) demonstrating that loss of IFN-γ regulation shifts an autoimmune cardiac response toward a constrictive-pericarditis phenotype (PMID:15505106) — a genuine translational/human-model-fidelity gap worth flagging for a dismech HUMAN_MODEL_MISMATCH discussion if curated.

7. Anatomical Structures Affected

Organ level: - Primary: pericardium (parietal and visceral layers), pericardial space/cavity. - Secondary/complication-driven: myocardium (myopericarditis/perimyocarditis overlap), right and left ventricles (diastolic filling impairment in constriction/tamponade), lungs and pleura (co-occurring pleuritis/pleural effusion, especially PCIS), liver (passive congestion, "cardiac cirrhosis" in chronic constriction), and systemic venous system (elevated JVP, peripheral edema, ascites in constrictive physiology). - Body systems: cardiovascular system primarily; secondary respiratory (pleuritic pain, pleural effusion) and, in autoimmune/uremic forms, renal and immune systems as upstream drivers rather than affected targets.

Tissue/cell level: mesothelial lining of the pericardium (site of primary injury and inflammasome activation); subserosal connective tissue (site of fibrosis/calcification in constrictive disease); in the myopericardial-overlap subset, subepicardial myocardium.

Subcellular level: NLRP3 inflammasome assembly at the level of the cytosol/mitochondria-associated membranes in mesothelial and macrophage populations (GO Cellular Component: inflammasome complex); disrupted TNFRSF1A intracellular trafficking/ER retention in TRAPS-associated cases.

Localization/laterality: Diffuse, non-lateralized process (unlike myocardial infarction) — a key clinical distinguishing feature (diffuse concave ST elevation vs. territorial STEMI changes). No meaningful unilateral/bilateral distinction applies to the pericardium itself, though co-occurring pleural effusions in PCIS can be unilateral or bilateral.

Suggested UBERON terms: pericardium, pericardial cavity, parietal pericardium, visceral pericardium (epicardium), fibrous pericardium, myocardium (for overlap phenotype), pleura (for PCIS co-involvement). Verify exact UBERON IDs via OAK before curation.

8. Temporal Development

Onset: Acute pericarditis can present at any age; peak incidence in young-to-middle-aged adults for idiopathic/viral forms; malignant, uremic, and radiation-associated forms occur predominantly in older or comorbid populations. Onset pattern is typically acute (days), though incessant (continuous >4–6 weeks but <3 months) and chronic (>3 months) courses occur, and tuberculous/uremic forms may present more insidiously.

Disease stages / progression: - Acute: days to a few weeks, self-limited in the majority with NSAID/colchicine therapy. - Incessant: continuous symptoms beyond the expected acute window without a symptom-free interval. - Recurrent: relapse after a documented symptom-free interval of ≥4–6 weeks; occurs in ~15–30% after a first episode, and in a subgroup evolves into multiple relapses requiring escalation to corticosteroids and ultimately IL-1 blockade. - Chronic: persistent (>3 months) low-grade inflammation. - Constrictive (late structural sequela): can develop as transient constrictive pericarditis (reversible with anti-inflammatory therapy, associated with CMR pericardial late gadolinium enhancement and elevated inflammatory markers predicting reversibility — Circulation, PMID underlying PMC3860810) or as fixed, fibrocalcific constriction requiring pericardiectomy.

Progression rate/course pattern: Highly etiology-dependent — viral/idiopathic pericarditis is typically monophasic-to-relapsing but rarely progresses to constriction; tuberculous and purulent bacterial pericarditis progress to constriction in a substantial minority (17–40% for TB) over months if inadequately treated; radiation-associated constriction can manifest years to decades after exposure.

Remission patterns: Spontaneous remission is common in viral/idiopathic acute pericarditis; treatment-induced remission is the norm with NSAID + colchicine; IL-1 blockade (rilonacept, anakinra) induces treatment-dependent remission in colchicine-resistant/steroid-dependent recurrent disease, with recurrence typically resuming on drug withdrawal in trial data (RHAPSODY).

Critical periods: Early initiation of colchicine (from the first episode) is the key intervention window for reducing recurrence risk; in tuberculous pericarditis, early diagnosis and antitubercular therapy (± adjunctive corticosteroids) is the critical window for preventing progression to constriction; in transient constrictive pericarditis, early aggressive anti-inflammatory therapy (guided by CMR LGE/CRP) can prevent the need for pericardiectomy.

9. Inheritance and Population

Epidemiology: - Incidence of acute pericarditis: ~27.7 per 100,000 person-years overall (commonly cited estimate); a Finnish population study reported 4.52/100,000 person-years in men vs. 2.11/100,000 in women. Acute pericarditis accounts for ~4.4% of ED presentations for non-ischemic chest pain, with an estimated 0.1% of all-cause and ~5% of chest-pain-related hospital admissions. - Recurrence after a first episode: ~15–30%. - Constrictive pericarditis incidence after non-TB pericarditis: <1–2%; after tuberculous pericarditis: 17–40%.

Inheritance pattern (for the genetic/autoinflammatory subset only — the great majority of pericarditis is acquired/non-Mendelian): - TRAPS (TNFRSF1A-associated): autosomal dominant, OMIM #142680. - FMF (MEFV-associated): classically autosomal recessive, OMIM #249100, though low-penetrance heterozygous variants (e.g., R202Q, E148Q) have been reported with apparent semi-dominant/reduced-penetrance patterns in recurrent-pericarditis cohorts. - Penetrance: incomplete and variable — particularly pronounced for the "low-penetrance" TNFRSF1A (R92Q) and MEFV (E148Q, R202Q) variants, which are relatively frequent in the general population but confer disease only in a minority of carriers, consistent with a susceptibility-allele rather than fully penetrant Mendelian model. - Expressivity: variable — even within TRAPS/FMF families, phenotype ranges from isolated recurrent pericarditis to full periodic-fever syndrome with polyserositis/rash/myalgia. - Genetic anticipation, germline mosaicism, founder effects: not specifically documented for pericarditis; FMF overall shows well-known founder-mutation enrichment in Mediterranean/Middle Eastern populations (Sephardic Jewish, Armenian, Turkish, Arab ancestries) — relevant background for MEFV-positive idiopathic recurrent pericarditis case ascertainment, though this is population structure of FMF broadly rather than pericarditis-specific. - Consanguinity: relevant to recessive FMF ascertainment generally, not documented as pericarditis-specific. - Carrier frequency: MEFV pathogenic-variant carrier frequency is notably elevated (~1 in 5–7) in some Mediterranean populations reflecting FMF founder effects — again, general-FMF-population data rather than pericarditis-cohort-specific.

Population demographics: - Sex ratio: male predominance overall, incidence ratio ~1.7–2.0:1 (men:women), with the largest sex gap in young adults; constrictive pericarditis specifically shows ~3:1 male:female predominance. - Geographic distribution: idiopathic/viral pericarditis predominates in high-income settings with low TB burden; tuberculous pericarditis dominates in sub-Saharan Africa and parts of Asia, where it is the leading cause of pericardial constriction, strongly modulated by HIV co-prevalence. - Age distribution: bimodal-ish — younger adults for idiopathic/viral/post-vaccination myopericarditis; older, comorbid populations for malignant, uremic, radiation-associated, and post-cardiac-surgery pericarditis.

10. Diagnostics

Clinical diagnostic criteria (ESC, reaffirmed 2025): ≥2 of 4 — 1. Typical pericarditic chest pain (pleuritic, positional) 2. Pericardial friction rub 3. New widespread ST-elevation or PR-depression on ECG 4. New or worsening pericardial effusion

Supportive findings: elevated CRP/inflammatory markers, evidence of pericardial inflammation on imaging.

Laboratory tests: - CRP/ESR — supports diagnosis, tracks disease activity, guides duration of anti-inflammatory therapy and tapering; LOINC-codable inflammatory markers. - Troponin — elevated in myopericarditis overlap (~15–30%); does not independently worsen prognosis absent regional wall-motion abnormality. - Complete blood count, renal function (to identify uremic etiology), autoimmune serologies (ANA, RF, ANCA) when systemic disease suspected. - Pericardial fluid analysis when pericardiocentesis performed: cell count/differential, protein, LDH (Light's-criteria-type exudate/transudate distinction), cytology (malignancy), ADA and mycobacterial culture/PCR (TB), Gram stain/culture (purulent).

Imaging: - Echocardiography: first-line, detects effusion, tamponade physiology, and (with Doppler) constrictive hemodynamics (respirophasic septal shift, hepatic vein flow reversal). - Cardiac CT: pericardial thickening/calcification, especially useful pre-pericardiectomy. - Cardiac MRI (CMR): pericardial late gadolinium enhancement (LGE) is a sensitive marker of active pericardial inflammation; elevated inflammatory markers plus pericardial LGE predict reversibility of constrictive physiology with anti-inflammatory therapy, distinguishing "transient constrictive pericarditis" from fixed fibrocalcific constriction requiring surgery (Circulation, PMID underlying PMC3860810/PMID:22262690-type series). - Chest X-ray: may show cardiomegaly ("water-bottle" silhouette) with large effusion; limited standalone diagnostic value.

Functional/electrophysiologic tests: ECG (4-stage evolution: diffuse ST-elevation + PR-depression → normalization → T-wave inversion → normalization); cardiac catheterization with simultaneous right/left heart pressure tracings for hemodynamic confirmation of constriction (equalized diastolic pressures, discordant respiratory variation in LV/RV systolic pressure — distinguishing constriction from restrictive cardiomyopathy).

Biopsy/pathology: Pericardial biopsy reserved for diagnostic uncertainty (suspected TB, malignancy, or purulent pericarditis) or at the time of pericardiectomy — histopathology shows fibrinous exudate (acute), granulomatous inflammation with caseation (TB), or dense fibrosis/calcification (chronic constrictive).

Genetic testing: Targeted TNFRSF1A and MEFV sequencing (single-gene or as part of a periodic-fever/autoinflammatory-disease gene panel) is reasonable in recurrent, colchicine-resistant/corticosteroid-dependent pericarditis, especially with a suggestive personal/family history of periodic fevers, serositis, rash, or relevant ancestry (Mediterranean for MEFV). Whole-exome/genome sequencing is not first-line but may be used in atypical multisystem presentations. No CMA, karyotype, FISH, mitochondrial, or repeat-expansion testing role is established for pericarditis.

Differential diagnosis: acute coronary syndrome/STEMI (most critical to exclude), aortic dissection, pulmonary embolism, pleuritis/pneumonia, costochondritis, esophageal disease (GERD, spasm), myocarditis (may coexist), restrictive cardiomyopathy (vs. constrictive pericarditis — key differential requiring invasive hemodynamics/CMR/CT tissue characterization).

Screening: No population-level screening program exists (acquired, largely sporadic disease); "screening" in practice is case-finding for underlying secondary causes (autoimmune serologies, TB testing, malignancy workup, renal function) once pericarditis is diagnosed, and cascade genetic counseling/testing of relatives when a monogenic autoinflammatory cause is confirmed.

11. Outcome/Prognosis

Survival/mortality: Idiopathic/viral acute pericarditis carries an excellent prognosis with mortality close to that of the general population. Prognosis is markedly etiology-dependent — purulent bacterial pericarditis and tuberculous pericarditis carry substantially higher mortality (TB pericarditis: >1 in 4 patients die within 6 months of diagnosis; mortality rises to ~40% with untreated HIV co-infection). Malignant pericardial effusion/tamponade is associated with poor prognosis reflecting the underlying cancer stage rather than the pericardial process per se.

Recurrence and chronicity: ~15–30% recurrence after a first episode; of recurrent cases, a meaningful subset become colchicine-resistant and corticosteroid-dependent, prompting escalation to IL-1 blockade.

Constrictive pericarditis outcomes (post-pericardiectomy): - Contemporary in-hospital/30-day mortality: ~2–8% (improved from historical rates of ~11–13.5%); actuarial survival ~91%, 85%, and 81% at 1, 5, and 10 years respectively. - Functional improvement (≥1 NYHA class) in ~80% of surviving patients. - Etiology strongly predicts surgical outcome: idiopathic and post-surgical constriction have the best outcomes; radiation-associated and neoplastic constriction have the worst long-term survival; need for reoperation and low cardiac output are additional adverse prognostic factors.

Morbidity/QoL: Recurrent pericarditis imposes significant chronic-pain and QoL burden (addressed above, Section 3); constrictive pericarditis produces a right-heart-failure-like disability burden (edema, ascites, exercise intolerance, hepatic congestion) until surgically corrected.

Prognostic factors/biomarkers: Persistently elevated CRP and pericardial LGE on CMR predict ongoing/recurrent inflammatory activity and identify the "transient" (reversible) constrictive phenotype amenable to medical therapy rather than surgery. High-risk features for a complicated first episode (per ESC criteria) include fever >38°C, subacute onset, large effusion/tamponade, failure to respond to NSAIDs within a week, myopericarditis, immunosuppression, trauma, and oral anticoagulant therapy.

12. Treatment

First-line pharmacotherapy (acute and first-recurrence pericarditis): - NSAIDs (ibuprofen, aspirin — aspirin preferred post-MI to avoid impairing infarct healing) — mainstay for pain/inflammation control. (NCIT:C15986 Pharmacotherapy; specific agent — CHEBI id per drug) - Colchicine — added to NSAID therapy from the first episode to reduce recurrence risk; foundational trial evidence: - COPE (2005) — colchicine + conventional therapy reduced recurrence in first-episode acute pericarditis (PMID:16186437). - ICAP (NEJM 2013, PMID:23992557) — colchicine added to standard anti-inflammatory therapy significantly reduced incessant/recurrent pericarditis in first-episode disease. - CORP (Ann Intern Med 2011) and CORP-2 (Lancet 2014) — colchicine reduced recurrence by >30% in patients with a first recurrence and in multiple-recurrence pericarditis, respectively. - Colchicine is now guideline-recommended as standard-of-care adjunct at every stage from first episode onward. (therapeutic_agent: CHEBI colchicine ID; treatment_term: NCIT:C15986 Pharmacotherapy) - Corticosteroids — reserved as second-line (NSAID/colchicine-refractory, contraindication to NSAIDs, or autoimmune-disease-associated pericarditis) because of an association with higher recurrence risk when used as first-line therapy; low-to-moderate dose with slow taper is preferred over high-dose pulses.

IL-1 pathway blockade (colchicine-resistant/corticosteroid-dependent recurrent pericarditis): - Rilonacept (ARCALYST) — soluble IL-1 receptor chimeric fusion protein neutralizing both IL-1α and IL-1β. Phase II (2020, PMC7925818) and pivotal Phase 3 RHAPSODY trial (NEJM 2021, PMID:33200890) demonstrated rapid resolution of pericarditis pain/inflammation and marked reduction in recurrence during randomized withdrawal. FDA-approved March 2021 — the first and only FDA-approved therapy specifically for recurrent pericarditis, for adults and children ≥12 years (weekly subcutaneous injection). (therapeutic_modality: MONOCLONAL_ANTIBODY-adjacent fusion protein — classify per dismech convention, likely OTHER/biologic; treatment_term: NCIT:C15986; therapeutic_agent: search NCIT/CHEBI for rilonacept) - Anakinra — recombinant IL-1 receptor antagonist; the AIRTRIP RCT demonstrated efficacy in colchicine-resistant, corticosteroid-dependent recurrent pericarditis. A systematic review/meta-analysis (PMC9730293) and review (PMC9152656) confirm efficacy of both anakinra and rilonacept, with anti-IL-1 therapy improving both QoL and clinical recurrence outcomes. - Mechanistic rationale directly ties to Section 6: NLRP3-inflammasome/IL-1β is the convergent pathway across etiologies, making IL-1 blockade a targeted (not merely empiric) therapy — an excellent candidate for a dismech target_mechanisms drug-mechanism edge onto an "NLRP3 Inflammasome Activation"/"IL-1β Release" pathophysiology node.

Etiology-directed therapy: - Tuberculous pericarditis: standard 4-drug antitubercular regimen ± adjunctive corticosteroids (evidence mixed/context-dependent, especially by HIV status); colchicine adjunct studied but not clearly beneficial in TB pericarditis specifically (PMC5412665). - Uremic/dialysis-associated pericarditis: intensified/optimized dialysis is first-line; NSAIDs/colchicine adjunctive; pericardiocentesis for tamponade. - Purulent bacterial pericarditis: targeted IV antibiotics + pericardial drainage (often surgical, given loculation risk). - Malignant pericardial effusion: pericardiocentesis ± pericardial window/sclerotherapy, and treatment of the underlying malignancy (chemotherapy/targeted therapy per tumor type). - Autoinflammatory-gene-positive recurrent pericarditis: IL-1 blockade is particularly rational and effective (anakinra specifically shown effective in MEFV R202Q-positive cases, PMC11508427).

Surgical/interventional: - Pericardiocentesis — for tamponade or large symptomatic/diagnostic effusion. (NCIT surgical/procedural term — verify) - Pericardial window — for recurrent/malignant effusions. - Pericardiectomy — definitive therapy for fixed constrictive pericarditis; outcomes summarized in Section 11 (best for idiopathic/post-surgical etiology, worst for radiation/neoplastic).

Supportive care: activity restriction until symptom/CRP resolution; analgesia; management of tamponade as an emergency.

Experimental/emerging: - Additional IL-1-pathway and broader anti-inflammatory agents continue to be studied for recurrent pericarditis (search ClinicalTrials.gov for current NCT-registered trials, e.g., colchicine-formulation and other anti-inflammatory candidates such as the CardiolRx/MAvERIC-Pilot program referenced in trial registries). - Ongoing refinement of CMR-LGE-guided therapy duration/tapering strategies.

Treatment algorithm (guideline-level, ESC 2025): NSAID + colchicine from first episode → corticosteroids only if NSAID-refractory/contraindicated → IL-1 blockade (rilonacept or anakinra) for colchicine-resistant, corticosteroid-dependent recurrent disease → surgical pericardiectomy reserved for fixed constrictive physiology unresponsive to anti-inflammatory therapy (with CMR/CRP used to first distinguish reversible "transient constriction" from fixed disease).

13. Prevention

Primary prevention: No population-level primary-prevention program exists for idiopathic/viral pericarditis (sporadic, largely unpredictable trigger). Etiology-specific primary prevention is more concrete: - TB pericarditis: TB control programs, HIV testing/ART access, and (where relevant) latent-TB treatment in high-risk populations. - Uremic pericarditis: adequate/timely dialysis initiation and dose optimization. - Post-cardiac-injury syndrome: no established primary prophylaxis, though perioperative colchicine has been studied to reduce postpericardiotomy syndrome incidence after cardiac surgery in some trial literature (not exhaustively reviewed here — worth a dedicated search if curating this specific claim). - Radiation-associated pericarditis: radiotherapy planning to minimize cardiac/pericardial dose (modern conformal/IMRT techniques).

Secondary prevention (recurrence prevention — the best-evidenced prevention domain in this disease): - Colchicine started at first-episode diagnosis is the single best-evidenced secondary-prevention intervention (COPE, ICAP, CORP, CORP-2 — Section 12), reducing recurrence by roughly one-third to one-half across trials. - IL-1 blockade (rilonacept, anakinra) functions as tertiary/secondary prevention specifically in the colchicine-resistant subgroup, with RHAPSODY demonstrating markedly reduced time-to-recurrence during drug-withdrawal periods. - Avoidance of high-dose corticosteroid monotherapy as first-line, since it is itself associated with higher recurrence risk relative to colchicine-based regimens.

Screening/early detection: CRP-guided activity restriction and treatment-duration decisions function as a form of tertiary prevention (of both symptomatic relapse and progression to constriction). Early CMR characterization of "transient" vs. fixed constrictive physiology allows early aggressive medical therapy to prevent the need for pericardiectomy.

Genetic counseling: For confirmed TNFRSF1A/MEFV-associated recurrent pericarditis, standard autoinflammatory-disease genetic counseling applies — informing relatives of inheritance pattern (AD for TRAPS, AR/reduced-penetrance for MEFV), variable penetrance/expressivity, and the availability of targeted IL-1-blockade therapy for confirmed carriers with recurrent symptoms.

Public health: TB control and HIV treatment access are the dominant public-health lever globally, given tuberculous pericarditis's outsized contribution to pericarditis morbidity/mortality and constriction burden in endemic, high-HIV-prevalence regions.

14. Other Species / Natural Disease

Naturally occurring pericarditis is recognized in veterinary medicine, most notably: - Traumatic reticulopericarditis ("hardware disease") in cattle — a well-known naturally occurring bovine pericarditis caused by ingested metallic foreign bodies migrating from the reticulum through the diaphragm into the pericardial sac, producing purulent/fibrinous pericarditis and, if chronic, constrictive physiology — a genuine natural-disease veterinary analog (relevant OMIA/veterinary literature, not deeply searched here but well established in veterinary cardiology). - Idiopathic pericardial effusion in dogs (and pericardial mesothelioma-associated effusion, notably in Golden Retrievers) is a recognized clinical entity in small-animal cardiology, though its mechanistic overlap with human idiopathic pericarditis is not well characterized at the molecular level in the literature surveyed here. - No specific NCBI Taxon-indexed comparative-genomics ortholog analysis for pericarditis susceptibility genes (TNFRSF1A, MEFV) across species was identified in this search; both genes are broadly conserved across mammals given their fundamental roles in TNF signaling and inflammasome biology, but disease-specific cross-species susceptibility data are not established in the pericarditis literature specifically. - No zoonotic transmission concern applies to pericarditis itself (it is a tissue-response phenotype, not a transmissible entity), though the causal pathogens in infectious pericarditis (e.g., some Coxiella burnetii cases) do have zoonotic origins.

15. Model Organisms

Compared with myocarditis, dedicated pericarditis-specific animal models are relatively sparse in the literature; most mechanistic animal data derive from cardiac-injury or autoimmune-myocarditis models with secondary pericardial involvement:

• Interferon-γ-knockout (IFN-γ KO) mouse model of cardiac-myosin-induced experimental autoimmune myocarditis — the most directly relevant genetic model identified: cardiac myosin immunization in IFN-γ-KO mice produces a novel model of constrictive pericarditis with grossly detectable pericarditis, decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling — recapitulating the human constrictive-physiology phenotype (Circulation 2004, PMID:15505106). This demonstrates that loss of IFN-γ-mediated immune regulation shifts an autoimmune cardiac inflammatory response toward pericardial constriction rather than isolated myocarditis, a mechanistically informative but human-fidelity-uncertain finding (candidate for a HUMAN_MODEL_MISMATCH framing if curated, since knockout of a single regulatory cytokine in mice is a strong artificial perturbation not established as directly translatable to sporadic human constrictive pericarditis).
• Experimental autoimmune myocarditis (EAM) — induced by subcutaneous immunization with cardiac myosin/α-myosin heavy chain peptide in complete Freund's adjuvant, strain-dependent susceptibility (A/J, BALB/c) — the parent model from which the IFN-γ-KO pericarditis-specific variant was derived; primarily a myocarditis model with pericardial involvement as a secondary/associated finding rather than the primary phenotype.
• Coxsackievirus B3 (CVB3)-induced murine myocarditis — models the viral-infection → myocarditis → chronic fibrosis/pericarditis → dilated cardiomyopathy sequence relevant to the viral-etiology branch of human pericarditis, though again pericarditis is a secondary/associated feature of a primarily myocardial model.
• Model limitations: no widely used model isolates pericardial-mesothelial NLRP3-inflammasome activation as the primary, independent phenotype (i.e., a "pure" pericarditis model without concomitant myocarditis); this is a genuine translational gap, and current mechanistic inference about NLRP3/IL-1β centrality in human pericarditis rests more on (a) clinical biomarker/effusion cytokine data and (b) the strong clinical-trial efficacy signal of IL-1 blockade (RHAPSODY, AIRTRIP) than on a dedicated animal model recapitulating idiopathic recurrent pericarditis end-to-end.
• Applications: existing models are primarily used to study autoimmune mechanisms of cardiac inflammation broadly and the transition from inflammation to fibrosis/constriction, rather than to test pericarditis-specific therapeutics — IL-1-blockade drug development for pericarditis instead proceeded largely from mechanistic/biomarker rationale directly into human trials.

Summary of Suggested Ontology Terms for Curation (require OAK verification before entry)

Key Citations (PMID-anchored where available)

1. Colchicine for acute pericarditis (COPE trial) — PMID:16186437
2. Colchicine for recurrent pericarditis (CORP trial) — Ann Intern Med 2011
3. Colchicine for acute pericarditis (ICAP trial) — PMID:23992557
4. Rilonacept Phase 3 (RHAPSODY) — PMID:33200890
5. Interleukin-1 antagonists for recurrent pericarditis (review) — PMC9152656
6. Rilonacept and anakinra meta-analysis — PMC9730293
7. TNFRSF1A mutation spectrum in idiopathic recurrent acute pericarditis — PMID:23745996
8. Recurrent pericarditis: autoimmune or autoinflammatory? — PMID:22884556
9. Pericarditis and autoinflammation — monogenic autoinflammatory disease screening — PMID:35658515
10. Anakinra-dependent recurrent pericarditis and MEFV R202Q — PMC11508427
11. Familial clustering of recurrent pericarditis unmasking TRAPS — PMID:20497634
12. NLRP3 inflammasome role in pericarditis (mechanistic review) — https://www.jacc.org/doi/10.1016/j.jacbts.2020.11.016
13. Post-cardiac injury syndrome: evidence-based approach — PMID:38559602
14. Dressler syndrome: not just a relic of the past — PMC9681686
15. Cardiovascular involvement in TB patients treated in Southern Africa — JACC Adv 2024
16. Uremic pericarditis, pericardial effusion, and constriction in ESRD — PMID:28873222
17. CMR pericardial LGE predicts reversibility of constrictive pericarditis — Circulation (PMC3860810)
18. Long-term outcomes of pericardiectomy for constrictive pericarditis — PMC4662820
19. FDA approval of rilonacept for recurrent pericarditis (2021) — Kiniksa/FDA press release
20. Novel model of constrictive pericarditis in IFN-γ-knockout mice — PMID:15505106
21. 2025 ESC Guidelines for the management of myocarditis and pericarditis — Eur Heart J 2025 (https://academic.oup.com/eurheartj/article/46/40/3952/8234483)

Note on evidence gaps: Several sections (epigenetics, single-cell/spatial transcriptomics of human pericardial tissue, modifier genes beyond TNFRSF1A/MEFV, pericarditis-specific animal models isolating pericardial inflammation from myocarditis, and comparative/veterinary molecular data) have thin or absent dedicated literature and are flagged rather than fabricated — consistent with this KB's evidence-discipline requirement to omit or flag unsupported claims rather than invent citations.