implanted >3 months ago) For definite clinical diagnosis: 2 major criteria or 1 major and 3 minor criteria or 5 minor criteria For possible clinical diagnosis: 1 major and 1 minor criterion or 3 minor criteria Amended ESC and AHA 2015 guidelines (see references 1 and 2) CT, Computed tomography; FDG, fluorodeoxyglucose; HACEK, Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, Kingella spp.; IE, infective endocarditis; PET, positron emission tomography; SPECT, single-photon emission computed tomography Modified from Li JS, Sexton DJ, Mick N, et al Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis Clin Infect Dis 2000;30:633–638 The criteria are very helpful, but they should be used for diagnosis in addition to clinical judgement Differential Diagnosis It may require differential diagnosis with chronic infection, rheumatologic, and autoimmune diseases or tumors Intracardiac Masses Tumors, although rare, should always be considered It should be noted that cardiac myxomas quite often manifest with low-grade fever, immune phenomena, and positive markers of inflammation and mimic IE to a great extent The nonbacterial thrombotic endocarditis (NBTE) described as a paraneoplastic process for multiple adult cancers44 seems not to be characteristic of pediatric tumors However, there might be direct extension into the right heart by hepatoblastoma, neuroblastoma, and Wilms tumor.45–47 Extension to the left heart via the pulmonary vein for pulmonary metastasis of hepatoblasoma48 or Wilms tumor,49 as well as direct metastasis to the left ventricle of neuroblastoma,50 have also been described Granulomatous polyangiitis (GPA, previously Wegener granulomatosis) is reported to cause intracardiac thrombus,52 as well as valve perforations,51 which might mimic IE Liebmann-Sachs endocarditis may be the first manifestation of systemic lupus erythematosus (SLE) in children53: it usually involves the mitral or aortic valve but may involve both54 or may also be located on the tricuspid valve.55,56 Although it may have a favorable evolution after starting treatment, it may require urgent surgery because excessive growth may create obstruction.57 In Churg-Strauss eosinophilic polyangiitis, cardiac manifestations usually occur with severe myocarditis but intracardiac thrombi have also been reported.58 Hypereosinophilic syndrome in childhood may have cardiac manifestations that are particularly notorious for initial infiltration, including mural and apical, that progresses quickly to fibrosis, thus leading to worsening regurgitation with little possibility for repair and almost universal need of replacement.59,60 It might also cause myocardial infiltration with restrictive cardiomyopathy as a concomitant feature.61 Biopsy might not always be helpful: echocardiograms and endomyocardial biopsies agree for presence or absence of cardiac involvement 60% of the time.62 Hyperhomocysteinemia due to a heterozygous C677T polymorphism in the methylenetetrahydrofolate reductase gene is a well-recognized thrombophilia condition that is phenotypically most well expressed in the homozygous recessively inherited metabolic disorder that has severe hyperhomocysteinemia and may potentiate intracardiac and valvar thrombi formation.63 It should be taken into account that for unknown reasons patients with IE may have mild hyperhomocysteinemia without necessarily having the polymorphism itself; this does not relate to bigger vegetations or increased embolic risk.64 From the other thrombophilias studied, it has been confirmed that mutations G20210A of the prothrombin gene and G1691A of factor V Leiden gene do not contribute to the susceptibility to IE.65 Periaortic Thickening Surgically related echocardiographic findings can appear like glue after valve replacement66 or hyperechogenicity of homografts (unpublished) Chronic periaortitis has been studied in detail and described in GPA, eosinophilic granulomatous polyangiitis, and polyarteritis nodosa,67–75 and it might very well mimic aortic root abscess Pyrexia Line infections are the most frequent cause of echo request for ruling out IE Pyrexia of unknown origin and bacteremia have become major indications for echo to rule out IE The number of requests has risen exponentially in the past 2 decades Different tools have been designed to indicate when an urgent echo is required An approximately 20% and 10% positive yield for IE diagnosis in community and nosocomial acquired staphylococcal bacteremia, respectively, justifies echo as a screening tool76,77; the percentage of pediatric IE cases among children with S aureus bacteremia is approximately 12%.78 It should be underlined that one of the most frequent causes of persistent bacteremia besides IE and line infection is osteomyelitis; tooth abscess has also been described Differential diagnosis is shown on Box 56.4 Box 56.4 Differential Diagnosis of Infective Endocarditis Intracardiac Masses Tumors ■ Myxomas ■ Extension via the inferior vena cava (neuroblastoma and Wilms tumor) ■ Nonbacterial thrombotic endocarditis in distant tumors (not characteristic of pediatric age) Noninfectious Intracardiac Thrombi ■ Acute rheumatic fever ■ Autoimmune diseases (GPA, SLE, APS, Churge-Strauss eosinophilic GPA) ■ Hypereosinophilic syndrome (acute leukemia, parasitic disease) ■ Thrombophilia (homocystinemia) Periaortic Masses ■ Surgical (glue) ... community and nosocomial acquired staphylococcal bacteremia, respectively, justifies echo as a screening tool76,77; the percentage of pediatric IE cases among children with S aureus bacteremia is approximately 12%.78 It should be... ■ Extension via the inferior vena cava (neuroblastoma and Wilms tumor) ■ Nonbacterial thrombotic endocarditis in distant tumors (not characteristic of pediatric age) Noninfectious Intracardiac Thrombi ■ Acute rheumatic fever ■ Autoimmune diseases (GPA, SLE, APS, Churge-Strauss eosinophilic GPA)