An 18-year-old male presented to our hospital with worsening fatigue. His past medical history was negative for any pathologies. He progressively developed pericardial and pleural effusions; subsequently, polyserositis was diagnosed. Therapy with ibuprofen, corticosteroids, and colchicine was started without any significant improvements; therefore, the patient was started on anakinra, which also did not contribute to any substantial improvement in the condition. Broad serological tests of infectious and collagen diseases were performed, including hepatitis viruses, toxoplasma, mycoplasma, venereal disease research laboratory (VDRL), cytomegalovirus, human herpes 6 (HH6), human herpes 8 (HH8), Epstein-Barr virus (EBV), human immunodeficiency virus, Coxsackie viruses, and antinuclear and rheumatic factors. All results were negative except for immunoglobulin M (IgM) antiviral capsid antigen (VCA) for EBV. Our patient was not related to a tuberculosis-endemic area; however, PCR for tuberculosis was performed in blood samples, sputum, and pericardial fluid, and the results were negative. Blood tests were found weakly positive for IgM VCA, and the extended autoantibody panel (ANA, ENA, ANCA, ASCA, and FR) was negative. Screening for celiac disease was also negative, and thyroid function tests were within normal limits. We also found tamponade pericardial effusion. It was, therefore, necessary to perform the first pericardiocentesis. Pericardial fluid was negative for malignant cells yet positive for inflammatory cells, and the polymerase chain reaction (PCR) test was positive only for EBV. Examinations for all other infectious agents (HH6, HH8, TB, CMV, Enterovirus) were negative. A chest computed tomography (CT) scan was performed, identifying lymph node conglobate in the right lung hilum, bilaterally in the supraclavicular and mesenteric areas. A bone marrow biopsy was also performed and was negative for lymphoproliferative disease. The transthoracic echocardiography showed moderate dysfunction of the left ventricle (LV) (with an ejection fraction of 46%), severe desynchrony of the ventricular septum, a global longitudinal strain (GLS) of -12.9%, the right ventricle (RV) with a normal function, and no significant regurgitation of the atrioventricular valve (Figure 1A). Cardiac magnetic resonance imaging (MRI) showed mild global biventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 46%, right ventricular ejection fraction (RVEF) 47%] and circumferential pericardial effusion (maximum thickness 15-16 mm); right pleural effusion was identified (maximum thickness 3.5 cm), and there were no signs of pericardial constriction. Several days after pericardiocentesis with the extraction of about 400 ccs of blood serum liquid, a positron emission tomography (PET) CT scan and whole-body MRI scan were performed to exclude any underlying neoplastic processes. Once clinical and hemodynamic improvements were achieved, the patient was discharged with indications for close follow-up. One and two months after the patient was discharged, the echocardiography showed a stable condition with the persistence of a slight amount of pericardial effusion in the apical site and along the lateral wall of the left ventricle. After 3 months and mainly after 4 months, the echocardiogram showed worsening of the condition toward effusive-constrictive pericarditis, with enlargement of atrial sizes, alterations of diastolic function, dilation of the hepatic veins and inferior vena cava, and thickening and hyper-reflection of the pericardial leaflets. Abdominal ultrasound revealed effusion in all quadrants. A cardiac MRI was performed also 6 months after the first one and confirmed constriction with diffuse fibrotic thickening of the pericardial sac and signs of ventricular interdependence evident in the dynamic sequences (flattening of the interventricular septum in maximal inspiration), suggestive of constrictive physiology (Figure 2). The persistence of pericardial effusion along the mid-apical lateral wall of the LV was also identified (maximal thickness 10 mm). Finally, to confirm a restrictive picture, cardiac catheterization was performed, highlighting multiple elements suggestive of constrictive physiology with equalization of the diastolic filling pressure of the cardiac chambers and left and right ventricular diastolic "dip and plateau" appearance. Marked ventricular interdependence during the respiratory cycle and post-capillary pulmonary hypertension was noted. A diagnosis of constrictive effusive pericarditis was made (Figure 3, Table 1). The pre-operative cardiac catheterization showed pressure in the pulmonary artery of 35/21-25 mmHg and pulmonary wedge pressure of 22 mmHg (Table 1). At this point, the patient underwent anterior and posterior pericardiectomy surgery with preservation of the phrenic nerves, a procedure performed in normothermic cardiopulmonary bypass with a beating heart (Figure 4). Both intraoperative and postoperative periods were uncomplicated. The histological sample confirmed marked fibrous thickening with extreme rarefaction and fragmentation of the elastic fibers and mild lymphoplasmacytic inflammatory infiltrate (CD3+, CD20+, and CD38+), as well as neutrophilic granulocytes with numerous hemosiderin deposits and neovascularization. The in situ hybridization investigation with the Epstein-Barr-encoded small RNA (EBER) probe for the detection of EBV was positive, confirming the clinical suspicion of chronic pericarditis caused by EBV. Transesophageal echocardiography performed immediately after surgical excision of the fibrous pericardium showed complete recovery and normalization of ventricular septal motion. A few weeks after surgery, abdominal ultrasound showed a complete absence of peritoneal effusion. One week after surgery, transthoracic echocardiography was repeated and showed normalization of left ventricular function (3D ejection fraction 55%), and the GLS improved (-18.3%) (Figure 1B). The follow-up at 3, 6, and 12 months revealed no signs and symptoms related to diastolic heart failure, and echocardiogram findings were normal.