Our patient is a 31-year-old previously healthy Nepalese gentleman who presented to the emergency department in June 2020 with complaints of abdominal pain and distention associated with bilateral lower limb swelling of about 1-month duration. His abdominal pain was mild to moderate in severity, and not associated initially with nausea, vomiting nor change in his bowel habits. As his symptoms progressed, the patient noticed bilateral lower limb swelling that was present at the time of presentation. Systemic review was unremarkable for fever, weight loss, night sweats nor any new skin rash.
Upon initial assessment, blood pressure was 106/68 mmHg, oxygen saturation of 98 % on ambient air, pulse rate 80 beats per minute and regular. Respiratory rate of 18 breaths per minute. Physical examination revealed muffled heart sounds with raised jugular venous pressure and bilateral lower limb pitting edema. There were no murmurs or added sounds appreciated on cardiac auscultation, and chest exam was clear. The abdomen was mildly distended, with no peritoneal signs and negative for shifting dullness. Systemically, there were no signs of temporal wasting, skin rash, or palpable lymphadenopathy.
Initial labs were significant for a total leukocyte count of 7.6 x 103/ uL with peripheral eosinophilia (9%; absolute eosinophil count 0.7 x 103/uL) other metabolic panels including liver and renal chemistry were within normal limits. Pro B-type natriuretic peptide (Pro-BNP) was elevated with value of 514.80 pg/mL. Basic metabolic workup and cardiac and inflammatory markers were insignificant (Table 1, Table 2). Transthoracic echocardiography was ordered and demonstrated normal global left ventricular function with ejection fraction of 53 % and no regional abnormality, however it also demonstrated the presence of a moderate pericardial effusion. Electrocardiogram (ECG) was ordered which excluded any prior ischemic injury.
Diagnostic pericardiocentesis was performed which showed bloody fluid. Pericardial fluid analysis revealed a White blood cell count (WBC) of 197100 u/L and red blood cells (RBC) of 150 u/L with a predominantly lymphocytic effusion (55 %) (Table 3), Acid fast bacilli (AFB) and Mycobacterial Tuberculosis complex (MTBc) -Polymerase Chain Reaction (PCR) from body fluid were negative. MTBc cultures at this point were pending. Ultrasound of abdomen showed only mild ascites. The patient was started on intravenous furosemide. Shortly after admission the patient started complaining of chest pain and increasing shortness of breath. Re-assessment of his vital signs were within normal parameters and repeated examination was unchanged from admission. An urgent ECG did not show any ischemic changes and repeated chest X ray remained clear (Fig. 1); Lab investigations however were significant for an increase in peripheral eosinophilia (12 %; absolute eosinophil count of 1.0 x 103/ uL) (Table 1).
Given the demographic data and pericardial fluid analysis, a clinical suspicion of tuberculosis related pericardial effusion was raised and additional work up with 2 sets of sputum AFB smears, MTB-PCR and MTBc culture were sent along with serum QuantiFERON Gold Plus test. AFB smears and PCR were negative, however QuantiFERON test returned positive. A presumptive diagnosis of pericardial tuberculosis was made, and patient was started empirically on anti-tuberculosis treatment. He received first line regimen with rifampicin, Isoniazid, Pyrazinamide and Ethambutol according to his weight, in addition to prednisolone. He was discharged home to be followed in tuberculosis clinic for the final MTBc cultures.
During clinical follow up the patient was adherent to medications however, still complained of on and off exertional shortness of breath, the final Mycobacterial Tuberculosis culture from sputum and pericardial fluid was negative hence repeated echocardiography was requested for re-evaluation.
At 2 months from anti-tuberculosis treatment, repeated echocardiography showed evidence of progressive pericardial effusion with signs of increased intra-pericardial pressure. Echocardiography demonstrated normal global systolic left ventricular function with ejection fraction of 54 % without regional wall motion abnormality but there was circumferential moderate pericardial effusion. There was no right ventricular diastolic collapse or right atrial systolic collapse. The inferior vena cava was borderline in diameter with < 50 % collapse.
The patient was re-admitted for further evaluation. At the time, examination again demonstrated raised jugular venous pressure with muffled heart sounds on auscultation along and pedal edema. He now had absent breath sounds over the left lung base. Chest x-ray demonstrated new minimal blunting of left costophrenic angle (Fig. 2). Computed Tomography (CT) of the thorax was done and showed bilateral pleural effusion along with congestive pulmonary changes and minimal atelectasis in both lungs and circumferential pericardial effusion of 2.5 cm thickness with no evidence of pericardial calcification (Fig. 3).
Thoracic surgery team was consulted on the patient and decided to do a thoracoscopic pericardial biopsy and drainage of the pericardial and pleural fluid. A left thoracoscopy was performed and upon inspection of the thoracic cavity multiple white pearly nodules on the parietal pleura and to lesser extent on the pericardium and visceral pleura were found, the pericardium was significantly thickened and inflamed, there were adhesions between the lung and the parietal pleura posteriorly, moderate serous pleural effusion was noted and large bloody pericardial effusion under pressure was relieved upon opening the pericardium (Fig. 4). After creation of the window, biopsies were taken from the pericardial tissue and parietal pleura for histopathology and samples from the pleural and pericardial fluid were sent for microbiology and cytology, tissue cultures were also sent from the pericardium and pleura.
Ziehl-Neelsen stain for acid fast bacilli and MTBc-PCR from pericardial and pleural tissue as well as fluid in addition to MTBc cultures came back negative. However Microscopic examination of the pleural biopsy revealed thickened and fibrotic pleura which in addition contains clusters and sheets of chronic inflammatory cells including lymphocytes, plasma cells, eosinophils and histiocytes. Few well-defined epithelioid granulomas are seen engulfing parasitic egg with thick cuticle (Fig. 5a) which is polarizable under polarizer/analyzer lens (Fig. 5b) compatible with Paragonimus Westermani. Retrospectively, the patient reported eating freshwater crabs in his home country about 2 years earlier and further work up with stool and sputum analysis for ova and parasite was sent but came back negative. Unfortunately, no serological testing could be done for further confirmation even in reference lab in cooperation with our institute.
Anti-tuberculous medications were therefore discontinued, and the patient was started on praziquantel 1800 mg for a total of 3 days (approximately 75 mg/kg in three divided doses) along with a single dose of albendazole 400 mg. Prednisolone was gradually tapered then discontinued. Following treatment patient's symptoms significantly improved and chest drain was removed after draining a significant amount of fluid. Follow up echocardiography showed almost complete resolution of the effusion and the patient was discharged in good clinical condition.
Chest CT upon recent admission. . Congestive pulmonary changes in the form of ground glass opacities and pleural effusion at the posterior inferior aspects of both lungs, more on the left. (Arrow heads) Circumferential pericardial effusion (red arrow).