The mystery of migrating pleural effusion: Diagnosing the improbable

Dear Editor, Nonmalignant pleural effusions represent the most frequently encountered pleural pathology and are associated with substantial morbidity, healthcare utilization, and mortality. In a retrospective analysis from Central India involving 280 patients, the most common etiologies of exudative pleural effusions were tuberculosis, malignancy, and bacterial infections.1 Migratory pleural effusions – defined as unilateral effusions that subsequently resolve and recur contralaterally – are uncommon and sparsely described in the literature.2 A man in his fifth decade, a reformed smoker with a known history of coronary artery disease and recent percutaneous transluminal coronary angioplasty (PTCA), presented with a 2-month history of left-sided pleuritic chest pain. He denied fever, cough, or dyspnea. Physical examination revealed reduced breath sounds on the left side. Chest radiography and high-resolution computed tomography demonstrated left lower lobe consolidation and a left-sided pleural effusion. Diagnostic thoracentesis revealed an exudative pleural effusion with the following biochemical profile: glucose – 3 mg/dL, protein – 6.6 g/dL, albumin – 2.7 g/dL, and adenosine deaminase (ADA) – 28 U/L. Cytological analysis showed a lymphocyte-predominant effusion. Microbiological studies, including pleural fluid bacterial culture, acid-fast bacilli (AFB) smear, and cartridge-based nucleic acid amplification test (CBNAAT) for Mycobacterium tuberculosis, were negative. A transbronchial lung biopsy was planned; however, due to recent PTCA and ongoing dual antiplatelet therapy, cardiology consultation advised against cessation of clopidogrel owing to high thrombotic risk. Therefore, flexible bronchoscopy with bronchoalveolar lavage (BAL) was performed instead. BAL analysis showed negative bacterial and fungal cultures, AFB smear, and CBNAAT for M. tuberculosis. However, the BAL galactomannan index was elevated (3.56), and cytology demonstrated 12% eosinophils. The patient was empirically started on oral voriconazole and advised follow-up. He experienced symptom relief but was lost to follow-up. Three months later, the patient returned with new-onset right-sided pleuritic chest pain and fever. Chest radiograph showed a right-sided pleural effusion with complete resolution of the prior left-sided effusion. Contrast-enhanced computed tomography (CECT) of the chest confirmed the right pleural effusion, subsegmental atelectasis, and fluid tracking along the right oblique fissure Figure 1.Figure 1: Mediastinal window of contrast-enhanced computed tomography of the chest demonstrating right-sided pleural effusion, subsegmental atelectasis, and fluid tracking along the right oblique fissureThoracentesis revealed exudative fluid with elevated ADA (105 U/L), lactate dehydrogenase (LDH) 5009 IU/L, low glucose (16 mg/dL), and persistent lymphocytic predominance. Repeat pleural fluid studies, including AFB smear, CBNAAT, and cultures for bacterial and fungal pathogens, were negative. Autoimmune workup – including antineutrophil cytoplasmic antibodies and rheumatoid factor – was negative. Medical thoracoscopy with pleural biopsy was performed. Histopathology revealed necrotizing granulomatous inflammation Figure 2, although pleural tissue CBNAAT remained negative. Based on the high ADA and granulomatous pathology, empirical antitubercular therapy (ATT) was initiated.Figure 2: Hematoxylin and eosin stain of thoracoscopic pleural biopsy showing necrotizing granulomatous inflammation. The image is 4x magnifiedDespite ATT, the patient had persistent fever and pleuritic pain. Notably, peripheral eosinophilia increased progressively from 2% to 27% over a 1-week period. On reinterview, the patient disclosed frequent consumption of freshwater crabs. This dietary history raised suspicion for pleuropulmonary paragonimiasis. Serological testing – including enzyme-linked immunosorbent assay (ELISA) for Paragonimus-specific immunoglobulin G – was performed at the Indian Council of Medical Research, Dibrugarh, and returned positive. A final diagnosis of pleuropulmonary paragonimiasis was made, and he was treated with praziquantel. He experienced complete symptomatic resolution, and follow-up imaging demonstrated radiographic clearance of the effusion. Paragonimiasis, also known as lung fluke disease, is a foodborne zoonosis caused by trematodes of the genus Paragonimus.1,2 Human infection typically occurs following ingestion of undercooked or raw freshwater crabs or crayfish harboring the infective metacercarial stage. After ingestion, metacercaria excyst in the gastrointestinal tract, penetrate the intestinal wall, and migrate transdiaphragmatically to the pleural cavity and lungs, eliciting local inflammation.3 Despite being considered uncommon, Paragonimus infection has a broad geographic distribution, with endemic foci in Asia, Africa, and the Americas.4 At least nine species of Paragonimus are known to cause pleuropulmonary disease in humans.4 In tuberculosis-endemic settings, paragonimiasis can mimic pulmonary tuberculosis both clinically and radiologically, leading to diagnostic challenges.5 The pleural fluid in paragonimiasis is typically turbid with a yellow-to-brown appearance. Biochemical characteristics often include elevated LDH and ADA levels, low glucose concentration, and a high eosinophil percentage.6 In a retrospective study by Hwang et al. involving 20 patients with pleuropulmonary paragonimiasis, the mean pleural fluid LDH was 3114 U/L, glucose 33.9 mg/dL, and ADA 46.6 U/L. Notably, eosinophils comprised over 50% of the pleural cellularity.6 However, unlike typical eosinophilic predominance, the fluid in our case was lymphocyte predominant – a pattern that has also been reported in the literature and can further confound diagnosis by mimicking tuberculous pleuritis.7 Histopathologic features of paragonimiasis can include necrotizing or epithelioid cell granulomas, although parasitic ova may not be visualized.8 Serologic testing, particularly ELISA using the F1 antigen fraction, offers >90% sensitivity and near 100% specificity.9 Case reports have also documented the demonstration of characteristic eggs of paragonimiasis by iodine mount of BAL fluid.10 Praziquantel 25 mg/kg three times a day for 2 days remains the drug of choice and shows satisfactory response. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.