Idiopathic lymphocytic–eosinophilic pleural effusion with clinical response to corticosteroids: a case report

Dear Sir, We present a novel local case report of a patient with recurrent idiopathic bilateral mixed lymphocytic–eosinophilic pleural effusion (EPE) that responded to corticosteroids. A 60-year-old Chinese woman with no past medical history presented on 3 April 2023 with cough and breathlessness on exertion for 1 week with no other associated symptoms or trauma. She is a housewife and a non-smoker, with no prior occupational exposure and no family history of pulmonary or autoimmune diseases. There was no recent travel, raw food ingestion or any new medication intake. Physical examination was only suggestive of bilateral pleural effusion. She was afebrile, haemodynamically stable and saturating well on room air. Investigations did not demonstrate any evidence of cardiac failure, hypothyroidism and liver or kidney impairment. There was no evidence of leucocytosis or peripheral eosinophilia, and extensive serum autoimmune markers were also negative. Initial chest radiograph (CXR) [Figure 1] showed bilateral pleural effusions (right > left). Ultrasonography revealed bilateral anechoic pleural effusion with no septations. A right ultrasound-guided diagnostic thoracentesis was performed, which demonstrated lymphocytic–eosinophilic exudative pleural effusion (lymphocytes 48%, eosinophils 20%, neutrophils 2%) — pleural fluid to serum protein ratio > 0.5, lactate dehydrogenase (LDH) ratio > 0.6 and pleural fluid LDH higher than two-thirds of the upper limit of normal. Pleural fluid pH was > 7.5, and adenosine deaminase was normal at 27 U/L. Respiratory, fungal and mycobacterial stains and cultures also yielded no positive results. Malignant cells were not detected on cytology. A computed tomography of the thorax, abdomen and pelvis was also negative for malignancy with no reported suspicious lesions in the aerated lungs. Serum Strongyloides immunoglobulin G (IgG) and Filaria IgG4 were also negative, which did not suggest parasitic infections.Figure 1: Initial chest radiograph on presentation (3 April 2023) shows bilateral pleural effusions.The patient was subsequently discharged on 7 April 2023. Unfortunately, her repeat outpatient CXR on 17 April 2023 demonstrated worsening left pleural effusion with persistence of right pleural effusion [Figure 2]. She was readmitted, and a left thoracentesis performed showed similarly exudative lymphocytic–eosinophilic effusion (lymphocytes 51%, eosinophils 33%, neutrophils 3%) albeit with a higher eosinophil count. We repeated similar biochemical, microbiological and cytological studies from the left pleural tap, which were once again unyielding. Thus, we performed a right thoracoscopy with pleural biopsies that were sent for microbiology and histopathology. They returned negative, except for organising fibrous pleuritis noted on histopathology. The patient was started on 1-month taper of oral prednisolone starting at 20 mg twice/day and discharged on 26 April 2023. In May 2023, interval CXRs during follow-ups [Figure S1, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A190] initially demonstrated improvement in pleural effusions before a recurrence [Figure S2, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A190] on 10 July 2023. As there were no new symptoms or signs to suggest an alternative aetiology for the recurrence, we decided to restart a second tapering regimen of prednisolone at a lower dose starting from 20 mg once/day over 1 month, which led to eventual resolution [Figure S3, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A190] of pleural effusions. She remains on active follow-up over the last 1.5 years since her initial presentation, and there has been no recurrence [Figure S4, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A190] since completion of the second tapering regimen.Figure 2: Repeat outpatient chest radiograph (17 April 2023) shows worsening of the left pleural effusion, with persistent pleural effusion.Eosinophilic pleural effusion is defined as pleural fluid with 10% or more eosinophils.[1] It is uncommon, with a reported incidence of 7.2% among all pleural effusions.[1] The pathogenesis of EPE involves increased eosinophil production from the bone marrow with subsequent migration to the lungs.[2] There are multiple possible aetiologies of EPE, including malignancy, infections, posttraumatic, miscellaneous, etc.[1] A thorough review of medications, occupational and infectious disease exposure, comorbidities, pleural fluid analysis, cross-sectional imaging and diagnostic thoracoscopy with pleural biopsy may be warranted,[3] as idiopathic EPE is a diagnosis of exclusion. Our patient had no clear primary aetiology despite extensive workup and evaluation. In Singapore, where tuberculosis is endemic (incidence rate of 27.6 cases per 100,000 population in 2024)[4], it is imperative to perform a thorough evaluation, especially given the reports on tuberculosis accounting for 10% of EPEs in Asia.[5] Pleural trauma with resulting pneumothorax or haemothorax and chronic asbestos exposure[6] have also been reported to be associated with EPE. However, our patient had no history of trauma or asbestos exposure. She also does not take any chronic or over-the-counter medications that could precipitate EPE.[7] After an extensive investigation with no clear aetiology, we decided on a tapering course of steroids with oral prednisolone to improve the patient’s condition. Interestingly, she responded to prednisolone, further reinforcing our diagnosis of idiopathic EPE. There is limited information on the treatment of this condition. There have been case reports[8,9] that recommend the use of corticosteroids in idiopathic EPE that have shown dramatic response, although there is no clear consensus on the optimal treatment dose and duration. Given that our patient responded fully without recurrence of EPE only after a second tapering regimen of corticosteroids, we suggest that the use of low-dose corticosteroids should be extended over a 2-month taper instead of one for better efficacy in treating idiopathic EPE, as there might have been inadequate treatment dose with a 1-month taper. This could be the first reported case of idiopathic EPE in Singapore treated with corticosteroids that gave resolution, and further research and literature are needed for greater understanding into idiopathic EPE. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.