Pleural fluid milkshakes: three cases with different aetiologies

Abstract

In clinical practice, chylothorax is usually suspected in any patient with milky pleural fluid. However, contrary to popular belief, milky appearance of pleural fluid is seen in less than half of patients with chylothorax. A high index of suspicion for chylothorax is therefore needed in any turbid, bloody, or serosanguinous effusions of unclear aetiology. In this case series, we present three patients with biochemically proven chylothorax: each with a different presentation, pleural fluid appearance, underlying cause, management strategy and clinical outcome. The first patient developed ‘milky’ chylothorax secondary to lymphoma while the second patient's ‘yellow’ chylothorax is related to pleural tuberculosis. The final patient suffered from ‘pink’ chylothorax in the setting of systemic amyloidosis. In each of the cases, prompt diagnosis of chylothorax followed by efforts to elucidate the underlying cause are crucial steps to guide subsequent management with the main aim to ensure a better clinical outcome.

Contrary to popular belief, the classical milky appearance of pleural fluid is seen in less than half of patients with chylothorax. In this case series, we present three patients with biochemically proven chylothorax: each with a different presentation, pleural fluid appearance, underlying cause, management strategy, and clinical outcome. Lymphoma, tuberculosis, and presumed amyloidosis are underlying causes in our patients.

INTRODUCTION

Chyle (from the Greek word ‘chylos’ which means ‘juice’) is a milky fluid composed of lymph and fatty acids absorbed from the intestinal system. Chylothorax refers to pathological accumulation of chyle in the pleural space. ¹ Diagnosis of chylothorax was (and still commonly is till today) initially based on milky appearance of pleural fluid. ² Nevertheless, studies have shown that milky pleural fluid may be seen in only 44% of patients with chylothorax. ³ Various gross appearances of chylothorax from milky to serous and serosanguinous have been reported. ³ Measurement of pleural fluid triglyceride levels and/or chylomicrons can confirm a chylous effusion. Pleural fluid triglyceride level beyond 1.24 mmol/L (110 mg/dL) is highly suggestive of chylothorax. ² Herein, we describe three patients with biochemically proven chylothorax: each with a different presentation, pleural fluid appearance, underlying cause, management strategy and clinical outcome.

CASE SERIES

Case 1: Milky chylothorax

A 30‐year‐old gentleman with no prior medical illnesses presented with a one‐week history of worsening shortness of breath, cough and night sweats. Physical examination revealed muffled heart sounds with stony dullness and reduced breath sounds on both lung bases of his chest. He was in respiratory distress upon arrival necessitating intubation and mechanical ventilation. Chest X‐ray and bedside ultrasonography showed bilateral pleural effusions (worse on the right side) and pericardial effusion (maximum diameter of 2.5 cm) leading to pericardial tamponade. He was urgently managed with pericardiocentesis followed by right thoracentesis and right chest tube insertion. A total of 160 mL of straw‐coloured fluid and 1.5 L of milky fluid were drained from the pericardium and pleural cavity respectively (Figure 1A). Whilst findings of pericardial fluid were unremarkable, biochemical analysis of pleural fluid was consistent with chylothorax with a triglyceride level of 11.7 mmol/L. Computed tomography (CT) of the chest showed an anterior mediastinal mass with bilateral mediastinal lymphadenopathies (Figure 1B). The mass was biopsied under ultrasound guidance which confirmed a diagnosis of B‐cell non‐Hodgkin lymphoma. He was referred to haematology team for commencement of chemotherapy consisting of rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone (R‐CHOP). Simultaneously, he was advised to low‐fat diet with medium‐chain triglyceride supplementation. This was accompanied by clinical and radiological improvements together with resolution of chylothorax allowing chest tube removal after 2 weeks. He was discharged well after more than 3 weeks of hospitalization. He had no disease recurrence on further follow‐up at 2 months.

FIGURE 1.

Milky chylothorax: (A) Milky appearance of patient's pleural fluid. (B) CT shows anterior mediastinal mass (red arrows) with multiple bilateral mediastinal lymphadenopathies. Ultrasound guided biopsy of anterior mediastinal mass confirmed B‐cell non‐Hodgkin lymphoma

Case 2: Yellow chylothorax

A 61‐year‐old lady with hypertension and type‐2 diabetes mellitus presented with a one‐month history of dry cough and a 1‐week history of worsening shortness of breath. Chest X‐ray and bedside lung ultrasonography confirmed a massive right pleural effusion. One hundred millilitres of yellowish cloudy pleural fluid were retrieved during diagnostic thoracentesis, prompting urgent chest tube insertion for drainage due to initial suspicion of empyema (Figure 2A). However, pleural fluid analysis later confirmed chylothorax with a raised triglyceride level at 1.90 mmol/L. Pleural fluid cytology results were predominantly lymphocytic but pleural fluid gram stain and acid‐fast bacilli were unremarkable. CT chest showed a right pleural effusion with bilateral mediastinal lymphadenopathies. She subsequently underwent medical thoracoscopy which revealed multiple whitish nodules at the right parietal pleura (Figure 2B). Pleural biopsy results showed necrotizing granulomatous inflammation with the presence of acid‐fast bacilli on Ziehl–Neelsen stain, consistent with pleural tuberculosis. She was commenced on quadruple anti‐tuberculosis chemotherapy consisting of ethambutol, pyrazinamide, rifampicin and isoniazid. Similar to be the previous case, she was advised on a low‐fat diet. This was accompanied by improvements in symptoms and resolution of chylothorax allowing chest tube removal after 2 weeks. She developed transient derangements in liver function related to anti‐tuberculosis medications resulting in a temporary interruption of treatment for 7 days. Sequential reintroduction of medications was subsequently successfully performed. There was no re‐accumulation of chylothorax 3 months later when she was reviewed at the outpatient clinic.

FIGURE 2.

Yellow chylothorax: (A) Yellowish fluid drained from patient's pleural cavity. (B) Multiple whitish nodules (black arrows) were seen on parietal pleura during medical thoracoscopy. Pleural fluid marked with black triangle

Case 3: Pink chylothorax

A 46‐year‐old lady was hospitalized for a 2‐week history of worsening shortness of breath and generalized body swelling. She has a background history of hypertension and biopsy proven renal amyloidosis (Mayo Clinic stage 2). A month before her admission, she received 2 courses of chemotherapy consisting of cyclophosphamide, bortezomib and dexamethasone (CVD regime). Chest X‐ray on arrival showed cardiomegaly and bilateral pleural effusions which was worse on the right side (Figure 3A). Diagnostic right pleural thoracentesis showed pink turbid pleural fluid, which was later confirmed as a chylothorax with raised triglyceride level at 3.88 mmol/L (Figure 3B). Her pro B‐type natriuretic peptide (proBNP) levels were significantly elevated at 5869 pg/mL. Echocardiography revealed pericardial effusion with left ventricular hypertrophy, which suggested possible systemic amyloidosis. Her condition was complicated with methicillin‐sensitive Staphylococcus aureus (MSSA) bacteraemia, so she was commenced on intravenous cloxacillin. She, unfortunately, continued to deteriorate despite being under intensive care with ventilatory and circulatory support and eventually succumbed after 2 weeks of hospitalization.

FIGURE 3.

Pink chylothorax: (A) Chest X‐ray showed cardiomegaly and bilateral pleural effusion worse on the right side (B) Pink coloured pleural fluid drained from patient

DISCUSSION

Chylothorax is a rare condition, accounting for approximately 3% of all pleural effusions. ⁴ It can be classified into traumatic or non‐traumatic aetiologies, with traumatic causes outnumbering all non‐traumatic aetiologies combined. The pathophysiology of chylothorax is complex and disease‐specific. Malignancy is the leading cause of non‐traumatic chylothorax while thoracic surgery is the major cause of traumatic chylothorax. ¹ , ⁵ Lymphoma, being the most common malignant cause, is responsible for up to 75% of cases of malignant chylothorax. ⁶ Lymphomatous infiltration of the thoracic duct or duct compression by enlarged lymph nodes is responsible for chylothorax among lymphoma patients. On the other hand, chylothorax is a very rare complication of tuberculosis, with only 37 cases reported to date. ⁷ A recent systematic review by Rajagopala et al. suggested direct pleural involvement and/or thoracic duct infiltration by tuberculosis as the main mechanisms for tuberculosis‐related chylothorax. ⁷ In our third case, the exact cause of her pink chylothorax remained not fully elucidated. We postulate that chylothorax in her case is related to amyloidosis. Albeit rare, case reports have described the occurrence of chylothorax in the setting of systemic amyloidosis. ⁸ , ⁹ It is postulated that lymphatic infiltration by amyloid is responsible for chylothorax among patients with amyloidosis. ⁹

A confident diagnosis of chylothorax can only be achieved through biochemical testing of pleural fluid due to variable gross appearance. Pleural fluid triglyceride level beyond 1.24 mmol/L (110 mg/dL) is highly suggestive of chylothorax. In contrast, triglyceride level below 0.56 mmol/L (50 mg/dL) renders chylothorax unlikely. Performing lipid electrophoresis analysis for chylomicrons helps to diagnose chylothorax when triglyceride level is between 0.56 and 1.24 mmol/L (50–110 mg/dL). ² Pleural fluid triglyceride levels of all our patients were higher than 1.24 mmol/L, making the diagnosis of chylothorax highly likely. Milky chylothorax has significantly higher triglycerides levels compared to non‐milky counterparts. ³ This is consistent with our cases where the first patient with milky chylothorax showed a high level of triglyceride of 11.7 mmol/L in contrast to 1.90 mmol/L from yellow chylothorax and 3.88 mmol/L from pink chylothorax. Patients with non‐milky appearance of chylothorax are more likely to be undiagnosed or diagnosed late. Our second case was initially treated as empyema due to yellowish and turbid fluid appearance before chylothorax was confirmed biochemically.

Following biochemical confirmation, further investigations are useful to determine the underlying cause and to identify the site of chyle leakage. CT chest can identify mediastinal lesions and lymphadenopathy secondary to lymphoproliferative disorders, tuberculosis and malignancy. Benign conditions such as misplaced central catheters and pacemaker wires leading to chylothorax can be identified on CT chest as well. ¹ , ⁶ Lymphangioscintigraphy, computed tomography lymphangiography and magnetic resonance lymphangiography are being increasingly used instead of invasive lymphangiography to locate the exact site of chyle leak, which can inform subsequent duct repair surgeries. ¹⁰

Although currently there is no clear consensus on the most suitable approach to manage chylothorax, efforts should be aimed at identifying and correcting the underlying cause. ¹ In our first 2 cases, commencement of disease‐specific therapy led to resolution of chylothorax with no recurrence. An initial conservative approach is feasible for control of chyle leak before considering more invasive modalities. Non‐invasive measures such as low‐fat diet with medium chain triglyceride supplementation to replace nutrients lost in chyle and to reduce chyle formation is successful in up to 50% of cases. ¹ Octreotide may be considered either in conjunction with dietary regimens or when chyle loss persists despite other measures. ¹ In cases with large, rapidly recurring, or refractory chylous effusions, more invasive interventions to provide symptomatic relief and to minimize nutritional loss may be required. Traditionally, various interventions from surgical thoracic duct ligation to pleuro‐peritoneal shunts and chemical pleurodesis have been described with varying levels of success. ¹¹ , ¹² , ¹³ Nevertheless, recent advancements in magnetic resonance identification of site(s) of chyle leakage in the lymphatic networks have enabled highly targeted and effective (success rates of up to 93%) thoracic duct embolization and/or interstitial embolization of retroperitoneal lymphatics. ¹⁴

In conclusion, these three cases illustrate that a high index of suspicion is required for the diagnosis of chylothorax given that most pleural fluid is not milky in appearance. Prompt diagnosis followed by efforts to establish the underlying cause with subsequent disease specific treatment remains crucial steps in the management of chylothorax. Local pleural fluid control interventions are needed in cases with large or refractory effusions not responding to conservative measures. Future large‐scale studies can help to devise the most appropriate management strategy for this condition.

AUTHOR CONTRIBUTIONS

Nai‐Chien Huan contributed to the design and implementation of case series. Nai‐Chien Huan, Hooi Ann Tan and Hema Yamini Ramarmuty wrote the manuscript. Nai‐Chien Huan, Shivaanand Letcheminan and Subramaniam Ponnuvelu carried out the procedures mentioned. Kunji Kannan Sivaraman Kannan supervised the project. All authors discussed the study and contributed to the final manuscript.

CONFLICT OF INTEREST STATEMENT

None declared.

ETHICS STATEMENT

The authors declare that appropriate written informed consent was obtained for the publication of this manuscript and accompanying images.

Huan N‐C, Tan HA, Ramarmuty HY, Ponnuvelu S, Letcheminan S, Sivaraman Kannan KK. Pleural fluid milkshakes: three cases with different aetiologies. Respirology Case Reports. 2023;11:e01116. 10.1002/rcr2.1116

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.