October 2022 Medical Image of the Month: Infected Dasatinib Induced Chylothorax-The First Reported Case

Figure 1. Upright PA chest radiograph (A) demonstrates a large left-sided pleural effusion with some lateral fluid suggesting loculation. Bedside ultrasound to guide thoracentesis (B) demonstrates multiple loculations within the effusion (arrowheads). Thoracentesis yielded 2 liters of milky white fluid (C).

Figure 2. Axial lung window (A) and soft tissue window (B) reconstructions from a chest CT with intravenous contrast performed following thoracentesis demonstrates a circumferential irregular left-sided pleural effusion with air space disease within the left lower lobe concerning for infection. A simple-appearing right-sided effusion is noted as well (*).

Case Report

A 45-year-old man with chronic myeloid leukaemia (CML) on dasatinib presented to the emergency department with a 2-week history of dry cough, worsening shortness of breath and left-sided chest pain that had worsened on the day of presentation. On examination, oxygen saturation was 98% on 2 L nasal cannula, respiratory rate 22 bpm, pulse 77 bpm, blood pressure 117/90 mmHg and his temperature was 37.9° C (100.2 F). Examination of the left chest showed no air entry and stony dull percussion note.

Laboratory results were significant for leucocytosis with a neutrophil count of 11.2, elevated CRP of 414, mildly elevated lactate of 1.1. Initial chest X-ray showed large left-sided pleural effusion and a small volume right effusion (Figure 1A). The patient was started on IV piperacillin /tazobactam, blood cultures were obtained and the dasatinib was held.

Ultrasound-guided left thoracentesis and drain placement was performed, on ultrasound the effusion demonstrated several loculations (Figure 1B). An 18Fr drain was inserted and 2L of white purulent/milky material fluid was drained (Figure 1C). Pleural fluid analysis showed abundant neutrophils, macrophages, lymphocytes and a few reactive mesothelial cells. Cytological analysis was negative for malignant cells. The fluid was exudative by Light’s criteria as total protein was 52.9 g/l and serum protein was 77 g/l with the ratio 0.68. Triglyceride level was 2.0 mmol/l and fluid cholesterol was 1.6 mmol/L indicative of chylothorax.

Over time, pleural cultures were positive for beta haemolytic Strep group C/G sensitive to penicillin G and erythromycin and both fungal and tuberculosis cultures were negative. Blood cultures were negative. Antimicrobial therapy was deescalated to Penicillin G. A subsequent chest CT (following intra-pleural fibrinolytic therapy) showed small left basal effusion with overlying consolidation and no occlusive lesion identified (Figure 2). After 9 days the pleural drain was removed, and the patient had no reaccumulation of their chylothorax. The patient remained clinically well and was discharged after a course of four weeks of antibiotics. At a 2 week follow up the patient was asymptomatic and had a normal physical exam. His inflammatory markers were back to normal CRP was 0.5 and WBC count was 6.5.

Discussion

Chylothorax is accumulation of chyle into the pleural space related to obstruction or disruption of the thoracic duct. It is a rare condition that may arise from diverse etiologies broadly categorized as traumatic or non-traumatic/spontaneous (1). Chylothorax is widely believed to be inherently bacteriostatic, with rare incidence of infected chylous effusions affecting a wide variety of patients with different causative organisms and a mostly benign course (2).

Dasatinib is a second-generation tyrosine kinase inhibitor that is recommended as the first-line therapy for newly diagnosed chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL) with positive Philadelphia chromosome (Ph+) or as an alternative for the failure of prior therapy for CML. Dasatinib is known to cause fluid retention which commonly presents as an exudative pleural effusion (3), chylothorax is rarely seen with 7 cases in total related to dasatinib use were published in the literature (4).

This is the first reported case of infected chylothorax among the population using dasatinib. Infected chylothorax in general is rare, affecting wide variety of patients with different organisms and mostly benign course (2). In this report the patient was stable on presentation and showed good response to antibiotics, chest drainage, holding of dasatinib and dietary fat restriction. Given the loculated appearance of the fluid the patient benefited from a dose of thrombolysis, which was reported as an option in such a scenario (5).

In patients with CML on dasatinib presenting with pleural effusion, the medication should be considered as one of the possible causes. Furthermore, infected chylothorax should be considered in the deferential diagnosis as a source of sepsis in patients presenting with a sepsis-like clinical picture and pleural effusion. The case also reflects the importance of bedside ultrasound in both clinically examining the patients and as a guide for thoracentesis and guidance for therapy.

Mortada Mohammed¹ MD MRCPI, Mohanad Abdelrahim² MD, Keshav Sharma³ MD MRCPI

¹Respiratory medicine registrar Wexford General Hospital, Wexford, Ireland

²Medical Senior House officer Wexford General Hospital, Wexford, Ireland

³Consultant Respiratory and General Medicine Physician, Wexford General Hospital, Wexford, Ireland

References

1. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med. 2010 Jan;104(1):1-8. [CrossRef] [PubMed]
2. Eubank L, Gabe L, Kraft M, Billheimer D. Infected chylothorax: a case report and review. Southwest J Pulm Crit Care. 2018 Aug 25;17(2):76–84. [CrossRef]
3. Keating GM. Dasatinib: A Review in Chronic Myeloid Leukaemia and Ph+ Acute Lymphoblastic Leukaemia. Drugs. 2017 Jan;77(1):85-96. [CrossRef] [PubMed]
4. Chen B, Wu Z, Wang Q, Li W, Cheng D. Dasatinib-induced chylothorax: report of a case and review of the literature. Invest New Drugs. 2020 Oct;38(5):1627-1632. [CrossRef] [PubMed]
5. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg. 2007 Aug;32(2):362-9. [CrossRef] [PubMed]

Cite as: Mohammed M, Abdelrahim M, Sharma K. October 2022 Medical Image of the Month: Infected Dasatinib Induced Chylothorax-The First Reported Case. Southwest J Pulm Crit Care Sleep. 2022;25(4):47-9. doi: https://doi.org/10.13175/swjpccs036-22 PDF

Medical Image of the Week: Chylothorax

Figure 1. A: CT of the chest (coronal image) demonstrating large right hilar and mediastinal adenopathy, leading to moderate to severe narrowing of the superior vena cava (SVC). B: CT of the chest (axial image) demonstrating moderate to severe narrowing of the pulmonary artery trunk due to compression from mediastinal adenopathy. A left pleural effusion is noted.

Figure 2. Pleural fluid sample demonstrating milky, pink fluid. The triglyceride level was 532 mg/dl and cholesterol level 63 mg/dl.

A 73-year-old man with untreated stage IV adenocarcinoma of the lung was admitted to the hospital with several days of progressively worsening dyspnea on exertion. The chest CT showed a large left pleural effusion with enlarging bilateral hilar and mediastinal lymphadenopathy, compression of the superior vena cava and right main pulmonary artery consistent with progressive lung cancer (Figure 1). Therapeutic and diagnostic left sided thoracentesis was performed, removing approximately 450 ml of milky, pink fluid suggestive of hemochylothorax (Figure 2). Analysis of the fluid was significant for 27,720 red blood cells, 476 total nucleated cells with lymphocyte predominance (87%), glucose 158 mg/dl, cholesterol 63 mg/dl, and amylase 28 U/L. The pleural fluid was exudative (protein 4.4 g/dl) with a significantly elevated triglyceride level of 532 mg/dl. No malignant cells were identified in the fluid.

This case illustrates a nontraumatic chylothorax secondary to metastatic adenocarcinoma of the lung. The leading cause of non-traumatic chylothorax is malignancy by compression and/or lymphangitic invasion (1). Thoracic duct invasion or leak can only be seen with nuclear medicine scintigraphy; however, this test was not performed on this patient. The appearance of the pleural fluid in chylothorax can be deceiving as less than half of pleural fluid samples will be milky in appearance (2). In addition, milky appearing pleural fluid is not specific for a chylothorax, as milky fluid can be seen in a cholesterol pleural effusion (pseudochylothorax) or an empyema. The detection of chylomicrons on pleural fluid lipoprotein electrophoresis is the definitive diagnostic criterion for chylothorax, however it is not widely available and is costly (3). The classic diagnostic criterion is a pleural fluid triglyceride level of >110 mg/dl in an appropriate clinical setting of mediastinal malignancy, lymphoma, recent thoracic surgery or penetrating trauma to the neck or thorax (4). A pleural fluid triglyceride level between 50 and 110 mg/dl does not exclude the diagnosis of chylothorax and clinicians should perform lipoprotein electrophoresis of the pleural fluid to detect chylomicrons. To distinguish a chylothorax from a pseudochylothorax (both have milky appearance), clinicians should obtain a cholesterol level on the fluid. The cholesterol level in a chylothorax is usually less than 200 mg/dl while a pseudochylothorax will have high levels, typically greater than 200 mg/dl.

The patient chose to undergo palliative radiation of the chest and symptomatic treatment of his dyspnea.  

John Dicken MD¹, Madhav Chopra MD², Faraz Jaffer MD² and Linda Snyder MD²

¹Department of Internal Medicine and ²Division of Pulmonary, Allergy, Critical Care and Sleep

Banner University Medical Center-Tucson

Tucson, AZ USA

References

1. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med. 2010 Jan;104(1):1-8. [CrossRef] [PubMed]
2. Maldonado F, Hawkins FJ, Daniels CE, Doerr CH, Decker PA, Ryu JH. Pleural fluid characteristics of chylothorax. Mayo Clin Proc. 2009 Feb;84(2):129-33. [CrossRef] [PubMed]
3. Hooper C, Lee YC, Maskell N; BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug;65 Suppl 2:ii4-17. [CrossRef] [PubMed]
4. Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc. 1980 Nov;55(11):700-4. [PubMed]

Cite as: Dicken J, Chopra M, Jaffer F, Snyder L. Medical image of the week: Chylothorax. Southwest J Pulm Crit Care. 2018;17(2):70-1. doi: https://doi.org/10.13175/swjpcc100-18 PDF