Discussion

Chylothorax is a rare type of pleural effusion in the paediatric population, wherein the lymphatic fluid is found in the pleural space. Chylothorax can be caused by several broad categories, including congenital chylothorax associated with lymphatic malformations or syndromes, traumatic chylothorax following invasive procedure or other trauma, chylothorax related to elevated central venous pressure, chylothorax associated with tumours, or other miscellaneous causes. ^{Reference Dubin, King and Gallagher12–Reference Van Aerde, Campbell, Smyth, Lloyd and Bryan14} Chylothorax is associated with many syndromes, including Down syndrome, Noonan syndrome, and Turner syndrome. ^{Reference C.H.A.N. and Ho5–Reference Fisher, Weiss, Michals, DuBrow, Hastrieter and Matalon8,Reference Yamamoto, Koeda and Tamura15} In Noonan syndrome, chylothorax may present as a congenital or spontaneous event and is also commonly seen in patients with Noonan syndrome after cardiothoracic surgical intervention. ^{Reference C.H.A.N. and Ho5–Reference Fisher, Weiss, Michals, DuBrow, Hastrieter and Matalon8} In one study of paediatric cardiac surgery admissions, patients with Noonan syndrome were 90% more likely to have postoperative chylothorax. ^{Reference Kriz, Flores, Villarreal, Bronicki and Loomba16} It is also interesting that our patient only had right-sided effusion, which may suggest a regional lymphatic abnormality or lymphatic system leak that occurred in the setting of SARS-CoV-2 infection. Recent literature using magnetic resonance lymphangiography has shown that the side of abnormal pleural perfusion does not always correlate with the side of chylothorax, which highlights the complex pathophysiology of lymphatic anatomy and physiology in patients with Noonan syndrome. ^{Reference Pieper, Wagenpfeil and Henkel17}

Chylothorax is identified by testing pleural fluid for triglycerides, like our case study. While not available for our patient, dynamic contrast magnetic resonance lymphangiography has been shown to be useful for patients with Noonan syndrome or chylous effusions to further assess the lymphatic system. ^{Reference Pieper, Wagenpfeil and Henkel17–Reference Nakano, Rankin and Annam19} Assessment of abnormal pulmonary lymphatic perfusion via magnetic resonance lymphangiography allows the detection of pulmonary lymphangiectasia, which may be present in patient with chylothorax, although there have been patients with a chylothorax with normal underlying pleural lymphatic perfusion. ^{Reference Pieper, Wagenpfeil and Henkel17} Once identified, chylothorax can be treated with a low-fat diet, diuresis, and, if respiratory status dictates, fluid drainage. ^{Reference Agrawal, Chaddha, Kaul, Desai, Gillaspie and Maldonado4} Octreotide use is also practised at paediatric centres, ^{Reference Agrawal, Chaddha, Kaul, Desai, Gillaspie and Maldonado4} although it was not used for our patient. In some circumstances of persistent chylothorax, lymphatic interventions may be indicated. In other cases, like Noonan syndrome, refractory chylothorax may be approached with a more targeted therapy like mitogen-activated protein kinase inhibition with trametinib. ^{Reference Dori, Smith and Pinto18–Reference Gordon, Moore and Van Zanten20} Notably, due to the underlying complex lymphatic dysplasia and chylothorax pathophysiology among patients with Noonan syndrome, treatments such as lymphatic drainage, low-fat diet, and diuretics can be particularly ineffective, which is precisely why mitogen-activated protein kinase inhibition has been trialled in this patient population. ^{Reference Nakano, Rankin and Annam19,Reference Gordon, Moore and Van Zanten20}

SARS-CoV-2 is a novel coronavirus that has caused a broad clinical spectrum from asymptomatic to critical illness with acute respiratory distress syndrome and even death. SARS-CoV-2 infections are rarely associated with chylothorax. ^{Reference Satriano, Scioscia and Cagnazzo1,Reference Bezirganoglu and Okur2} In one case report, a young infant with spontaneous chylothorax was subsequently diagnosed with acute SARS-CoV-2 infection and died at 2 months of age due to pulmonary hypertensive crisis and respiratory failure. ^{Reference Bezirganoglu and Okur2} In another published case, a 78-year-old man diagnosed with acute SARVS-CoV-2 infection was found to have right pleural effusions later diagnosed as chylous. ^{Reference Satriano, Scioscia and Cagnazzo1} He had developed partial thrombosis in the superior vena cava, and the distal right subclavian vein was thought to be the underlying cause of his chylothorax with resultant poor lymphatic drainage. ^{Reference Satriano, Scioscia and Cagnazzo1}

To our knowledge, this is the first reported case of a patient with Noonan syndrome having chylothorax related to acute infection with SARS-CoV-2. It is also important to note that our patient had normal estimated right atrial pressure based on an echocardiogram. While patients with Noonan syndrome can have chylothorax congenitally or spontaneously related to acute infectious processes or cardiothoracic surgery, it has not been associated previously with this specific infectious disease. Also curious in this case is that this patient has had cardiothoracic surgeries without prior history of chylothorax. There is no clear history of thrombus impairing lymphatic drainage, but the lymphatic malformations associated with Noonan syndrome coupled with systemic inflammation and cytokine storm shown to be underlying SARS-CoV-2 may have been enough to lead to chylothorax. This case demonstrates that while patients with Noonan syndrome are known to have a higher risk of chylothorax, the exact reason why a patient with Noonan syndrome will have a chylothorax in response to one process and not others is still not predictable.