3.2.2 Management Considerations
Respiratory issues secondary to pleural effusion represent a frequent presentation of individuals with GLA. Although the exact incidence is unclear, pleural effusions in GLA appear to be common with an approximate prevalence of 40-70% [5, 22]. Historically, thoracic involvement in GLA portended significant morbidity and poor prognosis, particularly in children [23]. One retrospective study of 69 children with CLA (35 GLA, 9 KLA, and 41 GSD) reported an overall mortality rate of 20% in patients with thoracic disease [5]. Of those 35 patients with GLA, 25 (71%) had thoracic lesions and 10 died (28%) over a 7-year period. As in the case of our patient, pleural and/or pericardial effusions are known to develop or worsen with illness, including common viral infections. Individuals with GLA are also at risk for worsening effusions during times of growth and hormonal surges, such as puberty and pregnancy.
Until recently, medical treatments were limited to therapies such as steroids, interferon, and chemotherapeutic agents which produced variable outcomes. The discovery of the beneficial effects of mTOR inhibition in LM has led to the use of sirolimus to control and improve disease complications in patients with GLA. In a retrospective study of 18 patients with complex lymphatic anomalies (13 GLA, 5 GSD) treated with sirolimus, 5 of 6 (83%) patients with GLA had improvement or complete resolution of their pleural effusions. Two of 3 (67%) GLA patients had complete resolution of their pericardial effusions. No GLA patients had worsening of pericardial or pleural effusions while on sirolimus treatment. Additionally, most patients with effusions also experienced improvement in one or more associated complications such as respiratory symptoms, functional impairment, and quality-of-life. Importantly, no deaths occurred over the 7.5-year study period [22]. Recent discovery of somatic PIK3CA genetic mutations in GLA also suggests a therapeutic role for PIK3CA inhibitors [6].
In our patient’s case, chest tube placement and pleural fluid drainage was indicated because of cardiorespiratory compromise. If the patient is asymptomatic or has tolerable mild symptoms, drainage is not necessary, even when the effusion is large. From our clinical experience, sirolimus also helps decrease the amount of pleural fluid output while the chest tube is in place and decreases risk of fluid re-accumulation when the drain is removed.