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.