Resolution of Refractory Chylous Effusions With Targeted MEK Inhibition in NRAS Q61R-Driven Kaposiform...

Kaposiform lymphangiomatosis (KLA) is a rare and aggressive lymphatic anomaly characterised by chylous effusions, respiratory failure and poor prognosis. Diagnosis is often challenging and delayed due to the mosaic distribution of causative somatic mutations.

A previously well four-year-old girl presented with pleural and pericardial effusions and methicillin-sensitive Staphylococcus aureus bacteraemia. She was treated with intravenous antibiotics, and chest and pericardial drains were inserted. Despite these measures, she developed high-volume, refractory chylous effusions. Management included dietary modification, as well as trials of octreotide and intravenous methylprednisolone, neither of which reduced chyle output. Magnetic resonance lymphangiography demonstrated diffuse abdominal and thoracic lymphatic abnormalities. She was subsequently treated with sirolimus, which was associated with reduced pleural and pericardial chylous drainage but ongoing clinical deterioration. Cell-free DNA analysis of pleural fluid identified a somatic NRAS variant (NM_002524.5 (NRAS):c.182A > G (p.Gln61Arg)). In the absence of histopathology, a presumed diagnosis of NRAS Q61R-driven KLA was made based on clinical, radiologic and molecular findings. She was started on trametinib, a MEK inhibitor. Over the subsequent 7 weeks, she was weaned from respiratory support and parenteral nutrition, transitioned to a fat-containing diet and experienced resolution of clinically significant effusions, allowing discharge home.

This case highlights the diagnostic challenges of complex lymphatic anomalies, demonstrates the utility of cell-free DNA analysis from effusions in identifying pathogenic somatic variants and underscores the therapeutic potential of targeted MEK inhibition in NRAS Q61R-driven KLA.