Approach to the Adult Patient with Chylomicronemia

Abstract Chylomicronemia, defined by fasting triglycerides ≥10 mmol/L (≥885 mg/dL) has diverse etiologies. When clinical features such as abdominal pain, lipemia retinalis, eruptive xanthomas, hepatosplenomegaly, pancreatitis or visibly lipemic plasma accompany the biochemical disturbance, the condition is called “chylomicronemia syndrome”. Subtypes include rare monogenic familial chylomicronemia syndrome (FCS), the more common multifactorial chylomicronemia syndrome (MCS), autoimmune chylomicronemia and lipodystrophy-associated chylomicronemia. Patients are at risk for acute pancreatitis and sometimes atherosclerotic cardiovascular disease (ASCVD). Accurate diagnosis includes medical history, physical exam, laboratory testing (including plasma apolipoprotein B and the ratio of triglyceride to total cholesterol), clinical scoring systems, as well as selective use of genetic testing when FCS is suspected. In adults the overwhelming majority of patients with chylomicronemia have MCS and not FCS. Treatment centers on dietary fat restriction, total alcohol avoidance, management of secondary factors, and traditional triglyceride-lowering therapies such as fibrates and omega-3 fatty acids. Acute pancreatitis management requires stabilization, analgesia, supportive care and preventive management of hypertriglyceridemia. Emerging RNA-based therapies targeting apolipoprotein C-III (e.g., volanesorsen, olezarsen and plozasiran) offer transformative potential for FCS and for some refractory patients with other chylomicronemia subtypes. A multidisciplinary approach—integrating clinical, biochemical, and genetic assessment—guides therapy and reduces pancreatitis risk.