Response to: Severe hypertriglyceridemia, acute pancreatitis and chyloptysis

To the Editor, We read with great interest Dr Sahu’s account of a patient with acute pancreatitis who they attributed to use of a tumor necrosis factor (TNF) alpha inhibitor in ‘Adalimumab Related Hypertriglyceridemia and Acute Pancreatitis’. With increasing utilization of TNF alpha inhibitors for various autoimmune diseases, there has been a concurrent rise in the incidence of uncommon adverse events from these medications such as the one described by Sahu et al.1–4 TNF serum levels are elevated during acute pancreatitis and have been implicated in the pathogenesis of acute pancreatitis in animal models.5 Theoretically, TNF antagonists such as adalimumab, etanercept and infliximab would have pancreatic-protective effects. However, there is controversy about this theory as there have been reports of these agents being pancreas-protective6,7 versus these agents being an inciting agent for pancreatitis as mentioned in the references of Sahu et al. report. There are various mechanisms of drug-induced pancreatitis such as direct toxic injury, indirect injury by hypertriglyceridemia and idiosyncratic reactions. At this time, there is a paucity of knowledge about the actual mechanism of adalimumab-induced hypertriglyceridemia and pancreatitis. Theoretically, these agents may induce lipogenesis by cytokine production and cause severe hypertriglyceridemia that in turn causes acute pancreatitis. In our case report, no causal agent could be identified for isolated severe hypertriglyceridemia causing acute pancreatitis and chyloptysis.8 Hereditary causes could also potentially explain the isolated events of severe hypertriglyceridemia in which loss-of-function mutations in genes such as LPL, APOC2, APOA5, LMF-1 and GPIHBP cause severe hypertriglyceridemia when exposed to inciting agents such as alcohol, obesity, drugs and infections.9 Screening for these gene mutations might be of value in patients who present with isolated events of severe hypertriglyceridemia and its complications such as pancreatitis and chyloptysis. In the case presented by Sahu et al., we are interested to know how the authors concluded that adalimumab causing hypertriglyceridemia leading to pancreatitis rather than alcohol use as reported by them in another report. Conflict of interest: None declared.