Winning Abstracts from the 2014 Medical Student Abstract Competition: Infliximab Induced Severe Hypertriglyceridemia and Eruptive Xanthomas
First Author: Ella Anne Damiano, Brown Medical School, Class of 2015
Introduction: Infliximab is an anti-tumor necrosis factor-alpha (TNF-a) therapeutic agent for treatment of inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Hypertriglyceridemia has been reported twice after anti-TNF-a therapy in patients with psoriatic arthritis. Severe hypertriglyceridemia results in lipemic serum and is a clinical emergency due to risk of pancreatitis, stroke or myocardial infarction. In this case report, we present an additional and most severe case.
Case Report: A 26-year-old woman with Crohn's Disease presented to the emergency department with diffuse pearly papular rash of three weeks duration. Upon arriving at the emergency department, she endorsed painful skin lesions, but denied chest pain, changes in vision, muscle weakness, abdominal pain, or vomiting. She had restarted infliximab six weeks prior after a six-month hiatus from the medication due to a Crohn's flare that resulted in an ileocolic resection. She had previously received infliximab for one year without any adverse effect. Her other medication was cholestyramine powder, started post-surgically for diarrhea. She had no family history of dyslipidemia, rarely consumed alcohol, and denies changes in diet. On physical exam, she had central obesity with normal cardiopulmonary, abdominal, and neurologic examinations. The rash included dozens of 1-2mm pearly papular lesions on her bilateral arms, legs, neck, chest, and back.
Biopsy of her skin lesions confirmed eruptive xanthomas. Her non-fasting lipid panel revealed triglycerides 14802 mg/dL, total cholesterol 1538 mg/dL, and HDL less than 10mg/dL. Apolipoprotein B was 193 mg/dL (normal range 49-103) and apolipoprotein A1 188 mg/dL (normal 101-198). A urine HCG was negative. Serum lipase was 20 U/L.
She was treated with insulin and dextrose infusion along with gemfibrozil, fish oil, and pravastatin. Infliximab and cholestyramine were discontinued. She was discharged on hospital day fifteen with triglycerides of 102 mg/dl.
Discussion: Although a diagnosis of exclusion, it is likely that the severe hypertriglyceridemia was due to an adverse drug reaction to infliximab. There are two previous reports of hypertriglyceridemia following anti-TNF-a therapy in patients with psoriatic arthritis - one with triglycerides of 1129 mg/dL after infliximab and another with triglycerides of 689 mg/dL after adalimumab. It is postulated that blocking TNF-alpha could up-regulate production of other cytokines, which would act on the liver to increase synthesis of triglycerides. Increased liver production of VLDL or chylomicron-remnants is consistent with our patient's high total cholesterol, high apolipoprotein B, and low HDL.
This is the third and most severe report of severe hypertriglyceridemia in the setting of anti-TNF-a therapy. TNF-a has a complex regulatory role in lipid metabolism with an unknown mechanism for this adverse reaction. We recommend increased vigilance for dyslipidemia after administration of anti-TNF-a, especially in those with a personal or family history of hypertriglyceridemia.
Back to July 2014 Issue of IMpact