Unmasking of severe hypertriglyceridaemia associated with antipsychotic therapy by atypical eruptive xanthomas

A 43-year-old male with a 2-year history of schizotypal and delusional disorders and known obesity with a body mass index (BMI) of 35 kg/m2, presented with non-pruritic, painless skin lesions. Over the course of 18 months, following commencement of an antipsychotic therapy with quetiapine and risperidone, there was a progression from single papules on the patient’s arms and legs to sudden eruption of multiple lesions scattered over the back and both sides of the arms and legs (Figure 1 A). These had been present for a number of weeks. Detailed dermatological examination revealed large, pink and polymorphous tuberous papules with a yellowish centre consistent with eruptive xanthomas (Figure 2 A). A histopathology test of the skin lesion (Figures 2 B, C) showed extensive accumulation of lipid laden histiocytes confirming the diagnosis. The patient was otherwise asymptomatic. Serum biochemistry demonstrated hypercholesterolaemia (total cholesterol (TC) of 11.25 mmol/l), severe hypertriglyceridaemia (fasting triglycerides (TG) of 35.3 mmol/l) and long-standing hyperglycaemia (fasting glucose of 19.7 mmol/l, HbA1c of 10.9%) that led to the diagnosis of a new onset of diabetes mellitus. Of note, his plasma LDL-cholesterol (0.78 mmol/l) and HDL-cholesterol (0.26 mmol/l) levels were extremely low. Other laboratory tests including hepatic, renal, pancreatic and thyroid functions were normal. Abdominal ultrasound revealed significant liver steatosis. An algorithm [1, 2] based on plasma TG, TC and apolipoprotein (Apo) B (71 g/l) excluded familial dysbetalipoproteinaemia (FD) with TC/Apo B ratio < 6.2, TG/ApoB ratio > 10.0 and ApoB/TC ratio > 0.15. The patient’s family history was positive for lipid disorders associated with type 2 diabetes in his father. A therapy with insulin, metformin and fenofibrate drugs was initiated and the patient was counselled on lifestyle changes including weight loss and a low-fat diet. A consulting psychiatrist decided not to discontinue the antipsychotic treatment. At 3 months’ follow-up, the lesions had resolved with reddish discoloration at the primary sites (Figure 1 B). A significant improvement in lipid and glucose metabolism was observed (TC of 4.6 mmol/l, TG of 10.1 mmol/l, glucose of 6.1 mmol/l), however in order to achieve the treatment goals [2], the therapy with quetiapine and risperidone was finally discontinued.
Xanthomas evolve as clusters of foam cells in the connective tissue of the skin, tendons and fasciae....


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