A 33-year-old man with a medical history of obesity (body mass index 31 kg/m2), uncontrolled type 2 diabetes mellitus, severe hypertriglyceridemia, and hypercholesterolemia was hospitalized due to acute abdominal pain secondary to recurrent acute hypertriglyceridemia-induced pancreatitis. In the previous year, he had been admitted to the hospital multiple times due to acute hypertriglyceridemia-induced pancreatitis. Because he had a suboptimal response to insulin therapy during his second hospital admission earlier in the year, the patient required initiation of plasma exchange, which was also required during each of his subsequent admissions.
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Nine years earlier, the patient was diagnosed with hypertriglyceridemia, hypercholesterolemia, and type 2 diabetes mellitus with a fasting serum triglyceride level of 9,000 mg/dL, hemoglobin A1c 10.8%, and total cholesterol 550 mg/dL. Initial management included fenofibrate 48 mg daily, niacin, fish oil supplements, metformin 1,000 mg twice daily, and insulin glargine and lispro combination. The patient reported intolerance to statin therapy (myalgias and fatigue) after a short trial. His course was complicated by dietary and medical nonadherence. Six years after being diagnosed with type 2 diabetes, he required treatment for osteomyelitis of the right great toe but did not complete recommended routine diabetes screenings.
At the time he was initially diagnosed with metabolic syndrome, the patient reported development of diffuse keloid-like xanthomas. On current presentation, he reported marked progression of the skin lesions over the previous 9 years. On current physical examination, he was found to have clusters of pronounced raised, pink, tendinous xanthomas with scattered yellow cholesterol deposits surrounded by keloid hypertrophic scars involving the face, the lower and upper extremities (Figure 1), and a majority of the trunk (Figure 2). Based on their distinct appearance and clinical presentation, the skin lesions were believed to be secondary to profound lipid derangement, due in part to chylomicronemia syndrome, augmented by uncontrolled diabetes and dietary noncompliance. The prominent fibroproliferative (keloid) scarring was believed to be induced by severe eruptive xanthoma and the inflammatory effect of clustered xanthomas.
(A) Clusters of keloid-like eruptive xanthomas and cholesterol deposits throughout the dorsum of the right hand and wrist. (B) Profound constellation of eruptive xanthomas involving a majority of the posterior right elbow with extension into the distal upper arm. (C) An organized collection of raised eruptive xanthomas involving the posterior left arm with multiple foci of cholesterol deposits scattered throughout.
Scattered xanthomatous cholesterol deposits involving a majority of the posterior trunk.
Chylomicronemia syndrome was considered based on the patient’s clinical presentation; however, the patient denied a family history of hypertriglyceridemia and declined genetic testing. Medication review and additional laboratory testing (comprehensive metabolic panel, thyroid-stimulating hormone, urinalysis, vitamin B12, serum toxicology screen, human immunodeficiency virus testing) were unremarkable.
Over the course of the next year, the patient’s lipid profile improved with escalation of medical therapies, including rosuvastatin 10 mg nightly (a repeat trial of statin therapy without recurrent side effects), fenofibrate 145 mg daily, icosapent ethyl 2 g twice daily, and a multimodal diabetes regimen. His adherence to the diabetes regimen improved but remained intermittent. The xanthomatous skin findings remained unchanged. Plasma exchange therapy resulted in resolution of acute pancreatitis and reduced his fasting triglyceride level to 540 mg/dL.
LINKED TO LIPID DISORDERS
Xanthomas, localized fatty deposits in the skin, can vary immensely in clinical presentation, ranging from subtle reddish-yellow papules over extensor surfaces to more severe tendinous xanthomas with a keloid-type appearance, as seen in our patient. Cutaneous xanthomas are commonly associated with lipid derangements, including severe hypertriglyceridemia, hyperlipidemia, and poorly controlled type 2 diabetes, with varying reported prevalence.1
The differential diagnosis includes both Langerhans histiocytosis and non-Langerhans histiocytosis, disseminated granuloma annulare, and generalized eruptive histiocytoma. In patients without profound lipid abnormalities, targeted biopsy is often required to establish a diagnosis.2
Treatment of xanthomatous skin findings involves aggressive correction of underlying triglyceride derangements with medical therapies, low-fat diet, alcohol avoidance, and improved glycemic control. Apolipoprotein C-III and angiopoietin-like 3 inhibitors are emerging therapies with early success, and should be considered in patients with severe hypertriglyceridemia that does not respond to medical therapy.3,4 Local xanthoma-directed therapies such as laser removal and surgical resection can be considered for cosmetic or symptomatic purposes, but are limited in patients with multiple skin lesions.5
Early detection of lipid disorders and initiation of appropriate therapies can decrease risk of premature cardiovascular disease and multiple downstream complications of metabolic syndrome. In patients who decline genetic testing and have clinical features of familial chylomicronemia syndrome, the use of well-validated scoring calculators to quantify the likelihood of familial chylomicronemia syndrome is recommended.6
Patients with hypertriglyceridemia-induced pancreatitis are often younger than patients with pancreatitis due to other causes but have higher risk of morbidity and mortality, emphasizing the importance of early recognition and intervention.7 When evaluating a patient with cutaneous xanthoma of any degree, it is crucial to obtain appropriate screening lipid profiles and treat metabolic derangements aggressively to avoid life-threatening complications.
DISCLOSURES
The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
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