Burton, Michael MMSc; Sikes, Martha L. MS, RPh, PA-C; Schmidt, Heather L. MS, PA-C
Michael Burton practices at Family Medical Clinic in McDonough, Ga. Martha L. Sikes is an associate academic coordinator and clinical assistant professor in the PA program at Mercer University in Atlanta, Ga. Heather L. Schmidt is a clinical assistant professor in the PA program at Mercer University. The authors have disclosed no potential conflicts of interest, financial or otherwise.
Michael D. Overcash, MPAS, PA-C, department editor
A 30-year-old woman presented to her primary care clinic with extremely pruritic pinkish-colored nodules on all her extremities and lower buttocks. She said the nodules started appearing about a month ago and have increased in number. She has not tried any topical medications. She is a stay-at-home mother and has not noticed similar lesions on her family members. The family recently moved to the area from out of state. Her past medical history includes type 2 diabetes, hyperlipidemia, peripheral neuropathy, chronic low back pain, anxiety, and depression. She has not adhered to her medication regimen for the last month. Her family history is significant for hyperlipidemia in both parents and pancreatitis in her mother.
Examination of the skin revealed numerous 2- to 5-mm, firm, pinkish nodules with waxy, yellowish centers and surrounding erythema (Figure 1). The nodules were distributed on the patient's extensor proximal forearms, distal extensor upper arms, lower buttocks, and extensor and flexural surface of the bilateral thighs and lower legs. No lesions appear on her trunk, face, hands, or feet. A 3-mm punch biopsy was sent for pathology.
THE MOST LIKELY DIAGNOSIS IS:
* cutaneous nodular amyloidosis
* necrobiosis lipoidica
* eruptive xanthoma
The patient was diagnosed with eruptive xanthoma resulting from her uncontrolled diabetes and resultant hypertriglyceridemia.
The differential diagnosis of eruptive xanthoma includes folliculitis, cutaneous nodular amyloidosis, and necrobiosis lipoidica. Folliculitis presents with multiple or singular inflamed pustule-like lesions on any skin bearing hair, and the hair shaft can often be visualized in the lesion itself. Often these lesions are swollen and with erythema if the deeper portion of the follicle is involved.1
Cutaneous nodular amyloidosis, which results from amyloid proteins being deposited extracellularly in the patient's skin, presents with waxy nodules on the face, scalp, trunk, and extremities. The nodules vary in size, can be single or multiple, are well demarcated, and are flesh to salmon-colored or brown to gray-brown in appearance. Despite its similar presentation, age predilection lowers this diagnosis, as most patients are diagnosed between 50 and 60 years old.2
Necrobiosis lipoidica is a skin disorder strongly associated with diabetes, particularly with poor glycemic control, and is often considered to be a marker for the presence of diabetes.3 Typically necrobiosis lipoidica presents with multiple well-demarcated, shiny yellow-brown to orange plaques with atrophic centers on the anterior and lateral lower leg surfaces.3,4 This process affects more women than men, and often occurs in patients in their 30s.4
Other conditions that should be considered in this differential diagnosis are sarcoidosis, granuloma annulare, generalized eruptive histiocytoma, molluscum contagiosum infection, and neurofibroma.
Eruptive xanthoma occurs in about 0.1% of patients with diabetes and is due to the accumulation of triglyceride-rich chylomicrons in cutaneous histiocytes.5,6 Initial histologic findings typically reveal neutrophils, foam cells, and extracellular lipids.7 As the lesions resolve, they contain more cholesterol than triglycerides, as cholesterol is more easily mobilized from the skin into the bloodstream. Plasma triglyceride levels are generally in excess of 1,000 mg/dL.
Uncontrolled diabetes (type 1 or 2) perpetuates hypertriglyceridemia through various mechanisms. Insulin is an essential regulator of lipoprotein lipase, which hydrolyzes triglycerides and releases fatty acids into peripheral tissues.8 In patients with insulin resistance, lack of glucose uptake by the cells causes release of triglycerides from adipocytes as the body uses triglycerides as an energy source. Excess glucose, beyond normal use and storage, is then used to synthesize free fatty acids and triglycerides. The net result from lipoprotein lipase dysfunction, consistently elevated glucose levels, inadequate insulin secretion, and insulin resistance leads to decreased clearance and metabolism of triglyceride-rich chylomicrons.8
The patient was restarted on her previous medications, which included metformin, glimepiride, regular insulin, sertraline, and clonazepam. Her atorvastatin prescription was changed to fenofibrate and nicotinic acid. She immediately restarted her prescribed medications but did not have her lipid panel drawn due to lack of insurance coverage and money. She was able to have her lipid panel redrawn about 2 weeks after restarting her medications; at that time, her triglyceride level was 1,397 mg/dL; total cholesterol, 474 mg/dL; and high-density lipoprotein (HDL), 20 mg/dL.
TREATMENT AND MANAGEMENT
Untreated hypertriglyceridemia may result in potentially fatal acute pancreatitis, and may be the initial presenting finding in patients with diabetes.
A 12-hour fasting lipid panel is recommended for optimum assessment of triglycerides. Aggressive lifestyle modifications should be instituted for all patients. Dietary saturated fats should be less than 7% of total daily calories and physical activity, which reduces overall body fat and triglyceride levels, should be instituted.6 These measures alone have shown to improve the xanthomatous lesions. Glycemic control (with a goal of less than 150 mg/dL) will also reduce hypertriglyceridemia by reducing insulin resistance, improving lipoprotein lipase function, and decreasing conversion of glucose to free fatty acids and triglycerides. The antidiabetic drugs metformin and pioglitazone also have been shown to have triglyceride-lowering effects.6 Fenofibrates are known to decrease triglycerides by up to 50% and increase HDL levels up to 30%, making them the drug of choice for hypertriglyceridemia.6 Fenofibrate drug monitoring should include watching for symptoms of cholelithiasis and myopathy, and periodically assessing hepatic function. Fish oil and nicotinic acid also decrease triglyceride levels, and may be used in combination with fenofibrates.6
At 2 weeks, the patient returned to discuss her lab results. Because she did not have health insurance, she declined further lab studies to evaluate the extent of her diabetes and concomitant metabolic syndrome. The patient was extensively counseled about the importance of following lifestyle modifications, medication compliance, and warning signs and symptoms of pancreatitis. The patient moved back to her previous residence in a different state and an attempt to follow up via phone 2 months later was unsuccessful.
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5. Van Hattem S, Bootsma AH, Thio HB. Skin manifestations of diabetes. Cleve Clin J Med
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6. Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med
7. Parker F, Bagdade JD, Odland GF, Bierman EL. Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscope study. J Clin Invest
8. Kalus AA, Chien AJ, Olerud JE. Diabetes mellitus and other endocrine diseases. In: Goldsmith LA, Katz SI, Gilchrest BA, et al., eds. Fitzpatrick's Dermatology in General Medicine
. 8th ed. McGraw-Hill Cos., Inc.; 2012.
© 2014 American Academy of Physician Assistants.