Tuberous Xanthomas in the Setting of Mild Dyslipidemia

RESIDENT RESOURCE CENTER Tuberous Xanthomas in the Setting of Mild Dyslipidemia

BY ALLYSON B. BRAHS, BS AND CYNTHIA LAZZARO, DO

A 41-year-old Asian male pre- >> sented with multiple, painless, yellowish-pink papules and nodules on the extensor surfaces of his elbows that were first noticed two years prior (Figure 1). Physical exam revealed smooth, dome-shaped, mobile lesions with firm-rubbery consistency at vari- ous stages of growth. The patient’s past medical history included hypertension, for which he took amlodipine and losartan-hydrochlorothiazide (HCTZ), initiated prior to the onset of the lesions. Family history was significant for cardiovascular disease with triple bypass in his father and a cerebrovas- cular attack in his grandfather. A punch biopsy showed the presence of many dermal foam cells, perivascular inflammation, fibrosis, and the occa- sional Touton giant cells and cholesterol clefts (Figure 2). Laboratory evaluation revealed borderline-high total choles- Fig. 1. Clustered tuberous xanthomas along bilateral elbows. Healing punch biopsy terol (227mg/dL), low-density lipopro- lesion on left elbow and two mosquito bites on the right. tein (LDL, 141mg/dL), very low-density lipoprotein (VLDL, 50mg/dL), high mone (TSH) were within normal limits. cholesterolemia, a well-known risk fac- triglycerides (250mg/dL), and mildly The clinical and histologic features tor for cardiovascular disease.1 Known depressed high-density lipoprotein were consistent with the diagnosis of causes of tuberous xanthomas include (HDL, 36mg/dL). Hemoglobin A1c was tuberous xanthoma. Fredrickson type IIa familial hyper- within the prediabetes range at 6.3 per- cholesterolemia (FH), type III familial cent; fasting glucose was 128mg/dL; and DISCUSSION dysbetalipoproteinemia, cerebrotendi- Alanine aminotransferase (ALT) was Tuberous xanthomas are localized nous xanthomatosis, ß-sitosterolemia, mildly elevated at 60IU/L. Otherwise, collections of lipids, especially in dermal and hyperlipidemia secondary to other the patient’s complete blood count histiocytes, and are typically distrib- disorders or medications.2 The familial (CBC), Comprehensive Metabolic Panel uted along extensor surfaces. They are hyperlipoproteinemias, FH and familial (CMP), and thyroid-stimulating hor- important signs of underlying hyper- dysbetalipoproteinemia, both produce a

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mulate, were unlikely because the patient lacked the neurologic symptoms and cataracts of cerebrotendinous xanthomatosis and lacked the arthralgia and childhood- onset of ß-sitosterolemia.2,5 Comorbidities, such as dia- betes mellitus, nephrotic syndrome, hypothyroidism, paraproteinemia, and biliary obstruction, or drugs like ß-adrenoreceptor blockers, thiazide diuretics, steroids, retinoic-acid derivatives, and ritonavir can produce hyper- lipidemic states that could lead to tuberous xanthoma formation2-3—though few studies have shown a direct correlation of these secondary causes of hyperlipidemia with tuberous xanthomas. With his elevated fasting glu- cose, elevated triglycerides, and reduced HDL, the patient fulfilled the criteria for metabolic syndrome,6 which has yet to be described as a potential etiology of tuberous xan- thomas. Additionally, he showed evidence of slight hepatic impairment and was taking HCTZ. Secondary factors such as these and polygenic vulnerability cannot be excluded as contributing factors to his dyslipidemia and resultant tuberous xanthomas. Fig. 2. Admixed lipid-laden histiocytes (foam cells), Touton giant According to the National Cholesterol Education cells (arrows), and dense irregular connective tissue. Program Expert Panel (NCEP) and Adult Treatment Panel III (ATP III) criteria that define lipid abnormalities, total cholesterol value well over 300mg/dL,1,3-4 which exceeds the patient’s cholesterol and LDL levels were classified as the total cholesterol level in the present case. borderline high.6 This case is unusual because tuberous Cerebrotendinous xanthomatosis and ß-sitosterolemia, xanthomas are predominantly associated with significant rare genetic defects that cause various sterols to accu- hypercholesterolemia;1 however, this patient shows that Dermatology Among Highest Paid Specialties

Dermatology ranks in the top 10 for specialties with the high- est average annual compensation, according to Doximity in its third annual Physician Compensation Report. However, data from the largest professional medical network show that after years of steady pay increases, national physician wages have plateaued for the first time since 2016. Dermatology ranks sixth among specialties with an average salary for $455,000. The study also shows that the gender pay gap is decreasing from prior years. Male physician pay has remained flat since 2017, while female physician pay has increased. Major variations in pay were found across metropolitan areas and within medical specialties. The report is based on the responses of nearly 90,000 licensed US doctors across six years, making it the largest repository of men and women, we see more movements to rectify this issue,” data available on physician compensation, Doximity says. says Christopher Whaley, PhD, in a statement. He is lead author “Compensation transparency is a powerful force. As more of the study and adjunct assistant professor at the University of data becomes available to us, exposing the pay gap between California, Berkeley School of Public Health.

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even mild dyslipidemia can be sufficient to manifest tuber- Match Day 2019 Sets Records ous xanthomas. The pathogenesis of this lesion resembles early atheroma formation.1-2 Therefore, since lipids can The 2019 Main Residency Match is the largest in National deposit in the dermis in such a mildly dyslipidemic state, it Resident Matching Program® (NRMP) history. A record 38,376 appli- is possible that a similar cholesterol deposition could con- cants submitted program choices for 35,185 positions, the most ever comitantly occur in the arteries. Further research regarding offered in the Match. additional factors that may be responsible for lipid depo- The number of Match registrants was the highest ever at sition in the setting of mild dyslipidemia can elucidate 44,603. The increase was due primarily to students/graduates of insight on atherogenesis. In conclusion, this case demon- U.S. osteopathic medical schools, whose numbers grew by 1,036 strates that tuberous xanthomas can form in mild dyslip- (17.1%) over 2018 to 7,090 this year. idemia in the absence of familiar etiologies. We also hope this serves as a reminder for physicians to have a keen eye for such lesions as timely recognition can prevent morbid- ity and mortality associated with cardiovascular disease. n

The authors have no conflicts of interest to disclose. Consent was acquired verbally from the patient.

Allyson B. Brahs, BS is a medical student at the College of Osteopathic Medicine of the Pacific, OMS III, Western University of Health Sciences in Pomona, CA. Cynthia Lazzaro, DO is a Clinical Assistant Professor of Dermatology, Western University of Health Sciences, Pomona, CA

1 Hata Y, Shigematsu H, Motoo T, et al. Serum lipid and lipoprotein profiles in patients with xanthomas: A correlative study on xanthoma and atherosclerosis (I). Jpn Circ J. 1981;45(11):1236-42. doi:10.1253/jcj.45.1236. 2 Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158(2):181-8. doi:10.5507/bp.2014.016. 3 Durrington P. Dyslipidaemia. Lancet. 2003;362(9385):717-31. doi:10.1016/s0140-6736(03)14234-1. 4 Burnside NJ, Alberta L, Robinson-Bostom L, Bostom A. Type III hyperlipoproteinemia with xanthomas and multiple myeloma. J Am Acad Dermatol. 2005;53(5 Suppl 1):S281-4. doi:10.1016/j.jaad.2005.04.009. 5 Alam M, Garzon MC, Salen G, Starc TJ. Tuberous xanthomas in sitosterolemia. Pediatr Dermatol. 2000;17(6):447-9. https://doi.org/10.1046/j.1525-1470.2000.01817.x 6 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97.

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