What Are These Yellow-Orange Plaques on the Face?

An 82-year-old otherwise healthy woman presented to our dermatology clinic with skin discolorations on her face for the past 1 year. She had no relevant past personal medical or family history. Physical examination showed poorly-demarcated yellow-orange plaques present bilaterally over the zygomatic and periorbital regions in an almost symmetric distribution (Figures 1A and B). Plaques covered an area of 3 × 5 cm on the left side and 1.5 × 6 cm on the right side, and were soft in consistency. 

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First described by Altman and Winkelmann in 1962, plane xanthomas are a rare and noninherited form of lipid deposition disease.¹ They can occur at any location, but are most commonly seen around the eyes, neck, trunk, flexural folds, and palmar creases. Other types of xanthomas include eruptive, tendinous, tuberous, and verruciform (Table 1).^2-10 Xanthomas may present as yellow-orange papules, plaques, or nodules (Figures 1A and B).  

Epidemiology

Epidemiologic data on xanthomas is limited. Xanthelasma is the most common variant, with an estimated prevalence of up to 4% in the general population. Other subtypes are seen less frequently.¹¹ 

Tendinous, tuberous, and plane xanthomas are often associated with the presence of underlying dyslipidemic or abnormal hematologic states.¹²

With the exception of those associated with familial hypercholesterolemia, xanthomas most commonly present in adulthood after the age of 50. Xanthomas arise with equal frequency in both sexes, showing no clear gender predilection.¹¹

Clinical Presentation

Plane xanthomas characteristically present as soft, yellow-orange plaques most commonly seen around the eyes (xanthelasma), neck, trunk, flexural folds, and palmar creases (xanthoma striatum palmaris). The various subtypes of plane xanthomas are discussed in Table 2.^2,13,14

The most common form of plane xanthomas is xanthelasma. Patients typically complain of asymptomatic plaques in the periorbital region. Xanthoma striatum palmaris, another subtype, may arise as orange-colored macules on the palmar creases. Certain subtypes such as diffuse plane xanthoma may present as symmetric eruptions of plane xanthomas on the face and upper trunk. In such cases underlying hematologic disorders must be ruled out. Diffuse plane xanthomas are frequently associated with monoclonal gammopathies, multiple myeloma, chronic myelomonocytic leukemia, myelodysplasia, and lymphoproliferative disorders (eg, Castleman disease).¹⁴ 

Pathogenesis

Information concerning the pathogenesis of plane xanthomas is unclear. One theory suggests a dysfunction between IgG and low-density lipoprotein (LDL) resulting in the formation of complexes. These complexes allow macrophages to phagocytose LDL particles with greater affinity, a process known as opsonization. As the macrophages consume and oxidize LDL particles, they transform into foam cells that are then deposited in the dermis.¹⁵

Histology

The characteristic histologic feature present in all xanthomas is the presence of lipid-laden macrophages (foam cells). When prepared with special stains, oil red O, the lipid present in these cells will stain red. Histologic features from the site of biopsy are also seen—for instance xanthelasma specimens may demonstrate the presence of vellus hair, thin striated skeletal muscle, and a thin epidermal layer.¹⁶ 

Plane xanthomas specimens may show an abundance of foam cells deposited in the papillary dermis with minimal inflammatory cell infiltrate (Table 1).² 

Differential Diagnosis

Xanthomas can oftentimes be mistaken for a variety of other skin lesions. Diagnosis should be made using history, physical findings, and biopsy results. Table 3 lists essential differentials that should be considered.^17-21

Treatment

Treatment of plane xanthomas is generally preferred solely for cosmetic reasons. Minor plane xanthomas, such as xanthelasma, can be treated with focal destruction or surgical excision. Surgical excision has traditionally been used with high patient satisfaction, and good cosmetic outcome.²² More recent interventions include focal ablation with 70% trichloroacetic acid chemical peels, cryotherapy, or erbium-doped: yttrium-aluminum-garnet (Er:YAG) lasers.^23-25 Recurrences, however, cannot be prevented. 

Ablative interventions are impractical for patients with widespread skin involvement, as in diffuse plane xanthomas. Although case reports have documented successful outcomes using probucol and Er:YAG laser, the best approach to treating these lesions is uncertain. Probucol is believed to prevent atherogenesis through its antioxidant properties.^26,27

When associated with hematological disease, diffuse plane xanthomas may persist despite treatment. Management of the underlying hematologic disease is necessary and lesions tend to improve with remission.¹⁵

Our Patient

Our patient’s initial presentation was typical of plane xanthomas. Potential occult gammopathies and paraproteinemias needed to be excluded. The patient agreed to undergo workup that included complete blood count, complete metabolic panel, serum protein electrophoresis, and lipid profile. Biopsy was not necessary due to the typical presentation, and follow up in our clinic was scheduled in 1 month. Following investigation, no underlying gammopathies or paraproteinemias were found. Lipid profile revealed a slight elevation in blood cholesterol (221 mg/dL). Discussion and counseling regarding possible treatment options was done. The patient chose to forgo any treatment, and was then scheduled for a 1-year follow-up.

Conclusion

Plane xanthomas characteristically present as yellow-orange papules or plaques on the skin. Diagnosis should be suspected based on history and physical examination findings, and confirmed with biopsy. Although seemingly benign, extensive workup should be done to exclude the presence of underlying dyslipidemic or abnormal hematologic states. The mainstay of treatment in patients without hematologic disease includes surgical excision or focal ablation of the lesion. 

Dr Khan is with Premier Dermatology, PC Dermatology Service in Ashburn, VA.

Dr Usman is with Premier Dermatology, PC Dermatology Service, in Ashburn, VA.

Dr Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at Veteran Affairs Medical Center, and the department of dermatology at the State University of New York Downstate, both in Brooklyn, NY.

Disclosure: The authors report no relevant financial relationships. 

References

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2. Patterson J. Cutaneous non-lymphoid infiltrates. In: Weedon D. Weedon’s Skin Pathology. 4th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2016:1129-1170.

3. Solak B, Kara RO, Acikgoz SB, Kosem M. First and only symptom of undiagnosed diabetes mellitus: eruptive xanthoma [published online September 24, 2015]. BMJ Case Rep. doi:10.1136/bcr-2015-212160

4. Bounouar M, Mernissi F. Eruptive xanthomas announcing severe acute pancreatitis. Pan Afr Med J. 2014:17:225. doi:10.11604/pamj.2014.17.225.2521

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6. Xu XL, Huang LM, Wang Q, Sun JF. Multiple verruciform xanthomas in the setting of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome. Pediatr Dermatol. 2015;32(1):135-137.

7. Curto-Barredo L, Segura S, Barranco C, et al. Verruciform xanthoma developing in recessive dystrophic epidermolysis bullosa: A sheep in wolf’s clothing. Am J Dermatopathol. 2014;36(6):506-509.

8. Romaní J, Luelmo J, Sáez A, et al. Localized xanthomas associated with primary lymphedema. Pediatr Dermatol. 2012;29(1):113-114.

9. Polonowita AD, Firth NA, Rich AM. Verruciform xanthoma and concomitant lichen planus of the oral mucosa. A report of three cases. Int J Oral Maxillofac Surg. 1999;28(1):62-66.

10. Harris L, Staines K, Pring M. Oral verruciform xanthoma [published online March 27, 2015]. BMJ Case Rep. doi:10.1136/bcr-2014-209216.

11. Deprez M, Uffer S. Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature. Am J Dermatopathol. 2009;31(3):256-262. 

12. Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol. 1988;19(1 Pt 1):95-111.

13. Schaefer E, Santos R. Xanthomatoses and lipoprotein disorder. In: Fitzpatrick T, Wolff K, Goldsmith L, Gilchrest B, Paller A, Leffell D, eds. Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill; 2012:1600-1613.

14. Lynch MC, Wood L, Anderson BE, Clarke LE. JAAD Grand Rounds. Asymptomatic dermal plaques. J Am Acad Dermatol. 2015;72(5):922-924.

15. Szalat R, Arnulf B, Karlin L, et al. Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy. Blood. 2011;118(14):3777-3784.

16. Burgdorf W, Zelger B. The histiocytoses. In: Elder D. Lever’s Histopathology of the Skin. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:667-688.

17. Sato T, Tanaka M. Linear sebaceous hyperplasia on the chest. Dermatol Pract Concept. 2014;4(1):93-95.