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Therapy Treatment

Systemic Therapy

Chemical peel

TCA is a form of destructive therapy, used topically at concentrations of 50%–100%. The approach is relatively simple. It is applied in a circular manner, carefully ensuring the greatest amount of TCA is smeared at the margin of the lesion. The treatment area is then neutralized with sodium bicarbonate.

Mourad et al.[19] reviewed the efficacy and tolerability of different concentrations of TCA in the treatment of patients with XP. TCA concentrations of 35%, 50%, and 70% were tested. The authors initially degreased the skin using cotton gauze soaked in acetone. Sensitive areas, for example, the inner canthus and nasolabial folds, were protected with petrolatum ointment. TCA was then applied using a cotton-tipped applicator until solid frosting without pink background was achieved. This was usually seen within 30s to 2min. The area was then neutralized and rinsed with cold water followed by the application of a thin coat of antibiotic ointment and sunscreen.[19]

TCA 70% was found to be the most effective concentration. It was well tolerated and associated with significant clinical efficacy. This concentration required the least number of sessions in the treatment of XP. Furthermore, it was noted that TCA 70% was particularly useful in treating papular lesions whereas TCA 50% was effective for macular xanthelasma. A study by Haque and Ramesh[20] mirrored these findings. They also concluded that TCA 70% was effective in treating flat plaques; however, TCA 100% was required for papulonodular lesions.[20]

Overall, TCA therapy for XP was found to be more effective for smaller lesions, with repeated procedures resulting in pigmentation and scarring.[21] In general, postinflammatory hyper- and hypopigmentation with TCA is reported at a frequency of 9%–12.5% and 21.5%–33.4%, respectively.[20],[22] Some studies reported that this was dependent on the TCA concentration, whereas others did not corroborate this association.[20],[22],[23] It is also important to note that if TCA is applied near the eyelid, there is a risk of scar formation and subsequent risk of ectropion development. Existing literature suggests recurrences ranging between 25% and 39%,[20],[21],[22] with Goel et al.[24] describing a recurrence rate of 34.5% at 6-month follow-up in their cohort.

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Probucol

There are reports of successful treatment using oral probucol in the literature. It is proposed that probucol, an antioxidant, acts by potentially inhibiting atherogenesis through limiting the oxidative modification of LDL cholesterol essential for foam-cell formation.[15] Miyagawa et al.[16] reported a case, of diffuse normolipemic plane xanthoma including XP, who was successfully treated with probucol. Harris et al.[17] showed 68% of xanthelasma regressed after probucol therapy.

Alirocumab

Alirocumab, a monoclonal antibody that belongs to a novel class of anticholesterol therapy through inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9), is primarily used in the treatment of hypercholesterolemia. Civeira et al.[18] reported rapid resolution of XP after treatment with alirocumab in a middle-aged man, with severely high levels of LDL cholesterol due to familiar hypercholesterolemia. The regression of the XP was associated with lowering of LDL cholesterol concentrations.[18]

Topical Therapy

Liquid nitrogen cryotherapy

Liquid nitrogen cryotherapy is a simple and effective treatment option. The risk of intense swelling due to the lax skin tissue in the eyelid is the reason this treatment is generally avoided in XP. However, Labandeira et al.[25] published a case series of XP treated with very short freeze time. They reported clearance of lesions in all cases with only minor swelling associated and no recurrences during a 10-year period.[25]

The proposed mechanism of action of cryotherapy is suggested to be associated with vasoconstriction and microthrombi formation caused by cryo-induced cell death. This leads to tissue ischemia and cell death. Potential adverse effects seen with cryotherapy include edema, vesicular formation, and blister formation depending on intensity of inflammatory response. These correlate with the length of freezing and thus the temperature that the tissue reaches.[25]

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Pingyangmycin

Wang et al.[26] described the treatment of XP with intralesional pingyangmycin, a broad-spectrum antitumor antibiotic. A total of 12 patients with 21 lesions received 2 treatment sessions, and in all patients except 1, the result was satisfactory. One patient experienced local recurrence 12 months after treatment. The authors described no severe associated complications.

Energy-based Devices

Radio-frequency ablation

Dincer et al.[27] evaluated the use of low-voltage radio-frequency (RF) ablation in the treatment of XP. Of the 15 patients who participated in the study, 9 achieved an improvement of greater than 75%. The authors concluded that this modality of treatment was effective in the treatment of XP, in particular lesions close to the eye and those that are multiple especially with indistinct borders.[27]

A comparative study by Reddy et al.[28] evaluated the efficacy of RF ablation versus TCA in the treatment of XP. Although both treatments resulted in similar improvement scores, RF ablation required fewer sessions to achieve more than 75% clearance of lesions. However, at 4 weeks posttreatment, 40% in the RF group and 15% in the TCA group had scarring, and 45% in the RF group and 30% in the TCA group had pigmentation.[28] Although fewer treatment sessions were required with RF ablation to achieve an excellent result, the treatment was associated with more complications comparatively.

Laser ablation

Laser ablation has been used to deliver targeted therapy in the treatment of XP. The mechanism of action is proposed to include (1) destruction of perivascular foam cells via thermal energy damage and (2) coagulation of dermal vessels leading to blockage of further lipid leakage into tissue, thus preventing recurrence. The use of a variety of lasers has been described in the literature, including carbon dioxide (CO2), argon, erbium (Er), and pulsed dye lasers. The CO2, neodymium-doped yttrium argon garnet (Nd:YAG), Er:YAG, and 1450-nm diode lasers all use longer wavelength of light absorbed best by cellular water, thus allowing their use in removal of epidermal lesions.[29] Argon and pulse dye lasers, on the other hand, use shorter wavelengths of light, preferentially absorbed by hemoglobin, and therefore are primarily used for vascular lesions.[29]

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Surgery

Traditionally, surgical excision has been used and often yields excellent cosmetic outcomes. Various surgical techniques have been advocated.

The classic blepharoplasty may be used to excise the xanthelasma in a serial staged approach, whereas Le Roux’s technique involves a modified blepharoplasty approach. Recurrence, however, is common and reported to be up to 40% and 60% following primary and secondary excision, respectively.

conducted a 4-year retrospective review of patients who received surgery for XP. Patients were classified into four grades according to the location and extent of the lesion. Ninety-five cases were reviewed, 70% of which were treated with simple excision in conjunction with blepharoplasty. The remaining 30% were treated with a combination of simple excision and local flaps or skin grafts. These were performed in patients with more advanced grades of the disease. There were no associated complications apart from postoperative scar contracture (4.2%) in patients graded III or IV. Recurrence was reported in 3.1% of patients at 12 months and this was found to be irrespective of the grade.[48] The incidence of recurrence, however, is increased with incomplete excisions and has been reported in the past to be up to 40% after primary surgical excision, 60% after secondary excision, and 80% with bilateral upper and lower eyelid involvement.The authors advocate that surgical excision should be the mainstay of treatment for XP lesions that involve the deep dermis or infiltrate the underlying muscle.

Other surgical techniques include a combination approach of surgery and chemical peeling. Zarem and Lorincz[50] recommend superficially excising the xanthelasma lesions using light electrodesiccation followed by the application of topical TCA.

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