|Ahead of print publication
Efficacy of ultrapulse carbon dioxide laser ablation versus 30% trichloroacetic acid in xanthelasma palpebrarum - A randomised controlled trial
Niyor Mukuta Das1, Radhakrishnan Subramaniyan2, Sandeep Arora3, Rajeshwari Dabas4, Manasa Shettisara Janney5, Sandeep V Lal6
1 Department of Dermatology, Base Hospital, Tezpur, Assam, India
2 Professor Dermatology & Brig IC Adm, CHCC, Lucknow, Uttar Pradesh, India
3 Department of Dermatology, Army College of Medical Sciences & Base Hospital Delhi Cantt, India
4 Department of Dermatology, Command Hospital Air Force, Bangalore, Karnataka, India
5 Department of Dermatology, Military Hospital, Dimapur, Nagaland, India
6 Department of Dermatology, Victoria (Women and Child) Hospital, Kollam, Kerala, India
|Date of Submission||24-Jun-2020|
|Date of Decision||16-Aug-2020|
|Date of Acceptance||21-Oct-2020|
|Date of Web Publication||01-Apr-2021|
Department of Dermatology, Command Hospital Air Force, Bangalore, Old Airport Road, Bengaluru - 560 007, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Xanthelasma palpebrarum (XP) is the most common cutaneous xanthoma that develops around the eyes. A number of treatment modalities have been tried for its removal, but none are truly satisfactory. Trichloroacetic acid (TCA) is commonly used in Indian setting as it is easily available and cost-effective whereas carbon dioxide (CO2) laser has been tried increasingly due to its favorable cosmetic outcome. Aims: This study aims to compare the efficacy of ultrapulse CO2 laser ablation with 30% TCA in the treatment of XP. Setting and Design: Prospective, interventional, randomized study at a Dermatology Centre of a Tertiary Level Hospital from January 2017 to June 2018. Methods: Seventy-four patients with 100 lesions of XP were divided into two groups of flat and elevated lesions. Each group was further randomly divided into two subgroups and administered CO2 laser once a month and 30% TCA once in 2 weeks respectively for 3 months. Patients were clinically assessed at baseline and then at monthly intervals using visual analog scale (VAS), patient satisfaction score (PSS), and standardized photographs. The follow-up was done at the end of 3 and 6 months. Statistical Analysis and Results: Mean PSS and VAS score of TCA and laser in flat and elevated lesions were compared using independent group Student's t-test. Response to laser in elevated lesions was found to be statistically better whereas in flat lesions the response to TCA and laser were similar. Recurrence was 17% and 6% at 3 months' follow-up and 24% and 11% at 6 months' follow-up in TCA and laser groups, respectively. Conclusions: The end results of ultrapulse CO2 laser and 30% TCA are comparable in flat lesions of XP. In elevated lesions, laser has better efficacy, requires fewer sittings with lesser chance of recurrence.
Keywords: Trichloroacetic acid, ultrapulse carbon dioxide laser, xanthelasma
|How to cite this URL:|
Das NM, Subramaniyan R, Arora S, Dabas R, Janney MS, Lal SV. Efficacy of ultrapulse carbon dioxide laser ablation versus 30% trichloroacetic acid in xanthelasma palpebrarum - A randomised controlled trial. J Mar Med Soc [Epub ahead of print] [cited 2021 Apr 23]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=312894
| Introduction|| |
Xanthelasma palpebrarum (XP) is a cosmetically disfiguring dermatosis frequently encountered in clinical practice. It is characterized by localized accumulation of histiocytes (xanthoma cells or foam cells) with intravacuolar deposits of esterified cholesterol in superficial reticular dermis in perivascular and periadnexal regions. XP can be associated with familial hypercholesterolemia and dyslipoproteinemia (Types IIa, IIb and III) and hence screening is recommended. Immunohistochemistry studies have demonstrated increased expression of inflammatory markers such as cyclooxygenase-1, nitric oxide synthase and myeloperoxidase in xanthelasma lesions akin to early stages of atherosclerotic plaque formation. They present as soft, velvety yellowish papules, plaques or nodules commonly on the medial aspect of upper and lower eyelids. Patients seek treatment as the lesions of XP are readily visible and esthetically unappealing.
Several accepted treatment modalities such as chemical peels, cryotherapy, radiofrequency ablation, electrofulgration, laser ablation, plasma sublimation, surgical excision, and lipid lowering drugs,, have showed varied results and recurrences as none of the above modalities address the inflammatory component of XP. Treatment modality is carefully chosen based on the lesional characteristics (number/size/thickness/proximity to lid margin), co-morbidities (hyperlipidemia), patient affordability, compliance to treatment and skill of treating dermatologist.
In this study, we intended to compare the efficacy of ultrapulse carbon dioxide (CO2) laser ablation and 30% trichloroacetic acid (TCA) in XP, both of which are recognized modalities but are two extremes in terms of affordability and expertise.
| Methods|| |
This was a prospective, single center, interventional, parallel group, randomized study conducted in patients of XP aged more than 18 years at a tertiary care center from January 2017 to June 2018. They were included in the study after taking written informed consent. Patients on lipid lowering drugs, history of treatment in the past 6 months, keloidal tendencies, pregnant and lactating women, and those who were unwilling were excluded. All patients in this study underwent a detailed clinical history, general physical, systemic and dermatological examinations and, a set of biochemical investigations including blood sugar, thyroid and lipid profile. The XP lesions were divided into flat and elevated groups, patients with mixed lesions were part of both the groups. Lesions in each group were further block randomized every week by odd-even number system and treated with either ultrapulse CO2 laser or 30% TCA.
In the laser group, after administering local anesthesia (injection 2% lignocaine) ultrapulse CO2 laser (Indus International, Israel) with pulse duration of 200 microseconds, frequency of 200 Hz, and 0.2 mm spot size was used to vaporize the lesions using power of 10 watts delivered through a hand piece with a focal length of 100 mm in ultrapulse mode with continuous exposure. After each pass, a saline soaked gauze was used to remove the debris. Endpoint of treatment was determined by removal of all of the yellowish lipid deposits and the appearance of pinkish soft tissue. Patients were advised to use antibiotic cream for 7 days and to avoid sun exposure between sittings. Subsequent sessions were given at monthly intervals till cure was achieved or to a maximum of three sessions, whichever was earlier.
The other group was treated with 30% TCA which was prepared by dissolving 30 g of TCA crystals with distilled water to bring the total volume to 100 mL. It was applied with a cotton tipped wooden applicator over the lesions while the surrounding area was protected with yellow soft paraffin. Subsequent sessions were done at 2 weekly intervals till cure was achieved or to a maximum of six sessions, whichever was earlier.
Serial visual analog scale (VAS) score and patient satisfaction score (PSS) were documented before the procedure every month and 1 month after the last session. In VAS score, improvement in percentage as noted by the physician is scored from 1 to 6. Percentage improvement from 0% to 20%, 21%–40%, 41%–60%, 61%–80%, 81%–95%, and more than 95% is scored with 1, 2, 3, 4, 5, and 6 points, respectively. Response to treatment as noted by the patient is expressed in terms of PSS ranging from five to one for the responses-very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied. Cure was defined as absence of any perceptible lesion after complete healing of the lesions.
Patients were followed up at the end of 3 and 6 months of treatment sessions or achieving cure whichever was earlier to assess for the recurrence rates, persistence of post treatment pigmentary abnormalities, or any secondary changes.
Monthly mean PSS and VAS score of 30% TCA and ablative ultrapulse CO2 laser were compared separately in flat and elevated lesions. Independent group Student's t-test was used to assess the level of significance.
| Results|| |
While recruitment of subjects for this study, 134 patients were screened, out of which 100 lesions in 74 patients were included for final assessment [Figure 1]. There was a female preponderance (n = 60) and majority of the study population were aged between 41 and 50 years (n = 52). On investigations, 20.27% of the study population (n = 15) had deranged lipid profile, 10.8% (n = 8) had elevated blood sugar levels and 4.05% (n = 3) had hypothyroidism. In subjects with lipid abnormalities, derangement in low density lipoprotein, triglycerides, and total cholesterol were seen in 20%, 26.6%, and 33.3% respectively. These patients had only borderline derangements and hence were advised dietary and lifestyle modification with no lipid lowering medications.
Out of the 100 lesions studied, 64 were flat lesions and 36 were elevated lesions. Of the 64 flat lesions, 32 each were treated with 30% TCA and ultrapulse CO2 laser. Of the 36 elevated lesions, 18 each were treated with 30% TCA and ultrapulse CO2 laser. 10 patients had a combination in of flat and elevated lesions of which 4 were treated with both modalities due to randomization.
Amongst the 32 flat lesions treated with TCA, 24 completely cleared after two sessions while the rest (8 lesions) cleared after four sessions. In the laser group, 26 lesions completely cleared after first session and the rest (6 lesions) required two sessions for clearance [Figure 2]. The mean PSS and VAS score of subjects with flat lesions treated with TCA and laser were compared using independent group Student t-test and the difference in scores between TCA and laser was not statistically significant [Table 1] and [Table 2].
|Figure 2: (a) Ultrapulse carbon dioxide laser (baseline). (b) Ultrapulse carbon dioxide laser (after single session)|
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Of the 18 elevated lesions treated with TCA, five completely cleared after the second session, six lesions cleared with six sessions and seven lesions did not regress even after six sessions [Figure 3]. In the laser group, six lesions completely cleared after first session, five lesions after two sessions and the remaining five lesions cleared after three sessions. Two elevated lesions persisted even after three sessions. The mean PSS and VAS score of those with elevated lesions treated with TCA and laser were compared using independent group Student's t-test and the difference between TCA and laser groups was found to be statistically significant [Table 3] and [Table 4].
|Figure 3: (a) 30% Trichloroacetic acid (baseline). (b) 30% Trichloroacetic acid (after 4 sessions)|
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In our study, adverse effects such as edema, erythema persisting beyond 24 h, itching and pain were assessed. While 20% patients in the laser group reported one of the above mentioned symptoms, almost twice the number (40%) of study subjects reported similar complaints in the TCA group. On subsequent follow-up at 3 months, hypopigmentation at the site of treatment was noted in 15% of lesions treated with TCA while 9% of lesions treated with laser had hypopigmentation. Hyperpigmentation was seen in 4% of lesions treated with TCA while it was not noted in the lesions treated with laser. About 2% lesions treated with TCA had a mixture of both hypo and hyperpigmentation. Scarring was not encountered in our study. At 6 months' follow-up, the persistence of hypopigmentation was found only in 8% of lesions treated with TCA while it was found in 4% of lesions treated with laser.
Recurrence of lesions was seen in 17% of lesions treated with TCA while it was noted only in 6% of lesions treated with laser at 3 months' follow-up, while at 6 months' follow-up recurrence was seen in 24% and 11% of lesions treated with TCA and laser respectively.
| Discussion|| |
XP is a common, benign periorbital dermatosis that has been found to be a risk factor for adverse cardiac events. It has a prevalence rate of approximately 1.1% in women and 0.3% in men and is more common in middle aged women as reflected in our study too. The incidence of dyslipidemia associated with xanthomas ranges between 20% and 50% according to various studies while it was found in 20% of our study population.,
TCA precipitates epidermal proteins and causes destruction of the upper dermis subsequently leading to sloughing of the necrotic layers. Varying dilutions of TCA have been used for the treatment of XP with higher concentrations giving better results. Cannon et al. used 95% TCA for XP with an overall success rate of 61%. In flat lesions, 50%–70% TCA was found to be effective while 100% TCA was required for papulonodular lesions by Haque and Ramesh. Dailey et al. in their study on histopathological changes of eyelid skin following repeated application of varying concentrations of TCA, found that medium and deep peels produced necrosis up to the depth of papillary dermis causing chances of ectropion, whereas these effects are least with superficial TCA peels which cause necrosis up to epidermis. Moreover, the pigmentary adverse effects are more with medium and deep TCA peels in Fitzpatrick skin phototype IV and higher. Hence, a concentration of 30% TCA was used for the study even though higher concentrations give better results.
Various lasers have been used in the management of XP including Argon, pulsed dye, 1450 nm diode, Nd: YAG, Er: YAG, and CO2 lasers. Argon and pulsed dye lasers use shorter wavelengths of light preferentially absorbed by hemoglobin which limits their use and is associated with higher recurrence rates. Q-switched Nd:YAG laser has been found to be of some benefit in yellowish pigmented xanthelasmas. Even though Er: YAG laser works on the principle of absorption by water and results in vaporization of water within cells thereby ablating skin layer by layer, its use is limited by reduced penetration and absence of hemostatic effects. Ultrapulse ablative CO2 lasers work by delivering high energy over extremely short pulses well within the thermal relaxation time of the surrounding tissue, vaporizing a thin layer of tissue with every pass causing destruction of perivascular foam cells and coagulation of dermal vessels in a precise and controlled manner. Fitzpatrick et al. have shown that skin up to a depth of 60 microns is ablated by a single ultrapulse CO2 laser treatment of 250 mJ pulse energy and the depth further increases to 130 microns on a second pass and to 316 microns on third pass aiding in layer by layer ablation.
In the present study, flat lesions and elevated lesions were assessed separately. In case of flat lesions, results of ultrapulse CO2 laser were marginally better as evident by the clearance of more number of lesions on follow up and the better PSS and VAS scores, but this difference in PSS and VAS scores was not statistically significant. Whereas, in case of elevated lesions, the response was considerably better with ultrapulse CO2 laser as compared to 30% TCA. Laser required lesser number of sessions for clearance of lesions and residual xanthelasma at 3 months' follow-up was found only in two lesions as compared to seven lesions in the TCA group. The mean PSS and VAS score showed statistically significant difference between the two treatment modalities. The main disadvantage of using 30% TCA was the irregular clearance of the lesions especially at the elevated borders and at the same time causing hypopigmentation in the relatively flatter areas. Multiple sessions were required with laser only for patients with large and irregular lesions, especially for clearing the deeper component.
Goel et al. carried out a similar study and observed that 30% TCA was equally efficacious as ultrapulse ablative CO2 laser in flat lesions while laser was superior in case of severe lesions. Mourad et al. studied efficacy of varying concentrations of TCA (35%, 50%, and 70%) and CO2 laser in treatment of XP and concluded that 70% TCA is equally efficacious as laser and 50% TCA was preferred in macular lesions while 70% in papular lesions. Al-Kady et al. studied fractional CO2 laser versus 50% TCA for treatment of XP and observed that there was no statistical difference between both the modalities. They found fractional CO2 laser (10,600 nm) to be ideal due to its better efficacy, less number of sessions and better patient satisfaction as compared to 50% TCA.
The assessment of depth of the lesion by the use of noninvasive imaging modalities like high resolution ultrasonography would help in determining the treatment modality. Lesions more than 5 mm in any dimension are better treated surgically to avoid adverse effects of deep scarring and ectropion. Penetration of 30% TCA would be a limiting factor in treating such lesions which was also observed in the outcome of elevated lesions in the present study.
The main side effects of edema and erythema were seen more in the laser group. Pigmentary abnormalities in the form of hypopigmentation, hyperpigmentation, and a mixture of both were observed mainly in the TCA group with improvement in hypopigmentation in subsequent visits. Scarring was not observed in any of the cases.
Recurrence rate in our study was 17% for TCA group at 3 months and 24% at 6 months' follow-up while that in the laser group was 6% and 11% at 3 and 6 months' follow-up, respectively. Recurrence was mainly seen among the elevated lesions treated with TCA and is presumed to be due to incomplete clearance. The recurrence rate in other studies varied from 25% to 39% with TCA while it was 9% to 16% with CO2 laser.
Limitation of study
Depth assessment by imaging was not carried out in the present study. Four patients were treated with both the modalities due to randomization which may have influenced the PSS.
| Conclusions|| |
XP is a benign but cosmetically significant dermatosis which requires proper evaluation before treatment. In case of flat lesions, both ultrapulse ablative CO2 and 30% TCA are equally efficacious, safe and well tolerated. Elevated and extensive lesions are better treated with ultrapulse ablative CO2 laser due to its better outcome, fewer sittings and comparatively lower recurrence rates.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]