Pigmentation after foam or cryo-laser cryo-sclerotherapy for lower limb reticular veins: A within-patient randomized trial

Abstract

Objective

Skin hyperpigmentation is a common complication after leg vein sclerotherapy and a primary concern for patients with cosmetic complaints. The aim of this study was to determine if cryo-laser cryo-sclerotherapy technique (CLaCS) presents a lower incidence and intensity pigmentation after procedure compared with 0.5% polidocanol foam sclerotherapy, 60 days after a single treatment of reticular veins.

Methods

This was an open-label, prospective, within-patient, randomized, active controlled, safety trial with blind evaluators. Interventions took place from August through September 2021, with a 2-month follow-up. Interventions were performed in a private clinic. Eligible patients were volunteers over 18 years old, with aesthetic discomfort related to bilateral lower limb reticular veins, similar length and distribution, with veins' internal diameter up to 2.2 mm in B-mode ultrasound. Patients underwent consecutive CLaCS treatment in one limb and 0.5% polidocanol foam in the contralateral limb on the same day. The primary outcome was the presence of post-procedure pigmentation in treated areas 60 days after a single treatment, determined through photo evaluation and objective measurement of skin color dissimilarity between the treated area and the adjacent skin, using a precision colorimeter. Patients’ aesthetic satisfaction improvement, vein diameter reduction, and minor/major adverse events were also assessed.

Results

Twenty-three women (46 limbs) were treated, and two were lost to follow-up. No significant statistical difference in the number of limbs that developed posttreatment pigmentation was found for both photo (7 CLaCS vs 5 foam; P = .8906) and colorimetric (9 CLaCS vs 13 foam; P = .1445) evaluations. The CLaCS group had significantly lower intensity of pigmentation in colorimetry (mean ΔE of 1.30 for CLaCS vs 1.44 for foam; P = .02735). No significant difference in veins’ diameter reduction was found. Both groups presented substantial improvement in patients’ satisfaction with their leg appearance.

Conclusions

Although no statistical difference was found regarding the number of limbs that developed hypercromia after treatment of the reticular veins, CLaCS resulted in a lower intensity of skin color dissimilarity, less microthrombi formation and drainage, less bruising and lower volume of sclerosant needed, without difference in diameter reduction rates, compared with polidocanol foam sclerotherapy. No major adverse events were reported.

Article Highlights.

• •Type of Research: Single-center, open, prospective, within-person, randomized, with active control, safety study
• •Findings: Despite comparison in the number of limbs that developed pigmentation in patients who underwent consecutive cryo-laser cryo-sclerotherapy (CLaCS) treatment in one limb and polidocanol foam in the contralateral limb showed no significant statistical difference, the CLaCS group demonstrated a significantly lower intensity of pigmentation in colorimetry, less microthrombi formation/drainage, less bruising and lower volume of injected sclerosant, with no significant difference in veins’ diameter reduction rate.
• •Take Home Message: The CLaCS procedure can be a safe and effective alternative for treating reticular veins, with less intense postprocedural hyperpigmentation.

Chronic venous disease is highly prevalent worldwide. Among its clinical manifestations, telangiectasias and reticular veins are frequent concerns, particularly in aesthetic practice. The management of reticular veins in the lower limbs has gained increasing relevance, especially among patients presenting with isolated cosmetic complaints, classified as C1 asymptomatic under the CEAP system.^1,2

Liquid and foam sclerotherapy may be successfully used to treat reticular veins, with sclerosant concentrations determined by vessel type, diameter, and wall thickness.3, 4, 5, 6, 7, 8 A well-documented complication associated with its use is post-sclerotherapy hyperpigmentation (PSH), especially for patients with Fitzpatrick IV to VI.^9,10 Although considered a minor adverse event, PSH can significantly affect patients’ quality of life and often undermines overall satisfaction and potentially deters them from the procedure.¹¹

The adjunctive use of laser has been shown to enhance the efficacy of sclerotherapy. The cryo-laser cryo-sclerotherapy (CLaCS) technique, which combines a 1064-nm Nd:YAG transdermal laser with liquid sclerotherapy using 75% dextrose, is performed under skin cooling and visual guidance with illumination devices and has been previously described.12, 13, 14, 15, 16

This study investigates the potential of the CLaCS technique to reduce the incidence of post-sclerotherapy pigmentation, given the consistently low rates reported in the literature.

Methods

Study design

This was an open, prospective, randomized, with active control, within-patient safety trial conducted at a single medical center.

The trial was registered on the Brazilian Registry of Clinical Trials (RBR-88mcd4c) and International Clinical Trials Registry Platform (UTN U1111-1265-8900), performed following the Consolidated Standards of Reporting Trials (CONSORT) guideline for randomized clinical studies with extension for within-person trials¹⁷ and the ethical principles of the Declaration of Helsinki. The local ethical committee approved the study protocol (Hospital Leforte Ethical committee 4.532.514), and all participants provided written informed consent before any procedure. Study data were collected and managed using REDCap (version 11.1.29) electronic data capture tools hosted at Yale University.

Participants

Eligibility criteria included patients over 18 years old, who signed informed consent, with lower limb reticular varicosities (with or without telangiectasias), with similar distribution in both legs (lesions to be treated had to be approximately of the same length and be located at the same part of the leg),^17,18 veins with internal diameter measuring up to 2.2 mm in B-mode ultrasound, standing position, considering the largest diameter along the segment to be treated. No contraindications for any of the procedures studied could be present.

Exclusion criteria were personal history of any local/systemic allergic reaction to polidocanol injection; pregnancy, puerperium, and breastfeeding; use of topical/systemic drugs that might induce skin hyperpigmentation (eg, isotretinoin, minocycline); local tissue damage or infection; and insufficiency of pelvic, perforator, or saphenous (great/small) veins connected to the studied area.

On the treatment day, after screening, patients signed informed consent and underwent standard clinical evaluations by a trained vascular surgeon. Before randomization, data on baseline characteristics, including demographics, comorbidities, aesthetic satisfaction, and clinical findings, were collected using the RedCap software.

Randomization and allocation

To ensure within-patient comparison, each participant received both treatments, one for each lower limb, with randomization performed based on limbs rather than patients. Prior to treatment, each participant had their right lower limb randomly assigned to either CLaCS or polidocanol foam sclerotherapy, via the RedCap electronic system.

Interventions

After randomization and photographic documentation, treatments were performed.

The limb assigned to the CLaCS technique was always treated first, followed by 0.5% polidocanol foam sclerotherapy on the contralateral limb. This sequence was adopted based on evidence suggesting lower risk of systemic complications for CLaCS and documented potential of systemic reactions to foam sclerotherapy.

The distance between treatment sites and the absence of carry-across effects allowed us to perform the sequential treatments.17, 18, 19 To ensure equipoise, each technique was assigned to a different leading investigator based on their expertise, and this investigator performed the given technique for all the limbs randomized to it.

The CLaCS technique involved applying a 1064-nm long-pulse Nd:YAG transdermal laser (Harmony, Alma Lasers) along the reticular vein, with a skin cooling device (Freddo, Fabinject) and augmented-reality guidance (Vein Viewer, Christie Medical).^20,21 Laser emission settings were a 6-mm spot size, 15-millisecond pulse duration, and energy adjusted according to Fitzpatrick Phototype Scale^22,23 (70 J/cm² for Fitzpatrick up to IV and 50 J/cm² for Fitzpatrick V). Liquid 75% dextrose (Victa Lab) was then injected intravenously into the same vessels under skin cooling and augmented-reality guidance.²⁴

Twenty minutes after the CLaCS procedure and data collection, polidocanol foam sclerotherapy was performed in the contralateral limb. The foam was obtained using the Tessari method,²⁵ mixing 0.5% polidocanol (Victa Lab) and ambient air in a 1:3 ratio. It was injected intravenously into the affected area, observing the technique’s limitations, especially the maximum volume per session.26, 27, 28

On both limbs, cotton balls held by adhesive tape were applied to puncture sites to stop bleeding, eccentric compression with a dental cotton roll was applied to the vessel site, and 24- to 30-mmHg compression stockings were placed.

Patients were instructed to remove eccentric compression and stockings after 24 hours and scheduled for follow-up visits after 7, 30, and 60 days for clinical evaluation, photographic documentation, and assessment of cosmetic satisfaction with an aesthetic numeric analog scale (ANA-scale).²⁹

Outcome measures

The primary outcome was the incidence of post-procedure skin hyperpigmentation 60 days after a single treatment session, evaluated through before-and-after photo documentation analysis by three independent and blind observers (vascular surgeons highly experienced in phlebology).

All the evaluators received access to high-definition before and after pictures of the patient’s legs that were designated for them, together with a before picture with a white tracing of the treated vessel, to identify exactly the treated areas (Fig 1). Then they were invited to answer the question “Do you think there is post treatment pigmentation in the treated areas of this limb, yes or no?” for each limb, according to their own expertise. The answer chosen by most of the evaluators was considered for data analysis.

Fig 1.

Example of before and after pictures sent to blind evaluators.

The co-primary outcome was the skin tone dissimilarity (expressed as ΔE) at treated and adjacent areas measured with digital colorimetry. This method was previously described and allows precise measures of skin color differences.^30,31

The ΔE value derives from the differences in the International Commission on Illumination L∗a∗b∗ (CIELAB) color space, which provides a systematic way to represent color differences based on three parameters: lightness (L∗), red-green chromaticity (a∗), and yellow-blue chromaticity (b∗). Measured CIELAB color space parameters enable the unique identification of every color that may be visually distinguished, and their use is proposed for the unambiguous communication of skin color information for clinical or scientific purposes.^32,33

This metric provides a structured approach to quantifying color differences, with specific intervals indicating varying levels of perceptibility that may be translated into different intensities of pigmentation.

• •0 < ΔE < 1: difference is unnoticeable (no pigmentation),
• •1 < ΔE< 2: difference is only noticed by experienced observer (mild),
• •2 < ΔE < 3.5: difference is also noticed by inexperienced observer (light),
• •3.5 < ΔE < 5: difference is noticeable (moderate),
• •5 < ΔE: gives the impression that these are two different colors (intense)

Patients were submitted to colorimetric analysis, ΔE being the skin color difference between the treated and the adjacent areas. For study purposes, a ΔE of 1 or higher was considered positive, even though only ΔE over 2 was considered to have a clinical impact (also noticed by inexperienced observers).

Secondary outcomes

The intensity of color dissimilarity at treated sites was calculated based on ΔE values (higher ΔE reflects more intense color difference). The treated vessel’s internal diameter reduction rate was calculated using baseline and D60 measurements of the largest diameter on the treated vein, on B-mode ultrasound using a 20-MHz probe with a standing patient.

Other variables collected were sclerosant agent volume and the number of vein punctures; occurrence of post-treatment ecchymosis, microthrombi and need of micro thrombectomy (all microthrombi were drained); minor adverse events such as scarring, cough, superficial venous thrombosis, telangiectatic matting, allergies, fainting, migraine, and scotomas; major adverse events rate such as chest pain, neurologic abnormalities, inadvertent arterial puncture, tissue necrosis, deep vein thrombosis, and pulmonary embolism; pain intensity measured using a pain visual analog scale after each treatment session; and patient’s cosmetic satisfaction before and 60 days after procedure, for each treated limb, using the ANA scale.

Sample size calculation

Considering a dichotomous endpoint (pigmentation yes/no), an 80% power at an alpha level of .05, and mean reported hyperpigmentation rate after the treatment of varicose veins as 31.6% for polidocanol foam³⁴ and zero for CLaCS.,^13,16 a sample size of twenty patients (forty limbs) was calculated. Assuming a drop-out rate of 15%, a minimum of twenty-four patients (forty-eight limbs) should be initially included.

Due to the complexities of within-patient trials sample size calculations, including estimating a correlation coefficient,¹⁷ the sample size was calculated considering parallel unpaired binary outcomes, which is known to require a higher sample than that needed for paired intrapatient data. Although a conservative approach, it was chosen to ensure the sample size was not underestimated.

Statistical methods

Statistical analyses were performed using R software (version 4.2.2). Descriptive statistics included absolute and relative frequencies for categorical variables, and measures of central tendency (mean and median), and dispersion (standard deviation, minimum and maximum values) for continuous variables.

For categorical paired outcomes, the McNemar test was applied in its unilateral form, using a one-tailed binomial test on discordant pairs to assess the directionality of the effects.

For the intragroup comparisons between the two treatment modalities (CLaCS and goam), the paired Wilcoxon signed-rank test was applied for continuous variables that did not meet parametric assumptions, using a one-tailed approach.

The significance level was set at 5% (P < .05).

Interrater reliability among evaluators was calculated using kappa concordance and gross agreement tests.

Results

Participant flow

From August through September 2021, 39 volunteers filled in an online pre-screening form and were invited to an on-site clinical assessment for eligibility. Twenty-six volunteers attended this clinical screening. Two patients were excluded for not meeting the study criteria. Twenty-four patients were randomized; one withdrew informed consent.

A total of 23 volunteer women, with mean age of 44.04 years (standard deviation [SD], 8.28 years) and Fitzpatrick skin types III (30.4%), IV (60.9%), and V (8.7%) were submitted to both treatments according to randomization allocation. Demographic characteristics are described in Table I. Two patients were lost to follow-up, and 21 patients completed the study. Forty-six limbs were assessed for baseline data and D7 secondary outcomes. Forty-two limbs were assessed for D60 primary and secondary outcomes, as shown in the CONSORT flowchart (Fig 2).

Table I.

Demographic and baseline characteristics of participants

Variables	Population
Sex (female)	23 (100)
Age, years	44.04 (8.28)
Hypertension	2 (8.7)
Diabetes	1 (4.3)
Thrombophilia	1 (4.3)
Gestations	1.91 (1.20)
Vein location
Popliteal fossa	12
Lateral thigh	10
Posterior thigh	1
Fitzpatricka
III	8 (34.7)
IV	13 (56.5)
V	2 (8.7)

Data are presented as number (%) or mean (standard deviation).

^aFitzpatrick: Fitzpatrick skin type classification.

Fig 2.

Consolidated Standards of Reporting Trials (CONSORT) flowchart. CLaCS, Cryo-laser cryo-sclerotherapy; D, days; LL, lower limbs; pp, people.

Outcomes and estimation

Systemic outcomes were assessed per patient, and local outcomes were assessed per limb.

Main outcomes

There were no significant differences in the number of limbs presenting with hyperpigmentation between the groups in both photo (7 CLaCS vs 5 foam; P = .8906) and colorimetric (9 CLaCS vs 13 foam; P = .1445) evaluations.

Secondary outcomes

In the colorimetric evaluation, CLaCS had significantly lower mean ΔE values, suggesting a lower intensity of pigmentation, since higher ΔE reflects more intense color difference, with mean ΔE of 1.3 (SD, 1.88) for CLaCS vs 1.44 (SD, 1.00) for foam (P = .02735). For patients with Fitzpatrick skin types III and IV, this difference is more noticeable, with mean ΔE of 0.91 (SD, 0.61) for CLaCS vs 1.48 (SD, 1.00) for foam (P = .006).

No statistical difference was found between treatments in the treated vessel internal diameter reduction rate, measured on B mode ultrasound, using a 20-MHz linear probe, with patients in orthostatic position.

The volume of injected sclerosants was significantly lower in the CLaCS group compared with the foam group (median 0.3 vs 2.0 mL; P < .0001), whereas the number of punctures for sclerosant injections showed no statistical difference.

The legs treated with polidocanol foam showed a significantly higher incidence of microthrombi formation and consequent need for drainage in the foam group (9 vs 3; P = .035, being 2 bilateral, 7 only for foam limb and 1 only for CLaCS limb).

Also, limbs treated with CLaCS presented with less bruising on day 7 when compared with limbs treated with foam (3 vs 9; P = .0156). Of those, three presented bruising bilaterally and six only for foam-treated limbs.

Other minor adverse events:

• -Two bilateral topic reactions and redness (one related to the tape used for blood-stopping and one related to the stocking silicon).
• -One matting (foam limb).
• -One blistering and scarring at the compression site (CLaCS limb), resulting in a dark scar. This was the only limb in the study that presented an intense pigmentation (ΔE of 9.1).

No major adverse events, such as chest pain, neurologic abnormalities, inadvertent arterial puncture, deep vein thrombosis, or pulmonary embolism, were observed.

Patients did not report high pain levels for either procedure. On a scale of 0 to 10, the mean pain value for the CLaCS limb was 2.72 (SD, 1.49) vs 1.85 (SD, 1.16) for foam limb, with a P = .9901.

Detailed statistic data on efficacy and safety outcomes for CLaCS and foam are described in Tables II (categorical) and III (continuous).

Table II.

Efficacy and safety results for cryo-laser cryo-sclerotherapy (CLaCS) and foam

Outcomes	No.a	CLaCS	Foam	Bilat	P valueb
Pigmentation on photo	21	7 (33.3)	5 (23.8)	3	.8906
Colorimetry ΔE >1	21	9 (42.8)	13 (61.9)	7	.1445
Colorimetry ΔE >2	21	3 (14.2)	7 (33.3)	2	.1094
Colorimetry ΔE >2 FP III/IV	20	2 (10)	7 (35)	2	.0312
Bruising D7	23	3 (13)	9 (39.1)	3	.0156
Micro thrombi/drainage	23	3 (13)	9 (39.1)	2	.0351
Matting	21	0	1 (4.7)	0	1
Scarring	21	1 (4.7)	0	0	1
Redness/topic reaction	23	2 (8.6)	2 (8.6)	2	1

Bilat, Patients that presented the outcome in both lower limbs; FP, Fitzpatrick skin type classification.

Data are presented as number (%).

^aNo. varies due to participant loss to follow-up.

^bP value calculated using McNemar test.

Table III.

Efficacy and safety results for cryo-laser cryo-sclerotherapy (CLaCS) and foam

Variable	Group	No.a	Mean	SD	Min	Median	Max	P valueb
ΔE intensity	CLaCS	21	1.3	1.88	0.12	0.8	9.1	.02735
	Foam	21	1.44	1	0	1.1	3.4
ΔE intensity FP III/IV	CLaCS	20	0.91	0.61	0.12	0.75	2.2	.006
	Foam	20	1.48	1.01	0	1.11	3.4
Reduction rate, %	CLaCS	21	62.34	25.65	10	62.5	100	.3475
	Foam	21	68.45	26.68	20	63.64	100
Sclerosant volume	CLaCS	23	0.5	0.6	0.1	0.3	3	<.0001
	Foam	23	1.85	0.73	0.5	2	3
Vein punctures	CLaCS	23	4.52	1.75	1	4	10	.9966
	Foam	23	3.13	1.42	2	3	6
Pain score, cm	CLaCS	23	2.72	1.48	0.2	2.3	6.5	.9885
	Foam	23	1.85	1.14	0.5	1.75	5

FP, Fitzpatrick skin type classification; Max, maximum value; Min, minimum value.

^aNo. varies due to participant loss to follow-up.

^bP value calculated using Wilcoxon statistical test for comparisons between the Foam and ClaCs groups.

Statistical analysis of the ANA scale demonstrated a significant improvement in patient satisfaction regarding leg appearance perception pre- and post-procedure for both methods. Changes in appearance showed no statistically significant differences between interventions (Table IV)

Table IV.

Patient cosmetic satisfaction: aesthetic numeric analog (ANA) scale

Intervention	Mean	SD	95% CI		Min	Median	Max	Pb
			Inferior	Superior
Foam								.526
ANA Pre	4.62	2.31	3.63	5.61	1.00	5.00	9.00
ANA Post	9.14	0.91	8.79	9.50	7.00	9.00	10.00
	<.001a
CLaCs
ANA Pre	4.48	2.31	3.48	5.47	1.00	5.00	8.00
ANA Post	9.48	0.68	9.12	9.83	8.00	10.00	10.00
	<.001a

ANA pre-post, ANA scale values before intervention and on day 60; CI, confidence interval; CLaCs, Cryo-laser and cryo-sclerotherapy; Foam, 0.5% polidocanol sclerosing foam; Min, minimum value; Max, maximum value; SD, standard deviation.

^aWilxocon.

^bOne-way analysis of variance for repeated measures.

Discussion

PSH is a common complication and a major concern for patients seeking leg aesthetical improvement. It presents as an abnormal deposit of melanin and/or hemosiderin, primarily due to a perivascular inflammatory status (post-inflammatory hyperpigmentation [PIH]). This inflammation is mainly caused by vessel rupture and blood extravasation, sclerosing agent’s action on the vein and surrounding tissues, and/or persistence of blood clots inside the vein lumen. As the formation of microthrombi is a well-known cause of inflammation and subsequent PIH, a greater formation of microthrombi in the foam group may have contributed to the observed difference in pigmentation intensity between the procedures.

When the veins are not entirely shut, the shadow of the vein may be visible and mistaken for pigmentation. Dermoscopy may be used to differentiate pigmentation from persistent veins.^2,35,36

The combination of transdermal LASER and sclerotherapy for reticular veins has emerged as a promising, minimally invasive treatment option and is also present in the latest European guidelines.²⁸ Recent studies indicate that CLaCS is associated with a favorable safety profile and practical outcomes, with no major complications reported. Combining thermal and chemical treatments, while using reduced laser energy and sclerosant volume, may promote varicose vein obliteration while preserving surrounding tissues, which is crucial for minimizing complications.^12,37,38 This might be linked to a lower inflammatory response associated with CLaCS, thus explaining the diminished post-procedure intensity of pigmentation when compared with foam treatment in the same patient.

The within-patient design was chosen to minimize bias related to patients’ personal pigmentation tendencies, ensuring equitable outcome comparisons. This design is particularly useful for stable conditions with localized, short-term effects, enhancing study sensitivity to detect treatment differences with fewer subjects than traditional randomized controlled trials, allowing direct intra-individual treatment comparison and minimizing variability due to individual differences.^17,18 In other words, this allowed us to observe if pigmentation was linked only to procedure and/or also patients’ matters. In fact, seven of the nine patients with ΔE >1 in the CLaCS group showed pigmentation in the contralateral limb. Also, two of the three patients that presented ΔE >2 in the CLaCS group had more intense pigmentation in the contralateral limb.

Our study population consisted of individuals with higher Fitzpatrick skin types (III: 30.4%, IV: 60.9%, V: 8.7%), which are known to be linked to a higher risk of pigmentation after sclerotherapy.^10,22 This likely reflects the predominant population in the city the study was conducted. Additionally, lesion locations in lateral thigh (43.5%) and popliteal fossa (52.2%) further increased hyperpigmentation risk.

It is also interesting to reinforce the fact that the results in this trial were measured after one single session and at an early moment (60 days); besides that, most of the positive results were mild/light pigmentation (Supplementary Fig, online only). This, along with all the other matters described, might have contributed to a higher incidence of pigmented limbs in this series.

As CLaCS and foam methods are performed differently, it was not possible to conceal them from patients or doctors/investigators. However, evaluators were blinded and unaware of which treatment was applied to the limb they evaluated in the before and after pictures. They also had no access to contralateral limb images.

Even though the blinded evaluators were experienced vein specialists, and the results of their responses matched the colorimetry conclusions (the alternative with the majority answers for either “yes” or “no” was considered), the inter-evaluators’ kappa calculation showed no significant statistical concordance, with gross agreement rates ranging from 52.4% to 70% (Supplementary Table, online only). On photo evaluation, a 100% concordance among the evaluators was found only for 13 of 30 limbs (44%) in the not-pigmented group, and three of 12 (25%) in the pigmented group. This highlights the personal and subjective nature of photographic evaluation, and enhances the importance of objective measuring tools, such as colorimetry, as a way of mitigating doubts, especially when patient complaints arise.

A crucial element of aesthetic treatment is not just the objectively positive outcome but also the level of patient satisfaction. Successful cosmetic procedures can enhance psychological well-being and social status, ultimately improving quality of life.^39,40

In the patient-reported outcome, the ANA scale²⁹ analysis showed a significant improvement in satisfaction with leg appearance pre- and post-procedure for both treatments. However, it is worth noting that all treated patients in this study were volunteers who received the treatments free of charge, which may have contributed to a higher degree of satisfaction for either treatment. In private practice, patients seem to be more likely to express dissatisfaction with the results.

The ANA scale was chosen to assess satisfaction with cosmetic results separately, per limb, in the same patient. As standard quality of life questionnaires are related to patients’ overall conditions, they were not applicable for this matter.^17,41, 42, 43

It is important to reinforce that, despite no statistically significant difference being observed when considering the entire study population, when analyzing only patients with Fitzpatrick skin phototypes III and IV—who are known to be prone to post-inflammatory hyperpigmentation—a statistically significant difference was found in the number of pigmented limbs (Table II). In addition, there was a significant difference in the overall intensity of pigmentation, which was more pronounced following foam sclerotherapy compared with CLaCS.

In conclusion, for patients who are intrinsically more likely to develop PIH and/or who have higher aesthetic expectations, CLaCS may represent a more suitable option to minimize post-treatment pigmentation, offering a favorable profile regarding hyperpigmentation intensity in the first 60 days post-treatment of reticular veins, in addition to a lower volume of sclerosant injection and less microthrombi formation, when compared with polidocanol foam sclerotherapy, markedly in patients with Fitzpatrick skin types III and IV, without compromising treatment effectiveness.

As for treatment session duration for a comparable extent of lesions, the difference in time from patient admission to discharge between the two interventions is minimal.

Because the initial cost of setting up a treatment suite equipped with laser devices represents a significant investment, CLaCS procedure tends to be predominantly offered in private clinics. In these settings, we suggest individualized treatment planning, incorporating all therapeutic options considered most beneficial for a given patient, with cost to the patient based on clinical complexity and physician expertise, rather than only on the specific technique used.

Clinical implications

Identifying patients at higher risk for pigmentation and tailoring treatment approaches can enhance outcomes. As this study showed that CLaCS may lead to less intense hyperpigmentation in the first 60 days post-treatment without compromising efficacy, for patients known to be more prone to pigmentation, it may be a suitable alternative for such cases.

The reduced need for sclerosant volume in the CLaCS procedure might allow for treating larger areas in one session, especially when the sclerosant used is limited to a safe per-session volume, thus reducing the number of visits needed for treatment completion, particularly in patients with extensive lesions.

Furthermore, the lower incidence of thrombus formation with the CLaCS technique may decrease the risk of PIH and the need for early returns for clot drainage, while also reducing patients’ discomfort, given that all patients who underwent microthrombi drainage have spontaneously reported this as the most uncomfortable part of the treatment.

Limitations

This study’s limitations include the small sample size, limited Fitzpatrick variety, lesion location in areas prone to pigmentation, and lack of blinding, which may introduce bias. The short follow-up period also limits our ability to assess long-term outcomes.

Despite these limitations, some highlights of the study are the prospective within-patient analysis, one designated expert investigator to apply each of the techniques, and the first-time use of objective colorimetry analysis for hyperpigmentation post-varicose vein treatment. Furthermore, the Fitzpatrick limitation ended up providing us with important data on patients that are known for a higher risk of developing pigmentation.

Future studies should explore the long-term outcomes and safety profiles of CLaCS in diverse populations with larger, varied samples to validate these findings and examine the long-term effects of both treatments on pigmentation and patient satisfaction. Further research into the mechanisms underlying individual variability in pigmentation response could also enhance treatment personalization.

Conclusions

Although this study showed no statistical difference in the number of limbs that developed PSH after treatment of reticular veins with either CLaCS or polidocanol foam sclerotherapy, the CLaCS procedure resulted in lower intensity of skin color dissimilarity compared with polidocanol foam sclerotherapy, in addition to a lower sclerosant volume usage and less microthrombi formation, without loss in efficacy. It can be a safe alternative for treating reticular veins in patients prone to pigmentation.

Author Contributions

Conception and design: AR, JP, CR, ER

Analysis and interpretation: AR, JP, CR, FS, SN, GS, MP, ER

Data collection: AR, JP, VS

Writing the article: AR, JP, SN, ER

Critical revision of the article: AR, JP, VS, CR, FS, SN, GS, MP, ER

Final approval of the article: AR, JP, VS, CR, FS, SN, GS, MP, ER

Statistical analysis: Not applicable

Obtained funding: Not applicable

Overall responsibility: AR

Funding

This was a self-funded study with modest support from the Science Valley Research Institute.

Disclosures

E.R. reports grants and consulting fees from Bayer and Pfizer; research grants from Bayer, Althaia, Pfizer, Novartis, Bios, and the Brazilian Ministry of Science and Technology; and personal fees from Aché Pharma, EMS, Novartis, and Daiichi-Sankyo, outside the submitted work. J.P. reports grants and consulting fees from Sigvaris, Supera, Merz, Urgo Medical, Essity, and Servier.

Appendix (online only)

Supplementary Fig (online only).

Different levels of pigmentation according to ΔE.