Hyperpigmentation after sclerotherapy: own experience in therapeutic Q-switched Nd:YAG laser treatment

Introduction

Chronic venous disorders and their complications are still among the more common problems encountered in everyday medical practice, despite growing knowledge on their pathogenesis and treatment options [1,2].
Even though spider veins and reticular veins are considered to be mainly a cosmetic defect, the high incidence of subjective symptoms of chronic vein diseases should be emphasised in this group of patients as well [3,4]. These discomforts can significantly affect the quality of life of treated patients [5,6]. The symptomatic nature of the disease also often affects patients with more advanced stages of chronic venous disease. In this situation, it is important not only to consider treatment that takes into account the cosmetic effect (removal of varicose veins), but also treatment aimed at reducing venous hypertension and the complaints reported by the patient [5,6].
Prospective studies on the effectiveness of foam sclerotherapy for varicose veins show that this type of treatment has a significant impact on improving quality of life [7-9]. However, when evaluating eligibility of patients for this type of treatment, the side effects and complications of sclerotherapy should not be forgotten.
Hyperpigmentation is an inherent part of sclerotherapy, and is to be expected in a certain percentage of cases. According to the literature, 10-30% of patients will experience hyperpigmentation in the months following the procedure [10]. Usually it is temporary: in 60% of cases it disappears within 6 months and in 90% within a year of the procedure. In some patients, the hyperpigmentation is permanent – this applies to 1-10% of patients [10].
Hyperpigmentation is usually a consequence, not an early side effect of sclerotherapy.
Hyperpigmentation is neither the physical presence of blood in the vessel that has been closed by sclerotherapy nor the occurrence of supeficial vein thrombosis after sclerotherapy. It should also not be confused with damage to the vascular wall with the formation of a haematoma or bruising, which causes a darker shade of skin along the vein.
Sclerotherapy unintentionally and often uncontrollably leaves a certain amount of blood damaged by the sclerosant in the vessel lumen [11]. The transformation of red haemoglobin into brown haemosiderin causes a change in the colour of the closed vein. However, it still does not indicate hyperpigmentation as long as a continuous structure can be seen on ultrasound or with vascular illuminators, either as a closed vein after sclerotherapy or as a surviving fragment of a vein with its own wall. The disintegration of the treated vessel while leaving behind haemosiderin deposits indicates a high probability of persistent hyperpigmentation. It is similar in the case of post-inflammatory melanin deposits in the vicinity of previously treated veins. The depth of hyperpigmentation after sclerotherapy can be easily determined with a Wood’s lamp using UV light [12].
Epidermal hypermelanoses, which appear as sharply defined brown patches under a Wood’s lamp, are known to be characteristic of post-inflammatory hyperpigmentation. Their occurrence is caused by the following factors: the presence of an increased number of melanocytes in the epidermal basal layer, increased melanocyte activity, an increased number or size of melanosomes, or an increased amount of melanin in epidermal keratinocytes [13].
Deeper-lying cutaneous hypermelanoses include pigment deposits that appear blue, blue-grey or grey in the Wood’s lamp, presenting a type of secondary tattoo. They are caused by the presence of melanin in the dermis in ectopic dermal melanocytes or the deposition of hemosiderin in dermal macrophages [13].
Sometimes, the occurrence of hyperpigmentation is more likely in a given group of patients.
The skin tendency to hyperpigmentation varies according to the extremes of skin phototypes; in phototype I on the Fitzpatrick scale, hyperpigmentation tends to be smaller but more striking, while with dark skin, it tends to be larger but less striking in phototypes III and IV [14].
The individual tendency to hyperpigmentation is worth tracing. The preoperative interview should include an assessment of the effects of previous treatments, healing of post-traumatic/post-infectious bruises, and an assessment of the appearance of any postoperative/post-traumatic scars in terms of hyperpigmentation.
In patients with a low BMI, with poor subcutaneous tissue or with veins located close to the surface, the number of visible pigmented patches will inevitably be higher.
Gravity, which causes veins to dilate, increases the amount of blood trapped in the vessels. Pigmented patches are most likely to occur below the knee, especially on the feet. The diameter of the veins most commonly affected by hyperpigmentation is known to be 0.6-1.2 mm [10].
There are three basic principles for reducing the likelihood of hyperpigmentation after sclerotherapy: prevention; a wait-and-see approach for several months after the appearance of first pigmented patches; and treatments to reduce the severity and size of hyperpigmentation.
It is the responsibility of both the doctor performing the procedure and the patient to take preventive measures.
In order to avoid hyperpigmentation in the treated area, inflammation around the treated veins should be avoided. Particular attention is paid to the drugs used in the perioperative period: iron preparations, in the treatment of anaemia; tetracyclines, in the long-term treatment of Lyme disease or acne; chloroquine and hydroxychloroquine, for the treatment of collagenosis; oestrogens, for contraception and hormone replacement therapy; metformin, for the treatment of diabetes, insulin resistance and polycystic ovary syndrome; all non-steroidal anti-inflammatory drugs [15].
Hyperpigmentation depends on the way sclerotherapy was performed. The type of sclerosant used affects the risk of post-procedure hyperpigmentation: the lowest risk is associated with sclerosants that are not registered in Poland: 70% dextrose and sodium salicylate. The use of polidocanol (POL) can be related to the 6.7-31% presence of hyperpegimentations, in the cases of the use of the sodium tetradecyl sulfate (STS) hyperpigmentations can occur in 11-80% and after hypertonic NaCl soultion injection their occurrence is expected in 10-30% cases [10].
The method of administration of the sclerosant is also important. Its use in the foam form (which has a stronger effect than a liquid solution at the same concentration) increases the effectiveness of the treatment, while increasing the risk of hyperpigmentation. It is reasonable to administer it at a lower pressure, as well as to avoid treating large areas of the limb surface with sclerotherapy from a single injection. Fractionated administration of small volumes of sclerosant is more rational, and also reduces the risk of complications (including hyperpigmentation and matting).
The concentration of sclerosant should be appropriate to the diameter of the treated vein and its administered volume adequate to the volume of the vein. There are several modifications to the way sclerotherapy is performed aimed at reducing the diameter of the vein prior to the injection of the sclerosant, as too large volume and too high concentration of sclerosant increase the risk of hyperpigmentation: raising the limb, Trendelenburg position, cooling the skin, prior administration of tumescent fluid around the treated vein.
The evacuation of the contents of the vessel being closed with sclerotherapy can be done in several ways: rinsing with NaCl solution before administering the sclerosant, emptying the vessel immediately after administration using the wash-out technique [16], subsequent administration of tumescent fluid around the treated vein, use of post-treatment concentric and/or eccentric compression therapy.
The occurrence of hyperpigmentation after sclerotherapy usually requires a waiting period of several months, as 90% of pigmented deposits disappear within 1 year [10]. In patients for whom the occurrence of patches with pigmented deposits is of critical importance, appropriate treatment should be implemented. Patients with chronic venous insufficiency undergoing sclerotherapy for medical indications have different aesthetic expectations, whereas patients with stage C1 have much higher ones. The treatment of hyperpigmentation may include local minimally invasive treatment, oral medication or a combination of both.
Post-treatment follow-up is always considered an important part of the treatment. Thrombectomy performed during the follow-up should be based on an assessment of the local condition, in particular the presence of hyperpigmentation in the area of the vessels treated with sclerotherapy and blood clots in the lumen of these vessels. It can be performed a few weeks after the sclerotherapy. In some cases, the thrombectomy procedure needs to be repeated, as blood clots in the vessel are often identified later on during further examination for persistent traces of hyperpigmentation. In such cases, re-thrombectomy is worth considering. Thrombectomy is defined as early (3-14 days), late (15-30 days) or remote (6-12 months) (in European guidelines on the sclero­therapy – thrombectomy currently has a recommendation strength of 1C) [17].
Local treatment can target both melanin and – which is more difficult and usually more relevant in post-sclerotherapy hyperpigmentation – hemosiderin.
Reducing melanin deposits includes:
• delaying the transport of melanin/melanosomes to keratinocytes – isoflavones, niacinamide;
• inhibition of tyrosinase – hydroquinone, arbutin, kojic acid, liquorice extract (glycyrrhizin);
• acceleration of the epidermal cycle – alpha hydroxy acids and retinoids;
• inhibition of inflammatory processes, linking numerous mechanisms – cell renewal and differentiation as well as modulation of melanocyte function – retinoids, tranexamic acid.
The reduction of hemosiderin deposits includes the use of iron chelating agents – creams with lactoferrin as well as systemic and minimally invasive treatments.
Systemic treatment aimed at both reducing inflammation and, as a result, the risk of hyperpigmentation can be achieved for egzample by the oral administration of sulodexide before and after sclerotherapy [18].
Minimally invasive treatment targets both types of deposits, hemosiderin and melanin and can be performed by transcuteneous laser. It involves the use of the following lasers: Q-switched 532/694/1064 nm or picosecond 532/755/1064 nm. Very short (nano- or picosecond) pulses with very high power (hundreds of megawatts or single gigawatts) penetrate the skin and break up the pigment deposits deposited in the tissue (photoacoustic effect). Some of it evaporates through microdamage to the epidermis or through its subsequent exfoliation. Some of it is dispersed into the tissue, and some is removed by the lymphatic system through phagocytosis processes – facilitated precisely by this dispersion.
The shorter the pulse is, the lower is the risk of a thermal impact on the tissue in which the pigment is deposited. With picosecond lasers, the beam is emitted up to three times faster than in the case of a Q-switched laser. Delivering the same amount of energy in a third of the time causes the pigment to break down into smaller fragments. In addition, the treatment area is exposed to high energy for a third of the time, which translates into less pain during the treatment [19-22].
Diagnostics for the presence of possible reflux in vessels adjacent to previously treated areas where hyperpigmentation is found is also an important part of the treatment. If this type of pathology is identified, re-treatment with sclerotherapy aimed at removing the venous insufficiency and the insufficiency of the vessels supplying the area in question is justified.

Material and methods

In the study, a prospective evaluation was carried out on 7 patients who underwent polidocanol foam sclerotherapy and ultrasound-guided polidocanol foam sclerotherapy for venous spider veins, reticular veins and varicose veins of the limbs, as C1 and C2 lesions, in the course of superficial venous incompetence. A duplex Doppler study was performed in all patients in the period before inclusion in the study. Three of them underwent prior laser ablation of the incompetent axial vein of the superficial system (saphenous, anterior accessory saphenous, small saphenous), and all patients were found eligible for foam sclerotherapy and ultrasound-guided foam sclerotherapy. After the sclerotherapy, the patients wore CCL-2 compression stockings for 48 hours non-stop (with an additional cotton wool pad to increase the compression level in the area of the sclerotised veins) and then for 1 month during daily activity (without cotton wool).
Women aged 36-67 with primary venous lesions in the stage of venous disease C1, C2, Ep, As1-5, PR according to the CEAP classification were included in the study. The average duration of the disease was 10 years. All patients experienced post-procedural skin lesions in the form of hyperpigmentation. The lesions took the form of one to several beige-brown patches of pigment deposits with a diameter of several mm to several cm located in the skin and subcutaneous tissue near the veins that had undergone sclerotherapy. These lesions occurred 4 weeks after sclerotherapy and persisted for many months despite repeated thrombectomy procedures. Ultrasound and vascular illuminator evaluation showed atrophy of the veins treated with sclerotherapy in this area. The recommended post-treatment compression therapy was not discontinued.
The diameter of the treated veins determined the concentration of the sclerosant used: 1% or 2% for varicose veins, 0.5% for reticular veins, and 0.5% polidocanol for telangiectasias. No correlation was found between the occurrence of hyperpigmentation and the concentration of polidocanol used or the method of sclerotherapy, while the extent of hyperpigmentation was determined by the width and length of the treated vein and the density of telangiectasias in the area.
Initial local treatment included the application of lactoferrin cream. Patients did not undergo topical or systemic steroid therapy. Several months after sclerotherapy, with regular examinations in the meantime and due to persistent occurrence of pigmented patches, the patients were offered laser ablation at 6-week intervals with 1064 nm/532 nm Q-switched Nd:YAG laser. After obtaining informed consent, 7 patients underwent 532 nm Q-switched nanosecond Nd:YAG laser treatment with a 4 mm spot and individual laser parameters set to achieve the visual effect characteristic of a correctly performed treatment. The first follow-up visit took place between the 7th and 14th day after the treatment. Paracetamol was used for post-treatment pain relief. The next follow-up appointment took place 6 weeks after the treatment and, if the patient agreed, another laser ablation session was performed. The minimum number of laser treatments was 1, the maximum 4. The exclusion criterion was lack of consent to laser ablation or lack of effect of the previous treatment (1 patient).

Evaluation of treatment results

The visual condition of the skin was assessed by the patient and the physician performing the procedure. Doppler ultrasound was also performed to assess the condition of the venous system and ultrasound morphology of the treated skin lesions.

Results

Before foam sclerotherapy, more than 90% of patients had subjective complaints of pain and/or heaviness and fatigue in the lower limbs associated with spider veins, reticular veins and varicose veins. They included a feeling of swelling, night cramps and itching. These complaints were significantly reduced upon inclusion in the study. However, the aesthetic effect of the treatment in the form of skin hyperpigmentation was rated poorly by the patients. During the final evaluation after laser treatment, no progression of complaints related to chronic venous disease was found. The use of laser treatment also resulted in a significant improvement in the aesthetic effect.
Whitening of skin lesions occurred in 86% of patients who underwent laser therapy and decided not to continue treatment because the effect obtained was satisfactory. Treatments were repeated 4 times in 1 patient, 3 times in 1 patient, 2 times in 3 cases, and single treatments were performed in 2 patients.
In one patient, the favourable effect of complete disappearance of pigmented deposits after one treatment resulted in the adverse situation related to local skin depigmentation of the treated area.
In one patient, no positive change within the hyperpigmented area was observed during the 6-month follow-up after the laser therapy. Another attempt to treat the hyperpigmentation with a picosecond laser was also unsuccessful.
The effects of the treatment are shown in Figures 1-4.
In the examined group, there was no abnormality in the superficial vein system in the treated area owing to the previous foam sclerotherapy being performed correctly.

Discussion

Despite the increasing number of studies on the possibility of obliterative treatment and the improvement of minimally invasive techniques, foam sclerotherapy is still associated with the risk of post-treatment hyperpigmentation.
Over the many years of performing sclerotherapy, the effectiveness of the treatment and possible complications have been evaluated more closely. The technique of this procedure has undergone some modifications, in particular due to the introduction of foam sclerotherapy, which enables the closure of varicose veins with a larger diameter. As can be seen in everyday practice, the group of patients with varicose veins of lower limbs is extremely heterogeneous in terms of the severity of chronic venous diseases and the diagnosed pathology. Varicose veins often coexist with more advanced forms such as trophic changes or active or healed ulcers, or they appear secondarily to changes in deep veins. According to the currently accepted modifications of the CEAP classification, when defining the stage of the disease according to this classification, not only the highest but also the other stages of the disease present in the examined patient should be taken into account [3].
Sclerotherapy treatment is associated with a number of possible complications, and the phlebologist performing the procedure should have in his arsenal methods and means to eliminate ailments and aesthetic defects resulting from these events.
The treatment of hyperpigmentation after sclerotherapy is long and difficult. Therapeutic options include the use of topical agents and systemic medications as well as minimally invasive laser treatments. Until now, there has been no simple and effective way to reduce the severity of chronic hyperpigmentation associated with sclerotherapy.
Q-switched Nd:YAG 1064 nm/532 nm lasers have been successfully used by aesthetic medicine for years. Laser removal of tattoos and hyperpigmentation involves breaking up the pigment deposits. Once dispersed, the pigment is more easily – although only partially – removed through the lymphatic system including macrophages. To achieve this effect, the laser must generate very short, high-power nanosecond pulses (megawatts) and needs to have a wavelength that is well absorbed in a given tattoo dye. These requirements are met by an Nd:YAG laser operating in Q-switched mode, using a wavelength of 532 nm or 1064 nm. Haemosiderin reaches its peak absorption at 410-415 nm, followed by a gradually decreasing curve across the entire visible spectrum. Melanin has an absorption spectrum from 250 to 1200 nm. Longer wavelengths are better for treating hyperpigmentation in the dermis due to their greater penetration capacity and lower absorption by the epidermis. Hemosiderin deposits after sclerotherapy can be located at a depth of up to 2.8 mm. Some believe that the other existing Q-switched lasers – ruby (wavelength 694 nm) and alexandrite (wavelength 775 nm) – are less useful here [23], but they also have their place because, if necessary, they have greater penetration than potassium titanyl phosphate (KTP) lasers or greater absorption than Nd:YAG lasers.
There have been relatively few papers published so far demonstrating the use of this type of laser in the treatment of skin lesions after sclerotherapy, despite favourable effects of such treatments on hyperpigmentation known since the 1990s [24]. According to some studies an mprovement was achieved in 92% of patients after 2 treatments with a 694 nm wavelength laser (the next treatment was performed at an average interval of 2.5 months) [19] and in 91% of patients after 2 treatments with a 532 nm wavelength laser (another treatment was performed at an average interval of 3.5 months) [25].
The performance of the scheduled laser treatments resulted in the reduction of hyperpigmentation caused by the previous sclerotherapy.

Conclusions

Hyperpigmentation is a common side effect of sclerotherapy and can last for many years.
The use of Q-switched 532 nm wavelength laser ablation reduces the severity of hyperpigmentation and constitutes an effective addition to standard treatment.

Disclosures

1. Institutional review board statement: Not applicable.
2. Financial support and sponsorship: None.
3. Conflicts of interest: None.

References