Pigmentation Mesotherapy

What Is Pigmentation Mesotherapy?

Pigmentation mesotherapy uses very fine needles to inject active ingredients that target pigmentation into the skin, in small amounts and at many points. Mesotherapy is the general name for a technique in which medicines are given into or under the skin by micro-injections, that is, injections of very small amounts. Pigmentation mesotherapy is this technique adapted for pigment problems.

The most studied active ingredient in this field is tranexamic acid. In medicine, tranexamic acid is used mainly to reduce bleeding. Because it has been reported to suppress pigment production, reduce inflammation and limit the formation of new blood vessels, it is also being tried in the treatment of pigmentation. It has been given by mouth, applied to the skin, injected into the skin and delivered with microneedling. It has been studied most in melasma, and in some countries it has been approved for this use (indication). For most other pigmentation disorders, however, it is still used off-label (outside the uses covered by the product's licence or approval).

There is also something you should know about the mesotherapy method itself. Although it is widely used in aesthetic dermatology, little is yet known about the details of the injections, their effectiveness and their side effects in melasma. There is also no internationally accepted, evidence-based standard for the different uses of mesotherapy. A set of international consensus guidelines, prepared to address this gap, stresses the need for high-quality research to continue.

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Melasma: Where Most of the Evidence Comes From

Most of the studies on pigmentation mesotherapy concern melasma. Melasma is a long-lasting pigment disorder that tends to recur; it usually appears as symmetrical brown patches on the face and mainly affects women. It has no single cause: ultraviolet rays from the sun, hormonal influences, structural changes in the skin, inflammation and the activity of mast cells (cells of the immune system) all play a part together.

Melasma is not a problem confined to the surface of the skin. Research has found changes in the deeper layer of affected skin (the dermis) as well: damage to the membrane that supports the upper skin from below (the basement membrane), pigment cells (melanocytes) dropping down towards the dermis, marked sun damage (solar elastosis), an increase in pigment-engulfing cells (melanophages) and mast cells, and the formation of new blood vessels. Besides its effect on pigment production, tranexamic acid has also been reported to act on inflammation and the formation of new blood vessels. This helps to explain why the medicine is being tried in a condition that also involves the dermis.

The diagnosis is made mainly by examining the skin; a Wood's lamp (an examination under a special light) and dermoscopy (examination with a skin magnifier) can support this assessment. According to an international consensus statement, treatment is chosen according to skin type, the depth of the pigment and the severity of the pigmentation. Not only the pigment cells but also the surrounding tissue, that is, connective tissue cells (fibroblasts), mast cells and blood vessels, should be taken into account. For this reason, in melasma, mesotherapy is seen not as a solution on its own but as one possible part of a broader plan.

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Sun Spots and Post-Inflammatory Hyperpigmentation

For sun spots and post-inflammatory hyperpigmentation, the data supporting injection treatments are clearly more limited than for melasma. Post-inflammatory hyperpigmentation is the darkening left behind after an inflammatory skin problem such as acne. For most pigmentation disorders other than melasma, such as post-inflammatory hyperpigmentation, tranexamic acid is still used off-label.

The international consensus statement treats pigmentation due to chronic sun damage, post-inflammatory hyperpigmentation, freckles (ephelides) and melasma as separate conditions, and bases treatment on the condition and the depth of the pigment. In everyday language they are all called ‘dark spots’, but the mechanisms behind them differ, and a result achieved in one cannot be carried over to another. There is one more important point about post-inflammatory hyperpigmentation: in studies of how to prevent it in darker skin, the only measure that consistently worked was sun protection.

The same warning applies whatever the type of pigmentation. Lentigo maligna and lentigo maligna melanoma are subtypes of melanoma (a type of skin cancer) that occur on facial and neck skin with long-term sun exposure. Because they resemble benign patches, they are difficult to diagnose early. Current data do not support the idea that examination with the naked eye or with devices can replace examination of a tissue sample (histopathology). A patch that is new, growing, or changing in colour or outline is not a cosmetic matter; it must be diagnosed first.

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Tranexamic Acid Injections: What Does the Evidence Say?

Randomised trials (trials in which participants are randomly assigned to groups) and meta-analyses (analyses that combine the results of several studies) have reported that tranexamic acid injected into the skin reduces melasma severity scores. However, the studies are small, their methods differ, and the results do not point in the same direction in every analysis.

In an analysis that combined 21 studies covering all routes of tranexamic acid use, treatment was associated with a reduction in the Melasma Area and Severity Index (MASI) and the melanin index. In studies looking only at injections into the skin (intradermal use), tranexamic acid given at different concentrations produced a significant improvement in melasma severity, and in some comparisons gave results similar to or better than established treatments. An analysis that combined a total of 184 patients from three randomised trials also found intradermal tranexamic acid to be associated with lower severity scores than a modified triple combination cream.

However, not every analysis reaches the same conclusion. In an analysis that grouped 28 randomised trials by route of use, tranexamic acid taken by mouth showed a significant difference compared with add-on treatment, whereas the intradermal route showed no significant difference at either week 8 or week 12. The researchers note that more data are still needed on the intradermal route and that the variation between studies is high. Another analysis, which assessed 358 participants in nine randomised trials, found the clearest improvement in the group that used tranexamic acid together with hydroquinone cream, and stressed the need for standard protocols and long-term studies.

Controlled studies paint a similar picture. In a randomised, double-blind trial in 34 women with darker skin (neither the patients nor the researchers knew which side received which treatment), tranexamic acid was applied to one half of the face and a placebo (a dummy treatment) to the other. The severity score fell more, and faster, on the tranexamic acid side, but there was no difference between the two sides in melanin and redness values measured with a device. The study was carried out at a single centre with a small group. In a non-randomised comparison of 60 patients, the severity score fell on the half of the face treated with tranexamic acid, while no significant change was seen on the half treated with saline.

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Injection, Microneedling or Oral: Does the Route Make a Difference?

Studies comparing the routes by which tranexamic acid is given do not paint a consistent picture. Most of the comparisons are based on small studies, and different analyses have reached different conclusions.

In a study in which 100 patients with melasma were randomly divided into two groups, tranexamic acid taken by mouth and tranexamic acid given into the skin by micro-injections were found to be similarly effective at the end of 12 weeks. In another randomised trial of 27 women, an assessor who did not know which side had received which treatment compared the two halves of the face. There was no difference in severity scores between micro-injections and microneedling (delivering the medicine into the skin with a device carrying many small needles). Patient satisfaction was higher on the microneedling side, but redness, flaking and swelling (oedema) were also significantly more common there.

In a pooled analysis of studies that used microneedling together with tranexamic acid, this combination showed no significant advantage over other treatments in overall clinical outcome; it was only found to be more effective than microneedling alone. Another analysis, reviewing randomised trials in which microneedling was used as an add-on treatment, reported that microneedling gave more marked results than micro-injections. When the active ingredients are compared, the picture is also unclear. In an analysis covering a total of 127 patients in five studies, there was no statistically significant difference between tranexamic acid and vitamin C given by mesotherapy in the change in severity score. In a quasi-experimental study (one in which participants were not randomly assigned to groups) of 110 patients, however, tranexamic acid mesotherapy was associated with a more marked reduction than vitamin C mesotherapy. In this study, a night-time pigmentation cream and a broad-spectrum sunscreen were added for both groups.

What this means in practice is that choosing a method is not just a matter of choosing an active ingredient and a route. In some of these studies, the injections were given not on their own but together with sun protection and a cream treatment, which makes it harder to attribute the result to a single method.

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Why Is Sun Protection the Foundation?

In melasma, strict sun protection is regarded not as an add-on to treatment but as its foundation. Current research clearly stresses that melasma needs to be tackled from several angles and that the foundation of this approach is strict protection from light. A consensus statement prepared by experts also recommends reducing known triggers and strict protection from light once the diagnosis has been made and the severity of the pigmentation has been assessed.

Protection is not limited to ultraviolet rays. Standard UVB/UVA protection alone may not be enough; long-wavelength UVA1 and blue light can also trigger pigmentation, especially in darker skin. This is where tinted sunscreens containing iron oxide stand out: they are reported to protect against visible light, to be a cosmetically acceptable option and to improve clinical outcomes in melasma.

There is also a real-life caveat: differences in the amount applied reduce the protective effect observed, and research under real-world conditions is needed. A sunscreen that is not used, or is applied too sparingly, does not give the expected protection. So when you are considering pigmentation mesotherapy, whether sun protection is part of the plan is at least as important a question as the injections themselves.

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Does Pigmentation Come Back?

Yes, it can. Melasma is a long-lasting, recurring condition. If pigmentation that has faded with treatment returns over time, this is considered part of the expected course of the condition.

The persistent, recurring nature of melasma makes treatment difficult. After laser and light-based treatments, which are considered in more severe cases, pigmentation can return within 3–6 months. Discussing expectations, the likelihood of recurrence and side effects with you individually is also considered an essential part of treatment. According to research, melasma usually responds only to a limited degree despite the many treatment options, and the recurrence rate is high.

Long-term recurrence data for injected tranexamic acid are limited. In studies of intradermal use, the recurrence rate at one of the concentrations used was lower than with laser treatment. In a randomised trial comparing the medicine taken by mouth with injections, pigmentation reappeared in two patients in the oral treatment group at week 24. These studies have short follow-up periods and are few in number; they are not enough to draw a general conclusion about how long results last.

A consensus statement prepared by experts recommends continuing cream treatment and strict protection from light after improvement has been achieved, to reduce the risk of recurrence. So the real question is not whether the job is done once the pigmentation has faded, but how to maintain the improvement.

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Limits of This Treatment

Pigmentation mesotherapy does not remove pigmentation permanently, does not eliminate triggers and is not a substitute for sun protection. Most of the scientific data relate to melasma; even there, the studies are small, protocols differ and long-term data are limited.

Little is known about the injection details, effectiveness and side effects of mesotherapy in melasma. In an analysis that grouped studies by route of use, intradermal tranexamic acid showed no significant difference compared with add-on treatment. According to another analysis of injected tranexamic acid, the best concentration, route and combination are still unclear; standard protocols and long-term studies are needed.

Part of melasma lies in the deeper layer of the skin (the dermis). Research has shown that in this layer the membrane supporting the upper skin is damaged, pigment cells drop down into the dermis and there are changes in the blood vessels. The international consensus statement also links the choice of treatment to the depth of the pigment. Research shows that melasma usually responds only to a limited degree despite the many treatment options; so the same response should not be expected from every patch.

In melasma, especially in more severe cases, other options such as laser and light-based treatments may also be considered; these are separate from pigmentation mesotherapy. This information is given not to discourage you but so that you can compare the options. Having no treatment at all is also a valid decision.

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Mixtures and Skin-Lightening Injections

Not all the substances used for pigmentation have the same level of evidence. Data on substances other than tranexamic acid are more limited, and treatments given into a vein (intravenously) are not the same as mesotherapy.

Little is known about the injection details, effectiveness and side effects of the various anti-pigmentation substances given by mesotherapy in melasma. The international consensus guidelines on mesotherapy also stress that the field needs to move from practice based on personal beliefs to evidence-based practice. If you are offered a mixture, the substances it contains and how much evidence there is behind each one are questions to ask before the treatment.

Among the treatments known as skin-lightening injections, glutathione stands out. When it is taken by mouth, significant but variable reductions in melanin levels have been reported, and forms applied to the skin have also been reported to reduce melanin. Glutathione given into a vein, however, is associated with safety concerns such as a severe allergic reaction (anaphylaxis) and liver damage, and there is no standard dosing protocol for this use. Until its long-term safety and the appropriate dose have been established, caution is advised, especially with intravenous use. This intravenous treatment should not be confused with mesotherapy, which is given into the skin.

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Known Risks

In studies of injected tranexamic acid, the reported side effects are mostly mild and temporary. They include pain, redness, swelling and a burning sensation at the injection site. The analysis covering all routes of use also found side effects to be mild; a small number of people reported stomach and bowel complaints, less frequent periods, lightening of the skin, hives and skin irritation.

Treatment for pigmentation can itself leave a new patch. In the randomised trial comparing micro-injections with microneedling, one patient developed post-inflammatory hyperpigmentation. A case report described permanent, mottled pigment patches spreading over the whole face after mesotherapy. In darker skin, the only measure shown to consistently help reduce the risk of such patches is sun protection; however, most of the cases in the research behind this conclusion developed after laser treatments.

Two rare but serious risks are infection and granulomas (inflammatory lumps that form in the skin). A review of non-tuberculous mycobacterial (NTM) infections linked to mesotherapy assessed 423 patients from 30 publications. These infections have been linked to injections contaminated with germs from the environment. Treatment could take weeks, more than one antibiotic was often needed, and healing could leave scars. These cases were mostly reported on the abdomen, buttocks and thighs. A case series of six patients also reported granuloma reactions after mesotherapy that were not caused by infection.

Tranexamic acid is a medicine that affects the blood's clotting balance and is used to reduce bleeding. An analysis of a database of reported drug side effects found a significant signal linking tranexamic acid with blood clots forming in the veins. This analysis covers all forms of use of the medicine and does not establish cause and effect. Before the procedure, you will be asked about blood thinners and antiplatelet medicines (which stop blood platelets clumping together), and about supplements that can affect bleeding. Do not stop any prescribed medicine on your own. If needed, the procedure is planned or postponed after consulting the relevant doctor.

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