Introduction:
Melasma is a very common complaint presented to Dermatologists and Cosmetologists in India where obsession for white color is phenomenal.
Melasma is a chronic acquired bilaterally symmetrical, circumscribed hyperpigmentation of the face.
Pathogenesis of melasma is not yet clear and it has a very high rate of recurrence. These two factors pose a challenging problem to treating clinician. Lack of safe and highly effective treatment and high rate of recurrence is clearly reflected by new brand or formulation of depigmenting cream introduced on day to day basis in the market.
It has highest prevalence in 3rdand 4th decade in women and in Fitzpatrick skin type III to V. However it can also be seen in 26% men as reported in an Indian study.
Etiology:
The most important risk factor is Sun Exposure (UV Radiation) in a genetically susceptible individual.
The other factors are Pregnancy, Oral Contraceptive Pills, Hormonal Imbalance, and other drugs like Phenytoin and Spironolactone.
Clinical Features:
Melasma is classified in various ways.
It can be classified on the basis of level of pigment distribution as Epidermal, Dermal and Mixed. However the consensus of opinion is there is no clear distinction and almost all the cases fall in the category of Mixed pattern.
The anatomical classification is Centrofacial(63%), Malar(21%0 and mandibular(10%) pattern.
In India, the malar pattern (23%) is most often seen.
Before we discuss various therapeutic strategies, let us understand the newer insights in the study of pigmentation and their therapeutic repercussions.
Melanogenesis:
Melanogenesis implies the conversion of Tyrosine to Dopaquinone in a two-step reaction controlled by enzyme tyrosinase. Melanin biosynthesis occurs in organelles situated in the melanocytes. These melanosomes are then transferred to keratinocytes and impart the color to skin. Pigmentation is a complex process regulated by various intrinsic and extrinsic factors. The intrinsic factors are hormones like MSH, ACTH and corticosteroids. Various other cellular factors are endorphins, endothelins, prostaglandin and stem cell factor.
Ultraviolet rays are the major extrinsic factor in regulating pigmentation.
Ultraviolet rays induced pigmentation is mediated through keratinocytes and fibroblasts. UV Rays induce melanogenic factor in both these cells and stimulate melanosome transfer and distribution within keratinocytes.
Refer to the diagrammatic representation of Melanogensis
In melisma, number of melanocytes remains the same. However, there is increase in deposition of melanin in the epidermis due to hyperactive melanocytes. Melasma skin also shows features of photodamage like solar elastosis, collagen degeneration and increased vascularity. Affected skin also shows defective barrier function.
Knowledge of these pathophysiological changes can help us device better treatment strategy.
Target of therapy for Melasma is
1) to prevent formation of melanin
2) to reduce the transfer of melanosomes to keratinocytes
3) to destroy melanosomes/melanosome laden keratinocytes
Treatment strategy:
1) To find out the underlying cause and treat or avoid it. Measurement of endocrine parameters have shown elevated levels of leutinizing hormone and decreased levels of estradiol suggesting mild subclinical ovarian dysfunction. Therefore hormonal evaluation in case of persistent melasma becomes important.
2) Sun Protection: is the main therapeutic component and counseling the patient for total sun protection is the most effective therapeutic approach.
3) Antioxidants: have an important role to play. Chronic sun exposure causes inflammation and damage to keratinocytes which in turn stimulate melanin synthesis as a protective measure.
4) Bleaching agents: Many bleaching agents are available and newer ones are entering the market as they form the main stay of treatment. However, evidence based drug still remains Hydroquinone. It inhibits the enzyme tyrosinase. The other molecules in this category are KojicAcid, Tetrahydrocurcumin, arbutin, liquorice and many more.
5 ) Retinoids have dual mode of action. They act by inhibiting the tyrosinase and increase epidermal cell turnover, thus eliminating melanin containing keratinocytes.
6) Azelaic Acid : also has dual mode of action. It inhibits tyrosinase and has toxic effect on melanocytes.
In order to get better results and reduce the adverse effects, all these drugs are used in combinations.
Oral Treatment:
Tranexamic Acid is a new entrant in this field of depigmenting agents.
It (trans-4-aminomethylcyclonexane carboxylic acid) is a synthetic derivative of amino acid Lysine. It is used as a hemostatic agent in surgical field and in menorrhagia due to its fibrinolytic action.
Njor in 1979, first studied and reported the action of TXA on melasma.
It has a novel and different mode of action than the drugs used so far.
Mode of action of TXA
Following UV exposure, there is an increase in melanosomes, their melanin content and their transfer to keratinocytes. UV exposure stimulated keratinocyte In turn stimulates melanin synthesis as shown in the diagram.
TXA down regulates the conversion of plasminogen to plasmin, by attaching to the lysine binding system of plasminogen. This step down regulates the synthesis of melanin.
TXA also reduces vascularization, and therefore, proves useful in melasma.
Various clinical studies have been conducted to determine the effective dose.
Suggested dose of TXA is 250 mg two to three times a day. This dose is much lower than the hemostatic dose. It is the duration of the treatment and not the dose, which makes the treatment effective.
One study done on 260 patients suggested the dose of 250 mg for three months.
Adverse Reactions: Venous thromboembolism, Myocardial Infarct, Cerebrovascular Accidents and pulmonary embolism
Contraindications: Defective Color vision and Hypersensitivity to TXA.
Proper patient selection and ruling out potential risk factors resulting in hyper coagulability is essential.
Considering the safety profile, low rate adverse reactions and effectivity Tranexamic acid can prove useful in treatment of Melasma in combination with other local therapy.
References:
1. Manoj k tembhre,SomeshGupta,StepheneCommo.Physiology of Pigmentation:New Biological Concepts associated with Skin and Hair pigmentation. In: Modern Cosmetic Dermatology (1stEdn). New Delhi:JaypeeBrothers Medical Publishers 2015; 62-71
2. HurleyME,GueveraIL,GonzalesRM,etal.Efficacy of glycolic acid peels in the treatment of melasma.Arch Dermatol.2002;138:1578-82.
3. TseTW,Hui E. Tranexamic acid: an important adjuvant in the treatment of melisma.CosmetDermatol. 2013;12:57-66
4. Leslie Baumann,InjaBogdanAllermann.Depigmenting Agents. In : Cosmetic Dermatology Principles and Practice(2ndEdn). New York: Macgraw-Hill Medical publishing Division; 2009;279-292
5. GodseKV,SakhiaJ. Triple combination and glycolic acid peels in melisma in Indian patients.JCosmet Dermatol.2011;10:68-9.
6. KarnD,KC S, AmatyaA,et al .Oral Tranexamic Acid for the Treatment of Melasma.kathmanduUniv med J 2012;10(4): 40-43
7. Cho HH,ChoiM,ChoS,etal.Role of oral Tranaxemic acid in melisma patients treated with IPL and low fluence QS Nd:YAGlaser.JDermatolog Treat.2013;24:292-6
8. TseTW ,Hui E, Tranexamic acid an important adjuvant in the treatment of melasma.CosmeDermatol. 2013;12:57-66
