Confluent hyperpigmented macules in a malar distribution.
Melasma is an acquired hyperpigmentation of sun-exposed areas. Melasma presents as symmetrically distributed hyperpigmented macules, which can be confluent, reticulated or punctate. Areas that receive excessive sun exposure, including the cheeks, the upper lip, the chin, and the forehead, are the most common locations; however, melasma can occasionally occur in other sun-exposed locations.
Chloasma is a synonymous term sometimes used to describe the occurrence of melasma during pregnancy. Chloasma is derived from the Greek word chloazein, meaning "to be green." Melas, also Greek, means "black." Because the pigmentation is never green in appearance, melasma is the preferred term.
See Diagnosing Dermatoses in Pregnant Patients: 8 Cases to Test Your Skills, a Critical Images slideshow, for help identifying several types of cutaneous eruptions associated with pregnancy.
The pathophysiology of melasma is multifactorial and not entirely characterized. A direct relationship with female hormonal activity appears to be present, because melasma occurs more frequently in females than in males and commonly develops or worsens during pregnancy and with the use of oral contraceptive pills. Indeed, one half of melasma cases present initially during pregnancy. Additionally, the expression of estrogen receptors appears to be up-regulated in melasma lesions.[1] Whether hormone levels play a role in male melasma development is still a topic of debate. Other factors implicated in the pathogenesis of melasma are photosensitizing medications, mild ovarian dysfunction, and certain cosmetics. An exogenous form of melasma known as ochronosis is very frequently caused by specific implicated medications. There is clearly some role for genetic predisposition as well, as family history of melasma is known to be an important risk factor for its development. Somewhere in the range of 55-64% of patients with melasma have a family history of this condition.[2]
The most important factor in the development of melasma is exposure to sunlight. UV light induces production of reactive oxygen species in the skin, which subsequently promotes melanogenesis.[3] Ultraviolet (UV) radiation is also known to induce increased production of alpha-melanocyte–stimulating hormone and corticotropin, as well as interleukin 1 and endothelin 1, all of which contribute to increased melanin production by intraepidermal melanocytes. Fibroblasts located in the dermal layer of the skin may also contribute to the development of melasma; overexpression of the tyrosine kinase receptor c-kit and certain stem cell factors have been identified in melasma lesions, and these are believed to increase melanogenesis.[4] Without the strict avoidance of sunlight, potentially successful treatments for melasma are doomed to fail.
A genetic predisposition is a major factor in the development of melasma. Melasma is much more common in women than in men. Persons with light-brown skin types from regions of the world with intense sun exposure are much more prone to the development of melasma. . In a global study of 324 women with melasma, 48% reported a positive family history of the condition.[5] Identical twins have been reported to develop melasma,[6] while other siblings under similar conditions did not.
Another major factor in melasma is exposure to sunlight. Ultraviolet radiation can cause peroxidation of lipids in cellular membranes, leading to generation of free radicals, which could stimulate melanocytes to produce excess melanin. Sunscreens that primarily block UV-B radiation (290-320 nm) are unsatisfactory because longer wavelengths (UV-A and visible radiation, 320-700 nm) also stimulate melanocytes to produce melanin. It has been demonstrated that light in the visible spectrum (415 nm) can cause increased pigmentation that is present in the skin for several months after development.[7]
Hormonal influences play a role in many individuals. The exact mechanism by which pregnancy affects melasma is unknown. Estrogen, progesterone, and melanocyte-stimulating hormone (MSH) levels are normally increased during the third trimester of pregnancy. Nulliparous patients with melasma have no increased levels of estrogen or MSH, but they may show elevated levels of estrogen receptors within lesions. In addition, the occurrence of melasma with estrogen- and progesterone-containing oral contraceptive pills and diethylstilbestrol treatment for prostate cancer has been reported.[8] The observation that postmenopausal woman who are given progesterone develop melasma, while those who are given only estrogen do not, implicates progesterone as playing a critical role in the development of melasma.
A case report of two women who developed melasma after sudden and profound emotional stress implicated the release of MSH by the hypothalamus as a cause. Additionally, one study demonstrated an association between the development of melasma and the presence of melanocytic nevi and lentiginous nevi; patients with melasma showed a significantly higher number of both types of nevi than a control population. This would indicate a relationship between the development of melasma and the overall presence of pigmentation.[9]
Exactly which hormones and what mechanisms are involved in the development of melasma are yet to be determined. Genetic and hormonal influences in combination with ultraviolet radiation are the two most important causes of melasma, yet phototoxic and photoallergic medications and certain cosmetics have been reported to cause melasma in rare instances.
Melasma is very common, affecting over 5 million people in the United States.[10] Prevalence rates range from 8.8% among females of Latino descent living in the southern United States, to 13.4-15.5% seen in a population of Arab-Americans living in the state of Michigan, to up to 40% in some females of southeast Asian populations.[11, 12, 13]
Persons of any race can be affected by melasma. However, melasma is much more common in constitutionally darker skin types than in lighter skin types, and it may be more common in light brown skin types, especially Latinos and Asians, from areas of the world with intense sun exposure.
Melasma is much more common in women than in men. Although the generally accepted ratio is approximately 9:1 females to males, a 2014 multicenter study of 953 patients from Brazil found a female-to-male ratio closer to 39:1.[14] When men are affected, the clinical and histologic picture is identical.
Melasma is rare before puberty and most commonly occurs in women during their reproductive years. Melasma is present in 15-50% of pregnant patients.
Melasma has no associated mortality or morbidity. There have been no reported cases of malignant transformation, and it has not been associated with an increased risk of melanoma or other malignancies. In fact, it is generally accepted that patients with melasma are considered to be at decreased risk for melanoma. This is likely secondary to lower rates of skin malignancies in patients with a dark complexion.
Dermal pigment may take longer to resolve than epidermal pigment because no effective therapy is capable of removing dermal pigment. However, treatment should not be withheld simply because of a preponderance of dermal pigment. The source of the dermal pigment is the epidermis, and, if epidermal melanogenesis can be inhibited for long periods, the dermal pigment will not replenish and will slowly resolve.
Resistant cases or recurrences of melasma occur often and are certain if strict avoidance of sunlight is not rigidly heeded.
Strict sun avoidance is essential for resolution and to prevent recurrence of melasma. Patients with melasma should apply bleaching creams to areas of darkening only. Resolution with strict sun avoidance and topical bleaching creams can take months; caution patients to expect slow but gradual lightening. Additionally, only bleaching creams that are medically approved should be used, as creams with high concentrations of bleaching agents can lead to paradoxical hyperpigmentation if overused or abused. Additionally, all bleaching agents should be used for no more than 3 months continuously and then discontinued for a window of time to avoid hyperpigmentation. An alternative program of every other day use is sometimes used and may be appropriate. In any case, patients should be cautioned to discontinue the agent and seek follow up if they note hyperpigmentation in the setting of strict sun avoidance.
Patients may inquire about progressive hyperpigmentation of the face, which may be temporally related to pregnancy or to the use of oral contraceptive pills. In the vast majority of cases, it is asymptomatic.
Some patients may report extrafacial melasma, but this very rarely presents in isolation and usually patients also exhibit findings on their sun-exposed face.
Intense or long-term exposure to sunlight worsens the condition and may precipitate melasma, but because the development of pigmentation is often insidious, patients may not recognize the association.
The macular hyperpigmentation of melasma is commonly tan to brown. Blue or black may be evident in patients with dermal melasma. The distribution is one of three patterns. Centrofacial involves the forehead, cheeks, nose, upper lip, and chin. Malar involves solely the nose and the cheeks. Mandibular affects the ramus of the mandible. It is unclear why certain characteristic areas of the face are most commonly involved, but it is believed that sebaceous gland density and activity in these regions may be involved. A rare pattern confined to the forearms is seen in women receiving exogenous progesterone and in Native Americans.
The excess melanin can be visually localized to the epidermis or the dermis by use of a Wood lamp (wavelength, 340-400 nm). Epidermal pigment is enhanced during examination with a Wood light and generally appears well-circumscribed with accentuation of borders. Dermal melanosis, on the other hand, tends to be less well-defined. Clinically, a large amount of dermal melanin is suspected if the hyperpigmentation is bluish black. In individuals with dark-brown skin, examination with a Wood light does not localize pigment, and these patients are thus classified as indeterminate.
Dermoscopy can also play a key role in the diagnosis of melasma and in identifying the level of pigment deposition. Dermoscopy findings include prominent vascularity and telangiectasias, accentuation of the pseudoreticular pigmentary network, and pigment structures including owl's eye structures. Dermoscopy may also be used for assessing melasma severity.[15]
The Melasma Area and Severity Index (MASI) is a common outcome measure that is validated as a tool to measure facial hyperpigmentation. It takes into account an area-weighted pigmentation score and pigment homogeneity across the cheeks, chin, and forehead.[16] It has now been correlated to the Melasma Severity Score, a global score incorporating patient assessment of their condition with rater's objective assessment. These tools are mainly used as objective measures in clinical trials.
There are no known medical complications associated with melasma. It does not carry an increased risk of melanoma or nonmelanoma skin cancers.
The psychosocial burden of melasma can be an important consideration for many patients. Patients are often quite displeased or distressed with the appearance of melasma and can become frustrated by the challenges of treatment and its tendency to recur if strict preventive measures are not used. Self-image and self-esteem may suffer as a result of this condition. Physicians should be cognizant of this component of evaluating and treating patients with melasma. The Melasma Quality of Life Scale (MelasQOL) is a validated tool to provide quantification of melasma’s impact on a patient's quality of life.[17] The results do not correlate with the MASI score referenced earlier.
Melasma is almost invariably a clinical diagnosis and does not require any type of skin biopsy or laboratory workup. If the diagnosis is in question, ruling out other conditions based on the patient's history and physical examination should be the initial approach.
Biopsy can be considered to confirm a diagnosis or to support a suspected diagnosis if the presentation is atypical or diagnosis is unclear.
Usually, no laboratory tests are indicated for melasma. Some studies have suggested mild abnormalities in thyroid function are associated with melasma, specifically pregnancy- or oral contraceptive pill–associated melasma; as such, it is reasonable to consider checking thyroid function tests. Wood lamp examination usually helps to localize the pigment to the epidermis or the dermis. Note that in many cases, the pigment is found in both locations.[18]
Melanin is increased in the epidermis, in the dermis, or (most commonly) in both locations in melasma patients. Epidermal melanin is found in keratinocytes in the basal and suprabasal area. In most cases, the number of melanocytes is not increased, yet the melanocytes that are present are larger, more dendritic, and more active. Dermal melanin is found in the superficial and mid dermis within macrophages, which often congregate around small, dilated vessels. Inflammation is sparse or absent.
Melasma is notoriously difficult to treat. The pigment of melasma develops gradually, and resolution is also gradual. Resistant cases or recurrences of melasma occur often and are certain if strict avoidance of sunlight is not rigidly heeded.[19] All wavelengths of sunlight, including the visible spectrum, are capable of inducing melasma. The most commonly accepted treatment remains strict sun avoidance often in combination with a topical combination hydroquinine cream. Limiting exposure to exogenous estrogens can play a critical role as well in exposed patients. A chemical peel or laser treatment may help in about a third of cases, a third of cases remain the same, and another third show hyperpigmentation.[20]
Prophylactic management is often the most effective means of prevention. Avoidance of sun exposure and use of broad-spectrum, high-SPF sunscreens (50+) in combination with a physical blocking agent (if not included) can prevent or slow the development of melasma. In one study of 200 Moroccan women who applied SPF-50+ sunscreen daily during pregnancy, less than 3% developed melasma. Although the study did not include its own control arm, this is well below the established rates of development in pregnancy (15-50%).[21]
The role of oral contraceptives in the development of melasma has been clearly defined, especially in women without a family history of the condition. Therefore, discontinuation of these medications and avoidance of oral contraceptive pills in the future is recommended when possible in women who have onset of melasma after starting these drugs.
The mainstay of treatment for melasma remains topical depigmenting agents. Hydroquinone (HQ) is a classic and commonly used first-line agent, both alone and when combined with other agents. It is a hydroxyphenolic chemical that inhibits tyrosinase, the enzyme that converts L-tyrosine to L-DOPA and the rate-limiting step in the pathway of melanin synthesis. Additionally, cytotoxic metabolites may cause interference with melanocyte function and viability. HQ can be applied in cream form or as an alcohol-based solution.
Concentrations vary from a 2% concentration available in the United States without a prescription to a standard 4% concentration and even higher when compounded. Efficacy is directly linked to concentration, but the incidence of adverse effects also increases with concentration. All concentrations can lead to skin irritation, phototoxic reactions with secondary postinflammatory hyperpigmentation, and irreversible exogenous ochronosis (reported even with long-term use of 2% HQ). Special care must be taken not to prescribe the monobenzyl ether of HQ (Benoquin), which causes an irreversible localized and generalized vitiligolike leukoderma. Outside the United States, topical creams with concentrations as high as 8% are available over the counter. These agents are associated with much higher rates of exogenous ochronosis and should not be used.
In recent years, concerns have been raised about the potential carcinogenic properties of HQ. This is based on the observation that hepatic metabolism of this agent results in the production of benzene derivatives during hepatic metabolism. In the case of topical application of HQ, this does not appear to be a concern, as the vast majority of metabolism of topically applied HQ is metabolized in the vascular system and renally excreted.[22] This knowledge has led to concern that free-radical metabolites could induce acute or chronic kidney injury; however, no association has been demonstrated in the 50+ year history of HQ’s use as a topical solution.[23] To date, all concerns regarding HQ’s potential toxic effect are considered speculative.
The use of topical retinoids (trans-retinoic-acid) can be effective as monotherapy. These agents are derivatives of vitamin A and lead to increased keratinocyte turnover and decreased melanocyte activity. They also increase the permeability of the epidermis, allowing for better penetration of adjunct therapies.[24, 25] Care must be taken with these agents, however, as retinoids are known teratogens. It is essential to avoid prescribing systemic retinoid therapy to pregnant patients or patients attempting to become pregnant. Additionally, although there is no evidence that topical retinoids are associated with congenital malformations, pregnant patients should be counseled concerning the risks and benefits of treatment for a cosmetic condition. The response to treatment with topical retinoids is also less than that with HQ and can be slow, with improvement frequently taking 6 months or longer.
Owing to tretinoin’s ability to increase the effectiveness of other therapies, combinations of tretinoin with HQ, with or without a topical corticosteroid, have been promoted.[24] In fact, the only topical ointment currently approved by the US Food and Drug Administration (FDA) for the treatment of melasma is a triple-combination cream, a composite of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Tri-Luma). Comparative studies of the effectiveness of the triple-combination cream versus topical HQ suggest that the combination cream is faster and more effective at reducing melasma pigmentation, but it does carry a slightly increased risk of an adverse reaction.[26] A 2010 study found that the triple-combination cream is safe and effective when used intermittently or continuously for up to 24 weeks.[27]
The major adverse effect of tretinoin is mild skin irritation, especially when the more effective, higher concentrations are used. Temporary photosensitivity and paradoxical hyperpigmentation can also occur. Tretinoin is believed to work by increasing keratinocyte turnover, thus limiting the transfer of melanosomes to keratinocytes. Adapalene is a synthetic retinoid analog that may be an alternative to tretinoin. A study in Asian Indian patients compared adapalene 0.1% topical to 0.05% tretinoin. After 14 weeks, reduction in MASI scores were equivalent between the two therapies, while the adapalene group developed fewer adverse effects and reported better tolerance to the therapy.[28]
Azelaic acid, available as a 20% cream-based formulation, appears to be an effective alternative to 4% HQ and may be superior to 2% HQ in the treatment of melasma.[29, 30] The mechanism of action is similar to that of HQ, but, unlike HQ, azelaic acid seems to target only hyperactive melanocytes and thus will not lighten skin with normally functioning melanocytes. The primary adverse effect is skin irritation. No phototoxic or photoallergic reactions have been reported. One benefit of azelaic acid is that it may be used in pregnancy. Other depigmenting agents that have been studied in the treatment of melasma are 4-N -butylresorcinol, phenolic-thioether, 4-isopropylcatechol, kojic acid, and ascorbic acid.[31, 32]
In an attempt to search for a new treatment for melasma, Wu et al studied oral administration of tranexamic acid (TXA) in Chinese patients. TXA tablets were prescribed to 74 patients at a dosage of 250 mg twice daily for 6 months. At follow-up, more than half the patients (54%) showed good results.[33] A 2018 review article examining the use of TXA in melasma determined that it is a safe and efficacious treatment modality for refractory melasma and may be administered in low doses over short periods and still demonstrate effect.[34] It is easy to administer with few and mild adverse effects, including nasal and sinus discomfort, musculoskeletal and back pain, abdominal pain, and oligomenorrhea. The most important adverse event to consider is a potential for increased thromboembolic events in at-risk populations; although data analysis does not show an increased risk of thrombosis—and surveillance of patients treated with TXA for menorrhagia has not demonstrated any serious adverse events—patients should be screened for contraindications to the use of TXA and for risk factors for thromboembolic events prior to starting therapy.
The use of Polypodium leucotomos extract (PLE) has been evaluated in recent years as well. This is a South American fern extract that is available over the counter with a demonstrated effect on the cutaneous minimal erythematous dose of UV light. It is used for the prevention of many light-sensitive conditions. Several small double-blinded randomized controlled trials have demonstrated that the addition of PLE to a regimen of sun avoidance, sun protection, and use of hydroquinone may improve MASI and MELASQoL scores.[35, 36]
It has been suggested that taking an oral proanthocyanidin (a class of flavonols) along with a vitamin regimen may significantly reduce pigmentation. At this time, the mechanism for this treatment method is not fully understood. Significantly more study is necessary before this method of treatment could be deemed effective. One major benefit to this mode, however, is that the use of proanthocyanidin is a natural treatment method, and it is a safe alternative in patients who exhibit a moderate or severe adverse reaction to a topical treatment.[37]
Quick fixes with destructive modalities (eg, chemical peels, lasers) yield unpredictable results and are associated with a number of potential adverse effects, including epidermal necrosis, postinflammatory hyperpigmentation, and hypertrophic scars.[38, 39] As such, they are considered second-line therapies, to be used after management with topical medications has failed. The precise manner in which these modalities can be used has not been fully delineated. However, in some experienced hands, they have been anecdotally reported to be safe and effective and to produce results much quicker than topical medications.
Superficial skin peels maybe effective and safe, but they do carry some risk of adverse outcomes. These peels use glycolic or salicylic acid–based compounds and are thought to hasten turnover of hyperpigmented keratinocytes. They are often titrated up slowly, applied first on a monthly basis and with low concentration formulas (20%) and progressing to weekly applications with higher concentrations. Lightening agents are usually used in conjunction with superficial peels for best results. Skin peels do carry risk, however, and should only be used after a trial of therapy with at least one skin-lightening agent. Close monitoring for skin dyspigmentation must be a primary consideration, and therapy should be halted if alterations in the patient’s pigmentation in the surrounding skin are noted.
The efficacy of lasers for the treatment of melasma is unclear and is often associated with equivocal or undesired cosmetic results. Their use should be considered in cases of extensive disease that is refractory to alternative modalities. Q-switched ruby laser treatment has been demonstrated to show no benefit for melasma and actually worsens the condition, especially in those with darker skin phototypes (Fitzpatrick IV to VI).[20] Manaloto et al tested erbium:YAG laser therapy in 10 melasma patients with refractory melasma and found no improvement in skin pigmentation, with the adverse effect of postinflammatory hyperpigmentation by 3-6 weeks post procedure, despite administration of oral steroids.[40] Given the adverse effects and need to administer systemic corticosteroid therapy, the risks seem to clearly outweigh the benefits.
Fractional resurfacing is another option within laser therapy that does not cause full-thickness epidermal burns. As such, it has reduced levels of postprocedure inflammation and, theoretically, dyspigmentation. A small study by Rokshar and Fitzpatrick showed promising results in 10 patients treated with fractionated laser for 4-6 sessions spread 1-2 weeks apart. They found a 75-100% clearing of melasma, with only one case of postinflammatory dyspigmentation.[41] However, follow-up studies were unable to reproduce these results and recommended against fractional ablative laser as a routine treatment modality for patients with melasma.[42]
Another study compared topical treatment with triple topical therapy with nonablative fractional laser therapy.[43] Both treatments were somewhat beneficial. However, the study did not clearly identify patients who experienced flare ups after the laser therapy. Typically, reactive hyperpigmentation develops in around a third of the cases, especially in patients with dark complexions. Patients must be warned of the potential for a flare-up. Absolute light avoidance is necessary; thus, a good sunscreen must be used during the day, even when inside.
Regardless of the treatments used, all will fail if sunlight is not strictly avoided. Prudent measures to avoid sun exposure include hats and other forms of shade combined with the application of a broad-spectrum sunscreen at least daily. UV-B, UV-A, and visible light are all capable of stimulating melanogenesis. Sunscreens containing physical blockers, such as titanium dioxide and zinc oxide, are preferred over chemical blockers because of their broader protection. Makeups containing zinc oxide or titanium dioxide can serve the dual purpose of covering melasma lesions that patients believe are unsightly, while also serving as protective and preventative therapy. In addition, patients should be forewarned that resolution is gradual and may take many months.
The major complications stemming from treatment of melasma is inflammation-associated hyperpigmentation. For this reason, all treatments must be carefully weighed to consider the risk of generating increasing hyperpigmentation if too aggressive or destructive of a treatment modality is used. Prolonged exogenous use of bleaching agents can also result in hyperpigmentation if used to aggressively or at unsafe concentrations. Patients should be appropriately counseled about the risk of hyperpigmentation that may occur with many of the commonly used melasma treatments.
Strict sun protection is the cornerstone of all melasma treatment plans. Success or failure often relys on patient compliance with recommendations for sun avoidance.
Management of melasma is challenging and treatment is often long-term, with potential for relapse or worsening of disease as a result of external factors.
Be aware of conditions or medications that may induce or exacerbate melasma, including medications the patient may be using for this purpose.[44]
The use of regular broad-spectrum and physical blocker sunscreens is effective for prevention of melasma and enhances the efficacy of therapies used in treatment.
Camouflage makeup can be an effective tool for managing melasma.
Hydroquinone, a tyrosinase inhibitor, is a safe and effective tool for treating disorders of hyperpigmentation. A combination hydroquinone, retinoid, and topical corticosteroid is frequently very effective treatment for melasma when used appropriately.
Tretinoin is a second-line topical agent for melasma. It may be effective but has the potential to cause skin irritation and often requires months of treatment before benefit is realized.
Tranexamic acid is an effective oral therapy for melasma that offers modest benefit with minimal adverse effects and is safe for use as long as patients are appropriately screened for risk factors prior to starting therapy.
Glycolic acid peels may be the most efficacious peeling agent for melasma, but they should be used with caution.
Q-switched ruby and erbium:yttrium-aluminum-garnet lasers are known to worsen melasma.
Fractional resurfacing laser is approved by the US Food and Drug Administration for melasma and has been shown to afford some benefit in a subset of patients.[45]
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Clinical Context: Hydroquinone produces reversible depigmentation of skin by inhibiting enzymatic oxidation of tyrosine to 3-(3,4-dihydroxyphenyl-alanine [dopa]) and suppression of other melanocyte metabolic processes. Exposure to sunlight or UV light causes repigmentation, which may be prevented by the broad-spectrum sunscreen agents contained in this product.
Clinical Context: Brand names include Alphaquin HP, Alustra, Eldopaque, Eldopaque Forte, Eldoquin, Eldoquin Forte, Esoterica, Esoterica Sensitive Skin, Glyquin, Glyquin-XM, Lustra, Melanex, Melanol, Melpaque HP, Melquin HP, Melquin-3, Nuquin HP, Solaquin, Solaquin Forte, and Viquin Forte. Hydroquinone suppresses melanocyte metabolic processes, especially enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylamine. Exposure to sun reverses effects and causes repigmentation. It lightens healthy and hyperpigmented skin.
Clinical Context: Azelaic acid may decrease microcomedo formation. It may have a bleaching effect on skin. It may also have an antimicrobial effect.
These agents inhibit DNA synthesis and mitochondrial enzymes to interrupt hyperactive melanocytes. Normally functioning melanocytes are not inhibited.
Clinical Context: Topical tretinoin inhibits microcomedo formation and eliminates lesions. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. Dosage formulations include 0.025%, 0.05%, and 0.1% cream; 0.01%, 0.025%, and 0.1% gel; and 0.05% solution.
Clinical Context: Adapalene binds to specific retinoic-acid nuclear receptors and modulates cellular differentiation, keratinization, and inflammatory processes.
Clinical Context: Tranexamic acid oral is an antifibrinolytic; it is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure.
Confluent hyperpigmented macules in a malar distribution.
Melasma in a man.
