Postinflammatory hyperpigmentation

INTRODUCTION — Postinflammatory hyperpigmentation (PIH), also known as postinflammatory melanosis, is a reactive hypermelanosis of the skin that occurs as a sequela of cutaneous inflammation (picture 1A-I) [1]. Common causes of PIH include acne vulgaris, eczematous dermatoses, and burn injury. PIH is a frustrating problem that can have a strong psychologic toll on affected patients.

The pathogenesis, diagnosis, and treatment of PIH will be reviewed here. Other causes of cutaneous hyperpigmentation are reviewed separately. (See "Acquired hyperpigmentation disorders".)

EPIDEMIOLOGY — Postinflammatory hyperpigmentation (PIH) is a common disorder that can occur at any age and has an equivalent incidence in males and females. Although PIH may occur regardless of skin color, risk for clinically significant PIH increases with darkening skin pigmentation.

Skin phototype, a measure defined by the self-reported tendency to sunburn or tan after sun exposure (table 1), correlates with skin pigmentation and is useful for stratifying risk for PIH. Compared with individuals with skin phototypes I or II, individuals with skin phototypes III to VI are more likely to develop PIH [2].

ETIOLOGY AND PATHOGENESIS — The provoking inflammatory process that leads to postinflammatory hyperpigmentation (PIH) can be endogenous or exogenous [1]. Common endogenous causes of PIH include acne vulgaris, atopic dermatitis, irritant contact dermatitis, allergic contact dermatitis, psoriasis, and lichen planus. Accidental burns, nonionizing radiation therapy, phototoxicity, chemical peels, and laser procedures are examples of exogenous causes [1,3,4].

The clinical manifestations of PIH result from the presence of excess melanin or an abnormal distribution of melanin in the epidermis and/or dermis. Epidermal melanosis is proposed to result from effects of the release and oxidation of arachidonic acid to prostaglandins and leukotrienes or the effects of other inflammatory mediators in inflamed skin [5,6]. Inflammatory mediators may stimulate melanocytes to increase production of melanin and transfer melanin to surrounding keratinocytes [5].

Dermal melanosis, also referred to as pigmentary incontinence, may occur when inflammation leads to a disruption of the basal layer of the epidermis, causing the release of melanin into the papillary dermis (picture 2). Macrophages in the papillary dermis then phagocytize the released melanin [7]. Alternatively, macrophages may enter the epidermis, phagocytize epidermal melanosomes, and return to the dermis [8]. Macrophages that have phagocytized melanin are often called "melanophages." Melanin may remain in dermal macrophages for years [7]. (See "Congenital and inherited hyperpigmentation disorders", section on 'Pathophysiology of skin pigmentation' and "Acquired hyperpigmentation disorders".)

The increased risk for PIH in individuals with dark skin color may be related to the greater amount of epidermal melanin present in melanosomes in the epidermis [2]. Some authors have also proposed that interindividual differences in the manner in which melanocytes respond to inflammation influence risk for PIH [9].

CLINICAL MANIFESTATIONS — Postinflammatory hyperpigmentation (PIH) manifests as hyperpigmented macules or patches on the skin. The configuration varies widely, matching the distribution of the preceding inflammatory dermatosis or injury (picture 1A-I). Involvement may be limited, widespread, sharply circumscribed, or diffuse with ill-defined borders. Patients in whom PIH accompanies an active inflammatory process may demonstrate hyperpigmentation within chronically inflamed papules, plaques, or nodules (picture 3A-D). In patients without an ongoing inflammatory process, PIH is asymptomatic.

The color of PIH depends on the position of excess pigment within the skin. PIH tends to appear as tan to dark brown when excess pigment is within the epidermis. In contrast, excess pigment in the dermis tends to manifest with a dark gray or blue-gray appearance [10].

HISTOPATHOLOGY — Histopathologic examination of postinflammatory hyperpigmentation (PIH) shows increased melanin in epidermal keratinocytes in specimens with epidermal melanosis and melanin deposition within dermal macrophages (melanophages) in specimens with dermal melanosis (picture 2) [2]. A Fontana-Masson silver stain can identify melanin. Occasional perivascular lymphocytes may be present in the superficial dermis [11].

DIAGNOSIS — Postinflammatory hyperpigmentation (PIH) is typically a clinical diagnosis. The disorder should be strongly considered in patients who present macular or patchy hyperpigmentation and a history of a preceding inflammatory condition or a previous injury to the skin. A biopsy of the skin usually is not necessary.

Patient history — Questioning the patient about a preceding inflammatory skin disorder or accidental or iatrogenic skin injury elicits helpful information for diagnosis. Knowledge of the inciting factor also aids in the identification and treatment of an underlying condition.

Physical examination — The classic clinical finding of macular or patchy tan, dark brown, gray, or blue-gray skin discoloration suggests PIH. Close attention should be paid to the shape and distribution of hyperpigmentation. The findings should correlate with the presumed cause. For example, multiple circular hyperpigmented macules on the face, chest, or back frequently represent PIH secondary to acne vulgaris (picture 1A-B). In contrast, a symmetrical eruption of irregular, hyperpigmented patches involving forehead, cheeks, and chin without preceding inflammation suggests a diagnosis of melasma (picture 4A-B). (See 'Differential diagnosis' below.)

A full skin examination may help to identify the cause of PIH in patients with an underlying inflammatory dermatosis.

Wood's lamp examination — In some patients with PIH, examination with a Wood's lamp can distinguish primarily epidermal melanosis from primarily dermal melanosis. In patients with skin phototypes I to IV (table 1), epidermal melanosis often manifests as well-circumscribed pigmentation with accentuated borders. In contrast, dermal melanosis typically appears poorly circumscribed and is not accentuated under Wood's lamp illumination [10]. The Wood's lamp exam is not very effective for making this distinction in darkly pigmented patients (skin phototype VI) and has limited effectiveness for skin phototype V patients [3].

Biopsy — A skin biopsy typically is not necessary for the diagnosis of PIH. Occasionally, a skin biopsy is performed to determine whether there is another cause of hyperpigmentation. In patients with an active inflammatory dermatosis, a skin biopsy may be helpful for confirming the underlying dermatosis. (See "Skin biopsy techniques".)

DIFFERENTIAL DIAGNOSIS — The inciting factor for postinflammatory hyperpigmentation is often clear, leading to relative certainty of the diagnosis. The possibility of other disorders should be considered in patients with hyperpigmentation of unclear cause. Examples include:

●Melasma – Melasma is a common disorder that manifests with a symmetrical eruption of irregular, hyperpigmented patches on sun-exposed skin (picture 4A-B). In most patients, melasma affects the face, particularly the forehead, malar areas, and chin. Melasma most frequently occurs in reproductive-age women. (See "Melasma: Management".)

●Acanthosis nigricans – Hyperpigmentation is a common feature of acanthosis nigricans, a cutaneous disorder that presents with velvety, slightly elevated plaques in intertriginous sites such as the neck and axillae (picture 5A-B). Acanthosis nigricans is often associated with obesity and diabetes mellitus. The velvety texture is a distinguishing feature. (See "Acanthosis nigricans".)

●Macular amyloidosis – Macular amyloidosis is characterized by confluent or ripple-patterned, hyperpigmented patches with associated pruritus (picture 6). The upper back is the most common location for macular amyloidosis. The extensor surfaces of the extremities are other common locations. (See "Acquired hyperpigmentation disorders".)

●Drug-induced hyperpigmentation – Drug-induced hyperpigmentation represents the occurrence of a drug-stimulated increase in melanin production or deposition of drug complexes or metals in the dermis. A table listing drugs and chemicals associated with skin hyperpigmentation and associated clinical features is provided (table 2). (See "Acquired hyperpigmentation disorders", section on 'Drug-induced'.)

●Erythema dyschromicum perstans – Erythema dyschromicum perstans, also known as ashy dermatosis, is an uncommon disorder that presents with oval or irregular, slate-gray to blue-brown macules or patches (picture 7A-B). Erythema dyschromicum perstans is most frequently diagnosed in young adults of Latin American origin. Early areas may have a thin, raised, erythematous border. The trunk is the most common site for involvement. (See "Acquired hyperpigmentation disorders".)

●Lichen planus pigmentosus – Lichen planus pigmentosus is a rare form of lichen planus that presents with oval or irregular, brown to gray-brown macules and patches (picture 8). Sun-exposed skin of the face and neck is a common site. Intertriginous involvement may also occur. Individuals with origin in India, Latin America, and the Middle East are most likely to develop this condition. (See "Acquired hyperpigmentation disorders".)

Common additional causes of hyperpigmentation include lentigines (circumscribed, brown macules or patches in sun-exposed areas (picture 9A-B)) and tinea versicolor (hyperpigmented macules and patches with fine scale on the trunk or proximal extremities (picture 10)). An overview of disorders of hyperpigmentation is provided separately. (See "Acquired hyperpigmentation disorders".)

TREATMENT — The treatment of postinflammatory hyperpigmentation (PIH) can be divided into essential measures to impede the persistence or exacerbation of PIH and treatment methods to disperse or destroy melanin in the skin. Topical interventions are the mainstay of medical treatment.

Essential measures — Photoprotection should be implemented in all patients treated for PIH. Potential exacerbating factors should also be eliminated.

Photoprotection — Photoprotection reduces the risk for additional ultraviolet radiation-induced darkening of affected skin and may allow for the best results of treatment. Therefore, sun-protective measures are crucial [3]. Patients should be instructed to:

●Apply a broad-spectrum sunscreen with a sun protection factor (SPF) of at least 30 to the entire affected area daily. Sunscreen should be reapplied every two hours during periods of sun exposure. (See "Selection of sunscreen and sun-protective measures".)

●Use sun-protective clothing to cover the affected area (eg, broad-brimmed hats for patients with facial involvement). (See "Selection of sunscreen and sun-protective measures", section on 'Photoprotective clothing'.)

Elimination of exacerbating factors — Medical treatment of PIH is often challenging. Therefore, the prevention of new areas of skin involvement through treatment of an active underlying cause, if present, is an essential component of management. For example, in patients with acne vulgaris-associated PIH, treatment of PIH should not be performed without treatment of active acne. (See "Acne vulgaris: Overview of management".)

In addition, other factors that may exacerbate PIH should be eliminated. Patients should avoid scratching, rubbing, manipulating, or traumatizing the affected area [3]. Exposure to furocoumarins and medications, such as chlorpromazine and tetracyclines, may also increase PIH [9]. Clinicians should review the patient's medications to identify medications that may exacerbate hyperpigmentation.

Medical treatment — A variety of medical therapies may accelerate improvement of PIH.

Patient selection — PIH tends to improve slowly over time. Therefore, medical treatment is not necessary for all patients. Medical therapy can be limited to patients who desire accelerated resolution of hyperpigmentation. (See 'Prognosis' below.)

The location of hyperpigmentation within the skin may influence the likelihood of a good response to treatment. The interventions available for hyperpigmentation primarily reduce the production or distribution of epidermal pigment. Therefore, patients in whom hyperpigmentation primarily results from the presence of melanin within dermal macrophages are less likely to respond well to treatment [9]. Performance of a Wood's lamp examination prior to treatment can help to guide clinicians and patients regarding expectations for the results of treatment. (See 'Wood's lamp examination' above.)

Many treatments for PIH have skin irritation as a potential side effect. This risk should be discussed with patients, as treatment-induced skin irritation may result in worsening of hyperpigmentation.

First-line therapy — Topical hydroquinone has been used for the treatment of PIH for many years and is considered the gold standard therapy.

Topical hydroquinone — Hydroquinone acts by inhibiting the conversion of dihydroxyphenylalanine to melanin by inhibiting the activity of the enzyme tyrosinase, thus reducing the formation and melanization of melanosomes [12]. Hydroquinone is less effective for hyperpigmentation in which pigment deposition is primarily in the dermal melanophages, as these cells have minimal or absent tyrosinase activity [13].

Other potential mechanisms of hydroquinone activity include inhibition of DNA and RNA synthesis, selective cytotoxicity toward melanocytes, and melanosome degradation by autoxidation and phenol oxidases leading to highly reactive oxygen radicals [2,12]. Oxygen radicals may prevent melanin production within melanosomes and increase the degradation of melanosome packages within keratinocytes:

●Efficacy – Although hydroquinone is widely used for PIH, data on its efficacy for PIH are limited. Evidence for efficacy for hyperpigmentation primarily stems from studies of patients with melasma, another common disorder characterized by hyperpigmentation. As an example, hydroquinone was effective for melasma in a trial in which 48 patients were randomly assigned to treatment with twice-daily application of hydroquinone 4% cream and daily sunscreen or sunscreen alone [14]. After 12 weeks of treatment, 40 percent of patients receiving hydroquinone had complete resolution of hyperpigmentation versus only 10 percent in the placebo group. (See "Melasma: Management", section on 'Topical skin-lightening agents'.)

Extensive clinical experience suggests that the efficacy of hydroquinone for melasma translates to PIH, although vehicle-controlled trials specifically evaluating efficacy for PIH are lacking. Most studies evaluating hydroquinone in PIH are uncontrolled, include other diagnoses, or evaluate hydroquinone combined with other therapies [15-17]. As an example, a 12-week, open-label study that evaluated twice-daily application of a product containing microencapsulated hydroquinone 4%, retinol 0.15%, and antioxidants in 17 patients with mild to moderate PIH and 4 patients with melasma found at least 75 percent improvement or complete improvement of hyperpigmentation in 12 of the 19 patients who completed the study (63 percent) [15]. Significant improvement was noted as early as four weeks after the start of treatment.

●Administration – Hydroquinone is most commonly prescribed in a 4% concentration [2]. In the United States, the drug is available up to a 10% concentration by prescription from compounding pharmacies. Hydroquinone is applied twice daily to the affected area.

Because a reduction in the pigmentation of both normal and hyperpigmented skin can occur during hydroquinone therapy, application to the entire face is preferred over "spot" treatment in patients with multiple areas of facial involvement to prevent irregular pigmentation [2]. In patients in whom hyperpigmentation affects a very small portion of the affected body site (ie, a few hyperpigmented macules on the face), treatment is often limited to the specific areas of hyperpigmentation. However, the patient should be warned of the risk for the development of a temporary "halo" of hypopigmentation at the periphery of the treated areas. The halo may take several months to resolve after treatment is discontinued.

Improvement from hydroquinone therapy is often evident within several weeks to a few months of treatment [13]. We typically reassess patients after 12 weeks. If PIH is improved, treatment may be discontinued or continued for up to an additional 12 weeks in patients with a partial response. Maximum efficacy occurs around 20 weeks of treatment and efficacy plateaus after around 24 weeks [2]. If there is absolutely no evidence of a clinical response after the initial 12 weeks of hydroquinone therapy, we discontinue treatment. In our experience, these patients are unlikely to improve with continued treatment.

●Adverse effects – Acute side effects of hydroquinone include local irritant contact dermatitis, allergic contact dermatitis, and nail discoloration [13]. The risk for irritant contact dermatitis increases with increasing concentration. Of note, concentrations of hydroquinone above 5 to 6% have also been associated with persistent hypopigmentation or depigmentation [13].

Exogenous ochronosis is a concerning chronic side effect of hydroquinone that occurs through an unclear mechanism. The disorder presents as reticulated, ripple-like, sooty pigmentation affecting sites of hydroquinone application (picture 11) [13,18]. A papular component with "caviar-like" papules may eventually develop [19]. Common affected sites are the cheeks, the forehead, and the periorbital areas [19]. Patients are asymptomatic. The characteristic histologic finding is banana-shaped, yellow-brown deposits in the dermis (picture 12) [19].

There is a correlation between exogenous ochronosis and the duration of hydroquinone use. Chronic use of hydroquinone (typically longer than six months), even at 2%, can be associated with increased risk for exogenous ochronosis, especially among patients with the darker skin phototypes (table 1) [20]. However, higher concentrations are more likely to induce exogenous ochronosis [19]. There is no effective treatment for exogenous ochronosis. Treatment with hydroquinone should be stopped.

Second-line therapy — Second-line therapies for PIH include several widely available and easily administered topical therapies for hyperpigmentation that have limited evidence for efficacy in PIH. Topical retinoids, hydroquinone-retinoid-corticosteroid triple-agent therapy, azelaic acid, and chemical peels are included in this category. Because PIH improves spontaneously over time, additional trials to confirm efficacy of these interventions would be useful.

There are insufficient data to determine relative efficacy among these treatments and in comparison with the gold standard, hydroquinone. Therefore, treatment selection is based upon factors such as availability, cost, clinician familiarity, and tolerability. Topical retinoids and azelaic acid are effective treatments for acne vulgaris, a feature that may be beneficial for patients with PIH secondary to active acne vulgaris.

Topical retinoids — Topical retinoid therapy may be useful for the treatment of PIH [21]. Topical retinoids increase epidermal turnover, thereby facilitating melanin dispersion and removal [22]. Topical tretinoin, tazarotene, and adapalene are commercially available topical retinoids:

●Efficacy – Data on the efficacy of topical retinoids for PIH are limited. Two topical retinoids, tretinoin and tazarotene, have demonstrated benefit in small, vehicle-controlled, randomized trials:

•In a randomized trial that compared once-daily application of tretinoin 0.1% cream with vehicle in 68 Black patients with PIH on the face or arms, improvement in hyperpigmentation was significantly greater in the tretinoin group after 40 weeks [23].

•In an 18-week trial in which 74 patients with acne and PIH (skin phototypes IV to VI) were randomly assigned to once-daily application of tazarotene 0.1% cream or vehicle, tazarotene was superior to vehicle for reducing the severity of PIH [24].

Benefit of adapalene 0.1% gel for PIH was reported in a 12-week, open-label study of 65 patients with acne and PIH [25]. However, a 16-week multicenter trial that compared the efficacy of tazarotene 0.1% cream with adapalene 0.3% gel in patients with moderate to severe acne found greater reductions in PIH in patients treated with tazarotene [26].

Topical retinoids are applied once daily. Traditionally, these agents have been applied at night due to the photoinstability of certain formulations of the original topical retinoid, tretinoin [27]. The patient should apply a very thin layer of the retinoid to the entire affected area. For patients undergoing treatment for facial hyperpigmentation, the tretinoin is applied to the entire face. Clinically significant improvement may take a few months to achieve. There is not a limit to the duration of topical retinoid use.

Irritant dermatitis is a common adverse effect of topical retinoids, particularly early in the course of therapy. In patients with darker skin phototypes, this is of particular concern because irritation may contribute to the development of additional PIH [3]. When necessary, methods to improve irritation include alternate-day use, mixing the topical retinoid with a moisturizer, and using a formulation with a lower concentration of medication.

Triple-agent therapy — Classic triple-agent therapy consists of the combination of hydroquinone, topical tretinoin, and a topical corticosteroid. In addition to the potential direct benefit of tretinoin on hyperpigmentation, tretinoin may also inhibit oxidation of hydroquinone and improve epidermal penetration of hydroquinone [18]. The inclusion of a corticosteroid reduces risk for irritant dermatitis, a common adverse effect of both hydroquinone and tretinoin. The corticosteroid may also inhibit melanin synthesis [18].

The original triple-agent formula, known as the Kligman formula, contained hydroquinone 5%, tretinoin 0.1%, and dexamethasone 0.1% [22]. Subsequently, other formulations with less potent corticosteroid components were developed to reduce risk of corticosteroid side effects. A commercial product containing hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% is available. This product has demonstrated efficacy for hyperpigmentation associated with melasma [28] and is often used for the treatment of PIH [7]. However, trials evaluating efficacy in PIH are lacking.

The commercial product containing hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% is applied once daily to affected areas. As with other skin-lightening therapies for PIH, the entire region of involvement (eg, entire face) should be treated to avoid inducing a negative cosmetic effect from irregular skin pigmentation. As with hydroquinone, patients with minimal facial involvement are a reasonable exception, provided patients are aware of the risk for a "halo" of hypopigmentation (see 'Topical hydroquinone' above). Improvement may be evident within the first two months. We typically re-evaluate patients after 8 to 12 weeks to assess for a response and side effects. Treatment may be continued for up to 24 weeks [29,30]. However, if there is absolutely no improvement after the initial 12 weeks, we discontinue treatment.

Due to the corticosteroid component, corticosteroid-induced atrophy is a potential adverse effect of triple-agent therapy. However, based upon a study performed in patients with melasma, the risk for cutaneous atrophy appears to be low in patients treated for up to 24 weeks [29]. Other potential adverse effects include hypopigmentation, skin irritation, allergic reactions, and exogenous ochronosis. (See 'Topical hydroquinone' above.)

Azelaic acid — Azelaic acid is a naturally occurring dicarboxylic acid isolate from the organism Pityriasis ovale that is commonly used for the treatment of acne, melasma, and PIH. Mechanisms through which azelaic acid may improve hyperpigmentation include inhibition of tyrosinase and selective cytotoxic and antiproliferative effects on abnormal melanocytes via inhibition of mitochondrial enzymes and DNA synthesis [31].

There is a paucity of data on the efficacy of azelaic acid for PIH. Efficacy for hyperpigmentation in general is suggested by a multicenter, vehicle-controlled, randomized trial (n = 52) that found 24 weeks of treatment with azelaic acid 20% cream significantly improved various types of facial hyperpigmentation in patients with skin phototypes IV to VI [32]. In addition, a separate 24-week randomized trial performed in patients with skin phototypes IV to VI (n = 65) found that hydroquinone 4% cream and combination therapy with azelaic acid 20% cream and glycolic acid 15 or 20% lotions were similarly effective for facial hyperpigmentation [33].

Azelaic acid is usually applied twice daily to the affected region. A few months of treatment may be necessary to achieve a clinically significant response. A local burning or stinging sensation on the skin is a common side effect.

Chemical peels — Chemical peel procedures involve the application of an exfoliating agent (typically an acid) to the skin surface, resulting in controlled skin wounding. Chemical peels are divided into superficial, medium-depth, and deep peels based upon the depth of skin injury induced.

Superficial chemical peels, which exfoliate part or all of the epidermis, may have a skin-lightening effect and are used for the treatment of PIH. The resulting epidermolysis and dispersal of melanin in the basal layer contribute to improvement in hyperpigmentation. Superficial chemical peels are often used in combination with other PIH therapies and may facilitate absorption of topical skin-lightening agents [34].

Glycolic acid and salicylic acid are among the most common superficial peeling agents used for PIH. A series of several peels is usually necessary:

●Glycolic acid – Glycolic acid is an alpha-hydroxy acid that is typically applied in concentrations ranging from 20 to 70% during chemical peels. In the medical setting, concentrations towards the higher end of this range are frequently used. Application of a neutralizing agent (eg, water or sodium bicarbonate) terminates the peel.

Studies evaluating glycolic acid peels for PIH are limited. A randomized trial in which 19 women (skin phototypes IV to VI) were randomly assigned to either treatment with a hydroquinone 2%-glycolic acid 10% gel twice daily and tretinoin 0.05% cream at night or to the same topical regimen plus six serial 50 to 68% glycolic acid peels found improvement in hyperpigmentation in both groups as assessed subjectively with a scoring system [35]. A trend towards faster and greater improvement in the chemical peel group was detected when data from colorimetric analysis was reviewed; however, there were no statistically significant differences in response between the two groups.

●Salicylic acid – Salicylic acid is a beta-hydroxy acid. Concentrations ranging from 20 to 30% are typically used for salicylic peels in clinical practice.

Similar to glycolic acid, efficacy data for PIH are limited. An uncontrolled study (n = 25) in which five patients with skin phototypes V or VI were treated for PIH with a series of five salicylic acid 20 to 30% peels following a two-week course of hydroquinone 4% found that four patients attained at least 75 percent improvement in PIH on photographic assessment [36]. In addition, a nonsignificant trend toward a skin-lightening effect was detected in a study of 24 Korean adults treated for acne and PIH with a series of salicylic acid 30% peels [37].

Patients of all skin phototypes generally tolerate superficial chemical peels well. PIH from chemical peel-induced skin irritation is a potential adverse effect. To minimize risk for PIH, daily sunscreen use is crucial before, during, and after chemical peels.

Other therapies — A variety of therapies used for hyperpigmentation have unclear efficacy for PIH:

●Lasers – Various laser and light devices are used for the treatment of cutaneous hyperpigmentation. However, efficacy data for PIH are limited to case reports and small series. These reports describe improvement in PIH after treatment with a 1064 nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, a 532 nm Q-switched Nd:YAG laser, a Q-switched ruby laser, a 1550 nm erbium-doped fractional laser, and fractional carbon dioxide (CO₂) lasers [38-42]. There are additional data on laser treatment for other disorders of hyperpigmentation, including melasma. (See "Laser and light therapy for cutaneous hyperpigmentation" and "Melasma: Management", section on 'Lasers and light therapies'.)

Of note, PIH is a potential side effect of laser therapy. This risk is highest in individuals with dark skin color, the population most likely to need treatment for PIH. Among nonfractional lasers, this risk is reduced (but not eliminated) with the use of longer-wavelength lasers (eg, 1064 nm Q-switched Nd:YAG). An additional advantage of long-wavelength lasers is the ability to penetrate more deeply into the skin than shorter-wavelength lasers. This characteristic may be useful for treatment of pigment deposition in the dermis. Laser therapy for PIH should be limited to use by experienced clinicians for select cases. (See "Laser and light therapy for cutaneous hyperpigmentation", section on 'Principles'.)

●Lignin peroxidase – Lignin peroxidase is an enzyme derived from the tree fungus Phanerochaete chrysosporium that can degrade melanin. A 12-week, split-face, randomized trial that compared treatment with topical lignin peroxidase with no treatment in 30 women as well as with treatment with hydroquinone 4% in an additional 30 women found that lignin peroxidase improved facial hyperpigmentation more than no treatment and had a similar effect on facial hyperpigmentation as hydroquinone [43]. Further study is necessary to determine the efficacy of this agent for PIH.

●Other topical therapies – Other topical agents that have been used to treat melasma, such as mequinol, niacinamide, ascorbic acid, kojic acid, and licorice, have not been formally studied in the treatment of PIH. (See "Melasma: Management", section on 'Non-hydroquinone agents'.)

Camouflage — Even with treatment, PIH may take weeks to months to improve, and improvement may be incomplete. Patients who are interested in making PIH less visible may benefit from camouflage products designed to minimize the appearance of skin disorders [44]. (See "Melasma: Management", section on 'Cosmetic camouflage'.)

PROGNOSIS — The clinical manifestations of epidermal melanosis may take months to years to resolve without treatment. Manifestations of dermal melanosis may persist for years and can be permanent. The duration of postinflammatory hyperpigmentation (PIH) may be longer in individuals with dark-colored skin compared with individuals with light-colored skin [9]. Persistent or relapsing inflammation and ultraviolet irradiation can exacerbate the condition [9].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Melasma and hyperpigmentation disorders".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis that occurs in response to cutaneous inflammation. PIH is common and may affect individuals of all skin types. Risk for PIH increases with increasing skin pigmentation. (See 'Epidemiology' above.)

●Pathogenesis – The clinical manifestations of PIH can result from an increase in epidermal melanin or deposition of melanin pigment within the dermis. (See 'Etiology and pathogenesis' above.)

●Clinical manifestations – PIH is characterized by the development of hyperpigmented macules or patches in the distribution of a preceding inflammatory dermatosis or skin injury (picture 1A-I). The color of PIH may be tan, brown, dark gray, or blue-gray. (See 'Clinical manifestations' above.)

●Diagnosis – The diagnosis of PIH can almost always be made based upon the clinical evaluation. A skin biopsy is not necessary in most cases. (See 'Diagnosis' above.)

●Management:

•Essential measures – The management of PIH includes methods to impede the persistence or exacerbation of PIH. Sun-protective measures, treatment of the underlying cause, and elimination of exacerbating factors are important interventions. (See 'Essential measures' above.)

•Role of medical intervention – Medical therapy for PIH is not required for all patients because the natural history of PIH is to improve slowly over time. The goal of medical treatment is to accelerate resolution. (See 'Patient selection' above and 'Prognosis' above.)

•Treatment selection – For patients who desire medical treatment to accelerate resolution of PIH, we suggest topical hydroquinone as initial treatment (Grade 2C). Other treatment options that may improve PIH include topical retinoids, triple-agent topical therapy, azelaic acid, and chemical peels. (See 'First-line therapy' above and 'Second-line therapy' above.)

•Risk for exacerbation – Therapies for PIH can cause skin irritation. Therefore, exacerbation of PIH is a risk of treatment. (See 'Patient selection' above.)