Post-Inflammatory Hyperpigmentation in Skin of Color: An Updated Review

Pigmentary disorders are among the five most common reasons for visits to dermatology clinics.¹ Post-inflammatory hyperpigmentation (PIH) is among the most common causes of acquired hyperpigmentation and accounted for 14.8% of self-reported pigmentary disorders in a worldwide survey.² In addition, dyschromia accounts for an estimated 1.4 million dermatology visits annually in the United States.³ Beyond its high prevalence, PIH is associated with substantial impairment in quality of life and self-esteem, underscoring its significant psychosocial burden. In this review, we discuss the pathophysiology, common causes, clinical presentation, and current management strategies for post-inflammatory hyperpigmentation.

Pathophysiology OF PIH in Skin of Color

PIH develops as a response to cutaneous insult to the skin. There is a complex interplay between keratinocytes and melanocytes in response to inflammation. Skin injury triggers a cascade of melanogenic mediators, including alpha-melanocyte–stimulating hormone (α-MSH), prostaglandins, leukotrienes, and inflammatory cytokines such as IL-18 and IL-33, as well as secondary melanogenic factors released by dermal fibroblasts.⁴ PIH refers to hyperpigmentation that is driven by the release of inflammatory cytokines and the subsequent dysregulation of melanin transfer to keratinocytes.⁵ The release of inflammatory cytokines triggers growth factor release from dermal fibroblasts, increasing melanin production by melanocytes and increased dermal and epidermal deposition of melanin.⁶ While many think of ultraviolet (UV) light exclusively impacting cutaneous injury, fewer think on the effects of visible light (VL). Approximately 50% of exposure to solar radiation comes from VL, which can lead to damage via generation of reactive oxygen species (ROS) as seen with UV. Furthermore, VL also contributes to PIH and its exacerbation.⁷

Duration and quality of PIH depend on whether inflammation is localized to the epidermis or penetrates into the dermis.⁸ Epidermal PIH is characterized by melanocyte hyperplasia, increased melanin production, and enhanced transfer of melanin to epidermal keratinocytes, with minimal dermal involvement. On Wood’s lamp exam, epidermal PIH will have sharply defined borders as the more superficial melanin will absorb UV light. Two main theories have been proposed to explain the pathogenesis of dermal PIH. The first suggests direct transfer of melanosomes into the dermis through a disrupted basement membrane. The second proposes that dyskeratotic keratinocytes containing melanosomes are phagocytosed by melanophages, which subsequently migrate into the dermis and deposit melanin within the papillary dermis.⁴ On Wood’s lamp exam, dermal PIH will have less sharply defined contrast, as there is less melanin that can absorb UV light. Patients can also present with mixed PIH which consists of both an epidermal and dermal pigmentary component.

Individuals with darker skin phototypes have larger and more heavily melanized melanosomes that are more resistant to degradation. These characteristics contribute to an enhanced melanogenic response following cutaneous injury, resulting in an increased risk and severity of post-inflammatory hyperpigmentation. Understanding the pathophysiology of PIH is important because it carries significant therapeutic implications, as topical therapies are generally less effective for dermal hyperpigmentation. 

Common Causes and Clinical Presentation

One of the most common triggers for PIH is acne vulgaris, commonly on the face and trunk.9 PIH due to acne vulgaris occurs due to an inflammatory response triggered by C acnes with increased release of interferon-γ and IL-17.¹⁰ Therefore, it is understandable that more severe presentations of acne vulgaris are associated with worse PIH.¹¹ Acne vulgaris PIH can also be caused by irritant contact dermatitis from topical treatments for acne.¹² Physical trauma to acne through picking also increases PIH, driven largely by the effects of endothelin (ET)-1.¹³ Research shows that for many patients, the PIH associated with acne is more bothersome than the acneiform lesions themselves.¹⁴ Duration of PIH varies among patients; if it is primarily epidermal, it can last 6 to 12 months, while dermal PIH can last years.

Essentially all forms of inflammatory dermatitis can lead to PIH, largely due to cytokine dysregulation. Atopic dermatitis causes PIH, especially in areas of long-standing chronic disease. This is driven by inflammatory cytokines and mechanical trauma from pruritus and subsequent scratching.¹⁵ There are early reports that dupilumab decreases PIH associated with atopic dermatitis, likely by quelling inflammatory cytokine-driven pathways.¹⁶ Other inflammatory dermatoses such as pseudofolliculitis barbae, lichen planus, lichen planus pigmentosus, erythema dyschromicum perstans, cutaneous lupus erythematosus, and bullous pemphigoid are also associated with PIH.¹⁷ 

Cosmetic processes can also lead to PIH, further underscoring the importance of going to a board-certified dermatologist with experience treating skin of color. Chemical peels, especially medium and deep chemical peels, can lead to PIH.¹⁸ The mechanism behind PIH is the same mechanism utilized when applying chemical peels for hyperpigmentation disorders; controlled epidermal injury and interference in melanosome transfer to keratinocytes.¹⁹ When utilized appropriately, dyschromias can be effectively treated. However, when incorrectly utilized or without appropriate photoprotective behaviors, injury leads to inflammation, and thus PIH. Laser procedures can also lead to PIH, with a recent meta-analysis finding that the most common cause of procedure-induced PIH was laser treatments.²⁰ The settings of the laser, including higher energy deliverance, can make it more likely to induce PIH due to the injury to the epidermis and/or dermis.²¹

Prevention and Patient Counseling 

Prevention of PIH relies heavily on photoprotection.5 Patients with PIH should be counseled to avoid physical trauma and irritation to impacted sites. Additionally, practice pattern analysis found that antimicrobial and antiviral prophylaxis agents are often utilized to reduce the risk of inflammation from infection.²² In addition to these agents, there are a myriad of pre-treatment options that reduce the risk of PIH, including lightening agents such as retinoids, hydroquinone, tranexamic acid, and photoprotection.²³ 

Photoprotection is of the utmost importance in the prevention and management of PIH. Use of broad-spectrum SPF of at least 30 to 50 prevents worsening of PIH and can help reduce its development. SPF helps protect against the damage from UV radiation; however, newer research shows that protection from visible light is also important in prevention and treatment of PIH, especially in patients with darker phototypes.²⁴ Therefore, tinted sunscreen with physical filters, such as titanium dioxide and zinc oxide, is preferred as these tinted physical filters protect from both visible light and UV radiation.²⁵ Patients with darker phototypes should be counseled to use tinted sunscreens with physical filters as these will provide the best cosmetic effect and help prevent and reduce PIH. Recently, the FDA approved the addition of a new UV filter for the first time in 20 years: bemotrizinol. Bemotrizinol protects against UVA and UVB rays and allows for more comprehensive protection than other comparable UV filters.²⁶ Due to the larger structural size and higher molecular weight, bemotrizinol does not penetrate into the skin as easily as other filters currently available, increasing its photoprotective ability; however, it does not have any protection against visible light.

Treatment of PIH

The initial step in the management of PIH is to identify and eliminate or adequately control the underlying inflammatory or injurious process responsible for its development. Once the inciting cause has been addressed, treatment should be individualized based on factors such as the anatomic location, extent and severity of pigmentation, skin phototype, and patient-specific goals. Treatment of PIH can be broadly categorized into topical, oral, and procedural therapies. In clinical practice, the greatest therapeutic benefit is often achieved through a multimodal approach that combines complementary treatment modalities, as synergistic effects frequently result in greater efficacy than any single intervention alone.

Topicals

Topical agents are generally considered the foundation of treatment for PIH and are often recommended as first-line therapy for mild to moderate disease (Table 1). These therapies primarily target melanogenesis, accelerate epidermal turnover, or reduce inflammation, thereby addressing multiple pathways involved in pigment formation and persistence. The following section reviews the available topical agents, their mechanisms of action, efficacy, and practical considerations for clinical use.

For topical agents, hydroquinone is a potent skin lightening agent that can be effective and safe when utilized correctly. It functions by inhibiting melanin synthesis via blocking the conversion of L-3,4-dihydroxyphenylalanian to melanin by inhibiting tyrosinase and can also be utilized topically alone or as an adjunct to other treatment options.²⁷  Retinoids are also commonly utilized, as they can be used pre-procedurally to expedite reepithelialization and epidermal healing, therefore reduce inflammation that leads to PIH. They should be stopped 24 to 48 hours pre-procedure to prevent unnecessary trauma. They can also be used successfully to help treat existing PIH. Corticosteroids are commonly used in adjunct with sunscreen topically to reduce PIH post-therapy. The primary mechanism by which topical corticosteroids reduce PIH is by reducing general inflammation via phospholipase A2 and interfering with melanogenesis.²⁸ There are numerous formulas available that combine many of these agents into one product for increased ease of application.²⁹ These include agents such as the modified Klingman’s formula, made of hydroquinone, retinoids, and topical steroids.

Topical tranexamic acid (TXA) has also been shown to reduce post-laser PIH, with an added benefit of reduced systemic side effects as opposed to oral TXA, though further research is warranted.³⁰ TXA prevents PIH by inhibiting the binding of plasminogen to keratinocytes, interfering with the activity of melanocyte tyrosinase.³¹ Furthermore, this is an expanding area of research, as a recent randomized controlled trial (RCT) found that topical treatment with lotus sprout extract had similar efficacy and tolerability to treatment with hydroquinone.³² 

There are also many topical over-the-counter (OTC) modalities available to patients. This includes niacinamide, which functions by reducing melanosome transfer to keratinocytes and reducing PIH and other forms of hyperpigmentation.³³ Ascorbic acid is commonly utilized and functions by interfering in the tyrosinase pathway.³⁴ There are numerous ascorbic acid products available, as well as many products utilizing various forms of vitamin C.³⁵ Azelaic acid is available in OTC formulations and by prescription (15% or higher), both functioning as an antioxidant and reducing hyperpigmentation via suppression of proliferation and differentiation of melanocytes.³⁶ Thiamidol is a newer OTC agent used in PIH, functioning as a tyrosinase inhibitor and thus reducing PIH.³⁷ Another new agent is 2-Mercaptonicotinoyl glycine, also known as melasyl, which reduces PIH by binding melanin precursors.³⁸ There are also a variety of plant-derived products, such as arbutin, kojic-acid, and lotus-based products, utilized by many consumers for PIH. Topical agents are discussed further in Table 1.

Oral Agents

Oral therapies serve as valuable adjuncts in the management of PIH, particularly for patients with more extensive, recalcitrant, or recurrent disease (Table 2). These agents may reduce ongoing inflammation, modulate melanogenesis, or provide antioxidant effects that complement topical treatment. 

In addition to topical agents, many oral agents are options. Oral TXA is available, with similar functions to those of topical TXA but with improved rate of efficacy as compared to topical formulations.³⁹ Oral agents derived from extracts of the topical fern Polypodium leucotomos (PL) have been found to be efficacious in the management of melasma.⁴⁰ The primary benefits from PL are due to its effect as an antioxidant and thus its ability to reduce the impact of ROS and membrane lipid peroxidation.⁴¹ While there are no large scale studies in the use of PL in PIH, this is an exciting area of active research that may yield strong benefit given PL’s efficacy in other pigmentary disorders.⁴² Finally, oral glutathione has been used to help increase skin brilliance and improve hyperpigmentation, via its action as an antioxidant and its effect in reducing the accumulation of hydrogen peroxide and other ROS.⁴³ The full clinical efficacy of glutathione is still not well studied and requires more robust RCTs, though early data appear promising.⁴⁴ Oral glutathione is preferred over intravenous as intravenous is associated with severe adverse effects, such as toxic epidermal necrosis.⁴⁵ Oral agents are discussed further in Table 2.

Procedural Interventions

Procedural interventions may be considered for patients with persistent PIH, inadequate response to medical therapy, or when more rapid clinical improvement is desired (Table 3). Available modalities include chemical peels, laser and light-based devices, microneedling, and other energy-based treatments, each with unique benefits and limitations. Careful patient selection, appropriate device or procedure choice, and individualized treatment parameters are essential to maximize efficacy while minimizing the risk of adverse effects.⁴⁶

Chemical peels address PIH by inducing keratolysis followed by desquamation. For best results, patients ought to stop retinoids 3 to 5 days prior to treatment. Additionally, most patients require a series of multiple peels to produce an effect. To minimize paradoxical worsening of PIH, patients should be instructed to use gentle skincare post-procedure with adequate barrier support to allow for appropriate skin healing. There are also data to support post-procedure topical steroids to help prevent further PIH from developing.⁴ Microneedling can also be utilized in the management of PIH, as the controlled micro-injury stimulates epidermal turnover and improves dyspigmentation. However, large, controlled trials are still needed to identify best treatment practices.⁴⁷ 

Fractional ablative lasers can also be utilized, and once again function via selective photothermolysis. The most used fractional ablative lasers in PIH include fractional CO₂ lasers, hybrid lasers, and the Erbium-doped yttrium-aluminum-garnet (Er:YAG). Studies have shown that in the management of PIH, reduced density is more important than lower pulse energy, and that, if possible, longer pulse durations with epidermal cooling should be selected.^48-50 Fully ablative lasers can be used to treat PIH once again via selective photothermolysis. For the safest profile, utilize a low energy, low pulse energy, and attempt to cover affected areas in a single pass.⁵¹ Of ablative lasers, the CO₂ and Er:YAG lasers are the most often utilized; however, both will require multiple treatments to see an effect. These, again, should be used with great caution in those with skin of color.

Nonablative fractional lasers function via selective photothermolysis, with the most common modalities used for the management of PIH being the 1927-nm thulium diode or the 1440-nm fractional diode. The 1927-nm, when used at a low energy and low density setting, has shown to be both safe and efficacious in skin of color.⁵² Nonablative fractional lasers are generally better tolerated in skin of color and therefore have a lesser side effect profile as compared to ablative lasers. 

Q-switched and picosecond lasers can also be utilized in the management of PIH, once again functioning through selective photothermolysis. For the highest efficacy, low fluence and a large spot size should be used with two passes for full face.⁴⁹ Picosecond lasers can be an excellent treatment modality for patients who have failed treatment with other Q-switched lasers.⁵⁰ 

Intense pulsed light (IPL) can help treat PIH via selective photothermolysis. Aim for one pass with 10% to 20% overlap and then cool the skin to 12° to 15°C. While IPL has been shown to have a decreased risk of inducing PIH as compared to diode and Er:YAG lasers, it can also produce severe adverse events including scarring and dyspigmentation in darker skin types.²¹ Procedural interventions for PIH are further detailed in Table 3. 

Conclusion and Future Directions 

Post-inflammatory hyperpigmentation (PIH) is among the most common causes of acquired hyperpigmentation and should be recognized early so that inciting factors can be promptly treated if possible. Tinted mineral sunscreen use is of vital importance in all disorders of hyperpigmentation, and PIH is no exception; therefore, patients should be counseled adequately. Management of PIH includes prevention, selecting appropriate topical agents and in-office procedures that are appropriately suited for each skin type. Treatments for PIH involve topical agents, oral agents, and procedures, the selection of which is determined on both depth of PIH and anatomic location. Awareness of PIH and appropriate treatments is of the utmost importance for the optimal treatment of diverse patient populations.