Postinflammatory Hyperpigmentation

Etiology

Although any inflammatory skin condition can result in hyperpigmentation, the most common causes of postinflammatory hyperpigmentation in patients with darker skin color are acne vulgaris, atopic dermatitis, and impetigo.[1][4] Other etiologies include:

• Infections
  • Viral exanthems
  • Fungal infections
  • Impetigo

• Allergic/immunologic causes
  • Contact dermatitis
  • Atopic dermatitis
  • Systemic sclerosis (scleroderma)
  • Sarcoidosis
  • Systemic lupus erythematosus
  • Dermatomyositis
  • Insect bite reactions

• Papulosquamous disorders
  • Psoriasis
  • Lichen planus
  • Pityriasis rosea
  • Lichen simplex chronicus

• Cutaneous injuries
  • Laser/light therapy
  • Burns
  • Cryotherapy
  • Chemical peels
  • Radiation therapy

• Miscellaneous conditions
  • Medication hypersensitivity reactions
  • Acne vulgaris
  • Mycosis fungoides
  • Erythema dyschromicum perstans

Epidemiology

Postinflammatory hyperpigmentation is more prevalent among individuals with darker skin tones, particularly those with Fitzpatrick skin types IV to VI. These patients have a greater baseline melanin production and more reactive melanocytes. Postinflammatory hyperpigmentation is particularly common in populations of African, Asian, and Latin American descent, where it represents a significant cause of dermatological consultations and often results from common inflammatory conditions such as acne or eczema.[5] The darker the skin color, the more intense and persistent hypermelanosis tends to be. The incidence of postinflammatory hyperpigmentation in individuals with darker skin tones with acne can be as high as 65%.[4][6] There is no gender difference in the prevalence of postinflammatory hyperpigmentation.

Pathophysiology

The pathophysiology of postinflammatory hyperpigmentation involves complex interactions between inflammatory mediators, melanocytes, and keratinocytes. Inflammation resulting from various skin insults—such as acne, eczema, trauma, or dermatologic procedures—triggers the release of inflammatory cytokines, prostaglandins, and reactive oxygen species. These mediators stimulate melanocytes to produce excess melanin, which is then transferred to surrounding keratinocytes in the epidermis and, in some cases, leaks into the dermis.[7]

Epidermal postinflammatory hyperpigmentation occurs when melanin accumulates in the epidermal layers, presenting as a brown discoloration. This type of condition tends to improve more readily over time. In contrast, dermal postinflammatory hyperpigmentation, often caused by more severe or chronic inflammation, results from melanin being engulfed by macrophages in the dermis, creating a blue-gray hue that is more persistent. The severity and persistence of postinflammatory hyperpigmentation depend on the degree of inflammation and the depth of melanin deposition. Individuals with darker skin types are more susceptible due to their higher baseline melanin production and more reactive melanocytes.[1][8]

Histopathology

The histopathology of postinflammatory hyperpigmentation reveals distinct features based on the location of melanin deposition in the epidermis or dermis. Epidermal postinflammatory hyperpigmentation has an accumulation of melanin within the basal and suprabasal layers of the epidermis. Melanocytes are typically intact but hyperactive in this form, leading to increased melanin production. This melanin is subsequently transferred to surrounding keratinocytes, resulting in brown discoloration of the affected skin. 

In contrast, dermal postinflammatory hyperpigmentation typically follows deeper or more prolonged inflammatory processes. In dermal postinflammatory hyperpigmentation, melanin granules escape into the dermis, where they are phagocytosed by dermal macrophages, forming melanophages. This process creates a blue-gray pigmentation, as the deeper melanin appears more diffuse and less accessible to spontaneous fading. Histopathological analysis may also reveal inflammatory cell infiltrates, depending on the chronicity and intensity of the original inflammatory event. Dermal postinflammatory hyperpigmentation is generally more resistant to treatment compared to epidermal postinflammatory hyperpigmentation due to the depth of the pigment within the skin layers. A biopsy may be useful in determining the etiology of the underlying inflammation.[9][10]

History and Physical

Patients with postinflammatory hyperpigmentation have a history of an inflammatory skin disorder or a skin injury within the same affected area. Once the underlying inflammation has resolved, postinflammatory hyperpigmentation is asymptomatic. However, psychological distress and an impact on the quality of life may persist.

On physical examination, postinflammatory hyperpigmentation presents as irregular, hyperpigmented macules or patches in the initial inflammation-affected or injury distribution. Epidermal hyperpigmentation appears as tan, brown, or dark brown and may persist for months to years without treatment but does tend to improve over time as the underlying inflammatory disorder resolves. Wood lamp examination of epidermal postinflammatory hyperpigmentation may reveal fluorescence. Dermal hyperpigmentation is blue-gray and can be permanent. Dermal and epidermal hyperpigmentation may be simultaneously present. If the inflammatory process is still active, erythematous papules, plaques, or nodules may also be visible.[1][9]

Evaluation

The diagnosis of postinflammatory hyperpigmentation is clinical. Wood lamp evaluation can help distinguish between epidermal and dermal postinflammatory hyperpigmentation. A biopsy may be helpful in confirming the diagnosis if the diagnosis is uncertain or if the underlying etiology has yet to be determined. Laboratory evaluation to rule out Addison disease and systemic lupus erythematosus may be necessary if associated signs and symptoms are present.[4]

Treatment / Management

The treatment of postinflammatory hyperpigmentation is typically stepwise and multimodal in addition to daily protection against ultraviolet radiation.[11] The initial step involves treating the causative inflammatory disorder if it is still active. Following this, topical lightening therapies, often used in combination, are implemented. For severe or refractory cases, chemical peels or laser therapy may be considered. Treatment, lasting months to years, is often required; patient education should set the expectation that improvement of hypermelanosis is slow and recurrences are common.[12]

Topical Therapy

Tyrosinase inhibitors prevent melanin production. The mainstay of treatment is a topical lightening agent such as hydroquinone.[13] Mequinol can be used if a less irritating agent is needed and is often combined with a topical retinoid with or without a topical steroid to enhance and speed effectiveness. A commonly used triple combination includes hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%. The topical steroid can lessen the irritant effects of the skin lightener and the retinoid. Still, the steroid should only be used for up to 8 weeks to minimize the likelihood of steroid-induced skin changes. Topical retinoids include tretinoin, adapalene, and tazarotene. These agents effectively treat underlying acne and postinflammatory hyperpigmentation and may be used long-term. Azelaic acid can also treat both acne and postinflammatory hyperpigmentation.[14]

Chemical Peels

Chemical peels work by removing the epidermal cells containing excess melanin. Experienced clinicians should use these peels with caution as they can cause skin irritation and additional hyperpigmentation. Commonly used peels include glycolic acid, salicylic acid, and trichloroacetic acid.[15][16]

Laser Therapy

Multiple laser types, including Q-switched ruby lasers, Q-switched Nd:YAG lasers, and picosecond lasers (short, intense pulse), have been used to treat postinflammatory hyperpigmentation as fractional photothermolysis. However, experienced clinicians should use them cautiously, as they can cause skin irritation and additional hyperpigmentation.[4][17]

Recent Advances

Recent advancements in research show that topical stabilized cysteamine can be used to treat postinflammatory hyperpigmentation. This option is now considered one of the most potent options available for managing hyperpigmentation disorders in humans.[18]

Differential Diagnosis

When evaluating postinflammatory hyperpigmentation, it is essential to consider a range of differential diagnoses, as several other skin conditions can present with similar pigmentation changes. Accurate diagnosis helps guide effective treatment and rule out conditions requiring different management approaches. The differential diagnosis of postinflammatory hyperpigmentation includes the following:

• Melasma
• Solar lentigines
• Tinea versicolor
• Acanthosis nigricans
• Lichen planus pigmentosus
• Macular amyloidosis
• Ochronosis (patchy hyperpigmentation)
• Erythema dyschromicum perstans morphea
• Discoid lupus erythematosus [9]

Prognosis

Epidermal hyperpigmentation typically resolves or significantly improves within 6 to 12 months, whereas dermal hyperpigmentation improves slowly and may be permanent. Apart from psychological distress, no additional morbidity is associated with postinflammatory hyperpigmentation; however, recurrences are common, particularly without adequate photoprotection.[8]

Complications

The complications of postinflammatory hyperpigmentation are often psychosocial, as the visible pigmentation can significantly impact an individual's self-esteem and quality of life. According to Rook's Textbook of Dermatology, postinflammatory hyperpigmentation can be persistent, especially in cases involving deeper dermal pigmentation. Individuals with darker skin types are more prone to prolonged hyperpigmentation, and treatments aimed at postinflammatory hyperpigmentation may not always be effective, which can lead to frustration and psychological distress.

Fitzpatrick's Dermatology in General Medicine further underscores that postinflammatory hyperpigmentation can sometimes worsen with inappropriate treatments or overexposure to sunlight. Treatments such as chemical peels or lasers, if not carefully tailored, may exacerbate inflammation and worsen pigmentation, especially in individuals with darker skin tones. In addition, sun exposure can intensify pigmentation, making it essential for patients to use sun protection consistently to avoid further darkening.[8][19]