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Preventing Post-inflammatory Hyperpigmentation In Skin of Color

Post Inflammatory Hyperpigmentation

Post inflammatory hyperpigmentation, or PIH, is darkening of the skin that results after an inflammatory process in the skin. It is much more common in dark skinned individuals and is the one of the most common reasons that darker racial/ethnic groups seek dermatological care.1 Common causes of PIH in skin of color include acne vulgaris and atopic dermatitis. PIH can be extremely distressing condition due to its undesirable cosmetic appearance, making it an important condition to prevent and treat if possible.

PIH results from the overproduction of melanin or irregular dispersion of pigment after inflammation.1 It manifests as macules or patches in the same distribution of the cutaneous inflammatory process, with the location of excess pigment determining the exact coloration of the hyperpigmentation.1 Excess pigment production in the epidermis (or top layer of skin) will appear tan, brown, or dark brown, while pigment in the dermis will have a blue-gray appearance. Epidermal hyperpigmentation can sometime resolve on its own, though may take months to years, while dermal hyperpigmentation is likely permanent.1

Mechanism of PIH as a Response to Wound Healing

The mechanism of PIH is not fully understood, but it is hypothesized to be mediated by several inflammatory factors that upregulate melanocyte activity. Multiple studies have shown that melanocyte-stimulating properties of leukotrienes (LT), prostaglandins (PGs) E2 and D2, thromboxane-2, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, epidermal growth factor, and reactive oxygen species such as nitric oxide (NO).1 Melanocytes are also considered anti-inflammatory cells that can act as free radical scavengers, thereby reducing oxidative damage. Therefore, within a wound it would be expected that they would be the first cell to enter given the role of oxidative damage in the initial wound healing response. However, melanocytes seem to enter the wound later, once it has re-epithelized, for reasons unclear,2 but likely due to their slower natural migration compared to keratinocytes.

Treatment of Acne in Ethnic Skin to Prevent PIH

PIH is a common sequalae of acne in people with darker skin. A recent survey of black, Hispanic, and Asian individuals showed that the percentage of people with acne and hyperpigmented macules (secondary to acne) to be 65%, 53%, and 47% respectively.3

PIH secondary to acne can be due to the inflammatory acne lesions themselves or irritating acne treatments. Early and aggressive therapy for acne patients of color is the best way to prevent PIH, with careful consideration to not use therapies that will cause significant irritation and worsen PIH.3

Special considerations when treating acne in dark-skinned patients3:

  • Use a gentle cleanser with careful consideration of cosmetics: Counsel patients to avoid irritating products and not to scrub or wash the face vigorously.
  • Use of topical retinoids: Physicians are often weary to prescribe retinoids due to the possibility of irritant contact dermatitis and subsequent development of hyper/hypopigmentation. However, careful use of retinoids is recommended, as it targets melanin production and possesses anti-inflammatory properties that are useful at preventing and treating PIH. It prevents melanin production by inhibiting tyrosinase, increasing keratinocyte turnover, and increasing keratinocyte pigment granule dispersal.4 Starting at a low concentration or with a short duration of exposure may be less irritating. Do not start if there are signs of irritation from previous acne therapy.
  • Use of azelaic acid: This is a naturally occurring substance that competitively inhibits tyrosinase, the enzyme responsible for producing melanin from tyrosine. Use of this medication may be helpful in preventing PIH due to its low potential for irritation, anti-inflammatory actions, and inhibition of melanin synthesis through tyrosinase and melanocyte proliferation inhibition.4 Azelaic acid also decreases the production of free radicals which are believed to play a role in PIH development.5 This medication can be combined with benzoyl peroxide wash and used on the trunk. Frequent use of azelaic acid

Preventing PIH after Dermatological Skin Procedures

Dermatological skin procedures, such as lasers and skin biopsies, cause destruction of the skin that can result in PIH secondary to the inflammatory phase of the wound-healing cascade. Treatment of this initial inflammatory process is important in order to prevent PIH and/or hasten its resolution. It should be noted that the literature is minimal in this area and more research would need to be done to further support the recommendations to follow.

Recommendations to prevent PIH after cutaneous procedures:

Application of corticosteroids

A study performed by Cheyasak et al. showed that the use of topical clobetasol was significantly more effective than petrolatum jelly at preventing PIH after CO2 ablative fractional resurfacing. 6 Steroids are thought to work due to the anti-inflammatory properties via inhibition of phospholipase A2, preventing the formation of PGs and LTs. While corticosteroids do have anti-proliferative effects, which could interfere with fibroblast activity and thus negatively impact wound healing, this study found no difference in healing time between the two treatment groups.6 The only adverse reaction noted in this study was an acneiform eruption that occurred on postoperative day 3-4 in 7.5% of subjects that resolved with clindamycin 1% solution and adapalene 0.1% gel.

In this study, subjects applied Clobetasol 0,05% ointment twice daily for the first 2 days following the procedure. A study performed by Takiwaki et al. compared the use of clobetasol 0.05%, 0.1% hydrocortisone, 1% indomethacin, and hydrophilic ointment after irradiation to evaluate the degree of hyperpigmentation prevented by the different topicals.7 These were applied and covered by a dressing for three hours after irradiation, then removed. This study showed that clobetasol had the strongest suppression of pigment development, followed by hydrocortisone then indomethacin (with statistically significant differences).7 Hydrocortisone was also applied at different time intervals, with a longer duration of treatment (20 hours) significantly preventing hyperpigmentation more effectively than shorter durations (6 hours and 1 hour).7 To our knowledge, no other studies have been performed evaluating steroids and prevention of PIH, but these two studies would suggest that a short course of clobetasol 0.05% ointment may be helpful to prevent PIH.

Application of topical NSAIDS

While there are no studies to support topical NSAID use after cutaneous procedures, topical indomethacin (along with corticosteroids) was shown to decrease UVB-induced hyperpigmentation in a study performed by Takiwaki et al.7 Mechanistically, it would be reasonable to suspect similar efficacy of topical NSAIDs in preventing PIH due to their inhibition of cyclooxygenase. Compared to steroids, however, topical indomethacin was less effective.

Application of botanicals

Several studies suggest that botanicals may prevent PIH due to their antioxidant and anti-inflammatory effects. These work better to prevent hyperpigmentation rather than treat it once it occurs because they act to decrease the initial inflammatory process as opposed to targeting melanin production to oppose skin darkening.4 These botanicals include grape seed extract taken orally and Glechoma hederacea extract used topically. Both contain the active component proanthocyanidin, which has both anti-inflammatory and ROS suppression activity.4 Soy extract applied in a moisturizer vehicle can be used both as preventative measure and treatment due to its ROS suppression n and serine proteases inhibitor activity that prevents melanosome transfer, causing lightening after PIH develops.4

Sun protection

This is an extremely important part of the treatment and prevention of PIH and should not be overlooked. Ultraviolet radiation can stimulate melanogenesis but upregulating intra and intercellular messengers, such as nitric oxide.2 It is necessary to educate your patients, especially dark-skinned individuals about the importance of photoprotection, as many people with higher skin phototypes do not wearing sunscreen or use other photoprotective measures. It is recommended to use broad-spectrum sunscreen daily (SPF >30) and practice sun avoidance or use sun-protective clothing. 2

Table 1. Overview of Therapies to Prevent PIH

Therapy

Anti-inflammatory properties

ROS Suppression

 Target melanin

(Suppress melanosome transfer or production or melanin)

Cell Turnover

Side Effects

Topical Retinoids

 X

 

 

 X

Redness, irritation, peeling

Azelaic Acid

 X X X

 

Irritation (though less than retinoids), itching

Topical Corticosteroids

X

 

 

 

Acneiform eruption

Topical NSAIDs

 

 

 

Minimal, especially if used for short duration

Proanthrocyanidin (oral)

X X

 

 

Not well reported, likely minimal. No drug interactions reported

Proanthrocyanidin (topical)

X X

 

 

Likely minimal, but not well reported

Soy extract (topical)

 

X X

 

Likely minimal, but not well reported

 

Key Takeaways

  • Dark-skinned individuals are extremely prone to development of PIH.
  • PIH can cause significant psychological distress to the patient
  • PIH can be induced iatrogenically via laser treatments, skin biopsies, or other cutaneous procedures that injure the skin
  • Careful consideration when treating acne in darker-skinned individuals. Treatment must be aggressive enough to avoid excess inflammation due to acne, while at the same time being careful not to cause too much irritation from the treatment itself.
  • Steroid ointment, topical NSAIDs, and/or certain botanicals can be used for a short time after cutaneous procedures to prevent PIH and will likely not negatively impact wound healing.
  • Photoprotection is extremely important in preventing and treating PIH.
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References

  1. Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthetic Dermatol. 2010;3(7):20-31.
  2. Chadwick S, Heath R, Shah M. Abnormal pigmentation within cutaneous scars: A complication of wound healing. Indian J Plast Surg Off Publ Assoc Plast Surg India. 2012;45(2):403-411. doi:10.4103/0970-0358.101328
  3. Callender VD. Acne in ethnic skin: special considerations for therapy. Dermatol Ther. 2004;17(2):184-195. doi:10.1111/j.1396-0296.2004.04019.x
  4. Fisk WA, Agbai O, Lev-Tov HA, Sivamani RK. The use of botanically derived agents for hyperpigmentation: A systematic review. J Am Acad Dermatol. 2014;70(2):352-365. doi:10.1016/j.jaad.2013.09.048
  5. Halder RM, Richards GM. Management of dyschromias in ethnic skin. Dermatol Ther. 2004;17(2):151-157. doi:10.1111/j.1396-0296.2004.04015.x
  6. Cheyasak N, Manuskiatti W, Maneeprasopchoke P, Wanitphakdeedecha R. Topical Corticosteroids Minimise the Risk of Postinflammatory Hyper­pigmentation After Ablative Fractional CO2 Laser Resurfacing in Asians. Acta Derm Venereol. 2015;95(2):201-205. doi:10.2340/00015555-1899
  7. Takiwaki H, Shirai S, Kohno H, Arase S, Soh H. The Degrees of UVB-Induced Erythema and Pigmentation Correlate Linearly and Are Reduced in a Parallel Manner by Topical Anti-Inflammatory Agents. J Invest Dermatol. 1994;103(5):642-646. doi:10.1111/1523-1747.ep12398276