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Surgery and Cosmetics

Doris M. Hexsel, MD

Postinflammatory Hyperpigmentation: Clinical and Surgical Issues

Doris M. Hexsel, MD

Tuesday, November 06, 2007

Please note that funding for the following research -- Baumann L, Grimes P, Pandya AG, et al. Triple combination cream is an effective treatment for postinflammatory hyperpigmentation. Poster presented at the annual meeting of the American Academy of Dermatology, Feb. 2-6, 2007, Washington, DC.(reference 8) -- was provided by Galderma Ltd.

Postinflammatory hyperpigmentation (PIH) is a common acquired excess of pigmentation in the epidermal and/or dermal layers of the skin1 and represents a pathophysiologic response to cutaneous inflammation.2,3

PIH can be caused by a previous injury to the skin or a skin irritation.4 Any inflammatory disorder can be associated with PIH, including acne, contact dermatitis, atopic dermatitis, lichen planus, and trauma.2-4

Lichen simplex chronicus and PIH

Figure 1. Lichen simplex chronicus and PIH

Recent data shows that PIH can affect all skin types. However, it is more obvious in ethnic and dark-skinned patients.2,3 This condition has no gender or age predominance.3

The lesions are characteristically hyperpigmented macules limited to the site of the preceding inflammation and have indistinct, feathered borders.3 The shape of the resulting lesion can closely follow the contours of the site of the original inflammatory response.5 This information may be important in correlating the lesion with its cause and helping to establish a differential diagnosis.5 If not treated, it can persist for years.

PIH 5 years after a burn

Figure 2. PIH 5 years after a burn

This condition may have a major impact because disfiguring facial or body lesions can significantly affect a person's psychological and social well-being, contributing to lower productivity, social functioning, and self-esteem.3

Ethnic and dark-skinned patients have an increased risk for developing PIH,6 presumably because they already have higher baseline epidermal melanin content.2 In these patients, PIH seems to be more evident and more difficult to treat.

It is very important to identify positive personal or familial history of PIH before any cosmetic procedure is performed. If a positive history of PIH is present, the occurrence of PIH in the postoperative period is predictable; some resistance to bleaching agents can also be expected. Moreover, the occurrence of PIH in the postoperative period may be interpreted by physicians and patients as recurrence of hyperpigmented lesions, such as solar lentigines and others.

Postinflammatory hyperpigmentation may exhibit epidermal, dermal, or mixed melanotic involvement. There is an increase in melanin production, but normal number of melanocytes.2

Melanophages near superficial vascular plexus containing melanin

Figure 3a. Melanophages near superficial vascular plexus containing melanin (pigmentary incontinency and melanophagy) (100 X). Courtesy of Dr AndrĂ© Cartel.

Melanophages near superficial vascular plexus containing melanin

Figure 3b. Melanophages near superficial vascular plexus containing melanin (pigmentary incontinency and melanophagy) (400X). Courtesy of Dr AndrĂ© Cartel.

Preventing and Treating PIH

A personal medical history and physical exam can predict PIH, and measures can be taken to help prevent it from developing in potential candidates.

The treatment of PIH is difficult and remains a challenge.7 It begins by aggressive management and control of the underlying inflammatory skin condition.2 In choosing therapies for dark-skinned patients, clinicians must find a balance between aggressive early intervention to target inflammatory lesions and gentle treatments to increase tolerability and avoid skin irritation.4 Based on my clinical experience, efficient anti-inflammatory agents, such as topical and oral corticosteroids may be used at this point.

An early approach is important, as lesions can persist for extended periods if untreated.1 As PIH is treated like melasma, topical bleaching agents and sunblocks2 are recommended for PIH. They can also be administered in the postoperative period of surgical procedures, such as laser therapy. Some authors also advocate their use preoperatively.2

Most of the therapies used for hyperpigmentation have been studied in melasma, another common acquired pigmentary disorder, and the same treatment principles hold for PIH.3

The therapeutic goals for hyperpigmentation include:

  • promoting the degradation of melanosomes
  • inhibiting the formation of melanosomes
  • retarding the proliferation of melanocytes

Because sun exposure is an important etiologic factor in pigmentation, sun protective measures should include all necessary measures for sun avoidance. These include the use of a broad-spectrum, high sun protection factor (SPF) sunscreen and protective clothes as well as minimizing sun exposure.3

Lynde et al. reported that combination therapy is more effective than single agents used in the treatment of melasma. The addition of tretinoin eliminates pigment and increases keratinocyte proliferation by preventing the oxidation of hydroquinone (HQ) and improving epidermal penetration. Further, adding topical corticosteroids reduces the irritative effects of hypopigmenting agents and inhibits melanin synthesis by decreasing cellular metabolism.3

One study on the effectiveness of triple-combination cream for PIH showed that triple-combination cream is efficacious for the treatment of PIH and very likely is more efficacious than the dyad comparators.8 It is unfortunate that this study was a small study and did not show statistical significance against all of the dyad comparators. Triple-combination cream did show statistical superiority over 2 of the 3 dyads (hydroquinone+tretinoin and fluocinolone+tretinoin) for the percent of patients who were clear or almost clear in 8 weeks (see Table 1). Furthermore, it is clear that patients were still improving at the end of the 8-week study period, suggesting that longer treatment periods may be necessary for full effect of the treatment. It is important to note that there are currently no approved treatments for PIH. For this reason, the potential efficacy of triple-combination cream may be important. PIH is a difficult condition to treat and carries significant risk of emotional scarring. Under these circumstances, triple-combination cream should be considered as a treatment option for PIH.

Table 1


Efficacy With Triple-Combination Cream
- 13% of patients were CLEAR in 8 weeks
- 45% of patients were CLEAR or ALMOST CLEAR in 8 weeks
Safety With Triple-Combination Cream
- No atrophy was reported
- Less irritation, dryness, erythema and desquamation compared to hydroquinone and tretinoin (H+T)
- More pigmentation changes were reported with triple-combination cream compared to dyads

Grimes and Callender conducted a double-blind, randomized, vehicle-controlled study using tazarotene cream for PIH and acne in dark-skinned patients.

Ortonne reported that topical retinoids such as all-trans-retinoic acid (RA), retinol, tazarotene, and adapalene improve depigmentation. The use of retinoic acid as monotherapy has improved PIH. Moreover, RA in combination with hydroquinone (HQ) or azelaic acid increases the potency of depigmenting agents for the treatment of PIH.10

Table 2


Treatment Uses Results and Benefits
Natural ingredients such as soy and licorice PIH and melasma The relative gentleness of these products makes them excellent choices for use in dark-skinned patients11
0.1% tretinoin cream PIH in dark-skinned patients The drug achieves significant lightening effects, but 50% of the subjects in the tretinoin group
experienced at least moderate dermatitis12
Microentrapped HQ 4% with retinol 0.15% PIH The treatment is safe and effective.13
Glycolic acid peels and a topical regimen of 2% hydroquinone, 10% glycolic acid, and 0.05% tretinoin cream PIH in dark-skinned patients Results showed therapeutic improvement with minimal adverse effects. However, caution must be taken when performing peels on dark-skinned patients because of the increased risk of hyperpigmentation14

Most patients with prominent or long-lasting PIH will require treatment with a topical retinoid and hydroquinone.6 Long-lasting PIH may be resistant to bleaching agents.

Preventive treatment is mandatory for patients undergoing surgical procedures if a positive personal history or lesions of PIH are identified. Preventive treatment includes some decisions in performing surgical procedures, including combining procedures that give similar depth and inflammatory changes. The avoidance of localized treatments minimizes the risks of PIH. The combination of localized procedures with resurfacing techniques is useful in risky patients in the prevention and management of PIH.

Anti-inflammatory agents can be used to treat inflammation during the postoperative period, and bleaching agents and sunblocks can be used as soon as the healing process is completed, before the appearance of PIH. Also, opaque camouflage may be used as part of the large armamentarium of topical treatments for PIH.1

Conclusion

Prompt presentation to a doctor at the first signs of skin inflammation and/or PIH, sun avoidance, and an earlier intervention in both inflammatory preceding process or disease and resulted PIH will significantly help improve treatment outcomes.2

Future perspectives in the treatment of PIH may include more effective bleaching agents and sunblocks, new techniques and procedures that may be helpful in removing the excessive melanin, and perhaps the control of hormones such as MSH, cytokines, and other compounds that actively participate in pigment production in hyperpigmented conditions, such as this normal but unaesthetic skin response of some individuals.

Facial lesions of PIH, before treatment

Figure 4a. Facial lesions of PIH, before treatment

Facial lesions of PIH, after 2 months of treatment with triple-combination cream and sun-protective measures

Figure 4b. Facial lesions of PIH, after 2 months of treatment with triple-combination cream and sun-protective measures

References

  1. Taylor SC, Burgess CM, Callender VD, et al. Postinflammatory hyperpigmentation: evolving combination treatment strategies. Cutis. 2006 Aug;78(2 Suppl):6-19.
  2. Cayce KA, McMichael AJ, Feldman SR. Hyperpigmentation: an overview of the common afflictions. Dermatol Nurs. 2004 Oct;16(5):401-17.
  3. Lynde CB, Kraft JN, Lynde CW. Topical treatments for melasma and postinflammatory hyperpigmentation. Skin Therapy Lett. 2006 Nov;11(9):1-6.
  4. Callender VD. Acne in ethnic skin: special considerations for therapy. Dermatol Ther. 2004;17(2):184-95.
  5. Peel M, Hughes J, Payne-James JJ. Postinflammatory hyperpigmentation following torture. J Clin Forensic Med. 2003 Sep;10(3):193-6.
  6. Callender VD. Considerations for treating acne in ethnic skin. Cutis. 2005 Aug;76(2 Suppl):19-23.
  7. Hasan AT, Eaglstein W, Pardo RJ. Solar-induced postinflammatory hyperpigmentation after laser hair removal. Dermatol Surg. 1999 Feb;25(2):113-5.
  8. Baumann L, Grimes P, Pandya AG, et al. Triple combination cream is an effective treatment for post-inflammatory hyperpigmentation. Poster presented at the annual meeting of the American Academy of Dermatology, Feb. 2-6, 2007, Washington, DC.
  9. Grimes PE, Callender VD. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind randomized, vehicle-controlled study. Cutis. 2006 Jan;77(1):45-50.
  10. Ortonne JP. Retinoid therapy of pigmentary disorders. Dermatol Ther. 2006 Sep-Oct;19(5):280-8.
  11. Baumann L, Rodriguez D, Taylor SC, et al. Natural considerations for skin of color. Cutis. 2006 Dec; 78(6 Suppl):2-19.
  12. Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et al. Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. N Engl J Med 1993; 328(20):1438-43.
  13. Grimes PE. A microsponge formulation of hydroquinone 4% and retinol 0,15% in the treatment of melasma and postinflammatory hyperpigmentation. Cutis. 2004 Dec;74(6):362-8.
  14. Burns RL, Prevost-Blank PL, Lawry MA, et al. Glycolic acid peels for postinflammatory hyperpigmentation in black patients. A comparative study. Dermatol Surg 1997; 23(3):171-4; discussion 175.
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