Best practices in: emerging treatment options for postinflammatory hyperpigmentation

Skin & Allergy News, Oct, 2007 by Susan Taylor

Postinflammatory hyperpigmentation (PIH) arises from an acquired increase in cutaneous pigmentation secondary to an inflammatory process. The condition occurs in people of all races and ethnic groups but has a greater prevalence and incidence among darker-skinned individuals. In a study of 2,000 African-American patients seeking dermatologic care, pigmentation disorders constituted the third most common diagnosis, and PIH was the most prevalent of those disorders [Curls 1983;32:388-390]. A variety of topical therapies have been used to treat PIH, yielding variable results. Hydroquinone has been a mainstay of therapy. However, toxicity concerns arising from preclinical models persuaded the European Union (EU), Japan, and Australia to ban the agent's use in cosmetics. The US Food and Drug Administration (FDA) has proposed a similar ban in the United States. Recent clinical investigation of the combination solution of mequinol 2% and tretinoin 0.01% suggests the product might represent a new therapeutic option for PIH.

Background of PIH Although PIH more often affects patients with skin of color, men and women have a similar prevalence and incidence, and PIH occurs in people of all ages. PIH arises from an acquired excess of pigment related to an inflammatory process, such as infection, an allergic reaction, a reaction to medication, trauma, or a proinflammatory disease. In particular, PIH often occurs as a consequence of inflammatory skin disorders, including ache, drug-induced eruptions, eczematoid disorders, and papulosquamous disorders [Semin Cutan Med Surg. 1997;16:36-43].

PIH often is the chief complaint of ache patients of darker races [J Am Acad Dermatol. 2002;46(2 suppl):S98-S106]. PIH is an especially common sequela of acne vulgaris. Many patients find PIH more upsetting than acne, and with good reason. Whereas an acne lesion has a duration of 7 to 10 days, PIH can persist for months or even years [Dermatol Ther. 2004;17:184-195; Dermatol Clin. 2003;21:609-615]. The condition should not be trivialized, as PIH can have a significant adverse psychological impact on patients [J Am Acad Dermatol. 2002;46(2 suppl):S98-S106].

Evaluation and Diagnosis The diagnosis of PIH usually can be made on the basis of the patient's history and physical examination. The history obviously should focus on identification of an inflammatory condition that could have induced the lesion formation. The differential diagnosis should include acanthosis nigricans, Addison disease, lichen amyloidosis, macular amyloidosis, lichen planus, melasma, and tinea versicolor.

The color of PIH lesions varies according to the site of pigment accumulation. Lighter brown lesions usually indicate involvement of the epidermis (epidermal melanosis), and a dark gray appearance suggests dermal involvement (dermal melanosis).

If a patient has no clear history of a preceding inflammatory process, a skin biopsy should be considered.

Treatment Because sun exposure can exacerbate hyperpigmentation, every patient should minimize exposure to sunlight and use a broad-spectrum sunscreen with a high sun protection factor on a daily basis. Multiple topical therapies and lightening agents have been used in the treatment of PIH. Treatment can evolve into a prolonged process that continues for as long as a year before desired results are achieved. The following discussion reviews some of the more commonly used agents.

* Hydroquinone. Hydroquinone's primary mechanism of action is inhibition of tyrosinase, leading to a reduced rate of conversion of dopa to melanin. Prescription formulations contain higher concentrations of hydroquinone (3%-4% versus 1%-2% in nonprescription formulations), which are associated with better efficacy.

Adverse events associated with hydroquinone include irritant and allergic contact dermatitis. Hypopigmentation of normal skin surrounding the treated area may also result. These effects usually resolve with discontinuation of therapy [Arch Dermatol. 1995;131:1453-1457].

Greater concern has surrounded laboratory evidence that hydroquinone might be carcinogenic and fetotoxic [Crit Rev Toxicol. 1999;29:283-330]. Those effects in preclinical models contributed directly to bans on hydroquinone-containing products already in effect and to the ongoing regulatory discussions about the market status of such products in the United States.

* Retinoids. Tretinoin 0.05% to 0.1%, the most commonly used agent in this class, reduces pigmentation by inhibiting tyrosinase and melanin synthesis. Desired results may require treatment for 6 months or longer. Tretinoin also may increase pigmentation secondary to irritation and may cause erythema and peeling [Arch Dermatol. 1995;131:14531457; Br J Dermatol. 1993;129:415-421]. For example, in one clinical trial, treated patients had significant lightening of lesions, but moderately severe dermatitis occurred in half of them [N Engl J Med. 1993; 328:S1438-1443]. Other retinoids used to treat PIH include adapalene, tazarotene, and topical isotretinoin.