| Patient Education |
|
Click here for patient education.
|
|
You are in: eMedicine Specialties >
Dermatology > DISEASES OF PIGMENTATION
Postinflammatory Hyperpigmentation
Article Last Updated: Mar 28, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Coauthor(s):
Nadia I Kihiczak, MD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey Medical School
Editors: Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
postinflammatory hypermelanosis, melanotic hyperpigmentation, PIH, dermal melanosis, epidermal melanosis, skin inflammation, hyperpigmentation
Background
Postinflammatory hyperpigmentation (PIH) is a frequently encountered problem and represents the sequelae of various cutaneous disorders as well as therapeutic interventions. This acquired excess of pigment can be attributed to various preceding disease processes that affect the skin; these processes include infections, allergic reactions, mechanical injuries, reactions to medications, phototoxic eruptions, trauma (eg, burns), and inflammatory diseases (eg, lichen planus, lupus erythematosus, atopic dermatitis). Typically, PIH is most severe in patients with lichenoid dermatoses in which the basal cell layer of the epidermis is disrupted.
Medscape's Aesthetic Medicine Resource Center and eMedicine's Skin Lightening and Depigmenting Agents article may be of interest.
Pathophysiology
PIH is caused by 1 of 2 mechanisms that result in either epidermal melanosis or dermal melanosis. The epidermal inflammatory response (ie, dermatitis) results in the release and subsequent oxidation of arachidonic acid to prostaglandins, leukotrienes, and other products. These products of inflammation alter the activity of both immune cells and melanocytes. Specifically, these inflammatory products stimulate epidermal melanocytes, causing them to increase the synthesis of melanin and subsequently to increase the transfer of pigment to surrounding keratinocytes. Such increased stimulation and transfer of melanin granules results in epidermal hypermelanosis. On the contrary, dermal melanosis occurs when inflammation disrupts the basal cell layer, causing melanin pigment to be released and subsequently trapped by macrophages in the papillary dermis, also known as pigmentary incontinence.
Frequency
United States
PIH is a universal response of the skin, but it is more common in pigmented, darker skin. PIH can be caused by any inflammatory process of the skin; however, it is more apparent in photo-induced dermatoses and more severe in lichenoid dermatoses.
International
Internationally, PIH is a common inflammatory response of the skin, developing more commonly in darker skin.
Mortality/Morbidity
- Morbidity associated with PIH is related to the underlying inflammatory process that causes PIH.
- To the author's knowledge, no cases of mortality have been associated with PIH.
Race
Although PIH occurs in whites, it is more common in dark-skinned individuals (eg, African Americans).
Sex
PIH occurs with equal incidence in males and females; it has no sexual predilection.
Age
PIH can occur in persons of any age.
History
A diagnosis of PIH should be considered if a history of a preceding pathologic process or injury to the affected area of hyperpigmentation is present.
Physical
- The distribution of the hypermelanotic lesions depends on the location of the original inflammatory dermatosis.
- The color of the lesions ranges from light brown to black, with a lighter brown appearance if the pigment is within the epidermis (ie, epidermal melanosis) and a darker gray appearance if lesions contain dermal melanin (ie, dermal melanosis).
Causes
- PIH can occur with various disease processes that affect the skin. These processes include allergic reactions, infections, trauma, and phototoxic eruptions. Fractional laser photothermolysis occasionally induces PIH.1
- Common inflammatory diseases that result in PIH include acne excoriée, lichen planus, systemic lupus erythematosus, chronic dermatitis, and cutaneous T-cell lymphoma, especially erythrodermic variants.
- Furthermore, lesions of PIH can darken with exposure to UV light and various chemicals and medications, such as tetracycline, bleomycin, doxorubicin, 5-fluorouracil, busulfan, arsenicals, silver, gold, antimalarial drugs, hormones, and clofazimine.
Acanthosis Nigricans
Addison Disease
Amyloidosis, Lichen
Amyloidosis, Macular
Lichen Planus
Melasma
Tinea Versicolor
Lab Studies
- A Wood lamp examination enables distinction of epidermal PIH from dermal PIH.
- Epidermal lesions tend to have accentuated borders under a Wood lamp examination, whereas those of dermal lesions are not accentuated with a Wood lamp examination.
Procedures
- If a history of preceding inflammatory dermatosis is unclear or absent, skin biopsy is warranted to exclude other underlying causes of hyperpigmentation.
- Staining of the biopsy specimen with Fontana-Masson silver stain for melanin enables localization of the melanin in the epidermis and/or the dermis.
Histologic Findings
Epidermal PIH involves increased melanin pigment in the basal cell layer of the epidermis. Occasionally, giant melanosomes are evident in the epidermis.
Dermal PIH involves the upper dermis, with pigment incontinence due to increased numbers of melanophages in the papillary dermis.
Medical Care
The treatment of PIH tends to be a difficult and prolonged process that often takes 6-12 months to achieve the desired results of depigmentation. Each of these treatment options potentially improves epidermal hypermelanosis, but none is proven effective for dermal hypermelanosis. Daily use of a broad-spectrum sunscreen (sun protection factor [SPF] 15 or greater) is an essential part of any therapeutic regimen. - A variety of topical treatments have been used to treat epidermal PIH, with varying degrees of success. These agents include hydroquinone, tretinoin cream, corticosteroids, glycolic acid (GA), and azelaic acid.2 Lightening of hyperpigmented areas may be achieved with one of the previously named topical agents; however, a combination of topical creams and gels, chemical peels, and sunscreens may be necessary for significant improvement.
- Topical tretinoin 0.1% has been effective in African Americans. GA peels, in combination with tretinoin and hydroquinone, are an effective treatment of PIH in dark-complexioned individuals.3 All-trans retinoic acid aqueous gel 0.1-0.4% may be applied concomitantly with hydroquinone–lactic acid ointment for bleaching.4 After sufficient improvement of the hyperpigmentation is achieved, a corticosteroid may be applied topically with hydroquinone to promote healing. This combination of various topical therapeutic agents has been shown to be beneficial, especially on the face.
- Topical azelaic acid, which has been approved for the treatment of acne vulgaris, is useful for postinflammatory hyperpigmentation.5 It may be desirable to use to treat acne itself for patients in whom PIH tends to develop. The efficacy of tazarotene 0.1% cream for the treatment of dyschromia associated with photoaging and for acne vulgaris may also be beneficial, particularly in people with dark skin.6
- Other treatment modalities include use of trichloroacetic acid and gentle cryotherapy with liquid nitrogen. Each method must be used with extreme caution to avoid necrosis or blistering of the treated skin. These 2 methods of treatment should be avoided in dark-skinned patients because of the risk of permanent depigmentation and scarring.
- Pigmented makeup creams have also been successfully used to camouflage hyperpigmented skin to a hue similar to that of the surrounding unaffected skin.
- More options will be available in the future. Retinaldehyde (RAL) has shown depigmenting activity, while glycolic acid (GA) decreases the excess of pigment by a wounding and reepithelization process. A combination of RAL 0.1% and GA 6% RALGA (Diacneal) in the treatment of acne vulgaris and PIH was noted as successful.7 The peroxidase inhibitor methimazole, a noncytotoxic inhibitor of melanin production, is a possible agent for topical use in the years ahead.8
- The efficacy and safety of a combined treatment regimen including serial GA peels, topical azelaic acid cream, and adapalene gel in the treatment of recalcitrant melasma was evaluated in 28 patients in a prospective, randomized, controlled trial lasting 20 weeks.9 Those receiving chemical peels underwent serial GA peels in combination with topical azelaic acid 20% cream (twice daily) and adapalene 0.1% gel (4 times daily, applied at night). Combined treatment with serial GA peels, azelaic acid cream, and adapalene gel may be an effective and safe therapy for recalcitrant melasma.
Topical treatments include hydroquinone, azelaic acid, corticosteroids, tretinoin cream, GA, and trichloroacetic acid. Wide-spectrum sunscreens are an integral part of any treatment regimen. Combined therapy using Q-switched ruby laser and cutaneous bleaching with tretinoin and hydroquinone may be used for periorbital skin hyperpigmentation in selected patients.10
Drug Category: Depigmenting agents
These agents are used for gradual bleaching of hyperpigmented skin.
| Drug Name | Hydroquinone (Ambi Skin Tone, Melanex, Nuquin HP) |
|---|
| Description | A 1,4-benzenediol that suppresses melanocyte metabolic processes, especially enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylamine. Exposure to sun reverses effects and causes repigmentation. |
|---|
| Adult Dose | Apply sparingly and rub in bid |
|---|
| Pediatric Dose | <12 years: Not established
>12 years: Apply as in adults |
|---|
| Contraindications | Documented hypersensitivity; sunburns |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Application area should not extend beyond face, neck, hands, or arms; avoid sun exposure on treated skin during treatment (patient should wear sun-protective clothing or broad-spectrum sunscreen to prevent increased hyperpigmentation or repigmentation) |
|---|
| Drug Name | Azelaic acid (Azelex, Finevin) |
|---|
| Description | May have bleaching effect on skin. Also, may have an antimicrobial effect. |
|---|
| Adult Dose | Wash area and apply sparingly bid |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | None reported |
|---|
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
|---|
| Precautions | Sensitivity or severe irritation (discontinue treatment); avoid contact with eyes |
|---|
Drug Category: Keratolytic agents
These agents cause cornified epithelium to swell and soften and then become macerated and desquamated.
| Drug Name | Trichloroacetic acid (Tri-Chlor) |
|---|
| Description | Cauterizes skin, keratin, and other tissues. |
|---|
| Adult Dose | Paint onto lesions, avoid uninvolved skin; repeat q1-2wk |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity; not for use on premalignant or malignant lesions |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | For external use only; restrict to treatment areas only; use with extreme caution to avoid necrosis of treated skin; avoid in dark-skinned patients (risk of permanent depigmentation and scarring) |
|---|
Drug Category: Retinoids
Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and modulate keratinocyte differentiation.
| Drug Name | Tretinoin (Avita, Renova, Retin-A) |
|---|
| Description | Inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Also available as 0.01% and 0.025% gels. |
|---|
| Adult Dose | Apply hs or qod; begin with lowest concentration and increase as tolerated; decrease frequency if irritation develops |
|---|
| Pediatric Dose | <12 years: Not established
>12 years: Apply as in adults |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | Increased toxicity with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Because of increased susceptibility to burning, patients should minimize exposure to sunlight or sunlamps; local erythema, burning, stinging, or peeling (avoid application to eyes, mouth, angles of the nose, and mucous membranes) |
|---|
Drug Category: Corticosteroids
These drugs have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
| Drug Name | Hydrocortisone (Cortaid, Dermacort, Westcort) |
|---|
| Description | An adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. Has mineralocorticoid and glucocorticoid effects, resulting in anti-inflammatory activity. |
|---|
| Adult Dose | Apply sparingly to affected areas bid/qid |
|---|
| Pediatric Dose | Apply as in adults |
|---|
| Contraindications | Documented hypersensitivity; viral, fungal, and bacterial skin infections |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Prolonged use, applying over large surface areas, applying potent steroids, and use of occlusive dressings may increase systemic absorption and cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria |
|---|
| Drug Name | Desonide (DesOwen, Tridesilon) |
|---|
| Description | Stimulates synthesis of enzymes that decrease inflammation. Suppresses mitotic activity and causes vasoconstriction. |
|---|
| Adult Dose | Apply sparingly bid/qid |
|---|
| Pediatric Dose | Apply as in adults |
|---|
| Contraindications | Documented hypersensitivity; viral, fungal, and bacterial skin infections |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Prolonged use, applying over large surface areas, applying potent steroids, and use of occlusive dressings may increase systemic absorption and cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria |
|---|
| Drug Name | Betamethasone (Alphatrex, Diprolene, Maxivate) |
|---|
| Description | Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. |
|---|
| Adult Dose | Apply thin film bid/qid until response occurs |
|---|
| Pediatric Dose | Apply as in adults, with caution |
|---|
| Contraindications | Documented hypersensitivity; paronychia; cellulitis; impetigo; angular cheilitis; erythrasma; erysipelas; rosacea; perioral dermatitis; acne |
|---|
| Interactions | None reported |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Do not use on skin with decreased circulation; can cause atrophy of groin, face, and axillae; may cause striae distensae or rosacealike eruption; may increase skin fragility; may suppress HPA axis (rare); in infection that is not responsive to antibiotic treatment, discontinue until infection is under control; do not use monotherapy to treat widespread plaque psoriasis |
|---|
Deterrence/Prevention
- Patients with PIH should use sunscreen on a daily basis to prevent any further darkening of lesions.
Prognosis
- PIH tends to fade with time and therapy, as previously discussed.
- Remnants of epidermal hyperpigmentation may persist for indefinite periods, typically 6-12 months, after the initial inflammatory process resolves.
- Dermal PIH may even persist for years.
Patient Education
- Educate patients about the cause of PIH, prolonged therapy, and persistence of hyperpigmented lesions.
Medical/Legal Pitfalls
- Patients should be informed that PIH is not easily treated.
- PIH is typically a persistent discoloration of skin that gradually resolves over 6-12 months.
Special Concerns
- Patients should never be treated with monobenzyl ether of hydroquinone because of the risk of developing disfiguring depigmented patches of skin either at the application site or at distal cutaneous sites.
| Media file 1:
Photo of a 42-year-old African American woman with macules of postinflammatory hyperpigmentation on the left side of her face as a result of acne excoriée. |
 |  View Full Size Image | |
Media type: Photo
|
- Graber EM, Tanzi EL, Alster TS. Side effects and complications of fractional laser photothermolysis: experience with 961 treatments. Dermatol Surg. Mar 2008;34(3):301-5; discussion 305-7. [Medline].
- Breathnach AS. Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies. Cutis. Jan 1996;57(1 Suppl):36-45. [Medline].
- Burns RL, Prevost-Blank PL, Lawry MA, Lawry TB, Faria DT, Fivenson DP. Glycolic acid peels for postinflammatory hyperpigmentation in black patients. A comparative study. Dermatol Surg. Mar 1997;23(3):171-4; discussion 175. [Medline].
- Yoshimura K, Harii K, Aoyama T, Shibuya F, Iga T. A new bleaching protocol for hyperpigmented skin lesions with a high concentration of all-trans retinoic acid aqueous gel. Aesthetic Plast Surg. Jul-Aug 1999;23(4):285-91. [Medline].
- Del Rosso JQ. The use of topical azelaic acid for common skin disorders other than inflammatory rosacea. Cutis. Feb 2006;77(2 Suppl):22-4. [Medline].
- Grimes P, Callender V. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis. Jan 2006;77(1):45-50. [Medline].
- Katsambas AD. RALGA (Diacneal), a retinaldehyde and glycolic acid association and postinflammatory hyperpigmentation in acne--a review. Dermatology. 2005;210 Suppl 1:39-45. [Medline].
- Kasraee B, Handjani F, Parhizgar A, Omrani GR, Fallahi MR, Amini M, et al. Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case. Dermatology. 2005;211(4):360-2. [Medline].
- Erbil H, Sezer E, Tastan B, Arca E, Kurumlu Z. Efficacy and safety of serial glycolic acid peels and a topical regimen in the treatment of recalcitrant melasma. J Dermatol. Jan 2007;34(1):25-30. [Medline].
- Momosawa A, Kurita M, Ozaki M, Miyamoto S, Kobayashi Y, Ban I, et al. Combined therapy using Q-switched ruby laser and bleaching treatment with tretinoin and hydroquinone for periorbital skin hyperpigmentation in Asians. Plast Reconstr Surg. Jan 2008;121(1):282-8. [Medline].
- Choi H, Ahn S, Lee BG, Chang I, Hwang JS. Inhibition of skin pigmentation by an extract of Lepidium apetalum and its possible implication in IL-6 mediated signaling. Pigment Cell Res. Dec 2005;18(6):439-46. [Medline].
- Epstein JH. Postinflammatory hyperpigmentation. Clin Dermatol. Apr-Jun 1989;7(2):55-65. [Medline].
- Harari Z, Sommer I, Knobel B. Multifocal contact dermatitis to nitroderm TTS 5 with extensive postinflammatory hypermelanosis. Dermatologica. 1987;174(5):249-52. [Medline].
- Lacz NL, Vafaie J, Kihiczak NI, Schwartz RA. Postinflammatory hyperpigmentation: a common but troubling condition. Int J Dermatol. May 2004;43(5):362-5. [Medline].
- Nordlund JJ. Postinflammatory hyperpigmentation. Dermatol Clin. Apr 1988;6(2):185-92. [Medline].
- Pandya AG, Guevara IL. Disorders of hyperpigmentation. Dermatol Clin. Jan 2000;18(1):91-8, ix. [Medline].
- Pérez-Bernal A, Muñoz-Pérez MA, Camacho F. Management of facial hyperpigmentation. Am J Clin Dermatol. Sep-Oct 2000;1(5):261-8. [Medline].
- Rokhsar CK, Fitzpatrick RE. The treatment of melasma with fractional photothermolysis: a pilot study. Dermatol Surg. Dec 2005;31(12):1645-50. [Medline].
- Ruiz-Maldonado R, Orozco-Covarrubias ML. Postinflammatory hypopigmentation and hyperpigmentation. Semin Cutan Med Surg. Mar 1997;16(1):36-43. [Medline].
- Tomita Y, Maeda K, Tagami H. Mechanisms for hyperpigmentation in postinflammatory pigmentation, urticaria pigmentosa and sunburn. Dermatologica. 1989;179 Suppl 1:49-53. [Medline].
- Winhoven SM, Ahmed I, Owen CM, Lear JT. Postinflammatory hyperpigmentation in an Asian patient: a dramatic response to oral isotretinoin (13-cis-retinoic acid). Br J Dermatol. Feb 2005;152(2):368-9. [Medline].
- Yoshimura K, Harii K, Aoyama T, Iga T. Experience with a strong bleaching treatment for skin hyperpigmentation in Orientals. Plast Reconstr Surg. Mar 2000;105(3):1097-108; discussion 1109-10. [Medline].
Postinflammatory Hyperpigmentation excerpt Article Last Updated: Mar 28, 2008
|
