Dr Vasanop Vachiramon, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Rajthevi, Bangkok 10400, Thailand E-mail: email@example.com
Postinflammatory hypopigmentation is a common cause of acquired hypopigmentary disorders. It can be a result of cutaneous inflammation, injury or dermatological treatment. There are also many specific conditions that present with hypopigmentation other than postinflammatory hypopigmentation. Most cases of postinflammatory hypopigmentation improve spontaneously within weeks or months if the primary cause is ceased; however, it can be permanent if there is complete destruction of melanocytes. This article reviews the aetiology, pathogenesis, clinical features, differential diagnosis and therapeutic options for postinflammatory hypopigmentation.
Postinflammatory hypopigmentation is an acquired partial or total loss of skin pigmentation occurring after cutaneous inflammation. The distribution and severity of pigment loss is related to the extent and degree of the inflammation. With certain inflammatory skin diseases, some individuals develop hyperpigmentation, while others develop hypopigmentation, and some individuals develop both. When there is severe cutaneous inflammation, loss rather than dysfunction of melanocytes occurs, resulting in depigmentation.1
Postinflammatory hypopigmentation is a very common pigmentary disorder. It can occur in all skin types. However, it is more common and prominent in people with darker skins, possibly because of the colour contrast with their normal skin. There is no gender difference in the incidence of postinflammatory hypopigmentation. Table 1 shows the incidence of postinflammatory hypopigmentation in particular conditions.2–9
Table 1. Incidence of postinflammatory hypopigmentation.
Patients, n/skin type
Incidence of postinflammatory hypopigmentation, %
LyP, lymphomatoid papulosis; NA, data not available; ND:YAG, neodymium:yttrium–aluminium–garnet; PLC, pityriasis lichenoides chronica; QS, Q-switched.
Alexandrite laser hair removal
Many cutaneous inflammatory conditions lead to postinflammatory hypopigmentation. Some, such as pityriasis lichenoides chronica (PLC) and lichen striatus (LS), tend to induce postinflammatory hypopigmentation rather than hyperpigmentation. Cutaneous injuries from burns, irritants and dermatological procedures (e.g., chemical peels, dermabrasion, cryotherapy, laser therapy) can also lead to postinflammatory hypopigmentation (Table 2).
Table 2. Causes of postinflammatory hypopigmentation.
Inflammatory skin diseases
Allergic contact dermatitis
Chronic graft versus host reaction
Discoid lupus erythematosus
Pityriasis lichenoides chronica
Patients with atopic dermatitis (AD) may present with postinflammatory hypopigmentation. The pigmentary changes are more common and intense if potent topical corticosteroids are used. Vitiligo-like depigmentation has been reported as a consequence of severe AD.10
LS is another common cause of postinflammatory hypopigmentation, with an incidence of up to 59%.4 The dermatosis resolves spontaneously within 2 years, leaving a transient hypopigmentation, especially in dark-skinned people. In addition, the inflammatory phase may be undetectable, and hypopigmentation may be the sole feature.
In many dark-skinned patients, PLC may present with extensive hypopigmentation with few characteristic scaly papular lesions.2
Pigmentary changes are common after thermal burns and freezing. In superficial burns, postinflammatory hyperpigmentation commonly occurs, whereas deep burns may produce postinflammatory hypopigmentation.11 Melanocytes are very sensitive to cold, and irreversible damage can occur at −4 to −7 °C.12 After skin freezing, transient hypopigmentation is seen, caused by the blockage of melanin transfer from melanocytes to keratinocytes, probably because keratinocytes and melanocytes are separated by oedema. Thereafter, melanocytes migrate into the lesion, resulting in an area of hypopigmentation with a hyperpigmented rim. The pigmentary changes persist for at least 6 months. After prolonged freezing, there is hypopigmentation with absence of melanosomes in keratinocytes, which may be due to a decrease in melanocyte number, reduction in melanosome synthesis or block in melanosome transfer.13
Postinflammatory hypopigmentation is also a possible complication of chemical peels. The use of Baker phenol peel in the past was associated with porcelain-white (alabaster) skin. The likelihood of hypopigmentation depends on the quantity of phenol applied, the level of occlusion, skin type (Fitzpatrick type I has a greater likelihood) and existing photodamage.14 Savant6 reported a study on dermabrasion in 65 patients with different facial conditions; 41 had permanent hypopigmentation.
Laser resurfacing commonly induces hypopigmentation, which seems to be related to the depth of resurfacing, and it may be permanent. It usually occurs 3–10 months after the procedure. In one study, the incidence was up to 22% after CO2 laser resurfacing.15 For pigment-specific laser, the rates of hypopigmentation after treatment of naevus of Ota with Q-switch ruby, Q-switch alexandrite, Q-switch neodymium:yttrium–aluminium–garnet (Nd:YAG) and a Q-switch alexandrite/Q-switch Nd:YAG combination are 16.8%, 10.5%, 7.6% and 40%, respectively. Factors associated with higher risk include the number of treatment sessions and the absorption spectrum of melanin; melanin absorbs ruby laser (694 nm) better than alexandrite laser (755 nm) or QS-Nd:YAG laser (1064 nm).7,8 Pigmentary changes have also been associated with alexandrite laser hair removal. Weisberg9 reported seven patients who developed similar pigmentary changes, described as initial hyperpigmented rings, followed by a wafer-like crust, hypopigmentation and finally resolution within 2 weeks to 6 months.
There is limited information about the mechanism and pathogenesis of postinflammatory hypopigmentation. The variation in individual response to cutaneous inflammation or trauma is not well understood. Ruiz-Maldonado16 proposed the term ‘individual chromatic tendency’ to describe this variation. Melanocytes can react with normal, increased or decreased melanin production in response to cutaneous inflammation or trauma. The chromatic tendency is genetically determined, and inherited in an autosomal dominant pattern. People with weak melanocytes, which have high susceptibility to damage, are more likely to develop hypopigmentation, whereas those with strong melanocytes tend to develop hyperpigmentation. However, dark-skinned people do not always have strong melanocytes, and those with weak melanocytes are prone to develop hypopigmentation.
Melanogenesis is a complex process, which includes melanin synthesis, transport and release to keratinocytes. It is controlled by multiple mediators (e.g., growth factors, cytokines) acting on melanocytes, keratinocytes and fibroblasts. Through the release of these mediators, cutaneous inflammation may cause aberration of melanogenesis. A study using histopathological examination of hypopigmented lesions occurring after laser resurfacing found variation in the quantity of epidermal melanin and number of melanocytes. It is suggested that hypopigmentation may result from inhibition of melanogenesis rather than destruction of melanocytes;17 however, severe inflammation may lead to loss of melanocytes or even melanocyte death, and thus permanent pigmentary changes.
The size and shape of hypopigmented lesions usually correlate with the distribution and configuration of the original inflammatory dermatosis, and the colour ranges from hypopigmentation to depigmentation (Fig. 1a–c). Complete depigmentation is commonly seen in cases of severe AD and discoid lupus erythematosus, and is more obvious in patients with darker skin. Pigmentary changes sometimes coexist with the original inflammatory lesions, making the diagnosis straightforward. However, in some conditions, the inflammatory phase is not always present, and hypopigmentation may be the only feature. Thus, repeated examinations are required to identify the primary inflammatory dermatosis. Pigmentary changes caused by pigment-specific laser are seen as small white macules that match the size and shape of the laser spot (Fig. 1d).
The differential diagnosis of postinflammatory hypopigmentation includes pityriasis alba, progressive macular hypomelanosis, pityriasis versicolor, leprosy, sarcoidosis, hypopigmented lesions in acantholytic disorders, hypopigmented lesions in extramammary Paget disease, hypopigmented mycosis fungoides (MF), infundibulomatosis, and hypopigmentation from medication, especially potent topical corticosteroids and intralesional corticosteroids. These conditions can be differentiated by clinical findings (e.g., epidermal changes, induration, presence of scales and lesion distribution) and histopathological examination.18–20
The differential diagnosis of postinflammatory depigmentation includes vitiligo, chemical leucoderma and depigmented extramammary Paget disease.
Investigations and diagnosis
Examination under Wood lamp accentuates the lesion, and helps distinguish between hypopigmented and depigmented lesions. In addition, it may help to exclude some conditions (e.g., progressive macular hypomelanosis displays punctiform red fluorescence, whereas pityriasis versicolor is coppery-orange). Confocal laser scanning microscopy may allow distinction between different hypomelanotic conditions, based on the melanin content and distribution patterns. Melanophages have been found in postinflammatory hypopigmentation but not in vitiligo and naevus depigmentosus. However, the contents of melanin and dermal papillary rings vary with the degree of the inflammation.21
Histopathology of postinflammatory hypopigmentation shows nonspecific findings, including decreased epidermal melanin, variable degrees of superficial lymphohistiocytic infiltration, and presence of melanophages in the upper dermis. In addition, there may be some histopathological evidence that can help to establish the diagnosis of the cause of postinflammatory hypopigmentation, such as in lupus erythematosus.22 Even if the biopsy shows nonspecific findings, it is still useful in excluding many dermatoses that present with hypopigmentation only, such as MF, sarcoidosis and leprosy.
The most important step of management is to identify the cause. Once the underlying cause is effectively treated, the hypopigmentation usually improves over time. To prevent iatrogenic hypopigmentation, dermatological and cosmetic procedures should be performed carefully, especially in high-risk patients.
Twice-daily application of a medium-potency topical steroid in combination with a tar-based preparation has been used to treat postinflammatory hypopigmentation, although the mechanisms behind this are currently not well understood. The steroid may affect inflammatory cells responsible for the inflammation,23 while the tar may photodynamically induce melanogenesis.24 A preparation of combined steroid and tar is more effective in stimulating melanogenesis.23
Topical pimecrolimus cream was reported to be beneficial in an open-label, pilot trial for the treatment of seborrhoeic dermatitis with associated postinflammatory hypopigmentation in dark-skinned patients.25 The regimen consisted of twice-daily application of 1% pimecrolimus cream for 16 weeks. The degree of improvement, assessed by a mexameter, was greatest during the first 2 weeks after the application.
Sun or ultraviolet (UV) exposure may help in repigmentation when there are functional melanocytes in the affected area; however, overexposure may enhance the colour contrast as a result of tanning of surrounding skin. Topical application of 0.1% 8-methoxypsoralen, 0.5–1% coal tar or anthralin followed by sun exposure can be helpful in the restoring the pigment.16 Various regimens of topical photochemotherapy (topical psoralen UVA; PUVA) have been used to treat postinflammatory hypopigmentation caused by various conditions, with favourable results. The regimen consists of topical application of 0.001–0.5% 8-methoxypsoralen in aquaphor or hydrophilic ointment to the affected area for 20–30 min, followed by UVA exposure 1–3 times per week at an initial dose of 0.2–0.5 J/cm2, increasing by 0.2–0.5 J/cm2 weekly.17,23
The 308-nm excimer laser may be used to stimulate pigmentation in hypopigmented scars, and had a response rate of 60–70% after nine biweekly treatments. However, regular subsequent treatment is needed every 1–4 months to maintain the results.26 For extensive involvement, narrowband UVB phototherapy or oral PUVA may be used 2–3 times weekly. The number of treatment sessions required is higher for repigmenting vitiligo lesions.23 The ablative fractional CO2 laser has been reported to be effective in the treatment of hypopigmentation associated with CO2 laser resurfacing.27
In depigmented lesions with total loss of melanocytes, epidermal or melanocyte grafting may be considered.28,29 Various methods of camouflage including high-coverage makeup, tanning products and tattooing may be an alternative option.
Course and prognosis
Minimal hypopigmentation usually resolves within a few weeks, but severe hypopigmentation and depigmentation associated with lupus erythematosus, scleroderma or burn may require years to become repigmented, and may be permanent.
Postinflammatory hypopigmentation is a common acquired hypopigmented condition that tends to affect dark-skinned people. There are many disorders that cause postinflammatory hypopigmentation. The most important key in its management is to identify and treat the primary cause. Current treatment options include topical medication, phototherapy and laser. However, there are limited data regarding the pathogenesis, natural course and treatment of postinflammatory hypopigmentation. Further studies are required to determine the underlying mechanisms and efficacy of each treatment.
• Many types of cutaneous inflammatory conditions and injuries are associated with postinflammatory hypopigmentation.
• Some inflammatory conditions have a tendency to develop postinflammatory hypopigmentation rather than hyperpigmentation, including PLC and LS.
• Skin biopsy can be of value to exclude dermatoses that present with hypopigmentation only, such as MF, sarcoidosis and leprosy.
• The most important step of management is to identify the cause of postinflammatory hypopigmentation. The hypopigmentation usually improves over time after the inflammation is ceased.
• Treatment options for postinflammatory hypopigmentation include topical tar, steroids, calcineurin inhibitors, phototherapy, excimer laser, fractional ablative CO2 laser, grafting and camouflage.
We thank Drs P. Suchonwanit and S. Kanokrungsee for their help in the preparation of the illustrations.
To review recent understanding related to the pathogenesis, causes and differential diagnosis of postinflammatory hypopigmentation, and to demonstrate up-to-date knowledge relating to the management of postinflammatory hypopigmentation.
Which of the following diseases may be followed by postinflammatory hypopigmentation?
b) Lichen striatus
c) Allergic contact dermatitis
d) Pityriasis lichenoides chronica
e) All of the above
Which of the following diseases may have complete depigmentation as a sequel?
b) Lichen planus
c) Insect-bite reaction
d) Severe atopic dermatitis
e) All of the above
Below what temperature does irreversible melanocyte damage start to occur?
a) 0 °C
b) −7 °C
c) −30 °C
d) −88 °C
e) −196 °C
Which of the following diseases may present with hypopigmentation or depigmentation?
c) Darier’s disease
d) Extramammary Paget disease
e) All of the above
What would you expect to see under Wood lamp in progressive macular hypomelanosis?