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Postinflammatory hypopigmentation

Article in Clinical and Experimental Dermatology June 2011

DOI: 10.1111/j.1365-2230.2011.04088.x Source: PubMed

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 Clinical dermatology Review article CED
Clinical and Experimental Dermatology

CPD

Postinflammatory hypopigmentation
V. Vachiramon and K. Thadanipon
Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

doi:10.1111/j.1365-2230.2011.04088.x

Summary 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.

Table 1 shows the incidence of postinflammatory hypo-

Introduction
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 inflam-
mation, loss rather than dysfunction of melanocytes
occurs, resulting in depigmentation.1
Epidemiology
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.
Correspondence: Dr Vasanop Vachiramon, Division of Dermatology, Faculty
of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road,
Rajthevi, Bangkok 10400, Thailand
E-mail: vasanop@gmail.com
Conflict of interest: none declared.
Accepted for publication 14 February 2011
pigmentation in particular conditions.29
Aetiology
Many cutaneous inflammatory conditions lead to
postinflammatory hypopigmentation. Some, such as
pityriasis lichenoides chronica (PLC) and lichen striatus
(LS), tend to induce postinflammatory hypopigmenta-
tion rather than hyperpigmentation. Cutaneous injuries
from burns, irritants and dermatological procedures
(e.g., chemical peels, dermabrasion, cryotherapy, laser
therapy) can also lead to postinflammatory hypo-
pigmentation (Table 2).
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

 The Author(s)
708 CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714
 Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon

Table 1 Incidence of postinflammatory hypopigmentation.

Incidence of
Patients, postinflammatory Study
Disease condition n skin type hypopigmentation, % location Ref.
2
PLC 5 dark-skinned 100 USA
3
LyP 9 NA 23 Spain
4
Lichen striatus 23 NA 59.1 Spain
5
Cryotherapy 135 NA 75 Italy
6
Dermabrasion 65 NA 63 India
7
QS ruby 101 NA 16.8 Japan
8
QS alexandrite 58 NA 10.5 Hong Kong
8
QS Nd:YAG 105 NA 7.6 Hong Kong
9
Alexandrite laser hair removal Hundreds phototypes IIIV 0.53 USA

LyP, lymphomatoid papulosis; NA, data not available; ND:YAG, neodymium:yttriumaluminiumgarnet; PLC, pityriasis lichenoides
chronica; QS, Q-switched.

Table 2 Causes of postinflammatory hypopigmentation. keratinocytes and melanocytes are separated by oede-
Inflammatory skin diseases
ma. Thereafter, melanocytes migrate into the lesion,
Allergic contact dermatitis resulting in an area of hypopigmentation with a
Atopic dermatitis hyperpigmented rim. The pigmentary changes persist
Chronic graft versus host reaction for at least 6 months. After prolonged freezing, there is
Discoid lupus erythematosus
hypopigmentation with absence of melanosomes in
Insect-bite reactions
Lichen planus
keratinocytes, which may be due to a decrease in
Lichen striatus melanocyte number, reduction in melanosome synthe-
Lymphomatoid papulosis sis or block in melanosome transfer.13
Pityriasis lichenoides chronica Postinflammatory hypopigmentation is also a possible
Psoriasis
complication of chemical peels. The use of Baker phenol
Sarcoidosis
Scleroderma
peel in the past was associated with porcelain-white
StevensJohnson syndrome (alabaster) skin. The likelihood of hypopigmentation
Infections depends on the quantity of phenol applied, the level of
Chickenpox occlusion, skin type (Fitzpatrick type I has a greater
Herpes zoster
likelihood) and existing photodamage.14 Savant6
Impetigo
Onchocerciasis
reported a study on dermabrasion in 65 patients
Pinta with different facial conditions; 41 had permanent
Pityriasis versicolor hypopigmentation.
Syphilis Laser resurfacing commonly induces hypopigmenta-
Procedure-related
tion, which seems to be related to the depth of resurfac-
Chemical peels
Cryotherapy
ing, and it may be permanent. It usually occurs 3
Dermabrasion 10 months after the procedure. In one study, the
Laser incidence was up to 22% after CO2 laser resurfacing.15
Miscellaneous For pigment-specific laser, the rates of hypopigmentation
Burns
after treatment of naevus of Ota with Q-switch ruby, Q-
switch alexandrite, Q-switch neodymium:yttriumalu-
Pigmentary changes are common after thermal burns miniumgarnet (Nd:YAG) and a Q-switch alexan-
and freezing. In superficial burns, postinflammatory drite Q-switch Nd:YAG combination are 16.8%,
hyperpigmentation commonly occurs, whereas deep 10.5%, 7.6% and 40%, respectively. Factors associated
burns may produce postinflammatory hypopigmenta- with higher risk include the number of treatment
tion.11 Melanocytes are very sensitive to cold, and sessions and the absorption spectrum of melanin; mel-
irreversible damage can occur at )4 to )7 C.12 After anin absorbs ruby laser (694 nm) better than alexan-
skin freezing, transient hypopigmentation is seen, drite laser (755 nm) or QS-Nd:YAG laser (1064 nm).7,8
caused by the blockage of melanin transfer from Pigmentary changes have also been associated with
melanocytes to keratinocytes, probably because alexandrite laser hair removal. Weisberg9 reported seven

 The Author(s)
CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714 709
Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon

patients who developed similar pigmentary changes,
described as initial hyperpigmented rings, followed by a
wafer-like crust, hypopigmentation and finally resolu-
tion within 2 weeks to 6 months.
Pathogenesis
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 deter-
mined, 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 melano-
cytes tend to develop hyperpigmentation. However,
dark-skinned people do not always have strong melano-
cytes, 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 histopath-
ological examination of hypopigmented lesions occur-
ring after laser resurfacing found variation in the
quantity of epidermal melanin and number of melano-
cytes. It is suggested that hypopigmentation may result
from inhibition of melanogenesis rather than destruc-
tion of melanocytes;17 however, severe inflammation
may lead to loss of melanocytes or even melanocyte
death, and thus permanent pigmentary changes.
Clinical features
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. 1ac). 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 straightfor-
ward. However, in some conditions, the inflammatory

(a) (b)

(c) (d)

Figure 1 Postinflammatory hypopigmentation caused by (a) lichen striatus, showing linear distribution of hypopigmented lesions along
Blaschko lines; (b) psoriasis, showing multiple well-demarcated hypopigmented lesions a similar size and shape to the original psoriasis
lesions. (c) Depigmentation secondary to discoid lupus erythematosus. The lesion is obvious in dark-complexioned skin because of the
colour contrast. (d) Hypopigmented and depigmented lesions secondary to low fluence Q-switched 1064-nm Nd:YAG laser therapy for
melasma. The configuration of the lesions corresponds to the size and shape of the laser spot.

 The Author(s)
710 CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714
 Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon
phase is not always present, and hypopigmentation may
be the only feature. Thus, repeated examinations are
required to identify the primary inflammatory derma-
tosis. 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).
Differential diagnosis
The differential diagnosis of postinflammatory hypo-
pigmentation includes pityriasis alba, progressive
macular hypomelanosis, pityriasis versicolor, leprosy,
sarcoidosis, hypopigmented lesions in acantholytic dis-
orders, hypopigmented lesions in extramammary Paget
disease, hypopigmented mycosis fungoides (MF), infun-
dibulomatosis, and hypopigmentation from medication,
especially potent topical corticosteroids and intralesion-
al corticosteroids. These conditions can be differentiated
by clinical findings (e.g., epidermal changes, induration,
presence of scales and lesion distribution) and histo-
pathological examination.1820
The differential diagnosis of postinflammatory de-
pigmentation 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 hypomelan-
osis displays punctiform red fluorescence, whereas
pityriasis versicolor is coppery-orange). Confocal laser
scanning microscopy may allow distinction between
different hypomelanotic conditions, based on the mel-
anin content and distribution patterns. Melanophages
have been found in postinflammatory hypopigmenta-
tion 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 hypopigmenta-
tion shows nonspecific findings, including decreased
epidermal melanin, variable degrees of superficial
lymphohistiocytic infiltration, and presence of mela-
nophages 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 Author(s)
CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714
Management
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, derma-
tological 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 postinflamma-
tory 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-meth-
oxypsoralen, 0.51% coal tar or anthralin followed by
sun exposure can be helpful in the restoring the
pigment.16 Various regimens of topical photochemo-
therapy (topical psoralen UVA; PUVA) have been used
to treat postinflammatory hypopigmentation caused by
various conditions, with favourable results. The regi-
men consists of topical application of 0.0010.5% 8-
methoxypsoralen in aquaphor or hydrophilic ointment
to the affected area for 2030 min, followed by UVA
exposure 13 times per week at an initial dose of 0.2
0.5 J cm2, increasing by 0.20.5 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 6070% after nine biweekly treatments.
However, regular subsequent treatment is needed every
14 months to maintain the results.26 For extensive
involvement, narrowband UVB phototherapy or oral
PUVA may be used 23 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 hypopig-
mentation associated with CO2 laser resurfacing.27
711
Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon
In depigmented lesions with total loss of melanocytes,
epidermal or melanocyte grafting may be consid-
ered.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 de-
pigmentation associated with lupus erythematosus,
scleroderma or burn may require years to become
repigmented, and may be permanent.
Conclusion
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.
Learning points
Many types of cutaneous inflammatory condi-
tions and injuries are associated with postinflam-
matory 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 hypo-
pigmentation. The hypopigmentation usually im-
proves over time after the inflammation is ceased.
Treatment options for postinflammatory hypo-
pigmentation include topical tar, steroids, calcineu-
rin inhibitors, phototherapy, excimer laser, fractional
ablative CO2 laser, grafting and camouflage.
712 CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714
Acknowledgement
We thank Drs P. Suchonwanit and S. Kanokrungsee for
their help in the preparation of the illustrations.
References
1 Papa CM, Kligman AM. The behavior of melanocytes in
inflammation. J Invest Dermatol 1965; 45: 46573.
2 Lane TN, Parker SS. Pityriasis lichenoides chronica in
black patients. Cutis 2010; 85: 1259.
3 Martorell-Calatayud A, Hernandez-Martin A, Colmenero I
et al. Lymphomatoid papulosis in children. Report of 9
cases and review of the literature. Actas Dermosifiliogr
2010; 101: 693701.
4 Peramiquel L, Baselga E, Dalmau J et al. Lichen striatus.
Clinical and epidemiological review of 23 cases. Eur J
Pediatr 2006; 165: 2679.
5 Rusciani L, Paradisi A, Alfano C et al. Cryotherapy in
the treatment of keloids. J Drugs Dermatol 2006; 5:
5915.
6 Savant SS. Facial dermabrasion in acne scars and geno-
dermatoses a study of 65 patients. Indian J Dermatol
Venereol Leprol 2000; 66: 7984.
7 Kono T, Nozaki M, Chan HH, Mikashima Y. A retrospective
study looking at the long-term complications of Q-switched
ruby laser in the treatment of nevus of Ota. Lasers Surg Med
2001; 29: 1569.
8 Chan HH, Leung RS, Ying SY et al. A retrospective analysis
of complications in the treatment of nevus of Ota with the
Q-switched alexandrite and Q-switched Nd:YAG lasers.
Dermatol Surg 2000; 26: 10006.
9 Weisberg NK, Greenbaum SS. Pigmentary changes after
alexandrite laser hair removal. Dermatol Surg 2003; 29:
41519.
10 Larregue M, Martin J, Bressieux JM et al. Vitiligoid achro-
mias and severe atopic dermatitis. Apropos of 4 cases. Ann
Dermatol Venereol 1985; 112: 589600.
11 El-Bishry MA, Nassar AM, El-Maghraby MZ. Tattooing, a
new hope for secondary leukoderma. Scand J Plast Reconstr
Surg 1979; 13: 14753.
12 Gage AA, Meenaghan MA, Natiella JR, Greene GW Jr.
Sensitivity of pigmented mucosa and skin to freezing
injury. Cryobiology 1979; 16: 34861.
13 Burge SM, Bristol M, Millard PR, Dawber RP. Pigment
changes in human skin after cryotherapy. Cryobiology
1986; 23: 42232.
14 Brody HJ. Complications of chemical resurfacing. Dermatol
Clin 2001; 19: 42738, viiviii.
15 Bernstein LJ, Kauvar AN, Grossman MC, Geronemus RG.
The short- and long-term side effects of carbon dioxide laser
resurfacing. Dermatol Surg 1997; 23: 51925.
16 Ruiz-Maldonado R, Orozco-Covarrubias ML. Postinflam-
matory hypopigmentation and hyperpigmentation. Semin
Cutan Med Surg 1997; 16: 3643.
 The Author(s)
 Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon

17 Grimes PE, Bhawan J, Kim J et al. Laser resurfacing-
induced hypopigmentation: histologic alterations and
repigmentation with topical photochemotherapy. Dermatol
Surg 2001; 27: 51520.
18 Verma S, Patterson JW, Derdeyn AS et al. Hypopigmented
macules in an Indian man. Arch Dermatol 2006; 142:
16438.
19 Rowley MJ, Nesbitt LT Jr, Carrington PR, Espinoza CG.
Hypopigmented macules in acantholytic disorders. Int J
Dermatol 1995; 34: 3902.
20 Yang CC, Lee JY, Wong TW. Depigmented extramam-
mary Pagets disease. Br J Dermatol 2004; 151:
104953.
21 Xiang W, Xu A, Xu J et al. In vivo confocal laser scanning
microscopy of hypopigmented macules: a preliminary
comparison of confocal images in vitiligo, nevus depig-
mentosus and postinflammatory hypopigmentation. Lasers
Med Sci 2010; 25: 5518.
22 Franca AF, de Souza EM. Histopathology and immuno-
histochemistry of depigmented lesions in lupus erythe-
matosus. J Cutan Pathol 2010; 37: 55964.
23 Halder RM, Richards GM. Management of dyschromias in
ethnic skin. Dermatol Ther 2004; 17: 1517.
24 Urbanek RW. Tar vitiligo therapy. J Am Acad Dermatol
1983; 8: 755.
25 High WA, Pandya AG. Pilot trial of 1% pimecrolimus
cream in the treatment of seborrheic dermatitis in African
American adults with associated hypopigmentation. J Am
Acad Dermatol 2006; 54: 10838.
26 Alexiades-Armenakas MR, Bernstein LJ, Friedman PM,
Geronemus RG. The safety and efficacy of the 308-nm
excimer laser for pigment correction of hypopigmented
scars and striae alba. Arch Dermatol 2004; 140: 95560.
27 Tierney EP, Hanke CW. Treatment of CO2 laser induced
hypopigmentation with ablative fractionated laser resur-
facing: case report and review of the literature. J Drugs
Dermatol 2010; 9: 14206.
28 Falabella R. Postdermabrasion leukoderma. J Dermatol Surg
Oncol 1987; 13: 448.
29 Suvanprakorn P, Dee-Ananlap S, Pongsomboon C, Klaus
SN. Melanocyte autologous grafting for treatment of
leukoderma. J Am Acad Dermatol 1985; 13: 96874.

CPD questions Question 3

Below what temperature does irreversible melanocyte

Learning objectives
damage start to occur?
To review recent understanding related to the pathogen- a) 0 C
esis, causes and differential diagnosis of postinflammato- b) )7 C
ry hypopigmentation, and to demonstrate up-to-date c) )30 C
knowledge relating to the management of postinflamma- d) )88 C
tory hypopigmentation. e) )196 C

Question 1 Question 4

Which of the following diseases may be followed by Which of the following diseases may present with
postinflammatory hypopigmentation? hypopigmentation or depigmentation?
a) Psoriasis a) Leprosy
b) Lichen striatus b) Sarcoidosis
c) Allergic contact dermatitis c) Dariers disease
d) Pityriasis lichenoides chronica d) Extramammary Paget disease
e) All of the above e) All of the above

Question 2 Question 5

Which of the following diseases may have complete What would you expect to see under Wood lamp in
depigmentation as a sequel? progressive macular hypomelanosis?
a) Psoriasis a) Punctiform red fluorescence
b) Lichen planus b) Punctiform green fluorescence
c) Insect-bite reaction c) Diffuse red fluorescence
d) Severe atopic dermatitis d) Diffuse green fluorescence
e) All of the above e) None of the above

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CED  2011 British Association of Dermatologists Clinical and Experimental Dermatology, 36, 708714 713
 Postinflammatory hypopigmentation V. Vachiramon and K. Thadanipon

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