1 oint
@aestheticsgroup @aestheticsjournaluk Aesthetics aestheticsjournal.com
PIH in Dark Skin
Dr Abirami Pararajasingam and Dr Sandeep Cliff explore
treatment for post-inflammatory hyperpigmentation in
individuals with Fitzpatrick skin types III-VI
What is post-inflammatory hyperpigmentation?
Post-inflammatory hyperpigmentation (PIH) is an acquired
hypermelanosis which occurs in all skin types, but it is more prevalent
among individuals of darker skin, defined as Fitzpatrick type III-VI.1
Dyschromias, of which PIH comprise a significant proportion, are
among the most common reasons for African and Asian patients
to seek the care of a dermatologist.2-4 PIH can have a significant
psychosocial impact on this cohort of patients as lesions often
occur more frequently and persist for a longer duration, with greater
severity.5 The condition typically arises following inflammation to the
skin (for example with acne, psoriasis or atopic dermatitis), but can also
occur after cutaneous injury including aesthetic interventions such as
dermabrasion, laser and epilation, to name a few.6-9
When there is inflammation or injury to the epidermis, melanocytes are
triggered to produce excessive melanin, which is then distributed to
surrounding keratinocytes. Although the exact mechanism is unknown,
the increase in melanocytic activity has been shown to be stimulated
by prostanoids, cytokines, chemokines and other inflammatory
mediators as well as reactive oxygen species.10-13 The excessive
melanin manifests as dyschromic macules or patches, which in
darker individuals can range in colour from red/purple to brown/black
depending on baseline skin tone and depth of discolouration.14 If the
basal layer is involved, melanin pigment is released and subsequently
engulfed by macrophages in the papillary dermis. This can give the
skin a blue-grey appearance and lesions may be exacerbated by
exposure to sunlight. PIH may remain at the site of inflammation/injury
long after the initial wound has recovered, typically resolving after
many months to years.15 Management of the condition is challenging
and therapeutic strategies often produce variable outcomes. Note
that many of the studies mentioned below do not specify the exact
Fitzpatrick type of the participants, so patients’ skin colour has been
referred to using the same terminology as the study.
Management options for PIH in darker skin
As with other medical conditions, prevention of PIH is better than
cure. The importance of controlling the underlying source of
cutaneous inflammation or injury must be emphasised. Shah et al.
showed that early and efficacious treatment of acne in patients with
darker skin helps minimise hyperpigmentation.16 This, of course, can
be challenging in severe cases. For severe or persistent lesions,
which often occur in darker-skinned individuals, there is a wide
range of safe and effective treatment strategies which include topical
agents, chemical peels, laser therapy and intense pulse light (IPL).
There are also treatments that aim to conceal hyperpigmented
lesions, remove the excessive pigment or regulate melanin
production, or a combination.
Topical formulations
There are several topical treatments which can help regulate
melanogenesis by targeting the enzyme tyrosinase, which converts
dihydroxyphenylalanine (DOPA) to melanin (Figure 1). The amino acid
Reproduced from Aesthetics | Volume 6/Issue 6 - May 2019
tyrosine undergoes hydroxylation to produce DOPA and subsequently
oxidation to produce DOPAquinone; both reactions are catalysed by
the enzyme tyrosinase.17 The addition of cysteine to DOPAquinone
leads to the formation of eumelanin. In the absence of cysteine,
DOPAquinone undergoes conversion to DOPAchrome, which leads to
the formation of eumelanin.18
Hydroquinone
Hydroquinone is an agent which acts on this pathway and continues
to play an important role in the treatment of hyperpigmentation
disorders. A concentration of 2-5% hydroquinone is commonly used
for this indication for all skin types.19,20 It can be used as a monotherapy,
or in formulation with other agents including corticosteroids and
retinoids. Hydroquinone formulations including cortiscosteroid allows
treatment of co-existent inflammation. In one study, hydroquinone
combined with retinol 4% and 0.15% micro-sponge in patients with
Fitzpatrick II-VI skin showed mean improvement in PIH of 39%, 77%,
and 77% from baseline to weeks four, eight, and 12, respectively.21
Similarly in another study microencapsulated hydroquinone 4% and
retinol 0.15% with antioxidants demonstrated 75% overall improvement
in pigmentation at week 12 in 63% of subjects.22 Hydroquinone
is currently only available on prescription and commercial use is
highly regulated because of the recognised complications, which
include contact dermatitis, permanent leukoderma and exogenous
onchronosis; these are true for all skin types. Carcinogenicity
of hydroquinone has been reported in animals, but there is no
established increased risk of cancer in humans.23
Retinoids
Another group of topical agents are the retinoids, which are structural
and functional analogues of vitamin A. In a randomised controlled
trial with 54 black patients, topical tretinoin cream 0.1% applied once
daily for 40 weeks was more effective than placebo at lightening PIH
lesions.24 However, 50% of patients developed dermatitis, which is an
important consideration and advocates titrating retinoid concentrations
Tyrosine
Tyrosinase
DOPA
Tyrosinase
DOPAquinone
-cysteine +cysteine
DOPAchrome Cysteinyl-DOPA
Eumelanin Pheomelanin
(Brown to black) (Yellow to Red)
Figure 1: Schematic of melanin synthesis.18
 @aestheticsgroup @aestheticsjournaluk Aesthetics aestheticsjournal.com

Before After
and usage with time.24,25 Newer generation retinoids, which include
adapalene and tazarotene, have also been shown to be efficacious
in the treatment of dyschromias in people with a dark skin tone.26,27 In
one open label study of 65 African patients with acne associated with
PIH, the severity of PIH significantly improved with 0.1% adapalene gel
at four, eight and 12 weeks.38 Similarly, in a randomised controlled trial Figure 2: A 37-year-old woman with a five-year history of melasma,
before and after four months of treatment with topical cysteamine cream.
involving 74 dark-skinned patients with acne, 0.1% tazarotene cream Fitzpatrick type not specified, however only those with Fitzpatrick skin
was found to be effective against PIH in terms of overall disease types III, IV and V were recruited to the study.36
Images courtesy of Scientis Pharma SA, Geneva, Switzerland.
severity.39 The oral form of retinoid, isotretinoin, is invaluable in the
treatment of severe acne and in one report its use was successful in Before After
the treatment of PIH in an Asian patient.28

Other topicals
Other topical treatments have also been implemented in the
management of PIH, although evidence is limited. Azelaic acid is
Figure 3: Another 37-year-old woman with a five-year history of melasma,
produced by malassezia furfur, an anthropophilic fungus which forms before and after four months of application of cysteamine cream.36
part of our natural skin flora. Its mechanism of action is complex and Images courtesy of Scientis Pharma SA, Geneva, Switzerland.
poorly understood, but its efficacy and safety in the treatment of PIH
in individuals with a dark complexion has been demonstrated.29-32 Before After

One randomised vehicle-controlled double-blind trial of 52 patients

(skin types IV-VI) with facial hyperpigmentation treated PIH with
topical azelaic acid 20%. It demonstrated greater improvement in
hyperpigmentation after 24 weeks of treatment versus vehicle, as
measured by the investigator’s subjective scale and chromometric Figure 4: A 36-year-old woman with a three-year history of melasma,
before and after four months of treatment with topical cysteamine.36
analysis. Side effects were mild and transient.33 Similar results Images courtesy of Scientis Pharma SA, Geneva, Switzerland.
were reported in a 16-week study looking at 15% azelaic acid in the
treatment of acne-related PIH in 20 individuals with Fitzpatrick skin
type IV-VI.34 Soybean is a legume that is native to East Asia and is a colour for a natural appearance. Products are usually waterproof,
substance which has emerged as an effective skin-bleaching agent non-comedogenic and long-lasting. As camouflage is non-invasive
with promising results in the treatment of PIH. In a double-blind, and avoids trauma to the skin, there is a favourable safety profile,
placebo-controlled clinical study of African-American, Hispanic, particularly for individuals with a darker skin tone who are inherently
and Asian patients with Fitzpatrick skin types III-V who had acne- more prone to developing PIH.42
induced PIH there was a significant improvement in PIH in patients
using over the counter anti-acne medications containing soy Chemical peels
compared to those without soy.35 Chemical peels, which involve the application of acid to remove
Cysteamine (2-mercaptoethylamine) hydrochloride has been known dead skin cells, are one of the most common non-surgical cosmetic
to have depigmenting effects for decades, although exact mechanism procedures performed in the UK.43 Most chemical peels are brief
remains unclear. Two randomised controlled trials showed positive procedures that require little recovery time, although multiple
outcomes in patients (skin types III-V) with melasma using a cream treatments are usually necessary to achieve best results. There
containing cysteamine compared to controls (Figure 2,3,4).36,37 is a long-standing myth that chemical peels are not safe to use in
Patients showed positive results after they were instructed to wash
their face in the evening using a prescribed syndet bar and then apply
a thin layer of the cream (placebo or cysteamine 5% w/w) to their
lesions 30 min later.22 Although the exact pathophysiology underlying
melasma and PIH are distinct, they are both considered disorders
of hypermelanosis, thus further studies may reveal benefit of topical For severe or persistent
cysteamine in PIH patients.
Other examples of depigmenting agents which have shown promising lesions, which often
results in the treatment of dyschromias include vitamin C cream (or
ascorbic acid), kojic acid (a potent inhibitor of tyrosinase by chelating occur in darker-skinned
copper at the active site of the enzyme), liquorice extract, niacinamide
(physiologically active derivative of vitamin B3 or niacin), N-acetyl individuals, there are a wide
glucosamine (an amino sugar that is a precursor to hyaluronic acid),
and arbutin.38-40 Evidence surrounding the efficacy of these products in range of safe and effective
PIH of all skin types is limited and further studies are required.
treatment strategies
Concealment
Skin camouflage is described as the application of pigmented creams
that are designed specifically to mask skin discolouration or scarring.41
The pigment-rich products are matched to the patient’s normal skin

Reproduced from Aesthetics | Volume 6/Issue 6 - May 2019

 @aestheticsgroup
darker-skinned individuals due to risks of pigmentation disorders;44
however, careful selection of the type and strength of peel can help
avoid this potential complication and achieve positive results. Options
include glycolic acid, salicylic acid, mandelic acid and trichloroacetic
acid peels. Glycolic acid peels, in combination with tretinoin 0.05%,
hydroquinone 2%, and hydrocortisone 1% have been shown to
produce more rapid reduction in pigmentation compared to topical
treatment alone for PIH in dark-complexioned individuals.45,46
Light therapies
Lasers have been described to treat skin conditions for more than
40 years. Although topical agents remain first line for treatment of
PIH, laser and light therapies may serve as useful adjuncts. Melanin-
specific high energy Q-switch laser systems can successfully lighten
or eradicate pigmented lesions in all skin types.47 The short pulse
laser systems effectively treat lesions by confining their energy to
the melanosome (tiny granules within pigment cells which contain
melanin). The results of the laser treatment depend on the depth
of the melanin and the colour of the lesion and is, to some degree,
unpredictable. Typically, energy from short wavelength lasers is more
efficiently absorbed by superficial or epidermal melanin, while longer
wavelengths penetrate deeper with more selective absorption by
dermal targets. A greater safety margin can be achieved using longer
pulse durations and cooling devices, while still maintaining efficacy
in darker-skinned individuals.48 In one study, the 1064 nm Q-switched
Nd:YAG laser with low-fluence was shown to be effective in the
treatment of PIH caused by procedures such as laser surgery and
chemical peeling in five Asian patients.49,50 A pulse-in-pulse mode
IPL worked well for facial PIH in 25 Korean patients, with 23 patients
showing more than 50% improvement.51 Use of the picosecond
755 nm Alexandrite laser produced similar results in three Korean
patients (skin type IV) with melasma or PIH.52 Combined therapy
using Q-switched ruby laser and cutaneous bleaching with tretinoin
and hydroquinone was used in 18 Japanese patients with 38.9%
and 44.4% showing excellent or good clearing of periorbital hyper
pigmentation, highlighting a potential role for combined strategies in
selected patients.53
Discussion
With the treatment options discussed, particularly chemical peels and
laser therapy, it is important to recognise that treatment itself may
exacerbate or cause PIH particularly in darker-skinned individuals.54
Patients should be counselled appropriately prior to commencing
interventions. Furthermore, although not considered as a treatment of
PIH, sun protection also plays an integral role in management. In one
study, regular use of sunscreen in 89 African-American and Hispanic
patients (types IV-VI) for eight weeks showed an improvement in
dyschromia and skin darkening as measured by colourimetry, which
is a device used to test the concentration of a solution by measuring
its absorbance of a specific wavelength of light.55 Daily use of broad
spectrum sunscreen (SPF 30 or more) and sun-protective measures
should be advised to patients in order to minimise the darkening
of lesions of PIH.56,57 This must be emphasised to darker-skinned
individuals with PIH as sun protection measures are often used less
frequently by this cohort of patients.58
Conclusion
PIH is common among those with darker skin and can cause a
significant psychological burden. Understanding available treatment
options are important to allow physicians to tailor an approach that is
Reproduced from Aesthetics | Volume 6/Issue 6 - May 2019
@aestheticsjournaluk Aesthetics aestheticsjournal.com
most acceptable and efficacious for the patient. There are currently
a wide range of safe and effective therapies for this condition which
we have discussed here. Although some options like hydroquinone
and laser therapy are well-established treatments, others have
less evidence underpinning their usage, highlighting a need for
more research in this area. Regardless of the chosen approach, it is
important to initiate treatment early, including the use of regular sun
protection and controlling the underlying inflammatory dermatosis.
Dr Abirami Pararajasingam has completed a Bachelor
of Medicine and a Bachelor of Surgery with Honours at
the University of Liverpool, as well as a Bachelor of Science
in Neuroscience at University College London. She is a
core medical trainee at East Surrey Hospital and has a keen
interest in dermatology as well as teaching and research. Her special
interests include inflammatory dermatoses and skin cancer.
Dr Sandeep Cliff is a consultant dermatologist at a
university hospital and has a particular interest in skin
cancer and inflammatory dermatosis. He has lectured
and demonstrated extensively throughout the world on
various non-invasive techniques for facial rejuvenation,
including lasers, dermal fillers and toxins. He has been principal
investigator for over six clinical research trials and is a clinical sub-
dean at Brighton and Sussex Medical School.
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