Topical corticosteroids induced hyper-pigmentation: a case report

Abstract

p>Hyper-pigmentation is a common skin condition in which increased melanin production results in darker patches of skin. Although hyper-pigmentation is harmless but still mostly people wish to get rid of them because of increasing craze of beautification in India. Topical corticosteroids (TC) application showed quick amelioration of post-inflammatory hyper-pigmentation patches. Prolonged and unsupervised use of TC leads to skin atrophy and reappearance of hyper-pigmentation patches. We present two cases of hyper-pigmentation induced by TC misuse. In case-1, a 20 year old female came to OPD with a complaint of hyper-pigmentation and itch sensation along with drug history of Betnovate cream for the last 2 years for acne treatment. On examination, she showed signs of hyper-pigmentation on cheeks. She was counselled to stop the further use of Betnovate cream and prescribed demelanizing agents along with sunscreen and emollients. The patches improved significantly with above management within 15 days. In case-2, a 33 year old female came to OPD with complaints of redness over whole face, increased facial hair growth and burning sensation along with drug history of using Betnovate cream for 2 years. On examination she showed signs of hyper-pigmentation and redness on cheeks, bruise and tearing of skin and increased facial hair growth. She was counselled to stop the further use of Betnovate cream. She was prescribed retinoic acid cream, sunscreen agents, anti-allergic tablets and emollient cream. The patches improved significantly with above management within 15 days.
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International Journal of Research in Dermatology | October-December 2019 | Vol 5 | Issue 4 Page 889
International Journal of Research in Dermatology
Saini B et al. Int J Res Dermatol. 2019 Nov;5(4):889-893
http://www.ijord.com
Case Report
Topical corticosteroids induced hyper-pigmentation: a case report
Bhawna Saini1*, Mohit Kumar2, Arkapal Bandyopadhyay1
INTRODUCTION
Hyper-pigmentation is darkening of skin colour due to
increased melanin production. Most common types of
hyper-pigmentation include age spots, melasma and post-
inflammatory hyper-pigmentation. Age spots, also called
liver spots or solar lentigines are brown, tan or black
spots that appear on skin after extended sun exposure on
face and hands in older adults. Melasma, also called
chloasma or "the mask of pregnancy" are large patches of
darkened skin on forehead, face and stomach affecting
women who are pregnant or taking control pills. Post-
inflammatory hyper-pigmentation are patches of
darkened skin that appear after an inflammatory skin
condition such as acne or eczema on face or neck.1 Other
causes of hyper-pigmentation include reactions to drug
use such as antimalarial drugs, topical corticosteroids and
tricyclic antidepressants.2-4 Chemicals added in topical
treatments can also cause hyper-pigmentation.
There are a range of possible treatment methods and
home remedies that people usually try without any
dermatologist advice. Topical treatments usually include
ingredients that lighten the skin, such as azelaic acid,
ABSTRACT
Hyper-pigmentation is a common skin condition in which increased melanin production results in darker patches of
skin. Although hyper-pigmentation is harmless but still mostly people wish to get rid of them because of increasing
craze of beautification in India. Topical corticosteroids (TC) application showed quick amelioration of post-
inflammatory hyper-pigmentation patches. Prolonged and unsupervised use of TC leads to skin atrophy and
reappearance of hyper-pigmentation patches. We present two cases of hyper-pigmentation induced by TC misuse. In
case-1, a 20 year old female came to OPD with a complaint of hyper-pigmentation and itch sensation along with drug
history of Betnovate cream for the last 2 years for acne treatment. On examination, she showed signs of hyper-
pigmentation on cheeks. She was counselled to stop the further use of Betnovate cream and prescribed demelanizing
agents along with sunscreen and emollients. The patches improved significantly with above management within 15
days. In case-2, a 33 year old female came to OPD with complaints of redness over whole face, increased facial hair
growth and burning sensation along with drug history of using Betnovate cream for 2 years. On examination she
showed signs of hyper-pigmentation and redness on cheeks, bruise and tearing of skin and increased facial hair
growth. She was counselled to stop the further use of Betnovate cream. She was prescribed retinoic acid cream,
sunscreen agents, anti-allergic tablets and emollient cream. The patches improved significantly with above
management within 15 days.
Keywords: Topical corticosteroids misuse, Hyper-pigmentation, Naranjo’s ADR probability scale, Hartwig’s severity
assessment scale
1Department of Pharmacology, 2Department of Pharmacology, All India Institutes of Medical Sciences, Rishikesh,
Uttarakhand, India
Received: 19 June 2019
Revised: 01 August 2019
Accepted: 03 August 2019
*Correspondence:
Dr. Bhawna Saini,
E-mail: bhanu.gsvm@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20194689

Saini B et al. Int J Res Dermatol. 2019 Nov;5(4):889-893
International Journal of Research in Dermatology | October-December 2019 | Vol 5 | Issue 4 Page 890
topical corticosteroids, hydroquinone, kojic acid,
retinoids, such as tretinoin and vitamin C.5 TC has been
reported most commonly misused drug for hyper-
pigmentation in studies conducted in the last 10 years.6
Basic purpose of starting the steroid cream is mostly to
look fairer, beautiful and have a blemish free skin. TC
has anti-inflammatory and pigment-lightening activity on
the skin. TC produces rapid alleviation of unpleasant
signs and symptoms of inflammatory changes on the
skin. Unfortunately, this "improvement" is short-lived
and can be followed by worsening of the original
condition if TCs are used for a long duration or not used
correctly. Steroids interfere with the synthesis of melanin
by smaller melanocytes, leading to patchy areas of hypo-
pigmentation which are reversible after discontinuation of
steroids.7
Prolonged uses of TCs leads to epidermal atrophy,
degeneration of dermal structure and collagen
deterioration after several months. Continued or overuse
of steroids can result in thinning of the skin as well as
skin dependency on the steroid. Sun exposure to such a
thin skin leads to darkening of superficial layer of skin,
hence patients present with hyper-pigmented patches on
sun exposed skin areas.8
CASE REPORT
Case 1
A 20-year-old female had been using Betnovate cream
from 2 years for acne treatment without dermatologist
prescription. Now she came to OPD with complaints of
hyper-pigmentation from 1 year and itch sensation from 3
months. On examination, she showed signs of
hyperpigmentation on face that was mainly on cheeks
(Figure 1). Rest all the examinations were within normal
limits. She was counselled to stop the further use of
Betnovate cream. She was prescribed demelanizing
agents for hyper-pigmented patches. She was advised
sunscreen agents also. To relieve itching, emollients were
given. The patches improved significantly with above
management within 15 days.
Case 2
A 33-year-old female had been using Betnovate cream
from 2 years for cosmetic purpose. She came to OPD
with complaints of redness over whole face and increased
facial hair growth for last 2 years. She also had burning
sensation for 1 year. On examination she showed signs of
hyper-pigmentation and redness on cheeks, bruise and
tearing of skin and increased facial hair growth (Figure
2).
Rest all the examinations were within normal limits. She
was counselled to stop the further use of Betnovate
cream. She was prescribed retinoic acid cream, sunscreen
agents, anti-allergic tablets and emollient cream. She was
also advised for laser for increased facial hair growth.
The patches improved significantly with above
management within 15 days.
Figure 1: Hyperpigmentation with acne on cheek
(case 1).
Figure 2: Hyperpigmentation and redness on cheek
(Case 2).
For case-1 and case-2, ADR causality assessment was
done. Naranjo’s scale shown this ADR as probable
(Table 1) and WHO scale shown it as probable or likely
(Table 2). Severity was level 3-moderate according to
Hartwig’s severity assessment scale (Table 3). ADR
preventability assessment with Shumock and Thornton
Preventability Scale shows it was definitely preventable
(Table 4). All the above assessments are summarized as
analysis of ADR and depicted in Table 5.

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International Journal of Research in Dermatology | October-December 2019 | Vol 5 | Issue 4 Page 891
Table 1: ADR Causality assessment (Naranjo scale).9
Question
Yes
No
Do not
know
Score
Case 1
Case 2
Are there previous conclusive reports on this reaction?
+1
0
0
+1
+1
Did the adverse event appear after the suspected drug was
administered?
+2
‐1
0
+2
+2
Did the adverse reaction improve when the drug was discontinued or
a specific antagonist was administered?
+1
0
0
+1
+1
Did the adverse event reappear when the drug was re‐administered?
+2
‐1
0
0
0
Are there alternative causes (other than the drug) that could on their
own have caused the reaction?
‐1
+2
0
0
0
Did the reaction reappear when a placebo was given?
‐1
+1
0
0
0
Was the drug detected in blood (or other fluids) in concentrations
known to be toxic?
+1
0
0
0
0
Was the reaction more severe when the dose was increased or less
severe when the dose was decreased?
+1
0
0
0
0
Did the patient have a similar reaction to the same or similar drugs in
any previous exposure?
+1
0
0
0
0
Was the adverse event confirmed by any objective evidence?
+1
0
0
+1
+1
Total score
5
5
Score: ≥9=definite ADR; 5-8=probable ADR; 1-4=possible ADR; 0=doubtful AD.
Table 2: WHO-UMC causality categories.9
Causality term
Assessment criteria (all points should be reasonably compiled)
Case 1
Case 2
Certain
• Event or laboratory test abnormality, with plausible time relationship to drug
intake.
• Cannot be explained by disease or other drugs.
• Response to withdrawal plausible (pharmacologically, pathologically).
• Event definitive pharmacologically or phenomenologically (i.e., an objective
and specific medical disorder or a recognised pharmacological phenomenon).
• Rechallenge satisfactory, if necessary.
Probable or
likely
• Event or laboratory test abnormality, with reasonable time relationship to
drug intake.
• Unlikely to be attributed to disease or other drugs.
• Response to withdrawal clinically reasonable.
• Rechallenge not required.
✔
✔
Possible
• Event or laboratory test abnormality, with reasonable time relationship to
drug intake.
• Could also be explained by disease or other drugs.
• Information on drug withdrawal may be lacking or unclear.
Unlikely
• Event or laboratory test abnormality, with a time to drug intake that makes a
relationship improbable (but not impossible).
• Disease or other drugs provide plausible explanations.
Conditional or
unclassified
• Event or laboratory test abnormality.
• More data for proper assessment needed.
• Additional data under examination
Unassessable
or unclassifiable
• Report suggesting an adverse reaction.
• Cannot be judged because information is insufficient or contradictory.
• Data cannot be supplemented or verified.
Table 3: Hartwig’s severity assessment scale.10
Assessment criteria
Case 1
Case 2
Level 1
 An ADR occurred but required no change in treatment with the suspected
drug
Level 2
 The ADR required that treatment with the suspected drug be held,
discontinued, or otherwise changed.
 No antidote or other treatment requirement was required. No increase in
length of stay (LOS).
Continued.

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International Journal of Research in Dermatology | October-December 2019 | Vol 5 | Issue 4 Page 892
Assessment criteria
Case 1
Case 2
Level 3
 The ADR required that treatment with the suspected drug be held,
discontinued, or otherwise changed.
 AND/OR an Antidote or other treatment was required. No increase in length
of stay (LOS).
✔
✔
Level 4
 Any level 3 ADR which increases length of stay by at least 1 day (or) the
ADR was the reason for admission.
Level 5
 Any level 4 ADR which requires intensive medical care.
Level 6
 The adverse reaction caused permanent harm to the patient.
Level 7
 The adverse reaction either directly or indirectly led to the death of the
patient.
Mild=level 1 and 2; Moderate=level 3 and 4; Severe=5, 6 and 7.
Table 4: ADR preventability assessment (Shumock and Thornton Preventability Scale).11
Assessment criteria
Case 1
Case 2
1. Was there a history of allergy or previous reactions to the drug?
Definitely
preventable
✔
✔
2. Was the drug involved inappropriate for the patient’s clinical condition?
3. Was the dose, route or frequency of administration inappropriate for the
patient’s age, weight or disease state?
4. Was a toxic serum drug concentration (or laboratory monitoring test)
documented?
5. Was there a known treatment for the adverse drug reaction?
6. Was required Therapeutic drug monitoring or other necessary laboratory
tests not performed?
Probably
preventable
7. Was a drug interaction involved in the ADR?
8. Was poor compliance involved in the ADR?
9. Were preventative measures not prescribed or administered to the patient?
10. If all above criteria not fulfilled
Not
preventable
Table 5: Analysis of the ADR.
Types
Case 1
Case 2
Causality- Naranjo
Probable
Probable
Causality- WHO-UMC
Probable or likely
Probable or likely
Severity- Hartwig
Moderate
Moderate
Preventability- Schumock and Thornton
Definitely preventable
Definitely preventable
DISCUSSION
Hyper-pigmentation is a harmless skin condition. Most
patients want to get rid of them. Thus, they take treatment
suggestions from their relatives and friends instead of
proper dermatologist advice. They tend to continue the
improper treatments for a very prolong period of time and
present to dermatology OPD after worsening of their skin
condition. In our cases, TC has been misused over 2 years
for cosmetic purposes. Patient presented to the OPD with
hyper-pigmented patches on face. Their facial skin had
significant thinning as compared to other body parts,
hence showing early signs of hyper-pigmentation than
other body parts. Both the ADRs had causal association
with drug used, moderate severity and were definitely
preventable. Although hypo-pigmentation is a common
ADR of TC misuse but hyper-pigmentation is also
reported as ADR after TC misuse over 6 months. The
incidence of hyper-pigmentation has been reported in few
studies like Bhat et al, Jha et al, Manzoor et al.6,12,13 Both
our patients presented with hyper-pigmentation after
chronic TC usage. The excessive, regular use of topical
corticosteroids on the face results in an array of skin
complications. Topical corticosteroids are very
commonly abused drugs mainly in youngsters, especially
females. Over the counter availability of these drugs in
our part of world is a major cause of their abuse.
Depigmentation is commonly associated with steroid use.
Hyper-pigmentation’s are mostly seen in intraoral
lesions.14 The facial is skin is thin hence the penetration
of the steroid’s ointments is considerably higher in
compared to other areas of body. Low potency steroids
should be preferred for topical application in facial skin.
Various underlying mechanism are suggested as a cause
of hyper-pigmentation. Use of the steroids leads to
vasoconstrictive and anti-inflammatory effects leading to

Saini B et al. Int J Res Dermatol. 2019 Nov;5(4):889-893
International Journal of Research in Dermatology | October-December 2019 | Vol 5 | Issue 4 Page 893
the clearance of the primary dermatitis. On chronic
unsupervised usage epidermal atrophy, degeneration of
dermal structure and collagen deterioration is seen. After
several months of usage, appearance of rosacea like
features are noted. It makes the fragile skin susceptible to
bacterial, viral, and fungal infections. Multiple pathways
including rebound vasodilatation and pro-inflammatory
cytokine release by chronic intermittent steroid exposure
induce rosacea-like eruption which on resolution
produces pigmentation.15,16
Facial hyper-pigmentation is a continued concern among
new generation of Indian population. Successful
treatment of facial hyper-pigmentation depends upon
their underlying aetiologies. Patients should be
encouraged to take advice of dermatologist for their
hyper-pigmentation problem rather than applying topical
corticosteroids without any proper advice.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: Not required
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Cite this article as: Saini B, Kumar M,
Bandyopadhyay A. Topical corticosteroids induced
hyper-pigmentation: a case report. Int J Res
Dermatol 2019;5:889-93.