You are on page 1of 6

E-STUDY

Year : 2013 | Volume : 58 | Issue : 2 | Page : 157-

A comparative study of the efficacy of 4% hydroquinone vs
0.75% Kojic acid cream in the treatment of facial melasma

Rochelle C Monteiro, B Nanda Kishore, Ramesh M Bhat, D Sukumar, Jacintha Martis, H Kamath
Ganesh
Department of Dermatology, Fr. Muller Medical College, Mangalore, India
Correspondence Address:
Rochelle C Monteiro
Department of Dermatology, Fr. Muller Medical College, Mangalore
India

Abstract

Background: Melasma is a common acquired cause of facial hyperpigmentation seen
predominantly among females with significant psychological and social impact. It is often
recalcitrant to treatment. Several topical hypopigmenting agents have been used to
combat melasma. Hydroquinone and Kojic Acid are well established monotherapeutic
agents for treating melasma. Objectives:This study focuses mainly on the efficacy of
once daily application of 4% Hydroquinone and 0.75% Kojic Acid cream (containing
0.75% Kojic acid and 2.5% vitamin C) so as to determine an effective modality of
treatment for facial melasma. Materials and Methods: A total number of 60 patients
with facial melasma attending the Out-patient department of Dermatology, Venerology
and Leprosy, Fr. Muller Medical College Hospital, Mangalore from Oct 2008-April 2010
were studied. Patients were allocated alternately to group A and group B. Group A
patients received 4% Hydroquinone cream and group B patient received a Kojic Acid
cream (which contained 0.75% Kojic acid and 2.5% vitamin C) and were advised to
apply topically once daily at night. Patients were followed up on 4
th
, 8
th
and 12
th
week.
At each visit side effects were noted and clinical response to treatment was calculated
using the MASI score. Statistical Methods: Chi square test, student «SQ»t«SQ»
test. Results: At the 4
th
week post treatment evaluation, facial hyperpigmentation
responded early to 4% Hydroquinone cream than to 0.75% Kojic Acid cream. At the end
of 12 week treatment period, 4% Hydroquinone cream had an overall superiority to
0.75% Kojic Acid cream as a topical hypopigmenting agent. Conclusion: The results of
the study show that 4% Hydroquinone cream is a better topical hypopigmenting agent
with rapid rate of clinical improvement when compared to 0.75% Kojic Acid cream.

How to cite this article:
Monteiro RC, Kishore B N, Bhat RM, Sukumar D, Martis J, Ganesh H K. A comparative study of
the efficacy of 4% hydroquinone vs 0.75% Kojic acid cream in the treatment of facial
melasma.Indian J Dermatol 2013;58:157-157

How to cite this URL:
Monteiro RC, Kishore B N, Bhat RM, Sukumar D, Martis J, Ganesh H K. A comparative study of
the efficacy of 4% hydroquinone vs 0.75% Kojic acid cream in the treatment of facial melasma.
Indian J Dermatol [serial online] 2013 [cited 2014 May 22 ];58:157-157
Available from: http://www.e-ijd.org/text.asp?2013/58/2/157/108070

Full Text
Introduction


Melasma is one of the most common causes of acquired hypermelanosis of the face. It is
characterized by tan-brown macules and patches with a predilection for sun exposed
areas, in particular the cheeks, forehead, upper lip, nose, and chin. Women are more
affected than men (female to male ratio, 9:1). [1],[2]

Because melasma is a facial disfigurement, it emotionally disturbs affected individuals
and also is a source of social prejudice in many cultures. A study conducted to determine
the effect of melasma on health-related quality of life reported that social interactions,
recreation, and emotional well-being were adversely affected by the condition.

In recognition of the importance to patients and physicians of treating the condition,
several current treatments have been used to combat melasma. These treatments
include hypopigmenting agents, and also chemical peels, dermabrasion and lasers. [3]
The most frequently used topical bleaching agent for the treatment of melasma is
Hydroquinone. Studies have reported that bleaching creams with hydroquinone in
concentrations of 2-5% are generally safe and have a fair efficacy. [3],[4]

Kojic acid a fungal metabolic product has been used in concentrations of 2-4% either
alone or in combination with 2% Hydroquinone in an alpha-hydroxy acid gel base. Kojic
acid has the advantage of not being oxidized in the skin care lotion, but compared to
Hydroquinone even though it is a lighter agent, it is known to be more irritating and
expensive agent. [5]

Since very few clinical trials based on the comparative study of efficacy and tolerability
of Hydroquinone and Kojic acid with vitamin C have been performed, this study focuses
mainly on the efficacy of topical Hydroquinone and Kojic acid with vitamin C, so as to
determine an effective modality of treatment for melasma.
Materials and Methods


This prospective study was conducted in the Out-patient Department of Dermatology,
Venereology and Leprosy, Fr. Muller Medical College Hospital, Mangalore during Oct
2008- April 2010. Ethical clearance for the study was obtained from the institutional
review board.

Data was collected from 60 patients with facial melasma Patients belonging to both
sexes, any age group and willing to undergo treatment and come for follow up were
included in the study.

Exclusion criteria included patients with dermal melasma, pregnant women or women on
oral contraceptive pills, photosensitizing drugs or thyroid hormones and those who were
not willing to come for follow up.

Treatment regimen

All patients who fulfilled the selection criteria were allocated alternately into groups A
and B. Group A patients received 4% Hydroquinone and group B patients received
0.75% Kojic Acid cream which in addition contained 2.5% vitamin C, and were advised
to apply topically once daily at night and wash their face the next morning. All patients
were advised to apply broad spectrum sunscreens with a minimum SPF of 15.
Pretreatment evaluation was done with detailed history, examination, melasma area
severity index (MASI) scoring, Wood's light examination and colour photographs [Figure
1], [Figure 2], [Figure 3] and [Figure 4]. Response to treatment was evaluated at weeks
4, 8 and 12. At each visit, clinical response to treatment and efficacy was assessed using
the MASI score. Side effects were noted using a four point scale, as none: 1, mild: 2,
moderate: 3, severe: 4, at all three visits. The MASI scoring was done as follows:

The severity of the melasma in each of the four regions (forehead, right malar region,
left malar region and chin) was assessed based on three variables: Percentage of the
total area involved (A), darkness (D), and homogeneity (H). A numerical value was
assigned for the corresponding percentage area involved as follows: 0 = no involvement;
1 = <10% involvement; 2 = 10-29% involvement; 3 = 30-49% involvement; 4 = 50-
69% involvement; 5 = 70-89% involvement; and 6 = 90-100% involvement. The
darkness of the melasma (D) was compared to the normal skin and graded on a scale of
0 to 4 as follows: 0 = normal skin color without evidence of hyperpigmentation; 1 =
barely visible hyperpigmentation; 2 = mild hyperpigmentation; 3 = moderate
hyperpigmentation; 4 = severe hyperpigmentation. Homogeneity of the
hyperpigmentation (H) was graded on a scale of 0 to 4 as follows: 0 = normal skin color
without evidence of hyperpigmentation; 1 = specks of involvement; 2 = small patchy
areas of involvement <1.5 cm diameter; 3 = patches of involvement >2 cm diameter; 4
= uniform skin involvement without any clear areas). To calculate the MASI score, the
sum of the severity grade for darkness (D) and homogeneity (H) was multiplied by the
numerical value of the areas (A) involved and by the percentages of the four facial areas
(10-30%). Total MASI score: Forehead 0.3 (D+H)A + right malar 0.3 (D+H)A + left
malar 0.3 (D+H)A + chin 0.1 (D+H)A

The data was analysed for statistical significance of qualitative variables in both groups
by Chi-SQUARE test and continuous numerical values by student 't' test.{Figure
1}{Figure 2}{Figure 3}{Figure 4}
Results


In the present study out of the 30 cases in each group, 8 male patients (26.7%) and 22
female patients (73.3%) received kojic acid 0.75% (KA) + 2.5% vitamin C cream and 3
male (10%) and 27 female (90%) received Hydroquinone (HQ) 4% cream. An overall
female preponderance was noticed, male to female ratio being 1:4.5. Upon tabulation of
the results, it was found that patients in both the groups were matched according to age
and sex.

The mean age of patients receiving KA 0.75% cream 37.7 and 39.93 yrs for patients
receiving HQ 4% cream. The distribution of the various clinical patterns among the two
regimens was uniform statistically [Graph 1]-[SUPPORTING:1]. A positive family history
of melasma had no statistically significant effect on the occurrence of melasma in the
4% HQ group and 0.75% KA group.

Of the 49 patients with history of pregnancy, only nine reported exacerbation of
melasma during pregnancy which was statistically insignificant. The efficacy of each
hypopigmenting agent was found to be statistically highly significant [Table 1].{Table
1}{Table 2}

In patients who received 0.75% KA there was a significant decrease in MASI score from
week 0 to week 12 (P ≤ 0.001). Further, there was no significant change from week 0 to
week 4 (P = 0.121), but there was a significant decrease from week 0 to week 8 (P <
0.001).

In patients who received 4% HQ there was a significant decrease in MASI from week 0
to week 12 (p ≤ 0.001). However unlike the KA group, there was a significant decrease
from week 0 to week 4 and week 0 to week 8 (P < 0.001). Hence, in comparison
between the drugs, at the 4 th , 8 th and also 12 th week 4%HQ showed better effect
(mean 3.433 ± 3.54; 0.630 ± 1.403; 7.553 ± 5.289) compared to 0.75% KA [[Table 2];
[Graph 2]-[SUPPORTING:2]. So, at the end of treatment 4% HQ showed statistically
better efficacy than 0.75% KA.

Side effects such as erythema were noted in one patient receiving 0.75% KA (3.3%) and
two patients receiving 4% HQ cream (6.7%) reported erythema and a mild burning
sensation which were insignificant.
Discussion


HQ and KA are both topical hypopigmenting agents used in the treatment of melasma.
Both the agents are tyrosinase inhibitors however; HQ is believed to have additional
actions such as degradation of melanosomes, destruction of melanocytes and inhibition
of DNA and RNA synthesis. [6],[7] These additional actions probably make it a better
skin lightening agent compared to KA. HQ when used as a sole agent has been found to
be efficacious with total improvement rates of melasma in 38%, 77% and 75% of
patients in different studies. [8],[9],[10] Side effects like irritation, pruritus, contact
dermatitis have been reported in previous studies. Exogenous ochronosis is a rare side
effect. [11] In our study HQ proved to be highly efficacious, with faster onset of action
compared to KA. A possible reason could be that KA is a lighter agent compared to HQ.
Side effect rate was low and statistically insignificant, with only one patient discontinuing
treatment due to erythema and mild irritation experienced.

KA in addition to its skin lightening action, is known to have photoprotective, anti-
inflammatory and pain relieving actions. KA is seldom used as monotherapeutic agent.
[6] It has been used in addition with Glycolic acid in previous studies. The Glycolic Acid
+ KA combination has shown good therapeutic efficacy, as reported by Cotellessa, et al.
[12] Side effects reported with KA like erythema, sensitization and irritant contact
dermatitis were not seen in any of our patients. Only one of our patient complained of a
burning sensation, which was temporary. In our study, the KA compound had vitamin C
in combination. Vitamin C inhibits melanin formation as well as reduces oxidized
melanin. However, it has poor penetration across the skin barrier when used as an
isolated agent. Hence iontophoresis is used most commonly to enhance its penetration
across the cutaneous barrier. [6] It is also used in combination with various other topical
skin lightening agents. The efficacy of KA in our study thus may have been potentiated
by vitamin C.

There have been several studies comparing the efficacy of different hypopigmenting
agents. Review of literature showed a single study by Garcia and Fulton [13] comparing
HQ and KA but both drugs were used in combination with Glycolic acid. There is no study
so far comparing the efficacy of HQ and KA with vitamin C.

At 4 th , 8 th and 12 th week of post treatment evaluation of MASI, the mean change in
MASI following application of 0.75% KA was less than that of 4% HQ, which was
statistically highly significant. These results were in contrast to those with Garcia and
Fulton [13] wherein glycolic acid with 5% KA showed better efficacy (28%) compared to
glycolic acid with 5% HQ (21%). However their results were not statistically significant
unlike ours where there was a statistically highly significant difference between HQ and
KA, the former being better. The possible explanation for this could be that the addition
of Glycolic Acid might have potentiated the action of Kojic Acid, both being acids.

The results of this study show that 4% Hydroquinone and 0.75% Kojic Acid + vitamin c
2.5% are effective topical hypopigmenting agents in the treatment of facial melasma.
However, 4% Hydroquinone is a better topical hypopigmenting agent with rapid rate of
clinical improvement when compared to 0.75% Kojic Acid cream. The side effects of both
the hypopigmenting agents were not significant.
References
1 Guevara IL, Pandya AG. Safety and efficacy of 4% hydroquinone combined with
10% glycolic acid, antioxidants, and sunscreen in the treatment of Melasma. Int J
Dermatol 2003;42:966-72.
2 Thappa DM. Melasma (Chloasma): A review with current treatment options. Indian J
Dermatol 2004;49:165-76.
3 Torok HM. A comprehensive review of the long term and short term treatment of
Melasma with a triple combination cream. Am J Clin Dermatol 2006;7:223-30.
4 Bandyopadhyay D. Topical treatment of melasma. Indian J Dermatol 2009;54:303-
9.
5 Stratigos AJ, Katsambas AD. Optimal management of recalcitrant disorders of
hyperpigmentation in dark skinned patients. Am J Clin Dermatol 2004;5:161-8.
6 Perez-Bernal A, Munol-Perez MA, Camacho F. Management of facial
hyperpigmentation. Am J Clin Dermatol 2000;1:261-8.
7 Pandhi R, Kaur I, Handa S. Comparative evaluation of topical preparations in
treatment of melasma. Indian J Dermatol 2002;47:76-9.
8 Ennes S, Paschoalick R, Alchorne MMDA. A double-blind, comparative, placebo-
controlled study of the efficacy and tolerability of 4% hydroquinone as a
depigmenting agent in melasma. J Dermatolog Treat 2000;11:173-9.
9 Haddad AL, Matos LF, Brunstein F, Ferreira LM, Silva A, Costa D, et al. A clinical,
prospective, randomized, double blind trial comparing skin whitening complex with
hydroquinone vs.placebo in the treatment of melasma. Int J Dermatol 2003;42:153-
6.
10 Amer M, Metwalli M. Topical hydroquinone in the treatment of some
hyperpigmentary disorders. Int J Dermatol 1998;37:449-50.
11 Lim JT. Treatment of Melasma using Kojic Acid in a gel containing Hydroquinone and
Glycolic Acid. Dermatol Surg 1999;25:282-4
12 Cotellessa C, Peris K, Onorati MT, Fargnoli MC, Chimenti S. The use of chemical
peelings in the treatment of different cutaneous hyperpigmentations. Dermatol Surg
1999;25:450-4.
13 Garcia A, Fulton JE Jr. The combination of glycolic acid and hydroquinone or Kojic
acid for the treatment of Melasma and related conditions. Dermatol Surg
1996;22:443-7.


Thursday, May 22, 2014
Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer
V-Bates Shopper
ConstaSurf Ads