Article Type : Research Article
Authors : Hassan BS, Hossain BA, Nisa RP and Shaude SE
Keywords : Melisma, Hydroquinone, MASI score, Hyperpigmentation, Skin disorder
Background: Melisma is a common acquired
hyperpigmentation disorder predominantly affecting facial areas. While various
treatment options exist, the efficacy of hydroquinone in treating melisma,
particularly in diverse populations, requires further investigation.
Objectives: To evaluate the efficacy of
hydroquinone in the treatment of facial melisma through assessment of Melisma
Area and Severity Index (MASI) scores.
Methods: An open clinical trial was
conducted over two years (July 2022-June 2024) at the Department of Dermatology
and Venereology, National Institute of Diseases of the Chest and Hospital,
Bangladesh. The study included 145 patients aged 20-50 years who met specific
inclusion criteria. Treatment efficacy was evaluated using MASI scores at 4, 8,
and 12-week intervals.
Results: The study population comprised
predominantly females with a malar distribution pattern being most common. The
largest age group affected was 36-40 years. Most participants were housewives
or service holders with varied educational backgrounds. After 12 weeks of
treatment, the majority of patients showed improvement in MASI scores, though
response rates varied significantly among participants.
Conclusion: Hydroquinone demonstrated mild
to moderate efficacy in melisma treatment with minimal side effects. While
improvement was observed in many patients, response rates varied, suggesting
the need for individualized treatment approaches. Further controlled studies
with larger sample sizes are recommended to establish definitive treatment
protocols.
A frequent acquired hyperpigmentation disease, melisma
is characterized by asymmetrical light to dark brown spots on the forehead,
cheeks, upper lip, and chin. 1% to 50% are the range of prevalence rates among
high-risk groups [1,2]. People with darker skin tones, expectant mothers, and
people living in places with high UV exposure are high-risk groups.
Centro-facial, malar, and mandibular patterns are among the distribution
patterns of melisma, with the former being the most prevalent. In certain
cases, the upper back, extensor arms, and neck are also impacted. Menopausal
women are most frequently found to have these non-racial zones. Erythema and
telangiectasias have increased in the afflicted areas, according to recent
research, which points to a vascular component to the illness [1]. Melisma
occurs in all races and ethnicities, but the overwhelming majority of patients
are women and individuals with Fitzpatrick skin types IV through VI, including
Hispanic, Asian, and individuals of African descent [1,4]. Less than 20% of
melisma instances are in men, making them the minority of patients. According
to published research, men's and women's melisma shares many clinical and
histologic characteristics [5,6]. One study reported low testosterone levels in
men with melisma [5]. It is often linked to a strong emotional impact by
resulting in cosmetic facial deformity. There isn't a single, all-encompassing
treatment for the illness; instead, different treatments have differing levels
of efficacy, and the illness typically recurs [7]. Melisma treatment is still
challenging, particularly for patients with dark skin. Before notable
therapeutic improvements are observed, demelanizing agent treatment must be
sustained for several months [8]. Treatment of melisma involves the use of
topical hypo-pigmenting agents, laser therapy and dermabrasion. Combination
treatment of glycolic acid (2%) and hydroquinone (2%) have shown good results
in several studies [9,10]. Hydroquinone (2%) has shown good results in several
studies [10]. The skin is efficiently brightened and whitened by hydroquinone,
a potent depigmenting chemical that completely blocks melanogenesis.
Hydroquinone (HQ) constituents have strong antioxidant properties [11]. It
affects both DNA and RNA production, which results in a reversible reduction of
cellular metabolism. Being a weak substrate of tyrosinase and a strong melanocyte
cytotoxic agent, hydroquinone competes with active melanocytes for tyrosine
oxidation and prevents the skin's tyrosine from being converted to melanin
[12]. The increased incidence of melisma in pregnant women is evidence of its
hormonal role on the etiology of the condition. Pregnant women frequently get
melisma, which is sometimes referred to as the "mask of pregnancy."
In fact, 10–20% of patients receiving OCT have melisma [13]. Since melisma is a
common finding in pregnant women, it is often deemed the “mask of pregnancy”,
with studies reporting a prevalence ranging from 36.4% to 70% [14].
Melanocyte-stimulating hormone (MSH), progesterone, and estrogen levels rise
during pregnancy, promoting melanogenesis via a number of regulatory routes
[15]. There are more progesterone receptors (PR) in the epidermal layer of
melisma lesions than there are estrogen receptors (ER) in the dermal layer,
according to research. Tyrosinase is activated when estrogen interacts with its
receptors on melanocytes and keratinocytes, which in turn encourages
melanogenesis. Furthermore, estrogen has the ability to increase the expression
of PDZ domain protein kidney 1 (PDZK1) and ?-melanocyte-stimulating hormone
(?-MSH), which increases tyrosinase synthesis and melanin formation [16]. The
impact of progesterone requires further clarification. However, sex steroid
hormones are unable to induce hyperpigmentation alone; instead, they work
synergistically with UVB radiation [17]. Chloasma gravid arum, sometimes known
as the "mask of pregnancy," usually goes away on its own within a
year after birth. However, in around 30% of women, it can last forever [14]. In
a subgroup of patients, a favourable family history highlights the genetic
susceptibility to developing melisma. Indeed, research indicates that between
55 and 64 percent of melisma patients report family relatives who have the
disorder [18]. Along with sun exposure, a positive family history is the most
prevalent risk factor identified in men, and in women, it is pregnancy. A therapeutic
option for melisma is limited and the results are somewhere not satisfactory to
some extent.
It was an opened clinical trial study. The study was
carried out for a period of 2 years from July 2022 to June 2024, in the
outpatient to department of Dermatology and Venereology, National Institute of
Diseases of the Chest and Hospital, Bangladesh. Patients suffering from melisma
were selected as study population. Purposive type of non-probability sampling
technique was followed. Data were recorded on pre designed data collection
sheet. Within the period of data collection, 145 patients of melisma were assigned
purposively considering exclusion and inclusion criteria of patient selection.
The inclusion criteria were patient of 18 to 50 years of age group of male and
female. Female not taking oral contraceptive pill and patient taking no other
medication for melisma treatment. Exclusion criteria were patient unwilling to
give informed consent to take part in the study, pregnant woman, patient
suffering from any endocrine disorder, liver disease, Patient taking oral
contraceptive pill, phenytoin, me phenytoin. Informed consent was sought from
the patients to take part in the study. At the baseline visit, history of
melisma regarding length of time present, relationship to pregnancy, oral
contraceptive,drug history was taken. Patients were asked about previous use of
any other medications and any hypersensitivity to those agents. Patient were
advised to apply the above-mentioned combination therapy over the melisma once
daily in the night and the patient were asked to report on each and every 4th,
8th, 12th weeks of 2 years for evaluation. The efficacy was evaluated using
Melisma Area and Severity Index (MASI) Score as proposed by Kimbrough-Green
et.al. At each visit, side effects were determined in the treatment area.
MASI Score
Melisma area severity index (MASI) is developed by Kimbrough-Green et al16 for the assessment of Melasma. The severity of melisma of each of the four regions (forehead, right malar region, left malar region and chin) are assessed based on three variables: Percentage of the total area involved (A), darkness (D) and homogeneity (H). A numerical value assigned for the corresponding percentage area involved is as follows:
0 = No involvement
1 = < 10% involvement
2 = 10% - 29% involvement
3 = 30% - 49% involvement
4 = 50% - 69% involvement
5 = 70% - 89% involvement
6 = 90% - 100% involvement
The darkness of melisma (D) is compared to the
Normal skin and graded on scale of 0 - 4 as follows:
0 = normal skin colour without evidence of
hyperpigmentation
1 = barely visible hyperpigmentation
2 = mild hyperpigmentation
3 = moderate hyperpigmentation
4 = severe hyperpigmentation
Homogeneity of hyperpigmentation (H) is also
Graded on scale of 0 - 4 as follows
0 = normal skin colour without evidence of
Hyperpigmentation
1 = specks of involvement
2 = small patchy area 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 severity Grade
for darkness (D) and homogeneity (H) is multiplied by the numerical value of
the areas (A) Involved and by the percentages of the four facial
Areas (10%-30%)
A = Area involvement, 0 = 0%, 1 = 10%, 2 = 10% - 29%,
3 = 30% - 49%, 4 = 50% - 69%, 5 = 70% - 89%, 6 = 90% - 100%
D = Darkness, 0 = absent, 1 = slight, 2 = mild, 3 =
Marked, 4 = severe
H = Homogeneity, 0 = absent, 1 = slight, 2 = Mild, 3 =
marked, 4 = severe
It was an opened clinical trial study the study was
carried out for a period of 2 years from July 2022 to June 2024, in the
outpatient to department of Dermatology and Venereology, National Institute of
Diseases of the Chest and Hospital, Bangladesh. Patients suffering from melisma
were selected as study population.
It was an opened clinical trial study. The study was carried out for a period of 2 years from July 2022 to June 2024, in the outpatient to department of Dermatology and Venereology, National Institute of Diseases of the Chest and Hospital, Bangladesh. To evaluate the efficacy of the hydroquinone for the treatment of facial melisma. Patients suffering from melisma were selected as study population. Within the period of data collection, 145 patients of melisma were assigned purposively. The efficacy was evaluated using Melisma Area and Severity Index (MASI) Score. The severity of melisma of each of the four regions (forehead, right malar region, left malar region and chin) are assessed based on three variables, percentage of the total area involved (A), darkness (D) and homogeneity (H).
Table 1: Socio-demographic characteristics of the respondents (n=145).
Variables |
n |
% |
Occupation |
||
Housewife |
72 |
49.7% |
Students |
15 |
10.3% |
Service
holder |
58 |
40.0% |
Total |
145 |
100% |
Level of Education |
||
Primary
level |
15 |
10.3% |
Secondary
level |
29 |
20.0% |
Higher
Secondary level |
29 |
20.0% |
Graduation
level |
15 |
10.3% |
Postgraduate
level (if applicable) |
57 |
39.3% |
Total |
145 |
100% |
Table 2: Distribution of the respondents by se (n=145).
variables |
n |
% |
Female |
111 |
76.6 |
Male |
34 |
23.4 |
Table 3: Socio-economic status of the respondents (n=145).
n |
% |
|
Upper class |
72 |
49.7% |
Middle class |
57 |
39.3% |
Lower class |
16 |
11.0% |
Total |
145 |
100% |
Table 4: Socio-economic status of the respondents (n=145).
Family history of melasma |
n |
% |
Positive |
29 |
20.0% |
Negative |
116 |
80.0% |
Total |
145 |
100% |
Age
Group (Years) |
n |
% |
20-25 |
15 |
10.3% |
26-30 |
25 |
17.2% |
31-35 |
30 |
20.7% |
36-40 |
35 |
24.1% |
41-45 |
25 |
17.2% |
46-50 |
15 |
10.3% |
Total |
145 |
100% |
Table 6: Distribution of the patients by change in MASI Score after treatment (n=145).
Change in MASI Score |
n |
% |
Decreased by ? 8 |
25 |
17.2 |
Decreased by 4-7 |
35 |
24.1 |
Decreased by 1-3 |
30 |
20.7 |
No change |
25 |
17.2 |
Increased by 1-3 |
15 |
10.3 |
Increased by ? 4 |
15 |
10.3 |
Total |
145 |
100 |
Among the patients, 76.6% of the patients were female
while 23.4% of the patients were male, which is accordance with the
observations of many authors, which is again similar to the research work of
Alicia Garcia, where 97% of the patients were female and 03% of the patients
were male [19]. A strong family history of melisma was present in 20% of the
patient in this study and suggests an important genetic factor in the
pathogenesis of this condition. With regard to the site of involvement of
melisma, 93% of the patients had malar distribution and 7% of the patients in
this study had Centro facial distribution, which is similar to the research
work of Alicia Garcia, where 91% of the patients had malar distribution and 9%
of the patients had Centro facial distribution [19]. This
study showed a little reduction of the severity of melisma demonstrated by MASI
score after 12 weeks of treatment when compared to their baseline. The result
of this indicates that daily night use of the hydroquinone has a mild
lightening effect on the melisma. After 12 weeks, the average MASI score
decreased by 20.7%. The limitations of the study were that it
was an opened, randomized and controlled clinical trial study performed on a
limited number of cases. Duration of the study was limited 2 years, which could
not reflect the proper efficacy and possible side effects of proposed therapy.
As study patients were mostly female and serv-ice holder, due to their lack of
time and carelessness and most importantly their tendency to give more
attention and priority to their family. So, unable to follow up and ensure
their progress properly. Limitation of time and financial support of my study
patients were my enormous restrictions. An attempt was made to evaluate the
efficacy of hydroquinone in the treatment of melisma. The study was carried out
among 145 patients, fulfilling inclusion criteria for a period of 2 years. So,
the result of this study may not be the representative of exact evaluation. It
needs further elaborate study on a larger number of patients over a longer
period of time. Still, it could be concluded that hydroquinone has a few
lightening effects on melisma, with no remarkable side effects.
This study demonstrates that hydroquinone exhibits modest efficacy in the treatment of melisma. The predominance of female patients and the presence of positive family history in a subset of cases aligns with existing literature regarding gender predisposition and genetic factors in melisma pathogenesis. While many patients showed improvement in their MASI scores after each and every 12 weeks of treatment for 2 years, some experienced either no change or worsening of symptoms, suggesting that hydroquinone alone may not be sufficient for all patients. The study concludes that hydroquinone remains a viable treatment option for melisma, offering mild to moderate improvement with minimal side effects.