Evaluation of the Efficacy of Hydroquinone in the Treatment of Melisma

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).

       Table 2: Distribution of the respondents by se (n=145).

Table 4: Socio-economic status of the respondents (n=145).