A Comparative Study of Two Modalities, 4% Hydroquinone Versus 30% Salicylic Acid in Periorbital Hyperpigmentation and Assessment of Quality of Life Before and After Treatment.

BACKGROUND: Periorbital hyperpigmentation (POH) is a common hyperpigmentary problem of the face, which can be psychologically distressing and it can influence an individual's quality of life. However, this condition has received less attention in literature. AIMS AND
OBJECTIVES: To study the clinico-etiological features and the effect of two therapeutic modalities on the quality of life in patients of POH before and after treatment.
MATERIALS AND METHODS: Fifty patients attending the outpatient clinic of Dermatology Department, with clinically evident POH were included. All patients were divided randomly into two groups of 25 each and one group was treated with 4% hydroquinone and another group with 30% salicylic acid for 12 weeks. Assessment with visual analog scale (VAS) was done at 4, 6, and 12 weeks, and outcome of the patients was analyzed statistically.
RESULTS: Majority of the cases, i.e. 26 (52%) were in the age group of 20-30 years. Females comprised 74% of the study population. On VAS, most of the patients showed mild improvement (10-30%) at 12 weeks of treatment in both the groups. Separately, both the treatments significantly improved the dermatological life quality index of the patients although there was no significant difference found between the two groups.
CONCLUSION: POH is less responsive to standard treatments due to its multifactorial etiology and deposition of melanin in both dermis and epidermis. However, even the mild to moderate improvement in appearance can cause an improvement in the quality of life of the patients.

RCT Entities:   Population Interventions Outcomes

What was known?

Periorbital hyperpigmentation is a common skin problem and less responsive to standard treatments

Patients have poor quality of life.

Introduction

Periorbital hyperpigmentation (POH) has also been referred to as “dark circles,” “infraorbital darkening or discoloration,” and “periorbital melanosis.” It is a common dermatological problem, reported more in females than in males. It is a condition which is neither health-threatening nor associated with any morbidity, but it can influence an individual's quality of life.[1234]

POH is considered to have a genetic basis.[5] Other causative factors include excessive pigmentation, postinflammatory hyperpigmentation secondary to atopic and allergic contact dermatitis, periorbital edema, shadowing due to skin laxity, and tear trough defect associated with aging.[23] Excessive pigmentation is seen in conditions like dermal melanocytosis such as ‘Nevus of Ota’, as observed in Japanese patients[6] and also can be an extension of pigmentary demarcation lines of face which are seen very commonly in south Asian patients[78] and other dermatological conditions e.g. lichen planus pigmentosus and drug induced.[910111213] Superficial location of vasculature and thin overlying skin are other common causes of infraorbital dark circles. Recently, a new etiology of POH has been suggested in adult females using kohl (surma) for long time.[1415]

Among the available alternatives to treat dark circles are topical agents such as hydroquinone (HQ), kojic acid, azelaic acid, topical retinoic acid, chemical peels, surgical corrections, and recently laser therapy, most of which are however tried for melasma, another common condition with hyperpigmentation.

Despite the great number of available topical medications to treat dark circles, there is a paucity of scientific studies to support their use, and most of the evidence-based studies have been on melasma and other causes of facial hyperpigmentation. However, HQ is the most prescribed bleaching agent worldwide for different types of facial hyperpigmentation, though it has not been studied as a monotherapy or compared to other common treatment options such as 30% salicylic acid (SA) peels on POH. In addition, although it is a cosmetically distressing condition, there are no studies on the quality of life of these patients before and after treatment.

Hence, this prompted us to compare the effect of topical HQ and 30% SA peels on these patients, and to study the effect of treatment on the quality of life of these patients.

Materials and Methods

The present randomized comparative prospective study was conducted in the Department of Dermatology in a tertiary care hospital in New Delhi from October 2010 to February 2012. The study was approved by the Institutional Ethical Committee.

Fifty consecutive patients of both the sexes attending the outpatient clinic of Dermatology Department, with clinically evident POH were included in the study. Pregnant females, lactating females, and patients with active bacterial, viral, fungal, or herpetic infection, or with keloidal tendency were excluded from the study. Realistic outcome of treatment was discussed with each patient and an informed written consent was taken before inclusion into the study.

Detailed demographic data and clinical history including the onset, duration of POH, aggravating factors, treatment received, any prolonged drug intake, cosmetic use, history of atopy, family history, and menstrual history of all the patients were taken and recorded in a preset pro forma. A complete dermatological examination was carried out. Detailed examination of the face under good illumination was conducted to assess the lesions, clinical type, and color of lesion.

Pro forma of Hindi validated translation of dermatological life quality index (DLQI) was filled by the patients at the baseline and completion of treatment. Any topical medications being taken for POH were discontinued 2 weeks prior to treatment, and all the patients were primed with a broad spectrum sunscreen for 2 weeks. Clinical photographs using standardized position were taken at baseline (0 week) and 12 weeks.

Patients were randomized into two groups of 25 each by using a random number table. The first group received 4% HQ daily and the other received 30% SA peel once in 2 weeks for 3 months.

The peel was applied serially at 2 weekly intervals at 0, 2, 4, 6, 8, and 10 weeks after the test peel. About 30% of SA was applied with cotton-tipped applicator in the infraorbital areas. Feathering was done to avoid sharp demarcation between peeled and nonpeeled areas. The patients were asked to apply sunscreen with sun protection factor more than 15 on their faces before stepping out of the clinic. The patients were advised to avoid or minimize sun exposure, and apply sunscreens whenever exposed to the Sun. In HQ group, patients were asked to apply 4% HQ cream during night in the infraorbital area for 12 weeks. Patients were advised to use HQ only once to avoid any possibility of irritation or other side effects because of the higher concentration.

Subjective assessment of the response was also made by the patient and the treating physician at 4, 8, and 12 weeks and was evaluated on a visual analog scale (VAS) as 1 (worse), 2 (no change), 3 (<30%), 4 (30–60%), and 5 (>60%).[16]

A score of 1–5 was given based on percentage improvement noted, and findings were noted separately by both patient and treating physician. After treatment, the patients were followed up at 6 weeks to note any recurrence and to record the side effects, if any. DLQI and photography were done at baseline and after completing 3 months of treatment, respectively. Out of 50 patients, 5 were lost to follow-up (2 patient in SA peel and 3 patients in HQ group).

Statistical analysis

The statistical analysis was carried out using Statistical Package for Social Sciences (version 15.0 for Windows, SPSS Inc., Chicago, IL, USA). All statistical tests were two-sided and P < 0.05 was taken as significant.

Results

Majority of the cases, i.e., 26 (52%) were in the age group of 20–30 years. Mean age was 29.18 ± 8.74 years. The youngest and the oldest patients were aged 18 years and 60 years, respectively. Mean age was comparable in both the groups (P = 0.937). Females predominated, comprising 74% of the study population. Family history was present in 22% of the patients [Table 1].

Table 1

Demographic variables

On examination, most of the patients, i.e., 78% had light brown pigmentation and 22% patients had dark brown hyperpigmentation.

Among other melanoses, 8 (16%) patients had facial pigmentary demarcation lines also, 5 had Type F (V-shaped), and 3 had Type G (W-shaped). About 2 (4%) patients had melasma, 2 (4%) had freckles, and 3 (6%) had perioral pigmentation.

On both the patient's and doctor's VAS, the maximum number of patients showed mild improvement (10–30%) only at the end of treatment in both the groups [Figures 1 and 2]. Maximum improvement of 30–60% was seen at 12th week in both the groups. The change in the VAS at 4, 8, and 12 weeks (both doctor's and patient's VAS) was found highly significant in both the groups (P < 0.05). There was no significant difference of VAS between the two groups at 4, 8, and 12 weeks [Table 2].

Figure 1

(a and b) Before and after treatment with 4% hydroquinone cream

Figure 2

(a and b) Before and after treatment with 30% salicylic acid peel

Table 2

The difference of visual analog scale between salicylic acid and hydroquinone group

There was no significant difference found in the mean DLQI between the two groups, but the difference between the pre- and post-treatment DLQI was found highly significant in both the groups separately [Table 3].

Table 3

Mean dermatological life quality index of both groups and change in pre- and post-t/t dermatological life quality index

No major side effects were noticed in the patients, except two patients in HQ group who developed mild erythema, which subsided on its own.

Discussion

POH or dark circles have always been a topic of interest among the dermatologists. Despite it being observed frequently, there are very few published studies about the dark circles, its etiopathogenesis, and treatment options.

A DLQI was developed and validated in the USA by Finlay and Khan[17] to note the effect of various dermatological problems over the quality of life of the patients. Although DLQI and other quality of life indices have been studied in other disorders of pigmentation, to the best of our knowledge, there are no published studies about the use of DLQI in POH.[181920]

Maximum number of cases (56%) in our study were seen to be in their second decade of life, which was in accordance with a study where 47.5% patients were under 25 years of age.[21]

Our study showed a female preponderance, with a male:female ratio of 1:3. The total number of females was 37 and males was 17. Female preponderance has also been seen in the previous studies.[21]

A positive family history was recorded in 22% of the patients in our study and these were in the first-degree relatives. In a case report, Goodman and Belcher[5] described a family with POH in most of the members in the family. Later, they studied three other families with the same condition. The presence of a family history suggests that genetic factors may play a part in the pathogenesis of dark circles.

Precipitating factors were present in 32 (64%) patients in our study. Stress was present in 16 (32%) patients and outdoor activity in sunlight was seen in 13 (26%) patients. About 5 (10%) patients had a history of kohl (kajal) application, 4 (8%) had sleep disturbance, and one developed POH following laser therapy for aesthetic rejuvenation. In the study by Ranu et al.,[3] it was shown that 51.1% and 41.5% of the patients had a history of sleep deprivation and insomnia, respectively, which is much higher than that reported in our study. No other study has delineated the etiological factors of the disease.

Pigmentary demarcation lines were present in 8 (16%) patients. This is in accordance with a Saudi Arabian study by Al-Samary et al.[8] where they found that 14% of their patients had PDL over the face, but it was not clear whether it was present in association with POH or not.

Treatment of periorbital melanosis is often difficult and disappointing for the patients and treating clinicians.

HQ had been used in the past for the treatment of POH, but it was combined with Q-switched ruby laser and tretinoin.[22]

SA is a very superficial and safe chemical peel and has very less side effects, also it has been used successfully in other facial melanosis in Asian and dark-skinned patients, without any side effects.[23] Hence, this prompted us to study the use of HQ and SA in the treatment of dark circles and also to compare the outcome of treatment with these measures.

There is no study conducted in the past with 4% HQ alone in POH.

In the present study, 25 patients were treated with 30% SA, and maximum number of patients showed <30% of improvement. Maximum improvement of 30–60% was seen at the end of treatment.

There has not been any scientific study conducted using 30% SA peel in POH. We have found that SA peel was well tolerated in POH, without any significant side effects.

In the present study, we compared the efficacy of 4% HQ and 30% SA peel, two different treatment modalities in the treatment of POH or dark circles.

When the improvement was compared at the end of treatment, using mean VAS of the patient and treating physician, the difference was not significant for both patient (P = 0. 585) and treating physician (P = 0.798). Hence, from the above results, it can be concluded that both agents have comparable efficacy in the treatment of POH and they only show mild to moderate improvement.

In both the groups, the difference between pre- and post-treatment DLQI was found to be significant (P < 0.05) showing that even if medical therapies cause mild to moderate improvement, these have a significant impact on the quality of life of the patients. However, there was no significant difference between the DLQI between the two groups (P = 0.881). There is no other study of POH where the DLQI has been used, hence we could not compare.

Conclusion

Stress and sun exposure were the major etiological factors in our patients of POH, followed by family history. This condition is mildly responsive to standard treatments as compared to other facial pigmentation, such as melasma. However, even the mild to moderate improvement in appearance can cause an improvement in the quality of life of the patients, hence topical therapies and simple physical therapies such as chemical peels should be used to treat the patients who are desirous of improving the cosmetic appearance of their face.

However, in view of the paucity of studies regarding the clinico-etiological profile of POH and comparative studies between these therapies, more studies in Indian patients using large sample size and longer duration of follow-up after treatment are needed to evaluate how long the lightening of pigmentation can be maintained by the treatment. In addition, a colorimeter would have been a better way of determining improvement in pigmentation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Both 4% hydroquinone and 30% salicylic acid significantly and equally improve the quality of life of such patients.