Hydroquinone is the controversial gold standard for skin lightening but there are a number of newer alternatives on the market. Dr Mukta Sachdev discusses current and emerging treatment options
In India, I generally work with Fitzpatrick skin types IV,V and VI. Contrary to the Western culture’s desire for tanned skin, there is a strong aspiration for a fairer skin complexion in many parts of the world. Across Asia—particularly in India, Japan and China—light or fair skin represents beauty, youth and affluence. Tanned skin has long been associated with a lower socioeconomic status and regarded as a result of manual labour and working in the sun for long hours.
In the Asia-Pacific region, it’s estimated that $13 billion is spent annually on skin lightening products and these figures are rapidly changing. Around 15% of the world’s population invests in skin lightening products and Asia is the largest market. In India alone, $432 million was spent on skin lightening creams as of a recent survey.
A global survey showed that 33% of Chinese women use a lightening product daily or weekly, 62% in India, 55% in Japan, and 22% in Taiwan, Senegal, Mali and South Africa.
An Indian survey revealed that 80% of Indian men use lightening creams; this would once have been unheard in India but now it’s become common practice for men to choose a lightening agent as part of their daily skin care routine.
We are constantly looking for safer and effective lightening agents. Pigmentation is one of the most common complaints dealt with in both a clinical and an aesthetic dermatology outpatient practice. I personally work both in a large private corporate hospital where the common conditions treated include psoriasis, eczema and bullous diseases and run a private aesthetic dermatology office practice. In both settings, pigmentation is the commonest problem.
Hydroquinone is the platinum standard for treating pigmentation. However, as dermatologists we are aware that it has its limitations and potential complications .While it is banned as an over-the-counter (OTC) agent in Europe and other parts of the world, the product is available by prescription so there is a misconception is that hydroquinone is a banned and dangerous; that we shouldn’t use it. Physicians worldwide continue to regularly prescribe it and, quite frankly, no other skin lightening product can compare to hydroquinone and the triple combination products.
The incidence of exogenous ochronosis is on the rise. The Journal of the European Academy of Dermatology and Venereology published an article saying that ochronosis is vastly underreported. It can often be misdiagnosed as melasma or hypermelanosis, but a simple skin biopsy confirms this condition.
Ochronosis is a definite potential side-effect of prolonged topical hydroquinone usage, so what are our treatment options?
Patients can stop the hydroquinone-containing products and use alternative lightening agents. However, unless ochronosis has been confirmed, it is a challenge to stop using hydroquinone—the product is almost universally recommended as induction treatment for facial melanosis, melasma or any form of hyperpigmentation.
Many physicians do not perform a diagnostic facial skin biopsy. Patients are often reluctant for this procedure, but it is now advocated for diagnosis. A two to three millimetre punch from the affected area provides a confirmed clinical diagnosis of the condition which one is treating and helps not only from a diagnostic and therapeutic perspective but also a prognostic significance.
Depigmenting agents target different steps in the production of melanin, most commonly inhibiting tyrosinase. The evidence-based agents are hydroquinone, azelaic acid, kojic acid, arbutin and certain liquorice extracts.
Other agents include retinoids, mequinol, ascorbic acid, niacinamide, n-acetyl glucosamine and soy, all of which have papers published and evidence to back them.
Certain procedures can also be effective in the treatment of post-inflammatory hyperpigmentation. However, there isn’t any one specific product or procedure for skin lightening. We have to combine our treatment modalities and often a combination of topical and procedures in now a routine regimen for the management of hyperpigmentation.
Cosmetic camouflage using make up has a place for the management of skin pigmentary disorders both in hyper and hypopigmentation. Melasma and other pigmentary disorders can be emotionally distressing and quality of life is seriously affected. If cosmetic camouflage is advised and patients are counselled this will have a significant benefit and the patients automatically become more compliant with medication. Cosmetic camouflage should always be included as part of the first line initial treatment regimen or protocol.
The key thing to remember is that when you’re using a lightening agent, you are using it more often than not to target pigmentation. Pigmentation is a dynamic process and will keep coming back, so it is important to adequately counsel the patient.
Topical mequinol has been tried and there is evidence to back it up. Topical retinoids also have significant evidence to show they are effective for pigmentation. Topical azelaic acid works but there can often be significant irritation in darker skins.
In India, there is no problem with the availability of topical kojic acid and it is an effective therapy as a lightening agent. It is banned in certain countries, but many OTC products contain the ingredient. It definitely has its place in the management of hyperpigmentation, albeit in the maintenance phase of therapy rather than as an initial treatment option.
Vitamin C is effective but stability can be an issue so one needs to choose products where the stability is proven to ensure effectiveness of the active. However, in India, products containing vitamin C, particularly serums, tend to be more expensive. This can therefore become a constraint for patients.
Arbutin, liquorice, soy, glycolic acid formulations and hydroxy acids work very well. The percentage of active ingredients needs to monitored and often one needs to change the prescription according to seasonal variations, as even the topical hydroxy acids can cause slight irritation.
Mulberry and liquorice extracts can work well. Liquorice contains glabridin and licochalcone A, which both inhibit tyrosinase activity. Glabridin is also anti-inflammatory so it has a dual function. Liquiritin is the other active ingredient commonly being included in many lightening formulations. It does not inhibit tyrosinase but causes depigmentation through melanin dispersion.
Nicotinic acid, niacinamide and resorcinol also help—they’re not as effective as the gold standard, but they are definitely beneficial.
However, we are working in an era of evidence-based medicine, and most of the products available combine multiple actives. On average, any given lightening product contains between three and six lightening agents, with limited evidence to back them as they are mostly included in the cosmeceutical category where regulatory is less rigorous as compared to drugs.
The enzyme lignin peroxidase is one of the newer ingredients which has found a place in pigmentation treatment for hydroquinone-intolerant patients—especially for those with sensitive skin and who require maintenance therapy.
As most lightening products contain a list of active ingredients, we often don’t know which active is really working. There are not always clinical trials to support any independent active ingredient, depending on individual country regulations. In clinical practice, one should use a chromameter or mexameter and imaging system to document any improvement but how do we know which active is working?
When you’re evaluating a product, read the clinical trials. Has a chromameter been used? Has a Mexameter been used? What imaging has been performed?
If the study is carried out on six patients, this isn’t enough evidence to put it out on the world-wide market and say, “This is brilliant.” We’re practising evidence-based medicine, so we, as physicians, have to make intelligent choices when prescribing for our patients in clinical practice.
Several oral and topical formulations are now available. There has been some interest about grape seed extract and pycnogenol—a trial in the Philippines involved the use of oral pycnogenol on 35 patients.
Topical ingredients include ellagic acid, resveratrol, linoleic acid, green tea extracts and mulberry tea extracts. Melanostatin is a new peptide available for topical use.
Tranexamic acid is generating a lot of interest in India, as regulation tends to be a little more relaxed. It is being used for the treatment of melasma, and there is now evidence in the worldwide literature supporting a potential benefit. There are now several ongoing controlled studies. However the drug has a number of side effects, including renal complications and needs to be evaluated thoroughly for this indication.
Trends seem to be favouring more aggressive treatments for lightening or when treating pigmentation. Home use peels are very much on the market and prescribed in stronger concentrations—many of the home use products contain 15–20% glycolic acid. This concentration is almost as strong as one performed in an office—and patients have access to this.
Natural ingredients are always of interest and currently include turmeric, tomato, tamarind and pomegranate. These are gaining popularity and generating a lot of interest in India. Tamarind is used extensively as a cooking ingredient and hair powder in India, and has garnered much interest for newer cosmeceuticals.
Fuller’s earth is also used for lightening in India and can be found in most households. It is easily available and people apply it regularly as a homemade face mask for fairness. Turmeric, or haldi powder, is a daily use Indian spice, mainly used in cooking and most Indian women will have, at some point, have applied it to their face for lightening.
Combination therapies are the order of the day. Physicians worldwide are combining topicals with peels, lasers or other aesthetic procedures. However, there can be complications with darker skins when physicians combine treatments and the risks become higher with more potential skin damage.
Patient education is a critical part of our pigmentation management protocol—we regularly see patients who have applied topical home remedies, such as lemon-garlic juice or toothpaste for acne, which has caused post-inflammatory hyperpigmentation persisting for six months post-application.
Recently a patient came to our outpatient with pigmented lesions on the nose and cheeks. On detailed history and examination she was found to have a habit of wiping her face because she was regularly exposed to cooking or heat, thereby developing frictional melanosis.
This emphasises the fact that when you are treating darker skins, it is important to keep in mind certain cultural or religious habits which the patient may not tell you about.
If you are aware of these specific habits, lifestyles and cultural traditions, it is extremely helpful in identifying and actually eliminating a lot of the causes. Pigmentation is therefore not just a melanocyte problem.
We now need to think out of the box for the medical management. Studies examining the benefits of combining a vascular laser with a Q switch laser for melasma are ongoing, depending on the aetiology, and combination treatments for rosacea are now aimed at treating pigmentation.
Lastly, in order to effectively treat hyperpigmentation, it is imperative to try and make an accurate diagnosis. Pigmentation is a sign of ageing in darker skins.
An older Asian woman might come in with blotchy pigmentation—she may have freckles, or lentigines, and these are signs of ageing. They may not display wrinkles or deep nasolabial folds, but they will have pigmentation so we need to treat that. As a dermatological expert, counsel and educate your patients as to what you’re really capable of delivering in terms of benefit. Counsel and prescribe, because you need compliance.
Skin lightening actives are here to stay. The market is increasing rapidly and an informed educated physician has a range of treatment choices of active ingredients in their therapeutic armamentarium.
Dr Mukta Sachdev is a Professor of Dermatology and Senior Consultant Dermatologist at Manipal Hospital, Bangalore, India and is also runs a private clinical practice and dermatology clinical research centre.