Hyperpigmentary Disorders

By Dr Barbara Kubicka / 07 Jun 2017

Dr Barbara Kubicka presents an overview of the main types of hyperpigmentary disorders and discusses her preferred approaches to treatment

Hyperpigmentation is a very common skin condition that can affect patients of all skin types, genders and ages.1 It is a benign condition, but one should not underestimate the potential social and psychological impact of its cosmetic appearance. 

However non-threatening to health, it can be a distressing aesthetic concern, especially if the affected area is the face, which is obviously more difficult to conceal.

There are different types of hyperpigmentation depending on aetiology and manifestation. Each of them has a slightly different response to the treatment, so correct diagnosis is crucial to avoid difficulties and complications.

Genetic disposition to hyperpigmentation (especially in regards to melasma) is known as a key factor, so it is very important to gather a detailed family history; as hyperpigmentation is often the result of genetics combined with external or internal factors.2,3

While hyperpigmentation can affect patients of all skin types, it is more prevalent in those with Fitzpatrick skin types IV to VI.2,3 

Epidemiology studies have suggested that hyperpigmentation is the most common reason that ethnic patients seek the help of dermatologists or an aesthetic physician.4-9 It is crucial to establish ethnic background in skin type assessment, especially with patients of mixed race.

Yet, for all patients, there is a common exogenous factor contributing to hyperpigmentation – the sun. Sun damage can be visible even years after exposure, hence, effective sun protection is a must for prevention and while treating hyperpigmentation.

In this article the key types of pigmentation disorders that are commonly seen within an aesthetic clinic and their causes will be outlined and the potential treatment options, together with potential risks and complications, will be discussed. An overview of these treatments and their potential side effects are summarised in Table 1.

Solar lentigines

The most common and recognised hyperpigmentation disorders are solar lentigines,10 usually referred to as age or liver spots. These are small, superficial patches of darker pigmentation, presented on exposed parts of the body – most commonly on the hands, face and décolletage. They vary in size and number and tend to increase with age. 

Figure 1: Patient presenting with lentigines pigmentation before and after treatment using three courses of 20-35% TCA peel, six weeks apart. Picture taken eight weeks after last treatment.

They are relatively easy to treat and there are a variety of different treatment approaches to consider, which can include, but are not limited to:1,10 cryotherapy;11 TCA peel (33% but other percentages can be considered), topical creams, as described in the literature1,10 e.g. triple combination cream – fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%; bleaching solution – 2% mequinol (4-hydroxyanisole, 4HA) and 0.01% tretinoin, intense pulsed light (IPL) treatment and lasers.

Figure 2: Patient presenting with lentigines pigmentation before and four weeks following last treatment using IPL (three sessions, three weeks apart) and 20-35% TCA peel (two sessions).

Melasma

Melasma, or chloasma faciei, is a symmetrical hyperpigmented lesion of the sun-exposed skin, characterised by hyperpigmented macules and irregular borders. Melasma is commonly associated with hormonal factors and is mostly prevalent among women.3,13 

Only 10% of men suffer from melasma.14 There is an association between pregnancy and melasma – during pregnancy there is a visible increase of expression of oestrogen receptors on melanocytes. Furthermore, higher levels of oestrogen in the blood stimulate enzymes involved in melanogenesis, in particular TYR, TRP1 and TRP2.1 Melasma also becomes more visible after sun exposure as the melanocytes become enlarged.1 

UV exposure results in persistent over expression of α-MSH (again responsible for activating melanocytes due to inflammatory processes) as well as elevations in inducible nitric oxide synthase (iNOS). This results in local increase of inflammation which leads again to melanocytes hyperactivation.3,13

There are three types of melasma, which are defined according to the area in which it appears on the face and the depth of the pigment. 

There are three types of melasma, which are defined according to the area in which it appears on the face and the depth of the pigment. These include central facial melasma, malar melasma or mandibular pattern melasma, and the depth of pigment types include epidermal melasma, dermal melasma or mixed-type melasma. 

The second classification is more important to identify as it will influence the treatment process.3 Melasma treatment is extensive and can take years. To maintain the results of treatment, patients are likely to require long-term maintenance (more than a year) and a lifetime commitment to photoprotection with SPF application every day. 

The subject of melasma has been studied in detail and there are many evidence-based studies available, which can assist with choosing the most appropriate treatment methods.2,15-19 The following treatment protocol is a general guideline and has been recommended in literature.13

First line treatment

First line topical treatment that affects the melanin synthesis pathway is usually recommended as followed: photoprotection and camouflage, topical agent hydroquinone (HQ), triple combination therapy – 4% HQ, 0.05% tretinoin and 0.01% flucinodone acetonide (as a modification of Kligman’s Formula).13

Second line treatment

As a second line treatment, chemical peels can be used bi-weekly, with the strength depending on skin type. The exact strength will be depending on the patients’ preparation prior to the chemical peel. 

The darker the skin, the weaker the chemical peel needs to be to be used safely. The most commonly used in chemical peels are glycolic acid 20-70%, lactic acid, salicylic acid 20-30%, TCA, tretinoin, phytic acid, and mandelic acid. The substance used will be dependent on skin type, sensitivity, ethnic background and skin preparation.13

Third line treatment

Third line treatment uses IPL and laser. IPL is usually effective only on superficial melasma.13 The use of more advanced lasers or combination lasers for melasma and post-inflammatory hyperpigmentation (PIH) still requires more research, which is currently being conducted.20

Combination treatments

Other topical depigmentation agents can also be used in combination with any of the previously mentioned procedures. They are substances that have been described in literature such as azeliac acid 20% cream,2 kojic acid 1-4%,2 arbutin, niacinamide, N-acetyl glucosamine, ascorbic acid, liquorice and soy.2,21 

When it comes to chemical peels, I prefer to use combination products like MeLine, Dermamelan and Cosmamelan, which are readily available preparations that are a blend of many depigmenting agents and should be used as a second line treatment.20,22 

In my experience, the combination treatment allows for a reduction of side effects and improved results, as well as a safer profile in skin of colour as there is a lower percentage of acids that increase the risk of post-inflammatory hyperpigmentation.23-26 

I have also noticed an interesting trend of combining plasma-based devices with depigmenting agents to increase transdermal penetration of products, thus increasing the absorption of the active substance. However, this hasn’t yet been studied in much detail.

Post-inflammatory hyperpigmentation

PIH occurs as a result of inflammation or injury.2 It can also be induced as a side effect of certain medicines and even of certain cosmetic treatments.

This is an acquired condition that can affect all skin types, although Fitzpatrick skin types IV-VI are affected more often and potentially with greater severity, raising the possibility of a psychosocial impact on the patient.2 A family history of PHI, medications that cause sensitivity to light, and prolonged use of bleaching products are also known to cause or increase the risk of PIH.12,27

In addition, fungal or viral skin infections, allergic reactions, contact dermatitis or rashes can trigger a rise in melanocyte activity, which are stimulated by prostanoids, cytokines, chemokines, and other inflammatory mediators, as well as reactive oxygen species that are released during the inflammatory process, leading to PIH.2

Figure 4: Patient presenting with melasma before and after a combination treatment of 12 weeks using IPL and TCA peel MeLine and hydroquinone.

The first step in managing PIH is to understand and treat the underlying cause. This is also important in determining an appropriate treatment that will not exacerbate the condition, for example, by using skin preparations that are too strong, causing dermatitis. Early treatment is likely to lead to faster results and prevent further hyperpigmentation. After treating the underlying cause, current research indicates the same algorithm as the treatment of melasma.

Side effects and complications

There are several possible complications and side effects for hyperpigmentation treatments, which are briefly outlined in Figure 4.

Figure 3: Summary of treatments and their potential complications and adverse reactions. YES indicates the treatment would be considered for that particular indication.2,9,28 

Conclusion

Hyperpigmentation is, in many cases, a lifetime condition, therefore it is important to be able to offer our patients a variety of treatments that are effective and safe and that will not cause further skin damage. 

Furthermore, with an increasing number of cosmetic procedures, we start to see more and more post-treatment hyperpigmentation, so awareness of potential risk factors (darker skin types, family history, medications that cause sensitivity to light, and prolonged use of bleaching products) is as important as the treatment itself. 

References

  1. Reinhart Speeckaert, Mireille Van Gele, Marijin M, Speeckaert, Jo Lambert, Nanja Van Geel, ‘The biology of hyperpigmentation syndromes’, Pigment Cell & Melanoma Research, 2014 p.512–524.
  2. Erica C Davis, Valerie D Callender, ‘Postinflammatory Hyperpigmentation, A Review of the Epidemiology, Clinical Features, and Treatment Options in Skin of Color’, The Journal of Clinical and Aesthetic Dermatology’, 2010, 3(7) pp.20-31.
  3. Ai-Young Lee, ‘Recent progress in melasma pathogenesis’, Pigment Cell & Melanoma Research’, 2015 p.648–660.
  4. Goh, C.L., Dlova, C.N, ‘A retrospective study on the clinical presentation and treatment outcome of melasma in a tertiary dermatological referral centre in Singapore’, Singapore Med J, 1999;40:455– 458.
  5. Moin, A, Jabery, Z, Fallah, N, ‘Prevalence and awareness of melasma during pregnancy’, Int J Dermatol, 2006;45:285–288.
  6. Achar, A, Rathi, S.K, ‘Melasma: a clinico-epidemiological study of 312 cases’, Indian J Dermatol, 2011;56:380–382.
  7. Tamega Ade, A, Miot, L.D., Bonfietti, C, Gige, TC, Marques, ME, Miot, HA, ‘Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women’, J Eur Acad Dermatol Venereol, 2013;27:151–156.
  8. Handel, AC, Lima, PB, Tonolli, V., Miot, LD, Miot, HA, ‘Risk factors for facial melasma in women: a case-control study. Br J Dermatol. 2014;171:588–594.
  9. KrupaShankar DS1, Somani VK, Kohli M, Sharad J, Ganjoo A, Kandhari S, et al. ‘Cross-sectional, multicentric clinico-epidemiological study of melasma in India’, Dermatol Ther, 2014.
  10. Lance H Brown, ‘Treating Solar Lentigines: Traditional treatments at a glance – plus a look at a cutting-edge option’, The Dermatologist, 2002.
  11. Robert A Schwartz, ‘Lentigo Treatment & Management’, Medscape, 2016.
  12. Halder RM, Grimes PE, McLaurin CI, et al, ‘Incidence of common dermatoses in a predominately black dermatologic practice, Cutis, 1983;32:388–390.
  13. Krupa Shankar, Kiran Godse, Sanjeev Aurangabadkar, et al, ‘Evidence-Based Treatment for Melasma: Expert Opinion and Review’, Dermatology and Therapy, 2014, 4(2) p.165-186.
  14. Gertrude-Emilia Costin, Stanca-Ariana Birlea, ‘Is There An Answer? What is the mechanism for melasma that so commonly accompanies human pregnancy?’ IUBMB Life, 2006.
  15. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al, ‘Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial’, Arch Dermatol, 1994;130(6):727–733.
  16. Haddad AL, Matos LF, Brunstein F, Ferreira LM, Silva A, Costa D, Jr, ‘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(2):153–156.
  17. Kang WH, Chun SC, Lee S, ‘Intermittent therapy for melasma in Asian patients with combined topical agents (retinoic acid, hydroquinone and hydrocortisone): clinical and histological studies’, J Dermatol, 1998;25(9):587–596.
  18. Godse KV, ‘Triple combination of hydroquinone, tretinoin and mometasone furoate with glycolic acid peels in melasma’, Indian J Dermatol, 2009;54(1):92–93.
  19. Chan R, Park KC, Lee MH, et al, ‘A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma’, Br J Dermatol, 2008;159(3):697–703.
  20. Pooja Arora, Rashmi Sarkar, Vijay K Garg, Latika Arya’, ‘Lasers for Treatment of Melasma and Post-Inflammatory Hyperpigmentation’, Journal of Cutaneous and Aesthetic Surgery, 2012, 5(2) p.93–103.
  21. Bahareh Ebrahimi, Farahnaz Fatemi Naeini, ‘Topical tranexamic acid as a promising treatment for melasma’, Journal of Research in Medical Sciences, 2014 19(8) p.753-757.
  22. Aleksandr Kuradovets , Luisa Leon , Victor Garcia Guevara , Fernando Bouffard Fita, ‘Innovation in the concept of controlled chemical dermabrasion: ME LINE, with depigmenting, rejuvenating and recovering effects on phototypes I-IV?’, Clinical Study 2015.
  23. Taylor SC, Torok H, Jones T, et al, ‘Efficacy and safety of a new triple-combination agent for the treatment of facial melasma’, Cutis, 2003;72(1):67–72.
  24. Sarkar R, Kaur C, Bhalla M, Kanwar AJ, ‘The combination of glycolic acid peels with a topical regimen in the treatment of melasma in dark-skinned patients: a comparative study’, Dermatol Surg, 2002;28(9):828–832.
  25. Grimes PE, ‘The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups’, Dermatol Surg, 1999;25(1):18–22.
  26. Balina LM, Graupe K, ‘The treatment of melasma, 20% azelaic acid versus 4% hydroquinone cream’, Int J Dermatol, 1991;30(12):893–895.
  27. Song JY, Kang HA, Kim MY, et al, ‘Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion’, Dermatol Surg, 2004; 30:390–394.
  28. Rita Lee, ‘How to Treat Hyperpigmentation – A Review of Brightening Ingredients’, Just about Skin, 2014. 

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