Hyperpigmentation is the medical term used to describe the darkening of an area of skin or nails caused by increased melanin, or in rare cases, other pigments.
Pathophysiology
editMelanin is responsible for producing colour in the body in places such as the eyes, skin, and hair. As the body ages, melanocyte distribution becomes less diffuse and its regulation less controlled in the body. Hyperpigmentation occurs when there is an increase in the production of melanin, or a change in its distribution.
Eumelanin and pheomelanin are pigments metabolized from melanin[1] and are responsible for determining skin colour. The ratio of these two types of melanin help account for ethnic differences in skin colour[2]. Individuals with melanocytes that produce more pheomelanin than eumelanin have lighter skin, whereas those who produce more eumelanin tend to have darker skin.[3] Compared to lighter skin types, skin that contains more eumelanin are found to be more prone to dyspigmentation and dyschromia, more specifically hyperpigmentation.[3]
Epidermal hyperpigmentation results from increased melanin deposited in the epidermis. Environmental and genetic factors play a role in the amount of melanocytes present within the epidermis, which can cause an increased number in melanocytes, or a normal amount of melanocytes that have increased production of melanin. Dermal hyperpigmentation does not occur as often. It can happen when epidermal pigment migrates into the dermis, melanin is produced by melanocytes found in the dermis, and when melanin binds with other pigments found outside the body that have inserted into the dermis. [2]
Causes
editHyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.[4][5][6]: 854
UV light stimulates melanocyte activity, and where concentration of the cells is greater, hyperpigmentation occurs. This makes people with darker skin tones more prone to hyperpigmentation, particularly with excess sun exposure.[7] Post-inflammatory hyperpigmentation (PIH) and melasma are the most common hyperpigmentation disorders.
Post-inflammatory hyperpigmentation (PIH) occurs as a response to inflammation and is commonly found in darker-skinned individuals. Inflammatory mediators can trigger the melanogenesis pathway to produce more melanin.[8][9] Some causes include radiation, acne vulgaris, atopic dermatitis, insect bites, contact dermatitis, and other conditions that can induce an inflammatory response.[1] Exposure to UV light may worsen this condition.[10] Post-inflammatory hyperpigmentation look like dark patches, or macules, found in places where the inflammatory response has occurred. Melanin deposited in the epidermis presents as tan or dark brown, whereas melanin found in the dermis is typically a darker brown or a blue/grey colour. Epidermal PIH is thought to be due to increased production and transfer of melanin to keratinocytes and dermal PIH occurs through the migration of melanin from the epidermis to the dermis.[1][10] Post-inflammatory hyperpigmentation found within the epidermis can go away on its own and heals faster than when found in the dermis, which requires treatment, may take longer and be permanent.
Melasma, also known as 'chloasma' or the “mask of pregnancy,” when it occurs in pregnant women. It is a common skin problem that causes dark, discoloured patchy hyperpigmentation. It typically occurs on the face and is symmetrical, with matching marks on both sides of the face. The condition is much more common in women than men, though men can get it too. According to the American Academy of Dermatology, 90 percent of people who develop melasma are women.[11]
Freckling is another form of hyperpigmentation that can occur from sun exposure. There are two types of freckling, ephelides, where genetics play a role and develop at a young age and solar lentigines, which occur later in life and can also be caused by photodamaged skin. [12]
Hyperpigmentation is associated with a number of diseases or conditions, including the following:
- Addison's disease and other sources of adrenal insufficiency, in which hormones that stimulate melanin synthesis, such as melanocyte-stimulating hormone (MSH), are frequently elevated.
- Cushing's disease or other excessive adrenocorticotropic hormone (ACTH) production, because MSH production is a byproduct of ACTH synthesis from proopiomelanocortin (POMC).
- Acanthosis nigricans—hyperpigmentation of intertriginous areas associated with insulin resistance.
- Acne scarring from post-inflammatary hyperpigmentation
- Linea nigra—a hyperpigmented line found on the abdomen during pregnancy.
- Peutz–Jeghers syndrome—an autosomal dominant disorder characterized by hyperpigmented macules on the lips and oral mucosa and gastrointestinal polyps.
- Exposure to certain chemicals such as salicylic acid, bleomycin, and cisplatin.
- Smoker's melanosis
- Coeliac disease
- Cronkhite–Canada syndrome
- Porphyria
- Tinea fungal infections such as ringworm
- Haemochromatosis—a common but debilitating genetic disorder characterized by the chronic accumulation of iron in the body.
- Mercury poisoning—particularly cases of cutaneous exposure resulting from the topical application of mercurial ointments or skin-whitening creams.
- Aromatase deficiency
- Nelson's syndrome
- Graves' disease
- Schimke immunoosseous dysplasia (SOID)[13]
- As a result of tinea cruris.
Hyperpigmentation can sometimes be induced by dermatological laser procedures.
Diagnosis
edit- A complete physical examination including a detailed medical history, usually sufficient for diagnosis.
- Thorough examination of the skin under visible light or Wood's light
- Reflectance confocal microscopy, a technique used to examine the epidermis and dermis at a microscopic level. It is not commonly used, but allows for diagnosis and monitoring of treatment without continuous skin biopsies.[2]
- Skin biopsy
Treatment
editThere are a wide range of depigmenting treatments used for hyperpigmentation conditions, and responses to most are variable.[14]
Hyperpigmentation disorders found within the epidermis (such as melasma, post-inflammatory hyperpigmentation) are mostly treated with topical therapies. Dermal hyperpigmentation is best treated with laser therapy[2]. Management of underlying conditions that may be inducing hyperpigmentation are considered to be a first-line treatment, such as acne-induced PIH and may involve the use of prescription products such as oral antibiotics, spirinolactone and isotretinoin.[10]
Chemical peels
editChemical facial peels are a newer form of treatment used to remove hyperpigmentation. The most commonly used peeling agents include glycolic acid and salicylic acid, as well as topical retinoids. Peels range from superficial to medium-depth to help reduce dark spots, although medium-depth peels have increased risk of developing PIH after and should be used with caution, especially in people with darker skin tones.[1][2][10]
Topical therapies
editTreatment of hyperpigmentation caused by melanin overproduction includes the use of topical depigmenting agents, which vary in their efficacy and safety, as well as in prescription rules.[15] Several are prescription only in the US, especially in high doses, such as hydroquinone, azelaic acid,[16] and koijic acid.[17] Some are available without prescription, such as niacinamide,[18][19] or cysteamine hydrochloride.[20][21] Hydroquinone is the most commonly prescribed hyperpigmentation treatment, however long-term safety concerns were raised when the medication was still new, [22] and the use of it became more regulated in several countries and discouraged in general by WHO.[23] Since then, it has become well-studied and hydroquinone monotherapy remains one of the most effective ways of treating hyperpigmentation disorders[2][24]. For the US, only 2% hydroquinone at present is sold over-the-counter, and 4% needs prescription. There are concerns of exogenous ochronosis with extended hydroquinone use as well as connection to malignant tumors, however ochronosis is considered a rare occurrence in North America and studies have not found a reason to link hydroquinone to malignancies[1][10][25]. Regardless, long-term use of hydroquinone is not recommended[1][10]. In the EU however, hydroquinone was banned from cosmetic applications and over-the-counter medications.[26]
Combination therapies of hydroquinone with other anti-inflammatory agents are also a recommended treatment alongside hydroquinone for hyperpigmentation,[10][27] Studies have shown that triple combination therapy with 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone (otherwise known as Tri-luma) produced significantly better results in treating hyperpigmentation than hydroquinone 4% alone or combined with one other agent and provided minimal skin irritation[1][10][24][27].
Oral medication with procyanidin plus vitamins A, C, and E also shows promise as safe and effective for epidermal melasma.
Laser therapy
Other treatments that do not involve topical agents are also available, including fraction lasers[28] and dermabrasion.[15]
Cosmetic camouflage
editMakeup containing iron oxide and zinc oxide provide the benefits of hiding hyperpigmentation, protection of skin, and preventing of photo-induced skin damage and darkening[2]. They can also be used during active topical therapy with other prescription products[25].
Sun protection
editProtecting the skin from sun exposure is considered a first-line treatment in post-inflammatory hyperpigmentation and melasma[1][10]. Avoidance of sunlight between the hours of 11:00 and 4:00pm, staying in the shade, and wearing sunscreen with an SPF of at least 30 and sun-protective clothing is beneficial in all cases[2].
See also
editReferences
edit- ^ a b c d e f g h Vashi, Neelam A.; Wirya, Stephen A.; Inyang, Meyene; Kundu, Roopal V. (April 2020). "Facial Hyperpigmentation in Skin of Color: Special Considerations and Treatment". American Journal of Clinical Dermatology. 18 (2): 215–230. doi:10.1007/s40257-016-0239-8. ISSN 1175-0561.
- ^ a b c d e f g h Vashi, Neelam A., Kundu, Roopal (November 21, 2019). "Acquired Hyperpigmentation Disorders". UpToDate. Retrieved December 28, 2020.
{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: url-status (link) - ^ a b D’Mello, Stacey; Finlay, Graeme; Baguley, Bruce; Askarian-Amiri, Marjan (2016-07-15). "Signaling Pathways in Melanogenesis". International Journal of Molecular Sciences. 17 (7): 1144. doi:10.3390/ijms17071144. ISSN 1422-0067. PMC 4964517. PMID 27428965.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ "Hyperpigmentation". Dermatalogic Disease Database. American Osteopathic College of Dermatology. Retrieved 2006-03-08.
- ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
- ^ Chandra, M; Levitt, J; Pensabene, CA (May 2012). "Hydroquinone therapy for post-inflammatory hyperpigmentation secondary to acne: not just prescribable by dermatologists". Acta Dermato-Venerologica. 92 (3): 232–5. doi:10.2340/00015555-1225. PMID 22002814.
- ^ Visscher, Marty O. (2017-02-01). "Skin Color and Pigmentation in Ethnic Skin". Facial Plastic Surgery Clinics of North America. Facial Scar Management. 25 (1): 119–125. doi:10.1016/j.fsc.2016.08.011. ISSN 1064-7406.
- ^ Zubair, Raheel; Lyons, Alexis B.; Vellaichamy, Gautham; Peacock, Anjelica; Hamzavi, Iltefat (2019-04-01). "What's New in Pigmentary Disorders". Dermatologic Clinics. Therapeutic Hotline: New Developments in Dermatology. 37 (2): 175–181. doi:10.1016/j.det.2018.12.008. ISSN 0733-8635.
- ^ a b c d e f g h i Kaufman, Bridget P.; Aman, Taulun; Alexis, Andrew F. (August 2018). "Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation, Pathogenesis and Treatment". American Journal of Clinical Dermatology. 19 (4): 489–503. doi:10.1007/s40257-017-0333-6. ISSN 1175-0561.
- ^ "Melasma". American Academy of Dermatology, Inc.
- ^ Praetorius, Christian; Sturm, Richard A.; Steingrimsson, Eirikur (May 2014). "Sun-induced freckling: ephelides and solar lentigines". Pigment Cell & Melanoma Research. 27 (3): 339–350. doi:10.1111/pcmr.12232.
- ^ "Schimke immunoosseous dysplasia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-03-13.
- ^ Gupta, AK; Gover, MD; Nouri, K; Taylor, S (December 2006). "The treatment of melasma: a review of clinical trials". Journal of the American Academy of Dermatology. 55 (6): 1048–65. doi:10.1016/j.jaad.2006.02.009. PMID 17097400.
- ^ a b "Variety of options available to treat pigmentation problems | American Academy of Dermatology". www.aad.org. Retrieved 2017-02-12.
- ^ Mazurek, Klaudia; Pierzchała, Ewa (2016-09-01). "Comparison of efficacy of products containing azelaic acid in melasma treatment". Journal of Cosmetic Dermatology. 15 (3): 269–282. doi:10.1111/jocd.12217. ISSN 1473-2165. PMID 27028014. S2CID 25303091.
- ^ Monteiro, Rochelle C.; Kishore, B. Nanda; Bhat, Ramesh M.; Sukumar, D.; Martis, Jacintha; Ganesh, H. Kamath (2013-03-01). "A Comparative Study of the Efficacy of 4% Hydroquinone vs 0.75% Kojic Acid Cream in the Treatment of Facial Melasma". Indian Journal of Dermatology. 58 (2): 157. doi:10.4103/0019-5154.108070. ISSN 1998-3611. PMC 3657227. PMID 23716817.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Hakozaki, T.; Minwalla, L.; Zhuang, J.; Chhoa, M.; Matsubara, A.; Miyamoto, K.; Greatens, A.; Hillebrand, G.G.; Bissett, D.L. (2002-07-01). "The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer". British Journal of Dermatology. 147 (1): 20–31. doi:10.1046/j.1365-2133.2002.04834.x. PMID 12100180. S2CID 39489580.
- ^ "Spotlight On: Niacinamide - FutureDerm". FutureDerm. 2007-10-30. Retrieved 2017-02-12.
- ^ Mansouri, P.; Farshi, S.; Hashemi, Z.; Kasraee, B. (2015-07-01). "Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial". The British Journal of Dermatology. 173 (1): 209–217. doi:10.1111/bjd.13424. ISSN 1365-2133. PMID 25251767. S2CID 21618233.
- ^ "Cysteamine Cream® -- New Hyper Intensive Depigmenting Treatment". Scientis Pharma. Retrieved 2017-02-12.
- ^ Draelos, Zoe Diana (2007-09-01). "Skin lightening preparations and the hydroquinone controversy". Dermatologic Therapy. 20 (5): 308–313. doi:10.1111/j.1529-8019.2007.00144.x. ISSN 1529-8019. PMID 18045355. S2CID 24913995.
- ^ Hyrdoquinone Guidance published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. World Health Organization. 1994. hdl:10665/39218. ISBN 9789241571579.
- ^ a b McKesey, Jacqueline; Tovar-Garza, Andrea; Pandya, Amit G. (April 2020). "Melasma Treatment: An Evidence-Based Review". American Journal of Clinical Dermatology. 21 (2): 173–225. doi:10.1007/s40257-019-00488-w. ISSN 1175-0561.
- ^ a b Grimes, Pearl E., Callender, Valerie D. (July 30, 2020). "Melasma: Management". UpToDate. Retrieved December 29, 2020.
{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: url-status (link) - ^ "Hydroquinone - Substance evaluation - CoRAP - ECHA". echa.europa.eu. Retrieved 2017-02-12.
- ^ a b Plensdorf, Livieratos, Dada, Scott, Maria, Nabil (December 15, 2017). "Pigmentation Disorders: Diagnosis and Management". American Family Physician. 96(12): 797–804.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Laser Skin Whitening - Advantages and Disadvantages | Skin Whitening News". skinwhiteningnews.org. 2014-04-05. Retrieved 2017-02-12.