Pigmentation is a complex condition that concerns many clients. In fact, complaints about pigmentation from clients often exceed that of aging. Yet, if this is the case, why are treatments for this condition failing? It is a multi-faceted question and the reasons can be numerous, so reviewing the pigmentation process called melanogenesis will aid in exploring the answers.
The melanocyte is the name of the cell responsible for the formation of pigment that colors skin, hair, and eyes. It is formed during the embryonic stage in the neural crest. As the fetus develops, the melanocytes migrate away from the neural crest, traveling through the body to the areas where pigment is usually found (the skin, hair, and eyes). Over 120 genes are involved in this cell movement and, hence, the potential for 120 reasons something could go wrong.
Melanocytes are genetically programmed before leaving the neural crest with a blueprint that predetermines the color of skin, hair, and eyes. Research highlights some reasons why skin conditions associated with pigmentation are so challenging to treat. There is no stem cell resource of melanocytes. Once the melanocyte has left the neural crest there is no return and no further development of this cell after birth. By the age of 18, the few regeneration cycles of the melanocyte have been completed. From the age of 35, 10 to 20 percent of functioning melanocytes are lost every 10 years. Melanocytes will eventually settle in the lowest region of the epidermis (basal layer), just above the dermal-epidermal junction that separates the epidermis from the dermis. Here, about one in every 10 cells is a melanocyte, with a ratio of one melanocyte to 30 keratinocytes (the leading cell of the epidermis).The melanocyte is a dendritic cell that is long-lived and slow cycling. This long lifecycle makes them highly susceptible to oxidative stress, leading to lipid peroxidation and, ultimately, mitochondria DNA damage due to its long but slow cycling lifecycle.
The melanocyte produces and distributes the pigment melanin, which is responsible for the color of skin with two pigments: eumelanin, the dark brown pigment, and pheomelanin, the red pigment. Melanin is an extremely complex polymer and there may be very minute differences between the melanin of different people and within races.
Skin has a different color in different areas. This is because there are more melanocytes in darker areas, such as the neck, versus lighter areas, like the face. However, within these areas, the concentration of about 1,000 to 2,000 melanocytes per cubic millimeter is the same for all race groups.
So, whether a client has light or dark skin, they will still have about the same number of melanocytes, but with a different balance of eumelanin and pheomelanin pigment granules inherited from the family gene pool.
There are some significant differences between lighter and darker skins. The most significant is that the melanocyte dendrite in darker skins is longer in length. This length enables the melanocyte to deposit pigment higher in the upper spinosum layer, affording earlier and greater protection from the hot, sunny climates in the countries from which many darker skin tones originate. The opposite is found in lighter skin and, here, the shorter dendrites place the pigment more horizontally through the spinosum layer. The melanosomes themselves and pigment granules are also smaller in lighter skin.
The melanocyte stands fourth in line of skin barrier defense, preceded by the antimicrobial barrier (previously referred to as the acid mantle), permeability layer (previously referred to as the corneocytes and multilamellar structure), Langerhans cell, and melanocyte.Individuals with a gene called melanocortin-1 receptor (red hair in the family gene pool) may have a high percentage of red pigment pheomelanin and this is reflected by a very short burn time. Redheads are known to have a greater risk of melanoma.
The melanocortin-1 receptor gene determines skin’s tanning potential, but, make no mistake, it does not mean that those with fair skin cannot tan. The skin will attempt to protect itself, but tan, in this case, comes with the risk of pigmentation, loss of pigmentation, and permanent damage to the melanocyte.The formation of melanosomes and melanin pigment is a process that requires much energy by the melanocyte mitochondria creating many radicals.
This oxidative process is controlled by built-in cellular defense, antioxidant super dismutase oxide, sometimes known as superoxide dismutase. Sadly, this built-in defense system declines with cellular age or may be lost due to mitochondria DNA damage or cellular senescence. The creation of the red pigment pheomelanin causes even more oxidative stress than the formation of the brown pigment eumelanin.
Thus, it is important to note that repeated unprotected sun exposure or sunburn may cause the pheomelanin to become altered in such a way as to allow it to become converted into a free radical, generating the superoxide anion, which can damage nearby skin cells, including the mitochondria DNA of melanocytes and keratinocyte stem cells. This is called intra-cellular oxidative stress.
Next, professionals must understand the steps involved in the formation of the melanin pigment. It is a complex process, but this article will attempt to keep it simple and relevant.
Exposure to ultraviolet radiation through the retina of the eye begins the melanin production process. Ultraviolet radiation stimulates the pituitary gland to form a protein called proopiomelanocortin, the precursor to the melanin stimulating hormone. The melanin stimulating hormone first adheres to the specific receptor protein within the cell membrane of the keratinocyte. The keratinocyte will then communicate with the melanocyte to turn on a melanin stimulating hormone receptor. When a molecule of melanin stimulating hormone binds to a receptor, a series of events occur; in this instance, it will be the first step in the formation of the melanosome that will eventually carry the pigment granules eumelanin and pheomelanin.
The enzyme tyrosinase plays a key role in melanin synthesis as a catalyst to the amino acid tyrosine and the formation of a pre-melanosome within the melanocyte. Within the melanosome, pigment granules of melanin are synthesized.Tyrosine converts to dopa-quinone and then to eumelanin and – combining dopa-quinone with cysteine – makes pheomelanin the red pigment. It is during the formation of the pheomelanin that large amounts of energy are used and radicals created aggravate oxidative stress within the melanocyte cell. Melanin pigment granules are formed within the melanosome. Melanosomes are small oval pods with thread-like structures within them. The melanin pigment granule is deposited on these threads in varying concentration, depending on the individual genetic code. (For example, five brown and eight red pigment granules.) The melanin pigment granules inside the melanosome at this time remain almost colorless until after the transfer to the keratinocyte.
The melanosomes pass down through the dendrites, maturing as they move. Once they reach the end of the dendrite, they will be transferred to the keratinocyte by a receptor called PAR-2 by phagocytosis, where they are dispersed into the cytoplasm, eventually settling over the nucleus. Here, they play an essential role in cell defense by protecting the nucleus DNA of the cell. In lighter skin, this process occurs mostly around the lower spinosum layer. Once the melanosome has been transferred into the cytoplasm of the keratinocyte, it becomes darker and visible as skin color. This is called immediate pigment darkening.
The keratinocyte cell will then continue its journey upward to the stratum corneum. All things going well, the keratinocyte will desquamate. The use of tanning beds or high levels of sun exposure will speed up melanogenesis. This results in increased melanosome transfer to the keratinocyte and an increase in turnover of the keratinocytes to pick up the melanosomes. Keep in mind, increased oxidative stress from the heat and light spectrum of ultraviolet radiation, including increased mitochondria energy, and resulting oxidative stress may result in reduced cellular energy and production.
DETERMINING A TREATMENT PLAN
If all pigment gets passed to the keratinocyte and all keratinocytes desquamate, why does pigmentation exist? There are more cells and systems involved in the color story of skin. Aside from the melanocyte (the cell of main discussion here), note that the keratinocyte, the innate immune system, circulatory system, and adaptive immune system all contribute to color.
The main reason professionals are not getting the best results for clients struggling with pigmentation is because they do not take the time to think through the process well enough to determine the best homecare and in-clinic treatment program for the individual in front of them.If the skin barrier is not functioning well to start with, then the results obtained will be limited at best. Skin health is equally as important as choosing the treatment modality. It is also vital to provide treatments in the right season to prevent an even higher risk of pigmentation for clients.The answers, of course, lie in an in-depth consultation process. Professionals must ask themselves many questions, too. Here are some of the questions to think about when a client presents with pigmentation.
Why Would There Be an Abnormal Increase in Pigment-Carrying Melanosomes?
Pregnancy or medications, such as oral contraceptive, in-vitro fertilization medication, or progesterone-based medication, cause the pituitary gland to make too much melanin-stimulating hormone. When this happens, the melanin stimulating hormone is continuously adhering to the receptors of the keratinocyte and, in turn, the melanocyte creates uncontrolled manufacturing of melanosomes. This uncontrolled release of the melanin-stimulating hormone is called the melanin stimulating hormone cascade and will be reflected in the butterfly pattern of pigmentation that is commonly seen in the center of the face and across the upper lip and forehead. Here is a before and after an image of good results with no clinical treatments as an intervention. It was accomplished over 18 months with appropriate skin care only. This illustrates the importance of improving cellular health.
What Would Stop the Keratinocyte from Picking Up Melanosomes?
The keratinocyte cell membrane is not viable or flexible enough to practice the phagocytosis method of picking up the melanosomes that have been transferred to the keratinocyte through a receptor called PAR-2. Essential fatty acid deficiency is often a leading cause here and if the keratinocyte is not viable or flexible, the melanocyte may also be in a compromised state.
Where Will the Melanosome Fall if Not Picked Up by a Keratinocyte?
Knowledge about the skin’s structure reveals that the keratinocyte mother cell and melanocytes are attached to the basal lamina of the dermal-epidermal junction by keratin filaments called hemidesmosomes. This junction is permeable and also referred to as the dermo- junction. The dermo-junction is made of sinusoidal connective tissue because it is filled with holes, pockets, and channels that allow the movement of fluids and immune cells (like the Langerhans) to move through from the dermis to epidermis. The epidermal side of this junction is called the basal lamina and is where the melanosome would rest if not picked up by the ascending keratinocyte. If this is ongoing, then a large amount of pigment could accumulate into this junction. All of the accumulated pigment that was in the junction will be released into the dermis as a result if or when the dermal-epidermal junction collapses. This is called dermal pigmentation.
What Will Be the Result if the Spinosum Layer Were Not Viable Enough for the Even Dispersion of Pigment?
There will an accumulation of pigment into smaller areas, which may reflect as pigmentation.
What Will Be the Results if the Melanocyte to Keratinocyte Ratio Were Not the Normal 1 to 30?
The melanocyte is programmed to make a specific number of melanosomes relative to the strength and length of sun exposure it has experienced. These melanosomes should be released across to 30 keratinocytes for pickup. If the melanocytes dendrites are not long enough to reach 30 keratinocytes or there is a lesser number of keratinocytes to pick up the melanosomes, it is likely that the 30 cells worth of melanosomes will be released out to fewer keratinocytes. It would reflect in a heavy deposition of pigment into a very small area with many melanosomes spilling into the dermal-epidermal junction.
The world is full of mixed ethnicities and there are many hidden dangers. Hair and eye color as an indication to establish phototype is now misleading. The melanocortin-1 receptor gene (redhead gene) can be hidden as a result of mixed ethnicity and this means that the client’s risk for skin cancer may not be obvious.
The answers lie in the consultation and sensible questions should cover information gathering about genetic heritage, tanning ability, redhead gene, and sunbed usage.
Powerful treatment modalities are available today, but they are not without risk and just because a modality is available does not make it the right choice for all clients with pigmentation-related skin conditions. It is the professional’s obligation to say no when a client carries too high a risk. Professionals should recommend treatment at a future date if the client is seeking treatment in a high-risk time, such as summer; professionals can minimize risk by delaying treatment. Professionals must say no when a client might be non-compliant with the necessary homecare protocols to perform safe and effective treatments.
Above all, it is a privilege to educate clients and give them every opportunity for fully informed consent.
1 Barrett-Hill, Florence. “Understanding Dermal Pigmentation.” Pastiche. Jul 20, 2017. http://www.pastiche-training.com/flosaid/understanding-dermal-pigmentation
2 Fernandes, Des. “The Melanocyte and the colour of skin.” https://emaniocreativecom.ipage.com/files/product-information/white-papers/skin- conditions/THE-MELANOCYTE-AND-COLOUR-OF-SKIN.pdf
3 “The A-Z Of Understanding Pigmentation.” Pastiche. https://www.pastiche-training.com/a-z-pigmentation.
4 Barrett-Hill, Florence. “Photosensitivity.” beautymag Online. http://www.beautymagonline.com/beauty-articles-2/934-photo-allergy-2W.
5 Barrett-Hill, Florence. “The Power of The Consultation.” Beautymag Online. http://www.beautymagonline.com/beauty-articles/1199-the-power-of-the-consultation.
6 “MC1R gene.” U.S. National Library of Medicine. https://ghr.nlm.nih.gov/gene/MC1R.
7 Schenkel, Laila Cigana, and Marica Bakovic. “Formation and Regulation of Mitochondrial Membranes.” International Journal of Cell Biology. 2014. https://www.hindawi.com/journals/ijcb/2014/709828.
8 “Mitochondria and Golgi Apparatus.” Organelles. https://introducingorganelles.weebly.com/mitochondria-and-golgi-apparatus.html.
9 “How This Normal Body Process Can Contribute to More Than 60 Diseases.” MERCOLA. https://articles.mercola.com/sites/articles/archive/2011/05/16/all-about-antioxidants.aspx
10 “Mitochondrial DNA.” U.S. National Library of Medicine. https://ghr.nlm.nih.gov/primer/basics/mtdna.
11 Agarwal, Sanjiv and R.S. Sohal. “Relationship between susceptibility to protein oxidation, aging, and maximum life span potential of different species.” Experimental Gerontology 31, no. 3 (1996): 365–72.
12 Bolognia, Jean L. and Seth J. Orlow. “Melanocyte Biology.” In Dermatology, edited by Jean L. Bolognia, Julie V. Schaffer, and Lorenzo Cerroni, Page 44. Elsevier Limited, 2007.
13 Prota, Giuseppe. Melanins and Melanogenesis. Elsevier Limited, 1992.
14 “Red-hair gene tied to melanoma.” keratin.com. Mar 2004.
15 Pawelek, John M. “Ultraviolet light and pigmentation of the skin.” Cosmetic & Toiletries 107 (1992).
16 “Note for Guidance on Photo-safety Testing.” The European Agency for the Evaluation of Medicinal Products. London, 2002.
17 “Some substances which cause photosensitivity.” National Occupational Health & Safety Commission. www.geocities.com/fragranceallergy.
18 Lyford, Willis Hughes. “Melasma.” Medscape. Oct 26, 2018. www.emedicine.com/DERM/topic260.htm.
19 Laumann, Anne Elizabeth. “Anetoderma.” Medscape. Apr 6, 2017. www.emedicine.com/DERM/topic221htm.
20 Scruggs, Jessica M. “Ephelides (Freckles).” Medscape. https://img.medscape.com/pi/iphone/medscapeapp/html/A1119293-business.html.
21 Jaku, Jeannette Rachel. “Poikiloderma of Civatte.” Medscape. Apr 28, 2017. www.emedicine.com/derm/topic603.htm.
22 Alikhan, Ali. “Berloque Dermatitis.” Medscape. Dec 21, 2018. www.emedicine.com/derm/topic52.htm.
23 Schwartz, Robert A.“Postinflammatory Hyperpigmentation.” Medscape. May 4, 2018. www.emedicine.com/derm/topic876.htm.
René Serbon, corneotherapy expert, industry educator, and speaker, gives skin care professionals a true point of difference in the industry. How? By handing them the ultimate drawing card: knowledge about the skin wrapped in savvy business strategy. Her keynotes and in-depth trainings educate on skin anatomy, physiology, and how to match cosmetic chemistry to specific skin conditions and by helping clinic owners and solo aestheticians blow the roof off their in-clinic results and business growth by 30 percent a year or more. Serbon is CIDESCO and CIBTAC certified, one of the world’s few Pastiche educators, and proudly serves on the International Association of Applied Corneotherapy (IAC) educational board. She personally swapped grooming services for corrective skin care the day she opened her appointment book and saw 10 hours of back to back waxing, hence her motto: “There’s life after waxing.”