Hyperpigmentation & Fire Stations

What on earth do these have in common?

Hyperpigmentation is a complex subject that few people fully understand. To make it easier to explain, I use the Fire Station analogy in my training sessions. But first…

There are many types of hyperpigmentation

• Pigment spots – such as age spots are caused by sun exposure. For this reason, they appear mainly on body parts that are frequently exposed, such as the face, hands and arms. They tend to be small, darkened patches of skin. The medical term for spots resulting from sun exposure is Solar Lentigenes. The medical term for age-related spots is Senile Lentigenes, although these result from a cellular waste pigment, called Lipofuscin, which is a totally different pigment from melanin. But most people in the industry say Age Spots when they mean Sun Spots. Lipofuscin is due to an accumulation of cellular rubbish, that comes with age. It is oxidized skin lipid that turns yellow or brown.

• Melasma –  often referred to as “the mask of pregnancy”, as it affects around 70% of pregnant women and occurs as a result of hormonal influences such as pregnancy and birth control pills. With melasma, the pigmentation is generally symmetrical and has clearly defined edges. It occurs on the forehead, temples, cheeks, nose, upper lip, and chin, and sometimes neck & arms. But mostly in the central third of the face. This pattern is sometimes called a butterfly mask. While it affects all races, melasma occurs most often in brown or olive skin tones.

• Freckles – caused by sun exposure, and commonly appear on the face. These are largely genetic in nature. The medical term for freckles is Ephelides or Lentigenes

• Post-inflammatory hyperpigmentation (PIH) – which occurs when a skin injury or trauma heals and leaves an area of discolouration behind. Things that can cause post-inflammatory pigmentation:
  • cystic acne or healing pimple
  • cosmetic procedures – lasers, IPL, microdermabrasion
  • deep chemical peels
  • chemical exfoliants – AHA’s and other acids
  • overuse of certain ingredients (e.g. Benzoyl Peroxide)
  • mechanical trauma – a wound that leads to a scar or discoloration
  • anything that causes excessive irritation
  • Post-inflammatory hyperpigmentation can occur in any skin type but is more common in Fitzpatrick Skin Types 4-6, which are darker skin tones.  If you have a darker skin, you need to be extra careful about exfoliation, cosmetic procedures, and wound care, because your skin is more likely to pigment (and scar) afterward.

   

Fire Stations

Fire Stations usually serve a certain radius, or a certain number of households and are usually based on roads with quick access to households and businesses they serve. Calls come in to the Station’s emergency line and fire engines are dispatched to the scene. Hold this thought.

Our skin’s basal layer (the dermal-epidermal junction) contains a few different cell types. It is, for example, where keratinocytes are born. These cells are the main constituent of the epidermis. As they mature they are pushed towards the surface by the newer cells born beneath them. When they die they become corneocytes and form the tough layers of the stratum corneum. In my analogy, keratinocytes are the ‘homes’ in a neighbourhood.

Melanocytes inhabit the basal layer too. They are the cells that produce melanin – the pigmentation in our skin. The role of pigmentation is purely to protect our skin. When you suntan you are actually inflicting an injury on the skin, leading to the production of melanin (pigmentation) to protect you from sun damage. Melanocytes are the ‘Fire Station’ in my analogy. In the same way that a Fire Station serves a neighbourhood, so a melanocyte serves its ‘neighbourhood’ by having dendrites (roads) that contact keratinocytes (homes). Typically, one melanocyte makes contact with around forty keratinocytes. This contact facilitates the transfer of melanin into keratinocytes, via melanosomes. It is these pigmented keratinocytes that rise to the upper skin layers and bring pigmentation to the surface.

Melanocytes contain organelles, called melanosomes and these melanosomes contain melanin. In my analogy, melanosomes are the fire engines and melanin is represented by firemen (and women!) – they are transported in the fire engine (the melanosome), taking them to the scene of the fire. These firemen have different skin and hair colour (pigmentation) – their ‘phenotypic’ appearance. Normally this is dark but could be blonde or red. Different forms of melanin give rise to these differences. There are 2 kinds of melanin:

1. Eumelanin – yellow to brown to very dark brown (almost black) color; seen in brown-black hair
2. Pheomelanin – red-yellow color; seen in red hair

The mixture of these melanins gives rise to different skin and hair colours.

Melanin is also responsible for the color of our eyes. Variation in the color of our eyes from brown to green depends on the amount of melanin in the iris, which in turn is determined genetically. There are three genes that affect eye color, so it’s hard to pinpoint the exact color that a child’s eyes will be. Individuals with black or brown eyes have eyes with more melanin to block the sun’s rays. Those with blue, green, or hazel eyes have little protection from the sun and may experience discomfort, irritation, burning, and tissue damage if the eyes are not protected by sunglasses when exposed to bright light.

keratinocytes put out the 911 call to the Fire Station (melanocytes) and they respond by sending out fire engines (melanosomes) and firemen (melanin). These infiltrate the homes (keratinocytes), spreading melanin and causing hyperpigmentation

Melanin plays an important role in your skin

It

• scatters UV light
• absorbs heat
• neutralizes Reactive Oxygen Species (ROS)
• protects DNA from UV damage
• protects cell membranes from oxidation

People with darker skins have larger melanocytes (with more dendrites), larger melanosomes, and more melanosomes. So there is more melanin overall. Lighter skins have smaller melanocytes (and fewer dendrites) and smaller melanosomes (less melanin).

There is a key difference in the distribution of those melanosomes (where they end up in the epidermis):

• In light skins, melanosomes are usually found in the basal layer of the epidermis and are smaller and clustered together (look like grapes). These melanosomes stay intact (the melanin remains inside)

• In dark skins, melanosomes are larger, more oval, denser, and scattered individually (they look like cucumbers). These melanosomes migrate to the upper epidermal layers, break down and release melanin into the keratinocytes there. The melanin is evenly spaced out, providing an even pigmentation.

Since darker skin has more overall melanin, it has more inherent photo-protection.

Have you ever wondered why many people with darker skin tones age so well? Their higher melanin content delays the signs of photoaging. Melanin is a natural sunscreen.

Key steps in the formation of pigmentation

Going back to our Fire Station analogy, we have these key steps in responding to an emergency call:

1. Home occupant senses a fire and calls 911
2. 911 responder answers the call and summons help
3. Fire Station mobilises and fire engines are fuelled
4. Firemen jump into fire engines
5. Fire engines travel to the scene of the fire and the firemen put out the fire.

In our skin, the equivalent steps are:

1. Keratinocytes declare an emergency. They do this by secreting α-MSH (Melanocyte Stimulating Hormone), which binds to the melanocyte’s MC1-R receptor. Think of this as the telephone connection to the Fire Station responder
2. This upregulates MITF (Microphthalmia-Associated Transcription Factor). MITF is the master regulator of melanocytes – the ‘mobiliser’ of the Fire Station
3. This mobilisation leads to the tyrosinase pathway and resultant melanin production. Tyrosinase is the key enzyme in this process. Think of it as the fuel in the fire engine (the melanosomes).
4. Melanosomes transport the melanin to the keratinocytes and deposit it.
5. The resulting pigmentation rises to the skin surface as the keratinocyte matures, and becomes visible on the skin surface.

So, what can we do about it?

Chemical peels and other physical procedures are extremely effective in dealing with hyperpigmentation when used correctly.

Most actives used to fight hyperpigmentation act on the tyrosinase pathway ie they deprive the fire engines of fuel, so that melanosomes, with their melanin payload, cannot leave the Fire Station. The actives most commonly used are:

• Vitamin C (ascorbic acid) – blocks the tyrosinase enzyme by attaching itself to the copper molecule on tyrosinase. We prefer to use a stable form of vitamin C, called Sodium Ascorbyl Phosphate, in our Fade Cream/Serum and Vitamin C Serum
• Green Tea catechins – see our previous blog on this
• Glutathione – an up and coming tool in the fight against hyperpigmentation and the basis of our Fade Serum
• Kojic Acid – derived from fungi. We favour the use of 1-Methylhydantoin-2-Imide (M2I) – a natural amino acid derivative, shown to be as effective as kojic acid
• Azelaic Acid – we favour using a natural equivalent called octadecenedioic acid
• Arbutin – a naturally occurring derivative of hydroquinone (it is composed of hydroquinone with a sugar group attached). It is believed to be one of the best alternatives to hydroquinone as it provides the skin-lightening effect of hydroquinone without some of the potential side effects.
• Hydroquinone – banned in a number of countries but the traditional gold standard for treating pigmentation issues. The combination of hydroquinone and the sun is a bad one. Increased risk of ochronosis and other side effects have been linked to excess sun exposure while using hydroquinone. We favour using 1-Methylhydantoin-2-Imide as a safe, natural alternative, albeit not as dramatic in outcomes.
• Niacinamide – currently the second most popular active for hyperpigmentation. Works best with N-acetyl-glucosamine in the ratio we use in Micellar Sensitive and Balance Cream
• Retinoids – like our Retinic A10
• Alpha-Lipoic Acid (LA)- research shows that LA reduced the microphthalmia-associated transcription factor, MITF, and tyrosinase promoter activities, resulting in depigmentation. We add LA to Fade Serum and Retinic A10
• Citric Acid – used in a number of our products to acidify eg Micellar Sensitive, Fade Serum etc
• Mandelic Acid

Stopping the emergency call in the first place

It seems logical to us that limiting the ‘fuel’ is one way to slow down hyperpigmentation but another approach we use in our products is to stop the emergency call coming in, in the first place. We use a peptide sequence in both our Fade products, to downregulate the production of α-MSH. It works well in association with ascorbic acid and has the same net effect as blocking the emergency call.

A second peptide sequence mimics the action of a cytokine called TGF-β (Transforming Growth Factor), which downregulates MITF, thereby preventing the differentiation of melanocytes and their downstream melanogenic genes, as well as a loss of dendricity. So, we limit the extent to which the Fire Station is mobilized. Ultimately, this results in reversible inactivation of the melanocyte lineage.

all pigmentation treatments are temporary and reversible

Let’s not forget though that hyperpigmentation is caused by an injury – UV exposure, physical or chemical insults, pollution etc. Your skin is sending you a warning sign that should never be ignored. Always use a good sun screen with SPF>30.