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Many people suffer from various discolorations of the skin as a result of locally increased skin pigment production. The pigment in the skin responsible is melanin, which also helps to protect us from the harmful effects of strong sunlight etc.

A variety of different influences, including the environment around us, or some internal factor, can cause some parts of the skin to produce more melanin. This results in hyper (excessive) pigmented skin spots or areas, such as: pregnancy mask, (often seen post pregnancy on the jaw line and other facial areas), liver-spots, age-spots and even hyper pigmentation after local skin damage, due to such things as acne or burns.e levels of Glutathione, chelate metals (such as iron and copper), quench diverse free radicals, and recycle antioxidants.

Pigment Types

Skin colour is normally the result of the combination of 4 pigments:

• In the epidermis (upper layer of the skin)
  • Melanin produced in the skin (brown-maroon);
  • Carotenoids which are taken into the skin from external sources (yellow)
• In the dermis (lower layer of the skin)
  • Red blood cells containing oxygenated red pigment (haemoglobin) in the capillaries (small arteries)
  • Red Blood cells containing de-oxygenated blue pigment (haemoglobin) in the venules (small veins)

Melanin
Among these pigments, melanin, which made in cells in the lower layer of the skin called melanocytes, is the main pigment causing differences in skin colour.

The definition of melanin is difficult and the exact chemical structures have not yet been fully worked out. However, the melanin in humans is divided into two main groups:

• Eumelanin - Brown/black pigment, prevalent in persons with dark complexions and hair

• Pheomelanin - yellow-reddish pigment, prevalent in persons with fair complexions, freckles and red hair

Manufacture of Melanin
The special melanin producing cells called melanocytes are located in the lower region of the epidermis, (the upper layer of the skin). These are cells equipped with special arm like projections (dendrites), which project both sideways and upwards towards other cells called keratinocytes.

In the fluid (cytoplasm) inside these melanocytes are special structures (organelles) called "melanosomes", which store the melanin as it is produced (melanin packets).

The melanocytes also make the enzyme called tyrosinase, which is taken up into the melanosomes (melanin packets). This enzyme is needed to make melanin.

Once the melanin is made in the melanosomes (melanin packets), it is transferred to the keratinocytes by a special mechanism: the keratinocytes take in (surround) the special arm like projections on the melanocytes, which are full of melanin containing melanosomes.

This is done by combining the cell membranes between the melanocyte projection and the keratinocyte, so that the melanin is transferred into the keratinocytes.

Each epidermal melanocyte transfers melanin to around 36 nearby keratinocytes, Together they constitute a biological unit called melanin-epidermal unit

Exposure to ultraviolet rays (in sunlight) accelerates the formation and passage of the melanosomes to the keratinocytes, bringing about sun tanning.

These keratinocytes containing melanin grow and develop and slowly move up towards the surface of the epidermis. The melanin is gradually broken down by other enzymes and as the dead surface layer of the skin sloughs away through normal wear and tear any melanin pigment left is also lost. So, pigmentation is not a static process but one undergoing constant renewal.

The differences in pigmentation of the various skin types are not due to a different number of melanocytes but in the way in which melanin is built up. The melanosomes (melanin packets) in black skin are larger (longer and wider) and when they are transferred to the keratinocytes they remain independent of each other i.e. they don't group together as do the melanin packets in white skin, which are also smaller.

Biochemistry of Melanogenesis
Both the eumelanins and pheomelanins are made from the amino acid tyrosine.
The process starts with tyrosine, which goes through a number of chemical reactions creating a variety of intermediate chemicals before it eventually becomes melanin. This entire process can be divided into two important phases:

The first few stages are controlled by an enzyme called tyrosinase and is called the Enzyme Phase The second stage consists of rapid changes to the molecule through reactions involving oxygen until you finally end up with melanin. This is called the 'Non Enzymatic Phase'.

Factors Influencing Melanin Production
Our colouration can vary on different areas of the body. There are three main factors which determine the level of melanin production and consequently our skin colouration:

• Genes

• Exposure to sunlight

• Hormonal factors

Our Constitutional colour is our 'native' colour. Our genes are the main influence in determining our skin colour in the absence of exposure to the sun or other influences.

Our Optional colour is the pigmentation taken on by the skin in relation to other influences - usually exposure to the sun or hormonal factors. Optional colour is also influenced genetically.

Hormones such as oestrogen have a pigmentogenic (pigment stimulating) action. Testosterone also stimulates melanin production. Changes in pigmentation occur during pregnancy (pregnancy mask, chloasma). Changes in hormone levels due to such things as oral contraceptives, ovary disturbances or Addison's disease can also change the rate of melanin production.

Pigment Disorders
Disorders linked to alterations in melanin pigmentation are divided into two groups:

1. The hyper-melanoses or hyper-chromias, characterised by a localised or a more widespread increase of melanin in the skin, which creates a darker colour than normal in the epidermis and excess pigment may be present in the dermis with a greyish or blue colour.

2. The hypomelanoses or hypochromias, characterised by a reduction in skin pigment so the skin appears whiter or lighter than its normal colour.

Due to there being many variations of cutaneous pigment disorder, diagnosis is better facilitated using a source of UV rays (Woods light).

Pigmentation alterations happen in many different ways as a result of multiple genetic and environmental factors. Hyper-pigmentation classification:

There are a very high number of conditions that may cause hyper-pigmentation. They are not easy to classify. They may be of genetic origin (e.g. ephelis, freckles, nevomelanoma etc.) or of acquired origin as previously mentioned.

Hyper pigmentation of cosmetic importance - Acquired Hypermelanoses

Cause	Brown colour(melanodermia)	Grey, slate or blue colour(cerulodermia)
Metabolic	Hepatic Illnesses Haemochromatosis, Pericholangiolitic cirrhosis Haematoporphyria	Haemochromatosis Macular cutaneous amiloidosis
Endocrine	Pregnancy mask Addison disease Contraceptives and Therapy with oestrogen's	Pregnancy mask Addison disease Contraceptives and Therapy with oestrogen
Chemical	Arsenic Bisulfan, Bleomycin Cyclophosphamide Adrimycin Psoralens Berloque's dermatitis Phyto photo-dermatitis	Minocycline Fixed eruption from medications, barbiturates. Phenothiazines Chlorpromazine Phenolphalein etc Chlorpromazine
Physical	Ultra violet light Ionising radiation Traumas
Nutritional	Pellagra Vit.B12 deficiency Kwashiorkor	Chronic nutritional deficiency
Post-Inflammatory	Eczema Lichen planus, lupus erythematosus Lichen and macular amiloidosis Systemic / morphea sclerosis	Pinta Dyschromic erythema perstans
Tumours	Acantosis nigricans Malignant tumours	Metastatic melanoma with melanogenuria

HYPERPIGMENTATION OF COSMETIC IMPORTANCE

Epidermal (MELANODERMIA)	Dermal (CERULODERMIA)
Melasma Sun lentigo Freckles induced by PUVA therapy Berloque’s dermatitis Post-inflammatory hypermelanosis traumas, excoriated acne, lichen planus Lupus erythematosus, post-dermal abrasion Post laser, post-infections, fixed eruption from pharmaceuticals	Riehl melanosis: occupational melanosis Hyper pigmentation induced by pharmaceuticals Minocycline, phenothiazine, silver Clotazimine, carolenorjerrnia Tattoos Erythema ab igne Dermal melasma Oral contraceptives Post-inflammatory Excoriated acne

MELASMA
Melasma is usually a brown or sometimes grey-brown area on the face, the neck and the forearms. The pigmentation may be in a line (a band running down from the cheeks) or confetti (patchy spots) like pigmented marks.

Three areas of melasma are identified: centre-facial, cheek or jaw. The colour is generally a uniform light or dark brown. However, there may be a variegated brown colour. It manifests on photo-exposed areas: the forehead, in arches above the eyebrows, on the bridge of the nose, on the cheeks with a butterfly aspect, on the upper lip like a moustache, on the chin (sometimes extending to the V of the neck) and on the back of the forearms.

There may also be only one area, but usually they are set out symmetrically on the face, it is most common in women of Hispanic origin and people who live in places where exposure to UV rays is higher.

Causes of Melasma

Hormonal factors	Genetic factors (family)
Pregnancy (multiple)	Melasma exacerbated by the sun
Oestrogen / progesterone alterations	Cosmetic ingredients
Oral contraceptives	Pharmaceuticals and photo-toxic agents
Thyroid disturbances (auto immune and not)

The most important factors in the pathogenesis of melasma are a genetic predisposition and exposure to the sun. Melasma may not be resolved after giving birth or after the interruption of oral contraceptives.

Classification of Melasma
Melasma can be divided into 3 types:

Epidermal - There is an increase in melanin in the basal and super-basal layers and in the horny layer. Under Wood's light (a test) the hyper pigmented maculae are more distinct and pigmentation is intensified.
Dermal - There is an increase of melanophages (macrophages full of melanin) in the surface and deep dermis. Pigmentation does not intensify under Wood's light. The maculae become less visible and their edges less distinct.
Mixed - Pigment in the epidermis and dermis.

SUN LENTIGO
These are brown coloured marks of about 1cm, which appear in photo-exposed areas (face, back, hands).

POST- PUVA THERAPY FRECKLES
These appear in exposed areas in more than 2% of patients after 2-3 years of prolonged therapy with photo chemotherapy, Psoralens and PUVA. They appear as star-shaped freckles, particularly evident in the elderly and in persons with fair complexions (photo-type I and II).

BERLOQUE'S DERMATITIS
This is a modest skin reaction, which generally appears as a delayed reaction and it is rare to remember the cause that triggered it. The name refers to the pendent or drop form of the marks. It arises due to contact with cosmetics (cologne, perfumes, and after-shave lotions).

The sides of the neck and the upper limbs are most affected; the shape matches the area of application. Susceptibility to its development is individual. Heat, humidity and exfoliation all increase absorption.

POST-INFLAMMATORY HYPERPIGMENTATION
Any acute or chronic inflammatory process may cause hyper pigmentation; it is more intense and persistent in dark skin. The response is due to the nature of the dermatosis rather than to the intensity of the inflammation. They usually appear in conditions in which there is damage to the keratinocytes of the basal layer.

Post-inflammatory hyper pigmentation may follow physical traumas, chemical peeling, excoriated acne and dermal abrasion in dark skinned persons.A particular form is erythema ab igne, which may break out in any area chronically exposed to a source of heat (warmer, hot-water bottle etc.).

RIEHL'S MELANOSIS
This is more frequent in women, probably due to a more extensive use of cosmetic products. Often the patient will give a positive patch test to cosmetic ingredients exhibiting a local contact dermatitis. The pigmentation is brown greyish, involves almost the whole face, in particular forehead and temples, and may also affect the neck, chest, scalp and sometimes hands and forearms. Horny taproots till the follicles and peeling also appears. The melanosis reduces in some months if contact with cosmetics is avoided. Sometimes the cause is unknown.

OCCUPATIONAL MELANOSIS
(Toxic melano-dermatitis)
Workers in contact with tar derivatives such as pitch, asphalt and mineral oils may develop diffuse melanosis in the parts exposed to the action of anthracene, phenanthrene and other photo-dynamic action substances