Disorders of pigmentation

Normal skin colour

The colour of normal skin comes from a mixture of

pigments

1. pink by oxyhaemoglobin in the blood within the

dermis.

2. brown of melanin

3. yellow from carotene mainly in subcutaneous fat

and in the horny layer of the epidermis.

There is no natural blue pigment

Hair colour is determined by the relative amounts of

the different types of melanin. Eumelanin

predominates in black hair and phaeomelanin in red.

Melanogenesis

Melanin is formed from the essential aminoacid

phenylalanine through a series of enzymatic steps in

the liver and skin.

Melanin is made within melanosomes

fully melanized melanosomes pass into the dendritic

processes of the melanocyte to be injected into

neighbouring keratinocytes and distributed

throughout the cytoplasm.

Skin color depend on nummber and size of

melanosomes

Melanins protect against UVR damage by absorbing

and scattering the rays, and by scavenging free

radicals.

Control of melanogenesis

Melanogenesis can be increased by several stimuli:

1. UVR is the most important

2. Melanocytestimulating hormone (MSH) peptides

from the pituitary and other areas of the brain

3. Oestrogens and progestogens (and possibly

testosterone too) may stimulate melanogenesis,

either directly (by acting on oestrogen and

progestogen receptors in the melanocyte) or by

increasing the release of MSH peptides from the

pituitary

Tanning

involves two distinct reactions.

A-Immediate pigment darkening (IPD) following

exposure to longwave ultraviolet (UVA 320–400 nm).

This pigment darkening occurs over minutes to days

responsible for the well-known phenomenon of a ‘false

tan’.

It is not brought about by melanin synthesis but oxidation

of preformed melanin and redistribution of melanin from

perinuclear melanosomes to peripheral dendrites.

B-Delayed tanning (DT): the production of new pigment

occurs some 3–4 days after exposure to medium-wave

ultraviolet (UVB: 290–320 nm) and UVA and is maximal

at 7 days

Genetics and skin pigmentation

Genetic differences determine the pigmentation of

the different races

A black person living in Britain and a white person

living in Africa will remain black and white,

respectively

Abnormal skin colours

These may be caused by:

1. Imbalance of the normal pigments

2. Presence of abnormal pigments

Some abnormal pigments

Endogenous

Haemoglobin-derived

Methaemoglobin, Sulphaemoglobin - Blue colour in vessels, cyanosis

Carboxyhaemoglobin -Pink

Bilirubin, Biliverdin -Yellow–green

Haemosiderin- Brown

Drugs

Gold- Blue-grey (chrysiasis)

Silver -Blue-grey (argyria)

Amiodarone- Blue-grey

Bismuth -Grey

Mepacrine- Yellow

Clofazamine- Red

Phenothiazines- Slate-grey

Diet

Carotene Orange

Exogenous

Tattoo pigments

Local medications

• Silver nitrate- Black

• Magenta paint- Magenta

• Gentian violet- Violet

• Eosin- Pink

• Potassium permanganate-Brown

• Dithranol (anthralin)-Purple

• Tar- Brown

• Iodine- Yellow

Decreased melanin pigmentation

Some causes of hypopigmentation.

Genetic

Albinism

Piebaldism

Phenylketonuria

Waardenburg’s syndrome

Chediak–Higashi syndrome

Tuberous sclerosis

Endocrine

Hypopituitarism

Chemical

Contact with substituted phenols (in rubber industry) Chloroquine and hydroxychloroquine

Post-inflammatory

• Eczema

• Pityriasis alba

• Psoriasis

• Sarcoidosis

• Lupus erythematosus

• Lichen sclerosus et atrophicus

• Cryotherapy

Infections

• Leprosy

• Pityriasis versicolor

• Syphilis, yaws and pinta

Tumours

• Halo naevus

• Malignant melanoma

Miscellaneous

• Vitiligo

• Idiopathic guttatehypomelanosis

Oculocutaneous albinism

genetic conditions in which there is a defect in the synthesis of melanin in the melanocyte, or a defective transfer of melanosomes to surrounding keratinocytes

Types

1. skin and eyes (oculocutaneous albinism)

2. eyes alone (ocular albinis)

Cause

oculocutaneous albinism of two main types:

1. tyrosinase negative, lies on chromosome 11q14- q21

2. tyrosinase positive, mapped to chromosome 15q11-q13

both being inherited as autosomal recessive traits. This explains how children with two albino parents can sometimes themselves be normally pigmented, the genes being complementary in the double heterozygote

Presentation and course

The whole epidermis is white

Albinos have poor sight, photophobia and a rotatory

Nystagmus as pigment is also lacking in the hair, iris

and retina

As they grow older, tyrosinasepositive albinos gain a

little pigment in their skin, iris and hair, also develop

freckles.

Sunburn is common on unprotected skin.

As melanocytes are present, albinos have non-

pigmented melanocytic naevi and may develop

amelanotic malignant melanomas.

Complications

sun-induced skin cancers even when they are young, confirming the protective role of melanin

Differential diagnosis

Piebaldism and vitiligo

Investigations

Prenatal diagnosis of albinism is now possible

The hair bulb test to distinguishes tyrosinase-positive from tyrosinase-negative types.

Treatment

Avoidance of sun exposure and protection with opaque clothing, wide-brimmed hats and sunscreen creams are essential and allow albinos in temperate climates to live a relatively normal life.

Early diagnosis and treatment of skin tumours is critical.

Piebaldism

a white forelock of hair

patches of depigmentation lying symmetrically on the

limbs, trunk and central part of the face, especially

the chin.

present at birth

inherited as an autosomal dominant

Melanocytes are absent from the hypopigmented

areas.

The depigmentation, often mistaken for vitiligo, may

improve with age.

There is no effective treatment.

Vitiligo

The word vitiligo comes from the Latin word vitellus

meaning ‘veal’ (pale, pink flesh).

It is an acquired circumscribed depigmentation, found in

all races

its inheritance is polygenic.

Cause and types

There is a complete loss of melanocytes from affected

areas.

There are two main patterns:

1. Generalized

2. Segmental, rare

Trauma and sunburn can precipitate both types.

Generalized vitiligo

including the acrofacial variant

Is a common type

usually starts after the second decade

positive family history in 30% of patients

associated with autoimmune diseases such as

diabetes, thyroid disorders and pernicious anaemia.

in this type, melanocytes are the target of a cell-

mediated autoimmune attack or self-destruct

because of an inability to remove toxic melanin

precursors.

Segmental vitiligo

is restricted to one part of the body, but not

necessarily to a dermatome.

It occurs earlier than generalized vitiligo

not associated with autoimmune diseases

Clinical course

Generalized type

sharply defined, usually symmetrical white patches are especially common on the backs of the hands, wrists, fronts of knees, neck and around body orifices.

The hair of the scalp and beard may depigment too. In

Caucasoids, the surrounding skin is sometimes partially depigmented or hyperpigmented (trichrome vitiligo).

The course is unpredictable: lesions may remain static or spread, sometimes following minor trauma (Köbnerphenomenon)

they repigment spontaneously from the hair follicles.

Segmental type

look like the generalized type but their segmental distribution is striking.

Spontaneous repigmentation occurs more often in this type than in generalized vitiligo

Differential diagnosis

1. Contact with depigmenting chemicals, such as

hydroquinones and substituted phenols in the

rubber industry

2. Pityriasis versicolor

3. Post-inflammatory depigmentation

4. patches of piebaldism

5. Leprosy must be excluded

6. leishmaniasis and pinta.

Treatment

Treatment is unsatisfactory

The cosmetic disfigurement from vitiligo can be

devastating to affected paients..

In the white patches pigment cells are only present

deep in the hair follicles and treatments mostly try to

get melanocytes to divide and migrate into affected

skin.

Repigmentation is thus often heralded by freckling at

follicles within patches

Recent patches

1. Potent or very potent topical corticosteroid, applied for 1–2 months. After this, the strength should be gradually tapered to a mildly potent steroid for maintenance treatment.

2. Alternatively, calcineurin inhibitors, such as 0.1% tacrolimus ointment

3. Psoralens (trimethylpsoralen or 8-methoxypsoralen, in a dosage of 0.4–0.6 mg/kg body weight), taken 1–2 h before graduated exposure to natural sunshine or to artificial UVA

4. Narrow-band (311 nm) UVB may also be effective

New lesions seem to respond best.

1. Less reliable treatments include excimer laser and antioxidant therapy

2. Autologous skin grafts if pigment is absent in hair follicles or skin without hair follicles

Established vitiligo

As a general rule,it is best left untreated in most

white people

Advice about suitable camouflage preparations

Sun avoidance and screening preparations are

needed to avoid sunburn of the affected areas and a

heightened contrast between the pale and dark

areas.

Black patients with extensive vitiligo can be

completely and irreversibly depigmented

Post-inflammatory depigmentation

1. Eczema

2. Psoriasis

3. Sarcoidosis

4. Lupus erythematosus

5. lichen planus

6. cryotherapy or a burn

In general, the more severe the inflammation, the more likely pigment is to decrease rather than increase

Pityriasis alba

is common on the faces of children.

The initial lesion is probably a variant of eczema (pinkish with fine scaling), which fades leaving one or more pale, slightly scaly, areas.

Exposure to the sun makes the patches more obvious.

Disorders with increased pigmentation

(hypermelanosis)

Some causes of hyperpigmentation.

Genetic

Freckles

Lentigines

Café au lait macules

Peutz–Jeghers syndrome

Xeroderma pigmentosum

Endocrine

Addison’s disease

Cushing’s syndrome

Pregnancy

Renal failure

Metabolic

Biliary cirrhosis

Haemochromatosis

Porphyria

Nutritional

Malabsorption

Carcinomatosis

Kwashiorkor

Pellagra

Drugs

• Photosensitizing drugs

• ACTH and synthetic analogues

• Oestrogens and progestogens

• Psoralens

• Arsenic

• Busulfan

• Minocycline

Post inflammatory

• Lichen planus

• Eczema

• Secondary syphilis

• Systemic sclerosis

• Lichen and macular amyloidosis

• Cryotherapy

• Poikiloderma

Tumours

• Acanthosis nigricans

• Pigmented naevi

• Malignant melanoma

• Mastocytosis

Freckles (ephelides)

so common that to describe them seems

unnecessary

They are seen most often in the redhaired or blond

person as sharply demarcated, light brown–ginger

macules, usually less than 5 mm in diameter.

They multiply and become darker with sun exposure.

Increased melanin is seen in the basal layer of the

epidermis without any increase in the number of

melanocytes, and without elongation of the rete

ridges

No treatment is necessary.

Lentigo

Simple and senile lentigines look alike.

They are light or dark brown macules, ranging from 1 mm to 1 cm across.

Are usually discrete, and may have an irregular outline.

Simple lentigines arise most often in childhood as a few scattered lesions, often on areas not exposed to sun, including the mucous membranes.

Senile or solar lentigines are common after middle age on the backs of the hands (‘age spots’, ‘liver spots’and on the face

lentigines have increased numbers of melanocytes.

They should be distinguished from a lentigo maligna

Treatment is usually unnecessary and prevention, by sun avoidance and the use of sunscreens is the best approach.

cryotherapy

laser

daily application of 0.1% tretinoin cream or 2–4% hydroquinone or a combination

Histology of a freckle and lentigo

Conditions associated with multiple

lentigines

1. Peutz–Jeghers syndrome

autosomal dominant condition

Scattered lentigines also occur on the buccal

mucosa, gums, hard palate, hands and feet.

association with polyposis of the small intestine

10 % of affected women have ovarian tumours.

2. Cronkhite–Canada syndrome

3. LEOPARD syndrome

Melasma (chloasma) acquired, symmetrical hypermelanosis occurring on sun-

exposed skin, especially the face.

The areas of increased pigmentation are well defined and their edges may be scalloped.

more common in women, affects all races but is most prevalent in dark-skinnned individuals with skin types IV–VI

hypermelanosis becomes darker after exposure to the sun.

There are many causes including:

1. Sunlight

2. pregnancy ‘the mask of pregnancy’

3. oestrogens and oral contraceptives

4. thyroid dysfunction

5. photosensitizing drugs

The placenta may secrete sex hormones that stimulate melanocytes.

Melasma Treatment

This is unsatisfactory

sunscreen

bleaching agents that contain 2–5% hydroquinone,

applied for 6–10 weeks.

Chemical peels

Endocrine hyperpigmentation

Addison’s disease

caused by the overproduction of ACTH

generalized or limited to the skin folds, creases of the palms, scars and the buccal mucosa.

Cushing’s syndrome

Increased ACTH production may cause a picture like that of Addison’s disease.

Pregnancy

There is a generalized increase in pigmentation during pregnancy, especially of the nipples and areolae, and of the linea alba. Melasma

The nipples and areolae may remain pigmented for a while after parturition.

Chronic renal failure

The hyperpigmentation is caused by an increase in levels of pituitary melanotrophic peptides, normally cleared by the kidney.

Porphyria

Formed porphyrins, especially uroporphyrins is endogenous photosensitizers induce hyperpigmentationon exposed areas

Nutritional hyperpigmentation

Any severe wasting disease, such as malabsorption, AIDS, tuberculosis or cancer, may be accompanied by diffuse hyperpigmentation.

Kwashiorkor presents a mixed picture of generalized hypopigmentation and patchy post-inflammatory hyperpigmentation,

Post-inflammatory

hyperpigmentation

common after lichen planus

systemic sclerosis

some types of cutaneous amyloidosis

cryotherapy

The end