disorders of melanin pigmentation · • pigmentation is homogenous or variegated with colour...

Disorders of pigmentation

Professor Danka Švecová MD, PhD

Dept.of Dermatovenerology

Faculty of Medicine, Comenius University

Melanin and melanin unit

• Melanin is the most important determinant of skin color

it is produced in melanosomes in melanocytes →

is transferredd to a group of keratinocytes → epidermal melanin unit

• Color of the skin → depends on the degree of melanisation

of melanosomes → their number, distribution

• Others →

▪ degree of vascularity

▪ relative amount of oxidized and reduced hemoglobin

▪ presence of carotenoids

▪ thickness of the horny layer

• Genetic factors, amount and wavelength of received UV light,

amount of secreted melanocyte-stimulating hormone (MSH)

http://www.melanplus.com/melanin_science.jpg

Disturbances in skin color

Disorders of melanin pigmentation

• increased pigmentation (hyperpigmentation)

• decreased pigmentation (hypopigmentation)

• absence of melanin (amelanosis)

Dyschromias

• endogenous or exogenous pigments deposited in the skin

Hyperpigmentation

Localised hyperpigmentation

Ephelides (Freckles)Tanned macules on the skin, multiple in numbers; appear at the age of 2 years, increase in number into young adulthood, at older age their number decreases

Etiology and pathogenesis

• Inherited as an autosomal dominant trait in individuals with fair skin and red or blonde hair

• Melanocortin 1 receptor gene polymorphisms → increased

melanogenesis, melanocytes are not increased in number, or they even may be decreased in number

• UVA and UVB exposure → ↑ the dopa reaction leads to the production of larger melanosomes producing the clinical findings

Hyperpigmentation


Clinical features

• Multiple small tanned macules with uniform pigmentation, diameter

from 1-5 mm; on sun exposed areas → nose, cheeks, shoulder,

upper part of the back; discrete or confluent macules, in winter they

fade and become smaller, asymptomatic, may be cosmetically

disfiguring

Hyperpigmentation


Sunburn freckles

• similar as simple freckles, but darker, irregular borders, several

millimeters

Diagnostic criteria clinical findings establish the Dg

DifDg permanent freckles in xeroderma pigmentosum (early onset

persisting in winter); freckles in neurofibromatosis → in folder

regions (axilla and groin) →axillary freckles are dg criterion for

neurofibromatosis; lentiginosis, multiple small plane warts

Therapy sunscreens protect against UVA and UVB, to avoid sun

exposure; chemical peels, cryotherapy, laser treatment

Hyperpigmentation


Peutz-Jeghers syndrome

Aetiology and pathogenesis

• autosomal dominant inherited disorder → intestinal hamaromatous

polyps, mucocutaneous melanocytic macules

• 15-fold increased risk of intestinal cancer→mutation of

serine/threonine kinase 11 (STK11) tumour suppressor gene→

almost 50% of patients develop cancer by the age of 57 years;

women have increased risk of breast cancer

Hyperpigmentation


Clinical features

• Mucocutaneous lentigines arise in early

childhood

• Small, flat, brown, or black to dark blue

spots with an appearance of freckles

• Size ranges from 1 to 12 mm in diameter

• Characteristic distribution→ around the

mouth, on the lips,they cross the vermilion

border, on the buccal mucous membranes;

scattered around the nose and face

• Also on fingers, toes, palms and soles

• Fade with age; buccal macules persist

• Polyps result in recurrent perirectal bleeding, abdominal pain,

obstruction, jelly-like stool

Hyperpigmentation


Diagnostic criteria

Clinical findings in buccal mucosa

DifDg Ephelides

Therapy

Genetic counselling, cutaneous findings do not require any treatment;

patient should be educated on the potential symptoms of intestinal

obstruction

Hyperpigmentation


Café au lait macule

• Prototypic lesion in neurofibromatosis

• Uniformly pigmented light brown macule

• Unevenly round or oval, 1.5-15 cm in diameter,

smooth, sharply bordered

• Present at birth and almost always present by the time

the patient is one year old

• Localisation: anywhere on the body, rarely on face

• In normal individuals can be seen

• are harmless and never undergo malignant

transformation

Café au lait macule

Therapy no treatment is needed; cosmetically disturbing → can be covered

with make-up; laser therapy is effective

Hyperpigmentation


Lentigo

• Small, sharply circumscribed, pigmented macule

surrounded by normally appearing skin

• Evolves slowly over years

▪ or eruptive

• Pigmentation is homogenous or variegated with colour

ranging from brown to black

• Anywhere on the body

Multiple clinical and etiologic varieties:

variable amount of melanocytes is present, may be increased in number but

do not form nests

Distinction of lentigo and melanotic lesions - melanotic nevi and melanoma

malignum is of major significance

Lentigines→ marker for UV damage, multiple lentigo can be associated with

systemic abnormalities

Hyperpigmentation


Lentigo simplex

• Most common form

• Round or oval macules 3-15 mm in diameter

• Few in number, anywhere on the skin or mucous membranes

• Asymptomatic

• Color ranges from brown to black

• The lesions appear in early childhood, can be present also at birth

or develop later

Hyperpigmentation


• Benign

• In individuals aged 30-50 years, in younger

(extensive sun tanning, artificial sources of UV

light)

• Sun induced in sun - exposed areas:

▪ face, lower arms, dorsa of the hands, upper part of the

trunk

• Initially, the spots are smaller than 5 mm, surface

is flat or depressed, or split by fine wrinkles

▪ color is brown, or ranges from yellow →tan to black;

older spots are dark brown or brownish black

▪ they increase in number and size, may coalesce to form

larger patches

Solar lentigo (actinic lentigo, senile lentigo, sunspot, liver spot)

Hyperpigmentation


PUVA lentigo

• 6 months or longer after the start of PUVA for psoriasis

• Greater cumulative doses of PUVA

• Anywhere, most common →upper part of the chest, back, groin,

buttocks, glans penis, penile shaft, 3-8 mm, stellate spots, as large

as 3 cm

• Irregular border can mimic ephelides

• Persist 36 months, stellate longer than 2 years

HyperpigmentationLocalised hyperpigmentation

Centrofacial lentiginosis

• Very rare syndrome inherited in an autosomal dominant patter

• Spots appear during the first year

• Increased in number, restricted to the mid face

• CNS and skeletal defects, mental retardation, epilepsy

• No treatment is needed


Melasma (chloasma)

• Acquired hyperpigmentation

of sun-exposed areas

• Rare disorder before puberty

• Women during reproductive

years

• Men may be also affected,

but rare


Etiology and pathogenesis is uncertain

• Genetic predisposition, persons with light brown skin types

• Geographical regions with intense sun exposure →

▪ UV stimulate melanocytes to produce an excess of melanin

• All wavelengths of sunlight including visible spectrum

• Hormonal influence →

▪ pregnancy

▪ contraceptive pills

▪ postmenopausal women using progesterone (critical role)

▪ ovarian dysfunction

▪ thyroid dysfunction

• Phototoxic and photoallergic medications and certain cosmetics


Clinical features

• Color ranges from tanned to brown

• Typical distribution

▪ malar prominences and forehead

• Pigmented patches are sharply

demarcated

• Large amount of dermal melanin→

hyperpigmentation is bluish black


Diagnostic criteria clinical picture

• Wood´s lamp light examination helps to localize the pigment in the

epidermis or dermis

▪ epidermal pigment is enhanced during examination with Wood´s light

▪ dermal is not enhanced

▪ in many cases the pigment is found in both

▪ Checking thyroid function

DifDg some phosensitive drugs (phenytoin, chlorpromazine) →

melasma-like hyperpigmentation; some cosmetics, patients with cachexia

→facial darkening

Therapy avoidance of sunlight, bleaching agents inhibit melanogenesis

and increase the turnover of keratinocytes; topical tretinoin, azelaic

acid, ascorbic acid, broad spectrum sunscreens


Secondary hyperpigmentation

Variety of triggering factors

▪ increased production of melanin with increased transfer to keratinocytes→brown

hyperpigmentation, spontaneously reversible

▪ dermal deposition is more permanent →blue-grey hyperpigmentation

• Chronic mechanical irritation (belt line, axilla, groin, neck in obese

individuals)

• Infrared irradiation and exposure to heat →postinflammatory hyper-

pigmentation

• Ionising radiation→stimulate melanin production

• Variety of photosensitising chemicals



Variety of triggering factors:

Skin disorders with postinflammatory hyperpigmentation

▪ lichen planus, psoriasis, atopic dermatitis, lupus erythematosus

(inflammation stimulate melanin production)

▪ erythroderma→ diffuse hyperpigmentation (widespread incontinence of pigment)

Systemic disorders→mechanism unknown

▪ cirrhosis, cardiac failure, arthritis, diabetes mellitus

morbus Addison (metallic grey hue, incontinence of melanin)

▪ chronic infection

▪ malnutrition

▪ chronic renal disease



Medication may induce hyperpigmentation

▪ oral contraceptives (melasma),

▪ ACTH → has MSH-like action

▪ phenothiazines and antimalarials →blue-grey hyperpigmentation in sun-exposed

are muddy brown hyperpigmentation on entire body surface

▪ cancer chemotherapy agents → localized or diffuse hyperpigmentation

Depigmentation

Vitiligo

Acquired pigmentary disorder of the skin and mucous membrane,

any age, age 10-30 years, females more frequently affected

Etiology and pathogenesis

• Multifactorial, polygenetic disorder, family history (earlier age),

autoimmune endocrine disease

• Precise cause is unknown

• Absence of functional melanocytes, loss of melanocytes by their

destruction - autoimmune mechanism, cytotoxic mechanism

• Itrinsic defects of melanocytes

• Oxidant-antioxidant mechanism

• Neural mechanism

Depigmentation

Vitiligo

• Autoimmune disorders associated with vitiligo

▪ hashimoto thyroiditis, Graves´s disease, Addison disease, diabetes mellitus,

alopecia areata

▪ inflammatory bowel disease

▪ Oxidant stress →accumulation of free radicals toxic to melanocytes

→ leads to destruction

▪ Nerve injury → hypopigmentation or depigmentation in denervated

areas → segmental vitiligo in a dermatomal pattern

▪ melanocytes may be present in depigmented lesion after years of onset and still

respond to medical therapy under appropriate stimulation

Depigmentation

Vitiligo

Clinical features

• Acquired white or hypopigmented

macules or patches

• Well demarcated; round, oval or linear in

shape

• Enlarge cintrifugally over time at

unpredictable rate → mm - cm in size

• Most frequently→ hands, forearms, feet

and face, favoring perioral and periocular

area

Depigmentation

Vitiligo

Clinical features

• Localized or generalized (involving more than

one general area of involvement)

• Symetrical or asymetrical lesions on both sides

of the trunk

• Repeated trauma

▪ bony prominences, dorsal aspects of hands, digital

phalanges, extensor forearms, ventral wrist

▪ around body orifices - lips, gingiva, areolas and

nipples

▪ Body hair are depigmented – localized patch of white

or grey hair

▪ Hair involvement → poor prognosis

▪ Koebner phenomenon in sites of trauma - cuts, burns,

abrasion

Depigmentation

Vitiligo

Diagnostic criteria

• Clinical findings

• Symptoms of hypothyroidism, diabetes

mellitus

• Wood´s light examination accentuates

the hypopigmented areas – axillae,

anus, genitalia (frequently unrecognized)

DepigmentationVitiligo

DifDg

• nevus anemicus

• piebaldism (partial albinism congenital patches – melanocytes are

completely absent)

• postinflammatory hypopigmentation (atopic dermatitis)

• pityriasis versicolor

▪ early lesions in systemic sclerosis

▪ early lesions lichen sclerosus et atrophicus

• leukoderma – healed psoriasis, secondary syphilis; exposure to

some chemicals

DepigmentationTherapy

• Repigmentation - activation and migration of melanocytes from

melanocyte reservoirs located in hair follicle → melanocytes divide

rapidly after any inflammatory process or following UV radiation

• Various therapy regimens – the response varies from individual to

individual, treatment is individualized ▪ Systemic phototherapy in early or localized disease

▪ narrow-band UVB (311 nm) in generalized vitiligo – 1.choice

▪ UVB narrow - band microphototherapy – targeting at specific small lesions

▪ PUVA- topical or systemic

▪ Laser therapy with monochromatic rays at 308 nm

▪ Topical agents▪ tacrolimus (head, neck)

▪ vitamin D analogues (calcipotriol, tacalcitol)

▪ corticosteroids

▪ Systemic corticosteroids

DepigmentationTherapy

▪ Surgical treatment in limited or localized vitiligo→

▪ epidermal grafts

▪ grafting suction-blistered epidermis

▪ punch minigrafts

▪ transplantation of in vitro cultured epidermis bearing the melanocytes

• Cosmetic camouflage

More than 40% involvement – to remove the remaining normal skin

pigment with 20% monobenzone (destroys melanocytes →

permanent procedure) patient will be sun-sensitive → use of

sunscreens during sun exposure

Depigmentation

Secondary hypopigmentation

• Vitiligo-like lesions

• Reversible → melanogenesis is blocked

• Permanent → melanocytes are destroyed (hydroquinone -

antioxidant in rubber and leather industry) → irregular depigmented

patches

• Topical medications

▪ topical retinoids, azelaic acid, intralesional corticosteroids

• Systemic medications

▪ chloroquine – hypopigmentation of hair after 2-3 months of therapy

▪ etretinate

▪ vit.E –may lighten the hair color

Depigmentation

Secondary hypopigmentation

Any disease with inflammation at the dermal-epidermal junction can

produce hypopigmentation

▪ lichen sclerosus et atrophicus

▪ lupus erythematosus

▪ systemic sclerosis

Postinflammatory hypopigmentation (leukoderma) many inflammatory

dermatoses

▪ spontaneously reversible – psoriatic leukoderma, syphilitic leukoderma, leprosy

leukoderma

Tinea versicolor → „umbrella effect“ + causative agent (yeast) produces

azelaic acid → interferes with melanogenesis

Pseudoleukodermalightening of skin color →a result of a contrast phenomenon

▪ psoriatic pseudoleukoderma caused by anthralin products (produce hyperpigmentation of adjacent normal skin)

Depigmentation

Dyschromias

Endogenous or exogenous pigments other than melanin are deposited

in the skin

Endogenous

▪ hemosiderosis(iron-rich pigment from erythrocytes)

▪ bile pigments

▪ carotenemia

▪ ochronosis (bluish black discoloration - homogentisic acid in the skin, cartilage-

alkaptonuria)

Exogenous

• Argyria (silver salts –slate grey)

• Chrysiasis (gold salts –blue grey)

• Tatoo

• Medication-induced pigmentary changes

▪ antimalarials (quinacrine- yellow)

▪ amiodarone- photosensitivity of blue-grey discoloration

▪ minocycline –blue-black pigmentation in acne scars and sun-exposed skin

disorders of melanin pigmentation · • pigmentation is homogenous or variegated with colour...

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