pigmentation, disorders, vitiligo, hyperpigmentation, hypopigmenattion, melanin

1. DISORDERS
OF PIGMENTATION
Dr. Angelo Smith M.D
WHPL

2. SKIN COLOR
 Determined by - melanin
- haemoglobin
- carotenoids
 Melanin - major determinant
Melanin is synthesized by melanocytes within
melanosomes and transferred to keratinocytes
Constitutive skin colour - genetically determined
Facultative skin colour - induced by sun and
hormones

3. AN OVERVIEW
Skin pigmentation has far-reaching social and
psychological implications
 White people strive for tanning which while
brown and black people strive for a lighter skin
Melanin pigmentation disorders are important
for medical and cosmetic reasons

4. • Human beings come in a glorious
spectrum of different colors: light, dark,
plain or freckly skin; black, brunette,
blond, auburn, and white hair; and eyes
that are blue, hazel, green, amber and
brown, to name just a few. It’s amazing
to realize that most of this color is
attributed to a single class of pigments:
the melanins.

5. MELANIN
= primary pigment producing brown coloration
• Tyrosine – tyrosinase –melanin- this occurs in the
melanosomes of melanocytes
• Then the melanosomes are transferred from the
melanocyte to a group of keratinocytes called the
epidermal melanin unit
• Variations in skin color is related to the number of
melanosomes, the degree of melanization, and
the distribution of the epidermal melanin unit

6. MELANIN
 Two types - eumelanin (black or brown)
- pheomelanin (reddish)
 Derived from tyrosine
Tyrosine
Tyrosinase
DOPA[3,4 dihydroxy phenylalanine]
Dopaquinone
Dopachrome
5, 6 dihydroxindole
Eumelanin
Cysteinyldopa
pheomelanin

9. NORMAL PIGMENTATION
• Normal skin pigmentation is influenced by:
-the degree of vascularity
-the amount & location of melanin
-the presence of carotene
-the thickness of the horny layer

10. MELANIN PRODUCTION
• The amount produced is dependent on:
-genetics
-the amount and the wavelengths of ultraviolet light
received
-the amount of melanocyte-stimulating hormone
(MSH) secreted
- the effect of melanoccyte stimulatingg chemicals
like furocoumarins (psoralens)

14. APPROACH TO A PATIENT
History
Onset : birth, infancy or later
Cause: sun exposure, drugs, occupation
Systemic complaints
Family history: neurofibromatosis, tuberous
sclerosis, vitiligo

15. Examination:
Type of lesion: brown, blue, hypopigmented (check
sensation), depigmented
 Shape: Ash leaf macules (tuberous slerosis)
Koebner phenomenon(vitiligo)
 Distribution pattern : linear/segmental (nevus
depigmentosus), symmetric (vitiligo), specific sites
(melasma, Addison’s disease)

16. Examination aids:
Hand lens
Oblique lighting for elevation or depression
Dermatoscopy
Wood’s lamp - 360 nm. Epidermal pigmentary
anomalies made more prominent
Histology- H and E for presence or absence of
melanin
Dopa reaction - melanocytes stain dark
Silver stains - melanin stains black

17. CLASSIFICATION
• GENERALIZED
• LOCALISED
• HYPERPIGMENTATION
• HYPOPIGMENTATION
• DEPIGMENTATION
• CONGENITAL
• ACQUIRED

18. HYPOPIGMENTATION

23. CLASSIFICATION
Genetic and Developmental:
Albinism, Nevus depigmentosus, Nevus
anaemicus, Halo nevus, Tuberous sclerosis (ash
leaf macule)
Endocrine:
Addison’s disease, Hypothyroidism,
Hypopituitarism
Nutritional:
Vit.B12 deficiency, Kwashiorkor, Malabsorption

24. Post-inflammatory:
Pityriasis alba, Eczema, Psoriasis, Pityriasis
rosea, Lupus erythematosus, Morphea,
Scleroderma, Bullous dermatoses
Infection:
Leprosy, Tinea versicolor, Candidiasis, Post
kala azar dermal leishmaniasis
Chemicals and Drugs:

25. Physical:
Burns, Trauma, Post dermabrasion, Post
laser
Miscellaneous:
Idiopathic guttate hypomelanosis, Vitiligo,
Mycosis fungoides

26. ALBINISM
Oculocutaneous albinism involves skin, hair and eyes or
the eyes alone (ocular albinism)
Mostly autosomal recessive
Absence of pigmentation from birth
Photophobia, reduced visual activity, nystagmus, pale
irides that transilluminate, hypopigmented fundi,
hypoplastic foveae, and lack of stereopsis
Sunburns, skin cancers common
Protection of eyes and skin by sunglasses, sunscreens
SPF > 20, clothing

27. • Top: albinism with
white hair, pale skin,
and translucent irides
• Bottom:
ophthalmoscopic view
of a patient with
albinism demonstrates
a pale fundus, poor
macular development,
and prominent choroidal
vasculature

28. PIEBALDISM • Rare, AD with variable
phenotype, presenting at birth
• White forelock, patchy absence
of skin pigmentation
• Depigmented lesions are static
and occur on the anterior and
posterior trunk, mid upper arm
to wrist, mid-thigh to mid-calf,
and shins
• A characteristic feature is the
presence of hyper pigmented
macules within the areas of
lack of pigmentation and on
normal skin

29. •White forelock and
patch of unpigmented
skin in a young girl
with piebaldism

30. • Segmental white patch
on the neck with a tuft of
white hair present from
birth

31. WAARDENBURG’S SYNDROME
Rare, autosomal dominant disorder
White forelock
Hypertelorism
Congenital deafness
Hypomelanotic macules
Heterochromic irides
Incomplete forms may occur

33. TUBEROUS SCLEROSIS
Autosominal dominant, neurocutaneous syndrome
with skin lesions, mental retardation and epilepsy
Skin lesions are ash-leaf macules, angiofibromas
and shagreen patches
Ash-leaf macules - present at birth in > 90% cases,
so important in early diagnosis
Oval or ash-leaf shaped, hypopigmented macules,
made prominent in Wood’s lamp
Long axis is axial on limbs and transverse on trunk

35. NEVUS DEPIGMENTOSUS
A hypo pigmented birthmark which is congenital
and stable
Irregular, geographic margins and quasidermatomal
distribution
Block in transfer of melanosomes from melanocytes
to keratinocytes
Sporadic occurrence, no medical significance and
no treatment required

37. KWASHIORKOR
Protein deficiency in post weaning years
 Reddish patches which turn into dark plaques
which turn white after exfoliation (crazy
pavement dermatosis)
 Disruption of melanogenesis is due to
multiple deficiencies
 Pigment changes and dyschromic hair are
reversible with proper diet

39. LEUKODERMA
• Postinflammatory leukoderma may result from
inflammatory dermatoses ie:
• Pityriasis rosea, psoriasis, herpes zoster,
secondary syphilis, and morphea,
sarcoidosis, tinea versicolor, mycosis
fungoides, scleroderma, and pityriasis
lichenoides chronica, and leprosy
• Other causes: burns, scars,
postdermabrasion, and intralesioal steroid
injections

40. • Post inflammatory
hypopigmentation in
a 4-month-old black
child with atopic
dermatitis

41. • Post inflammatory
hypopigmentation
following
resolution of
guttate psoriasis

42. TINEA VERSICOLOR
Common, superficial fungal infection
Overgrowth of Malasezzia furfur - a normal
resident
Common after puberty; face, neck, upper trunk
affected
Nonpruritic or mildly pruritic, hypo or
hyperpigmented lesions with fine scales
Common in tropics; during summers

45. LEPROSY
Both hypo pigmented and erythematous
lesions common
Hypo pigmented macules common in
tuberculoid type of disease
Each hypo pigmented lesions in leprosy
endemic areas should be examined for
sensations of touch, pain, temperature
 Treatment according to type of leprosy

47. PITYRIASIS ALBA
A common disorder in children
Hypo pigmented lesions with powdery scaling;
chiefly affecting face
Etiology not known but may be a feature of atopy or
malnutrition
To be differentiated from indeterminate leprosy and
early vitiligo
 Treatment with emollients

49. •Ill-defined hypopigmented
oval patches are generally seen
on the face, upper arms, neck,
and shoulders of affected
persons
•It can be differentiated from
vitiligo by its fine adherent
scale, partial
hypopigmentation, and
distribution

50. IDIOPATHIC GUTTATE HYPOMELANOSIS
• AKA leukopathica symmetrica progressiva
• Very common aquired disorder affecting women more
frequently than men
• Usually occurs after age 40
• Lesions occur on the shins and forearms; are small (6
or 8mm), rarely become very numerous ( a dozen or
two at most), and never occur on the face or trunk
• Lesions are irregularly shaped and very sharply
defined, like depigmented ephelides, and are only of
cosmetic significance

52. VITILIGO
• Usually begins in childhood or young adulthood
• An acquired Pigmentary anomaly of the skin
• Manifested by depigmented white patches surrounded by
a normal or a hyper pigmented border
• There may be intermediate tan zones or lesions , halfway
between the normal skin color and depigmentation – so -
called trichrome vitiligo
• Hairs in vitiliginous areas usually become white also
• Rarely, the patches may have a red, inflammatory border
• Patches are of various sizes and configurations

53. TYPES • Localized or focal (including segmental)
• Generalized
• Universal
Acrofacial

54. VITILIGO
• Local loss of pigment may occur around nevi and melanomas,
the so-called halo phenomenon
• Vitiligo-like leukoderma occurs in 1% of melanoma patients
• In those previously dx with melanoma, it suggests metastatic
disease
• Paradoxically, patients who develop leukoderma have a better
prognosis than patients without it
• Halo nevi are more common in patients with vitiligo
• Lesions are hypersensitive to UV light and burn easily when
exposed to the sun

55. HENNA INDUCED VITILIGO

56. CHEMICAL DEPIGMENTATION
• Chemical
depigmentation due to a
germicidal detergent
• Pts usually improve with
discontinuation of the
offending agent

57. HYPERPIGMENTATION

60. DISORDERS OF HYPERPIGMENTATION
May be epidermal or dermal
Epidermal hyperpigmentation due to
- Increased melanin with normal number of
melanocytes
- Increased number of melanocytes
 Dermal hyperpigmentation due to
- Melanin from epidermis transferred to dermis
- Melanin formed in dermal melanocytes
- Melanin pigments appears blue-gray due to Tyndall
effect

61. CLASSIFICATION – EPIDERMAL
Physiologic:
Pigmentary demarcation lines, sun tanning
Genetic and Developmental:
Lentigines, Freckles, Peutz-Jeghers
syndrome, Melanocytic nevus, Café-au-lait
spots, Xeroderma pigmentosum, Becker’s
nevus, Nevus spilus, Acanthosis nigricans

62. Post-inflammatory:
Eczema, Psoriasis, Lichen planus, Lupus
erythematosus, Scleroderma, Morphoea,
Vagabond’s disease
Infection:
Tinea versicolor, Tinea nigra
Nutritional:
Kwashiorkor, Pellagra, Vit.B12, Vit.C, Folic acid
deficiency

63. Physical:
Trauma, Radiation dermatitis
Endocrine:
Melasma, Addison’s disease, Cushing’s
syndrome, Phaeochromocytoma, Acromegaly,
Hyperthyroidism
 Neoplastic:
Malignant melanoma, Seborrhoeic keratosis,
Pigmented basal cell carcinoma

64. DERMAL PIGMENTATION
Genetic and Developmental:
Mongolian spots, Nevus of Ota/Ito,
Incontinentia pigmenti
Inflammatory:
Stasis dermatitis, Post inflammatory to
eczema and fixed drug eruption
Chemicals and Drugs:
Anti-malarials, OC Pills, Minocycline,
Clofazimine, Topical hydroquinone, Tattoos

65. Endocrine:
Melasma
Physical:
Thermal burns, Post traumatic
Infection:
Syphilis, Yaws, Pinta
 Neoplastic:
Metastasis of melanoma

66. Nutritional:
Chronic nutritional deficiency
Metabolic:
Hemochromatosis, Alkaptonuria, Macular /
Lichen amyloidosis
Miscellaneous:
Pigmented purpuric dermatosis, Purpura

67. PDL
• Pigmentary demarcation lines (PDL) were first described by
Matzumoto on the upper and lower limbs of Japanese
people in 1913
• Also known as Futcher’s or Voight’s lines
• Pigmentary demarcation lines are borders of abrupt
transition between more deeply pigmented skin and that of
lighter pigmentation
• They do not correspond to Blaschko’s lines or
dermatomal lines but to voigt’ lines
• Considered by some to be a variant of normal pigmentation

68. • Can be divided into ffiivvee categories:
• Group A - lines along the outer upper arms with
variable extension across the chest
• Group B - lines along the posteromedial aspect
of the lower limb
• Group C - Paired median or paramedian lines on
the chest, with midline abdominal extension
• Group D - medial, over the spine
• Group E - bilaterally symmetrical, obliquely
oriented, hypopigmented macules on the chest

69. • More than 70% of
blacks have one or
more lines
• These are much less
common in whites
• Type B lines often
appear for the first
time during
pregnancy

71. MELANOCYTIC NEVI
Benign proliferations of melanocytic nevus cells at
the dermo-epidermal junction
 May be congenital or acquired
 Acquired nevi are more common
 Appear in infancy or childhood, slowly grow and
mature and then regress in older life
 Important for cosmetic reasons and as precursors for
melanoma (esp in white)

73. ACQUIRED NEVI
Round or oval, uniformly coloured and sharply
bordered lesions
 Appear after birth
 Increase in frequency during childhood and
adolescence and plateaus during middle age
 Most of them start as junctional nevi which are
flat and histologically confined to dermal-epidermal
junction

74. ACQUIRED NEVI
Gradually mature to compound nevi which have nests
and columns of nevus cells in dermis along with the
junctional component.
These are raised, rounded, brown or black
 Intradermal nevi : Compound nevi mature to
intradermal nevi with nevus cells only in dermis having
neuron like appearance.
These are dome shaped, nonpigmented and may have
one or more coarse hairs

77. CONGENITAL MELANOCYTIC NEVI
Small < 1.5
Intermediate: 1.5 to 20 cms
Giant > 20 cms
Malignant potential for giant nevi is 4-6%
Excision justified for cosmetic reasons and
risk of malignancy

79. CAFÉ AU LAIT MACULES (CALM)
Circumscribed, brown macules with irregular
margins, 2-5 cm in size
Present at birth
Isolated CALM may occur in 10-20% of normal
population
No increase in the number of melanocytes
 Five or more CALM of size >0.5 cm in
prepubertal age group and >1.5 cm in an adult
are strongly suggestive of neurofibromatosis

81. BECKER’S NEVUS
Acquired, pigmented, hairy plaque common on
trunk, more common in males
 Appears in first or second decade
Common sites: shoulder, chest, back
 May become verrucous with hair growth and
then remains stable
 No treatment needed

83. EPHELIDES (FRECKLES)
Tiny (<0.5 cm), discrete brown macules
Common in fair skinned
Appear in childhood on sun exposed parts; lighten in
absence of sun exposure
Melanocytes are not increased in number but are
hyperactive
 May be part of some syndromes

85. MELASMA
A common macular brown coloured lesion seen on face in
males and females 90% (darker skin)
Common in pregnancy: Mask of pregnancy (clears in few
months)
Etiology: hormones (OC Pills) (remains for yrs after
stoppage) and sunlight
May disappear or remain after delivery
Forehead, nose, cheeks affected.
The three clinical patterns are: centrofacial, malar,
mandibular
Exacerbation on sun exposure
Histologically may be epidermal, dermal or mixed

88. POST-INFLAMMATORY HYPERPIGMENTATION
After resolution of specific eruptions
Common after lichen planus, atopic dermatitis,
acne vulgaris, contact dermatitis, psoriasis,
pyodermas etc.
Discrete macules exactly on the sites
previously affected by eruptions
May persist for months

92. FIXED DRUG ERUPTION (FDE)
NSAIDs, antibiotics, barbiturates etc.
Reddish brown macule → edematous →
desquamation → pigmentation
Recurs at same site on rechallenge
May become generalised or blistering
Melanin is increased in epidermis and dermis
(melanophages)

94. MONGOLIAN SPOTS
Common in Asian newborns on buttocks or
lower back
Due to arrest of migrating melanocytes in the
dermis
No treatment is needed as they spontaneously
disappear by 2 to 10 yrs of age

96. NEVUS OF OTA AND ITO
Nevus of Ota (around eyes) and nevus of Ito
(shoulder area) are other examples of dermal
pigmentation

98. • Characterized by
hyperpigmented macules on
the lips and oral mucosa and
polyposis of the small
intestine
• Dark brown or black
macules appear typically on
the lips, especially the lower
lip, in infancy or childhood
• Similar lesions may appear
on buccal mucosa, tongue,
gingiva, and genital mucosa
• Macules may also occur
around the mouth, on the
central face, backs of the
hands, especially the fingers,
and on the toes and tops of the
feet.
• Associated polyposis involves
the small intestine
• But, hamartomatous polyps of
the stomach and colon may
occur
• Symptoms of hamhartomas of
the small intestine may cause
repeated bouts of abdominal
pain and vomiting, and
intussusception
PEUTZ-JEGHERS

99. • Incidence of malignancy within the polyps is 2-3%
• Incidence of GI malignancy is low, but increased incidence of
other kinds of cancer - breast, and gynecologic malignancies
in women.
• Syndrome is inherited and transmitted as a simple
mendelian dominant trait

102. INDUSTRIAL
HYPERPIGMENTATION
• Occurs in coal miners, anthracene
workers, pitch workers, etc
• Pigmentation of the face may occur
from the incorporation in cosmetics of
derivatives of coal tar, petrolatum, or
picric acid, mercury, lead, bismuth, or
furocoumarins (psoralens)

103. SYSTEMIC DISEASES
• Syphilis, malaria, pellagra, and diabetes
• Diabetes produces diffuse bronzing of the
skin
• Patients with virilizing adrenal tumors usually
develop hyperpigmentation and
hypertrichosis

104. ADDISONS DISEASE
• diffuse melanosis pronounced in the axillae and
palmar creases, and nipples and genitals, and
buccal mucosa

106. Diffuse skin hyperpigmentation, increased pigmentation of the palmar creases and wrists
compared to a normal female control (far right), her hyperpigmentation resolved

107. HEMOSIDERIN HYPERPIGMNETATION
• Pigmentation due to deposits of hemosiderin
occurs in:
-purpura
-hemochromatosis
-hemorrhagic diseases
-stasis ulcers

108. HEMOCHROMATOSIS
Characterized by:
• Gray-brown mucocutaneous
hyperpigmentation
• Diabetes mellitus
• Hepatomegaly
Usually are present:
• Cirrhoisis
• Hypogonadism
• Liver cirrhosis

109. • Skin pigmentaion is
usually generalized
• But, more pronounced on
face, extensor aspect of
the forearms, backs of the
hands, and the geniocrural
area
• Iron is deposited in the
skin
• Iron is present as granules
around blood vessels and
sweat glands and within
macrophages
• The actual
pigmentation is caused
by increased basal -
layer melanin
• Mucous memebranes
are pigmented in up to
20% of patients
• Koilonychia is present
in 50%
• Localized ichthyosis in
40%
• Alopecia is common

110. METALLIC DISCOLORATIONS
• Pigmentation from deposition of fine
metallic particles in the skin
• Metal may be carried to skin from the
blood stream or may permeate into it
from surface applications

111. • Localized or widespread
slate-colored pigmentation
• Due to silver in the skin
• Most noticeable in parts
exposed to sunlight
• Tissue silver may stimulate
melanocytes
• Initially discoloration is hardly
perceptible, having only a
faint blue color, but a slate-gray
color develops with time
• Local tx with a silver-containing
product may
produce argyria
• Examples: conjunctivae, from
eye drops; a wound from
sulfadiazine cream, earlobes
from silver earings; and from
silver acupuncture needles
• Can also occur from
occupational exposure,
usually silversmiths
• In localized exposures, the
appearance may be
separated by many years
from the exposure
ARGYRIA

113. BISMUTH
• Rarely associated with deposition of metallic particles
in gums when used IM or orally
• Also known as the bismuth line
• Presence of stomatitis or peridontitis increased the
risk
• Generalized cutaneous discoloration, in addition to
oral mucous membrane and conjunctival pigmentation
resembling argyria has occurred but has not be
reported in the last 50 years

114. LEAD
• Chronic lead poisoning can produce a “lead hue”
with lividity and pallor
• Deposit of lead in the gums may occur and is
known as the “lead line”

115. GOLD
• Chrysiasis may be induced by parenteral
administration of gold salts, usually for the
treatment of rheumatoid arthritis
• More commonly recognized in white patients
• A mauve, blue, or slate/gray pigmentation
develops initially on the eyelids, spreading to
the face, dorsal hands, and other areas
• Pigment is accentuated in light-exposed
areas, and sun protected areas do not
demonstrate gold

117. MERCURY
• Mercurial pigmentation in the
skin is rare, especially since
the use of mercurials has
been strictly controlled
• Most common presentation is
subcutaneous nodules that
result from accidental
implantation of elemental
mercury from a thermometer
into skin

118. CANTHAXANTHIN
• Orange-red pigment canthaxanthin is present in
many plants ( notably algae and mushrooms)
and in bacteria. Crustaceans, sea trout, and
feathers
• When ingested for the purpose of simulating a
tan, its deposition in the panniculus imparts a
golden orange hue to the skin
• Stools become brick red and the plasma orange,
and golden deposits appear in the retina