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Disorders of Pigmentation
Digital Lecture Series : Chapter 14
Dr. Nilendu Sarma
Assistant Professor,
NRS Medical College
CONTENTS
Skin colour
Hyperpigmentary Disorder
Melanocytes & melanin
•
Classification
Classification
•
Individual description
Approach to patient
Treatment
Hypopigmentary disorders
MCQs
• Classification
• Individual description
Photo Quiz
Skin colour
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.
Melanocyte
Dendritic cells
Derived from neutral crest
Migrate to epidermis
Epidermal melanin unit - one melanocyte connected to about 36
keratinocytes by dendrites.
Synthesize melanin in organelles called melanosomes.
Melanosomes are then transferred to keratinocytes through
dendrites.
Melanin
Two types
• Eumelanin (black or brown)
• Pheomelanin (reddish)
Derived from tyrosine
Tyrosine
Tyrosinase
DOPA [3, 4 dihydroxy phenylalanine]
Dopaquinone
Dopachrome
Cysteinyldopa
5, 6 dihydroxindole
pheomelanin
Eumelanin
Disorders of pigmentation - 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.
Classification
Hypopigmentation :
reduced or absent pigment
eg. Vitiligo, Pityriasis alba
Hyperpigmentation :
This can be subdivided into epidermal (brown) and dermal (blue/
slate grey hyperpigmentation) (see more later)
Other important points in classification
Localised, generalised
Segmental, non-segmental, Blasckoid, reticulate (shape/ pattern)
Dyschromia (presence of both hypo and hyperpigmentation)
Approach to a patient
History
Onset : birth, infancy or later
Cause : sun exposure, drugs, occupation
Systemic complaints
Family history : neurofibromatosis, tuberous sclerosis, vitiligo
Approach to a patient
Examination : Inspection
Color : Hypopigmented, depigmented, brown, slate grey,
Shape : Ash leaf macules (tuberous slerosis)
Koebner phenomenon(vitiligo)
Pattern : linear/segmental
Symmetry (vitiligo),
Distribution : specific sites (melasma, Addison’s disease)
Margin : feathery, serrated, shaded (trichrome vitiligo)
Examination
Sensation
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.
Melanin stain - Silver stains (Masson-Fontana stain).
Examination
Examine other organs
Eye
Hair
Oral mucosa
Nails
Hematological, hormonal assay (cortisol, ACTH, thyroid)
Neurological
Hypopigmentation disorders
Hypopigmentation
Depigmentation
Classification : Hypopigmented / depigmented lesions
Genetic and Developmental :
Albinism, Nevus depigmentosus, Nevus anaemicus, Halo nevus.
Endocrine :
Hypothyroidism, Hypopituitarism.
Nutritional :
Vit.B12 deficiency, Kwashiorkor, Malabsorption.
Post-inflammatory :
Pityriasis alba, Eczema, Psoriasis, Pityriasis rosea, Lupus
erythematosus, Morphea, Scleroderma, Bullous dermatoses.
Classification : Hypopigmented / depigmented lesions
Infection :
Leprosy, Tinea versicolor, Candidiasis, Post kala azar dermal
leishmaniasis.
Chemicals and Drugs :
Phenols, Arsenicals, Hydroquinone, Steroids.
Physical :
Burns, Trauma, Post dermabrasion, Post laser.
Miscellaneous :
Idiopathic guttate hypomelanosis, Vitiligo, Mycosis fungoides.
Albinism
Oculocutaneous albinism involves
skin, hair and eyes.
Reduced pigment in eye is universal.
Mostly autosomal recessive.
Absence of pigmentation from birth
Photophobia, reduced visual activity,
nystagmus,
Sunburns, skin cancers common.
Rule out similar phynotypic diseases
like Hermansky-Pudlak and ChediakHigashi syndromes.
Protection of eyes and skin by
sunglasses, sunscreens SPF > 20, sunavoidance.
Lighter hair diseases : Griscelli syndromes
Autosomal recessive. Mutations in MYO5A gene, RAB27A gene and
Mlph gene (in type 1, 2 and 3 respectively)
Perinuclear aggregation of melanosomes in melanocytes
Clinical : Congenital hypomelanosis and hypopigmented hair. Eyes are
normal. There are three subtypes based on the loci of mutation.
Complication : Death may occur due to various complications and
systemic involvement.
Management : Multidisciplinary management involving the
ophthalmologist, neurologist, haematologist and dermatologist
Lighter Hair Diseases : Chediak-Higashi Syndrome
Autosomal recessive. Mutations in CHS1 gene.
Pathogenesis : Defects in the function of neutrophils, platelets,
cytotoxic and NK cells and giant inclusion bodies occur in virtually all
granulated cells.
Clinical
•
•
•
Oculocutaneous albinism,
Recurrent pyogenic infections, enhanced tendency for bruising
and neurologic dysfunction.
Lighter colored hair
Complication and management same as Griscelli syndrome.
Piebaldism
Autosomal dominant.
Pathogenesis : Defect in melanoblast development, proliferation,
migration, or survival, decreased receptor tyrosine kinase signaling
and finally decrease in melanogenesis.
Clinical
•
•
Congenital, sharply demarcated and roughly symmetric
depigmented patch, usually over frontal scalp, forehead, ventral
chest, abdomen and extremilties.
Other : Café-au-lait macules and axillary and/ or inguinal
freckles.
Waardenburg’s syndrome
Rare, genetically heterogeneous, 6 genes involved (PAX3, MITF,
SOX10, EDN3, EDNRB, SNAI2White forelock).
White forelock, broad nasal root, congenital sensorineural deafness,
and partial or total heterochromia of the iris, lateral displacement of
the medial canthi (dystopia canthorum).
Other associated defects - limb defects, Hirschsprung disease.
Incomplete forms may occur.
Tuberous sclerosis
Autosominal dominant
Mutations in either genes encoding
hamartin (TSC1) and tuberin (TSC2)
Hypopigmenetd Ash-leaf macule
(develops very early), angiofibromas,
Shagreen patch, subungual fibromas.
Other pigmentary changes Generalised guttate hypopigmented
macules (confetti macule),
Polygonal hypopigmented macules (thumb print shape),
Café-au-lait macules,
Other problem - epilepsy, renal and brain hamartoma
Diagnosis : Specific criteria
Nevus depigmentosus
A hypopigmented birthmark which is
congenital, stable and non-familial
Irregular, geographic margins and
quasidermatomal distribution
Block in transfer of melanosomes from
melanocytes to keratinocytes
Management : Surgical techniques,
excimer laser
Nevus anemicus
This is not a true hypopigmentation
disorder.
Congenital, sharply demarcated macule
or patch of paler areas usually in
females
It is caused by increased reactivity of
the α-2 receptors of the lesional
vasculature to catechols resulting in
persistent vasconstriction.
Hypomelanosis of Ito
Etiology : Genetic mosaicism
Clinical :
Macular hypopigmentation following lines of Blaschko.
Whorled shape/ V-shape/ wave pattern.
Associated defects: Mental retardation, epilepsy, learning
disabilities, vesico-ureteric reflux and musculoskeletal deformities.
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.
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.
Treatment : Topical and systemic
antifungal.
Woods lamp findings of t. versicolor
Leprosy
Both hypopigmented and erythematous
lesions common.
Hypopigmented macules common in
tuberculoid type of disease.
Each hypopigmented lesions in leprosy
endemic areas should be examined for
sensations of touch, pain, temperature.
Treatment according to type of leprosy.
Pityriasis alba
A common disorder in children.
Hypopigmented 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.
Disorders of hyperpigmentation
Hyperchromia is a term that may include melanotic and nonmelanotic pigmentation.
Non-melanotic pigmentation can be due to deposition of nonmelanin substance. This can be endogenous (porphyrin, ochronosis)
and exogenous (drugs, heavy metals).
Simple thickening of skin can also cause hyperchromia.
Hyperpigmentation is called when it is due to melanotic
pigmentation.
Melanotic hyperpigmentation can be due to increased melanin or
melanocytes.
Hyperpigmentation is also classified based on the depth like
epidermal and dermal. Epidermal pigmentation is brown and dermal
is slate-grey / bluish.
Epidermal hyperpigmentation
Physiologic
Pigmentary demarcation lines, suntanning.
Genetic and Developmental
Lentigines, Freckles, Melanocytic nevus, Café-au-lait spots.
Post-inflammatory
Eczema, Psoriasis, Lichen planus, Lupus erythematosus, Scleroderma,
Morphoea, Vagabond’s disease.
Infection
Tinea nigra.
Nutritional
Kwashiorkor, Pellagra, Vit.B12, Vit.C, Folic acid deficiency.
Epidermal hyperpigmentation
Physical
Trauma, Radiation dermatitis.
Endocrine
Melasma, Addison’s disease, Cushing’s syndrome,
Phaeochromocytoma, Acromegaly, Hyperthyroidism.
Neoplastic
Malignant melanoma, Seborrhoeic keratosis, Pigmented basal cell
carcinoma.
Dermal hyperpigmentation
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.
Dermal hyperpigmentation
Endocrine
Melasma
Physical
Thermal burns, Post traumatic
Infection
Syphilis, Yaws, Pinta
Neoplastic
Metastasis of melanoma
Dermal hyperpigmentation
Nutritional
Chronic nutritional deficiency.
Metabolic
Hemochromatosis, Alkaptonuria, Macular/Lichen amyloidosis.
Miscellaneous
Pigmented purpuric dermatosis, Purpura.
Diffuse hyperpigmentation
Addison’s disease
Haemochromatosis
HIV infection and AIDS
Drugs
•
Clofazimine
•
Chlorpromazine
•
Amiodarone
•
Anticancer agents
Melanocytic nevi
Benign proliferations of melanocytic nevus cells at the dermoepidermal 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).
Congenital melanocytic nevi
Small < 1.5
Intermediate : 1.5 to 20 cms
Giant > 20 cms
Malignant potential for giant nevi is 46%.
Excision justified for cosmetic reasons
and risk of malignancy.
Acquired nevi
Round or oval, uniformly coloured and sharply bordered lesions
Appear after birth.
Junctional nevi: 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.
Acquired nevi
Compound nevi :
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.
Treatment
Elliptical excision and biopsy
Destructive methods (cautery, cryotherapy) not recommended as
recurrence with atypical appearance may occur.
Indications of excision :
Cosmetic reasons
Irritation due to clothing, belts, straps
Atypical appearance: sudden increase in size, varied pigmentation,
irregular borders, bleeding.
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.
Mongolian spots
Common in Asian newborns on
buttocks or lower back.
Etiology : Arrest of migrating
melanocytes in the dermis.
No treatment is needed as they
spontaneously disappear by 2 to 10
yrs of age.
Nevus of Ota and Ito
Nevus of Ota (Blue-gray pigmented
macule or patch on the upper half of
face).
Nevus of Ito : shoulder area
Both are congenital dermal
pigmentation.
Pathogenesis : Migration arrest of
melanoblast that arises from neural
crest.
Nevus of Ota
Generally present at birth
When develop later and is not associated with any eye or
extracutaneous involvement is called nevus of Hori
Females are more commonly affected
Pigmemtation at other sites: Iris, cornea and even optic nerve and
periosteum, eustachian tube, tympanic membrane, nasal mucosa,
and in pharynx.
Glaucoma is a rare complication.
Melanoma may develop in nevus of Ota.
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
Reticulate pigmentation disorders
Reticulate acropigmentation of Kitamura
Dowling-Degos disease
X-Linked Reticulate Pigmentary Disorder
Dermatopathia Pigmentosa Reticularis
Dyschromatosis Universalis Hereditaria
Reticulate pigmentation disorders
X-linked Reticulate Pigmentary Disorder
(Familial cutaneous amyloidosis or X-linked cutaneous amyloidosis)
Onset : Early childhood
Mostly males
Generalised, reticulate hyperpigmentation.
Linear hyperpigmentation in a blaschkoid distribution in females
Other : Coarse, unruly hair, upswept eyebrows and hypohidrosis
Extracutaneous manifestations
Reticulate pigmentation disorders
Dermatopathia Pigmentosa Reticularis
Ectodermal dysplasia syndrome
Autosomal dominant
Reticulated hyperpigmentation,
Other : Palmoplantar keratoderma,
hypohidrosis and developmental
anomalies.
Dyschromatosis Universalis Hereditaria
Hyper- and hypopigmented macules localised or extensive
Dowling-Degos disease
Autosomal dominant
Progressive reticulate
hyperpigmentation in flexures.
Small keratotic dark brown papules
mostly in flexures
Reticulate acropigmentation Of Kitamura
Autosomal dominant
Childhood onset
Hyperpigmented, sharply demarcated, atrophic macules on the
dorsa of the hands and feet.
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
Melasma (chloasma)
A common macular brown to brownish
grey coloured patch on face in males
and females
Etiology: Genetic (common in
pigmented race), female more than
male, sun exposure, pregnancy, drugs
(OC Pills, diphenylhydantoin).
Pathogenesis : Unknown. Possible role
of Estrogen and progesterone, vascular
endothelial growth factor (VEGF), genes
like TYR, MITF, SILV, TYRP1.
May disappear or remain after delivery.
Sites : centro facial, malar and
mandibular area. Occasionally, also on
extensor arms and upper chest.
Diagnosis
Diagnosis is clinical
Helpful aids :
Wood’s lamp (depth analysis)
Dermoscopy
Reflectance confocal microscopy
Histology is needed only to evaluate
depth and not usually used for
diagnosis
Treatment of melasma
Sunscreens and bleaching agents
•
Physical sunscreens to be used daily
•
Bleaching agents : Hydroquinone 2-4%, Kojic acid 2-3%, Tretinoin
0.025-0.05%, Arbutin
Chemical peels : tretinoin peels (1%), amino fruit acid peel, Obagi
blue peel
Lasers : Flashlamp-pumped PDL (510 nm), frequency doubled Q
switched neodymium: Yttrium aluminium garnet-532 and 1064 nm,
Q switched ruby (694 nm)
Complete resolution is uncommon.
Relapse is frequent.
Dermal melasma even slower to respond.
Fixed Drug Eruption (FDE)
Rash occurs on same sites on every
exposure. New sites may be added
Rash may be erythema or even blister
It heals with pigmentation that persists
for many months
Common drugs : NSAIDs, antibiotics,
barbiturates
Melanin is increased in epidermis and
dermis (melanophages)
Post-inflammatory hyperpigmentation
After resolution of specific eruptions
Common in darker skin types
Common after lichen planus, atopic
dermatitis, acne vulgaris, contact
dermatitis, psoriasis, pyodermas
Pigmentation exactly on the sites of
disease
Etiology : Increased melanin in
epidermis and dermis. Dermal pigment
(called incontinence) may be free or
within macrophages (melanophages)
Post-inflammatory hyperpigmentation
Management:
May persist for months to years.
Prevention is more helpful. Broad spectrum sunscreen should be
added.
Overall management is similar to all other pigmentation.
Topical hydroquinone (2-4%), tretinoin, topical corticosteroid,
azeleic acid.
Chemical peeling (alpha-hydroxy acids).
Treatment of hyperpigentation
Agents used
Tyrosinase
Inhibitors
Melanocyte
cytotoxic
Others
Hydroquinone
Azelaic acid
AHA
Arbutin
Resorcinol
Kojic acid
Vit. C
Licorice extract
Tretinoin
Vit. E
Treatment of hyperpigmentation
Hydroquinone (2 - 4%) :
Inhibits tyrosinase activity by 90%
Affects DNA, RNA synthesis
Safety concerns like irritation, exogenous ochronosis
May be combined with topical steroids, tretinoin, kojic acid
Tretinoin :
Adjuvant
Inhibits tyrosinase in cells cultures
Exact mechanism of action unknown
Treatment of hyperpigmentation
Kojic acid :
Fungal metabolite
Food additive - Japan
Suppresses tyrosinase by chelating copper
Stability
Sensitization
A.H.A :
Natural saturated dicarboxylic acid
Diminished corneocyte cohesion
Faster desquamation due to increased turnover
Side effects : irritation, hyperpigmentation
Glycolic, lactic, mandelic acid
Drugs
Azelaic acid :
Antiproliferative, cytotoxic
Inhibits tyrosinase
As effective as hydroquinone
Azelaic acid 20% + Glycolic acid 15-20% is an effective combination
Vit. C :
Problems with penetration and stability
Newer agents
Not known whether they are more effective
• Tranexamic acid
• 4-n-butyl resorcinol,
• Oligopeptides,
• Silymarin,
• Botanical extracts like grape seed extract, pycnogenol, cinnamic
acid, green tea extracts.
Physical modalities
Chemical peels with increasing concentrations of glycolic acid,
trichloroacetic acid, salicylic acid.
Lasers
• Q switched Nd: YAG laser
• Alexandrite laser
• Pulse dye laser
• Intense pulse dye laser
MCQ’S
Q.1)
A.
B.
C.
D.
Drugs known to precipitate melasma
Phenytoin
Barbiturates
NSAID
Clobazam
Q.2)
A.
B.
C.
D.
Eye involvement is not seen in
Albinism
Griscelli syndrome
Hermansky-Pudlak syndrome
Chediak-Higashi syndrome
MCQ’S
Q.3) Select the wrong one
A. Waardenburg syndrome is caused by failure of melanocyte
differentiation
B. Hypomelanosis of Ito is caused by mosaicism
C. Tuberous sclerosis is not characterised by confetti depigmentation
D. Dowling-Degos disease is a reticulate pigmentation disorder
Q.4)
A.
B.
C.
D.
Café-au-lait macule is not found in :
Neurofibromatosis
Albright’s syndrome
Tuberous sclerosis
Hypomelanosis of Ito
MCQ’S
Q.5)
A.
B.
C.
D.
Focal hyperpigmentation of skin is seen in
Addisons disease
Haemochromatosis
Systemic sclerosis
FDE
Photo Quiz
Q. Identify the conditions?
Photo Quiz
Q. Identify the condition?
Thank You!