Disorders of

Pigmentations
FK UPH
2020
 SKDI 2012
• Vitiligo
• Melasma
• Albino
• Post inflammatory hyperpigmentation
• Post inflammatory hypopigmentation
Vitiligo
 Definition
• Common autoimmune disease of the skin
• Causes depigmentation
• Through T-cell–mediated destruction of melanocytes
 Prevalence
• World: 0,5-1,0%
• Island of Bornholm, Dernmark: 0,38%
• Subpopulation of India: 8,8%, chemically induced
• Begin at any age
• > ½ : before 20 y.o.
• 1/3: before 12 y.o
• Males = females
 Clinical Features
• Asymptomatic, white, nonscaly, distinct margins
• Fluorescent illuminated by Wood lamp examination
• Usually symmetrical, except segmental variant
 Clinical Features – Pattern (1/3)
• Acrofacial:
• Adults
• Hands, feet & face (orifices)
• May evolve to generalized
• Mucosal
• Oral and/or genital mucosa
• Focal
• Small, isolated Mucosal vitiligo, limited to the lips
• 50%: progress larger
 Clinical Features – Pattern (2/3)

• Pattern:
• Universal
• Rare form
• Adults > children
• > 80% body surface area
• Segmental
• 10-15% of the variants
• Unilateral & segmental / block shaped
• Poliosis (+) Unilateral, block-like depigmentation of the
segmental variant of vitiligo
 Clinical Features – Pattern (3/3)

• Pattern:
• Mixed,
• Rare form
• Eq. segmental + additional patch

Mixed vitiligo, segmental lesion on back plus additional bilateral lesions in remote
areas
 Clinical Features –
Clinical Markers Of Disease Activity (1/4)
• Koebner phenomenon
• Isomorphic response
• At the site of skin trauma (linear/non-linear)
• Trichrome vitiligo
• 3 distinct colors: depigmented, normal,
& hypopigmented skin
• Blurring of lesional borders
• Active, rapidly spreading vitiligo
Linear depigmentation in locations of skin
trauma.
 Clinical Features –
Clinical Markers Of Disease Activity (2/4)

• Confetti-like depigmentation
• Multiple small macules clustered together
• Inflammatory vitiligo
• Very rare form
• Erythema, scale, & itch at the border (+)
• Transient, but rapidly progressing to large areas

Multiple scattered macules of confetti depigmentation in

vitiligo.
 Clinical Features –
Clinical Markers Of Disease Activity (3/4)

• VIDA scores
• Range
• From +4 (activity lasting 6 weeks or less)
• To −1 (vitiligo stable for 1 year or more
with spontaneous repigmentation)
• Cons:
• Patient’s recollection  recall bias
• Different lesions  different scores,
difficult in daily practice
 Clinical Features –
Clinical Markers Of Disease Activity (4/4)

• K-VSCOR
• Koebner phenomenon & anatomical
location
• Six areas (forehead + scalp areas,
eyelids, wrists, genital + belt areas,
knees & tibial crests) + duration
• Score: 0 to 56
• Pic. ref.:
https://www.semanticscholar.org/paper/Develo
pment-and-validation-of-the-K-VSCOR-for-in
-Diallo-Boniface/f8a71afb6c41cb6a317b159a
2f92f44be91459c8/figure/0
 Etiology & Pathogenesis
• Autoimmune disease
CXCL10 & other Melanocytes
CD8+ T cells IFN-γ
chemokins destruction

• Cellular stress
• Exogenous oxidative stress
• Emotional stress
• Chemical toxicity / chemical theory
• Neural changes / neural hypothesis
 Risk Factors
• Genetic factors
• Environmental factors (chemicals)
• Monobenzone (leather factory workers)
• 4-tert-butyl phenol and 4-tertbutylcatechol (in a lubricating oil)
• Permanent hair dyes
• Etc.
 Diagnosis
• Clinical (usually enough) • Histology
• Well-defined, symmetrical • Only for unusual presentation
depigmented or segmental
• Complete loss of melanocytes
• Wood lamp examination (epidermis)
• Laboratory (additional) • CD4+ and CD8+ (interface pattern)
• TSH
• Complete blood count
• Antinuclear antibody testing
 Differential Diagnosis (1/5)

Non Segmental
• Piebaldism • Postinflammatory
• Waardenburg syndrome hypopigmentation
• Tuberous sclerosis
• Idiopathic guttate hypomelanosis
• Ito hypomelanosis
• Tinea versicolor • Progressive macular
• Treponematoses (syphilis, pinta) hypomelanosis
• Leprosy (tuberculoid/
 Differential Diagnosis (2/5)

Piebaldism Tinea versicolor

 Differential Diagnosis (3/5)

Ash-leaf macules in tuberous

Hypopigmented patches of leprosy
sclerosis
 Differential Diagnosis (4/5)

Hypopigmented patches of
mycosis fungoides
 Differential Diagnosis (5/5)

Segmental
• Nevus anemicus
• Nevus depigmentosus
 Management
• Nonsegmental
• Segmental
Management

TIM: Topical
immunomodulator
(pimecrolimus/tacrolimus
)
Management

TIM: Topical
immunomodulator
(pimecrolimus/tacrolimus
)
 Management
Topical Therapies
Topical steroids Topical calcineurin inhibitors
• Adult: class I steroid (clobetasol) • Tacrolimus, pimecrolimus
• Child: class II (mometasone) • Pros:
• Cons.: • Excellent safety profiles (face, neck,
intertriginous, children)
• Side effects >>
• Orbital area use  glaucoma
 Management
Phototherapy & Others
Phototherapies Others
• Psoralen + UVA • Psychological interventions
• Narrowband UVB • Cosmetics
• Targeted UVB: excimer laser, • Depigmentation therapy (>80%
lamp BSA or significant poliosis)
• Surgical
 Reference
• Ezzedine K, Harris JE. Vitiligo. In: Kang S, Amagai M, Bruckner A, Enk
AH, Margolis DJ, McMichael AJ, et al (eds.) Fitzpatrick’s dermatology.
9th ed. New York, USA: McGraw-Hill Education; 2019. p. 1330-50
Melasma
 Melasma
• Most common disorders of pigmentation
• Synonims: chloasma or mask of pregnancy
• Acquired light-brown to dark-brown macules
• Poorly circumscribed
• More common: colored-skin person; malar skin, nose, forehead, and upper lip
• Gold standard: hydroquinone
• Other therapy: physical and oral
 Epidemiology
• 9% (Hispanic populations, southern US) to 40% (Southeast Asians)
• Premenopausal women > men & postmenopausal women
 Clinical Features
• Diffuse light-brown to dark-brown, central face
• Predisposition:
• Centrofacial (63%: forehead, nose, chin, and upper lip)
• Malar (21%: nose and cheeks)
• Mandibular (16%: ramus mandibulae)
• Spares: periorbital skin, lips, neck, & ears
 Etiology & Pathogenesis
• Not completely understood
• Most important: active melanocytes, genetic, hormonal & UV light
• Specific precipitants: oral contraceptives, estrogen replacement therapy
• Recent: visible light, vascularity ↑& vascular endothelial growth factor
↑
 Diagnosis
• Wood lamp
• Dermal vs epidermal melasma
• Wood light–enhancing lesions: epidermal
 Differential diagnosis
• Postinflammatory pigmentation
• Maturational dyschromia
• Medication-induced pigmentation
• Lichen planus pigmentosus
• Poikiloderma of civatte
 Clinical Course & Prognosis
• Chronic and relapsing
• Exacerbations:
• Pregnancy
• Sun or visible light exposure
• Hormonal treatments
 Management (1/2)
• Managing expectations & counselling
• Cessation of any obvious triggers
• Photoprotection: sun avoidance, protective clothing, and regular application broad-
spectrum sunscreen, visible light (Fitz skin type IV-VI) avoidance
• Gold standard: 4% hydroquinone
• Others: tretinoin, azelaic acid, and kojic acid
• Nonprescription: soy, licorice, lignin peroxidase, & niacinamide for mild epidermal
melasma
 Management (2/2)

• Treatment adjuncts:
• Superficial chemical peels
• Low-fluence quality-switched Nd:YAG laser
• Intense pulsed light, erbium:YAG, nonablative 1550-nm and 1927-nm fractional
lasers
• Recent: tranexamic acid (topical, intralesional, & oral forms
 Reference
• Rodrigues M, Pandya AG. Hypermelanoses. In: Kang S, Amagai M,
Bruckner A, Enk AH, Margolis DJ, McMichael AJ, et al (eds.)
Fitzpatrick’s dermatology. 9th ed. New York, USA: McGraw-Hill
Education; 2019. p. 1351-89
Albinism
 Albinism
• Hypopigmentation of skin, hair & eyes
• Subtypes
• Non-syndromic: restricted to impared melanin biosynthesis
• Syndromic:
• Hermansky-Pudlak syndrome
• Chediak-Higashi syndrome
• Griscelli syndrome
 Subtypes

Non-syndromic
• Hypopigmentation of skin & hair
• Ocular changes
• Reduced iris pigment
• Nystagmus
• Impared visual acuity
• Foveal hypoplasia
Syndromic
• Non-pigmentary symptoms:
• Bleeding diasthesis
• Lung fibrosis
• Imunodeficiency
 Oculocutaneous Albinism
• A group of rare genetic disorders
• Autosomal recessive inheritance
• Characteristics: hypopigmentation of skin, hair & eyes
• Seven subtypes & 6 responsible genes
• Prevalence: 1: 10,000 – 20,000
Oculocutaneous Albinism
 Oculocutaneous Albinism

OCA1A OCA4
 Oculocutaneous Albinism
Clinical Course, Prognosis, And Management
• No curative treatment
• Early diagnosis  initiation appropriate interventions for skin and eye
• Skin: sun protection; protective clothing & regular sunscreen; regular skin check-ups
for skin cancer
• Eyes: early referral to ophthalmologist; corrective glasses or surgical correction of
strabismus & nystagmus; dark sunglasses may alleviate photophobia
• With the exception of OCA1A, hypopigmentation of skin and hair tends to
be alleviated as individuals mature
 Ocular Albinism
• A rare inherited disorder
• Characteristics: hypopigmentation of the eyes and visual disturbances
• Most common type is X-linked ocular albinism (OA1)
• Hypopigmentation of skin and hair can be seen in some individuals,
usually mild and not as evident as oculocutaneous albinism
• Visual disturbances: nystagmus, impaired visual acuity, & stereoscopic
vision
 Ocular Albinism
Clinical Course, Prognosis, And Management
• No curative treatment
• Early referral to ophthalmologist for appropriate intervention
• Visual impairment: wearing corrective glasses
• Dark sunglasses for photophobia
• Surgical for strabismus and nystagmus
• OA1 is likely to be a nonprogressive, sometimes improves until adulthood
 Hermansky-Pudlak Syndrome
• A rare autosomal recessive genetic disorder
• Hypopigmentation of skin, hair, and eyes
• Nonpigmentary: bleeding diathesis (storage pool deficiency & ceroid accumulation)
• Prevalence: 1:500,000 to 1:1,000,000
• Ten forms of HPS identified
• HPS1 & HPS4 associated with interstitial pneumonia or granulomatous colitis
• HPS2 & HPS10 associated with immunodeficiency & uncontrolled lymphocyte &
macrophage activation
Hermansky-Pudlak Syndrome

Hermansky-Pudlak syndrome type 4 (HPS4), 6-year-old

Girl. Blonde hair, white skin, and light gray irides with
nystagmus are seen. Purpura is also seen on her lower leg.
 Griscelli Syndrome
• A rare autosomal recessive genetic disorder
• Characteristics:
• Hypopigmentation of skin and hair
• Large clumps of pigment in the hair shaft on light microscopy
• Three forms of GS have been identified
• GS1 and GS2: neurologic and hematologic abnormalities
• GS3 is restricted to hypopigmentation
 Griscelli Syndrome

(A) Photomicrograph of the hair shaft revealed large sized melanin granules, distributed mainly near the medulla (×100), (B)
photomicrograph showing the hair shaft under polarized light where the hair appeared uniformly white (×100). (Mishra K, Singla
S, Sharma S, Saxena R, Batra VV. Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in
2 siblings: a diagnostic conundrum. Korean J Pediatr. 2014 [cited 2020 Apr 2] ;57(2):91–95. Available from: (
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965801/#)
 Chédiak-Higashi Syndrome
• A rare genetic disease with autosomal recessive inheritance
• Characteristics:
• Reduce pigmentation of skin and eyes (silvery or metallic colored hair)
• Neurologic disorders: low IQ scores, cerebellar ataxia, peripheral neuropathy
• Hematologic disorders: lymphoproliferative syndrome (fatal)
Chédiak-Higashi Syndrome

Infant with Chediak-Higashi syndrome presenting with hypomelanotic

skin and white hair with a metallic sheen. From Carden et al, Br J
Ophthal, 1998, 82:189-195, with permission from BMJ Publishing
Group. (https://emedicine.medscape.com/article/1068184-overview)
 Reference
• Hayashi M, Suzuki T. Albinism and other genertic disorders of
pigmentation. In: Kang S, Amagai M, Bruckner A, Enk AH, Margolis DJ,
McMichael AJ, et al (eds.) Fitzpatrick’s dermatology. 9th ed. New York,
USA: McGraw-Hill Education; 2019. p. 1309-29
Postinflammatory
Hyperpigmentation
 Definition
• Common reactive melanosis caused by numerous preceding inflammatory
& cutaneous insults
Preceding Inflammatory Cutaneous Insults
Acne Drug & phototoxic reactions
Lichen planus Infections
Psoriasis Physical injury or trauma
Etc. Alergic reactions
 Epidemiology
• More common in darker-skin types (Fitzpatrick Types III-VI)
• Any age
 Clinical Features
• Macular hyperpigmentation at the site of inflammation
• Epidermal inflammation  brown discoloration
• Dermal inflammation  gray-brown discoloration
• Wood lamp examination for determining depth of hyperpigmentation
• Severity of PIH correlates
• Severity of inflammation
• Degree of basement membrane disruption
 Etiology & Pathogenesis
• Inflamatory stimulates melanocyte  PIH
• Epidermal inflammation  epidermal keratinocytes ↑
• Dermal inflammation  pigment incontinence into dermis
• Increased susceptibility of PIH ∞ increase amount of melanin in
melanosomes
 Differential Diagnosis
• Urticaria pigmentosa
• Darier sign (+)
• History of itching
 Clinical Course & Prognosis
• Depends on the location of skin
• More persistent in darker-skin types & lichenoid inflammatory processes
• Epidermal PIH: spontaneous but slow fading
 Management
• Remains difficult, important to treat primary dermatosis
• Photoprotection is important
• Pretreatment & posttreatment for physical therapies (peels & lasers)
• Gold standard: topical hydroquinone
• Hydroquinone alternatives: licorice, soy, niacinamide, kojic acid, retinoid, etc.
• Topical corticosteroids
• Epidermal PIH: more amendable to topical therapy than dermal PIH
 Reference
• Rodrigues M, Pandya AG. Hypermelanoses. In: Kang S, Amagai M,
Bruckner A, Enk AH, Margolis DJ, McMichael AJ, et al (eds.)
Fitzpatrick’s dermatology. 9th ed. New York, USA: McGraw-Hill
Education; 2019. p. 1351-89
Postinflammatory
Hypopigmentation
 Definition
• An acquired partial or total loss of skin pigmentation occurring after
cutaneous inflammation.
 Etiology
• Many cutaneous inflammatory conditions
• Pityriasis lichenoides chronica (PLC) & lichen striatur (LS): hypopigmentation >
hyperpigmentation
• Atopic dermatitis
• Cutaneous injuries: burn, irritants, dermatological procedures (chemical peels,
dermabrasion, cryotherapy, laser)
Postinflammatory hypopigmentation caused by (a) (b) psoriasis, showing multiple well-demarcated
lichen striatus, showing linear distribution of hypopigmented lesions a similar size and shape to
hypopigmented lesions along Blaschko lines; the original psoriasis lesions.

(c) Depigmentation secondary to discoid lupus
erythematosus. The lesion is obvious in dark-
complexioned skin because of the colour contrast.
(d) Hypopigmented and depigmented lesions
secondary to low fluence Q-switched 1064-nm
Nd:YAG laser therapy for melasma. The
configuration of the lesions corresponds to the size
and shape of the laser spot.
 Pathogenesis
• Limited information, not well understood
• ‘Individual chromatic tendency’
• Melanocytes can react with normal, increased or decreased melanin production
• Genetically determined
 Differential Diagnosis
• Pityriasis alba • Hypopigmented lesions in
extramammary Paget disease
• Progressive macular hypomelanosis
• Pityriasis versicolor
• Hypopigmented mycosis fungoides
• Infundibulomatosis
• Leprosy
• Hypopigmentation from medication,
• Sarcoidosis
• Potent topical corticosteroids
• Hypopigmented lesions in
• Intralesional corticosteroids
acantholytic disorders
 Investigations & Diagnosis
• Wood lamp examination
• Accentuates the lesion
• Distinguish between hypopigmented and depigmented lesions
• Exclude some conditions
• Progressive macular hypomelanosis: punctiform red fluorescence
• Pityriasis versicolor: coppery-orange
• Histopathology: nonspecific findings
 Management
• Identify the cause
• Treat underlying cause  hypopigmentation usually improves over time
• Medium-potency topical steroid in combination with a tar-based:
• Steroid may affect inflammatory cells, while tar photodynamically induce melanogenesis
• Topical pimecrolimus
• Sun or UV exposure may help, but overexposure enhance the contrast
• Topical 0.1% 8-methoxypsoralen, 0.5–1% coal tar or anthralin followed by sun
exposure
 Course & Prognosis
• Minimal hypopigmentation usually resolves within a few weeks
• Severe hypopigmentation & depigmentation require years to be
repigmented, and may be permanent
 Reference
• Vachiramon V, Thadanipon K. Postinflammatory hypopigmentation. Clin
Cosmet Investig Dermatol. 2011; 36: 708–14
Thank you