Pigmentary Disorders Introduction😊

Pigmentary Disorders Introduction

• Include all disorders associated with pigmentation.

• Terms:
• Hypopigmentation:
• Decrease or little loss of pigmentation.
• Depigmentation:
• No pigment;
• complete absence.
• Hyperpigmentation:
• Increase in pigmentation.

Fitzpatrick scale grades skin types (1 to 6):

• Type 6: Black.
• Always tans.
• Never burns.

• Type 1: Very fair.
• Tends to burn.
• Never tans.

Melanin and Skin Colour

• Melanocytes transfer melanin via melanosomes to 36 keratinocytes.
• Called the epidermal melanin unit.

• Skin colour is not dependent on melanocyte number.

Melanin types:

• Eumelanin:
• Brown or black.
• Protective.
• Helps to tan, protects from sunburns.

• Pheomelanin:
• Orangish or yellowish.
• More in lighter skin types.
• Not protective.
• Causes burning.
• Mnemonic: Fo means fake (not helping).

Skin colour depends on:

• Type of melanin.

• Number of melanosomes.

• Distribution of melanosomes.

• Mnemonic: Solely depends on somes

Patients with light skin:

• Melanocytes present in clusters.

Patients with dark skin:

• Individual melanosomes are larger.

Hyperpigmentary Disorders

Cafe au Lait Macule (CALM)

• Hyperpigmented lesion: Single or multiple.

• "Coffee on milk".

• Present at birth.

• Typically has a serrated border.

• Basic defect: Increased number of melanosomes.

• Mnemonic: Cafe () coffee (Coffee on milk) → In Coast of California and Maine ()

Types:

Acquired Melanocytic Nevi (Moles)

• Commonly seen on faces and other body parts.

• Defect: Some proliferation of nevi cells in the epidermis.

Types:

• Junctional nevi:
• Nevi cells proliferating at dermo-epidermal junction.
• Black in colour and more flat.
• Highest tendency to turn into a melanoma among acquired melanocytic nevi.

• Dermal nevi:
• Nevi cells in the dermis.
• Actually skin-coloured or lightly coloured.

• Compound nevi:
• Present in both junction and dermis.
• More raised and hyperpigmented.
• Not as black as junctional nevi.

Congenital Melanocytic Nevi

• Usually present at birth.

• Usually single lesions.

• Associated with hypertrihosis 
• excessive hair growth

• Rubosities are present.

Large congenital nevi

• covering whole/part of trunk

• Called bathing trunk or garment nevi.

• High tendency to develop into a melanoma.

Note:

• Becker's nevi
• hypertrihosis at adolescence, not birth.

Dermal Melanocytic Nevi

• Pigment in dermis appears bluish due to Tyndall effect.
• Smaller wavelengths (violet/indigo) reflected.
• (Epidermal → brown)

Mongolian Spots:

• Bluish spot, usually in sacral area.

• Typically seen in Mongoloid races.

• Present at birth.

• till 2 years

• No treatment needed

Nevus of Ota:

• Bluish lesions in conjunctiva and forehead

• Unilateral.

• Also called Nevus fuscoceruleus ophthalmo-maxillaris.

• More common in Japanese population.

• Present along ophthalmic and maxillary division of trigeminal nerve.

• Associated with scleral deposits of pigmentation.

• Mnemonic: Otta kannu

Nevus of Ito:

• Bluish lesions.

• Present along acromial and clavicular nerve distribution (branches of brachial nerve).

• Will be on shoulders and upper back.

• Also called Nevus fuscoceruleus acromio-clavicularis.

• All dermal melanocytic nevi are asymptomatic lesions.

Nevus of Ota and Nevus of Ito

• Treated using lasers.
1. Alexandrite
2. Ruby
3. Q-switched Nd : YAG (pigment-specific).

Melasma

• Melasma → Most common pigmentary disorder → photoexposed areas → Sun exposure, Pregnancy (chloasma), OCP use, Hypothyroidism → Always hyperpigmented macules → Sunscreen is a must → Topical depigmenting agents → Triple combination cream (Hydroquinone (depigmenting),Tretinoin (exfoliating),Mild steroid )→ Kligman's formula → Oral Tranexamic acid → Q-switched Nd:YAG

• Classical predisposing factors:
• Sun exposure.
• Pregnancy (chloasma).
• OCP use.
• Hypothyroidism.

• ESTROGEN

• Most common pigmentary disorder.

• Typically in photoexposed areas.

Pathogenesis:

• Melanocytes become 
• hyperactive
• larger
• more dendritic
• produce more melanin

Presentation

• Always hyperpigmented macules.

• Asymptomatic.

Types (based on site):

• Centrofacial.

• Malar.

• Mandibular.

Types (based on depth of pigmentation):

Types	Appearance
Epidermal melasma	Mainly epidermal.
Dermal melasma	Mainly dermal, appears bluish.
Mixed melasma	Both epidermal and dermal.

Diagnosis/Differentiation:

• Wood's lamp.

Treatment:

• Sunscreen is a must

• Topical depigmenting agents:
• Hydroquinone.
• Kojic acid.
• Arbutin.
• Glycolic acid.

• Triple combination cream:
• Kligman's formula.
• Combines:
• Hydroquinone (depigmenting).
• Tretinoin (exfoliating).
• Mild steroid (hydrocortisone, for inflammation).

Oral treatment:

• Tranexamic acid (also topical).

Peels:

• Glycolic acid, lactic acid, others.

Lasers:

• Mostly Q-switched Nd:YAG or other pigmentary lasers.

Depigmentary/Hypopigmentary Disorders

Nevus Depigmentosus

• Is stable:
• Does not increase in size
• (only proportional to body growth).

• Type of nevi with depigmented to hypopigmented macule.

• Present since birth (congenital).

• Commonly confused with vitiligo.

Unlike vitiligo:

• Usually a single lesion.

• Present since birth.

• Localized to one area.

• Does not grow/spread.

• Totally asymptomatic.

Nevus Anemicus

• Presents with depigmented lesion.

• A pharmacological nevi 
• not congenital
• Capillaries hyper-responsive to catecholamines:
• Leads to vasoconstriction and pale appearance.

Differentiation from Nevus Depigmentosus:

Test: Diascopy 

• blanch with glass slide

• When blanched, further vasoconstriction.

• Margins will merge with normal surrounding skin.

• Margins will not change.

• Not dependent on vasoconstriction.

Albinism

• A congenital disorder.

• Universal absence of eumelanin synthesis.

• Skin, hair, and eyes all affected.

• Also called "albino kids".

Types:

• Ocular Albinism:
• Affects just the ocular area.
• X-linked recessive.

• Oculocutaneous Albinism (OCA):
• Autosomal recessive.
• Kids are also called albino kids.

Further divided:

• Tyrosinase negative (OCA1):



• No tyrosinase (important for eumelanin synthesis).
• Patient will never have pigmentation.

• Tyrosinase positive (OCA2):



• Some tyrosinase activity.
• At birth, complete pigment loss from hair, eyes, skin.
• Gradually patient will get some pigmentation.

Complications:

• Since melanin is protective, OCA patients are prone to:
• Sunburn.
• Seborrheic keratosis.
• Skin cancers.
• Malignancies.

• Genetic disorder with no treatment.

Piebaldism

• Inherited in an autosomal dominant pattern.

• Defect: 
• Mutation in the KIT gene on chromosome 14.

• Mnemonic:
• Bald → dominant → father to son
• when 14 yr old (CHr 14)
• Pie → Need KIT (KIT gene) to make

Clinical Features:

• Isolated congenital leukoderma or white skin.

• Typically present in a distinct ventral midline pattern.

Classical features

1. Pie-shaped area of depigmentation
• Typically present in median and paramedian area.

2. islands of sparing/normal pigmentation.

3. white hair or poliosis.

Differentiation from other syndromes:

NOTE:

ㅤ	Waardenburg Syndrome
ㅤ	• White forehead • Piebaldism + • Dystopia canthorum • Cochlear deafness. • Heterochromia iridis. Bald (Piebald) ayittulla Wardernu (Wardenburg) Vote kodutha Aarada (Vogt Harada)
ㅤ	Vogt Koyanagi Harada (VKH) Syndrome:
CF	• Granulomatous Panuveitis
Age	• Third or fourth decade
Signs	• Sunset glow fundus • Perilimbal Vitilligo: Suiguira sign
3 Phases	1. Meningoencephalitic phase (Distinguished) 2. Uveitis and Choroiditis (Distinguished) 3. Leukoderma, poliosis, and alopecia
ㅤ	Sympathetic ophthalmitis
CF	• Granulomatous Panuveitis
Signs	• Retrolental Flare • Dalen Fuchs nodules
Pathology	ㅤ
↳ Exciting Eye	• Eye that sustains initial injury. • Penetrating Trauma • Affecting ciliary body
↳ Sympathizing Eye	• The fellow eye, not initially injured. • Develops after 2 weeks (>2 weeks) from initial trauma.
Treatment	• Steroids
Prevention	• Enucleation of the traumatic eye within 14 days

• Granulomatous Panuveitis seen in
• Sympathetic Ophthalmitis
• VKH syndrome

• Wardenberg syndrome

• Wartenburg sign
• Involuntary abduction of little finger at rest
• Loss of hypothenar function → Digiti minimi

• Wartenburg syndrome
• Radial cutaneous nerve
• Also called Cheiralgia paresthetica.
• Both Warts in Hand

---

Type	Cause
Posterior	• Lowe syndrome ↳ Oculo Cerebro Renal syndrome • Opacity at posterior capsule center
Anterior	SAW Spina bifida Alport syndrome Waardenburg syndrome

---

Fuchs Terms	Notes
Fuchs heterochromia iridocyclitis	Chronic AU ⇒ • U/L Diffuse Iris atrophy + Heterochromia + Posterior SCC • Painless, No redness, No posterior synechiae Positive Amsler's Sign: ◦ Bleeding into Anterior chamber on paracentesis ◦ Without trauma to Iris/Angle ◦ D/t abnormal fragile Iris Stellate Keratin Precipitates ↳ Herpetic uveitis ↳ Toxoplasmosis ↳ Fuchs Heterochromia Iridocyclitis • Young stella → Fucked () by Toxic () Herpes () Guy
Dalens Fuchs	• Seen in Sympathetic ophthalmitis ↳ (granulomatous panuveitis) • Dalen Fucked Granny () sympathetically ()
Foster Fuchs	• In Pathological Myopia • Bleeding at macula • Fucking in Foster () home ↳ Blind child (Pathological myopia) ↳ Bled (Bleeding at macula)
Fuchs Endothelial dystrophy	• Cornea guttata: • Wart-like excrescences on posterior cornea • Fuck her Guts→ endothelial Stages • Stage 1: Central corneal guttata that spreads peripherally • Stage 2: Corneal oedema - beaten metal-like appearance • Stage 3: Bullous keratopathy • Stage 4: Subepithelial scarring and superficial vascularization

 

Vitiligo

• T-cells mediated autoimmune destruction of melanocytes → melanocytopenia.

• Has a positive family history (20-30%).

• Presents with depigmented macules.
• Asymptomatic.
• Not raised.
 

• Commonest association: 
• Thyroiditis
• especially Hashimoto's thyroiditis.
• Pernicious anemia, Type 1 DM, others.

Theories for pathogenesis:

• Genetic disorder:
• Defect in catalase gene.

• Immune hypothesis:
• Autoimmune disorder.

• Autotoxic, self-destructive, or free radical hypothesis:
• Products self-destroy, leading to loss.
• Depigmented macules + leukotrichia or white hair.

Levels of pigmentation:

• Trichrome vitiligo:
• Three layers (depigmented, hypopigmented, hyperpigmented).

• Quadrichrome vitiligo:
• Four zones (trichrome + perfollicular pigmentation).

• Shows positive Koebner phenomenon (isomorphic phenomena).

Types:

Segmental Vitiligo:

• Probably neurogenic hypothesis holds true.
• Neural hypothesis:
• Certain neurotransmitter causes melanocytopenia.
• Especially true for segmental vitiligo.

• Has a stable course;
• usually does not spread.
• Intially grows → then stops progressing
• Does not show Koebner phenomenon.

• Presentation
• Since childhood.
• Depigmented lesion
• along a segment or dermatome.

• A/w leukotrichia.

Treatment

• Does not respond to medical treatment.

• Usually requires surgical treatment.

Non-Segmental Vitiligo:

Focal:

• Single or two-three lesions in a foci, or just mucosal vitiligo.

Generalized or Diffused:

Three forms:

• Vitiligo Vulgaris:
• Bilateral symmetrical depigmented lesions.
 

• Acro facial Vitiligo/ Lip tip variant:
• Acral areas (hands, feet, face),
• mucosal involvement.
• Poor prognosis, poor treatment response.

• Vitiligo Universalis:
• Almost >90% of body surface area depigmentation.
• Repigmentation difficult; 
• Monobenzyl ether of hydroquinone (MBH) 
• Reverse treatment 
• used for depigmenting.
• Causes depigmentation of remaining 10%.

Treatment:

• General treatment:
• Topical agents: Localized disorder
• Topical tacrilimus
• Corticosteroids,
• topical calcineurin inhibitors.
• Avoiding Koebner phenomenon.
• Avoid trauma, rubber chappals, any trauma.

• Topical phototherapy.
• Phototherapy:
• NB-UVB, PUVA, excimer lasers (targeted).

• Medical treatment:
• Systemic agents:
• Steroids.
• Cyclophosphamide.
• Azathioprine.
• Levamisole.
• JAK inhibitors: Tofacitinib.

• Surgical treatments:
• For stable patches not repigmenting.

1. Topical tacrolimus

2. Clobetasol

3. Isotretinoin

4. PUVA

Chemical Leukoderma

• Presents similar to vitiligo.

• Lesions in area exposed to a chemical.
• Depigmented patches at site of contact.

Common examples and agents:

NOTE:

ㅤ	Waardenburg Syndrome
ㅤ	• White forehead • Piebaldism + • Dystopia canthorum • Cochlear deafness. • Heterochromia iridis. Bald (Piebald) ayittulla Wardernu (Wardenburg) Vote kodutha Aarada (Vogt Harada)
ㅤ	Vogt Koyanagi Harada (VKH) Syndrome:
CF	• Granulomatous Panuveitis
Age	• Third or fourth decade
Signs	• Sunset glow fundus • Perilimbal Vitilligo: Suiguira sign
3 Phases	1. Meningoencephalitic phase (Distinguished) 2. Uveitis and Choroiditis (Distinguished) 3. Leukoderma, poliosis, and alopecia
ㅤ	Sympathetic ophthalmitis
CF	• Granulomatous Panuveitis
Signs	• Retrolental Flare • Dalen Fuchs nodules
Pathology	ㅤ
↳ Exciting Eye	• Eye that sustains initial injury. • Penetrating Trauma • Affecting ciliary body
↳ Sympathizing Eye	• The fellow eye, not initially injured. • Develops after 2 weeks (>2 weeks) from initial trauma.
Treatment	• Steroids
Prevention	• Enucleation of the traumatic eye within 14 days

• Granulomatous Panuveitis seen in
• Sympathetic Ophthalmitis
• VKH syndrome

• Wardenberg syndrome

• Wartenburg sign
• Involuntary abduction of little finger at rest
• Loss of hypothenar function → Digiti minimi

• Wartenburg syndrome
• Radial cutaneous nerve
• Also called Cheiralgia paresthetica.
• Both Warts in Hand

---

Type	Cause
Posterior	• Lowe syndrome ↳ Oculo Cerebro Renal syndrome • Opacity at posterior capsule center
Anterior	SAW Spina bifida Alport syndrome Waardenburg syndrome

---

Fuchs Terms	Notes
Fuchs heterochromia iridocyclitis	Chronic AU ⇒ • U/L Diffuse Iris atrophy + Heterochromia + Posterior SCC • Painless, No redness, No posterior synechiae Positive Amsler's Sign: ◦ Bleeding into Anterior chamber on paracentesis ◦ Without trauma to Iris/Angle ◦ D/t abnormal fragile Iris Stellate Keratin Precipitates ↳ Herpetic uveitis ↳ Toxoplasmosis ↳ Fuchs Heterochromia Iridocyclitis • Young stella → Fucked () by Toxic () Herpes () Guy
Dalens Fuchs	• Seen in Sympathetic ophthalmitis ↳ (granulomatous panuveitis) • Dalen Fucked Granny () sympathetically ()
Foster Fuchs	• In Pathological Myopia • Bleeding at macula • Fucking in Foster () home ↳ Blind child (Pathological myopia) ↳ Bled (Bleeding at macula)
Fuchs Endothelial dystrophy	• Cornea guttata: • Wart-like excrescences on posterior cornea • Fuck her Guts→ endothelial Stages • Stage 1: Central corneal guttata that spreads peripherally • Stage 2: Corneal oedema - beaten metal-like appearance • Stage 3: Bullous keratopathy • Stage 4: Subepithelial scarring and superficial vascularization