Pigmentary Disorders

Melanin synthesis occurs in melanosomes which are present in melanocytes.

Tyrosine is the precursor of melanin and tyrosinase is the enzyme involved
in melanin formation.
Usually macule/patch
Melanin Sun exposure
Melanocyte count
production effect
Ephelides  in number +
(Freckles)
Normal 
darker
B. Lentigo (Lentigines)
- A benign melanocytic skin lesion
Lentigo
Normal  - NOT typically get darker with sunlight
(Lentigines)
Lentigo Simplex Solar Lentigo (Senile Lentigo)
Melanocytic
  Simple lentigo or juvenile lentigo Senile lentigo or liver spots
Nevus
Present at birth/during childhood Seen in older individuals
 in number +
Melasma Normal  Mucous membranes, palms/soles Only in sun-exposed areas
darker (worsen)
Sign of genetic disorders when Lentigo maligna with atypical
Post
widespread: borders/growth
Inflammatory
Normal / darker (worsen)  Peutz-Jeghers Syndrome
Pigment
 Xeroderma Pigmentosa
Changes
Vitiligo  (absence) 
OCA Normal 

A. Ephelides (Freckles) Ephelides vs Lentigo

- Commonly appear during childhood
- Normal number of melanocytes with increased melanin production
- Increase in number and become darker with sun exposure  marker
for sun damage the skin
- Diagnosis: clinical diagnosis
- Treatment: sun protection and may lessen with age
Lentigo: presence at birth vs Ephelides: develop during childhood
Lentigo: not worsen with sun exposure vs Ephelides: worsen with sun
exposure
B.1. Peutz-Jeghers Syndrome
- Autosomal dominant
- Multiple lentigines on the oral mucosa and lips develop in childhood.
- Hamartomatous polyps in the small bowel  GI bleeding, GI Well-circumscribed
obstruction, intussusception +/- Hair growth

B.2. Xeroderma Pigmentosum (XP)

- Autosomal recessive – Defect in nucleotide excision repair enzyme 
cannot repair UV-induced DNA damage
- Risk for multiple skin cancers: BCC, SCC, melanoma
- Treatment: avoid all sunlight, close monitoring with skin checks
D. Melasma
(=Mask of pregnancy or chloasma)
- Benign melanocytic skin disorder of the face
- Symmetric hyperpigmented tan to brown macules and patches
- Distributions: Centro-face (forehead, cheeks, nose, upper lip, chin)

C. Melanocytic Nevus
(= Mole/nevus)
- Diagnosis: Clinical
- A benign proliferation of melanocytic nests in the epidermis or dermis
- Treatment:
Giant Congenital Melanocytic
Congenital Melanocytic Nevus  First line: sun avoidance, discontinue any culprit medications
Nevus
 Second line: hydroquinone, topical tretinoin, chemical peels
Present at birth
Low potential for malignancy Risk of neurocutaneous melanosis 
E. Post Inflammatory Pigment Changes
(small size) risk of malignant melanoma.  - Inflammation induce production and deposition of melanin OR the
Darkly pigmented, larger in size >40 cm in size drop out of melanin
than acquired nevi
 - Associated with autoimmune diseases.
Generalized
Localized Universal
(vitiligo vulgaris)
Most common, Affecting one body region: Rare, almost total
affecting > 1 - Mucosal: depigmented depigmentation
body region mucous membrane
- Focal: few isolated lesions
- Segmental: unilateral body
segment
- Acrofacial: fingers and
perioral areas
- Well-demarcated, smooth depigmented macules and patches
surrounded by normal skin

Poliosis
Depigmented hair bearing areas (even the hair)

- May darken with sun exposure

- Treatment: resolves in months to years but can persist indefinitely
Sun protection, retinoids (tretinoin) or lightening creams
(hydroquinone) to speed up the process.

F. Vitiligo - Diagnosis: clinical diagnosis (best initial test) + biopsy (most accurate)
- Acquired chronic melanocytic skin disorder. - Treatment:
- Loss of function and destruction of melanocytes  absence of  First line: consider observation with no treatment for localized disease
melanin production in affected areas
  Second line: consider oral immunosuppressive for extensive rapidly  Ophthalmology: evaluation with corrective lenses and photoprotective
progressive disease eyewear
 Can also consider total depigmentation therapy if extensive
H. Chediak-Higashi Syndrome
G. Oculocutaneous Albinism (OCA) - Defect of LYST gene causes abnormal neutrophil chemotaxis
- Autosomal recessive- Partial or total absence of melanogenesis due to - Clinical features:
tyrosinase enzyme defect 1. Immunodeficiency = recurrent infections
2. Oculocutaneous albinism
3. Neurologic problems

I. Piebaldism
- Autosomal disorder- Mutation in KIT or SNAI2 genes  defective
melanocyte development and migration during embryogenesis
- Fixed depigmented patches of skin (= leukoderma) and (hair =poliosis)

- Present from birth

- Diagnosis: clinical diagnosis
- Treatment: none

J. Café-au-lait Macules (CALMs)

- Patients have ocular dysfunction - A common birthmark
- High risk for skin cancers! - Hyperpigmented patch with sharp borders
- Diagnosis: Clinical diagnosis
- Treatment: no cure
 Photoprotection!
 Dermatology: Close monitoring for skin checks
- If more than 3 CALMs are present, may be associated with a genetic
disorder:
• Neurofibromatosis
• McCune Albright syndrome

K. Neurofibromatosis
- Autosomal dominant – Mutation in tumor suppressor genes

Skin—CALMs and Multiple cutaneous neurofibromas + Crowe’s sign

Bone—Scoliosis from bone dysplasia
CNS—Visual defects from optic nerve gliomas and iris hamartomas (Lisch
nodules)

- Diagnosis: Clinical diagnosis (best initial test) + genetic test

(confirmatory test)
o Brain MRI  intracranial tumor
 o For NF1 evaluate for Lisch nodules
o For NF2 evaluate for lenticular opacities
- Treatment: No cure