13.5 Changes In Skin Colour Flashcards
Determinant of skin colour
Exogenous Pigments
- Introduced from outside the body
- E.g. Through injection or ingestion
- Carotenoderma: Consumption of large amounts of fruit/ vegetables high in β-carotene such as carrot, sweet potato, and pumpkin.
- tattoos
- Ingestion of certain heavy metals such as lead can cause blue/black pigment at gum margin
Endogenous Pigments
- Produced within the body
- E.g. Melanin and breakdown of Hb
- Melanin:
➡️Major determinant of skin colour
➡️Brown pigment produced by melanocytes
➡️Found in the skin, choroid of the eye, hair, mucous membranes and meninges
- Pigments derived from Haemoglobin breakdown: Bilirubin; Haemosiderin
Dark vs Light skin number of melanocytes
- Darkly pigmented and Lightly pigmented skin have the SAME number of melanocytes
- Increased melanocyte activity (Larger melanosomes that contain more melanin)
- Decreased melanocyte activity (Smaller melanosomes that contain less melanin)
Epidermal melanin unit
Association of 1 melanocyte with 30-40 surrounding keratinocytes to which it transfers melanosomes
Melanin biosynthetic pathway
Tyrosine (aminoacid)
⬇️ Tyrosinase {metabolite}
Dihydroxyphenylalanine (DOPA)
⬇️ Tyrosinase
DOPAquinone
⬇️ Series of reactions
Melanin
Tyrosinase is the key regulatory enzyme in the melanin biosynthetic pathway, which controls the initial biochemical reactions in the pathway
UV radiation and pigmentation
Immediate pigmentary darkening
Delayed darkening
At cellular level
Immediate Pigmentary Darkening:
- Follows exposure to UVA radiation
- Occurs within minutes and fades over 20-30min
- Represents oxidation of pre-existing melanin or melanin precursors
Delayed Tanning:
- Follows exposure to UVB and UVA radiation
- Visible within 24-72 hours of exposure to UVA/UVB
- Represents new pigment formation via an ↑in tyrosinase activity
At a Cellular Level
Following a single exposure to UVR:
- ↑ size of melanocytes observed
- ↑ tyrosinase activity
Repeated exposure to UVR:
- ↑ number of melanosomes transferred to keratinocytes
- ↑ number of active melanocytes
Vitiligo
General
Pathogenesis
- Vitiligo is an acquired multifactorial disorder which results in the autoimmune destruction of melanocytes
- Presents with depigmented macules and patches in a localized or generalized distribution
- Areas of skin affected have an absence of functional melanocytes
Pathogenesis
- autoimmunity
- oxidative stress
- genetics
- enviromental factors
- melanocyte detachment from BM
- neural hypothesis
- “Convergence theory” (multiple causes)
Autoimmunity as cause of Vitiligo
General
Process
- Vitiligo has been associated with multiple autoimmune diseases such as: Hashimoto’s thyroiditis, Graves disease, T1DM, RA, Alopecia areata, Addison’s Disease
- The immune system plays a central role in the pathogenesis
- Numerous activated cytotoxic T lymphocytes have been reported in perilesional area of vitiligo skin (predominantly cytotoxic CD8 lymphocytes)
Process
Melanocyte Stress (by genetic / environmental exposures)
⬇️
Melanocyte stress signals sent via exosomes to APC’s in the skin
⬇️
Antigen presentation leads to T Cell activation in lymph nodes and production of chemokines
⬇️
Recruitment of cytotoxic CD8 T cells which attack melanocytes
⬇️
Destruction of melanocytes
⬇️
Depigmented skin
Oxidative stress as causes of Vitiligo
- Melanocytes from vitiligo patients have intrinsic defects that reduce their capacity to manage cellular stress
- Melanocytes respond to stress by releasing reactive oxygen species (ROS)
- The production and accumulation of ROS triggers DNA damage and compromises cellular function.
- Oxidative stress triggers the immune response and recruitment of T Cells
Examples of exogenous stressors:
- UV radiation, trauma, cytotoxic compounds
Example of endogenous stressor:
- Melanin synthesis itself
Oculocutaneius Albinism (OCA)
Def
Pathogenesis
Types
Def:
- Group of genetic disorders characterized by hypopigmentation due to partial or total absence of melanin in the skin, hair follicles and eyes.
- Multiple subtypes of OCA: OCA1 & OCA2 = 90% of cases
- Almost always inherited in an autosomal recessive manner
Pathogenesis
- Defect in the melanin biosynthesis pathway
- Mutations in genes that encode proteins involved in the melanin biosynthesis pathway.
- Normal number of melanocytes
- Reduction in amount of melanin present in each melanosome
Types
OCA Subtypes — Gene Mutation — Gene Product
OCA1 — TYR — Tyrosinase
OCA 2 — OCA2 — P-protein
OCA1 clinical subtypes
OCA1A
- Severe gene mutation of TYR
- Absent tyrosinase activity
- Inability to produce pigment throughout life
- Absent melanin in hair, skin, eyes
OCA1B
- Milder gene mutation of TYR
- Reduced tyrosinase activity
- Low level of pigment production throughout life
- Variable dilution in hair and skin pigment
OCA2
- Mutations in OCA2 gene (previously known as the P gene) which encodes the P-protein
- “Tyrosinase-positive” OCA (Tyrosinase is functioning normally)
- The P-protein is involved in the biogenesis of melanosomes & processing and transport of melanosomal proteins and pH-regulation that supports melanogenesis
- Melanin synthesis
Melasma
Def
RF & Triggers
- Melasma is an acquired disorder of hyperpigmentation
- Results in brown to grey macules and patches on sun exposed areas of skin
- Common, chronic and recurring disorder
- Most commonly affects females with darker skin types
RF & Triggers
- Skin Phototype: More common in skin phototype III-IV
- Sunlight Exposure: UVR and possibly visible light
- Hormonal Factors: Pregnancy, oral contraceptives, hormone therapy, hyperestrogenic states
- Genetic Predisposition: Strong familial occurrence, especially in 1st degree relatives
- Medications: Photosensitizing drugs, anti-epileptics e.g. phenytoin
Melasma
Pathogenesis
- Hyperpigmentation arises from hyperfunctional melanocytes that deposit an excess amount of melanin in the dermis and epidermis
- Normal number of melanocytes but larger number of melanosomes in affected skin
UVR plays an important role in melasma pigmentation
- Induces the production of alpha-melanocyte stimulating hormone
- Can directly stimulate melanocytes and increase melanin production.
- Chronic UVR can cause damage to the basement membrane of epidermis
→Basement membrane disruption: Penetration of melanocytes and melanin into the dermis
Pityriasis vesicular
Def
Def
- Common, benign, superficial fungal infection of the skin
- Caused by Malassezia spp, a dimorphic lipophilic fungus which forms part of the normal skin flora
- Results in dyspigmentation of the skin affected
- Presents with multiple oval-round macules/patches/plaques with fine scale which can be:
• Brown/hyperpigmented
• White-tan/hypopigmented
• Pink
Dimorphic fungus = a fungus that can grow both in a yeast form and a mycelial form
Lipophilic = Lipids essential for growth
Pityriasis Versiculor
Pathogenesis factors
Clinical presentation
- Clinical disease occurs when the round yeast of Malassezia transforms to the mycelial form (hyphae)
- Factors that may promote this conversion include:
• High temperature and humid climate
• Oily skin
• Excessive sweating
• Immunodeficiency
• Poornutrition
• Pregnancy
• Corticosteroid use
• Use of bath oils/skin lubricants may encourage Malassezia growth (because the yeast is lipophilic)
• Not due to poor hygiene
Clinical presentation
1. Brown or Hyperpigmentation:
- The yeasts induce enlarged melanosomes within
the melanocytes with subsequent increased melanin production.
- Underlying mechanism not known.
2. White-tan or Hypopigmentation:
- Chemicals (dicarboxylic acids) are produced by Malassezia (via metabolism of surface lipids) which diffuses into the epidermis and impairs the function of melanocytes and synthesis of melanin
3. Pink:
- Secondary to mild inflammation of the epidermis caused by Malassezia or its metabolites
