Changes In Skin Colour Flashcards
1
Q
Determinants of skin colour
A
Exogenous pigments
- introduced from outside (injection/ingestion)
Endogenous pigments
- produced within (melanin & breakdown of Hb)
2
Q
Exogenous pigments
A
Carotenoderma
- consumption of large amounts of fruit/ veg high in beta-carotene eg: carrot, sweet potato & pumpkin
Tattoos
Ingestion of certain heavy metals eg: blue/black pigment at gum margin
3
Q
Endogenous pigments
A
Melanin
- determinant = skin colour
- brown pigment produced by melanocytes (pigment producing cells)
- skin, choroid of eye, hair, mucous membranes & meninges
Pigments from haemaglobin breakdown
- bilirubin
- haemosiderin
4
Q
Melanocytes
A
- dendritic cells in basal layer of epidermis
- intracytoplasmic organelles = melanosomes
- melanosomes = site of melanin synthesis, deposition & transportation to keratinocytes
- Epidermal melanin unit = association of 1 melanocyte with 30-40 surrounding keratinocytes to which transfers melanosomes
- darkly & lightly pigmented skin = same number of melanocytes
Dark = increased melanocytes activity, larger melanosomes - more melanin
Light = decreased melanocytes activity, smaller melanosomes - less melanin
5
Q
Melanin bio synthetic pathway
A
- Tyrosine (amino acid) (=metabolized by enzyme tyrosinase to = DOPA, further metabolised form DOPAquinone
TYROSINASE (key regulatory enzyme = controls initial biochemical reactions , no = no melanin) - Dihydroxyphenylalanine
TYROSINASE - DOPAquinone
SERIES OF REACTIONS - melanin
6
Q
Immediate pigmentary darkening
A
- follows exposure to UVA radiation
- Within minutes & fades over 20-30min
- oxidation of pre-existing melanin/ melanin precursors
7
Q
Delayed tanning
A
- follow exposure to UVB & UVA radiation
- visible within 24-72hrs of exposure to UVB/UVA
- new pigment formation via increase in tyrosinase activity
8
Q
Single exposure to UVR (cellular level)
A
- increase size of melanocytes observed
- increased tyrosinase activity
9
Q
Repeated exposure to UVR (cellular level)
A
- increase number of melanosomes transferred to keratinocytes
- increased number of active melanocytes
10
Q
Vitiligo
A
- acquired multifactorial disorder = autoimmune destruction of melanocytes
- depigmented macules & patches in localized/ generalized distribution
- areas of skin affected = absence of functional melanocytes
11
Q
Vitiligo Pathogenesis
A
- multi factorial
- autoimmunity
- genetics
- oxidative stress
- environmental factors (exposure to chemicals)
- melanocytes detachment from BM
- neural hypothesis (nerve ending near pigment cells in epidermis, release cytotoxic neurochecmical mediators = melanocyte destruction)
- “convergence theory” (multiple mechanisms = melanocyte destruction & loss)
12
Q
Autoimmunity (vitiligo Pathogenesis)
A
- associated autoimmune diseases: Hashimoto’s thyroiditis, Graves’ disease, TiDM, RA, Alopecia areata, Addison’s disease
- immune system = central role in Pathogenesis
- numerous activated cytotoxic T lymphocytes = perilesional area of vitiligo skin (mainly cytotoxic CD8 lymphocytes)
13
Q
Autoimmunity process(vitiligo Pathogenesis)
A
- Genetic factors, environmental exposures
- Melanocytes stress
- Melanocyte stress signals sent via exosomes to APCs in skin
- Antigen presentation leads to T cell activation in lymph nodes & production of chemokines
- Recruitment of cytotoxic CD8 T cells which attack melanocytes
- Depigmented skin
14
Q
Oxidative stress (vitiligo Pathogenesis)
A
- melanocytes from vitiligo patients have intrinsic defects = reduce capacity to manage cellular stress
- melanocytes respond to stress by releasing reactive oxygen species (ROS)
- production & accumulation of ROS triggers DNA damage & compromises cellular function
- oxidative stress tiggers immune response & recruitment of T cells = destruction of melanocytes
15
Q
Examples of exogenous stressors
A
- UV radiation
- trauma
- cytotoxic compounds
16
Q
Examples of endogenous stressor
A
- Melanin synthesis itself
- melanogenesis can be toxic to melanocytes itself = energy consuming process performed by melanocytes
17
Q
Oculocutaneous Albinism (OCA)
A
- group of genetic disorders = hypopigmentation due to partial / total absence of melanin in skin, hair follicles & eyes
- multiple subtypes of OCA: OCA1 & OCA2 = 90% of cases
- almost always inherited in autosomal recessive manner
18
Q
OCA Pathogenesis
A
- defect in melanin biosynthesis pathway
- mutations in genes that encode proteins involved in pathway
- normal number of melanocytes
- reduction in amount of melanin present in each melanosomes
19
Q
OCA 2
A
- mutations in OCA2 gene encodes the P-protein
- “tyrosinase-positive” OCA (tyrosinase normal, p protein problem)
- P-protein is involved in the biogenesis of melanosomes & processing & transport of melanosomal proteins & pH-regulation that supports melanogenesis
- without p protein = melanin synthesis impaired
20
Q
OCA1A
A
- OCA1 = TYR (gene mutation) * tyrosinase (gene product)
- severe gene mutation of TYR
- absent tyrosinase activity
- inability to produce pigment throughout life
- absent melanin in hair, skin, eyes
21
Q
OCA1B
A
- milder gene mutation of TYR
- reduced tyrosinase activity
- low level of pigment production throughout life
- variable dilution in hair & skin pigment
22
Q
Melasma
A
- acquired disorder of hyperpigmentation
= brown to grey macules & patched on sun exposed areas of skin - common, chronic & recurring disorder
- mostly commonly affects females with darker skin types
23
Q
Risk factors & triggers of melasma
A
- multifactorial
- genetic predisposition (familial, 1st degreee relatives)
- sunlight exposure (UVR & visible light) NB
- skin phototype (skin phototype III-IV, medium pigmented)
- hormonal factors (pregnancy, oral contraceptives, hormone therapy, hyperestrogenic states)
- medications (photosentizing drugs, anti-epileptics eg: phenytoin)
24
Q
Melasma Pathogenesis
A
- hyperpigmentation arises from hyper functional melanocytes that deposit an excess amount of melanin in dermis & epidemis
- normal number of melanocytes, larger number of melanosomes is affected skin
UVR plays NB role in Melasma pigmentation - induces production of alpha-melanocyte stimulating hormone
- directly stimulate melanocytes & increase melanin production
- chronic UVR = damage to BM of epidermis: penetration of melanocytes & melanin into dermis
Increased number of mast cells in skin - UVR triggers release of histamine from mast cells & histamine bind to H2 receptors in skin = activating tyrosinase pathway = melanogenesis
Chronic UV exposure increases vascularisation of Melasma lesions = pigmentation within skin
25
Q
Pityriasis versicolor
A
- common, benign, superficial fungal infection of skin
- Malassezia spp, dimorphic lipophilic fungus (grow both in yeast form & mycelial form) which forms part of normal skin flora
= dyspigmentation of skin - presents multiple oval-round macules/ patches/ plaques with fine scale
— brown/ hyperpigmentation
— white-tan/ hypopigmented
— pink/ erythematous
26
Q
Pityriasis versicolor Pathogenesis
A
clinical disease occurs when round yeast of Malassezia transforms to mycelial form (hyphae)
Factors may promotes conversion
- high temp & humid climate
- oily skin
- excessive sweating
- immunodeficiency
- poor nutrition
- pregnancy
- corticosteroids use
- bath oils/skin lubricants = Malassezia growth (yeast lipophilic)
- not poor hygiene
- “spaghetti & meatball”
- organism found both yeast (spore) & filamentous (hyphal) form
27
Q
Brown/ hyperpigmentation in PV
A
- yeasts induce enlarged melanosomes within melanocytes = increases melanin production
- Underlying mechanism not known
28
Q
White-tan/ hypopigmentation in PV
A
- chemicals (dicarboxylic acids) = produced by Malassezia (metabolism of surface lipids)
= diffuses into epidermis & impairs function of melanocytes & synthesis of melanin
29
Q
Pink in PV
A
- secondary to mild inflammation of epidermis caused by Malassezia or its metabolites
30
Q
Post-lesional changes in skin colour
A
- secondary to variety of insults to skin: cutaneous inflammation, physical/chemical injuries
- hyperpigmentation = inflammatory causes, eg: acne vulgaris, atopic dermatitis, impetigo, insect bites, lichen simplex chronicus
- Hypopigmentation = iatrogenic causes, eg: medical procedures such as biopsies, cryotherapy, intralesional steroids, laser therapies, surgical procedures
- depigmentation = injury type cause, eg: thermal/chemical burns, lacerations (physical/chemical injury)
31
Q
Variations in post-lesional changes in skin colour
A
- same insult, but one patient presents with hypo & hyper
- variation in individual response to trauma/inflammation = not well understood
- individual’s genetic tendency or inheritable traits
- thought = robust melanocytes react with increased melanin production= hyperpigmentation
- less robust melanocytes = susceptible to damage = hypopigmentation
- greater frequency, severity, duration of PIH (post inflammatory hypo/hyperpigmentation) is darkly pigmented skin
32
Q
Post-lesional hyperpigmentation Pathogenesis
A
- acquired excess of melanin pigment following cutaneous inflammation/ injury
- inflammatory mediators (eg: prostaglandins) enhance pigment production
Epidermal = increased melanin production &/ transfer keratinocytes
Dermal = melanin enters dermis via damaged basement membrane, phagocytosed & subsequently resides within dermal macrophages (melanophages)
(Grey to blue/brown discoloration of skin)
33
Q
Post-lesional hypopigmentation & depigmentation
A
- cutaneous inflammation may inhibit melanogenesis & inhibit transfer of melanosomes to keratinocytes
- severe inflammation = loss of functional melanocytes/ melanocyte death = depigmentation & permanent pigmentary changes
34
Q
Leprosy
A
- slowly progressive infectious disease = Mycobacterium leprae
- granuloma formation in nerves & skin
- primary skin lesions = hypopigmented/ erythematous & often anaesthetic (lack sensation)
- cutaneous hypomelanotic macules = earliest expression of leprosy
- lepromatous & tuberculoid
3 things
1. Contagious person
2. Close/intimate contact
3. Susceptible person (genetic)
35
Q
Leprosy Pathogenesis
A
- M.Leprae: intracellular acid-fast bacillus = predilection for macrophages & Schwann cells
- grows best in cooler temps = predilection for skin & peripheral nerves close to skin
- spread nasal & oral droplets
- inoculation via nasal mucosa or less commonly through breaks in skin barrier
- Average incubation period: 4-10 years (ranges 6months-20years)
- majority of exposed individuals do not develop disease = genetic factors increase susceptibility to develop disease
- certain animals are environmental reservoir of leprosy
36
Q
Hypopigmentation due to leprosy
A
- mechanism of hypopigmentation in leprosy not well understood
- hypothesized that patients with leprosy = lack tyrosine cause by overuse of amino acid by M. leprae
- alternative hypothesis for hypopigmentation is disruption in transfer of melanosomes to keratinocytes
