W25 UV Radiations and skin cancer Flashcards
UV Radiation reaching the Earth contains how much UVA and UVB?
Which UV penetrates deeper?
▪ 95% UVA
▪ 5% UVB
- UVA penetrates deeper
▪ Reaching the dermis (20% deep dermis) - UVB have lower penetration
▪ 70% the stratum corneum,
▪ 20% lower epidermis sublayers,
▪ 10% the dermis
What are the 3 types of UV radiation?
- UVA - Longest wavelength (320-400nm)
▪ Can pass through the ozone and clouds (even glass) - UVB - Intermediate wavelength (320-400nm)
▪ Filtered by the Ozone layer and clouds - UVC - Shortest wavelength (100-290 nm)
▪ Do not reach the Earth (absorbed by the ozone)
What does UVA cause?
higher penetration
▪ skin ageing, wrinkles
▪ Potential DNA damage → cancer risk
What does UVB cause?
lower penetration
▪ Tanning: Melanocytes stimulation to release melanin → skin pigmentation
▪ Redness: Vasoactive mediator → inflammatory responses
▪ Sunburn: At high dose, inducing keratinocyte apoptosis
▪ Vitamin D3 biosynthesis
▪ Skin cancerogenic (more than UVA) → Risk of skin cancer development
Vitamin D3 biosynthesis:
What are the 3 affecting factors that reduce the process?
- UVB photons are absorbed by 7-dehydrocholestrol (PRO-Vitamin D3) in the epidermis, which is photochemically converted into PRE-vitamin D3
o Ageing
o sunscreen
o melanin levels/skin pigmentation
- Pre-vitamin D3 undergoes a thermal isomerisation to form vitamin D3 (within 24/48h)
- Endogenous or dietary Vitamin D3 is released into the bloodstream
- Vitamin D3 can also be obtained with the diet (limited) and supplementation
Vitamin D3 synthesis
What is vitamin d3 converted into in the liver and kidneys?
- Vitamin D3 (inactive) is converted to 1,25-
dihydroxyvitamin D3 (calcitriol – active
form) by two hydroxylations in the liver and
kidneys - Calcitriol acts as a hormone:
➢ Ca++ & phosphate homeostasis in target organs
- Calcitriol acts as a hormone:
Vitamin D3 effect in the skin
What is thr role of keratinocytes?
- Keratinocytes respond to vit. D3 or analogues → psoriasis treatments
▪ They include the nuclear vitamin D receptors (VDRs)
▪ Vitamin D3 deficiency is associated with psoriasis and atopic dermatitis - Vit. D3/receptor complex acts as transcription factors
- Interacts with DNA regions to modify gene expression regulating:
▪ Reducing the proliferation rate of stem cells in S. basale
▪ Regulating keratinocytes differentiation –keratin granules and lipid
production – to maintain the skin barrier integrity
▪ Mild immunosuppression to obtain an anti-inflammatory effect
Phototherapy
What is it used to treat?
What are the 2 main forms?
- Skin treatment → controlled administration of UV radiation
➢ Psoriasis
➢ Chronic Eczema
➢ May be beneficial for acne, Vit. D3 deficiency, vitiligo - Narrowband UVB
- PUVA – Psoralen with UVA
-Typically, 2–3 times per week for 6–10 weeks until skin lesions are cleared
Typically, 2–3 times per week for 6–10 weeks until skin lesions are cleared
Narrowband UVB wavelength - (311-312 nm)
- Same effects of UVB but better tolerated and less cancerogenic
- Can be combined with topical retinoids, vit. D3 analogues, & steroids in difficult cases
PUVA → in patients who have failed to respond to UVB
* Combining Psoralen (natural phototoxic molecule) & UVA
What is the mechanism?
▪ Psoralen is taken (topically or orally) 2 hrs before UVA exposure
▪ UVA photons activate psoralen → becoming phototoxic to:
➢ interferes with DNA → reducing mitosis and keratinocytes formation
➢ Induces apoptosis in Langerhans cells → immunomodulation and anti-inflammation
Phototherapy mechanism in psoriasis
What are the 4 effects?
- Anti-inflammation effect:
Dec cytokine production
Dec keratinocyte proliferation - Keratinocytes regulation
Dec mitotic activity
Inc keratinocytes apoptosis
Activating procaspase 3 into caspase 3=
Apoptotic pathway and DNA degradation - Antipruritic effect
- Immunosuppression effect
Dec infiltration of T cells
Dec Langerhans cells activation/apoptosis
What are the Short term adverse effects of phototherapy? (5)
- Skin rash, blistering
- Nausea (only PUVA)
- Increased insensible water loss
- Bronze baby syndrome → harmless greyish-browndiscoloration of the skin
- May result in hypocalcaemia
What are the Potential long-term adverse effects of phototherapy?
- Skin ageing
- skin cancers → cancerogenic (higher risk with PUVA)
▪ PUVA is not suitable for long-term use
What is skin cancer?
- Potentially serious condition
- Three main types of cancer affecting:
▪ various cells
▪ distinct stratums of the epidermidis - Largely preventable
- Uncontrolled cell divisions of cancerous cells,
lose of cell differentiation/specialisation/shape
oncogenes and tumour suppressor genes are mutated
UV radiation contribute to DNA damage:
- Free radicals generation → DNA degradation
- UVB induce incorrect base pairing between
non-complementary bases of a duplex DNA e.g thymine and thymine
▪ Cells can repair DNA mutations, but not always
▪ Unrepaired mutations can distort DNA → breaks
▪ Altering expression or products of key genes
Pigmentation and risk of skin cancer
- Melanocytes release melanin in vesicles (melanosomes)
- Melanosomes are absorbed by keratinocytes determining skin pigmentation (different phototypes)
- Inc melanin Inc phototype Dec skin cancer risk
- Melanin can absorb UV photons and induce DNA repair
MAIN Types of Skin Cancer
What are the 2 categories? and some examples?
- Pre-Cancerous
▪ Actinic keratosis - Cancerous
▪ Squamous cell carcinoma
▪ Basal cell carcinoma
▪ Melanoma
▪ Others
What is Actinic Keratosis?
What are the clinical manifestations?
What is the treatment?
A pre-cancerous skin growth
* It might progress (as a precursor) into squamous cell carcinoma (low chance)
Clinical manifestations
* dry, rough and scaly patches (1-2 cm)
▪ body’s area often exposed to the sun
▪ face, hands and arms, ears, scalp and
legs
Treatment
* It can be removed with liquid nitrogen (cryotherapy) or surgical removal
What is Basal cell carcinoma
What is the Clinical manifestation - Warning signs?
- > 75% of all skin cancers
- mainly in middle aged/elderly individuals
- Arises in basal cells of the stratum basale
- Mostly found on face, nose, forehead, checks
- Slow-growing and very low metastasis risk
- Generally curable (surgical removal, radiation
or topical medications – e.g. fluorouracil)
Clinical manifestation - Warning signs
▪ Small, smooth, pale, or waxy shiny lump
▪ Firm, translucent red/brown lump
▪ A lump that bleeds or develops a crust
Basal cell carcinoma
What is Squamous cell carcinoma?
Whereis it found?
What is the Clinical manifestation - Warning signs? (3)
- Approx. 20% of all skin cancers
-
Occurs in squamous cells in the stratum corneous
▪ Uncontrolled division and loss of differentiation - Mostly found on ears, face, lips, mouth, hands
- Can form metastasis (less than melanoma)
▪ Cancer cells spread to a different site through the blood
Clinical manifestation - Warning signs
▪ Red scaly patch
▪ Elevated with central depression
▪ Can resemble a wart that persists
What is Melanoma?
What are risk factors?
- 5% of all skin cancers
- Arises in epidermal melanocytes
- The most aggressive skin cancer:
-treatment-refractory
-Metastasis (and invasive)-prone
-Early detection is vital - Found on many sun-exposed areas
- Most arise out of pre-existing moles
-Type and No. of moles are risk factors
What are the melanoma warning signs?
ABCDE
▪ A- Asymmetric – Irregular shape
▪ B- Borders – Irregular/ragged borders
▪ C- Colours – multiple/variety
▪ D - Diameter (>6mm)
▪ E – Evolving - change quickly in shape/elevation, itching, bleeding
For normal and abnormal features
Sun exposure protection
How can one prevent UV-adverse effects?
- Reduce sun exposure during high solar radiation:
▪ Season → e.g. summer months (central day hours)
▪ Latitude (compared to the Equator) and altitude of the area
▪ Cloud cover – Clouds cannot completely protect!
▪ Others: e.g. Ozone coverage - Physical barriers
▪ to minimise the direct exposure of the skin to sunlight
What are the uses of sunscreen preparations?
- Use of sunscreen preparations
➢ Sun Protection Factor (SPF) - UVB protection
▪ the No.is the protection level against UVB
▪ SPF30 or more is the advised
➢ A five UVA Stars rating - UVA protection
▪ 4-stars or higher is the advised
Recommendations:
➢ 6-8 teaspoons (to cover the entire body) every 2 hours
➢ Extra care for babies, moles and photodermatoses
