Week 3 - D - Skin Types, UV exposure, Excision repair, Xeroderma pigmentosum, Albinism, Immunosuppression & Vitiligo

Question 1

UV radiation being a risk factor depends on both the person’s sun sensitivity and the duration/type of UV exposure What does skin colour indicate? What are the 6 different Fitzpatrick skin types?

Answer 1

Skin colour indicates how sensitive you are to sun and the risk for getting skin cancer

I - always burns, never turns

II - usually burns, can tan

III - always tans, can burn

IV - always tans, rarely burns

V - brown skin

VI - black skin

Question 2

What type of UV exposure is related to the different types of skin cancers?

Answer 2

Squamous cell carcinoma - chronic cumulative UV exposure - usually in outdoors workers

Melanoma and basal cell carcinoma - associated with intermittent burning episodes of sun exposure

UV beds - increases risk of all three and accelarates skin ageing - photoageing

Question 3

What is the principle carcinogenic UV ray and by how many more times if the sun was overhead? How do the UV rays and UVB rays affect the skin?

Answer 3

UVB rays are approx 1000 times more damaging if overhead a person than UVA rays

* UVB (290-320nm) is the principle carcinogen for damaging DNA and does this directly

* UVA induces DNA damage indirectly via oxidative damage UVB rays are more superficial. UVA rays penetrate deeper.

Question 4

How is the induced damage to the DNA by UVB and UVA rays usually repaired?

Answer 4

Excision repair: Damage to one or a few bases of DNA is often fixed by removal (excision) and replacement of the damaged region.

UVB - nucleotide excision repair.

In nucleotide excision repair, a patch of nucleotides is removed.

UVA - base excision repair

In base excision repair, the damaged base is removed.

Question 5

What is an example of a condition that affects the DNA excision repair mechanism? What is the mode of inheritance?

Answer 5

Xeroderma pigmentosum - autosomal recessive condition

Question 6

What is xeroderma pigmentosum? How does it increase the risk of skin cancers?

Answer 6

Xeroderma pigmentosum (XP) is a very rare skin disorder where a person is highly sensitive to sunlight, has premature skin ageing and is prone to developing skin cancers.

Xeroderma pigmentosum is caused by cellular hypersensitivity to ultraviolet (UV) radiation, as a result of a defect in the DNA repair system

(specifically the nucleotide excision repair system - repairs damage DNA from UVB rays)

Question 7

What are the symptoms of xeroderma pigmentosum?

Answer 7

Increased photosensitivity - usually a history of acute sunburn on minimal UV exposure with diffuse and prolonged erythema

The majority will have developed solar lentigines by the age of 2, and dryness (hence xeroderma) atrophy and telangiectases, and actinic keratoses

Neurological degenration but not well understood

Question 8

What is the genetic condition characterised by the congenital absence of melanin? What systems are affected here? What is the mode of inheritance?

Answer 8

Albinism (aka oculocutaneous albinism) is a genetic condition characterised by the congenital complete or partial absence of melanin in the skin, hairs and eyes It is autosomal recessive in inheritance

Question 9

What caused the genetic condition albinism? What are the symptoms/signs of the condition?

Answer 9

It is caused due to the absence or defects in tyrosinase (which synthesises melanin from tyrosine)

Symptoms usually are

• * Lack of pigment leads to completely white
• * Increased sun-sensitivity,
• * Increased skin cancers
• Visual defects
• * Photophobia
• * Nystagmua
• * Ambylopia (lazy eye)

Question 10

Inflammatory bowel disease increases the risk of skin cancer Which type of skin cancer? Which type of IBD is associated with a higher percentage increase in the risk?

Answer 10

Ulcerative cololitis - 23% higher risk of malignant melanoma

Crohn’s disease - 80% higher risk of malignant melanoma

Question 11

Immunosuppressants also increase the risk of skin cancer Which skin cancer type is increased the most after organ transplant?

Answer 11

Squamous cell carcinomas are the most common skin cancer type seen in immunosuppressed organ transplant patients (thought to be due to increased HPV risk in these patients)

Question 12

What are 4 different important measures that can taken to aid in skin cancer prevention?

Answer 12

* Behaviour

• * Avoid sun at its height and avoid sunbeds
• * Use shade whenever possible Clothing
• * tightly woven, loose fitting, long clothing

Sunscreens

• * broad spectrum with UVA protection
• * Apply twice in sufficient quantity

Regular (self) surveillance

Question 13

What is vitiligo?

Answer 13

Vitiligo is an acquired, chronic depigmentation disorder characterized by white patches on the skin.

It is classified according to its distribution and extent.

It is thought to be multifactorial

Question 14

What are the two types of vitiligo and which is more common?

Answer 14

Non-segmental vitiligo - typically has a bilateral and symmetrical appearance and accounts for the majority of cases (up to 90%)

Segmental vitiligo - typically has a dermatomal distribution - it less common and usually presents in children if the cause

Question 15

What is thought to be the cause of vitiligo?

Answer 15

In non-segmental vitiligo (the most common), the cause is thought to be due to autoimmune destruction of melanocytes causing depigmented macules and patches on the skin

In segmental vitiligo (known as segmental because it typically only affects a segment of the body), it is thought to be neuronal — certain neurochemical mediators released from nerve endings in the epidermis become toxic to melanocytes.

Question 16

What conditions are vitiligo assoicated with?

Answer 16

Personal or family history of other autoimmune diseases.

Thyroid disease is the most common group of autoimmune conditions associated with vitiligo, in particular Hashimoto’s thyroiditis.

* Other associated autoimmune conditions include Addison’s disease, pernicious anaemia, systemic lupus erythematosus, discoid lupus, diabetes mellitus, alopecia areata,

Question 17

What is thought to trigger the onset of vitiligo?

Answer 17

Triggers include

Emotional stress

Hormonal changes following pregnancy skin damage, such as severe sunburn or cuts (this is known as the Koebner phenomenon ) exposure to certain chemicals

Question 18

What are associated symptoms of vitiligo other than the skin depigmentation? How is vitiligo diagnosed?

Answer 18

Without treatment, individual lesions usually enlarge over time and patches may merge to form extensive geographical patterns.

Itch often accompanies the developing patches - usually if suburn

Vitiligo is a clinical diagnosis

Question 19

What is advised with regards to sunburn for patients with vitiligo?

Answer 19

Because of a lack of melanin, your skin will be more vulnerable to the effects of the sun.

Make sure you use a strong sunscreen to avoid sunburn.

Vitiligo may also be associated with eye problems, such as inflammation of the iris, inflammation of the middle layer of the eye (uveitis), and a partial loss of hearing (hypoacusis).

Problems with confidence and self-esteem are common in people with vitiligo, particularly if it affects areas of skin that are frequently exposed.

Question 20

If vitiligo is severe or making you unhappy, you may want to consider treatment. What is the treatment for vitiligo?

Answer 20

If the patches are relatively small, skin camouflage cream can be used to cover them up. - cosmetic camouflage *

Steroid creams can also be used on the skin to restore some pigment.

Topical calcineurin inhibitors (immunosuppresant) (eg tacrolimus) are an option as alternative

* If steroid creams do not work, phototherapy (narrowband UVB or PUVA) may be used.

Surgery is an option if previous treatments fail and in cosmetically-sensitive sites