Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Dermatology > Allergies; Photodermatology; Skin Immunology; Photocarcinogenesis > Flashcards

Allergies; Photodermatology; Skin Immunology; Photocarcinogenesis Flashcards

You may prefer our related Brainscape-certified flashcards:
Dermatology Board Prep flashcards
1
Q

What is the normal cutaneous photosensitivity scale

A

Fitzpatrick Sun-reactive skin prototypes (SPT I-IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Common “sparing” site in photosensitivity?

A

Behind the ears.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Porphyrias

  • general description
A

A group of diseases in which PORPHYRINS build up, affecting the skin and the nervous system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Main groups of Porphyrias

A

a) Phototoxic skin porphyria - pain and burning (prickly and burny)
b) Blistering and fragility skin porphyria
c) Acute attack porphyria (some with no skin involvement; some causing blistering and fragility)
d) Severe congenital porphyria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Example of a photo toxic skin porphyria?

A

Erythropoietic protoporphyria

also can be congenital

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Porphyria cutanea tarda (PCT) Type 1

Presentation.

A 
Blistering
Skin fragility
Erosions
Milia (firm nodules, not as hard as calcium)
"Tight" skin

Hyperpigmentation
Hypertrichosis
Solar urticaria
Morphoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Porphyria cutanea tarda

Investigations

A

Woods lamp//

Pink fluorescence of urine if patient has PCT (420nm)

Spectrophotometer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Different porphyrias have different…

A

Wavelengths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Porphyria cutanea tarda//

Underlying causes

A

Alcohol
Viral hepatitis
Oestrogens
Haemochromatosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Porphyria cutanea tarda//

Management

A

Aims of treatment

  • relieve the skin disease
  • treat underlying skin disease
  • reduce risk of liver cirrhosis
  • hepatoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Erythropoietic protoporphyria

A

Deficiency in the Ferrochelatase enzyme
leads to abnormal increase in protoporphyrin (used in formation of haemoglobin and myoglobin)

Acute photoallergy (i think)

626-639nm or so

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Erythropoietic protoporphyria//

Investigations

A
  • Quantitative RBC porphyrins

Fluorocytes

Transaminases

Haemoglobin conc.

Biliary tract USS

Phototesting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Erythropoietic protoporphyria

Management

A

Explain diagnosis
Genetic counselling

6 monthly LFTs & RBC porphyrins

Prophylactic TL-01 phototherapy

Anti-oxidants - beta carotene, cysteine, high does vit C

avoid IRON

VISIBLE light photo protection measures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What kind of light do sufferers of Erythropoietic protoporphyria need to be careful of?

A

VISIBLE light

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Photoprotection measures

A
  • Behavioural (avoid middle of day sunlight)
  • Clothing (DARK CLOTHING)
  • Environmental (shade trees, window films)
  • Topical sunscreen

(titanium oxide and zinc oxide cream)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What should you avoid in Erythropoietic protoporphyria?

A

Iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Liver cirrhosis/ Liver failure related Erythropoietic protoporphyria

Management

A

Oral charcoal
Cholestyramine
ALA synthase inhibition?/

Transplant liver, bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acute intermittent porphyria

A

Deficiency of porphobilinogen deaminase, affecting the production of heme.

consider in diagnosis //

Acute abdomen
Mononeuritis multiplex
Guillain-Barré syndrome
Psychoses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Hypersensitivity

A

Immune response that causes collateral damage to self

Exaggeration of normal immune mechanisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Allergy

A

Hypersensitivity disorder of the immune system

Allergic reactions occur when a person’s immune system reacts to normally harmless substances in the environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Type 1 Allergy

What is it

Routes of exposure

A

IMMEDIATE reaction - occurs within minutes and up to 2 hours after exposure to allergen

Routes: Skin contact, inhalation, ingestion, injection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clinical presentation of Type 1 allergy

A

Urticaria//

very itchy (hives, wheels, nettle rash)

Angioedema// localised swelling of subcut tissue or mucous membranes

Non pitting oedema

Not itchy (unless associated with urticaria)

Wheezing/asthma
- resp function significantly reduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

ANAPHYLAXIS

Clinical presentation

A

Compromised airways (pharyngeal or laryngeal oedema)

Breathing difficulty - bronchospasm w/tachypnoea

Hypotension
Tachycardia

Skin and mucosal changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Type 1 Allergy Investigations

A

Hx

Specific IgE (RAST)

Skin prick or prick prick testing

Challenge test

Serum mast cell TRYPTASE level (during anaphylaxis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When should the challenge test be done?

A

If skin prick test comes back negative.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Type 1 allergy - management

A

Allergen avoidance

Anti histamines

Anti inflam (CORTICOSTEROIDS)

Adrenaline autoinjector

also…

Mast cell stabiliser - sodium cromoglycate

Immunotherapy

Medic alert bracelet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chemical that can block mast cell activation?

A

Sodium cromoglycate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Adrenaline Autoinjector

Doses
How many pens per patient?

A

300 µg ADULTS

150µg CHILLUN

All patients should ne prescribed 2 pens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Can drugs cause mast cell degranulation?

A

Yes.

Morphine (opiates)

Aspirin

NSAIDs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Type IV allergy

A

DELAYED hypersensitivity

Antigen specific

T cell mediated

24-48 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Allergic contact dermatitis - allergy type/

A

Type IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Which compound is used to identify nickel? (in nickel allergy)

A

Dimethylglyoxime

pink

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Thiuram

A

Rubber accelerator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Colophony

A

Adhesive used in bandages/plasters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Type IV allergy - Patch testing

A

GOLD STANDARD

Allergens prepared on Finn chambers

Finn chambers applied on the back
(removed after 48 hours)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What other factors could cause dermatitis?

A

Endogenous
Allergic
Irritant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Irritant contact dermatitis

A

Non-immunological process

Contact with agents that abrade, irritate and traumatise skin directly

Pattern depends on exposure

e.g. Nappy rash
Lip lick dermatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Endogenous dermatitis

A

Atopic eczema - dry skin & flexural. Assoc w/ asthma & hay fever

Psoriasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Management of contact dermatitis

A

Allergen/irritatn avoidance

Allergen/ irritant minimisation

Emollients

Topical steroids

UV phototherapy

Immunosuppressants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Normal Immune response

A

Infection controlled

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Immunodeficiency

A

Infection not controlled

tumours may form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Keratin layer features

or stratum corner

A
  • Tough, lipid rich, PHYSICAL barrier
  • Formed by terminal differentiation of Keratinocytes to Corneocytes
  • Filaggrin/ Involucrin/ Keratin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Keratinocytes (in the epidermis)

A

Structural and functional cells of the epidermis

Sense pathogens via cell surface receptors and help mediate an immune response

Produce cytokines and chemokines

Produce antimicrobial peptides (AMPs) that can directly kill pathogens.
- AMPs have been found at high levels in skin of patients with psoriasis

Produce cytokines and chemokines
- recruit and regulate cell of the adaptive and innate immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Langerhans cells

A

> Type of dendritic cell that intersperse with keratinocytes in the epidermis
Main skin resident immune cell

> Antigen presenting cells

> Act as sentinels in the epidermis
they process lipid Antigen and microbial fragments and present them to effector T cells
Help activate T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are langerhans cells characterised by?

A

The BIRBECK granule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

T Cells in epidermis/dermis

A

> Large number of T cells in both epidermis and dermis

> MAINLY CD8+ T cells in EPIDERMIS

> CD4+ and CD8+ in the DERMIS

Other subsets of T cells are also found (NK)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Which type of T cell is found mostly in the epidermis?

A

CD8+ T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Which type of T cell is mostly found in the DERMIS

A

CD4+ T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Which type f T helper cell is associated with psoriasis?

A

TH1

TH17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Which type f T helper cell is associated with atopic dermatitis?

A

TH2

TH17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

T cells

A
  • Produced in bone marrow
  • Sensitised in THYMUS
  • CELL MEDIATED IMMUNITY
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What does antigen recognition and T cell activation involve?

A

Interaction with T Cell receptor (TCR) and the Major Histocompatibility Complex (mHC). Enhanced by co receptors:

CD4+
& CD8+

53
Q

Helper T cells

A

CD4+

Th1 - activate macrophages to destroy microorganisms
IL2, IFNƔ

TH2 = help B cells to make Ab
IL4, IL5, IL6

Help other cells of the immune system to carry out their roles

The “conductors”

54
Q

Dendritic cells in the dermis

A

> Dermal dendritic cell
- Ag presenting and secreting city/chemokines

> Plasmacytoid DC (pDC)
- produce IFNα

> APCs (antigen presenting cells)

  • transmit info to T &B cells
  • Dendritic, langerhans
55
Q

Cell types in dermis.

A

> Macrophages
Neutrophils (attracted to tissue by chemokines)

> Mast cells

  • found in “barriers”
  • IgE mediated immune response effectors
  • binding of IgE –> release of inflammatory mediators
  • also activated by physical trauma/certain drugs/micro-organisms
56
Q

What are lymphocytes attracted to the injured tissue by?

A

Chemokines

57
Q

Preformed mediators in mast cells

A

Tryptase, chymase, TNF, histamine

58
Q

Newly synthesised mediators in mast cells

A

ILs, TNF, TGFβ, IFNƔ, PGD2, PGE2….

59
Q

Mast cells

A
  • found in “barriers”
  • IgE mediated immune response effectors
  • binding of IgE –> release of inflammatory mediators
  • also activated by physical trauma/certain drugs/micro-organisms
60
Q

Why do you have pain, erythema, oedema in cellulitis?

A

Cytokines causing dilation of blood vessels

toxins

61
Q

IgE - other main function (organism immunity)

A

Immunity to helminths (worms/parasites)

62
Q

MHC

  • which chromosome?
  • classes
A

Chromosome 6

Class 1

  • almost all cells
  • present Ag to cytotoxic T cells
  • present endogenous Ag

Class 2

  • found on Antigen presenting cells (b cells, macrophages)
  • present to Th cells
  • present Exogenous Ag

Immunolgocial recognition and transplant rejection

Control immune response through recognition of self and non self

63
Q

Koebner phenomenon

A

Skin lesions on lines of trauma

64
Q

Are psoriasis plaques reversible?

A

Yes

65
Q

Is psoriasis associated with arthritis?

A

Yes, psoriatic arthritis can occur (in about 30% of patients)

66
Q

Psoriasis - immunopathogenesis

A

> Keratinocytes

  • release factors that stimulate pDC to produce IFNα
  • release IL-1β/IL-6 and TNF

> Chemical signals activate Dendritic cells

  • these migrate to skin draining lymph nodes to present to and activate t cells
  • TH1 & TH17

> T cells are attracted to the dermis by chemokines and secrete IL-17A/17F/22

stimulates KC proliferation , AMP release and neutrophil attracting chemokines

CD8+ cells

Dermal fibroblasts become involved - release KC and epidermal growth factor

67
Q

Atopic Eczema - immunopathogenesis

A

Impairment of skin barrier function is a key factor

Mutations in FILAGGRIN gene associated with severe/early onset disease

Decreased AMP in the skin

T cells (TH2), DC, KC, macrophages and mast cells are involved/ found in the lesions

Defective skin barrier allow access/sensitisation to allergen and promotes colonisation by micro organisms

(Block IL4 and it blows away the disease)

68
Q

Autoimmunity in the skin

A

Lymphocyte abnormalities

Intercell communication

Genetic predisposition

Anatomic alterations

Hormonal influence

Infection

69
Q

Immunodeficiency

A

INADEQUATE IMMUNE RESPONSE

Primary (genetic)

  • inherited defect
    • specific
    • non specific

Secondary (acquired)

  • AIDS
  • Malignancy
  • Aging
  • Diabetes, renal malfunction, burns, alcoholic cirrhosis, malnutrition
70
Q

Type 1 hypersensitivity

A

Antibody mediated - IgE

Early exposure to allergen causes the production of IgE, which binds to FcεR1 receptor on mast cells. Later exposure causes rapid crosslinking of the receptors, signal transduction and degranulation of the mast cell.

Very rapid early response: minutes (wheal & flare)

Late response: hours (cellular infiltration, nodule)
Pollen (birch, oilseed rape)
Drugs (penicillin)
Food (nuts, eggs, seafood)
Insects & animals (bee sting, cat hair)

71
Q

Type II & III hypersensitivity

A

Antibody mediated: IgG, IgM

Type II mechanisms important in autoimmunity & transplantation

  • Haemolytic disease of the newborn
  • Blood transfusion recipients

Skin testing in type III hypersensitivity leads to an Arthus reaction, which is slower than a type I skin response, but faster than a type IV skin response

Type III - immune complexes

72
Q

Type IV hypersensitivity

A

Cell mediated: TH1 cells.

Delayed hypersensitivity is based on a T cell-mediated response, which then recruits other cells to the site.

  • Tuberculin reaction
  • Contact allergy

Peaks at 24-48h after contact with Ag.
Metals (nickel, chromate), drugs.

73
Q

Factors affecting skin immune response

A

> Organ transplant
- immunosuppression

> Sunlight/UV

  • immunosuppression
  • structure

> Ageing
- changes in skin structure

  • decreased ability to detect malignant cells
  • Decreased ability to detect Ag- Infection risk
  • Decreased ability to distinguish “self” from “non-self”(tolerance)- Autoimmunity
74
Q

Cell types involved in skin immunity

A

EPIDERMIS

> Non immune cells
- Keratinocytes

> Immune cells

  • Langerhans cells
  • T cells (esp CD8+)

> Others
- melanocytes

DERMIS

> Immune cells

  • dendritic cells
  • macrophages
  • T cells (CD4+ & CD8+)
  • NK cells

> Others

  • fibroblasts
  • lymph/vasculature (transport/access)
75
Q

Defining cancer

A

An accumulation of abnormal cells that multiply through uncontrolled cell division and spread to other parts of the body by invasion and/or distant metastases via the blood and lymphatic system.

Abnormal malignant cell that can multiply in an uncontrolled fashion.

76
Q

What does the emergence of cancer involve?

A

Multi-step gene damage

Cancers originate from a single cell.

Genetic mutations (change to normal base sequence of DNA)

A series of mutations accumulate in successive generations in a process known as CLONAL EVOLUTION

Cells accumulate enough mutations to become cancerous

77
Q

Clonal Evolution

A

The accumulation of mutations in successive generations

78
Q

Evolution of cancer cells

A

Initiating mutation

–> second mutation (then second clonal expansion)

–> 3rd mutations (then 3rd clonal expansion)

–> 4th mutation (then fourth expansion)

79
Q

Field Cancerisation in skin tumours

A

Biological process in which large areas of cells at a tissue surface or within an organ are affected by a carcinogenic alteration(s).

80
Q

Dynamic clonal diversification rather than linear clonal succession

A

Initiating mutation

Second mutation

INCREASED MUTATION RATE

Multiple independent mutations
–>

MULTIPLE PARALLEL CLONAL EXPANSION

81
Q

Hallmarks of cancer

A

> Sustaining proliferative signalling

> Resisting cell death

> Evading growth suppressors

> Activating invasion and metastasis

> Enabling replicate immortality

> Inducing angiogenesis

82
Q

Emerging hallmark of cancer

A

Deregulation of cellular energetics

Avoiding immune destruction

83
Q

Enabling characteristics of cancer

A

Genome instability and mutations

Tumour-promoting inflammation

84
Q

Potential side effects of TNFα blocker

A

Can perhaps cause malignancies - effectively blocking immune system from blocking the cancer cells.

85
Q

Oncogene

A

Over-active form of a gene that positively regulates cell division

Drives tumour formation when activity or spy number is increased (accelerator)

e.g. Ras, Raf, growth factor receptors

86
Q

Proto oncogene

A

The normal, not yet mutated form of an oncogene

87
Q

Tumour suppressor

A

Inactive or non-functional form of a gene that negative regulates cell division

Prevents formation of a tumour when functioning normally (brake)

e.g. Rb, TP53

88
Q

P53 is important for

A

Destroying damaged DNA

G1 checkpoint

Apoptosis triggered if repair is impossible.

89
Q

Skin cancer types

A

> Malignant melanoma

> non melanoma skin cancer (NMSC)

    • BCC
    • SCC
90
Q

Risk factors for skin cancers

A 
> UV radiation
> Genetics
> Age
> Chemical exposure
> Immune suppression
91
Q

UV radiation

> Chronic/long term
Intense intermittent
Burning
Artificial UV

A

> Chronic exposure

    • SCC, 77% increased risk
    • Outdoor worker

> Intense intermittent

(i) Holidaing in locations with strong sunlight
ii) Outdoor leisure

i) Melanoma (60%)
ii) BCC (43%)

> Burning

  • pain/blistering following exposure
  • melanoma & BCC
  • double the risk

> Artificia UV

  • sunbed
  • SCC, Melanoma, BCC (higher risk of melanoma)
92
Q

Genetics

Skin type risk
Predisposition

A

> Fair skinned with light coloured hair and eyes

Those more likely to burn than tan

Skin types I, II & III

> Genetic predisposition

  • albinism
  • xeroderma pigmentosum
  • Xp associated genes are involved in the repair of DNA damage
  • 2000-fold risk of skin cancer before age 20; skin cancers appea in XP children median age 10
93
Q

Chemical exposure - skin cancer risk

A

Occupational exposure to certain chemicals can increase the risk of non melanoma skin cancer

  • coal tar pitch
  • soot
  • creosote
  • petroleum products
  • shale oils
  • arsenic
94
Q

Immune suppression - skin cancer risk

A

> Autoimmune conditions

  • UC (23% higher risk of malignant melanoma)
  • Crohns (80% higher risk of malignant melanoma)

> Immunosuppressants

  • azathioprine
  • cyclosporine
  • adalimumab

> Organ transplant recipients

  • NMSC risk 30x higher, esp SCC
  • malignant melanoma risk more than double
95
Q

Ultraviolet radiation and skin cancer - UVA & UVB

A

> UVB (290-320nm) causes DIRECT DNA damage
- 1000x more damaging the UVA when direct sunlight overehead

> UVA (320-400nm) causes INDIRECT oxidative damage
- UVA penetrates more deeply into the skin than UVB

> UV-induced immunosuppression also plays a role

96
Q

UVB induced DNA lesions

A

2 major types.

> Cyclobutane pyrimidine dimers (CPDs)

> Pyrimidine-pyrimidone (6-4) photo products

TT –> CC UV SIGNATURE

Both are formed by covalent bonding between adjacent pyrimidines on the same DNA strand

97
Q

Repair of UVB induced DNA lesions

Steps
Removal by NER

A

CPDs and 6-4PPs are relatively stable structures

Removed by NUCLEOTIDE EXCISION REPAIR (NER)

  1. Recognition of the damaged DNA
  2. Cleavage of the damaged DNA on either
    side of the photoproduct
  3. DNA polymerase fills in the gap, using
    the undamaged strand as a template
  4. DNA ligase seals the ends

Sometimes damage is so extensive that it cannot be repaired and leads to genetic mutations.

98
Q

Error prone DNA repair

A

Unrepaired UV induced photoproducts interfere with base pairing during DNA replication leading to mutations.

In most cases, polymerase will insert the correct bases (A-A)

Polymerase is error prone
so it may not correctly “guess” the structure of the lesion and instead insert G-G opposite the thymidine dimer

99
Q

Indirect damage by UVA

A

UVA causes indirect damage via oxidation of DNA bases

C –> A point mutation

Esp deoxyguanosine to form 8-oxo-deoxyguanosine

8-oxo-dG can mislaid with deoxyadenosine rather than forming a normal base pari with deoxycytosine

If 8-oxo-dG is NOT removed, when DNA is replicated, dA rather than dC can be incorporated causing GC–> AT point mutation

100
Q

Repair of 8-oxo-dG lesions

A

Oxodised lesions repair by BASE EXCISION REPAIR (BER)

  1. Recognition of the chemically altered base causing slight helix distortion
  2. Cleavage of the altered base from the deoxyribose by DNA glycosylase
  3. Base-free deoxyribose cleaved away by endonuclease
  4. Single nucleotide gap filled by DNA polymerase β
  5. DNA ligase seals the ends
101
Q

UV-induced immunosuppression

A

UV induced DNA damage also leads to immunosuppression:

> Depletion of Langerhans cells in the skin and reduced ability to present antigens

> Generation of UV induced regulatory T cells with immune suppressive activity

> Secretion of anti-inflammatory cytokines e.g. IL-10 by macrophages and keratinocytes.

102
Q

Mutations in PTCH1 are associated with…

A

BCC development

103
Q

Hedgehog Signalling Pathway

A

This pathway activate the transcription factors Gli1/2

–> induction of cell proliferation genes (cyclins D/E) and angiogenesis activators.

–> Vismodegib binds to SMO (smoothened) to block hedgehog signalling and prevent cell cycle activation and angiogenesis.

VIDEO

104
Q

Which mutations are common in melanoma?

A

Mutations in Ras/Raf/MAPK signalling pathway are common melanomas

> 50% have B-Raf mutation, mostly V600E,K,R,M & D.

Can produce signalling in uncontrolled fashion –> proliferation –> melanoma formation.

105
Q

Which drugs target mutated form of B-raf?

A

Vemurafenib and Dabrafenib

106
Q

What drug targets MEK?

A

Tramatenib

107
Q

Familial melanoma mutations

A

Two genes.

CDKN2A & CDK4

When these proteins are “turned off” they do not stop the proliferation and mutation of cells.

108
Q

Proteins encoded for by CDKN2A?

A

p16INK4a and p14ARF

109
Q

CDKN2A

A

Prevents cells from replicating when they contain damaged DNA by activating the G1/S

Inactivating mutations in p16 permits cell division in presence of unrepaired DNA

110
Q

CDK4

A

Cyclin dependent kinase 4

Permits cell cycle progression by Phosphorylation of retinoblastoma protein (Rb)

Activating mutations in CDK4 accelerates cell cycle

111
Q

Non melanoma skin cancer

A

Arise from keratinocytes within the epidermis.

BCC s arise from keratinocytes within the basal layer of the epidermis

SCC arise from supra basal layers.

112
Q

Melanoma survival depends on…

A

Tumour depth

113
Q

Breslow Thickness

A

<1mm - 5 yr survival = 95%

> 4mm - 50%

Metastases - 5% survival (invading dermis)

EARLY DIAGNOSIS IS ESSENTIAL

114
Q

Diagnose melanoma early

ABCDE

A 
A - asymmetry
B - border
C - colour
D - diameter
E - Evolution

Multicoloured - abnormal

Light brown/dark brown - normalish

115
Q

Ugly duckling sign

A

MM often deviates from this nevus pattern.

Multiple myeloma - cancer of plasma cells

116
Q

BCC - Presentation

A

slow growing lump or non-healing ulcer

painless and often ignored

‘pearly’ or translucent

visible, arborising blood vessels

central ulceration - “rodent ulcer”

can present as scaly plaque - ‘superficial’

can be infiltrative - ‘morphoeic’

locally invasive, but rarely metastasize

> 40 yrs, but can be 3rd or 4th decade

117
Q

“Rodent ulcer”

A

BCC presentation.

Ulcerated in middle due to poor vascular supply.

118
Q

Pigmented BCC

A

Simulated melanoma

Treat as a melanoma until you know what the result from the biopsy is.

119
Q

Squamous cell carcinoma

A

25% of NMSC

hyperkeratotic (crusted) lump or ulcer

arises on sun-damaged skin

grow relatively fast, may be painful &/or bleed

majority - well differentiated low risk SCC

minority - poorly differentiated high risk SCC

risk of metastasis about 5%

poor prognosis once metastatic

precursor lesions - actinic keratoses and Bowen’s disease (carcinoma-in-situ)

Keratoacanthoma - self-resolving

120
Q

Lip and scalp are high risk areas for?

A

Squamous cell carcinoma

121
Q

Actinic keratoses

A

Rough, scaly patch. Due to years of sun exposure

Precancerous skin lesions

AK are multiple lesions

Highly associated with risk of developing SCC or BCC.

122
Q

Xeroderma pigmentosum

A 
> Photosensitivity
> Skin cancers on UV exposed sites
> Neurological degeneration
> Increased risk of other cancers
> Defect in one of seven Nucleotide Excision Repair (NER) genes
123
Q 
Naevoid BCC 
(Gorlin's syndrome)
A

Autosomal dominant familial cancer syndrome

Major features:

  • early onset/ multiple BCCs
  • palmar pits
  • jaw cysts
  • ectopic calcification falx

Minor

  • skeletal abnormmality
  • OFC > 97th centile
  • cardiac/ovarian fibroma
  • medulloblastoma
124
Q

Butterfly disease

A

Recessive dystrophic epidermolysis bulls (RDEB)

High risk of skin cancer

125
Q

Hereditary Type VII collagen deficiency

A

High risk of skin cancers.

126
Q

“Transplant hands”

A

Pre cancerous lesions

Transplant patients

Red hands, lesions, sores, crusty.

127
Q

Skin cancer prevention

A
  1. Behaviour
  • avoid sun at its height (11am-3pm)
  • use shade wherever possible
  • particular care of babies/children
  • avoid sunbeds
  1. Clothing
  • tightly woven, loose fitting clothing (dark)
  • long sleeves, trousers, skirts
  1. Sunscreens
    - broad spectrum (SPF25+) with UVA protection
  2. Regular (self-) surveillance

NO SUNBEDS

128
Q

True sign of anaphylaxis?

A

Raised serum tryptase

Dermatology (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions