week 7-skin Flashcards
what is acne? treated
Very common
• Characterised by blackheads and whiteheads and pustules
• Mostly affects face, the upper part of the chest, and the back
where most sebaceous follicles
• Severe acne is inflammatory, but acne can also manifest in
non-inflammatory forms
• Lesions are caused by excess oil and dead skin cells clogging
up follicles – Propionibacterium acnae grow, triggering
inflammation and pus
• In adolescence, acne is usually caused by an increase in
testosterone, which accrues during puberty
• Acne scars are the result of inflammation within the dermis
brought on by acne (1 in 5 sufferers have scarring)
• Benzoyl peroxide, antiseptics, antibiotics, hormonal
treatments, retinoids
what are 3 main skin cancers?
Basal cell carcinoma
• Squamous cell carcinoma
• Malignant melanoma
what is basal cell cacinoma?
Slow-growing and locally invasive tumours
• 4 times more common than other skin cancers
• Caused by UV exposure and proliferation of basal
keratinocytes
• Commonly on head and neck
• Morbidity related to local tissue invasion and
destructions
• Imiquimod cream treatment
what is squamous cell carnioma?
• Malignant invasive proliferation of epidermal
keratinocytes
• Second most common skin cancer
• More common in men and the elderly
• Caused by UV exposure
• Common in white skin that burns easily
• Also caused by topical carcinogens – arsenic, or
chronic immunosuppression
• With treatment overall remission rate is 90%
what is maligant melanoma?
Malignant proliferation of melanocytes
• Incidence and mortality are increasing
• Highest incidence in Australia and New Zealand
• Caused by UV exposure
• Mortality rate of 25%
• ‘Limited’ treatment options
- recent high-profile successes of immune system
modulation
what ares some risk factors for melanoma?
UV exposure Intense short exposure in childhood Fair skin Red and blonde hair Blue eyes Difficulty to tan Freckles Benign naevi/dysplastic naevi
what are some signs of melanoma?
A Asymmetry B Border is irregular C Colour variegation D Diameter (>6 mm) E Evolving – any change size, shape, colour elevation bleeding, itching crusting
what actually happens causing melanoma?
- in the epidermis you have melanocytes in the basal layer
- when we get proliferation of them they can turninto beign moles
- but soemtiemes they grow our of controland you get dysplastic nevus
- overtime youll get radio growth phase they grow in epidermal layer
- they they exoand into dermal layer then evenually become metastatic melanoma and reach bood vessles and can move to otther to form metatsisis
what can affect the survival of the melanaoma?
the thickness more than 4mm 5years survival is 37-50%
less than 1mm 5 year survial is 95-100%
what is treatment for melanoma?
• Surgery – Simple or wide – Sentinel node biopsy • Chemotherapy – Dacarbazine iv infusion or Temozolomide oral – Taxanes (docetaxel, paclitaxel) and platinum agents – Targeted therapy • Interferon alpha 2b • IL2 • Ipilimumab (anti-CTLA4) • Anti-BRAF • Anti-PD1
what is warts and verrucas?
• Caused by human papillomavirus – causes excess keratin
production on epidermis
• Virus can spread through close skin to skin contact,
contaminated objects eg towels, shoes, communal
changing areas, more likely to spread if skin wet, soft and in
contact with rough surface
• Clear up after about 2 years
• Salicylic acid containing creams , gels and paints
• Cryosurgery
Genital warts - very common, sexually transmitted
• Months or even years to develop after HPV infection
• Liquids and creams, eg Imiquimod, a topical cream that
stimulates the immune system to fight papillomavirus by
encouraging interferon production
• Keratolysis and cryosurgery
what is impetigo?
• Common highly contagious skin infection causing sores
and blisters – often Streptoccocus/Staphylococcus
infections
• 2 types –
– Non-bullous – most common - nose and mouth, sores
quickly burst – leave yellow-brown crust
– Bullous – trunk, fluid-filled blisters that burst after few
days – leave yellow crust
• Very common in young -1/35 children in UK aged 0-4
• Topical antibiotics, stay away from other people.
• Severe cases – systemic antibiotics (eg. Flucloxacillin).
what are fungal infections?
• Several types of infections eg dermatophytes and yeasts,
result in inflammation
• Fungi invade and grow in dead keratin
• Dermatophytes
– Athletes foot –
• Ringworm growing between toes
• Itchy flaky red skin
• Contaminated floors
– Nail infections – usually toenails – start from edge to base
– Ringworm – body, scalp, groin
• Small areas treated with topical application of imidazoles
(2%)
• Severe cases with systemic antifungal agents (griseofulvin, itraconazole)
• Immunocompromised patients (Candida and Aspergillus).
what is vitiligo?
Also called leucoderma
• Loss of skin colour in patches – discoloured
areas usually get bigger with time
• Affects any part of the body, hair and inside
the mouth but more often around eyes,
nostrils, mouth, navel, knees and elbows
• Melanocytes die or stop functioning leading
to loss of melanin
• Affects people of all races and all skin types
• 95% develop it before age 40
• Not contagious or life threatening and not
linked to cancer
• No cure
• 3 Types
– Focal, Segmental, Generalised
• Aetiology
– Autoimmune component
– 30% of patients have a family history
– 15-24% have autoimmune disease
– Immune system attacking its own melanocytes
– Triggers – stress, skin damage, hormonal changes, chemical
exposure (phenol) , liver/renal disease
• Pathogenesis
– Autoimmune component
– Body makes autoantibodies to tyrosine hydroxylase in nonsegmental vitiligo
– Increase in ROS production also in mitochondria of affected cells
what is Psoriasis?
Chronic autoimmune, inflammatory skin disease with periods of remission and relapse • Affects 2-3% UK population • Equally in men and women, any age • Peaks in late teens-early 30s and 50-60 • Normal skin cells produced faster than they are shed resulting in itchy, skin lesions/plaques – pink/red with white scales, variety of shapes and sizes – can split – painful • Can develop psoriatic arthritis
whats plaque psoriasis?
Most common
• Alone or in combination with other type(s)
• Red, itchy, sore plaques with white or silvery
scales – well demarcated
• Occurs anywhere on body – usually different
type if on palms or soles or where skin
touches skin
what is the aetiology of psorosis?
• Genetic predisposition
– Complex inheritance but 1/4 children of affected
parent
– Several susceptibility loci
• Keratinocytes normally take 3-4 weeks from
basal layer to shedding – 3-4 days in psoriasis
• Inflammatory cells increased in all layers
• Trigger often outside event – eg throat infection
(streptococcal) , stress or injury to skin, virus (HIV
or HPV) or withdrawal of corticosteroids
what is the treatment for psorosis?
• Unique to each individual
• Topical treatments
– Moisturisers and emollients
– Vitamin D derivatives (calcipotriol, tacalcitol, calcitriol)
– Topical steroids (eumovate, betnovate, dermovate),
– Dovobet (betamethasone and Vit D derivative)
– Coal Tar preps – scalp
– Dithranol – for well-defined plaques not on sensitive
areas
– Calcineurin inhibitors
• Phototherapy
• Systemic treatments
– Immunosuppressants – methotrexate and ciclosporin
– Vitamin A derivative (Acitretin)
– Apremilast – inhibits phosphodiesterase 4
– Dimethyl fumarate – activates Nrf2
– Anti-TNF (infliximab, adalimumab, etanercept, certolizumab)
– Anti-IL23 (ustekinumab (anti-Il12/Il23), guselkumab, rizankizumab, tildrakizumab)
– Anti-IL17/IL17A (secukinumab, brodalumab, ixekizumab)
what is psoriatic arthritis? and treatment
• Inflammatory joint disease affecting both joints (eg knees, hands and feet) and tendons (eg heel and lower back) • Relapsing and remitting • Generally occurs after skin lesions • Not linked to severity of psoriasis • Joints become tender, swollen and stiff – worse in morning and ease with exercise • Inflammation of tendons without joints • Often associated with nail psoriasis Treatment of psoriatic arthritis • Painkillers • NSAIDs – ibuprofen, diclofenac, COX-2 inhibitors • Corticosteroids • DMARDS – leflunomide • Biologicals – Anti-TNF – adalimumab, etanercept, certolizumab – Apremilast – anti-PDE4 – Tofacitinib – JAK inhibitor
what is the aetiology for atopic eczema?
Genetic predisposition – atopic families
• Defects in the skin barrier – repair and maintain
• Lack of anti-microbial peptides
• Defect in the filaggrin gene - important for maintaining
the skin barrier – in most eczema patients
• Abnormalities in the normal inflammatory and allergy
responses
• Barrier defects makes the skin in affected patients
much more susceptible to infection and to irritation
and allows allergy-inducing substances to enter the
skin, causing itch and inflammation
whats the clinical features of atopic eczema?
Often age-specific
– Flexural eczema in children
– Hand eczema in adults
• Dry skin
• Itching, may be severe, especially at night
• Red to brownish grey patches on affected areas
become lichenified
• Raw, sensitive, swollen skin from scratching
• Skin infections and sores can occur when
scratching breaks the skin
whats the treatment for eczema?
• Emollients
• Topical corticosteroids
• Antibiotics if eczema infected
• Phototherapy
• Systemic corticosteroids
• Topical calcineurin inhibitors (TCIs) – pimecrolimus and
tacrolimus
• Immunosuppressants – ciclosporine, azathioprine
• Dupilimumab – mAb inhibiting IL4/IL13 signaling
• Alitretinoin – for chronic hand eczema refractory to
steroids (retinoid)
whats allergic contcat dermatisi?
– Majority of occupational skin disorders
– Type IV hypersensitivity reaction
– Over time of exposure , immune response builds up
– Nickel, rubber, perfumes, preservatives in cosmetics, dyes
– Diagnosis by patch testing
whats the treatment for coontcat dermatisis?
• Avoid irritants and allergens • Emollients • Topical corticosteroids • Oral corticosteroids • Alitretinoin for chronic hand contact dermatitis refractory to steroids (retinoid)
what is seborrhoeic dermatitis and treat,ment?
• Infants aged 3-8 months • Yellow, waxy scales on the scalp, thick and difficult to remove • Pink flaky patches on forehead, eyebrows, behind ears, nappy area • Due to developing sebum glands
• Infants
– Emollients or mineral oils (for scalp)
– Topical steroids with antifungal (for body)
• Adults
– Shampoos with ketoconazole, Zn pyrithione, Se sulfide
(anti-yeast)
– Steroid scalp lotions/mousses
– Topical mild corticosteroids with salicylic acid (for scalp)
– Topical mild corticosteroids with anti-yeast – creams/
ointments (clotrimazole, miconazole and nystatin)
– Oral antifungals (severe cases)
what is a wound?
break in the epithelial
integrity of the skin – may affect
deeper layers even to bone
what are the diff types of wounds?
• Superficial – Damage to epithelium – Heals rapidly through regeneration of epithelial cells • Partial thickness – Involves dermal layer – Vascular damage • Full thickness – Involves subcutaneous fat and deeper – Longest time to heal – new connective tissue required – Contraction during healing
what are the 4 main stages of wound healing?
- bleeding
- inflammation
- proliferative
- remodeling
what happens during wound healing
- injury to the skin leading to bleeding where a blot clot from to stop the bleeding
- inflammation occurs to stop infection occurring so lots of immune cells come into the area and encourage new vessels
- proliferation= making more connective tissue and pull the wound closed formed a new epidermal
- remodelling to bring it back to normal decrease immune cells there
what are the cells and mediators involved in acute wound healing
- durining inflammation= neutrophils and macrophage they ll produce MMP ROS,IL,PDGF
- GRANULATION=fibroblasts, macrophages, endotheial cels TNF,IL
- Re-epithelialisation= keratinocytes, MMP, KGF, EGF
- Tissue remodelling= fibroblasts, collagen , MMPs, TGf3
how does haemostatsis occur during would healing?
• Microvascular injury – blood seeps into
wound
• Injured vessels contract
• Coagulation cascade activated by tissue
factor
• Clot formation and platelet aggregation
• Platelets trapped in clot release PDGF, IGF,
EGF, TGF-β which attract and activate
fibroblasts, macrophages and endothelial
cells
• Also release serotonin, which increases
vascular permeability
what is the early inflammatory phase?
• Activation of complement
• Infiltration of neutrophils within 24-48h
• Diapedesis into wound and phagocytosis of
bacteria and foreign particles, with ROS and
degrading enzymes – prevent infection
• Dying cells cleared by macrophages or
extrusion to wound surface
what is the late inflammatory phase?
• Blood monocytes arrive and become
macrophages (48-72 hr)
– key cell type for repair
– cytokines and growth factors to recruit fibroblasts,
keratinocytes and endothelial cells to repair damage
– Collagenases to degrade tissue
– Poor wound healing when inadequate monocytes/
macrophages
• Lymphocytes enter wound (>72hr) and are
involved in remodelling
what is the proliferative phase?
Fibroblast migration
– produce fibronectin, hyaluronan, collagen, proteoglycans
– Proliferate and construct new ECM
• Collagen synthesis – strength and integrity
• Angiogenesis
– TGF beta and PDGF from platelets, TNF and bFGF from macrophages
– Capillary sprouts invade fibrin/fibronectin-rich wound clot and organise
microvascular network
• Granulation tissue formation
– Mainly proliferating fibroblasts, capillaries ,macrophages in matrix of
collagen GAGs and fibronectin and tenascin
• Epithelialisation
– single layer of epidermal cells migrate from wound edges to form
delicate covering, basal cells increase proliferation, new basement
membrane
– EGF stimulates epithelial mitogenesis and chemotaxis, bFGF and KGF
stimulate proliferation
what is the remodelling phase?
• Matrix matures and remodels
– Fibronectin and HA broken down
– Collagen bundles increase in diameter and strength
(80% of strength of original)
– Ongoing collagen synthesis and breakdown by TGFbeta and MMPs
– Collagen becomes more organised and shrink to bring
wound margins closer together
– Fibroblasts and macrophages apoptose
– Capillary outgrowth halted and blood flow reduced
– Acellular, avascular scar results
what are some local factors affecting wound healing?
- Pressure
- Mechanical injury/Trauma
- Infection/Foreign substances
- Oedema
- Necrosis
- Topical agents
- Lack of oxygen delivery (Ischemia)
- Desiccation and dehydration
what are some systemic factors affecting wound healing?
Old age • Obesity • Chronic diseases eg diabetes, anemia • Connective tissue disorders • Immunosuppression • Smoking • Malnutrition • Vascular insufficiency • Stress • Radiation or chemotherapy
what are some causes of chronic wounds?
• Neuropathy
– Diabetes mellitus, Spinal injuries
• Ischemia
– Atherosclerosis, PVD, Microangiopathy (DM)
• Peripheral oedema
– DVT, Varicose veins, renal or cardiac failure
• Pressure
– Poor mobility, spinal cord injuries, dementia, diabetes
mellitus, old age, terminal illness
• Other
– Connective tissue disorders leading to vasculitis, Systemic
diseases, malignancy, smoking, drugs such as corticosteroids
and hydroxyurea
what are some clinical features of chronic wounds?
- Presence of necrotic and unhealthy tissue
- Excess exudate and slough
- Lack of adequate blood supply
- Absence of healthy granulation tissue
- Failure of re-epithelialisation
- Cyclical or persistent pain
- Recurrent wound breakdown
- Clinical or sub-clinical infection
what is thr funcion of the skin?
- Protective barrier – physical and chemical
- Involved in mechanical support
- Prevents loss of moisture
- Reduces harmful effects of uv radiation
- Sensory organ – touch, temperature, pressure etc
- Helps regulate body temperature
- Immune organ to detect infections
- Involved in production of vitamin D
- Excretion of waste products
what is the anatomy of the skin?
epidermis>dermis>hypodermis
what are the major epidermis cell types?
Keratinocytes – Main cell type – Numerous layers – Stem cells • Merkel cells – Pressure, attached to nerves – Different locations in skin • Melanocytes – Melanin, protect from uv – Basal region • Langerhans cells – Immune - Dendritic cells – All layers of epidermis • T cells – CD8 positive
what are keratinocytes?
-theres stem cells in the stratum basale that Stem cells – self renew Rapidly proliferate – Responsible for replenishing tissue Differentiate into different cells -10-20µm 15-25 flattened, stacked hexagonal cornified cells (corneocytes) -Cells have died and lost nuclei Enriched lipids and keratin
how is the red oigment and brownpigment made in our skin?
- tyosinne is metabolised to dopa and then todopaquinone through tyrosinase
- in the presense of cystein dopaquinen becomes pheomelanins that are the red pigment that people with freckles and red hair have more of
- but dopaquinine can be metabolised to eventually for eumelanins that are the blackand brown pigemnt shown in darker skin
what is the dermis?
Middle skin layer, 1-6mm fibrous and elastic tissue. Made of connective tissue Supportive and cushioning tissue composed mainly of collagen (70%), elastin and fibrillin • Immune cells – several types • Number of structures found – Nerve endings – Blood vessels – Lymph vessels – Piloerector muscles – Hair follicles – Sweat glands – Sebaceous glands
what occurs in the subcutaneous tissue (hypodermis)?
Subcutaneous fat layer acts as a:
– Mechanical protector
– Thermal insulator
– Energy store
Heat regulation uses subcutaneous fat pad
(hypodermis) and skin blood supply
Thickness depends on whole body adiposity but need
a minimal amount for skeletal and organ protection
what is the skin appendages?
where • Sweat glands
• Oil glands
• Hairs and follicles
• Nails
what occurs to cause inflammation of the skin?
• Signal-mediated response to cellular insult by:
– Infectious agents
• Bacteria, Fungi, Viruses, Parasites etc
– Toxins
• Chemical, Radiation, UV, Biological etc
– Physical stresses
• Mechanical, Burns, Trauma, etc
• Protective response – ultimate goal to remove initial
cause of injury and consequences of injury – the
necrotic cells and tissues
what is the skin microbiome?
• 1cm2 human skin contains up to 1b microorganisms – bacteria, fungi, viruses, mites • Beneficial – Protect against disease • Detrimental – Exacerbate skin lesions – Promote disease – Delay wound healing • Interact with host immune system – Bi-directional • Affected by lifestyles
how can there be a change in skin due to microbes?
- chnage in amount due to n the skin due to infection of long term antibiotic use or over growth
- leads to inflammation in the skin producing proinflammatory cytokines which can damage the barrier to the skin allowing the immune system to infiltrate, disrupt physical barrier and microbes can infilitrate
how can there be a chnage to the skin due host biology?
-if they have a chronic illness like diabtete
or wounds
-chnages the microbl community that can be taken over by pathogens and they penearte to sterile tissues leading to inflammation leading to breakdown of barrier, impaired wound healing
