Skin Pharmacology Flashcards
State the functions of the skin:
Protective barrier
Involved in mechanical support
Prevents loss of moisture
Reduces harmful effects of UV radiation
Sensory organ- touch, temp, pressure etc
Helps regulate body temp
Immune organ to detect infections
Involved in production of vitamin D
Excretion of waste products through sweat
Describe how the skin is a protective barrier:
Physical- cells tightly packed together
Chemical- antimicrobial peptides and oils
Describe how the skin reduces the harmful effects of UV radiation:
Melanin production- a pigment adapted from tyrosine
Describe how the skin helps regulate body temperature:
Vascular rich region-many capillaries
Name and briefly describe the layers of the skin:
Epidermis- outer layer of epithelial cells, no blood supply, nutrients come from nearby capillaries, replace every 2-3 days
Dermis- middle, vascular rich, hair follicles, glands (receptors), connective tissue
Hypodermis- adipose tissue
Name the 5 layers of the epidermis:
1) stratum basale (closest to dermis)
2) stratum spinosum
3) stratum granulosum (dark layer)
4) stratum lucidim
5) stratum corneum (dead keratinocytes)
Name the main cell types in the epidermis:
Keratinocytes
Merkel cells
Melanocytes
Langerhan cells
T cells
Describe the keratinocytes in the epidermis:
Main cell type
Numerous layers, starts off in the basal layer as cuboid cells but as move up to surface begin to flatten out and die
Stem cells
Describe Merkel cells in the epidermis:
Present in stratum basal
Pressure/light attached to sensory neurones
Different locations in skin
Describe melanocytes in the epidermis:
Near basal layers- stratum spinosum
Produce melanin, protect from UV
Describe Langerhans cells in the epidermis:
Immune/ dendritic cells - detect self and non self
All layers in epidermis
Describe T cells in the epidermis:
CD8+ T cells- dendritic cells can present to T cells
What is another name for keratinocytes?
Corneocytes
Describe the lifetime of a keratinocyte:
In stratum basal- have stem cells which self renew and rapidly proliferate and differentiate into any other cell types in the area
Cuboidle cells which have nuclei once in granules layer, start to flatten and lose nuclei and then in stratum lucidium fully flattened and eventually die in the corneum, where they are enriched with lipids and keratin
What is the function of keratinocytes?
Secrete IL1-B important in maintaining homeostasis and if cells become damaged
Describe the dermis:
Middle layer, 1-6mm fibrous and elastic tissue
Made of connective tissue
Has 2 layers
Name the 2 layers of the dermis:
Papillary layer 20%- next to the epidermis
Reticular layer
Describe the papillary layer of the dermis:
Vascular rich region, lots of capillaries which release O and nutrients near epidermis to provide for epidermis, that’s why the keratinocytes become flattened further up (dead)
Supportive and cushioning tissue composed mainly of collagen (70%), elastin and fibrillin which allows more exchange of oxygen and nutrients
Describe the reticular layer of the dermis:
Majority of dermis
Dense irregular connective tissue- elastin and fibirillin
Immune cells, several types
Number of structures found
Name the structures found in the reticular layer of the dermis:
Skin appendages
Meissner’s corpuscle
Pacinian corpuscle
Hair shaft
Eccrine sweat glands
Apocrine sweat glands
Describe the function of the Meissner’s corpuscle:
Sense receptors for light or discriminative touch (epidermal layer)
Describe the function of the Pacinian corpuscle:
Detects vibration in the skin
Describe the function the hair shaft:
Hypodermis
Root hair plexus- detects fine touch
Sebaceous (oil) gland- keeps skin and hair moist
Describe the function of the eccrine sweat gland:
Watery sweat- urea/CO2 etc
Describe the function of the apocrine sweat gland:
Present in armpit/ pubic
Protein rich sweat bacteria
Describe the diversity of the skin on the face:
Sebaceous
High density of sebaceous glands
Hair and eccrine glands
Evironmentally exposed
Describe the diversity of the skin on the palm:
Dry
Thick stratum corneus
Hairless
High density of eccrine glands
Describe the diversity of the skin on the axilla:
Moist
Apocrine glands present
High density of hair
Occluded, humid environment
Describe the subcutaneous tissue in the hypodermis:
Fat layer acts as a:
-mechanical protector
-thermal insulator
-energy store
Thickness depends whole body adiposity but need a minimal amount for skeletal and organ protection
Heat regulation uses SC fat and blood supply
Name the components of the skins immune system in the dermis:
Dendritic (dermal/plasmacytoid)
CD4 T cell (Th1,Th2,Th17)
NK cells
g ∂ T cells
Macrophages
Mast cells
Fibroblasts- remodels skin like collagen if damaged
What factors can cause signal mediated responses to cellular insult?
Infectious agents- bacteria, fungi, viruses, parasites
Toxins- chemical, radiation, biological etc
Physical stresses- mechanical, burns, trauma
Describe the skin microbiome:
1cm2 human skin has up to 1 billion MOs e.g bacteria, fungi, viruses, mites
What are the advantages of the skins microbiome?
Inhibit pathogen growth
Educate and prime adaptive immunity
Enhance host innate immunity
What are the detrimental/ disadvantages of the skins microbiome?
In acne, this bacteria clogs sebaceous glands
Exacerbation skin lesions
Promote disease
Delay wound healing
How does the skin microbiome interact with the hosts immune system?
Bi-directional
We provide the bacteria with nutrients and space and they protect us
What type of bacteria is majorly found in the upper body?
Actinobacteria
What type of bacteria is majorly found in the limbs/middle body?
Proteobacteria
What type of bacteria is majorly found in the foot/leg?
Firmicutes
How does the skin resident microbiome inhibit pathogen growth?
Occupy space and nutrients
Produce AMPs/ bactericidal compounds- antimicrobial peptide
Inhibit S aureus biofilm formation
How does the skin resident microbiome educate and prime adaptive immunity?
Tune local cytokine production
Epigenetically prime APCs to educate adaptive immunity
Influence T regs in epidermis
How does the skin resident microbiome enhance host innate immunity?
Increase AMP production
Decrease inflammation after injury
Strengthen epidermal barrier
How can the microbial communities on the skin cause things to go wrong?
Shift in community composition e.g infection
Altered host immune response release pro-inflammatory cytokines
Impaired barrier homeostasis- immune infiltration- disrupted physical barrier
Microbes escape typical niches/ overgrow into sterile tissues
How can the hosts biology/ pathology cause things to go wrong for the skin microbiome?
Alterations in the skin barrier/immune functions e.g genetic predisposition (filigrin gene)/chronic condition
Changes in distribution of microbes causes overgrowth of potential pathogens into sterile tissues
Altered/inappropriate immune responses increase inflammation, opportunistic infections, impaired wound healing
Name the different types of wound:
Superficial
Partial thickness
Full thickness
What is a superficial wound?
Epidermal layer
Heals rapidly through regeneration of epithelial cells- no bleeding as no vascular system, keratinocytes
What is a partial thickness wound?
Involves dermal layer
Vascular damage
What is a full thickness wound?
Involves the SC fat and deeper
Longest time to heal, new connective tissue required
Contraction during healing
Name the 4 stages of wound healing:
- Bleeding
- Inflammatory
- Proliferative
- Remodelling
Describe the bleeding stage of wound healing and how long does this occur?
Injury to skin, haemostasis, blood clot to stop bleeding
Takes less than a day- platelet/ complement activation
Describe the inflammatory stage of wound healing and how long does this occur?
Linked with bleeding
Stop infection, lots of immune cells e.g fibroblasts
Framework for new bv growth- scab
Within 72 hours
Anything between 1-10 days
Peak after a day- neutrophils (granulocytes)
2-3 days after- macrophages
Describe the proliferative stage of wound healing and how long does this occur?
Fibroblasts proliferating- more connective tissue to replace damages, new dermal layer (delicate)
After 3 days:
-deposit matrix, fibroplasia, angiogenesis, collagen, proteoglycans, extraceullar matrix synthesis, epitheliaization
Describe the remodelling stage of wound healing and how long does this occur?
Freshly healed dermis/epidermis- avascular scar
Month- extracellular matrix synthesis, degradation and remodelling
Increase tensile strength, decrease cells, decrease vascularity
- can take up to a year
Describe the steps in haemostasis:
Microvascular injury- blood seeps in wound
BVs contract-limits blood in wound
Coagulation cascade activated by tissue factor
Clot formation and platelet aggregation
Platelets trapped in clot release PDGF,IGF,EGF,TGFb which attract and activate fibroblasts, macrophages and endothelial cells
Also release serotonin, which increases vascular permeability, BVs relax so immune cells can come into area
Describe early inflammatory phase:
Activation of complement
Infiltration of neutrophils (within 24-48hrs)
Diapedesis into wound and phagocytosis of bacteria and foreign particles with ROS and degrading enzymes- prevent infection
Dying cells cleared by macrophages extrusion to would surface
Describe late inflammatory phase:
Blood monocytes arrive and become macrophages (48-72hrs)
Key cell type for repair
Cytokines and GFs to recruit fibroblasts, keratinocytes and endothelial cells to repair damage
Collagenases to degrade tissue
Lymphocytes enter wound (72hrs) and are involved in remodelling
Name the processes that occur in the proliferative phase:
Fibroblast migration
Angiogenesis
Granulation tissue formation
Epithelialisation
Describe fibroblast migration:
Produce fibronectin, hyaluronan, collagen, proteoglycans
Proliferate and construct new ECM
Collagen synthesis- strength and integrity
Describe angiogenesis:
TGFB and PDGF from platelets, TNF and BFGF from macrophage
Capillary sprouts invade fibrin/fibronectin rich wound clot and organise microvascular network
Describe granulation tissue formation:
Mainly proliferating fibroblasts, capillaries, macrophages in matrix of collagen GAGs (glycosaminoglycans) and fibronectin and tenascin (ecm GP)
Describe 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
How can chronic wound and impaired healing occur?
When normal processes of healing disrupted at one of the stages, usually inflammatory or proliferative
Disturbances in GF, cytokines, proteases
Describe which cells and how are involved in the matrix maturing and remodelling stage:
Fibronectin and HA broken down
Collagen bundles increases in diameter and strength 80% of strength of original
Collagen synthesis and breakdown by TGFb and MMPs
Collagen becomes more organised and shrink to bring wound margins closer together
Fibroblasts and macrophages apoptose
Capillary outgrowth halted and blood flow reduces
Acellular, avascular, scar
What are the local factors which affect wound healing?
Pressure
Mechanical injury/ trauma
Infection/ foreign substances
Oedema
Necrosis
Topical agents
Lack of oxygen delivery (ischemia)
Desiccation and dehydration
What are the systemic factors which affect wound healing?
Old age
Obesity
Chronic diseases e.g diabetes
Connective tissue disorders
Immunosuppression
Smoking
Malnutrition
Vascular insufficiency
Stress
Radiation/ chemo
Name and describe some causes of chronic wounds:
Neuropathy e.g DM, spinal injuries
Ischemia e.g atherosclerosis
Peripheral oedema e.g DVT
Pressure e.g poor mobility
Describe 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-epitheliasation
Cyclical or persistent pain
Recurrent wound breakdown
Clinical or sub clinical infection
How does motor neuropathy cause diabetic ulcers?
Muscle atrophy/ bone changes- deformed foot- changes in gait- new pressure distribution- ulcer- infection- gangrene
How does sensory neuropathy cause diabetic ulcers?
Painless trauma leads to ulcers and infection/ gangrene
How does autonomic neuropathy cause diabetic ulcers?
Decreases sweating- dry skin cracks- chronic ulcer which leads to infection and ischamiea
What is the difference between eczema and dermatitis?
Eczema= inflammation of the epidermis
Dermatitis= inflammation of the dermis
Name the different types of dermatitis:
Atopic
Contact
Seborrhoeic
Dyshidrotic
Nummular
Neurodermatitis
Stasis
Describe atopic dermatitis:
Chronic disorder with flare ups and remissions- may clear up for long periods
Type IV hypersensitivity
Often occurs with asthma/ hayfever (atopic triad)
Commonly affects knees, elbows, wrists, neck and face
What population does atopic dermatitis commonly affect?
1-2% adults- hand eczema
15-20% school children- flexural eczema
Males and females equally affected
Describe the aetiology of atopic dermatitis:
Genetic predisposition
Defect in the filaggrin gene- important for maintaining the skin barrier
Defects in the skin barrier
Lack of anti-microbial peptides
Abnormalities in the normal inflammatory and allergy response
Barrier defects makes the skin in affected patients much more susceptible to infection and to irritation and allows allergy- inducing substances to enter skin, causing an itch and inflammation
Describe the pathophysiology of atopic dermatitis:
Allergen- dendritic cell- T cell- change in balance of the Th1/2 and so expansion of Th2 which secretes IL4- activates B cells causing class switching of antibodies so produced IgE- blood to mast cells, so allergen can be taken up (adaptive IR)- pro inflammatory mediators
What are the clinical features of atopic dermatitis?
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 due to breaks in the skin
What could be the causes of flare ups of atopic dermatitis?
Heat, dust, smoke, irritants, soaps, stress
What would be the preventions of flare ups for atopic dermatitis?
Moisterisers
Identify and avoid triggers if possible
Mild soaps and short showers/ baths
What are the first line treatments for atopic dermatitis flare ups?
Emollients
Topical corticosteroids
Antibiotics if eczema infected
Phototherapy
What are the second line treatments for atopic dermatitis flare ups if first line not sufficient?
Systemic corticosteroids
Topical calcineurin inhibitors (TCIs)
What is the third line treatment for atopic dermatitis flare ups if first line not sufficient?
Immunosuppresents -ciclosporin, azathioprine
Dupilimumab- MAB inhibiting IL4/IL13 signalling
What would be the treatment for eczema on the hands in adults?
Last treatment option
Alitretinoin- for chronic hand eczema refracory to steroids
Name some topical calcinerin inhibitors and how do they work?
Pimecrolimus and Tacrolimus
Inhibit T cell response so no IL4
Describe contact dermatitis:
Mainly substances responsible
2 types:
-irritant
-allergic
More common in adults than children as associated with workplace
Common in network
Atopic dermatitis pts have increase susceptibility
Describe irritant contact dermatitis:
Very common (75%)
Exposure to acute toxic insult or cumulative damage from irritants
Detergents and solvents which strip skin of natural oils
Amount of exposure important
Excess hand washing, dribble rashes or nappy rashes
Occurs under jewellery
Diagnosis by knowing which substances irritate
Describe allergic contact dermatitis:
Majority of occupational skin disorders
Type IV hypersensitivity reaction
Over time exposure, immune response builds up
Nickel, rubber, perfumes, preservatives in cosmetics
Diagnosis by patch test
Describe the pathophysiology of irritant contact dermatitis:
Innate
Irritant will directly effect keratinocytes and will switch on and secrete lots of pro-inflammatory cytokines such as TNF,IL1,IL8,GM-CSF and will secrete IL1 to activate dendritic cells
Causes endothelial cells to be upregulated- vasodilation- cellular recruitment into skin area- neutrophils, macrophages, lymphocytes and mast cells- local inflammatory response
Describe the pathophysiology of allergic contact dermatitis:
Combination of atopic and irritant CD
What is the treatment for contact dermatitis?
Avoid irritants and allergens
Emollients
Topical corticosteroids
Oral corticosteroids
Alitretinoin for chronic hand dermatitis refractory to steroids
What population does seborrhoeic dermatitis in adults affect?
1-3% of the population
More common in males over the age of 20
What are the clinical symptoms in seborrhoeic dermatitis in adults?
Harmless rash with skin flakes, itchy and sore inflamed red skin with greasy looking white or red scale
Ranges from mild (dandruff) to severe on the scalp
Occurs in sebaceous skin zones- face, *scalp, chest, ears, skin, folds, axillaie, groin
What causes seborrhoeic dermatitis in adults?
Over growth of malassezia yeasts, which are normal part of skin flora but they metabolise sebum and trigger inflammatory response
Not contagious, aggravated by stress
What age does seborrhoeic dermatitis (cradle cap) commonly occur in infants?
3-8 months
What are the symptoms of cradle cap?
Yellow, waxy scales on the scalp, thick and difficult to remove
Pink flaky patches on forehead, eyebrows, behind ears, nappy area
What causes cradle cap in infants?
Due to developing sebum glands
Yeast metabolises sebum into fatty acids which penetrates skin and causes inflammation
What are the treatments of seborrhoeic dermatitis in infants?
Can be stubborn and often returns
Emollients or mineral oils for scalp
Topical steroids with antifungal for body
What are the treatments of seborrhoeic dermatitis in adults?
Shampoos with ketoconazole, Zn, pyrithone, Se sulphide (anti yeast)
Topical mild corticosteroids with salicylic acid for scalp
Topical mild corticosteroids with anti-yeast creams e.g clotrimazole
Oral anti fungal (severe case)
Describe nummular (discoid) dermatitis:
Round/ oval blistered dry lesions
Usually lower legs/trunk/arm
Affects males and females equally
Unknown cause
Treat with emollients, steroids, antibiotics and phototherapy
Describe neurodermatitis:
12% of population, commonly mid to late adulthood (esp 30-50)
Localised area caused by repeated rubbing/ scratching
Possibly due to compressed nerve or presence of other
Very persistent
Treat with emollient and steroids
What is stasis dermatitis caused by?
Adults with varicose veins (where vascular insufficiency), DVT, or ulcers or where increase pressure in the veins of the legs
Other risk factors are overweight/ standing up
More common in women
Often associated with signs of venous hypertension
What are the symptoms of stasis dermatitis?
Mainly seen in the lower legs
Skin becomes fragile, thin, shiny, inflamed, itchy and flakey
How would you treat stasis dermatitis?
Emollients, steroids, compression stocking, exercise, weight loss, elevation of legs and surgery for varicose veins (removing the trigger)
Describe dyshydrotic dermatitis:
Common in people with atopic eczema under the age of 40
Affects hands and feet
Unknown cause but aggravated by heat and stress
Tiny itchy blisters
Treat with emollients, steroids, antibiotics, systemic immunosuppressents and phototherapy
What is psoriasis?
Chronic autoimmune, inflammatory skin disease with periods of remission and relapse
What population does psoriasis affect?
2-3% of UK population
Equally in men and women, any age
Peaks in late teens, early 30s and 50-60
What are the symptoms of psoriasis and why?
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
Name the different types of psoriasis:
Plaque psoriasis
Scalp psoriasis
Guttate psoriasis
Pustular psoriasis
Nail psoriasis
Psoriatic arthritis
Describe plaque psoriasis:
Most common
Alone or in combo with other types
Red (due to increased blood flow), 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
Describe scalp psoriasis:
Similar to other parts of the body but thick build up of scaly skin leading to dandruff like flakes
Also visible around the hairline, forehead, neck and ears
If severe can cause thinning of the hair
Describe guttate psoriasis:
Can also be called tear drop or rain drop
Bright pink or red on fair skin, less red and more darkening on dark skin
Widespread across torso, back and limps
Eventually clears up
Common in children and younger adults
Often triggered by strep throat
Describe pustular psoriasis:
Small white or yellow fluid filled blisters (pustules) on top of red or darkened skin, can turn crusty when burst
If generalised needs to see doctor ASAP
Palms of hands or soles of feet
Can be painful and requires dermatologist for treatment
Describe nail psoriasis:
Up to 50% of psoriasis and 80% of psoriatic arthritis patients
Can only affect the nails
Fingernails and/or toenails
Mild to severe, often mistaken for a fungal infection
Nail discolouration, pitting, crumbling, cracking, splitting, detaching
Describe the genetic aetiology of psoriasis:
Genetic predisposition:
-complex inheritance but 1/4 of children of affected parent
-several susceptibility loci
PSORS1, IL12B
Genotype IL23 receptor
Describe the science aetiology of psoriasis:
Keratinocytes normally take 3-4 weeks from basal layer to shedding, 3-4 days in psoriasis
Inflammatory cells increase in all layers
Trigger often outside event e.g throat infection, stress or injury to the skin or withdrawal of corticosteroids
Describe one route of the pathogenesis of psoriasis:
Trigger causes stressed keratinocytes which release DNA and produces LL-37, which forms DNA-LL-37 complexes (autoantibodies) which are picked up by plasmacytoid dendritic cells which causes INFa activation
This activates dermal dendritic cells which secrete IL23+IL12
Leads to T cell clonal expansion (Th17) and Th1-> IFNg/TNF which activated dendritic cells which leads to inflammation and also chemokine
Leads to a chemokine gradient which helps macrophages which increases pro-inflammatory cytokines e.g KGF,EGF,TGF to fibroblasts and collagen
Describe a second route of the pathogenesis of psoriasis:
Trigger causes stressed keratinocytes which produces pro-inflammatory cytokines (IL1B, IL6 and TNFa)
This activates dermal dendritic cells which secrete IL23+IL12
Leads to T cell clonal expansion (Th17) and Th1-> IFNg/TNF which activated dendritic cells which leads to inflammation and also chemokine
Leads to a chemokine gradient which helps macrophages which increases pro-inflammatory cytokines e.g KGF,EGF,TGF to fibroblasts and collagen
Name the topical treatments for psoriasis:
Moisturisers and emollients
Vit D derivates
Topical steroids (eumovate, betnovate, dermovate)
Dovobet (betamethasone+vit D derivative)
Coal tar preps (anti-inflammatory and descaling)
Dithranol- toxic so used for well defined plaques not on sensitive areas
Calcinerin inhibitors
Phototherapy
Name and describe the function of Vit D derivates as a treatment for psoriasis:
Calcipotriol, Tacalicitol, Calcitriol
Inhibits proliferation and induces differentiation of keratinocytes
Name and describe the systemic treatment for psoriasis:
Immunosuppressants- MTX, ciclosporin
Vit A derivative (Acitretin)
Apremilast- inhibits phosphodiesterase 4- local inflammation
Dimethyl fumarate- activates Nrf2 (TF) modifying responses against
Anti TNF- Infliximab, adalimumab, etanercept
Anti-IL23- ustekinumab, guselkumab
Anti-IL17/A- secukinumab
What is psoriatic arthritis?
Inflammatory joint disease affecting both joints and tendons
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
What is the treatment for psoriatic arthritis?
Painkillers
NSAIDs
Corticosteroids
DMARDs-leflunomide
Biologics- last resort:
-AntiTNF (adlimumab, etanercept)
-Apremilast (anti-PDE4)
-Tofacitinib (JAKi)
What is acne caused by?
Lesions caused by excess oil and dead skin cells clogging up follicles- propioni bacterium acnae grow, triggering inflammation and pus as lives off dead skin cells
In adolescence, acne is usually caused by an increase in testosterone
How are acne scars caused?
Inflammation within the dermis
What are treatments for acne:
Benzoyl peroxide
Antiseptics
Antibiotics
Hormonal treatments
Retinoids- systemically or locally
Name the different types of skin cancer:
Basal cell carcinoma
Squamous cell carcinoma
Malignant melanoma
Describe squamous cell carcinoma:
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 e.g arsenic
With treatment overall remission is 90%
Describe malignant melanoma:
Malignant proliferation of melanocytes
Incidence and mortality are increasing
Highest incidence in Australia and New Zealand (thin Ozone layer)
Caused by UV
Mortality rate of 25%
Limited treatment options
What are the risk factors for developing skin cancer?
UV exposure
Intense short exposure in childhood
Fair skin
Red and blonde hair
Blue eyes
Difficult to tan
Freckles
Benign navei/ dysplastic navei
What are the common signs of melanoma following a rule?
Asymmetric
Border is irregular
Colour variegation
Diameter (>6mm)
Evolving, any change:
-size, shape colour
-elevation
-bleeding, itching
-crusting
Where is the most common place for a man and woman to have a melanoma?
Women- leg (39%)
Man- trunk (41%)
Describe the pathophysiology of melanomas:
In epidermis there are melanocytes, in the basal layer, proliferation can cause benign nevus (moles), too much proliferation can cause dysplastic nevus (asymmetric)
-radial growth phase- through epidermis
-vertical growth phase-dermal layer
-metastatic melanoma- gets into BVs in dermal layer
What is the Breslow thickness?
Less than 1mm- 5yr survival 95-100%
1-2mm- 5yr survival 80-96%
2.1-4mm- 5yr survival 60-75%
More than 4mm- 5 yr survival 37-50%
Name the treatments for skin cancer:
Surgery- sentinel node biopsy
Chemotherapy- dacarbazine IV infusion or temozolmide oral
-Taxanes (docetaxel, paclitaxel) and Pt agents
Targeted therapy- IL2, Ipiliumab (anti CTLA4), -Anti-BRAF, Anti-PD1
How do melanoma cells grow in cancer?
Due to EGF which stimulate S cells through TRK-> Ras, Raf, MEK, ERK
BRAF in melanoma cells (40-50% have mutations)
Describe the new anti-melanoma therapies:
Target protein- protein interactions
CTLA4 present on T cells and B7 on melanoma or PDL1 on melanocytes
e.g Ipilimumab
Block immunological check points so melanoma cells don’t become resistant to T cells trying to kill them
Name the different types of warts:
Common- round, firm, raised, knocks
Verrucas- white, soles of feet, flat
Plane- clusters, yellowish, smooth, young people
Filiform- long, slender, neck and face
Periungual- nails, change shape, painful
Mosaic- tile like clusters, palms and soles
What are warts caused by?
HPV causes excess keratin production on epidermis
What are the counselling points with warts?
Can spread through close skin to skin contact, contaminated objects e.g towels, shoes, communal changing areas, more likely to spread if skin is wet and soft
Clear up after about 2 years
What are the treatments of warts?
Salicylic acid containing gels
Cryosurgery- liquid nitrogen
What are genital warts caused by?
Very common, sexually transmitted
Months or even years to develop after HPV infection
What are the treatments for genital warts?
Liquids and creams e.g imiquimod, which stimulates the IS to fight HPV by encouraging IFN production
Keratoylsis and cryosurgery- shaving keratin off
What is impetigo caused by?
Common in children, highly contagious
Caused by steptoccocus/ staphylococcus infections
Causes sores and blisters
Very common in young (1/35) children in UK aged 0-4
What are the 2 types of impetigo?
Non-bullous:
most common, nose and mouth, sores burst quickly and leave a yellow/brown crust
Bullous:
trunk, fluid filled blisters that burst after a few days, leave yellow crust
What is the treatment for impetigo?
Topical antibiotics, stay away from other people
Severe cases systemic antibiotics e.g flucloxacillin
What fungi causes fungal infections?
Dermatophytes and yeast invade and grow in dead keratin
What is the treatment for fungal infections?
Small areas treated with topical imidazoles (2%)
Severe cases with systemic antifungal agents (griseofulvin/ itraconazole)
What can cause fungal infections?
Immunocompromised patients- candida and aspergillus
Use of antibiotics- killed normal bacteria so fungi can invade
Describe what causes hypo pigmentation:
Vitiligo
Decrease production of melanin
Albinsim
Infections, blisters
Burns
Phototherapy
Describe what causes hyperpigmentation:
Enhanced melanin production
Pregnancy, Addisons
UV exposure
ABs and antimalarials
Hydroquinone
What is vitiligo?
Also called leucoderma
Loss of colour of skin in patches- usually get bigger with time
Affects any part of the body, hair and inside of mouth but more often around eyes, nostrils, mouth, navel, knees and elbows
Melanocytes die or stop functioning
What population does vitiligo most commonly affect?
Affects people of all races and skin types
95% develop before age of 40
Name and describe the 3 types of vitiligo:
Focal- few spots missing
Segmental- patches on one side of body (unusual)
Generalised- many patches on body, often symmetrical
What is the aetiology of vitiligo?
Autoimmune components
30% of patients have family history
12-24% have an autoimmune disease
Immune system attacks its own melanocytes
Triggers- stress, skin damage, hormonal changes, phenol exposure, liver/ renal disease
What is the pathogenesis of vitiligo?
Auto antibodies to tyrosine hydroxlase in non-segmental vitiligo (enzyme in melanin synthesis)
Increase in ROS production in mitochondria of affected cells
Describe topical use:
External use
Localised action
Reach systemic circulation in sub therapeutic drug concentration
Describe transdermal use:
External use
Skin isn’t primary target
Drugs transport through percutaneous route to systemic circulation
Name different examples of topical formulations:
Solutions
Colloidion
Emulsions (lotions)
Semisolids (ointments, creams, pastes)
Solids (powders, aerosols)
Spray (lidocaine)
Suspensions
Name and describe the 5 target regions in dermatology:
Surface treatment- protective layer, insect repellent, suncream
Stratum corneum- emollient, keratosis
Skin appendage- acne, antibiotics, antiperspirant
Viable epidermis- dermis- anti-inflammatory, anaesthetics, antihistamine
Systemic treatment- transdermal
Describe the route for transdermal drug delivery:
Across the stratum corneum into the systemic circulation (vascular within dermis)
What are the advantages of transdermal drug delivery?
Avoids first pass metabolism in the liver
Consistent site of absorption
Can give contact drug input rate
Can stop dose by removing patch
Name and describe the 2 types of drug penetration across the skin barrier:
Intercellular- between cells
Transcellular- through cells (lipid based)
What factors are important for transdermal delivery?
Physiochemical nature
Potency
Timescale of drug exposure
Site and condition of the skin
Formulation
Alteration of the skin barrier
Skin hydration
Describe timescale of drug exposure in transdermal deliveries:
Creams, lotions, ointments applied OD,BD,TDS
Patches OD or every 72 hours
Describe site and condition of the skin in transdermal deliveries:
SC thickness varies across body
Broken or inflamed skin more permeable
Hirsute (hairy) skin may be more permeable- as faster through the hair follicle
Describe the skin hydration state in transdermal deliveries:
Hydrated skin is generally more permeable to drug
Thought to be due to looser packing of SC lipids, less restrictive path to drug diffusion
Opens up SC and increase SC penetration 10 fold
Describe the alteration of skin barrier by formulation in transdermal deliveries:
Can include penetration enhancers
Ointments are greasy and restrict water loss from skin so stratum corneum becomes more permeable
Describe the formulation of glucocorticoids:
Target inflammation of the skin
Fatty acid esters of active drugs to promote absorption
What are the different classes of glucocorticoids and name examples:
Mild-hydrocortisone
Moderate- alclometasone dipropionate, clobetasone butyrate, fluocortisone
Potent- beclomethasone esters
Very potent- clobetasol propionate, diflucortolone valerate
What is the mechanism of glucocorticoids?
Inhibit release of inflammatory mediators- NFkB, neutrophil activation and emigration, mast cell release, immune cell activation
What are the SEs of glucocorticoids?
Short term, low potency generally safe
Prolongued use:
-steroid rebound
-skin atrophy (breakdown) 1-3 weeks of starting
-systemic effects (buffalo hump/moonface)
-spread of infection
-steroid rosacea in face
-stretch marks and superficial dilated BVs
Name examples of retinoids:
Tretinoin
Isotretinoin
Adapalene
Describe the MoA of retinoids:
Binds to RXR and RAR nuclear receptors in keratinocytes and sebaceous glands to decrease cell proliferation and sebum production
Anti-inflammatory effects through pleiotropic actions on immune system
What are the SEs of retinoids?
Dry, flaky skin
Stinging, burning
Joint pains
Teratogenic
Describe the MoA of Vit D analogues:
Act via Vit D receptor to modulate gene transcription in keratinocytes, fibroblasts, Langerhans and sebaceous glands
Inhibits proliferation and pro-differention of these cells
Inhibits T cell activation- antiproliferative effect and improved differentiation
What are the SEs of vit D analogues?
Possible effects on bone and potential skin irritation
When are systemic side effects of topical corticosteroids more likely to occur?
Potent topical steroids
Long term treatment- more than 2 weeks
Large areas
What is the process for choosing which topical corticosteroid to use?
Select the lowest potency likely to work within 7-14 days based upon:
-severity of inflammation
-response to treatment
Review in 7 days- max prescribe 2 weeks
How do topical calcinerurin inhibitors work?
Reduce inflammation through suppression of T lymphocyte responses
What are the benefits of using topical calcineurin inhibitors?
Suitable for use on the face as doesn’t cause skin atrophy
Suitable for children ages over 2
What is the treatment for moderate eczema?
Manage triggers
Emollients
Moderate topical steroid
Topical calcineurin inhibitors
Bandages
Why is bandaging used in eczema?
Occluding the area
Prevent scratching, decreases pruritus
Keeps creams in contact with the skin
Can apply them over emollient if chronic lichenified eczema
Over emollient and steroid (specialist use as increase absorption)
What is the treatment for severe eczema?
Managing triggers
Emollients
Moderate topical steroid
Topical calicneurin inhibitors
Bandages
Phototherapy
Oral corticosteroid
Describe the use of systemic corticosteroids in eczema:
E.g prednisolone
Short term in severe/ wide spread
Gain control very rapidly
Not recommend for children
Describe the use of immunosuppresents in eczema:
Ciclosporin- not recommend for children
Extremely effective in chronic severe eczema
Describe the use of oral antibiotics in eczema:
Treats visibly infected skin with oral Abs
Flucloxacillin first line
-erythromycin in penicillin allergy or resistant
-clarithromycin if erythromycin not tolerated
Treat with 1-2 week course
What infection is normally present in eczema?
S aureus 90% colonist
Swab from infected lesion if resistance suspected or not SA infection
Describe the use of topical antibiotics for eczema:
Fusidic acid
Small localised infection
Max 2 weeks treatment
What are the general measures in eczema to prevent infection/ spreading?
Don’t leave tub of cream open
Use clean spoons to remove cream
Re-order new pot of cream after infection
Describe the use of antihistamines in eczema:
Not for routine use
Trial with non-sedating antihistamine
-4 weeks
If non-sedating failed, short term use of sedating antihistamine at night
Oral only, topical cause sensitisation and have no place in management
What is flexural (inverse) psoriasis?
Red glazed plaques confined to flexures- back of knee etc
-groin, natal cleft and sub mammary
Usually no scale
Lesions are shiny and smooth as scales being rubbed
Skin very tender
Infection risk as folded and moist area
What is the 1st line layer of treatment for psoriasis?
Emolients
Vit D analogues
Topical steroids
Dithranol
Coal tar
What are the counselling points when using emollients?
Apply regularly and liberally
Creams used as a soap substitute
Bath or shower emollients- not in older people due to slipping
-add to bath water
-apply to wet skin and rinse
Describe the use of topical corticosteroids in psoriasis:
E.g clobetasone butyrate 0.05%
No mild as thickened skin so won’t be effective
Stronger agents on palms and soles of feet
Inappropriate for widespread psoriasis
Long term use
-potent, max 8 weeks
-very potent, max 4 weeks
How does dithranol work?
Anti-proliferative effect on epidermal keratinocytes
Inhibits thymidine into DNA and ATP to be supplied to epithelial
What is the dosing like for dithranol?
Start with low conc (0.05%) and gradually increase depending on tolerance (max 3%)
Proprietary preps (e.g Dithrocream) usually washed off after 5-60 mins
Specialist nurse intensive treatment overnight
What are the counselling points when using dithranol?
Very irritant- careful to avoid the normal skin
Difficult to use with many small lesions
Stains skin, clothing and bath fittings red/brown
Unsuitable for face, flexures or acutely inflamed psoriasis
Describe coal tar as a treatment for psoriasis:
Anti-inflammatory and keratolytic activity
Mainly used for scalp psoriasis
Efficacy enhanced when used with UVB
Known carcinogen? little evidence
What is the second line treatment for psoriasis?
UVB and PUVA
MTX and ciclosporin
Acitretin
Describe the use of UVB in psoriasis:
Slows cell proliferation- vit D in inactive form into active vit D (calcitrol)
Light of wavelength 290-320nm
Responsible for sunburn
Used alone or with emollients
Dose given 3x a week until clear for usually 4-6 weeks
Describe the use of PUVA in psoriasis:
Psoralen plus UVA
Psoralen activated by UVA to interfere with DNA synthesis
Decrease epidermal cell turnover
Allows deeper penetration of UV light
What are the counselling points when undergoing treatment for PUVA?
Dark goggles worn during and 8 hours after treatment to prevent cataracts
What is the CI of PUVA therapy?
If genetic risk of melanoma
Describe the use of MTX in psoriasis:
Most effective treatment for psoriatic arthritis
Anti-proliferative (antifolaxe effect) and T cell suppressor
Describe the use of ciclosporin in psoriasis:
T cell suppressor
Renal function and BP monitored
Avoid over exposure to the sun and shouldn’t receive concurrent UV therapy
Describe the use of Acitretin in psoriasis:
If MTX and ciclosporin unsuccessful
Oral vit A analogue
Bind to nuclear retinoid acid receptors
-involved in controlling development and maturation of cells
-induce keratinocyte differentiation and decrease epidermal hyperplasia
Enhances the action of PUVA allowing decrease of dose
Name and describe the 3rd line treatment in psoriasis:
TNF agonists-decrease T cell mediated effects
MAB- adalimumab and inflixiamb
Fusion proteins- entanercept
Describe the use of 3rd line treatment in psoriasis:
Most effective 60-80% having at least 75% within 12 weeks
Long term SEs unknown
-infection -increase malignant disease
Restricted use for only severe psoriasis and failed to respond or can’t tolerate conventional systemic treatments
What should be the precautions with electrical burns?
May have cardiac arrhythmia- even with minor burns
Check how they are feeling, heart rate
What are the functions of antihistamines prescribed in babies for eczema?
Does’t stop the itch, just makes them drowsy
Describe the components and effectiveness of emollient foams:
Lots of water content so absorbed easily but not for long
Describe the components and effectiveness of creams:
Less water content- more emollient, quite quickly absorbed, few hours relief
Describe the components and effectiveness of ointments:
Greasy, low water content, hydrate for a long period of time as takes a while for the skin to absorb them
For babies it makes scratching more difficult
