Skin Flashcards
Skin most common conditions:
They are all inflammatory chronic conditions
-Excema
-Psoriasis
-Acne Vulagairs
Skin ?
It acts as a barrier and is impermeable to water
-prevents the loss of moisture and ingress of substances
-protects tissue against thermal and mechanical damage
-shields tissues from UV radiation and infection
-functions as part of thermoregulation
-synthesises vitamin D3 via UV exposure and is a sensory organ
Layers of skin:
1.)Epidermis: formed of multiple layers, contain keratinocytes
2.)Dermis: where sweat glands, hair, air follicles, muscles, sensory neuron’s and blood vessels are. Formed of the papillary layer and reticular layer
3.) Hypodermis: formed by adipose, lobules and ski appendages such as hair follicles, sensory neurones and blood vessels.
Looking inside the eperdermis
STRATUM CORNEUM
The upper most layer, consisting of 20-30 cell layers.
Consists of keratin and horny scales made up of dead keratinocytes.
STRATUM LUCIDUM
Present in skin found in the palms and soles, consisting of 2-3 cells.
STRATUM GRANULOSUM
Containing keratohyalin granules and lamellar granules.
Keratohyalin granules contain a keratin precursors, which aggregate and form bundles.
STRATUM SPINOSUM
8-10 cell layers, containing cells with cytoplasmic processes, such as Langerhans cells (a dendritic cell).
Langerhans cells engulf microorganisms and foreign bodies.
STRATUM BASALE
Consists of mitotically active stem cells that constantly produce keratinocytes.
Cells of the eperdermis:
-Keratinocytes: - originate from the basal layer, produce keratin and responsible for the formation of the epidermal water barrier
- Melanocytes: found in the stratum basal, produce melanin giving skin pigment
-Langerhans cells: found in the stratum spinosum, a dendritic cell, playing a significant role in antigen presentation
-Merkles cells- found in the stratum basal, a mechanoreceptor used in light touch
What is Excema?
A chronic, pruritic, inflammatory skin condition known as atopic dermatitis
Common features of Excema:
generalised skin dryness, early years disease onset, personal or family history and atopic disease (asthma, allergic rhinitis).
Commonly develops in the first year of life but can occur at any age
Eczema and how it can occur
It can occur in one of three ways
1.) genetic- family history, loss of function of filaggrin, variation in phenotypical expression of cytokines
2.)microbiome- S aureus colonisation
3.) epidermal barrier dysfunction- elevated trans epidermal water loss of pH, physical damage and allergic inflammation
Function of keratinocytes:
Become disrupted/reduced presence of natural moisturising factors
Function of corneocytes
This is differentiated keratinocytes, they shrink due to water loss
Function of eperdermis:
It dehydrates, gaps between keratinocytes allow inclusion of irritants
Inflammation occurs propagating pruritis and further disruption of the eperdermis
Management of eczema:
Triggers, complete emollient therapy and flare up therapy
Non pharmacological treatments: education and risk management
Patients need to be educated about the pathophysiology of eczema and factors that provoke it, how to recognise flare up of the condition and how to recognise symptoms and signs of bacterial infections
Give lifestyle advice: consider psychosocial difficulties, avoid extreme hot or cold weather/humidity and irritating clothing like wool, keep nails short and dont use potent soaps and detergents and make sure skin hydration is maitained
Non pharmacological treatments: hydration complete emollient therapy
This is clinically proven to largely reduce the number and severity of Excema flare ups, reduces amount of treatment to stop a treatment by 75%
Topical application of lotions, cream, gels, ointments and oils.
Emollients occlude the disrupted epidermal barrier, therefore reducing dehydration of the epidermis.
Occlusion impedes ingress of irritants and pathogens into the epidermis.
Specific emollients nourish the epidermis with humectants, a synthetic replacement of NMF.
Humectants draw and hold moisture in the epidermis.
The occlusion of complete emollient therapy:
Emollients efficacy dependent on products richness
-depends on patients and richness describes the ratio of aqueous and organic/greasy excipients of a formulation
Richness of complete emollient therapy :
Low richness
Least greasy.
Shorter-lived occlusion time.
Greater patient acceptability.
High richness
Most greasy.
Long lasting occlusion time.
Less patient acceptability.
Humecrants:
Humectants: substance, especially a skin lotion or a food additive, used to reduce the loss of moisture.
Examples of them are; glycerine, glycolic acid, lactic acid, propylene glycol, hyaluronic acid, urea, pantheons, gelatine, sorbitol
Complete emollient therapy process:
1.)Emollient as leave-on product:
4-6 applications per day (every 3 hours)
Emollients should be wiped onto the skin, in the same direction as the hair grows.
Emollients should not be rubbed into the skin.
Patient should use 0.5 Kg – 1 Kg per week, depending on age and severity of their condition.
2.)Emollient as ‘soap’ substitute:
Instead of any soap, handwash or shower gel.
Infers and additional 0.5 Kg of emollient use per month.
3.) Emollient as a bath additive:
Added directly to bath water, or lightly applied and rinsed from the skin during bathing.
Patients should be advised to pat dry, rather than rub dry, their skin after washing.
Infers and additional 0.5 Kg of emollient use per month.
Pharmacological treatments:
It is the management of flares of eczema; topical corticosteroids and calcineurin inhibitors
About topical corticosteroids:
Main stay of treatment for flare-ups of eczema:
Effective
Cheap
Vast clinical experience
Widely used for inflammatory and hyperproliferative disorders.
Different potency treatments available.
Long term use (especially high potency) on large body areas can lead to adrenal suppression.
Other side effects- skin thinning, telangiectasias, folliculitis and contact dermatitis.
Topical corticosteroids inflammation:
Swelling, redness, pain and the later proliferative changes in chronic inflammation.
Mast cells, present in the dermis, are activated in response to inflammation and therefore release histamine.
Lymphocytes in the dermis also generate an inflammatory response.
Following an inflammatory response the genes of the keratinocyte cell produce mRNA which is translated into inflammatory cytokines to further propagate the inflammatory response.
Mechanism of action of topical corticosteroids:
Corticosteroids exert their effects via the glucocorticoid receptor
Glucocorticoid receptors can be present in several forms:
Corticosteroids exert their effect via the α-isoform (interacts with endogenous cortisol) of the glucocorticoid receptors.
High presence of the glucocorticoid receptor β-isoform (regulatory roles) can result in resistance.
Glucocorticoid receptors can be found in most of the cells in of the body.
Glucocorticoid receptors are specifically expressed in the keratinocytes and fibroblasts of the epidermis.
When unoccupied, glucocorticoid receptors are usually present in the cytoplasm.
Glucocorticoids: mechanism of action:
The glucocorticoids diffuses into cell and binds to the glucocorticoids receptor which is activated by the removal by the removal of the heat shock protein.
The activated receptor-glucocorticoid complex enters the nucleus and binds to steroid response elements on target DNA molecules and the subsequent response can either induce the synthesis of specific mRNA or inhibits transcription factors which represses genes
Glucocorticoids: mechanism of action: when its an anti inflammatory response:
After a inflammatory response this happens:
The phospholipid membrane of certain cells is converted to arachidonic acid by the enzyme phospholipase
The arachidonic acid is convert to inflammatory mediated to the COX enzyme (inflammatory mediators prostaglandins, leukotrienes, thromboxane).
Glucocorticoids inhibit both enzymes COX and phospholipase A2
Thereby inhibiting the formation of the inflammatory mediators.
This also results in the upregulation of anti-inflammatory proteins such as lipocortin (phospholipase A2 inhibitor)
Topical corticosteroids: optimised therapy:
No evidence to support that you should apply more than once daily, match potency of therapy to severity of flare up, short course of 7-14 days and counsel on fingertip unit application
Potency of a topical corticosteroid therapy factors:
:
Choice of corticosteroid.
Concentration of corticosteroid used.
Formulation.
Topical calcineurin inhibitors:
Non-steroidal immunomodulating agents
Used where there is a high clinical risk of skin damage.
If skin is already damaged by topical corticosteroids.
Where regular/long course of more potent topical corticosteroids are needed for a patient.
Where more potent topical corticosteroids are needed on thin skin (face, flexures, groin or genitalia)
Examples: Tacrolimus and pimecrolimus
Topical calcineurin inhibitors limitations:
More irritant when initially applied (burning sensation only generally lasts first few days of treatment)
Far less clinical experience of safety.
Fare more expensive.
Mores restricted product license.
Topical Calcineurin inhibitors: Mechanism of Action
Topical calcineurin inhibitors inhibit the synthesis of pro-inflammatory cytokine (interleukin 2), which are required for the activation of the immune response, which results in inflammation.
In the cytoplasm of the T cell these bind to the intracellular protein FKBP (macrophilin-12).
This complex inhibits calcineurin (a calcium-calmodulin dependant phosphatase).
Prevents calcium dependant NFATc (Nuclear Factor Activation T-cells) activation.
Inhibits NFATc translocation to nucleus.
Prevents the expression of interleukin-2, the cytokine signalling for T-cell activation and migration.
Results in immunosuppressive activity.
Topical calcineurin inhibitors have anti-inflammatory activity due to T-helper activity affecting the synthesis and release of pro-inflammatory cytokines.
What is psoriasis?
A systemic, immune mediated, inflammatory skin disease which typically has a chronic relapsing remitting course, and may have nail and joint involvement.
Epidemiology of psoriasis:
Around 1-3% people globally have psoriasis
Can occur at ant age but two peaks in incidence 20-30 wand 50-60
Men and women equally affected
The prevalence of psoriasis varies on ethnicity- more common in white people than other ethnic groups
Aetiology of psoriasis: (causes of disease)
Believed to be a multi system disorder
1.)genes- skin specific, innate and adaptive immunity
2.)Immune system- dendritic cells, keratinocytes
3.)environment- trauma, drugs, smoking, stress and microorganisms
What is the typical sensitisation phase?
Immune mediated inflammatory response:
Microbes on surface of the skin – captured by dendritic cells and broken down. Fragments presented to T cells
T cells respond by releasing cytokines
Resulting inflammation causes increased keratinocyte proliferation
Neutrophils also recruited to infection site
Immunological response usually returns to normal after microbe destroyed
Psoriasis effector phase?
Secondary trigger – later local skin damage or other disturbance
Resident immune cells stimulated to produce cytokines
Neutrophils recruited to the epidermis which collect in stratum corneum
Further cytokines produced which stimulate Keratinocytes resulting in hyperproliferation and the evolving vicious cycle
Hyperproliferation of the eperdermis:
Following the propagation of the effector phase:
More epidermal keratinocytes actively growing – proliferate excessively
Cells do not differentiate appropriately – Mature abnormally
Terminal differentiation to cornified epidermal cells in 4 days rather than 28
Results in thick, keratinised, scaly epidermis - Parakeratosis
Types of psoriasis:
1.)Plaque
2.)Guttate
3.)Flexural
4.)Scalp
What is plaque psoriasis?
Accounts for 90% of psoriasis
-Very well-defined raised edges
-Deep red/pink plaque
-Covered in silvery scales
-When de-scaled plaque is shiny in appearance
-Thick and itchy (painful)
-Most common sites: elbows, knees, shins, low back
-Often symmetrical
What is guattate psoriasis?
-Paintbrush splatter
-Drop-like small red macules
-Typically follows streptococcal pharyngitis
-Exotoxin ‘super-antigen’ trigger
-Most common in young adults
-Often leads on to chronic (plaque) psoriasis
What is Flexural psoriasis?
-Sub-mammary, axillary and anogenital flexures
-Do not scale due to friction
-Generally very red and ‘glistening’
-More common in women/elderly
-Facial and hairline psoriasis needs similar care when treating
What is scalp psoriasis?
-With/without plaque psoriasis
-Commonly extends just beyond hairline/scalp margin
-Similar in appearance to plaque psoriasis but hair means scale becomes thick and difficult to remove
-Localised hair loss can occur which regrows in remission
Psoriasis management:
Type of psoriasis
Assess severity
Managed to meet 3 aims:
Induce remission
Maintain remission
Improve comfort and appearance until treatment takes effect
Treatment based on severity of psoriasis:
Mild/moderate- topical
Severe or unctrolled by topical treatments or with arthritis: systematic agents/phototherapy
Severe or with arthropathy and uncontrolled by topical treatment systematic/phototherapy- biologicals (TNF blockers/monoclonals)
Types of topical treatments:
-Emollients
-Keratolytics – salicyclic acid
-Vitamin D analogues
-Coal tar
-Dithranol
-TCS
-TCI
-Vitamin A analogues
Emmollients of psoriasis:
Pros: prevents and reduces drying, cracking and scaling
Soothes
Pre-softens plaque to aid penetration of treatment. I.e. a less greasy emollient 30 minutes between treatment
Cons: does not control psoriasis- adjunct to other treatments
THIS SHOULD BE PRESECRIBED FOR ALL PATIENTS-ISED IN FLARES AND REMISSION
Keratolytics- salicylic acid
Salicylic acid is the breakdown of keratin to reduce scaling
Pros: useful if heavy scaling
Removing scaling before treatment and preventing re-scaling during treatment
Cons: very irritant to surrounding healthy skin
Hence not useful for small/thin plaques, widespread plaques or poorly defined plaques
Limited availability of preparations for skin
Does not control psoriasis- adjunct to other treatments in heavily/hyperkertatotic psoriasis
Alternatives to keratolytics:
Sebco® for scalp (Coal Tar, Salicylic Acid, Sulfur):
Massaged into scalp (often needs 2 consecutive nights)
Occlude with shower cap and leave on overnight
Comb out with fine tooth comb before washing
Hair loss due to extent of scaling not treatment and is temporary
Mechanical descaling
Thorough rubbing (using emollients)
Occlusion
Heavy emollient under dressing for smaller plaques
25% Urea balm/ointment
Flexitol/Dermatonics much cheaper and more readily available than ‘specials’
What are vitamin d analogues?
Calcitriol, Calcipotriol and Tacalcitol
Vitamin D and its analogues exert an effect through the steroid like VDR group of receptors in keratinocytes to modulate gene transcription
This reduces keratinocyte proliferation
Hence differentiation and turn over of epidermal cells normalise
Licenses limit application per week due to hypercalcaemia risk
Pros and cons for vitamin d analogues?
Pros:
Clean and convenient
Calcitriol and tacalcitol may be considered in face and flexural psoriasis, guttate psoriasis, and where scalp psoriasis extends beyond hairline (but more irritant than TCS and TCIs)
Cons:
Short duration of remission so constant treatment may be required.
Calcipotriol too irritant for flexural psoriasis
Risk of hypercalcaemia especially with overuse of tacalcitol
What are topical corticosteroids (TCS)?
Anti-inflammatory and anti-proliferation
Due to plaque thickness longer courses needed than eczema
Pros and cons of topical corticosteroids (TCS)?
Pros:
Clean and convenient
Does not irritate healthy surrounding skin (although care needed due to side-effects with frequent exposure)
Mild to moderate TCS useful for face/ flexural psoriasis and where scalp psoriasis extends beyond hairline
Cons:
Short duration of remission: Regular treatment may be required
Potent TCS needed to penetrate thick plaques
Risk of skin atrophy/damage and systemic adrenal suppression increases with potency and length of treatment
Potent/very potent should not be used on thin plaques due to high risk of this
Rebound psoriasis: Need to wean off
Use without other treatments on large areas, abrupt withdrawal, or use on generalised psoriasis can cause dangerous psoriatic reactions i.e. erythrodermic psoriasis/generalised pustular psoriasis
TCS formulations and the scalp:
Traditional scalp applications tend to be non-viscous with high alcohol content
Stinging and irritation on application
Run down face and neck causing irritation and risk of TCS related adverse effects
Newer treatment options are:
Locoid® lotion – Hydrocortisone butyrate lotion BD
Synalar® gel – Fluocinolone gel BD
Dovobet® gel – betamethasone/calcipotriol OD
Clarelux® foam – clobetasol BD (scalp only)
Etrivex® L’oreal shampoo – clobetsol OD for 15 mins (scalp only)
What is coal tar?
MoA poorly understood but involves modulating DNA replication
Anti-inflammatory, anti-bacterial, anti-fungal, anti-pruritic and anti-mitotic
Traditional treatment but modern preparations are less messy, smelly and staining
Effective in managing Sebo-psoriasis
Pros and cons of coal tar?
Pros:
Safe, effective and non-irritant
Hence ideal for ill-defined/widespread lesions
Coal tar shampoos left on for 10 minutes before washing off 3 times a week maintain remission of scalp psoriasis
Cons:
Even modern preparations have a ‘Marmite’ smell and can stain clothing and light coloured hair
What is dithranol?
Very little information on MoA
Anti-inflammatory and anti-proliferative
Inhibits DNA replication
The most effective topical treatment but very limited patient acceptability
10-60 minute contact depending on guidance
Pros and cons of dithranol?
Pros:
Very effective and safe
Prolonged remission
Cons:
Unpleasant smell
Very irritant – have to increase strength every 3-5 days as tolerated
Stains everything! -
Skin, clothes, linin, bathroom suite
What is vitamin A analogues (retinoids)?
Topical – Tazoratene (licensed for psoriasis)
Vitamin A normally acquired from dietary sources
Can undergo irreversible oxidation to retinoic acid which has potent effects on the skin
Retinoid drugs are derivatives of retinoic acid
Pros and cons of vitamin A analogues (retinoids):
Pros:
Where other topical treatments are unsuitable or ineffective a trial may be considered to avoid systemic treatment
Cons:
Max 10% body surface due to systemic absorption
Irritant (mild-moderate TCS applied other end of day to reduce inflammation)
Photosensitivity (applied at night and sunscreen may be needed)
Teratogenic (caution and complimentary contraception in women of child-bearing age)
Limited efficacy
