skin 7

Question 1

what is natural moisturising factor?

Answer 1

Natural Moisturising Factor (NMF) is an endogenous breakdown product from filaggrin hydrolysis
is a hygroscopic mixture including amino acids, pyrrolidone carboxylic acid (PCA), lactic acid and urea

NMF plays a significant role in maintaining free water within the stratum corneum
NMF generation together with other processes such as corneocyte maturation, desquamation and lipid biosynthesis regulate stratum corneum hydration
Stratum corneum has been described as having a “biosensory function”, responding to external humidity to maintain optimal water content.

Question 2

how is NMF generated?

Answer 2

profilaggrin -> desphorylation -> filaggrin –> hydrolysis –> NMF

Amount of NMF?
Individuals have 10, 11 or 12 filaggrin repeat units
fewer units cause drier skin.

Role:
Mechanical properties of SC – flexibility, integrity, cohesion, hydration.
Buffers – pH increases when NMF decreases.

Question 3

what does the loss of filaggrin result in?

Answer 3

Corneocyte deformation (flattening of surface skin cells),

• Which disrupts the organisation of the extracellular lamellar lipid bilayers?.

A reduction in Natural Moisturising Factor(s),

• Including metabolites of pro-filaggrin.

An increase in skin pH which encourages serine protease activity

-The enzymes which digest lipid-processing enzymes and desmosomes.
Serine proteases also generate active cytokines (e.g. IL-1a and Il-1beta) and promote skin inflammation.

Question 4

what is ECZEMA (DERMATITIS)
symptoms
treatment

Answer 4

Derived from Greek word for “boiling” (skin can become so acutely inflamed that fluid weeps out/vesicles appear)

Many forms of eczema but all have certain features in common. In subacute eczema, skin is erythematous, dry, flaky, oedematous and crusted (esp. if infected). In chronic eczema, skin is often thickened or lichenified (thickened epidermis, prominent normal skin markings)

Almost always itchy

TREATMENT
Treatment: emollients e.g. aqueous cream?!, emulsifying ointment to maintain hydration of stratum corneum and reduce water evaporation. Helps avoid dryness and cracking of skin.

Topical steroids e.g. 1% hydrocortisone will reduce inflammation and itchiness.

Sedating oral antihistamines e.g. chlorpheniramine (Piriton) at night.

Avoid soap (dries the skin / surfactants), wool fabrics and synthetic materials (irritate skin).

Question 5

what is atopic eczema?
who is it most common in
symptoms
treatment

Answer 5

Commonest form of eczema (occurs in up to 5% of UK population), especially in babies from 3 mths. Occurs in 10-15% of all children

Appears as dry, scaly, erythematous and itchy rash particularly noticeable on face, scalp, neck, inside elbows, behind knees

Often resolves in childhood (~75% of cases) but can continue into adulthood

Question 6

what is aptopy

Answer 6

“a predisposition towards developing allergic hypersensitivity

Question 7

what is atopic march

Answer 7

Atopic march: a typical sequence of immunoglobulin E (IgE) antibody responses

Question 8

what is IRRITANT CONTACT ECZEMA
causes

Answer 8

causes:
Results from damage to skin from topically applied liquids
or chemicals in absence of an allergic mechanism

Occurred shortly after patient had baby.
Can be due to excessive hand washing,
chemical/irritant exposure e.g. soaps,
cleansers, or exposure to cold. Contact with certain vegetables can lead to eczema e.g. garlic, onions, tomatoes

Caused by frequent licking of lips
(saliva-induced)

Question 9

what is allergic contact eczema
causes

Answer 9

Mediated through an allergic mechanism whereby patient is allergic to a
specific allergen and whenever skin comes into contact with that allergen
then get eczematous rash e.g. nickel (jewellery, jean studs), leather (shoes,
watch straps), dyes, plants

Allergic contact eczema in response to Rhus (poison oak) species

Not always blisters: allergy to nickel and potassium dichromate

Question 10

can aqueous cream used for eczema

Answer 10

Is widely recommended
Though advice in BNF recently changed

BUT
Contains 1% sodium lauryl sulphate (harsh anionic surfactant)

Growing evidence of adverse reactions
“Itchy cream”
Recent research shown that aqueous cream BP reduces stratum corneum thickness, increases transepidermal water loss, affects stratum corneum pH and so enzyme activity and so NMF and so…..
Should not be used as a leave on emollient in AD

Recommend emollient without SLS, e.g. E45 Cream (but lanolin may cause irritation), and only advise aqueous cream as a soap substitute….

Question 11

number of fingertips to apply for certain parts of the body

Answer 11

check lecture slid - week 22 - skin 7 - slide 17

Question 12

how can order of applications effect drug delivery

Answer 12

Order of application can affect drug delivery.
Occlusion effects of emollient on top could increase drug delivery
Emollient on skin first could provide an additional barrier
Or, excipients in emollient could act as permeation enhancer and increase subsequent steroid diffusion
Or excipient could influence on the corticosteroid formulation, structure and release (increase or decrease)

Unpredictable:
Corticosteroid cream or ointment can behave differently
Different emollients have different effects on steroid delivery

For now, I’d generally advise corticosteroid first, leave an hour, then emollient (UK National Eczema Association advice)

Question 13

what is seborrhoeic eczema?
symptoms
how can it be aggravated
what advice should be given
treatment - scalp and face, ear and chest

Answer 13

Common, harmless scaling rash affecting scalp, face
and other areas (eyebrows, ears, folds of underarms and groin)

Dandruff (pityriasis capitis) is seborrhoeic eczema of the scalp

Cradlecap in infants up to 6mths may be same condition

Related to proliferation of a normal skin yeast (Pityrosporum ovale)

Not contagious and not related to diet

Can be aggravated by illness, psychological stress, fatigue, change of
season and reduced general health

Patients with neurological disorders e.g. Parkinson’s, stroke
especially at risk

May predispose to psoriasis

Advice:
Reduce exposure to allergens e.g. house dust mite, moulds, grass pollens, animal dander
Keep cool - wear loose cotton clothing, avoid wool and dusty
conditions, wear gloves when handling chemicals, solvents, detergents
Use soap-free cleansers

TREATMENT
Seborrhoeic eczema in adults may be very persistent.
Generally kept under control with regular use of antifungal agents and intermittent applications of topical steroids.
Infantile seborrhoeic eczema usually clears up completely before baby is 6 mths old; rarely persists after one year. If treatment is required, mild emollients, hydrocortisone cream and / or topical ketoconazole are useful.
Treatment of seborrhoeic eczema depends on which part of the body is involved. It is likely to need repeating from time to time.

Scalp
Medicated shampoos containing ketoconazole, selenium disulphide, zinc
pyrithione, coal tar, and salicylic acid, used 2x wk for at least a month.
Steroid scalp applications reduce symptoms, and should be applied daily
for a few days every so often.
Tar creams can be applied to scaling areas and removed several hours later by shampooing.

Face, ears, chest & back
Cleanse affected skin thoroughly 1-2x each day.
Ketoconazole cream once daily for 2-4 wks.
Hydrocortisone cream can also be used, applied up to 2x daily for 1-2 wks.
Severe cases may receive a course of UV radiation

Question 14

what is SYSTEMIC LUPUS ERYTHEMATOSUS
causes

Answer 14

mainly affects women between 35-45 yrs

one symptom is classic “butterfly” rash on cheeks and nose.

can be confused with eczema

Question 15

what is psoriasis
causes

Answer 15

Chronic, scaling disease with associated skin redness (skin types 1-4) or inflammation.

Appears as raised, rough, reddened areas covered with fine silvery scales; can appear grey on skin type 4 & 5.

Represents abnormality in which epidermal cell differentiation at much faster rate (~10x) than normal.

Commonly eruption first appears at back of elbows and front of knees (flexor surfaces). Patches can also be on other parts of body e.g. scalp

CAUSES
Specific cause remains unknown although genetic and environmental components. Factors that may trigger psoriasis include:

1.  Infection - some throat and upper respiratory tract infections lower threshold for psoriasis

2.  Trauma - e.g. surgical incisions, burns, rubbing, scratching, picking, sunburn and/or local infection of skin

3.  Emotional stress/anxiety

4.  Climatic factors - in general, sunlight is beneficial (moderate sun) but sunburn is detrimental. In some patients, any sunlight makes condition worse

5.  Certain drugs e.g. lithium, chloroquine, -blockers, NSAIDs, ACE inhibitors, alcohol abuse (psoriasis can appear months after drug started)

Clear role for immune system; innate / adaptive cross-talk

Question 16

what are the types of psoriasis

Answer 16

Plaque psoriasis - most common form (~90% of cases). Manifests itself in form of scattered, raised, scaly patches, often on elbows, knees and scalp. Lesions can become itchy and sore

Guttate (teardrop shaped) psoriasis - consists of numerous, small discrete patches scattered all over body. Commonly seen in the young and may follow throat infections in predisposed individuals. Up to one
third of patients will spontaneously resolve.

Flexural (inverse) psoriasis - affects areas of skin-to-skin contact e.g. armpits, groin, buttocks. Tends to occur in later life

Generalised pustular psoriasis - acute, severe eruption of superficial pustules with reddening of the skin and high fever. Pustules do not contain bacteria, and not caused by infection. Can occur following use of large quantities of strong steroid creams or steroid tablets to treat psoriasis. Uncommon

Pustular psoriasis - chronic, localised form on hands and feet occurring in middle age.

Psoriatic arthritis - inflammatory joint disease, usually affecting small joints of hands and feet. In most patients, skin changes appear before onset of joint pain. Approx. 5% of individuals develop this form of psoriasis

Question 17

what are the nail changes in psoriasis

Answer 17

Nail changes occur in 25-50% of patients who have psoriasis
Very common in patients with psoriatic arthritis
Small indents (pitting) of nails are common as is lifting up of nails (onycholysis), discoloration, thickening and crumbling

Question 18

what is the treatment of psoriasis

Answer 18

Concerned with control and management NOT cure
Aim to reach a point where the patient can tolerate symptoms
Variety of therapeutic approaches available; often individualised and generally escalate from mild to aggressive treatments. Commonly:

Emollients - always use for hydrating skin. May also have anti-proliferative effect in psoriasis e.g. emulsifying ointment, aqueous cream. Esp. good for inflammatory psoriasis and plaque psoriasis on palms/soles

Topical corticosteroids - may see early improvement but not generally used as sole treatment. Can treat specific sites e.g. face, flexures (use mild corticosteroid e.g. hydrocortisone) or scalp, hands and feet (use strong steroid e.g. betamethasone, dermovate)

Calcipotriol (Dovonex) - synthetic vitamin D3 analogue that interferes with cell division and differentiation. Formulations are suitable alternatives for patients who have tried coal tar or dithranol
Each of above should be applied 1-2x a day to palpable lesions. Once lesions have flattened treatment can be stopped.

Dermatologists generally adapt treatment to patients & their preferences and aiming to use mildest effective treatment.

Commonly (NICE recommendations) for chronic psoriasis;
Emollient – eg Diprobase cream
plus a steroid and vitamin D analogue – eg Dovobet ointment – or gel - (betamethasone dipropionate as the corticosteroid AND calcipotriol as the vitamin D analogue)

For mild / onset psoriasis, Cochrane review shows corticosteroids are as effective as calcipotriol, with fewer side effects than the vitamin D analogue.

So some clinicians prefer to start with emollient and corticosteroid, then add in calcipotriol or similar
Or for patients with sensitivity

Coal tar - anti-inflammatory and anti-scaling properties. Useful in chronic plaque psoriasis. Crude coal tar (coal tar BP) is most effective form (1-10% in soft paraffin base) but few patients tolerate smell/mess. Proprietary preps are cleaner but can take longer to work.

Salicylic acid - used as a keratolytic in scalp psoriasis (in combination with emollient/other agents)

Dithranol - most likely to induce remission c.f. other topical treatments. Esp. effective for chronic plaque psoriasis. Apply to chronic extensor plaques only; avoid normal skin. Problems with irritation of normal skin and stains skin and clothing. Not generally suitable for widespread lesions. Do not use on face/flexures. Start with low (0.1%) conc. then increase gradually up t o3%. Protect hands with gloves when applying.

Retinoids - 0.05% tazarotene (vitamin A analogue). Recently been used topically for mild - moderate plaque psoriasis affecting up to 10% of the skin

Phototherapy

UVB light - effective for chronic stable psoriasis and guttate psoriasis. Consider in patients where topical treatment has failed. May irritate inflammatory psoriasis

PUVA therapy - combination of long-wave UVA radiation with psoralen. Available in dermatology centres.

Psoralen (orally or topically) enhances effect 
of UVA. Usually taken 2hrs before UVA 
exposure (allows drug time to reach skin).
Effective in most forms of psoriasis. Early 
adverse effects include phototoxicity, pruritis. 
High doses lead to skin ageing, risk of 
cataracts and skin cancer.

Systemic treatment
Required for severe, resistant, unstable or complicated forms of psoriasis.
Only initiate under specialist supervision. Systemic drugs for psoriasis
include:

Acitretin - a retinoid often combined with other treatments. Therapeutic
effect after 2-4 wks with maximum benefit 4-6 wks after. Available only in
hospital pharmacies and a small number of specified retail pharmacies.

Cyclosporin - by mouth, used for severe psoriasis and severe eczema

Methotrexate - for severe psoriasis. Usual dose is 10-25 mg weekly by
mouth. Folic acid sometimes given to reduce possibility of methotrexate
toxicity (liver damage/bone marrow suppression)

Question 19

what is adalimumab

Answer 19

Adalimumab was the first fully human monoclonal antibody approved by the U.S. FDA
The brand name Humira stands for “human monoclonal antibody in rheumatoid arthritis”.

Used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, chronic psoriasis, etc.

TNF-inhibiting, anti-inflammatory.
Binds to tumour necrosis factor-alpha (TNFα), which normally binds to TNFα receptors, leading to the inflammatory response of autoimmune diseases.
By binding to TNFα, adalimumab reduces this inflammatory response.
Because TNFα is also part of the immune system, which protects the body from infection, treatment with adalimumab may increase the risk of infections.

Ustekinumab (Stelara)
Blocks interleukin IL-12 and IL-23 which help activate certain T-cells. It binds to the p-40 subunit of both IL-12 and IL-23 so that they subsequently cannot bind to their receptors.

Guselkumab (Tremfya), for plaque psoriasis.
Targets the IL-23 subunit alpha (p19 subunit) hence preventing it from binding cell receptors that would otherwise be activated by its presence.

And a strong pipeline:
Dupilumab (Dupixent) for eczema, moderate to severe atopic dermatitis (& asthma?)
Brodalumab for moderate to severe plaque psoriasis
Binds to the interleukin-17 receptor and so prevents interleukin 17 (IL-17) from activating the receptor
Nemolizumab
blocks the interleukin-31 receptor A; for itch in atopic dermatitis.
Siplizumab
selectively suppresses the function of T and NK cells
Zanolimumab ….

But common side effects; when suppress immune system, prone to infections (can be serious)
Hence search from more specific mabs, rather than globally suppressing interleukins…