Eczema/ Dermatitis

Question 1

Pathology of eczema

Answer 1

-Intracellular epidermal oedema= spongiosis
-Lymphoid infiltrate in dermis and epidermis
-Chronic= acanthosis (thickening of viable epidermis) and hyperkeratosis (thickening of stratum corneum so scaling) dominates so spongiosis less apparent

-Processes
=Immune system behaves abnormally/ inappropriately
=Skin barrier function compromised so noxious agents penetrate skin and worsen inflammation/ defects in barrier allow foreign antigens to provoke immune response

Question 2

Clinical features of eczema

Answer 2

-Acute= erythema, induration, oedematous, blisters and erosions reflect underlying spongiosis, itch
-Chronic= thick (acanthosis= thickening of epidermis), rough, dry, fissures (narrow ulcers), lichenification (exaggeration of the normal skin markings as a result of continued rubbing of itch)

Question 3

Three major eczema syndromes

Answer 3

-Contact allergic dermatitis
-Contact irritant dermatitis
-Atopic dermatitis

Question 4

Pathophysiology of Contact Allergy Dermatitis

Answer 4

-A hapten (small molecule that needs to bind to another molecule to become antigenic) or antigen penetrates the skin barrier
=Processed by Langerhans cells or other macrophage/ APC within skin
=Presented in turn to T cells at regional lymph node
=Memory for antigen develops over 1-3 weeks
=Exposure of individual antigen results in eczema features at 24-96 hours

-Type 4 hypersensitivity reaction (delayed)
-Happens in people genetically susceptible
-More likely to occur if disturbance to skin barrier leads to greater antigen penetration

Question 5

Clinical features of contact allergic eczema

Answer 5

-Body site distribution (does it match exposure to a chemical, e.g. colophony is the usual chemical in plasters that causes problems, nickel on ears)
-Temporal pattern (worse at work, better on holidays?)
-Occupational history and knowledge of hobbies etc

Question 6

Investigation of contact allergic dermatitis

Answer 6

-Patch testing
=Suspect antigen applied to back, 24 hrs, removed, examined 48-96 hours

Question 7

False negatives and positives in patch testing

Answer 7

-Base rate of positive reactions to antigens in the population= presence of a positive eczematous response doesn’t prove that that particular antigen is the cause of the individual’s disease, it may just be a false positive.
=20% of the population are sensitive to nickel. In a patient who is known to be allergic to nickel, the presence of eczema developing on the scalp, does not mean that exposure to nickel has caused the eczema – it would be much more likely to relate to sensitivity to some of the perfumes or preservatives in shampoos, or be a non-contact allergic eczema.

-False negatives= negative patch test on a patients back to a particular antigen, when there is good evidence that the same antigen can provoke eczema at a different body site (e.g. the eyelid)

Question 8

Patch vs prick testing

Answer 8

-Contact dermatitis, patch= delayed hypersensitivity
-Contact urticaria, prick= immediate/ type 1 hypersensitivity reaction

Question 9

Pathophysiology of contact irritant dermatitis

Answer 9

-Localised inflammatory reaction not initiated by antigen-specific immune system but involves innate immune system in response to epidermal cytotoxic damage from chemicals/ other stimuli

Question 10

Examples of contact irritant dermatitis

Answer 10

-Scrubbing in and glove wearing
-Wet hands, soap and detergent
-A doubly incontinent person develops an itchy rash around their buttocks and genitals

Question 11

What and why is something an irritant?

Answer 11

-Agents that emulsify or dissolve lipids will damage and overwhelm the upper epidermis layer
=substances can pass into viable layers of epidermis and damage viable keratinocytes (since living cells are rich in lipids)
=Inflammation

-Subsequent keratinocyte mediated activation of innate immune system= contact irritant dermatitis

Question 12

Why are gloves irritant?

Answer 12

-Occluding skin increases aqueous vapour pressure
=changes in differentiation (molecular signal for formation of normal pattern of keratinocyte differentiation)
=defective barrier

-Just like over washing damages lipid barrier

Question 13

Differences between contact allergic and irritant dermatitis

Answer 13

-CID
=No period of sensitisation= inflammatory response to first exposure
=Dose response: more exposure to irritant= more normal homeostatic responses overcome= greater degree of eczema
=Everyone sensitive to irritants to some degree

-CAD
=Clinically silent first exposure leads to sensitisation- subsequent challenge leads to evident disease (memory of adaptive immune system)
=Reaction to antigen all or nothing response/ same dose of antigen produces different magnitude of responses in different people

Question 14

What determines susceptibility to irritant eczema?

Answer 14

-Risk factor: history of atopic dermatitis
-Depends on function of exposure (repeated and frequent) and individual susceptibility

Question 15

Management of irritant eczema

Answer 15

-Minimise exposure to soaps, detergents, noxious agents
-Hand care: wear gloves in cold weather (cold weather dries the epidermis out); avoid washing dishes, and exposure to irritant foodstuffs in the kitchen; avoid all soaps, and shampoos; and avoid polishes and many household cleaners

Question 16

Epidemiology of atopic dermatitis

Answer 16

-20-30% of children, most common 2 - 4, 2-10% of adults/ lifetime prevalence 15%
-Often improves later during childhood, but not uncommonly recurs as facial eczema in adolescence or hand dermatitis in adulthood.
-In some patients severe atopic eczema is lifelong, in others it clears only to return with a later relapse.
-Some people develop what seems clinically identical to atopic dermatitis in middle age with no evidence (or history) of atopy

Question 17

Factors of pathogenesis in atopic dermatitis

Answer 17

1. Atopy, and the relation between IgE, an altered immune system and atopic dermatitis.
2. The role of an abnormal barrier in the pathogenesis of atopic dermatitis.
3. The role of infection or infectious agents including the microbiome in atopic dermatitis

Question 18

Definition of atopic dermatitis and atopy

Answer 18

-Atopic dermatitis = type of dermatitis that is frequently seen in atopic individuals.

-Atopy:
=individuals who have a personal, or family history of a group of disorders that are atopic (hay fever, atopic dermatitis and asthma)
=individuals who have raised IgE antibodies and have a tendency to mount IgE responses to a range of common antigens which, as far as we can tell, don’t seem to threaten the integrity of the individual(e.g. house dust mite)

Question 19

What role does IgE play in atopic dermatitis?

Answer 19

Positive IgE responses are not directly causal of the eczema, but merely reflect an abnormal immune system (they might be useful as a diagnostic marker, but they are not the cause of the skin rash)

=Removing the antigens from the environment of the patient will not be expected to improve the patient if the antigens are not causal and the patient’s skin is intact

Question 20

Describe the role of an abnormal barrier in the pathogenesis of atopic dermatitis

Answer 20

-Patients with atopic eczema have inherited skin barrier abnormality
=A filaggrin deficient cornified envelope leads to a defective cytoskeletal barrier with abnormalities in lamellar bodies and the normal stratum corneum lipid barrier.

-Mutations of filaggrin occur in ~ 10% of many populations, and those with a mutation on one allele are three to five times more likely to develop atopic eczema (most apparent for patients with severe atopic dermatitis)
-Around 40% of patients with severe atopic eczema harbour loss of function mutations in the filaggrin gene on one or both alleles.
-You can develop atopic eczema without filaggrin mutations, but many suspect there may be similar functional effects from either mutations of other genes which, as yet, have not been identified, or from post-translational defects in the filaggrin pathways

Question 21

Describe the role of the microbiome in atopic dermatitis

Answer 21

-Atopic dermatitis skin colonised with staph aureus, whereas in normal controls rates are ~5%.
-Disease worsens= staph density increases =other aspects of the skin microbiome change.
-Production of defensins by keratinocytes (innate immune system) decreased in AD =inability to deal with staph aureus on skin.

Question 22

Genetics in atopic dermatitis

Answer 22

-Strongly familial (barrier dysfunction, atopy)
-Complex inheritance and the sex incidence is equals.
-Empirical risk estimates suggest that an offspring of a parent with atopic eczema has a 20% chance of developing the disease; if both parents are affected then the chance is close to 50%.
-Some of these loci appear to relate to molecules that have immune functions, and one locus reflects the effects of filaggrin mutations

Question 23

Secular changes in atopic dermatitis

Answer 23

-Incidence and prevalence of atopic eczema has increased by a factor of 3 over the last 40 years.
-More common in populations that have undergone industrialisation.
=improved hygiene (‘hygiene hypothesis’)- reduced infective or parasitic load on children is associated with the development of atopy

Question 24

Diagnosis of atopic eczema

Answer 24

-Prick testing or measures of IgE have no role in routine clinical practice for the diagnosis of atopic eczema

Question 25

Typical presentation of atopic dermatitis

Answer 25

-Erythema with little scale initially, through to erythema with a lot of scaling. Poorly demarcated from normal skin
-Scratching/ excoriations (linear marks or gouges)/blood under the nails
-Sleep disturbance
-Acute: ‘wet’ skin (widespread spongiosis and incipient blisters) exudative
-Lichenification. Chronic: skin plaques markedly thickened and rough, with an exaggeration of the normal skin folds (lichenification, and is a response to chronic scratching and rubbing) or discrete nodules
(focal response to scratching, called nodular prurigo, nummular eczema)
-Skin looks ‘dry’ and feels like sandpaper
-Focal lesions measuring millimetres (follicular eczema) rather than patches or plaques measuring centimetres may be seen (Follicular patterns =skin of colour, severity underestimated due to masking of erythema)
-Infants: cradle cap (yellow crusts and scale on the scalp)
-Pityriasis alba: white slightly scaly patches on the face and trunk of children that may be confused with vitiligo
-Dennie-Morgan folds: a double fold of the skin of the lower eye lid, secondary to rubbing.
-Increased peri-orbital pigmentation
-Periocular eczema in adults is markedly symptomatic
-Cheilitis= consequent licking of the lips leads to an irritant dermatitis around the mouth (‘lip-licking dermatitis’)
-Recurrent conjunctivitis (due to rubbing), cataracts (excessive topical steroids absorbed by ocular mucosae)
-Hands/soles: frank blisters, small vesicles, hyperkeratosis, filaggrin mutations: hyperlinear palms
-Secondary infection (staphylococci/ herpes simplex -herpes encephalitis in young children/ eczema herpeticum)
=Many ulcers that appear monomorphic and maybe punched out
-More common on the face and extensor aspects of limbs in infants,
and the flexor aspects in children and adults

Question 26

Differentials of atopic dermatitis

Answer 26

-Fungal infection
-Primary staphylococcal infection (impetigo)
-Scabies
-Contact allergic eczema
-Ichthyosis (absence of obvious inflammation, presence of lots of scale)

Question 27

How does eczema severity vary over time?

Answer 27

-Low ambient humidity especially if the room temperature is warm (skin dries, cracking and scaling occur, scratch increases= itch-scratch cycle
-Wool= irritant, especially in the presence of sweating so use cotton
-Psychological stress increases scratching
-Exposure to water dries the skin out.
-Soap and detergent exposure
-An initial localised Staph. aureus infection of the skin
-Atopics have an increased rate of Type 1 reactions to foodstuffs= urticaria= increased itching and scratching

Question 28

Prognosis of atopic dermatitis

Answer 28

-Uncomplicated eczema does not result in scarring or permanent damage to the skin.
-Majority grow out of it
-The more severe the childhood disease, the greater the chance that the disease will persist into adulthood, or that after clearing, the disease will return

Question 29

Avoidance and prevention in atopic dermatitis

Answer 29

-Soaps, detergents and other agents
-Wool (use cotton)
-Hot environments (Bedrooms kept cool)
-Bath water should not be too hot
-No evidence that avoidance of type I antigens such as house dust mites makes atopic dermatitis better
=If the skin is broken — as is often the case in atopic dermatitis due to scratching — then exposure to a type I antigen may provoke a type I response = more scratching

Question 30

Use of emollients in atopic dermatitis

Answer 30

-First treatment tried in nearly all patients, especially in young children with mild disease.
=Hydrate, restore the skin barrier, and make the skin feel more comfortable.
=Reduce the need for topical corticosteroid treatment
-Aqueous based /greasier ones that maybe more effective, but are messier
-Some emollients cause an (immediate) stinging sensation in some patients within minutes or seconds of application (switch)
-Can be added to the bathwater (slipping!)
-The best emollient is the one the patient will use
-Dermol, double base, epa, liquid paraffin (more greasy)

Question 31

Antiseptics in atopic dermatitis

Answer 31

-Topical antiseptics are ‘drying agents’ and the skin in acute atopic dermatitis is frequently weepy and wet (not dry!)
=In these situations, potassium permanganate or chlorhexidine added to the bathwater can help.
=Such antiseptics are also used (usually with systemic antibiotics) when the skin is obviously infected as is the case when there is widespread crusting and numerous pustules.

Question 32

Acute vs chronic atopic eczema

Answer 32

-Acute: wet due to spongiotic epidermis ‘breaking open’ (blisters)/ red and oedematous without much scale
-Chronic: dry and thickened, with or without lichenification,

-If eczema is wet= needs drying out, and ointments should be avoided (the lipids float on the skin like oil on water — so use creams). Topical antiseptics are useful drying agents, and creams (which are water based) should be used.
-If the skin is dry, use ointments rather than creams

Question 33

Bandaging in atopic dermatitis

Answer 33

-Protects the skin from damage due to scratching
-Reduce the sensation of itch by minimising the effects of external stimuli on the skin
-Promotes healing of broken skin

=Does not just involve applying crepe bandages to the skin — this would just result in the material sticking to the oozing skin resulting in tears and worse disease when the bandages have to be removed or soaked off

Question 34

Main toxicities in topical corticosteroids

Answer 34

-Skin atrophy (thinning, telangiectasia, striae and easy bruising)
-Systemic absorption leading to the symptoms and signs of Cushing’s syndrome
-Combining steroids and antibiotics can cause sensitisation

Question 35

Use of corticosteroids in atopic dermatitis

Answer 35

-Weakest topical corticosteroid as achieves a useful clinical effect
-Systemic absorption is greatest in children and in flexural areas
-Side effects of atrophy are a particular concern on facial skin (permanent telangiectasia)
-Do not underuse
-Hydrocortisone < Eumovate <Betnovate< Dermovate

-Topical calcineurin inhibitors (e.g. tacrolimus) provide an alternative to topical corticosteroids, especially on the face or skin creases. Do not combine with UV
=Suppress T cell activation= reduce cytokine induced inflammation
=Less potent than the most potent topical corticosteroids but are free from the risks of causing skin atrophy
=immunosuppressive= increase the risk of skin cancer? Herpetic infection?

-Phophodiesterase-4 inhibitors

Question 36

Antihistamines in eczema

Answer 36

-Itch is a characteristic of all types of eczema, especially atopic dermatitis: not mediated by histamine= topical antihistamines have no role to play in the management of atopic eczema
-Sedative anti-histamines are used (particularly in atopic eczema) because they are ‘acceptable’ sedatives with a long safety history for both children and adults
=sedation diminishes awareness of itch and results in less scratching (the ‘itch-scratch’ cycle is broken)
=Sedation may be a serious side effect in those who drive, operate heavy machinery, work at heights, or those who are frail and subject to falls
=Sedative effects are synergistic with alcohol
=Antihistamines are considered to be more useful therapeutically in children than adults

!!!Non-sedative anti-histamines have no role to play in the management of eczema

Question 37

Non-topical treatment of eczema

Answer 37

-Phototherapy: UVB and PUVA
=UVB is safer but probably less effective than PUVA (better in psoriasis)
=Can get worse.
=Widespread acute eczema responds poorly, or may even get worse

-Systemic immunosuppressives
=Prednisolone, azathioprine, ciclosporin, and methotrexate.
=Short courses of systemic prednisolone can bring severe atopic dermatitis under control speedily, but toxicity precludes long term use.
=Topical treatment needs to be failing before systemic therapy is considered (especially children)
=Ciclosporin is highly efficacious in eczema, rapidly resolving the pruritus within days, but given the chronic nature of eczema, chronic toxicity severely limits its use.
=Methotrexate is considerably less efficacious in this clinical context than ciclosporin.
=Azathioprine has a long track record of use but its effects usually take several months to kick in. Its major toxicities relate to its marrow suppressive activities (and the need to check TPMT (thiopurine methyltransferase) levels because there is considerable genetic polymorphism in the ability to metabolise azathioprine. Full blood counts for the initial 1-2 months need to be done weekly. Its effects are often not striking.
=Retinoids: systemic agent alitretinoin is used in some severe cases of hand eczema. =Dupilumab: self administer subcutaneously, every two weeks. It is aimed at patients with moderate or severe disease

Question 38

Describe varicose (venous) eczema

Answer 38

-Legs of those with venous incompetence.
-Manage vascular system
-Risk of support stockings developing contact allergic eczema from the creams or dressings used, or rubber in the support stockings

Question 39

Describe Discoid eczema

Answer 39

-Well demarcated annular areas most common in middle aged adults.
-May be no obvious precipitating factors.
-Treat with corticosteroids.

Question 40

Describe seborrheic eczema

Answer 40

-Response to the yeast Pityrosporum (Malassezia species, metabolises lipids on skin surface) that is found on skin.
=If you kill the yeast, the rash goes.
-Presentation: erythematous and scaly condition usually seen in areas rich in sebum, young and middle-aged adults (who produce most sebum), face- nasolabial folds,- forehead- upper chest and back.

-Treatment: Anti-yeast agents are the best treatments. Severe seborrheic dermatitis may reflect an underlying HIV infection. Shampoos or creams that contain azoles (e.g. ketoconazole) are effective. Sometimes topical corticosteroids are added in to speed resolution (but are often not needed).

Question 41

Differentials of dermatitis

Answer 41

-Seborrheic dermatitis: greasy scale, not pruritic, nappy area often affected
-Contact irritant: nappy area, face, extensor surfaces, less pruritic, patch test
-Allergic: well-circumscribed erythematous asymmetrical lesions, resolve removing offending allergen, patch testing
-Scabies: severe pruritus at night, burrows, peripheral, family members and close contacts, microscopy
-Psoriasis: well-circumscribed erythematous lesions with silver scale on extensor surfaces, nail pitting

Question 42

Eczema presentation in pigmented skin

Answer 42

-Brown, grey or purple bumps (papular eczema or follicular
eczema)
dry scaly itchy patches can be erythematous in
paler skin or grey/ brown in richly pigmented skin
- Perifollicular and extensor, rather than flexural, patterns may also be more common in patients of African descent.
-particular risk of developing lichen simplex and nodular prurigo with scratching and rubbing.
-Post inflammatory hypo- and hyper-pigmentation occurs more commonly with skin of colour and can be more noticeable than in ethnic white skin, resulting in significant psychological distress