Eczema/ Dermatitis Flashcards
(42 cards)
Pathology of eczema
-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
Clinical features of eczema
-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)
Three major eczema syndromes
-Contact allergic dermatitis
-Contact irritant dermatitis
-Atopic dermatitis
Pathophysiology of Contact Allergy Dermatitis
-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
Clinical features of contact allergic eczema
-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
Investigation of contact allergic dermatitis
-Patch testing
=Suspect antigen applied to back, 24 hrs, removed, examined 48-96 hours
False negatives and positives in patch testing
-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)
Patch vs prick testing
-Contact dermatitis, patch= delayed hypersensitivity
-Contact urticaria, prick= immediate/ type 1 hypersensitivity reaction
Pathophysiology of contact irritant dermatitis
-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
Examples of contact irritant dermatitis
-Scrubbing in and glove wearing
-Wet hands, soap and detergent
-A doubly incontinent person develops an itchy rash around their buttocks and genitals
What and why is something an irritant?
-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
Why are gloves irritant?
-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
Differences between contact allergic and irritant dermatitis
-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
What determines susceptibility to irritant eczema?
-Risk factor: history of atopic dermatitis
-Depends on function of exposure (repeated and frequent) and individual susceptibility
Management of irritant eczema
-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
Epidemiology of atopic dermatitis
-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
Factors of pathogenesis in atopic dermatitis
- Atopy, and the relation between IgE, an altered immune system and atopic dermatitis.
- The role of an abnormal barrier in the pathogenesis of atopic dermatitis.
- The role of infection or infectious agents including the microbiome in atopic dermatitis
Definition of atopic dermatitis and atopy
-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)
What role does IgE play in atopic dermatitis?
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
Describe the role of an abnormal barrier in the pathogenesis of atopic dermatitis
-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
Describe the role of the microbiome in atopic dermatitis
-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.
Genetics in atopic dermatitis
-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
Secular changes in atopic dermatitis
-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
Diagnosis of atopic eczema
-Prick testing or measures of IgE have no role in routine clinical practice for the diagnosis of atopic eczema
