dermatology core diseases Flashcards
acanthosis
temporary thickening of the epidermis due to an increase in keratinocytes
may be caused by rubbing
acantholysis
keratinocytes separating from each other
eg pemphigus where the autoimmune process inactivates desmosomal structures within the epidermis so that the cells float free from each other
alopecia
loss of hair
scarring alopecia
loss of hair due to destruction of the follicles (hair cannot regrow as the follicles are destroyed)
atrophy
loss of volume
eg loss of dermal substance you see in sun damaged skin on the dorsum of the hand in elderly lady
atrophy secondary to a disease process such as Discoid lupus erythematous where the dermis is reduced in volume as a result of inflammatory processes
epidermal atrophy
much harder to detect as the epidermis is usually thin and many people use the term to describe different things
-means a reduction in the spindle cell layer, and a reduction in the rete ridges and dermal papillae
atrophy of the dermis
also may mean that the vascular component of the dermis is more visible to the eye
-because the loss of collagen means you are better able to see the normal vascular structure because there is less collagen blocking the transmission of incident light
papule
small <1cm solid elevated palpable lesion
nodule
a papule larger then >1cm
macule
small non-palpable area of colour change
flat focal
patches
larger macule
plaque
flat palpable lesion
vesicle
<0.5cm fluid filled sac
pustule
pus filled sac
blisters or bulla
collection of fluid in epidermis >0.5cm
due to either cell to cell or cell to basement membrane or basement membrane to dermis loss of attachment
weal
localised oedema
crust
refers to dry exudate
commonly seen in eczema and impetigo
diascopy
means pressing on the lesion with a glass
eg to check that it blanches on pressure
if it blanches you know the colour is due to blood in vessels
erythema
redness of skin due to an increase in intravascular blood
fissure
a narrow ulcer
common on hands in hand eczema
hyperkeratosis
refers to thickening of the stratum corneum so that there are more layers of corneocytes then there should be
parakeratosis
thickening of stratum corneum but with corneum cells that have nuclei (usually anuclei)
hyperplasia
same as acanthosis
lichenoid
typically if lesions are small papules that are flat topped and resemble lichen planus- then it is lichenoid
also used to describe exaggerated skin markings and thickening seen in lichenification
milium (plural milia)
small epidermoid cyst
seen in newborns, on face of adults and secondary to some diseases eg PCT porphyria cutanea tarda
necrobiosis
degeneration of collagen which is found within palisading granulomas
-necrobiosis lipoidica - rash most commonly seen on diabetics shins, and granuloma annulare
nikolsky sign
refers to the ability to induce a blister on apparently normal skin by applying simple frictional force across the skin
feature of pemphigus and TEN
oncholysis
distal lifting away of nail plate from nail bed
commonly seen in psoriasis or dermatophyte tinea nail infections
panniculitis
inflammation of subcutaneous fat
eg erythema nodosum
pompholyx
skin on palms and soles has a different organisation in terms of tethering of the epidermis and dermis, as the epidermis is much thicker
oedema due to spongiosis, more readily forms vesicles that are relatively robust to trauma
vesicular appearance in eczema at these sites is known as pompholyx
petechiae
non blanching mm petechiae
purpura
non blanching >petechiae
ecchymosis
bruise
palpable purpura is a sign of
vasculitits
scale
small piece of stratum corneum
sclerosis
refers to change in dermis when the tissue feels harder and stiffer than normal and may relate to increases in collagen production
spongiosis
intercellular oedema within the epidermis
one of the cardinal signs of eczema
telangiectasia
small visible blood vessels
ulcer
full thickness break in dermis and epidermis
erosion
superficial- epidermis
psoriasis other presentation
inflammatory polyarthropathy
increase CVD risk and metabolic
presentation psoriasis
scaly red plaques
extensor surfaces, nails and scalp
waxing and waning course
some itch but not as itchy as eczema
pathology of psoriasis
- Epidermal hyperproliferation- keratinocytes
2. inflammatory infiltrate
epidermal hyperproliferation in psoriasis
- epidermal differentiation is derranged in psorasis with hyperproliferation
- parakeratosis- retention on nulcei
- absence of granular layer
- acanthosis: thickening of epidermis
- time taken for epidermal differentiation is shortened-rushed through in an immature state
inflammation in psoriasis
oedema in the dermis
T cell rich inflammatory infiltrate in dermis
polymorphs in dermis and epidermis
capillaries in dermis are increased
munro microabscesses
epidermis polymorph collection in psoriasis
psoriasis causes
mostly unknown- and based on what drugs works for what
-highly heritable - genes involved in innate, adaptive immune system and skin barrier function and keratinocyte
-APC, T cells, HLA, TNF, IL
HLA cw6
HLA B27
Linkage disequilibrium
-MHC on chromosome 6
risk of developing psoriasis if one parent affected
risk if both
15%
40-50%
% psoriasis prevalence
2%
2 peaks of onset of psoriasis
type1= starts in later teen years. early adulthood and more linked to HLA groups
type 2- onset in 5th or 6th decade
Triggering factors for psoriasis
- often presents first time after a strep sore throat- immune system
- HIV can aggrevate
- certain drugs: lithium, betablockers, INF a and chloroquine
- receiving a bone marrow transplant
- obesity, smoking and alcohol
- psychogenic- stress
koebner phenomenon
in some situations injury or damage to the skin causes the development of a psoriatic plaque at the site of the insult
-usually lag of 2 weeks
eg sunburn, surgery, exathema, accupuncture
Types of psoriasis 7
stable plaque guttate erythrodermic pustular flexuaral or inverse palmoplantar nail
stable chronic plaque psoriasis features
- scaly red well demarcated plaque, mostly seen on extensor surfaces of elbow and knees
- can occur also on genitals and scalp
- usually red unless obscured by an excess of silvery scale seen in plaque psoriasis
- called stable as tends not too change week to week
- well defined
how can scale of stable plaque psoriasis be removed
with keratolytic agents eg salicylic acid
emolients
why does psoriasis look white
untreated plaque psoriasis looks white is because of the light refracted at the stratum corneum
- in psoriasis the sc is thickened and disorganised so contains more air so more light is reflected than usually so the skin looks white
- increase refractive index
Auschpitz sign
bleeding when scratch off the plaque
guttate psoriasis
characterised by several hundred small lesions, which often follow a strep sore throat by 2-3 weeks
- most common on the trunk
- often first episode of psoriasis an individual develops and can then go onto develop stable
- raindrops
- usually resolves as guttate 6 months later
erythrodermic psoriasis
most of the skin is affected looks less like psoraisis red all over erythroderma refers to any rash >90% can be difficult to diagnose on first episode as many causes of erythroderma medial emergency as can get hypothermia as skin feels hot, dehydration -need admitting to hospital -dehydration
causes of erythroderma
- psoriasis
- eczema
- iatrogenic
- cutaneous T cell lymphoma
pustular psoriasis
pustules present due to collections of polymprophs (munro micro-abscesses) in epidermis which become large enough so can see
if pustules are all over the body- generalised can become quite unwell
2 forms of pustular psoriasis
- palmoplantar pustular psoriasis– palms and soles mostly affected
- generalised pustular psoriasis
- can become very ill although pustules are sterile
- pyrexia, rigors, severe malaise
other states in which pustules in psoriasis can be seen 2- induced
- plaques that are continually treated with steroids may become pustular- steroid induced pustular
- patients with very acute psoriasis if treated with strong concentrations of dithranol or tar, may develop pustular psoriasis
flexual or inverse psoriasis
-some patients get psoriasis predominantly in flexures eg natal cleft, under boob, antecubital fossa
-red and shiny
generally lack the scale
-needs different treatment and can be harder to target with phototherapy
nail psoriasis 3 changes
- pitting of nail plate
- oncholysis- separation of distal nail bed
- oily spots/ salmon patches = yellowy brown
cause of nail pitting in psoriasis
parakeratosis in dorsal nail matrix
scalp psoriasis
Scalp is very commonly affected lesions are usually discrete and spread beyond the hair line on to the borders of the scalp scales usually adhere to the hair shafts very rarely alopecia may develop itch can be a big problem
palmoplantar psoriasis
some patients with psoriasis have chronic hyperkeratotic psoriasis without pustules that is often indistinguishable from chronic hand eczema
systemic aspects of psoriasis
- inflammatory seronegative arthropathy
-patients can present with psoriatic arthritis and develop psoraisis later on
more usually other way round
-cardiovascular- increase risk of MI, peripheral vascular disease and emboli more common
diagnosis of psoriasis
clinical diagnosis
- describe as discomfort, irritation or pain
- rarely itch
differential scalp psoriasis
sebhorreic dermatitis
solitary plaques of psoriasis differentials
bowen disease- intra epithelial carcinoma
eczema- chronic hand eczema
assessment score for psoraisis
PASI
psoriasis area severity index
management of psoriasis
- Avoid precipitants- smoking and alcohol?, treat HIV infections, drugs
- Active treatments in psoriasis
- Topical- creams and ointments
- UVR- UVB or PUVA
- Older systemic- methotrexate, ciclosporin
- newer eg biologics
bad drugs in psoriasis
lithium
chloroquine
beta blockers
antimalarials
which type of psoriasis is assoc. to smoking
palmoplantar pustular
Topical treatments for psoriasis
- easy and safe but less effective
1. emollients- bland with or without salicyclic acid - which breaks down desmosomes of the SC to make plaques less visible
- Topical corticosteroids: mainstay of management, reduce thickness of plaque and reduce some scaling
- vitamin D analogues: normalises epidermal differentiation and inhibits epidermal hyperproliferation, neutrophils
- vitamin D analogues plus steroids
SE of topical steroids
-local atrophy with telangiectasia
striae
systemic absorption
-rebound effect
older treatments psoriasis
anthralin- dithranol and tar
pro- inflammatory but show anti-psoriatic activity
-tar put on and then dressings and then UVB
-3 to 4 week inpatient
phototherapy two main treatments
UVB
PUVA
UVB therapy
-shorter of the two wavelengths
-accounts more for sunburn
2-3x a week for 10-15 weeks
narroband UVB mostly used 311-313
works best for small plaque psoriasis especially guttate
risks of UVB therapy
- sunburn
- long term increase in rate of non melanoma skin cancer
PUVA therapy
psoralen and UVA
- tablet taken and inert until activated by UVA
- or in bathwater
- only active in areas therefore that UVA can get to
- hence wear glasses to block= cataracts avoid
how does psoralen work
-when activated it
-inhibits proliferation of both keratinocytes and any inflammatory cells present in skin
also
-causes mutations if the cell manages to replicate
PUVA or UVB
-PUVA is more effective
but more toxic in terms of skin cancer risk of both non-melanoma (SCC) and melanoma
systemic agents for psoriasis
Methotrexate
ciclosporin
systemic retinoids
how does methotrexate work and SE
- folic acid antagonist - limits DNA synthesis
- acts on immune system in psoriasis
main SE
- hepatic fibrosis and cirrhosis
- bone marrow inhibition
- teratogenicity and mutagenic on sperm
- can affect response to live vaccines
- increase malignancy and infection risk
- nausea- so use IM
how long do men that want to have children have to stop methotrexate and wait
3 months
monitoring methotrexate
weekly FBC and LFT and UandE routine basis
then 3 months after 3 to 6 months
drugs/ disease that interfer with methotrexate
NSAID- increase toxicity in bone marrow
renal disease impairs its excretion
ciclosporin action and SE
calcineurin inhibitor blocks T cell activation
short term management 3-4 months
SE -nephrotoxicity hypertension increase in risk of some viral cancers eg EBV, HPV and non melanoma skin cancer -hypertrichosis -gingival hyperplasia -vaccination and infection
Retinoids action and SE
-vitamin A like actions act on nuclear receptors
= ACITRETIN
SE -teratogenicity -elevates triglycerides -pancreatitis CVD mortality -mucosal and cutaneous dryness -hair loss -MSK pain
how long do women after acitretin need to wait before conceiving children
and how long for other types of retinoids
3 yrs
5 weeks for isotreinoin alitretinoin
what is Isotretinoin used for
Acne
shorter half life
retinoid
what is alitreinoin used for
some hand eczema
5 weeks before pregnancy
Biologics for psoriasis
- Tumour necrosis factor inhibitor
2. block other cytokine pathways
TNF inhibitors psoriasis examples 3
-eg etanercept, infliximab, adalimumab
ustekinumab blocks
IL12 23
Ixekizumab blocks
IL17
Guselkumab blocks
IL23
Risks with TNF inhibitors
- TB
- reactivation of eg JC
other systemic agents in psoriasis
fumarates
mycophenolate
hydroxyurea
aprelimast- phosphodiesterase inhibitor
what serious infection is assoc. to severe psoriasis
undx HIV
what is acne
disorder of pilosebaceous unit- hair follicle and sebaceous gland
types of comedones
whiteheads= closed blackheads= open
charaterisation of acne
comedones, inflammatory papules, pustules and scars
some also get nodules forming with sinus formation and cysts (cavities lined with epithelium) and pseudocysts (inflammatory masses)
pathogenic factors of acne
- abnormal keratinisation of follicular epithelium - hyperkeratinisation
- increased sebum excretion
- infection with gram positive rod Propionibacterium acnes P. acnes
abnormal keratinisation of the infundibulum in acne
- earliest change in acne is formation of microcomedones
- instead of desquammation breaking up the keratinocytes-
in the follicle, the keratinocytes all stick together along with sebum so form a plug towards the top of the follicle
- as the plug gets larger it becomes more visible- evnetually it distends the follicle and ruptures and bursts causing an inflammatory response
- get closed comedones and later open comedones
what are open comedoens
Black heads
filled with dead cells and sebum
due to melanin makes it black
sebum in acne
- sebum is necessary but not sufficient for development of acne
how is sebum produced
-by cell death of sebocytes in sebaceous glands with release of lipid cell contents in the lumen of the follicle
evidence that sebum production is under androgen control
teenages
PCOS
body builders
prepubertal enuchs dont get acne as little sebum
what is p.acne
propionibacterium acne
- found in everyone skin
- numbers are greater in those with acne with heavy colonsiation of follicular epithelium
how does p. acne relate to acne
- P.acne uses sebum as a substrate and breaks down products into free fatty acids
- the more sebum the more p.acnes
- some fatty acids are powerfully chemotactic for polymorphonucleates and cause abnormalities of follicular keratinisations and sitimulates innate immune system
so p.acne stimualates the innate immune system
inflammatory process of acne
=finally ruptures due to increasing pressure and
-direct release of p.acne lipases, chemotactic factors and enzymes leads to comedone rupture which results in exudation of keratin, sebum, p.acnes and cellular and vellus hair material into the surrounding dermis
- this drives an inflammatory casacde with neutrophil infilitration and release of oxygen reactive species and lysosomal enzymes- t cell infiltrate
nodulocystic acne describes
patents that get multiple inflammatory nodules whether there are true cysts or not
scarring in acne
worse the inflammation the greater risk of scarring
-different people scar to a different degree
-
types of scars
- Ice pick scars= narrow and deep
- keloid scars= large unsightly scars also seen after surgery and trauma
- also can just be shallow irregularity of skin’s normal surface
- hyperpigmented areas also
why are blackheads black
due to melanin
genetics of acne
- higher in identical twins
- sebum excretion rates under some genetic control
diet and acne evidence
aka little evidence
not due to food or washing
main types of acne 9
- comedonal acne
- papulopustular acne
- acne fulminans
- acne conglobata
- acne ecxoriee- des junes filles
- infantile acne
- mechanical acne
- chloracne
- cosmetic acne
comedonal acne
simple acne where comedones predominate over the inflammatory lesions of papules and pustules
ie lots of blackheads/ white heads
papulopustular acne
inflammatory lesions and pustules are more evident than the comedones
-note comedones may not be easily visible but are still present- cant have acne without comedones
acne fulminans
severe variant of acne with abrupt onset of nodular suppurating (pus producing) lesions
often following a deterioration of pre-existing acne in teenage boys
lesions ulcerate and result in severe scarring
emergency management
systemic features of acne fulminans
-joint pains
-pyrexia
hepatosplenomegaly
osteolytic lesions
high ESR
leukocytosis
protineuria
anaemia
acne conglobata
refers to severe form of nodulocystic acne with multiple painful abscesses and scarring
possible extensive involvment of chest, face, back, arms, scalp and buttocks
- unlike acne fulminans there are no systemic manifestations
- may occur with acne inversa
acne excoriee de jeunes filles
clinical picture when the acne appears fairly minimal but the patient seems to squeeze, excoriate or pick to an excessive degree the individual lesions
often young women
infantile acne
few months to 1 year
reflects androgen activity seen in both sexes but more males
in males elevated LH leads to testicular andorgen production and, in both sexes raised DHEA produced by the adrenals may be the explanation
fades after one year and then re-starts with puberty
seen as comedones, pustules and scarring
mechanical acne
mechanical damage or frictional occlusion of the skin from headbands eg chin straps or even leaning on your hands excessively can lead to increased in number of comedones and worsening of acne
chloracne
severe type of comedonal acne- usually secondary to dioxin exposure either from military campaigns, industrial accidents
cosmetic acne
variety of chemicals, especially oils or tar derivatives or aromatic hydrocarbons induce comedone formation leading to acne
- many are found in cosmetics
- although most inducers no longer used- oils based still cause problems
post-adolescent acne
- acne may persist beyond the twenties well into middle age, especially in women
- areas around the jaw and mouth may be particularly affected
- pre-menstrual flares are common
Endocrine causes of acne 5
inx
- hyperandrogenism in women- change in voice, body build, androgenicalopecia and cliteromegaly
- A normal menstrual cycle is strong evidence against any systemic endocrine abnormality,
- PCOS
- CAH congenital adrenal hyperplasia
- androgen secreting tumours
- androgens in body builders
- evaluation should include testosterone, DHEAS and hydroxyprogesterone
- steroid production adrenal and ovarian
when to consider endocrine causes of acne
severe acne
age of onset in unusual- childhood or middle age
Management options for acne approach
- single topical retinoids or benzoyl peroxide
- topical combination therapy - BPO, retinoids, abx
- antibiotic oral or hormonal methods in females
- systemic retinoids
management targets for acne
- reverse the keratinisation defect
- reduce sebum production
- kill of bacteria- p.acne
Topical retinoids used in acne
how it works
eg Isotretinoin, tretinoin
- vitamin A activity
- topical or systemic
- work by normalising follicular keratinisation
- and reversing the excess adhesion of dead corneocytes in the follicle
- do not affect sebum production
SE of topical retinoids and dosing
- tend to promote a mild inflammatory reaction
- means that they produce a slight toxic or irritant reaction like a mild sunburn -erythema, dryness, scaling
- therefore use once a day or if inflamamtory response prominent then every other day
predominant comedonal acne best treatment
retinoids best agent to start with
Benzoyl peroixde BPO action on acne
works by reducing the levels of P.acne within the follicle
-reduction in bacteria then leads to a reduction in pro-inflammatory free fatty acids and inflammatory activation
SE of benzoyl peroxide and dosing
- tend to promote a mild inflammatory reaction
- means that they produce a slight toxic or irritant reaction like a mild sunburn -erythema, dryness, scaling
- therefore gradually increase them
what oral antibiotics are used in acne
tetracyclines eg doxycyline or erythromycin
how long does a patient need to be on an antibiotic to see it taking an effect against acne
2 months
using oral antibiotics for acne
-systemic antibiotics are used for 3-6 months but then withdrawn
but continue with topical retinoid or BPO
-may need to commence the antibiotic again but people argue increasingly for therapeutic holidays to minimise resistance
which antibiotic can be used in pregnancy for acne
erythromycin
when are tetracyclines contraindicated
<12 as deposits and stains teeth and in bone
pregnancy teratogenic teeth and bone effects
which topical antibiotics are used for acne
erythromycin, tetracyclines, clindamycin
topical abx are commonly used with topical BPO
when will topical antibiotics not be suitable
for extensive chest and back involvement
other topical agent option for acne
azelaic acid- possess antibacterial, anti inflamamtory, and anti-comedonal effects
hormonal method acne options
- combined pill mainstay
- co-cyprindiol- oestrogen and anti-androgen but not used as much and is a teratogen
-in females can be used instead of oral antibiotics
oestrogen and progesterone on acne
oestrogen decreases sebum
progesterone increases sebum
how combined pill affects acne
- contains some oestrogen which decreases sebum
- inhibits ovulation which reduces ovarian androgen production and thus reduce sebum production
which systemic retinoid is used for acne
systemic isotretinoin
how does systemic isotretinoin work
potently reduces sebum excretion
(rem topical retinoids do not reduce sebum excretion
-does this by inducing a temporary and reversible atrophy of the sebaceous glands
when are systemic retinoids used in acne
if no response to conventional treatment
acne that is causing severe acne
how long is systemic retinoids prescribed for
4 months
-can be a delay before any beneficial effect is seen
complications of systemic retinoids
- can precipitate acne fulminans when starting so may need to use steroids to dampen down immune response
- highly teratogenic- need 2 methods of contraception
what needs to be checked before starting isotretinoin
FBC
LIPIDS
LFT
pregnancy test
side effects of isotretinoin systemic
-interferes with lipogenesis not just in sebacous but also in other keratinocytes so also get
chelitis, dry eyes, dry nose, nose bleeds, dry skin and eczema
? depression and mood
what do people on systemic isotretinoin potetnially need to stop wearing
contact lenses
monitoring when on on systemic retinoids
- blood test at start and after one month
- pregnancy test monthly and five weeks after stopping isotretinoin
how long after isotretinoin are you not allowed to get pregnant
5 weeks
shorter half life then acitretin
other treatments for acne 3
- potent peels (alpha hydroxy acids)
- photodynamic therapy (blue light plus topical porphyrins)
- comedone extraction or electrocaytery of comedones
dont need to know anymore
scarring in acne treatment
-scaring is irreversible- although can become less obivious
RX
-dermabrasion
drug induced acne presentation
papulopustular eruption or folliculitis without comedones
drugs that cause drug induced acne
steroids
anti-epileptic medications
lithium
complication of use of tetracycline for acne
can develop a widespread gram negative folliculitis
-need to stop the tetracyclines
EGF receptor inhibitors complication
can cause a widespread acne like pustular eruption with no comedones
acne inversa pathology
- disease is centred around follicles and sebaceous glands like acne
- occlusion of the follicular infundibulum and rupture of the follicle is central to its pathogenesis
rupture of the follicle with dispersion of its contents into the surrounding dermis and secondary inflammation
-this leads to initially
where does acne inversa mostly affect
groin axillae perineum peri-anal
presentation of acne inversa
- foul smelling discharge comprising of blood pus and serous exudate
- pain
- malaise
complications of acne inversa
squamous cell carcinoma in chronic lesions
infection can contribute- not primary problem
diff dx of acne inversa
often misdiagnosed as bacterial abscess
who and when gets acne inversa
women and young adults
not before puberty
treatment of acne inversa
- psychological important to consider as devastating disease
- systemic antibiotics combinations
- systemic retinoids
- systemic anti androgens
- systemic steroids in flare ups
but response is usually poor and get recurrences
- surgical: laser or excision (can be curative)
- TNFalpha inhibitors can improve some patients
cardinal lesions of urticaria
weal -raised dermal oedema
angioedema can also commonly be seen with urticaria
weal vs angioedema
angioedema is oedema in the deep dermis or subcutis
how long does urticaria last for
<24 hours
what are urticarial dermatoses
-same morphology as urticaria but last longer than 24 hours eg urticarial vasculitis urticarial drug reactions pemphigoid
pathology of formation of a weal
-exogenous vasoactive compounds injected into skin -eg nettle sting- dont act on mast cells
or
-endogenous mediators which have same effect
from H1 or non H1 mediators but act on mast cells to produce this
which proteases are found in mast cells on the skin
tryptase
chymase
determines what stimuli they react too-why the lungs and skin might react to different stimuli
what do mast cells contain type 1
- mast cells contain a range of inflammatory mediators- mostly histamine but also prostaglandins, leukotrienes, cytokines, proteases and heparin
- these are grouped together in granules
- if the mast cells are activated they degranulate and these contents are released
triple response weal and why get each one
- initial erythema-erythema close to injection site
- larger flare of erythema- axon reflex in which stimulation of peripheral nerves is transmitted along sensory nerves and then back along other sensory nerves causing release of mediators leading to vasodilation= antidromic stimulation
- collection of dermal oedema: due to increased permeability of post capillary venules leading to a transient increase in local oedema
predominant symptom of urticaria
itch
type 1 hypersensitivity reaction pathology
and is all urticaria caused by this
IgE molecules are present in a sensitised individualthat binds to high affinity IgE receptors on mast cells
antigen causes crosslinking of IgE receptors leading to a signalling cascade of mast cell so get urticaria
-not all urticarial reactions are caused by this type 1 reaction though as some are non-immunologically mediated (dont need sensitisation) and others involve IgG or complement
main types of urticaria
- acute urticaria
- chronic symptomatic urticaria
- contact urticaria
- physical urticaria
- solar urticaria
- cold urticaria
- cholinergic urticaria
- aquagenic urticaria
main causes of angioedema without urticaria
ACEi induced angioedema
C1 esterase inhibitor deficiency
acute urticaria definition
Urticarial episode lasting <6 weeks
causes of acute urticaria
- NSAID
- recent infection
- foods especially shellfish
- aspirin
- insect bites
- antibiotics- penicillin
- dyes in radiology
inx of acute urticaria
-most dont need any inx beyond a detailed hx
-if severe reaction refer to dermatological allergy service for inx
includes
- IgE testing
-prick testing
-biopsy only if think it is vasculitis
length of time a weal lasts vs length of time urticaria lasts
-weals are the lesion of urticaria
-weals last only 24 hrs
-they come and go
-draw around a few weals and review patient next day
if weals are persisting >24 hours then consider an alternative dx such as vasculitis
hence urticaria itself can last a few weeks but weals dont
if weals persist >24 consider
vasculitis
treatment of acute urticaria
- remove precipitant eg stop drugs
- commence antihistamines non sedative- fexofenadine, cetrizine
- prednisolone short course
- anaphylaxis own management with adrenaline
if risk of anaphylaxis give epipen
chronic symptomatic urticaria definition
-urticaria lasting longer than 6 weeks
association of chronic symptomatic urticaria
-autoimmune disorders
thyroid, vitiligo, rheumatoid, pernicious anaemia
pathology of chronic symptomatic urticaria
most patients have IgG anti IgE antibodies
or IgE antibodies to the high affinity IgE receptor on mast cells
these autoantibodies cause activation and degranulation of mast cell
trigger for why this autoimmune process suddenly occurs is unknown
other cause of CSU
-dietary: low levels of aspirin, azo-dyes or penicillin in the diet
but really there are some patients where the cause is unknown
management of CSU
- exclude other causes
- non sedative anti-histamines
- 2nd line= trial a different non sedative anti-H
rarely immunosuppression may be used eg ciclosporin, steroids
-omalizumab anti IgE monoclonal biologic used if failed H1 blockade
aspirin CSU - management
give leukotriene antagonists
2 mechanisms of contact urticaria
- non-immunological contact urticaria
2. immunological contact urticaria
non immunological contact urticaria pathology and cause
-either due to toxic agents from plants or animals that cause mast cell degranulation or weals directly
eg jelly fish, antropod, fragrances, benzocaine, alcohol, benzoic acid
immunological contact urticaria pathology
- these are usually protein products that require prior sensitisation
- LATEX
- examples include animal amniotic fluid exposure in vets, latex in surgical gloves and almost any foodstuff in the right individual
physical urticarias pathology
- specific physical agents are able to precipitate urticaria in some individuals
- mechanism linking the physical agent to the activation of mast cells is usually unclear
-in some cases there is a circulating factor- IgE that can transmit the disease eg from transplant if serum given to another
dermographism
-development of a weal immediately under area of skin that has had pressure applied to it
delayed pressure urticaria and management
-onset several hours later
can be provoked on the hands by carrying shopping or by pressure from a chair on posterior thighs
-can give NSAIDs
solar urticaria pathology
-triggers
- patients develop widespread urticaria under exposure to UV radiation (or even visible light) over a period of 10-15 mins
- onset is usually sudden
- can follow a recent infection or new drug
- if over a large area can result in collapse due to generalised histamine release
cold urticaria
- urticaria due to cold stress
- patients can present with airway problems after eating ice cream or with generalised collapse if immerse themselves in cold water
-not always related to direct contact and can occur with cold wind blowing
cholinergic urticaria cause
provoked by exercise, emotional stress or heat exposure
results in many very small 1-2 mm itchy lesions
aquagenic urticaria
urticaria from water contact on the skin
angioedema definition
refers to deeper swelling involving the subcutis and submucosae seen in sites such as lips, eyes tongue and other body sites eg hands and face
management of urticaria with angioedema
manage as urticaria
management of angioedema without urticaria and 2 main causes
much more serious as dont primarily involve mast cells
- ACE inhibitor induced angioedema
- C1 ESTERASE inhibitor deficency
Ace inhibitor induced angioedema pathology
- abnormalities of kinin metabolism eg bradykinin are central to the production of angioedema
- ACEi may cause angioedema because the ACE normally breaks down kinins
- can present a yr or so after starting
- can rarely present with lifethreatning airway obstruction
C1 ESTERASE inhibitor deficiency pathology
- C1 esterase inhibitor acts so as to inhibit a range of proteases
- This action inhibits the production of bradykinin as need proteases for the production
- therefore deficiency of c1 esterase= increased bradykinin
presentation of c1 esterase inhibitor deficiency
- fhx of sudden death
- phx of RECURRENT EPISODES of angioedema lasting several days with abdo pain, diarrhoea, upper airway obstruction
NO URTICARIA
treatment of c1 esterase inhibitor deficiency
-treat episodes with either c1 esterase inhibitor or
subcut icatibant - bradykinin B2 receptor antagonist
anaphylaxis presentation and pathology
-urticaria is often a feature
but urticaria rarely progresses to anaphylaxis
-widespread mast cell degranulation causes- vasodilation, hypotension, bronchoconstriction and circulatory collapse
inx test for solar urticaria
monochromator
eczema same as dermatitis
commonest inflammatory skin disease
pathology of eczema cardinal features…
- intercellular epidermal oedema- spongiosis
- lymphoid infilitrate of the dermis and epidermis
as the disease becomes chronic get
- acanthosis- thickening of the viable epidermis
- hyperkeratosis= thickening of the stratum corneum
- the spongiosis can then become less apparent
clinical features of acute eczema
- red
- oedematous
- blisters- reflect underlying spongiosis
- erosions
- weeping skin can stick to clothing or bed sheets
clinical features of chronic eczema
- skin appears thick, rough and dry
- can be fissures- narrow ulcers
- with continued rubbing as a result of itch- lichenification - exaggeration of normal skin markings
lichenification appearance
exaggeration of normal skin markings -from itching
presentation of eczema
- can be either acute or chronic or both at the same time
- many times it is hard to know how to classify an individual lesion
- ITCH!!! and therefore scratch key
two main pathological processes of eczema
- immune system behaving abnormally
- skin barrier function is in someway compromised such that noxious agents penetrate the skin and worsen inflammation, or defects in the barrier allow foreign antigens to provoke an immune response
3 major eczema syndromes
- contact allergic dermatitis
- contact irritant dermatitis
- atopic dermatitis - most common
contact allergic deramtitis pathology
- a hapten or an antigen penetrates the skin barrier and is processed by a langerhans cell or other macrophage or APC cell in the skin
- this is presented to a T cell at the regional lymph node
-T cell memory for the particular antigen develops over 1-3 weeks and subsequent exposure of the individual to this antigen - anywhere on the skin’s surface- results in the clinical features of eczema in 24-96 hours
=type 4 hypersensitivity reaction- T cell mediated and delayed response
contact allergic deramtitis pathology
- a hapten or an antigen penetrates the skin barrier and is processed by a langerhans cell or other macrophage or APC cell in the skin
- this is presented to a T cell at the regional lymph node
-T cell memory for the particular antigen develops over 1-3 weeks and subsequent exposure of the individual to this antigen - anywhere on the skin’s surface- results in the clinical features of eczema in 24-96 hours
=type 4 hypersensitivity reaction- T cell mediated and delayed response
-skin barrier also plays a role to an extent as if you have a damaged skin barrier leads to greater antigen presentation so more likely to develop
example of contact allergic dermatitis
nickel sensitivity
20% of the population
at some point in their life when nickel placed on skin they became sensitive to it
initially get acute eczema response
- erythema and induration
- weeping and blister
- itch
but if reaction is prolonged then itching and subsequent scrathing leads to acanthosis and hyperkeratosis
why doesnt everyone have nickel sensitivity
some antigens like nickel only provoke a response in individuals who are genetically susceptible in terms of the way antigens are presented to the immune system
-depends genetically on their propensity to recognise antigens as foreign
-also reflects on society eg allergic dermatitis is rising in henna tattoos due to PPD antigenic dyes
ALSO eg increase in nickel sensitivity amongst men as there is less different in men and women wearing jewellery nowadays
clinical features of contact allergic eczema
- body site distibution eg glasses and watch strap, plaster
- temporal pattern- better when on holidays, worse at work
- occupational hx and hobbies eg cashier and nickel in coins get hand contact allergic
examples of contact allergic eczema
- bricklayers and dichromates in cement= hand
- nickel coins and cashier= hands
- rubber bandages
- medications topical
- preservatives or dye in tannin leather= shoes rash
- steroids
- aftershave and fragrances
- eye drops
inx for contact allergic dermatitis is
patch testing
applied to back and left for 24 hours then skin examined at 48-96 hrs after removal
-know what to avoid then
can get false positives or false negatives
contact irritant dermatitis pathology
-it is a localised inflammatory reaction that is not initiated by the antigen specific immune system but may involve the innate immune system in response to epidermal cytotoxic damage from a range of chemicals and other stimuli
examples of contact irritant dermatitis
- hand washing- breaks the barrier eg surgeon, kitchen work
- doubly incontinence
what makes something irritant? pathology of contact irritant dermatitis
if they are able to emulsify or disolve lipids this will damage and overwhelm the barrier so they can pass into the epidermis, dermis and damage keratinocytes
-this results in inflammation so get all the clinical and pathological hallmarks of eczema
eg soaps, detergents, alcohol wipes, acids from fruit
contact irritant dermatitis vs contact allergic
contact irritant
-no period of sensitisation -so can have a inflamamtory response on first time exposed, and not a delayed response
- dose response in contact irritant, greater the exposure to irritants the more the barrier will be damaged so greater degree of eczema
- everybody in the population is to some degree sensitive to irritants whereas- for allergic it is either you are or not
what determines susceptibility to irritant eczema?
-level of exposure to irritants eg gloves, hand cleaning
eg healthcare workers
-individual susceptibility
-biggest risk factor is hx of atopic dermatitis
latex allergy presentation
contact urticaria
type 1 reaction so immediate
(NOT eczema)
inx for contact irritant dermatitis
- depends
- can do patch testing if need to exclude contact allergic eczema
management of irritant dermatitis
- aim to minimise damage and treat what left
- minimise exposure to soaps, detergents and other noxious agents
- protecting hands with gloves in the cold and gloves for washing dishes
atopic dermatitis most common age and clinical course
- 2 to 4
- often improves later during childhood but not uncommonly recurs as facial eczema in adolescence or hand dermatitis in later adulthood
- in some patients severe atopic eczema is lifelong in others it clears only to return with a later relapse
three factors in the pathology of 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
atopy definition 2
- those individuals who have a personal or fhx of a group of disorders we have labelled as atopic- hay fever, dermatitis, asthma
- individuals who have raised IgE antibodies and have a tendency to mount IgE responses to a range of common antigens eg house dust mites
what does a RAST test measure
allergen specific IgE antibodies in blood
how come IgE is raised in atopic eczema but it the rash of atopic eczema is not like urticaria another IgE response
positive Ige REPONSES ARE not directly causal of eczema but merely reflect an abnormal immune system
- so might be a useful diagnostic marker but are not the cause of the skin rash
- therefore removing the antigens from the environment of the patient will not be expected to improve the patient as the antigens are not causal
what type of reaction is hayfever
type 1 hypersensitivity reaction
do you have to have other features of atopy to have atopic eczema
no you can just have the cutaneous features of IgE atopic eczema but not the atopic (based on hx, fhx, ige levels or prick testing)
what protein is implemented in the abnormal barrier seen in patients with atopic dermatitis
- filaggrin-filament aggregating proteins
- patients with atopic eczema have an 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
- these mutations occur in 10% of the population and those with a mutation in one allele are three to five times more likely to develop atopic eczema
-you can develop atopic eczema without a filaggrin mutation -but probably means their is a mutation in another gene not known about
which bacteria is found on the skin of patients with atopic eczema and why
- staph aureus
- some products of the innate immune system such as defensins produced by keratinocytes are decreased in atopic eczema
- which can contribute to an inability to deal with staph aureus on the skin -which in turn exerts an effect on the cutnaeous immune system
- efficacy about treatments targeting this arent full proof
genetics in atopic dermatitis
-strongly familial due to inheritance of barrier dysfunction and inherited nature of atopy
chance of having eczema if one or both parents have it
20%
50% for both
secular changes and atopic dermatitis
-relates to hygiene hypothesis causing an increase in eczema in the last 40 yrs
a baby develops an itchy rash with scaling on the face and scalp at 6-12 months of age
the rash spreads involving many of the extensor surfaces
itch is a prominent feature with the child scratching and rubbing the affected areas. sleep disturbance can be prominent.
as the child grows older the rash appears worse in the flexures behind the knees and elbows with skin feeling weepy and sticking to the pyjamas
by contrast much of the rest of skin feels rough and dry
soap and detergents make it worse
in the teenage years the rash subsides but facial appears intermittently and the child also develops hayfever and asthma
atopic dermatitis hx
diagnosis of atopic eczema
- clinical features and hx
-not prick testing or IgE measures
(may be undertaken for assoc. type 1 clinical syndromes such as urticaria or food allergy)
clinical feautures of atopic eczema
- erythema with little scale initially through to erythema with a lot of scaling -usually poorly demarcated
- itchy!!-excoriations, scratching
- “wet” oozy skin due to spongiosis and blisters in acute state
- lichenification: in chronic form plaques of skin may be markedly thickened and rough, with an exaggeration of the normal skin folds. response to scratching
- nodular prurigo is another response to scratching in which you get focal nodules in response
-the skin all over may feel and look dry and feel like sandpaper
- pityriasis alba
- dennie morgan folds
- chellitis
- recurrent conjunctivitis
-focal lesions measuring mm- papular eczema rather than patches or plaques measuring cm can be seen
what is cradle cap
atopic dermatitis in infants
yellow crust and scale on the scalp
what is pityriasis alba
white slightly scaly patches on the face and trunk of children that may be confused with vitiligo
what is dennie morgan folds
double fold of skin of the lower eye lid secondary to rubbing
increased peri-orbital pigmentation is also common and markedly symptomatic
peri-ocular eczema
cheilitis is
sometimes seen
consequent of licking of lips leads to an irritant dermatitis around the mouth
why can patients with atopic eczema get conjunctivitis
due to rubbing of the eyes
atopic dermatitis ocular assoc.
recurrent conjunctivitis
cataracts
risk of applying excessive topical steroids to the eye
can be absorbed into the ocular mucosae
physical signs of palms and sole eczema
can be different
- frank blisters
- lots and lots of very small vesicles
- pomphyolyx eczema ie small blisters/ vesicles eczema seen first on the side of fingers -
- can be marked hyperkeratosis and can mimic psoriasis so need a biopsy
- hyperlinear palms- in filaggrin mutations
secondary infections eczema
- can occur in all types of eczema
- particularly with staphylococci
- but also Herpes simplex which is a major concern and carries a risk of death = eczema herpeticum
appearance of eczema herpeticum and risk in children
many ulcers that appear monomorphic and may be punched out
-herpes encephalitis
diff dx of eczema
- fungal?
- impetigo?
- scabies?
- contact allergic eczema?
- ichythosis- also filaggrin mutation and get abscence of inflammation and presence of lots of scale
IF there are no signs of scratching reconsider your dx of atopic eczema
precipitants of eczema 7
- low ambient humidity- warm temp makes disease worse as skin dries and cracks and scale occurs and scratch increases
- wool- wool is an irritant especially in the presence of sweating- use cotton instead
- psychological stress- tends to increase scratching and make disease worse
- exposure to water- paradoxically dries out the skin -soap and detergent exposure also worsens disease-and avoid hot and long baths
- initial localised staph aureus infection of the skin can lead to generalised worsening of the disease
- atopics have an increased in rate of type 1 reactions to foodstuffs-more of a problem in children in which urticaria may develop after ingesting foods leading to increased itching and scratching and resulting in worsening eczema
Treatment of atopic dermatitis
- avoidance and prevention
- emoilients, antiseptics and bandaging
- topical steroids or topical calcineurin inhibitors
- new topical agents eg crisaborole - not yet licensed
- sedative antihistamines not to target histamine but sedation reduces itch
- phototherapy
- systemic immunosuppressive -prednisolone, aza, ciclosporin, methotrexate
aim of treating atopic dermatitis
- difficult to balance- psycho-social issues
- big issue is sleep disturbance
- physical signs vary over time
- aim to not banish disease but reduce extent of it
prognosis of atopic eczema
- uncomplicated eczema does not result in scarring or permanent damage to the skin
- many children with atopic dermatitis do grow out of it -majority grow out
- but more severe childhood disease the greater the chance that the disease will persist into adulthood
avoidance and prevention advice in atopic dermatitis
- avoid soap and detergents and other agents that damage the barrier and make it worse
- avoid wool
- keep cool - bedrooms and cotton bed sheets
- dont soak in a bath and not too hot
- avoiding antigens- DOES NOT CAUSE THE RASH OF ECZEMA- but if the skin is broken then exposure to a type 1 antigen can provoke a type 1 response- ie urticaria which results in itching and will therefore worsen the eczema
- same for food allergies and type 1 response - if a child has food allergies then they can get urticaria which causes scratching and worsening of atopic dermatitis
-practically dont need to banish pets or super-clean the house
emoilients for dermatitis
-first line
rehydrate and restore skin barrier
-range
aqueous based to greasier ones
complication of emoilients in dermatitis
- sometimes can get a stinging sensation immediately when applied
- should switch emoilients
antiseptics use for dermatitis examples and use in atopic dermatitis
- potassium permanganate or chlorhexidine can be added to bathwater
- tend to help with acute atopic dermatitis as act as drying agents-
-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
acute eczema clinical features
- wet due to spongiotic oedema
- breaking open
- small blisters or large
- red and oedematous without much scale
chronic eczema clinical featurs
if a patch of dermatitis appears dry and thickened with or without lichenification it is referred to as chronic eczema
-can have both acute and chronic at the same time a
acute eczema treatment
- avoid ointments
- use creams instead - water based ones
- topical antispetics are also useful drying agents
chronic eczema main principles of treatment-
dried out skin
so use ointments rather than creams
bandaging in eczema action
- protects skin from damage due to scratching
- reduce sensation of itch by minimising effects of external stimuli on the skin
- promotes healing of broken skin
main toxicities of steroids topical
- atrophy of skin- thinning, telangiectasia, striae and easy bruising
- also get systemic absorption leading to cushing’s- greatest in children and flexural areas
principles of prescribing topical steroids for eczema
-dont combine with antibiotics- sensitisation
-antiseptics can be used in combination
weak
topical calcineurin inhibitors eg tacrolimus for eczema situation and method of action
- useful on the face or skin creases
- alternative to topical steroids-less potent but dont cause skin atrophy
- worry about risk of skin cancer and herpetic infection
-suppress t cell activation and reduce cytokine inflammation
crisaborole action
phosphodiesterase 4 inhibitors
how are antihistamines effective for eczema
- itch of all types of eczema is not mediated by histamines
- so dont use topical antihistamines
- can use systemic sedative antihistamines- which work by sedation of awareness of itch
phototherapy for dermatitis
both UVB and PUVA have been used
- UVB is safer but less effective
- also more variable response to UVB in dermatitis- can get worse
systemic immunosuppressants for eczema 6 and efficacy and how long used for and what for
prednisolone- only short courses and not children
ciclosporin-highly efficacous but short courses
methotrexate-less efficacous
aza-takes a while to kick in and measure TPMT
retinoids- alitretinoin for hand eczema
dupilumab
duplimumab action
-blocks IL4 and IL13 receptors
SC every 2 weeks
moderate or severe disease
varicose eczema presentation and management
- legs of those with venous incompetence
- target the primary problem of the venous insufficiency
- however eg use of support stockings with rubber and cream can increase risk of contact allergic dermatitis
discoid eczema presentation and treatment
- well demarcated annular areas , venous oedema, venous flare, varicose veins
- middle aged adults
- treat with steroids
sebhorreic eczema cause and presentation
yeast pityrosporum
treat the infection
-also called cradle cap, neonate and early life then a teen peak with grease
-scaly and fine
contact allergic dermatitis main pointers in hx
- body site distribution eg plaster
- temporal pattern
- occupation and hx
bullous disorders 3 main ones
- immunobullous- pemphigoid, pemphigus and dermatitis herpetiformis
- erythema multiforme, stevens johnson and toxic epidermal necrolysis TEN
- staph scalded skin syndrome SSSS- young children
