Transcript ATOPIC ECZEMA-2x - Medical Council of Guyana

ATOPIC ECZEMA
DR Heather Morris-Wilson, MD
Doctor-in-charge Public Health Skin Clinic
Director(ag) National Leprosy Program
Objectives
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Explain pathogenesis and natural history of Atopic Eczema
Diagnosis of Atopic Eczema
Recognize impact of Atopic eczema on patient and family
Understand indication for allergy testing
Know prescription of different strengths of topical steroids
Understand indications for other treatment
Discuss role of antihistamines
List systemic therapies for patients with atopic eczema
Recognize different types of infection in atopic eczema and understand
indications for skin swabs and antimicrobial therapy
List 3 reasons for poor response to therapy
Understand the indications for referral to secondary care
Case 1
An 8 week old child
presents with a 3
week history of red
inflamed patches of
eczema affecting
cheeks, elbow and
knee flexures.
Parents have only
tried aqueous cream
and is concerned
that child is
increasingly
scratching and
rubbing and
becoming irritable
Case 2
This 4 year old has
suffered from eczema
since infancy, which
becomes particularly
itchy and troublesome
around the elbow and
knee flexures despite
regular emollients and
occasional mild topical
steroids.
He has needed 2
courses of oral
antibiotics from his GP
over the last 6 months
for infected eczema
Definition
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Synonyms: Eczema, Atopic Dermatitis
Inflammatory, chronically, relapsing, pruritic disease
Predominantly childhood disease
Persist into adulthood in around 1/3 of cases (affects <
2% of adults in western countries) Front. Immuno 2015
• Complex interactions between genetic and
environmental factors
Epidemiology and Prognosis
• Approx 70% patients develop AD in first 5 years of
life(Williams 2000, Spergel 2010)
• Overall prevalence: appears similar in males and
females
• Approx 90% children with mild-moderate disease
• Around 60-70% are clear of disease by early
adolescence
• Recurrences in adult life as Hand Eczema(Williams
2000, Williams 1998)
- Early onset AD
- Severe widespread disease(early infancy)
- Asthma/hay fever
- Family hx of AD
Impact of Atopic Eczema on the Family
Psychological factors to consider
1. Sleep disturbances can affect behaviour pattern and
educational development(Lawson 1995)
2. Teasing and bullying leading to low self-esteem
3. Increased dependency and clinginess(Daud 1993)
4. Impact on school or leisure-time activities
5. Time commitments for treatment applications and
health care visits(Daud 1993)
6. Disruption to family function and relationships(Howlett
1999)
7. Parental/carer stress and exhaustion
Diagnostic Criteria(Williams 1994)
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MUST HAVE:
Itchy skin condition or Reports of scratching in a child
PLUS 3 OR MORE OF THE FOLLOWING
Hx of itchiness in skin creases
Hx of asthma or hay fever/atopic disease in 1st degree relative in
children < 4years
3. General dry skin in past year
4. Visible flexural eczema/eczema affecting cheeks/forehead and
outer limbs in child < 4 years
5. Onset in first 2 years of life
SKIN as a barrier(normal)
Stratum corneum
Maintenance of skin barrier function
• Skin barrier function maintained by:
• Regular desquamation
• Intercellular lipid bilayers
• Natural Moisturizing Factors
• Production of antimicrobial peptides
Pathogenesis
• Complex and multifactorial
• Interactions between a number of genetic and
environmental factors
• Results in defective skin barrier and altered immune
function
Two hypotheses
(Boguniewicz 2010, Elias 2010, Barnes 2010):
1) Inside-out
Immunological disturbance causes Ig-E mediated
sensitization, epithelial barrier
dysfunction is secondary
2) Outside-in
Epidermal barrier dysfunction allows
irritants and allergens into the skin, with
immunological disturbance secondary
Itch
Scratch
Dysfunction
Eczema
Inflammation
Leaky skin
barrier
GENETICS
• Importance of this reflected in data from twin and family
studies
• Twin studies: concordance rates of approx. 0.75 for
monozygotic/0.25 for dizygotic twins(Barnes 2010)
• Family studies: shown that the risk of developing AD
 is approx. 20-25% in those with single 1st degree family
member with atopy but
 50% in those with 2 or more family members with atopy
• There is an absence of clear mode of inheritance which
supports the involvement of multiple genes.
Gene-environmental interaction
Filaggrin gene mutations(FGM)
• Worldwide studies: filaggrin mutations are strongest and
most replicated genetic risk factor for AD, occurring in
50% of patients
• Filaggrin gene found on chromosome 1q21, with other
genes for epidermal differentiation(O’Reagan 2010,
Akiyama 2010)
• Protein with central role in keratin filament aggregation
during formation of outer cornified layer of epidermis
• FGM also increase risk of allergic sensitisation, allergic
rhinitis, asthma in people with AD
ENVIRONMENTAL
• Wide variation in disease prevalence both within
and between countries by similar ethnic groups
• Suggests factors such as a “western lifestyle”
may be important
• Studies in migrant groups: demonstrated
increased disease prevalence in people in less
developed countries who move to industrialized
countries(compared to genetically similar groups
in their country of origin)
Implicated environmental factors
• Decreased exposure to infections(“hygiene
hypothesis”)(Flohr 2005)
• Increased exposure to house dust mites(HDM) in
modern home environment(McNally 2001)
• Increased exposure to indoor and outdoor pollution
• Exposure to more varied and potentially antigenic diets
Not sure if environmental factors
- Act by altering the immune system
- Act by increasing susceptibility to irritation/sensitization
by other agents
IMMUNOLOGICAL
• AD characterized by predominance of Th2 over Th1
helper lymphocytes
• Normal to have a switch to Th1 predominance later in
infancy
• Th2 lymphocytes produce inflammatory cytokines(IL-4,
5, 13) which in turn
1. Increase IgE production and eosinophil levels
2. Increase susceptibility to infections(De Benedetto 2009,
Werfel 2009)
Allergy Testing in AD
• Allergic factors: important role in exacerbating AD, but
usually as a consequence of abnormal skin barrier
function rather than a primary cause
• Identifying avoidable allergic factors: improve not “cure”
eczema
• Positive allergy tests: not 100% specific, may support
trial of allergen avoidance, eczema may not improve
• Negative allergy tests: provides strong support that
allergen being tested for not playing a role
- Common allergic triggers may be clear from history( no
specific tests required)
- Irritant skin reactions to topical/airborne
irritants(preservatives in cosmetics, toiletries, pollution)
confused with skin allergy
IgE mediated allergy
Non-IgE mediated allergy
Onset of symptoms
Usually within minutes of contact with
allergen
Within hours to days
Skin signs
Acute urticaria +/- angioedema,
pruritus, erythema
Exacerbations of eczema, pruritus,
erythema
Gastrointestinal signs
(eg foods)
+/ nausea, vomiting, diarrhoea, colicky
abdominal pain
+/- gastro-esophageal reflux, loose
stools +/-blood or mucus, constipation,
abdominal pain, colic
Respiratory signs
(e.g aeroallergens, sometimes foods)
+/- nasal itchin, sneezing, rhinorrhea or
congestion +/- conjunctivitis, cough,
chest tightness, wheezing or shortness
of breath
+/- anaphylaxis
+/- cough, chest tightness, wheezing or
SOB
Examples of allergens in AD
Foods, aeroallergens(house dust mites,
pollens, animal dander)
Foods, aeroallergens, contact
allergens(fragrances, preservatives,
metals, plants, rubber additives)
Basic pathophysiology
IgE cross-linking leads to mast cell
degranulation and histamine release
T-cell activation leads to production of
inflammatory cytokines/interleukins
Types of allergy tests
Skin prick test
Blood test for specific IgE
Trial of allergen avoidance
Patch testing if contact allergy
suspected( not routinely used for foods
or aeroallergens)
Atopy patch testing for foods and
+/- Generalised
Food allergy
• IgE mediated(immediate) food allergy common, common in first few
years of life
• Cross reactions between food and aeroallergens also occur
• Common: cow’s milk, hen’s egg, wheat, soy, tree nuts,
peanuts(Darsow 2010)
• Manifestations: urticaria, lip/tongue swelling, occasionally
anaphylaxis within minutes of eating food
• Contact urticaria: development of wheals at site of contact with
specific foods on the skin
• Tests: blood/skin-prick valuable in confirming diagnosis before
committing patient to dietary avoidance
• NICE Guidelines 2007/Sackeyfio 2011
1. No clear history of immediate food hypersensitivity but
patient suspects food making eczema worst hours or
days after ingestion(non-IgE-mediated)
 Eliminate food for 2-6 weeks under supervision of
dietician
2. Babies and young children with suspected IgE or nonIgE mediated
allergy to cows’ milk
 Offer 6-8 week trial of hypoallergenic formula/milk
substitute
 Refer to dietician if following cows’ milk-free diet for
>8 weeks
3. Patients with suspected food allergy
 Consider referral to secondary care/specialist care
 May need +/- food challenge if there is
I. Faltering growth in combination with GI symptoms
II. No response to single-allergen elimination diet
III. History of one or more acute systemic reactions
IV. History of one or more severe delayed reactions
V. Confirmed IgE-mediated food allergy and concurrent
asthma
VI. Severe AD where multiple/cross reactive food allergies
suspected
• Contact allergens
- Recent studies have shown that allergic contact
dermatitis is common on patients with AD as in the
general population, if not more(Fonacier 2010)
- Common contact sensitizers: metals, fragrances,
neomycin, lanolin, rubber, plants, allergy to topical
corticosteroids(uncommon)
- Presents as worsening of eczema, particularly in
localized areas in contact with allergen
- Sensitized atopic patients may react to very low
concentrations of contact allergens because of impaired
skin barrier function
CLINICAL FEATURES
DISTRIBUTION
INFANCY(0-2years):
CHILDHOOD ONWARDS
- feet, scalp, particularly
cheeks, subsequently
extends unto trunk in diffuse
pattern, then to
limbs(extensor surfaces in
infants)
- Nappy area rarely affected
- Localization to flexures
- Very common:
antecubital/popliteal
fossa, wrists, ankles,
neck
OTHER SITES
- Behind ears at point
where ear lobe joins the
cheek- fissuring
- Around eyes: periorbital
darkening, infraorbital
folds(Dennie Morgan
folds), lichenification of
eyelids
• Around mouth: dryness of
lips, angular cheilitis,
accentuation of skin
creases
MORPHOLOGY
Acute phase
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Erythema
Oedema/papulation
Oozing/crusting
Vesiculation
Excoriations
Chronic phase
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Lichenification
Dryness
Scaling
Cracking/fissuring
Post-inflammatory
hyper/hypo pigmentation
• Erythema
Excoriations
Oedema
Oozing/Crusting/Infected
Crusting
CHRONIC PHASE
Lichenification
Lichenification
Scaling
Cracking/Fissuring
Hyperpigmentation
Hypopigmentation
OTHER PATTERNS OF ECZEMA
Follicular
Follicular
Discoid eczema
Atopic Hand eczema
MANAGEMENT
• Aims
Relief of symptoms in the short term
Reduction in further flare-ups in long term
Overall improvement in quality of life(QoL)
• Ultimate success depends greatly on
Motivation of parents
CLEAR EXPLANATIONS of practical
aspects by DOCTORS and NURSES
EDUCATION
• AD is complex disease-many contributing/interacting
factors
• Manipulation of environmental factors may help some
patients but
• Currently no “cure” for disease
• Management: revolves around symptom control and
flare prevention
• It is a chronic disease: encourage active involvement of
patients and carers from the start
• Recognise psychological/social implications/provide
appropriate support for children and families
• Written information(books, internet, National Eczema
Society)
Avoidance of irritants
• Common: soaps, detergents, solvents, cigarette smoke
• Extremes of temperature/humidity: keep bedroom cool at
night
• Avoid: rough clothing like wool, some synthetic fibres
and use fine cotton clothing.
• Keep nails short to reduce damage from scratching
Treatment choices
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Emollients and Moisturisers
Topical steroids
Topical immunomodulators
Bandages
Light therapy/immunosuppressive tablets
Others
Emollients
• Should be used constantly, even in remission to keep
skin hydrated
• Unperfumed emollients to be used every day for
moisturising, washing and bathing( bath emollients)
• Immediately after bathing, in direction of hair growth,
preferably allowing 30 minutes before applying other
treatments
• Choice will depend on patient preference: ointments,
water-based creams, pump dispensers, added
antimicrobials
• Do not recommend aqueous cream since it irritates skin
• Once daily bathing
Emollients
Topical corticosteroids(TCS)
• Treating areas of active, red, inflamed eczema
• TCS ointments: preferable for body, limbs- more
hydrating than creams/less likely to contain
preservatives
• TCS creams for face, flexures- cosmetically acceptable
• TCS scalp applications, lotions, gels- scalp eczema
• Localised areas of mild infections with crusting- often
respond to simple TCS therapy, as bacterial density
reduces as skin barrier is restored.
• TCS/antibiotic combos( Fucidin H, Fucibet): not to be
used for > 2 weeks( bacterial resistance)
Potency
Examples of preparations
Suggested use
Mild
Hydrocortisone 1%
First line in infants
Face and flexures in all age groups
Moderate
Hydrocortisone 0.2%
Hydrocortisone 2.5%
Bethamethasone valerate cream/foam
Clobetasone butyrate(Eumovate)
Infants and children not responding to
mild TCS
Face(3-5 days bursts) and flexures in all
age groups if not responding to mild
TCS
Potent
Betamethasone valerate ointment
Mometasone furoate
Fluticasone propionate
Short bursts in children aged > 12
months not responding to mild and
moderate TCS (e.g. 3-5 day bursts).
Longer bursts in children and adults
with chronic lichenified eczema (e.g. 714 day bursts).
Avoid on face. Use with caution in skin
flexures.
Do not prescribe in children < 12
months without advice from Consultant
Dermatologist.
Very potent
Clobetasol propionate
Rarely used except for chronic
lichenified or discoid eczema
unresponsive to weaker preparations,
particularly palms and soles.
Avoid on face or skin flexures.
Do not prescribe in children without
advice from Consultant Dermatologist.
• Prescribing principles
1. Only once/twice daily
2. Only to areas of active eczema( eczema active in last
48 hours)
3. Consider treating problem areas of eczema with twice
weekly TCS(reduce flare-ups in children with 2 or more
flares/month)
4. Controlled eczema: reduce to lowest strength that will
maintain control when applied intermittently
5. Parents may usually require 2 or 3 different potency
TCS at home( different body sites, manage flare-ups)
• Side effects
- skin atrophy(clinically translucent finely wrinkled skin,
visible vasculature)
- Striae atrophicae: prolonged use, changes in flexures,
over breasts, abdomen, upper arms, thighs
- Glaucoma, cataracts with periorbital use
- Systemic absorption/adrenal suppression: prolonged use
of potent preps, especially under occlusion
- SE rare if health care providers(HCPs): follow a
guideline for prescribing, use lowest potency TCS
needed to control disease, avoid potent preps on face,
flexures, applying treatment intermittently(less skin
thinning)
Topical Calcineurin Inhibitors(topical
immunomodulators)
- Inhibit calcineurin(phosphatase that regulates
transcription)
- Suppresses inflammatory cytokine release from Tlymphocytes
- Steroid-free preparations with no associated risk of skin
atrophy( used any part of body including face, neck, skin
flexures)
Preparations
Protopic ointment(topical
tacrolimus)
Elidel cream( topical
pimecrolimus)
• Prescribing principles
1. Once/twice daily until clear, repeated as necessary
2. Consider proactive treatment on eczema problem areas
with twice weekly therapy( patients with regular flareups)
3. Do not penetrate thick lichenified eczema effectively as
TCS so treat these areas first with appropriate strength
TCS(usually potent) for 1-2 weeks
4. Clinical trials 0.1% Protopic is as effective as a potent
TS
5. Although 0.03% Protopic weaker, it is still > effective
than a mild TCS
PREDNISOLONE
• Generally only for short bursts to bring severe
eczema back under control
• Never for prolonged periods except in
exceptional circumstances( under the
supervision of a dermatologist)
• Typical course: 20-40 mg for 1-2 weeks
• Side effects
• Burning, tingling sensation after application, occasionally
folliculitis (Protopic, Elidel)
• Increased skin sensitivity to hot or cold
temperatures(Protopic)
• Flushing with alcohol(Protopic)
• Both should not be used in infected eczema until treated
• Concerns about potential increased long term risk of skin
cancer/lymphoma
BANDAGES and GARMENTS
• types: Wet wrapping bandaging with tubular cotton
bandages
• Garments(Tubifast® or Comfifast®) applied over
emollients/mild to moderately potent TCS
• Helpful for short bursts at night
• Wet wraps
- 2 layers of tubular bandage
- Bottom layer soaked in warm water, squeezed out
- Put on skin over emollient/TCS
- Dry layer(bandage, garment) put on top wet layer
• Silk garments(DermaSilk), either as undergarments in
day or as nightwear
• Paste bandages containing zinc and ichthammol(
Ichthopaste) useful for lichenified eczema of limbs,
secured with Coban
LIGHT THERAPY
• UVA(form of psoralen-UVA or PUVA) and UVB
• Effective when given 2 or 3 times a week for 6-12 weeks
• Regular hospital attendance may be impractical for some
patients
• Useful for breaking chronic cycle of itching and
scratching
• Photocarcinogenic risks for children limits use
CICLOSPORIN
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Severe eczema: 2-5mg/kg
More suitable long-term treatment than steroid tabs
Only under close supervision of paediatric dermatologist
Monitor RFTs and Bp every 2 weeks for first 4-6 weeks,
then every 1-2 months once on stable therapy.
AZATHIOPRINE
• Alternative to Ciclosporin: 1-3mg/kg
• Risk of myelosuppression if low levels of main
metabolising enzyme in the body(thiopurine methy
transferase)
• Monitor FBC, LFTs weekly during 1st month, then every
2-3 months once therapy established
• Close supervision of paediatric dermatologist
ANTIHISTAMINES(AH)
• Useful sedative effect when used at night
• No good evidence that they improve itch associated with
AD
• Offer I month trial of non-sedating AH to
1. severe AD
2. mild or moderate AD with severe itching/urticaria
• If successful, continue AH while symptoms persist.
Review every 3 months
• Offer 7-14 trial of sedating AH to
1. Children over 6 months during acute flares if sleep
disturbance has significant impact
2. Repeat for subsequent flares if successful
OTHERS
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Evening primrose oil
Topical doxepin
Topical cromoglycate
Behavioural therapy
Relaxation therapy
Massage
Biologics(monoclonal antibodies like omalizumab,
rituximab, inhibitors of Th2 cell activation)
8. Herbal remedies
Complications of Atopic Eczema
• Bacterial infections
- Note difference between COLONISATION and
INFECTION
- Investigations: treatment dependent on clinical
presentation(against S aureus and Strep)
1. Widespread: systemic antibiotics for 1-2 weeks
2. Localized: topical antibiotics including combined with TCS for
maximum of 2 weeks
3. 1st line S. aureus with allergy/resistance to flucloxacillin:
erythromycin
4. If intolerance to erythromycin/allergy/resistance to flucloxacillin:
clarithromycin
5. Adjunct therapy for decreasing bacterial loads in recurrent infected
AD: antiseptic containing emollients, antiseptics like triclosan,
chlorhexidine
• Eczema herpeticum(Kaposi’s varicelliform eruption)
1. Areas of rapidly worsening painful eczema
2. Clusters of monomorphic vesicles
3. Vesicles rapidly progress to punched out erosions(13mm, uniform in appearance
4. Coalescence of vesicles
5. Asymmetrical initially, mostly on face especially in
proximity of eyes
6. Associated with fever, lethargy, malaise
7. Urgent: referral for same day specialist review,
opthalomological review(around eyes), IV acyclovir
Eczema herpeticum
• others
• Viral: chicken pox can mimic eczema herpeticum,
molluscum contagiosum, viral warts
• Allergic contact dermatitis
• Growth retardation: failure to thrive can be marked in
infants with extensive and severe disease which can
indicate another problem such as nutritional deficiency or
food allergy
Reason for poor response to therapy
1. Poor patient compliance
2. Inadequate strength of TCS prescribed in
primary care
3. Secondary bacterial or herpetic infection
4. Superimposed contact allergy
Indications for referral to secondary care
• Severe atopic eczema which has not responded to
topical therapy after 1 week
• Treatment of secondary bacterial infection has failed
• Uncertain diagnosis
• AD on face not responding to appropriate treatment
• Suspicion of contact allergic dermatitis/food allergy
• AD causing significant social/psychological problems
• AD associated with severe/recurrent infections
• Children with AD who fail to grow at the expected growth
trajectory
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Case 1
Mild eczema
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Non-perfumed leave-on emollient instead of
aqueous cream
Consider adding additional bath additive if skin
very dry
Mild TCS to apply to all affected areas once/twice
daily, until skin clear for > 48 hours, repeating as
necessary
Emphasise: safety of mild CS in all age groups,
apply to all inflamed red areas, including areas of
broken skin, to restore skin barrier
If no response in 3-5 days, step up to moderately
potent steroid ointment once/twice daily until skin
clear for >48 hrs only on face and neck
Longer bursts o 7-14 days on body and limbs if
needed
Explain to parents: topicals don’t cure eczema, so
repeat treatment bursts likely to be necessary
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Case 2
Moderate eczema
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Consider antimicrobial emollient(Dermol
lotion/cream) to reduce bacterial
colonization, and greasier emollient at night
on lichenified areas(Epaderm, Hydromol)
Step up to moderately potent TCS to all
active areas until clear for > 48 hrs, repeating
as necessary
Explain to carers: application for 7-14 day
bursts, esp. in lichenified areas, until
thickened skin texture returns to normal
Use moderately potent tcs on face/ neck for
3-5 day bursts if no response to mild tcs
Any patches of eczema don’t clear
completely with 7-14 day bursts, step up to
potent tcs(Betnovate or Elocon) on body and
limbs, initially for 3-5 day bursts but no longer
than 14 days continuously.
Continued….
• EMPHASISE to not use on face and neck at all, and only used with
caution in flexures (e.g. very thickened areas usually for 3-5 days
followed by moderately potent TCS on remaining days, repeating as
necessary)
• If child require tcs to face/flexures on daily basis long term consider
topical tacrolimus 0.03%
• Introduce when skin well controlled. Explain side effects to parents:
it is very common for 1st 1-2 weeks and tends to settle, nneds suncare precautions
• Consider proactive therapy: twice weekly moderately potent tcs or
0.03% topical tacrolimus to problem areas that are repeatedly
flaring.