Atopic eczema

Dr. khola aijaz

pg d-derm
 DEFINITION.
❄ Atopic Eczema or atopic dermatitis is an itchy,
chronic or chronically relapsing inflammatory skin
condition.

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 WHAT IS ATOPY?
❄ Atopy is a personal or familial tendency to produce
Ig E antibodies in response to low doses of
allergens, usually proteins, and to develop typical
symptoms of asthma, rhino conjunctivitis or
eczema/dermatitis’

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 ❄ AE can be described in two forms:

1. Extrinsic eczema High levels of IgE (>200 ku/l).

2. Intrinsic eczema normal levels of IgE.

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 EPIDEMIOLOGY
❄ International Study of Asthma and Allergies in
Childhood (ISAAC) With close to 2 million
children from 106 countries affected from atopic
eczema.

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 AGE AND SEX
❄ AE starts during infancy (usually less than 2 years
of age).
❄ Slightly higher prevalence among females

MORBIDITY AND COST

❄ $338/year for each affected individual.

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Pathophysiology

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 GENETICS
❄ Epidermal differentiation complex (EDC) on
1q21.Nonsense Mutation of 1q21 locus for the gene
encoding filaggrin protein (FLG).

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EPIDERMAL BARRIER
DYSFUNCTION
❄ Frequent use of detergents and water hardness upregulation
in protease activity
❄ skin barrier impairment by reduction in natural moisturizing factor
increase in skin pH are associated with an increase in AE risk.
❄ Impaired ceramide production were characteristic of AE epidermal
barrier defects.
❄ Increased activity of serine proteases enzymatic activity in the
epidermis analogous to that seen in Netherton syndrome

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Cleavage of • dephosphorylation
profillagrin • matriptase

Free fillagrin
• (-)of LEKT1
monomers

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❄ Tight junctions are important cellular adhesion molecules in the
stratum granulosum.
❄ Recent work has also suggested that tight junction proteins
including claudin 1 and 23, are expressed at lower levels in skin of
AE patients
❄ In older treatments, Coal tar application up regulates FLG
expression.

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ENVIRONMENTAL FATORS

50% reduction

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 Environmental factors
UV radiation have well‐established immunosuppressive effect.
❄ Good evidence of higher eczema burden in cities compared to the
countryside.
❄ High intake of refined grains, cured and red meats, as well as
saturated and unsaturated fatty acids) leads to an increase in AE
risk.
❄ High fish intake during pregnancy lowers AE risk in the offspring
up to 5 years of age by 25–43%

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❄ High fish intake during late infancy.
❄ Exclusively breastfed for 6 months.
❄ Obesity may cause AE because inflammation mediated by
adipokines such as leptin.
❄ Effect of TV viewing greater than 5 hour positive risk of AE.

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❄ Less evidence that AE risk in the offspring with maternal smoking
during pregnancy or environmental tobacco exposure postnatally.
❄ washing and use of household cleaners, are weakly associated
with risk.
❄ Raw cow’s milk.
❄ Direct contact with farm animals reduces AE risk in early life

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❄ Pets have been implicated as potentially protective against AE.
❄ Perinatal priming of the immune system with helminth parasites
can provide protection against AE.
❄ AE risk increase associated with antibiotics.

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 Immune dysregulation
❄ The cellular infiltrate in early lesional AE is predominantly T
lymphocytes (CD4+ : CD8+ ratio 7 : 1) but eosinophils are also
present.
❄ Allergens evoke Th2 responses in lymphocytes from atopic
subjects.
❄ Th2 responses expressing IL‐4, IL‐5 and IL‐13 in early
lesional.
❄ In chronic lesions IL‐5, granulocyte– macrophage colony ‐
stimulating factor (GM‐CSF), IL‐12 and IFN‐γ predominate.

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❄ T‐regs in regulating allergic responses
❄ Staphylococcus aureus, produce super antigens. It stimulate Th2
lymphocyte responses and subvert T‐reg function, leading to
enhanced inflammation.
❄ Modulation of Th2 responses towards Th1 is associated with
disease improvement. correction of atopy may be achieved by
bone marrow transplantation

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 Regulatory T cells in atopic disease

Immune dysregulation poly endocrinopathy (IPEX syndrome)

❄ Genetic disorders which are characterized by a lack of regulatory
T cells
❄ X‐linked syndrome
❄ Spontaneous dermatitis, hyper‐IgE and food allergy.

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❄ Atopic march describes the progression within an individual from
AE to other atopic diseases including allergic rhinitis and food
allergy.
❄ Allergic responses to milk, egg, wheat, soy, peanut and fish
account for 85% of reactions.

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❄ The small blood vessels in AE show a tendency to
vasoconstriction responses
❄ Pallor of the skin after stroking – white dermographism.
❄ Delayed blanch with acetylcholine (ACh).
❄ White reaction to nicotinic acid esters.
❄ Abnormal reactions to histamine in affected skin.
❄ Low finger temperature
❄ Pronounced vasoconstriction on exposure to cold .

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 Clinical features
History
between 2 and 6 months even before it.
less than 2 years of age.
Itch
Aggravated by warmth, sweating, bathing, exercise, emotional upset
and woolen clothes.

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 Clinical variants
❄ Infantile phase
❄ Childhood phase
❄ Adult phase

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 Infantile phase

Extensor aspect of the

knees and elbows
involved
chronic fluctuating
course

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 CHILDHOOD PHASE
❄ 18 to 24 months onwards.
❄ Elbow and knee flexures.
❄ Erythema, crusting, excoriation, hyper‐ and hypopigmentation,
and warty lichenification on the sides of the neck, wrists and
ankles
❄ The sides of the neck may show a striking reticulate pigmentation,
sometimes referred to as ’atopic dirty neck’
❄ Involvement of the hands, sometimes with nail change.
❄ Secondary bacterial or viral infection

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 Adult phase (12 y and older)
❄ Lichenification of flexures and hands.
❄ Involves nipples in young women & vermilion border
of lips.
❄ Face, upper arms and back with areas of maximal
thermal sweating or Malassezia sensitivity
❄ Photosensitivity Frequently, facial and hand
involvement.

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 Atopic hand eczema
❄ More than 50% of patients with active AE
❄ A patchy, somewhat vesicular and lichenified eczema is a
common manifestation of AE in childhood.
❄ The nails are often involved, resulting in coarse pitting and
ridging.
❄ Diffuse, chronic lichenified eczema in extensive AE.
❄ occupational dermatitis particularly if associated with loss ‐of ‐
function filaggrin mutations
❄ Atopics may be at risk of occupational food‐related hand
dermatosis.

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 diagnosis
❄ History
❄ Clinical examination.

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 White Dermographism

❄ Pallor of skin after stroking

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HANFIN & rajka’s diagnostic criteria of
AE
❄ An itchy skin condition (or parental report of scratching or
rubbing of child)
❄ Plus three or more of the following:
❄ 1  Onset below age of 2 years (not used if child is under 4 years)
❄ 2  History of skin crease involvement.
❄ 3  History of a generally dry skin
❄ 4  Personal history of other atopic disease (or history of any atopic
disease in a first‐degree relative in children under 4 years)
❄ 5  Visible flexural dermatitis

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 Differential diagnosis
❄ Scabies
❄ Infantile seborrhoeic dermatitis
❄ Human T‐lymphotropic virus 1 (HTLV‐1) infection.
❄ Occupational contact dermatitis
❄ Lip-lick chelitis
❄ Contact-sensitivity like tooth-paste

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Differential diagnosis having AE like rash

❄ Hyper‐IgE syndrome
• Hypereosinophilic syndrome
• Agammaglobulinaemia
• Anhidrotic ectodermal dysplasia
• Ataxia telangiectasia
• Netherton syndrome (ichthyosis, bamboo hairs)
• Phenylketonuria
• Wiskott–Aldrich syndrome (infections and thrombocytopenia)

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 Classification of severity
❄ SCORing Atopic Dermatitis (SCORAD)
❄ Eczema Area and Severity Index (EASI)
❄ Patient Orientated Eczema Measure (POEM)
❄ Global assessment of severity, itch and loss of sleep on a 0–10
scale could be a simple clinical aid to assessing severity.

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 Complications and co‐
❄
morbidities
Psychosocial aspects
❄ AE results in impairment in quality of life
❄ Severe eczema promotes family dysfunction, causing exhaustion,
sleep deprivation and emotional distress and may predispose to
later problems with mental health.
❄ Depression, anxiety, conduct disorder and autism were similarly
increased in frequency in AE

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• Growth delay: due to severely affected child treated with steroids.
• Secondary bacterial infections
• Viral infections (erythema herpeticum)
• Ocular manifestations like Dennie- Morgan fold, conjunctival
irritation.
• Cataracts, retinal detachments are observed.

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 • Lymphomas
• Cartilagenous pseudocyst in external ear.
• Allergic rhinitis and asthma.
• Dryness (xerosis): icthyosis vulgaris and KP are associated.
❄ Infantile seborrhoeic dermatitis
❄Allergic contact dermatitis
❄Lip‐lick cheilitis
❄Food allergy
❄Alopecia areata
❄Urticaria

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 Erythema herpeticum
Herpes simplex virus (HSV) poses an increased risk for individuals
with AE and superficial dissemination on the skin known as ’Kaposi
varicelliform eruption’ or eczema herpeticum. Constitutinal symptoms
+ve.
Rapid detioration of
❄Eczema. Papulovesicle eruption.
❄Ddx
❄Impetigo, chickenpox.

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Disease course and prognosis
❄ Well‐defined populations suggest that only 60% of children with
AE grow out of their disease by adolescence.
❄ Factors that indicate a worse prognosis include severe childhood
disease, early onset and a concomitant or family history of asthma
or hay fever.
❄ Children with raised IgE antibodies to foods and inhalant antigens
at 2 years of age may also have a poorer prognosis

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Disease prevention and occupational
advice
❄ Manipulation of allergen exposure
❄ Altering the diet of the newborn child with supplements (omega‐
3 or ‐6)
❄ Prebiotics or probiotics or hydrolysed milk formulations.
❄ Epidermal barrier and its protection and rapid healing with
emollients

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 Investigations
• Serum Ig E
• Prick test
• Gold-standard is double-blind placebo controlled food-challenge.
• Atopic patch test for aeroallergens and food-allergy in late phase.
• Immunoglobulins, WBCs, platelets, HIV screening.
• Bacterial swabs
• T zanck smear, PCR

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ATOPIC PATCH TEST

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The APT consists of a petrolatum preparation of protein allergens
applied in 12‐mm diameter Finn chambers for 48 h to non ‐abraded,
non‐tape‐stripped skin of the upper back for 48 h. The test is read at 48
and 72 h assessing erythema as well as number and distribution pattern
of the papules according to the EFTAD guidelines.
There is a 15‐ min immediate weal and flare due to histamine release
from skin mast cells. A late‐phase response comprising erythema and a
deeper edematous reaction occurs between 6 and 24 h, and there is a
delayed response at 48 h.

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 • Raised Wbcs,
Skin biopsy eosinophils
• Raised IgE
Skin • On scratchin
scratch/prick shows
test allergens
• To detect
Total &
environmental
specific IgE allergens
 Management
❄ First assessment
❄ Comprehensive history of the patient’s disease, family history,
recognized trigger factors and home environment,

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treatment

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 1st line
• Apply emollients, Urea creams Oils once a day after bathing and
whenever skin feels dry.
• Hydrocortisone 1-2.5% applied to all skin
• Stronger potency steroids used in non-facial and genital areas.
• Oral corticosteroids (0.5 mg/kg)
• H1-receptor antagonists (hydroxyzine, promethazine or
trimeprazine) HS useful in nocturnal itch.
• Oral flucloxacillin or erythromycin for secodary bacterial
infections

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 2nd line
Topical immunosuppressants and topical calcineurin inhibitors like
tacrolimus (adults 0.1% children 0.03%) and pimecrolimus.
Used when continuous use of topical steroids are not useful and not
advisable
Phototherapy: UV light can be an effective treatment
Combined UVA & UVB therapy is more useful than single UVA or
UVA therapy
Also helpful in reducing bacterial infections.

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 Wet wrap technique
❄Two layers of absorbent tubular bandage are applied to the skin. The inner
layer is presoaked in warm water and the outer layer is dry. A generous
quantity of a low‐potency topical corticosteroid is applied to the skin before
the dressings. The dressings can be used overnight or changed every 12 h.
This regimen can be used in hospital or for short‐term out‐patient treatment.
Close supervision should be maintained because suppression of the
hypothalamopituitary axis can occur when topical steroids are employed.
❄Regimens using emollient only under the wet dressings have become
popular but are somewhat less effective. Localized areas of severe
lichenification can be treated with occlusive colloid dressings or paste
banding that is left on for several days.
 Third line
Anti-histamines for itching
Linoleic acid and linoleic gamma for pruritis
Macrolide and cephalosporin for bacterial infections.
Acyclovir of herpeticum eczema.

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Advanced therapies

Cyclosporin

Methotrexate

Biologics (anti-IgE i.e

Azathiprione
Omalizumab)
• Ciclosporin:
• Highly effective in adults and children.
• Initial dose 2.5-3.5 mg/kg/day with maximal daily dose of 5
mg/kg/day.
• Reduction in 55% patients in 6-8 weeks.
• Regular monitoring of renal function and blood pressure.
• Azathiprine:
• Dosage depends on thiopurine methyltranferase (TPMT) activity in
RBCs.
• Those with high TPMT activity 1-3mg/kg/day
• Low TPMT activity 0.5-1 mg/kg/day.
• Regular blood monitoring as it can cause neutropenias

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Methotrexate : 10 mg/week following a 5 mg test dose and increasing
by 2.5 mg weekly to max 25 mg/week.
Maximum effect in 10 weeks
Mycophenolate mofetil: failed to respond on azathioprine or
methotrexate.
Forth line agent
2 g/day
Side effects: GI disturbance, leukopenia lymphopenia and anemia.
Alitretinoin (9-cis retinoic acid) for hand eczema

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❄ Biologics (anti-IgE i.e omalizumab)
• Rituximab
• Duplimab ( fully human monoclonal antibody)

• Topical phosphodiesterase inhibitors and are under work.

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 immunodysfunction
❄ Primary immonudeficiencies:
❄ Wiskott-Aldrich Syndrome:
• X-linked
• Clinical triad of micro thrombocytopenia, eczema and recurrent
infections.
• Eczema is d/t abnormal T-cell response.
• Eczema appears in first month.
• Fulfills rajka’s criteria.
 Hyper ig-e (job) syndrome
Characterized by recurrent abscesses, recurrent pneumonia with
pneumatocele, eczematous dermatitis and raised Ig-E levels.
AD, AR
Skeletal, connective tissue and dentition.
Th-17 deficiency, Il-17 high (FLG down-regulation -> skin barrier
dysfunction).
Coarse faces, a prominent forehead, a
broad nasal bridge, and a bulbous
nose.
 Omenn syndrome
AR form of severe combined immunodeficiency .
Erytheroderma, desquamation alopecia, chronic diarrhea,
lymphadenopathy,
hepatosplenomegaly, failure to thrive.
Virtual absence of B-cells and presence of autoreative T-cells.
Elevated IL 4, IL 5, Ig-E, eosinophils.
Omenn syndrome. Unique dermatitis resembling eczema but later
panchydermia.
 Ipex syndrome
❄ Immuno dysregulatory, poly endocrinopathy, enteropathy, x-linked
syndrome.
❄ Early onset ID DM, severe watery diarrhea often with failure to
thrive, spontaneous dermatitis, food allergies and hyper igE.
❄ Males only
❄ fOXP3 mutations
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 Question 1
❄ Most common site of atopic dermatitis
❄ 1.scalp
❄ 2. antecubital fossa
❄ 3. trunk
❄ 4. nail

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 answer
❄ Antecubital fossa

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 Question 2
❄ Age of onset of atopic dermatitis most commonly.
❄ At 40 yr
❄ At 50 yr
❄ Before 3 year
❄ At old age

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 answer
❄ Before 3 yr

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 Question 3

❄ Phases of atopic dermatitis

❄ Clinical features
❄ Immunoglobulins raised?

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 .

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