Atopic Dermatitis

by

Leow Atomic Chuan Tse (Group1)B.Agri.Sc(Hons); Dip.Ed., PhD (Toxicology);

Grad.Dip.CS (1st Class Hons); MDiv (1st Class Hons)

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Eczema/Atopic Dermatitis Eczema is a nonspecific term for many types of skin inflammation (dermatitis). Atopic Dermatitis is a type of eczema,

and it is a long term skin disease. “Atopic” refers to a tendency to develop allergy conditions. “Dermatitis” means swelling of the skin or inflammation of

the skin.

The most common The most common inflammatory skin inflammatory skin

conditioncondition

Most confusing skin Most confusing skin ailment for both patients ailment for both patients

and their and their nondermatologic health nondermatologic health

care providerscare providers

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Atopic dermatitis is the most common type of eczema. It is a chronic, inflammatory, itchy skin condition with unpredictable course of flares and remissions. It affects 5% to 10% of the United States population.

Most cases begin in childhood (often in infancy); however may start any

age.

The disease The disease frequently remits frequently remits spontaneously-spontaneously-

reportedly in 40% reportedly in 40% to 50% of to 50% of

children- but it children- but it may return in may return in adolescence or adolescence or adulthood and adulthood and possibly persist possibly persist for a lifetime. for a lifetime. Typically families are advised that children “will grow Typically families are advised that children “will grow

out of eczema” (out of eczema” (About 2 in 3 children with atopic eczema grow out About 2 in 3 children with atopic eczema grow out of it by their mid teens)of it by their mid teens)

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Atopic dermatitis is an inherited Type I hypersensitivity

disorder of the skin. It is usually

associated with personal or family

history of hay fever, asthma, allergic

rhinitis or sinusitis.

MGrandfather

M.

Grandmother

P. Grandfather

P. Grandmother

MOM DAD

BABY

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Type 1 Hypersensitivity• In type 1 hypersensitivity, an antigen is presented to CD4+ Th2

cells specific to the antigen that stimulate B-cell production of IgE antibodies also specific to the antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity the antibody is IgE instead of IgA, IgG, or IgM. During sensitisation, the IgE antibodies bind to Fcε receptors on the surface of tissue mast cells and blood basophils.Mast cells and basophils coated by IgE antibodies are "sensitised." Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotriene (LTC4 and LTD4), and prostaglandin that act on the surrounding tissues. The principal effects of these products are vasodilation and smooth-muscle contraction.

• Type 1 hypersensitivity can be further classified into an immediate and late-phase reaction. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines.

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Normal Skin

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Skin of Acute Eczema

Eczematous epidermis contains intercellular and intracellular fluid that appears in a sponge-like formation (spongiosis);

Vasodilatation of the dermis occurs, resulting in the clinical manifestation of ACUTE eczema.

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Allergic ADAllergic AD　　　　　　

(Extrinsic(Extrinsic ）） ADAD 　　

Allergic ADAllergic AD　　　　　　

(Extrinsic(Extrinsic ）） ADAD 　　

Non-allergic AD Non-allergic AD (Intrinsic(Intrinsic ）） ADAD

Non-allergic AD Non-allergic AD (Intrinsic(Intrinsic ）） ADAD

IgE mediated IgE mediated AD AD （（ Classical Classical

ADAD ））

IgE mediated IgE mediated AD AD （（ Classical Classical

ADAD ））

Non IgE ADNon IgE ADNon IgE ADNon IgE AD

T cellsT cells

Eosinophils Eosinophils

IgGIgG （（ AutoantiboAutoantibodydy ））

Etc.Etc.

T cellsT cells

Eosinophils Eosinophils

IgGIgG （（ AutoantiboAutoantibodydy ））

Etc.Etc.

Allergy 2001:56:813-824 　

EczemaItch

Xerosis

Classification of atopic dermatitis(AD)/eczemaClassification of atopic dermatitis(AD)/eczema

●Impaired barrier function

●Abnormal sweating

●Altered innate immunity(Defensin, Toll like receptor, NALP proteins (linked to autoimmune disease))

●Emotional stress

●Impaired barrier function

●Abnormal sweating

●Altered innate immunity(Defensin, Toll like receptor, NALP proteins (linked to autoimmune disease))

●Emotional stress

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Horny layer

Epidermis

Dermis

Chemokines

Inflammatory cells

Barrier dysfunction

Th2 Allergic Inflammation

Mast cells

AllergensBacteria

Th2 Lymphocytes

Cytokine

Chemicals

IgE

FcR1

Dendritic cell

Pathphysiology of atopic dermatitis

IgE

FcR1

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Stratum corneumStratum corneum

epidermisepidermis

dermisdermis

SCRATCHSCRATCH

chemical mediatorschemical mediators

Elongation of peripheral nerveElongation of peripheral nerve release of substance Prelease of substance P

Damage of barrier functionDamage of barrier function and keratinocytes and keratinocytes

FcR1Dendritic cell

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Immunology of Atopic Dermatitis

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Mechanism of PruritusN ENGL J MED 2008; 358:1483-1494April 3, 2008

The most important symptom in atopic dermatitis is persistent pruritus, which impairs the patient's quality of life. The lack of effect of antihistamines argues against a role of histamine in causing atopic dermatitis–related pruritus. Neuropeptides, proteases, kinins, and cytokines induce itching. Interleukin-31 is a cytokine produced by T cells that increases the survival of hematopoietic cells and stimulates the production of inflammatory cytokines by epithelial cells. It is strongly pruritogenic, and both interleukin-31 and its receptor are overexpressed in lesional skin. Moreover, interleukin-31 is up-regulated by exposure to staphylococcal exotoxins in vitro. These findings implicate interleukin-31 as a major factor in the genesis of pruritus in atopic dermatitis.

Intense Itching and Unceasing Scratching

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Clincal features of atopic dermatitis

Scratching aggravates atopic Scratching aggravates atopic dermatitisdermatitis

Itch is an unpleasant Itch is an unpleasant sensation to evoke sensation to evoke

scratching scratching Rothman S1941(Samuel Hafenreffer 1660)Rothman S1941(Samuel Hafenreffer 1660)

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Acute Eczema Appears as “itchy” erythematous patches, plaques, or papules that may develop into vesicular lesions, or may continue as a less nonvesicular, erythematous eruption.

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Chronic Eczema Later, the epidermis will

thicken (acanthosis) and retain parakeratosis (abnormal keratinization of the squamous epithelium), resulting in an overabundance of cellular infiltrate in the dermis.

These changes account for the scale and lichenification of CHRONIC eczema. The epidermis shows

hyperkeratosis, acanthosis, and a prominent granular layer.

There is liquefaction degeneration at the dermal-

epidermal interface.

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Lichens on a tree• The word “Lichen” has a Greek origin and

denotes the superficial growth of an algae and fungus on the bark of a tree

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Chronic Eczema(aka: Chronic eczematous dermatitis)

• Has a hallmark lichenification (plaque with an exaggeration or hypertrophy of the normal skin markings).

• Scale and hemorrhagic crusts can result from scratched or drying vesicles.

• Older lesions exhibit hypo or hyper pigmentation.

Lichenification

Hypo-pigmentation

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Severity

Atopic dermatitis can present with a wide spectrum of severity.

mild, recurrent, localized itchy rash on “dry” skin or

more severe, extensive eruption that can be accompanied by unremitting pruritus, sleepless nights, secondary cutaneous bacterial infections, and/or embarrassing lichenification.

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Psychosocial EffectsPsychosocial problems, such as poor self-image, anger, and frustration may lead to depression and

social isolation.

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Different Phases of Atopic Dermatitis

The character and distribution of the skin rash tends to vary according to the patient’s age.

Any or all manifestations of atopic dermatitis may exist in a single patient.

The different phases of atopic dermatitis are not always clearly distinct.

Infantile Phase Childhood Phase Adolescent and Adult Phase

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Infantile PhaseEruption may become generalized, in most cases it first manifests with severe “cradle

cap” or severe intertriginous (inflammatory) rashes (groin, neck, axillae). As the patient approaches age 2 years, the flexor creases become involved.

Lesions consist of scaly, red, and occasionally oozing plaques that tend to be symmetric.

Occurs on theOccurs on the scalp scalp face, face, particularly particularly cheekscheeks neckneck chest chest extensor extensor extremitiesextremities

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Childhood Phase(patients aged 2 years to 12 years of age)

These patients tend to be less acute and lesions less exudative than These patients tend to be less acute and lesions less exudative than those seen in infancy.those seen in infancy.Inflamed lesions become lichenified (especially in Asian and Inflamed lesions become lichenified (especially in Asian and African-American patients)African-American patients) secondary to chronic rubbing symmetrically, with characteristic secondary to chronic rubbing symmetrically, with characteristic distribution in the flexural folds and scratching.distribution in the flexural folds and scratching.Lesions tend to occur.Lesions tend to occur.

Occurs on the:Antecubital and popliteal fossaeNeck, wrists, and anklesMay occur on the eyelids, lips, scalp, and postauricular areas

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Adolescent and Adult Phase(patients 12 years and older)

Post inflammatory hyper or hypo pigmented changes tend to be seen.

The appearance of atopic dermatitis may change to a more poorly defined, itchy, erythematous rash,

possibly with papules and/or plaques.

Lichenified Lichenified plaques of atopic plaques of atopic

dermatitis are dermatitis are typically less well typically less well demarcated than demarcated than are the plaques are the plaques

seen in psoriasis. seen in psoriasis. These plaques tend These plaques tend

to blend into to blend into surrounding surrounding normal skin.normal skin.

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Possible ComplicationsPruritus (itching) may interfere with sleep. Pruritis is

increased by repeated scratching and rubbing, which leads to lichenification, oozing, and secondary bacterial infection.

Secondary infection with Secondary infection with Staphylococcus aureus may trigger Staphylococcus aureus may trigger

relapse of atopic dermatitisrelapse of atopic dermatitis..

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Clinical AspectsClues to diagnosing Atopic Dermatitis:

• Persistent Xerosis (abnormal dry, “sensitive” skin)• “Allergic Shiners” (darkened or tanned coloring

in the periorbital areas) • Hyperlinear palmar creases (exaggerated skin

creases or lines in the palms of the hand.• Follicular eczema (Lesions accentuated around

hair follicles )• Ichthyosis vulgaris (an inherited skin disorder in

which dead skin cells accumulate in thick, dry scales)

• Keratosis Pilaris (skin condition that looks like small goose bumps)

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Differential Diagnosis Diagnosis of atopic dermatitis is generally not difficult, especially in patients with atopic history. The following

should be considered or excluded:

Determine whether the patient was exposed to a substance that could cause contact dermatitis. The location of the lesions may suggest an external cause.

Contact DermatitisContact Dermatitis

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Differential Diagnosis

Lesions are generally in extensor locations (elbows, knees, and other large joints) rather than the flexor creases. May be palmar or plantar as seen in this image.

Patients typically have a positive family history of psoriasis.

PsoriaPsoriasissis

Psoriasis is less pruritic Psoriasis is less pruritic than eczema, lesions tend than eczema, lesions tend to be clearly demarcated to be clearly demarcated from normal surrounding from normal surrounding

skin, and the scale of skin, and the scale of psoriasis tends to be thicker psoriasis tends to be thicker

in appearance. in appearance.

However, psoriasis may at However, psoriasis may at times be clinically times be clinically

indistinguishable from indistinguishable from atopic dermatitisatopic dermatitis

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Differential Diagnosis

A positive KOH test or fungal culture result will

confirm

(remember, an unresolved eczematous-like rash,

worsening with topical corticosteroids could be

tinea)

TineaTinea

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EmolientsEmolientsTacrolims(Face) Tacrolims(Face) Steroid ointment Steroid ointment

Anti-hisitamineAnti-hisitamineImunosuppresantsImunosuppresants

EmolientsEmolientsTacrolims(Face) Tacrolims(Face) Steroid ointment Steroid ointment

Anti-hisitamineAnti-hisitamineImunosuppresantsImunosuppresants

DiagnosisDiagnosisDiagnosisDiagnosis

Assessment of dermatitisAssessment of dermatitisAssessment of dermatitisAssessment of dermatitis

Clean of the skinClean of the skin 　　　　

　　　　　　　　　　　　 BathinBathin

gg ・・ ShoweringShowering ・・

EmolientEmolient

Clean of the skinClean of the skin 　　　　

　　　　　　　　　　　　 BathinBathin

gg ・・ ShoweringShowering ・・

EmolientEmolient

Drug Drug

therapytherapy

Drug Drug

therapytherapyEvaluation of Evaluation of

Aggravation factorsAggravation factors

　　

Evaluation of Evaluation of

Aggravation factorsAggravation factors

　　

Appropriate guidance Appropriate guidance

for for

patients in daily lifepatients in daily life

Appropriate guidance Appropriate guidance

for for

patients in daily lifepatients in daily life

Skin careSkin care 　　

Rectification of aberrant Rectification of aberrant

skin barrier functionsskin barrier functions

Skin careSkin care 　　

Rectification of aberrant Rectification of aberrant

skin barrier functionsskin barrier functions

Japanese guide line for atopic dermatitisJapanese guide line for atopic dermatitis

Katayama et al.(JSA) Allergology International 2011

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Narrow Band UVB Phototherapy• Eczema light therapy refers to the use of ultraviolet

(UV) light to treat the skin rash and itching of eczema. Exposing the skin to UV light suppresses overactive skin immune system cells that cause inflammation

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ManagementIn children, NICE ( National Institute for Health and Clinical

Excellence) suggest a treatment schema based on severity:• mild atopic eczema

– emollients– mild potency topical corticosteroids

• moderate atopic eczema – emollients – moderate potency topical corticosteroids– topical calcineurin inhibitors e.g. pimecrolimus – bandages

• severe atopic eczema – emollients – potent topical corticosteroids – topical calcineurin inhibitors– bandages – phototherapy– systemic immunosuppressive therapy (cyclosporine,

azathioprine, interferon-gamma)

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Aggravating factors in atopic dermatitisAggravating factors in atopic dermatitis

InfantsInfants ～～ 2 2 yy

2 y2 y ～～ 1313 y y 13 13 yy ～～ AdultAdult

1.Foods (Egg,milk,wheat,etc)1.Foods (Egg,milk,wheat,etc)

2.2.SweatSweat,dryness,scratching,dryness,scratching

3.Slaver,soap,shampoo, cloth3.Slaver,soap,shampoo, cloth

4.Environmental factors4.Environmental factors

5.Bacteria, fungus etc.5.Bacteria, fungus etc.

11.Sweat.Sweat,dryness,scratching,dryness,scratching

2.Slaver,soap,shampoo, 2.Slaver,soap,shampoo,

clothcloth

3.Bacteria, fungus,etc.3.Bacteria, fungus,etc.

4.Environmental factors4.Environmental factors

55.Stress.Stress

66.Foods.Foods*Aggravation factors *Aggravation factors arare different in each patient.e different in each patient.

Start to eliminate responsible factors after sufficient evaluation.Start to eliminate responsible factors after sufficient evaluation.

Katayama et al.(JSA) Allergology International 2011

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AvoidanceIrritants:– Recommend non-irritant

fabric, such as cotton. Wool may induce itching

– Overheating and sweating: Excess dryness or

humidity should be avoided.

An air conditioner or humidifier in a child’s bedroom may help to avoid the dramatic changes in climate that may trigger outbreaks.

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Avoidance

Allergens:Allergens: Environmental Environmental elimination of elimination of airborne substances airborne substances may bring lasting may bring lasting relief.relief.

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Thank You