journal reading the infectious aspects of atopic dermatitis

7/28/2019 Journal Reading the Infectious Aspects of Atopic Dermatitis

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JOURNAL

READINGTHEINFECTIOUS

ASPECTS OFATOPICDERMATITISPresented by: Bill Kartolo

(UNTAR 406127058)


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Atopic

Dermatitis

Chronic inflammatory skindisease

Can cause morbidity

Often characterized by:

Chronic inflammation Pruritus interupted by acute flares

Bacterial infection

AD patients More severe skin disesase

>> tendency skin infection

Most common skin infection : S.aureus (colonized) and HSV


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Pathogenesis ofAD: Skin BarrierDefects

Stratum Corneum (SC)prevent water loss, protectfrom intrusion by irritants or

microbes

TEWL studies: SC of AD skin is defective and

thinner (12.2 microns vs 19.7microns)

TEWL in AD lesions >>>

Proteins and lipids (filaggrin,

involcrin, cholesterol, FFA,ceramides)


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Susceptibility of ADPatients toInfections

In AD, deficiency in hostdefense molecules (first-line

defense) contribute to theincreased infections.

Sphingosine (skin lipid with anti-S.aureus activity)

Dermcidin (AMP antimicrobialpeptide)

2 major classees of AMPs (beta-

defensins and cathelicidin)


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AdaptiveImmunity Role

Cell wall of S.aureus trigger the

production of TSLP by epithelialcells including keratinocytes

TSLP >> CCL17 and CCL 20 (Th2-associated chemokines) by

macrophages >> infiltration ofTh2 cells express >> of IL-4 and IL-13


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These cytokines responsible for:

Favor the attachment of S.aureus in AD skin

Suppress filaggrin further barrier compromise in AD

Suppress AMP (HBD-3) expression by keratinocytes

Decreased IL-17 expressions


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The Role ofS.aureus in AD

> 90% of AD patients arecolonized with S.aureus (only10% in healthy individuals)

Correlates with the severity ofAD

S.aureus is detected bypattern recognition receptorsin the innate immune system,i.e.: TLR2


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The Role of S.aureus in AD

TLR2 polymorphism dysregulation ofcytokine production inflammation in

AD

Alpha toxin inducing immunedysregulation in AD

Enterotoxins (superantigen)


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The Role of StaphylococcalSuperantigens in AD

50% of S.aureus from AD patients secretesuperantigens (80% are superantigen-producing)

Superantigen presented on MHC II activate T cells

In normal only induces erythema

In AD patients flaring of skin disease


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The Role of StaphylococcalSuperantigens in AD

Superantigens corelates with severity of AD

Directly activate T-cells

Induce the production of superantigen-specific IgE

Antigen-IgE binding activate basophilsIgE mediated inflammation


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The Role of Viral Skin Infectionin AD

Life-threatening infection Eczemaherpeticum (HSV), Eczema vaccinatum

(VV)

Fever, malaise, generalized vesicles

Complications: keratoconjunctivitis,viremia, meningitis, encephalitis, bacterialsepsis


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Beck et al.: a subgroup of AD patients particulary

susceptible to EH

> severe disease

> circulating eosinophils

> serum CCL17 > asthma and specific IgE sensitization to allergens

> secondary S.aureus skin infection


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Lab Finding

IL-4 & IL-13 suppress:

Cathelicidin AMP (LL-37) potent anti-viral

againts HSV or VV

Expression of S100A11 down-regulation of

IL-10R2 receptor for IFN-gamma

IFN-gamma activity againts VV


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Gao et al. :EH in AD associated with FLG mutations

Patera et al. :

Acute AD lesions increase expression of IL-17 IL-17increased the virulence of VV suppress NK activity

againts VV


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The Role of Fungi in AD

Colonization by Malassezia species

Still controversion

Malassezia induce inflammatoryresponses in macrophages via mincle

Malassezia-specific IgE exclusive in ADpatients


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The Role of Other MicrobialPathogen in AD

Group A beta hemolytic Streptococcusassociated with severe AD

Molluscum contagiosum higher risk inAD patients

Lead to disfiguring scars


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Clinical Implication FLG mutations as a predisposing factor

Development of targeted therapy e.g.

increasing the expression of filaggrin Help prevent the development of asthma

IL-4 and IL-13 important targets in thetherapy of AD

IL-17 as a therapeutic target of viral infectionin AD


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THANK YOU

journal reading the infectious aspects of atopic dermatitis

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