JOURNAL READING THE INFECTIOUS ASPECTS OF ATOPIC DERMATITIS

Presented by: Bill Kartolo (UNTAR 406127058)

 Chronic

disease

inflammatory skin

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

Atopic Dermatitis

 Stratum

Corneum (SC) prevent water loss, protect from intrusion by irritants or microbes

TEWL studies: SC of AD skin is defective and thinner (12.2 microns vs 19.7 microns)

TEWL in AD lesions >>> Proteins and lipids (filaggrin, involcrin, cholesterol, FFA, ceramides) <<< Filaggrin gene mutations childhood-onset AD

Pathogenesis of AD: Skin Barrier Defects

 In

AD, deficiency in host defense molecules (first-line defense) contribute to the increased infections.

Sphingosine (skin lipid with antiS.aureus activity) Dermcidin (AMP antimicrobial peptide) 2 major classees of AMPs (betadefensins and cathelicidin)

Susceptibility of AD Patients to Infections

Cell wall of S.aureus trigger the production of TSLP by epithelial cells including keratinocytes TSLP >> CCL17 and CCL 20 (Th2associated chemokines) by macrophages >> infiltration of Th2 cells express >> of IL-4 and IL13

Adaptive Immunity Role

 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

>

90% of AD patients are colonized with S.aureus (only 10% in healthy individuals) with the severity of

Correlates

AD

S.aureus

is detected by pattern recognition receptors in the innate immune system, i.e.: TLR2 The Role of S.aureus in AD

The Role of S.aureus in AD

TLR2

polymorphism dysregulation of cytokine production inflammation in AD toxin inducing immune dysregulation in AD

Alpha

Enterotoxins

(superantigen)

The Role of Staphylococcal Superantigens in AD

50% of S.aureus from AD patients secrete superantigens (80% are superantigenproducing) Superantigen presented on MHC II activate T cells In normal only induces erythema In AD patients flaring of skin disease

The Role of Staphylococcal Superantigens in AD

Superantigens corelates with severity of AD Directly activate T-cells Induce the production of superantigenspecific IgE Antigen-IgE binding activate basophils IgE mediated inflammation

The Role of Viral Skin Infection in AD

Life-threatening

infection Eczema herpeticum (HSV), Eczema vaccinatum (VV) malaise, generalized vesicles

Fever,

Complications:

keratoconjunctivitis, viremia, meningitis, encephalitis, bacterial sepsis

 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

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

 Gao

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

Patera

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

The Role of Fungi in AD

Colonization Still

by Malassezia species

controversion

Malassezia

induce inflammatory responses in macrophages via mincle IgE exclusive in AD

Malassezia-specific

patients

The Role of Other Microbial Pathogen in AD

Group

A beta hemolytic Streptococcus associated with severe AD contagiosum higher risk in AD patients

Molluscum

Lead to disfiguring scars

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 the therapy of AD IL-17 as a therapeutic target of viral infection in AD

THANK YOU