Atopic dermatitis is a complex inflammatory skin disease with different phenotypes and underlying molecular mechanisms (endotypes). It involves complex cytokine and immunological networks of Th2, Th1, Th17 and Th22 cells. The disease presentation and molecular profiles differ based on factors like age, chronicity, ethnicity, filaggrin mutations and immune status. Understanding the distinct endotypes can help develop personalized treatment approaches targeting specific cytokines and pathways. Further research is still needed to better characterize endotypes in relation to aspects like microbiome, specific allergens and autoantigens involved.
4. Atopic Dermatitis
Inflammatory
cutaneous
disease
Atopic
diathesis
Multifactorial
onset and
aggravation
Skin barrier
dysfunction
Allergology International 66 (2017) 230-247
and/or predisposition to overproduce
immunoglobulin E (IgE) antibodies
Personal or family history of asthma,
allergic rhinitis and conjunctivitis,
and/or atopic dermatitis
Environmental factors, sweating,
physical irritation (including scratching),
microbes/fungi, stress, and allergens
(dust mites, foods)
Decreased expression of ceramide and
filaggrin (primary or secondary),
increased transepidermal water loss,
lowered treshold of itch
Th2
Th1 Th17
5. J Allergy Clin Immunol 2019;144:362-74
• Skin = active immune organ
• Contact with Ag:
• Tolerance vs Immunity
• Immunological cells:
• Dendritic cells
• T reg lymphocytes
Toleroge
n
Immunoge
n
33. Atopic dermatitis: summary
TSLP, IL-25, IL-33
Alarmins g Th2
polarization
IL-4, IL-5, IL-13
Th2 g h IgE, i FLG, h Eos
IL-9
MC, Bas g h FceR, h
Histam
CRTH2
PGD2 g h Th2, ILC2, Eos,
Ba
Histam, IL-31, NK
Sensory neuron g h
Pruritus
OX40, JAK, PDE4
Activation g Th2
polarization
IL-12, IL-23
Th17 polarization
IL-17, IL-22
Epidermal
hyperplasia
IFNg, TNFa
Eczema, spongiosis
41. Atopic dermatitis:
conclusions• Heterogenous inflammatory skin disease
• Different phenotypes based on:
• age, chronicity, ethnicity, FLG and immune
status
• Underlying molecular mechanisms (endotypes) g
personalized medicine
42. Atopic dermatitis: questions
• Endotypes related to microbiome?
• Endotypes related to specific allergens?
• Endotypes related to autoantigens?
• Different cytokine networks in AD types?