Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, itchy skin lesions. It is associated with elevated IgE levels and a family history of atopic diseases. The causes involve genetic susceptibility and environmental triggers that disrupt the skin barrier and promote a TH2-mediated immune response. Treatment focuses on identifying and avoiding triggers while improving the skin barrier with emollients and controlling inflammation with topical corticosteroids and calcineurin inhibitors. New targeted therapies that block cytokines and immune cells involved in AD pathogenesis are under investigation.

1. ATOPIC DERMATITIS
Manal Bosseila
Prof of Dermatology
Faculty of Medicine, Cairo University

2. Reference
DERMATOLOGY Text Book. 3rd Edition 2012. Eds: Jean L Bolognia, Joseph L Jorizzo, Julie V Schaffer. ElSevier Publishing
Atopic Dermatitis

3. DEFINITION OF ATOPY
The term “atopy” is tightly linked to the presence of allergen-specific IgE antibodies in the serum, as documented by positive fluorescence enzyme immunoassays (previously radioallergosorbent [RAST] tests) or skin prick tests.
Atopic Dermatitis

4. SPECTRUM OF AD
Spectrum of AD
An IgE associated or allergic form of dermatitis corresponds to AD in the strict sense (formerly known as extrinsic AD
The remaining 20–30% of patients with the clinical phenotype of AD who have no evidence of IgE-sensitization are categorized as having a non-IgE-associated or non-allergic form of dermatitis (formerly known as intrinsic AD).
Atopic Dermatitis

5. THE ATOPIC MARCH
Atopic Dermatitis

6. PATHOGENESIS of Atopic Dermatitis
AD
Genetic
Environ- mental
Immunologic Mechanisms
Epidermal Barrier Dysfunction
Atopic Dermatitis

7. GENETICS
The entities in the atopic triad cluster together in families.
AD is a complex genetic disease, and both gene– gene and gene–environment interactions have pathogenic roles.
Existence of genes specific to ADermtitis
Genes encoding proteins with immunologic functions
Genes encoding epidermal proteins
Atopic Dermatitis

8. Filaggrin
Mutations in the filaggrin gene (FLG), which encodes a protein that aggregates keratin filaments during terminal differentiation of the epidermis.
The presence of the filaggrin variants is correlated with early-onset, relatively severe, “extrinsic” (specific IgE-associated) AD that tends to persist into adulthood.
Affected individuals have an increased risk of eczema herpeticum and peanut allergies as well as a propensity to later develop asthma
Atopic Dermatitis

9. Epidermal Barrier Dysfunction
The consequence of epidermal barrier dysfunction and an altered stratum corneum leading to increased transepidermal water loss
Cork et al. Journal of Investigative Dermatology
(2009) 129:
1892–1908
Atopic Dermatitis

10. IMMUNOLOGIC MECHANISMS
Main component/player
Disturbed Item
Degradation of corneodesmosomes, deficiency of Filaggrin
Impairment Of The Epidermal Barrier
Increased epidermal protease activity, dyscohesion
Mechanisms Of Inflammation In The Absence Of IgE-mediated Sensitization
high levels of thymic stromal lymphopoietin (TSLP) by keratinocytes leads to Th2 polarization
Epicutaneous Sensitization
Langerhans cells (LCs) and inflammatory dendritic epidermal cells:
present allergens to Th1/Th2 cells
Role Of Dendritic Cells (Dcs)
TH 2 predoninates in acute,
Th1 in chronic
T-cell Responses, Cytokines And Chemokines
decreased levels of antimicrobial peptides, S. aureus adherence to skin
Role Of Microbial Colonization
circulating IgE antibodies
Role Of Autoimmunity
Atopic Dermatitis

11. PRURITUS & IL-31
Classic antihistamines are ineffective in AD
neuropeptides, proteases, kinins, and cytokines such as interleukin (IL)-31 are known to induce itch.
IL-31 is strongly pruritogenic and exerts its biologic activity through a heterodimeric receptor composed of the IL-31 receptor A and oncostatin M receptor β protein, both of which are overexpressed in lesional skin of AD.
Atopic Dermatitis

12. CLINICAL FEATURES
Disease Course
In childhood AD (age 2 to 12 years)
Adult/adolescent AD (age >12 years)
Infantile AD
(age <2 years)
Senile AD (age >60 years)
Atopic Dermatitis

13. Clinical diagnosis of AD
Atopic stigmata
1.Xerosis
2.Keratosis Pilaris
3.Ichthyosis Vulgaris
4.Dennie Morgan lines
5.Periorbital darkening
6.White dermoographism
Pruritus
eczematous skin lesions in typical age-specific distribution patterns,
a chronic or chronically relapsing course,
Early age at onset,
A personal and/or family history of atopy.
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14. Associated Features
Associated Complications
Pityriasis Alba
Pruritus
Atopic Stigmata
Infections, esp eczema herpeticum
Occular complications
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15. Diagnostic criteria of AD
Validated scores to assess the severity of AD
1.EASI (Eczema Area Scoring Index)
2.SCORAD (SCORing Atopic Dermatitis)
3.POEM (Patient- Oriented Eczema Measure
Differential Diagnosis
Seborrheic dermatitis in infants.
Allergic Contact Dermatitis
Mycosis Fungoides
Pathology: mainly to exclude other mimics (as MF).
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16. MANAGEMENT CONCEPTS
Avoidance of trigger factors, including irritants, relevant allergens and microbial agents.
 Skin care that aims to compensate for the genetically determined impaired epidermal barrier function.
 Anti-inflammatory therapy to control subclinical inflammation as well as overt flares.
 In selected cases, adjunctive or complementary modalities.
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17. Avoidance of Trigger Factors
Intermittent use of intranasal mupirocin ointment over a 1- to 3-month
S. aureus strains that colonize and superinfect patients with AD are more likely to be susceptible to first-generation cephalosporins (e.g.cephalexin)
Cleansers and emollients containing antiseptics???
use mild, non-alkaline cleansers
Atopic Dermatitis

18. Avoidance of Trigger Factors
According to Patch test/RAST IgE test
Avoid House mites
Avoid Food Allergens
A continuous basic therapy with emollients, even in periods and sites in which the AD is not active.
Atopic Dermatitis

19. Topical Anti-inflammatory Therapy
The corticosteroid with appropriate potency to quickly gain control of the flare, continuation of daily therapy until active dermatitis minimized.
In moderate to severe AD, risk of relapse can be significantly reduced by proactive maintenance with twice-weekly application of a mid-potency topical corticosteroid.
Topical calcineurin inhibitors (TCIs)
Atopic Dermatitis

20. Phototherapy: UVA1, UVA combined with UVB, and narrowband UVB
Narrowband UVB and high-dose UVA1 can both be helpful for chronic AD, and UVA1 may also be useful in the treatment of acute flares.
T cell apoptosis, reduction of dendritic cells, and modified cytokine expression, (e.g. decreased IL-5, IL-13 and IL-31 with UVA1).
UVB reduces S. aureus colonization of the skin in AD patients.
Atopic Dermatitis

21. Systemic Anti-inflammatory Therapy
Systemic corticosteroids should be avoided
Mycophenolate mofetil (1–2.5 g/day); 25–50 mg/kg/day in children
Azathioprine 2–3.5 mg/kg/day, watch for TPMT deficiency
Oral cyclosporine typically leads to rapid improvement of skin disease and associated pruritus (5 mg/kg/day, reduced to 2mg /kg/day)
Atopic Dermatitis

22. Adjunctive Pharmacologic Therapy
Alternative/Complementary Therapy
Sedating antihistamines (e.g. hydroxyzine)
Non-Sedating antihistamines in very high doses.
Leukotriene inhibitors
Antimicrobial agents
Dietary lipid supplements (e.g. evening primrose and borage oils)
Chinese herbal therapy
Hypnotherapy
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23. Targeted Molecular Therapy (“Biologics”)
Emerging Therapies
Anti-IgE monoclonal antibody omalizumab, which inhibits the binding of IgE to its high-affinity receptor (FcεRI), is FDA-approved for the treatment of asthma in patients ≥12 years.
The anti-CD20 monoclonal antibody rituximab (administered via 2 IV infusions separated by 2 weeks), which inhibits mature B cells
mepolizumab inhibits IL-5, a crucial factor for growth and differentiation of eosinophils. Although mepolizumab can decrease the eosinophil count in patients with AD, it failed to lead to a significant clinical improvement
Goals of blocking factors such as cytokines involved in the regulation of IgE synthesis (e.g. IL-4) or chemoattractant receptor- homologous molecule expressed
on Th2 cells (CRTH2).
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24. Primary Prevention
Educational Programs
For infants with a family history of atopy, exclusive breastfeeding during the first 4-6 months.
Administration of probiotics (e.g. lactobacilli) or prebiotics (nondigestible oligosaccharides that promote the growth of desirable bacteria) to pregnant mothers and infants led to decreased frequencies of AD at 1 to 4 years of age.
Accepting “control” rather than a “cure”
Parents are anxious about corticosteroid use, which often leads to delayed, inadequate treatment
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25. Resumé: The APPROACH TO AD
Management should not be concentrated solely on the treatment of acute flares, but also be directed towards improving the underlying genetically determined epidermal barrier dysfunction and preventing active dermatitis (e.g. via maintenance therapy).
Such an approach could potentially block the sensitizations and ongoing inflammation that drive the atopic march forward
Atopic Dermatitis