This document summarizes information about atopic dermatitis presented by José Antonio Ortega Martell, M.D. at Atopic Dermatitis Advances 2018. It discusses the pathophysiology of atopic dermatitis involving skin barrier dysfunction and immune system dysregulation. It also summarizes new therapeutic options for atopic dermatitis including the PDE4 inhibitor crisaborole and the biological agent dupilumab, which is a monoclonal antibody that targets the IL-4Rα receptor. The document concludes by noting the promising future of personalized treatment for atopic dermatitis using biological agents and biomarkers to target specific disease endotypes.

1. Atopic Dermatitis 2018
José Antonio Ortega Martell, M.D.
Hidalgo State University, México
World Allergy Organization
drortegamartell@prodigy.net.mx

2. José Antonio Ortega Martell, M.D.
• La Salle University
• National Institute of Pediatrics
• Autonomous University of Hidalgo State, México
• National Board of Clinical Immunology and Allergy
• Mexican College of Pediatricians Specialized in Clinical
Immunology and Allergy (COMPEDIA)
• World Allergy Organization (WAO)
Medicine
Allergy Immunology
Pediatrics

3. José Antonio Ortega Martell, M.D.
• Participation as Speaker and Advisory Groups:
§ COMPEDIA
§ CMICA
§ CONICA
§ SLAAI
§ CONAPEME
§ WAO
§ Vifor Pharma
§ UCB Pharma
§ Sanofi Aventis
§ Astra Zeneca
§ Glaxo Smith Kline
§ Pierre Fabre Med
Medical Societies Pharmaceutical Industry

4. Patophysiology
Therapeutic options
Atopic Dermatitis Advances 2018

5. Patophysiology
Atopic Dermatitis Advances 2018

6. Ann Allergy Asthma Immunol 120 (2018) 34-41.
AD: Pathophysiology
Skin Barrier
Immune System
Systemic
involvement

7. Environment
Genetics / Epigenetics
Microbiome
Atopy
Autoallergic
Dermatitis
Non atopic
Dermatitis
Atopic
Dermatitis
Sensitization
Allergens
Sensitization
Auto Ag
Malassezia
Itch g scratch
Filaggrin
Skin Barrier
weather, toxins, pH
Irritants Allergens
Dust Mites, food
Permeability
dysfunction
Immune system
dysfunction
Staph aureus
Ceramide
DC
Th2
B
ILC2
IgE
IL-4
IL-5
IL-13
Eos
MC
IL-31
Th1
Th17
IL-22
Th22
Tissue damage

8. J Allergy Clin Immunol 2017;140:633-43
IL-4 & IL-13
• IL-4Rα: type I and II receptors
• Effects on:
• Keratinocytes, lymphocytes,
afferent nerve fibers

9. IL-31
• Receptors in:
• Keratinocytes
(ii Barrier)
• Nerve endings
(hh Pruritus)
J Allergy Clin Immunol 2017;140:633-43

10. Therapeutic options
Atopic Dermatitis Advances 2018

11. Eczema
Atopic
Dermatitis
Allergic
March
HIES AR
HIES AD WASP
Omenn
IPEX
Barrier defect
Dysregulation
FA g Asthma g
Rhinitis
IgE >1000, Virus,
Atopy
IgE >1000,
pneumatocele
Infections,
plaquetopenia
Erythroderma,
lymphopenia
Dm I, FA,
enteropathy

12. * Crisaborole * Dupilumab
12 more Biologic agents
6 small molecule inhibitors
2019
* Nemolizumab

13. Crisaborole: PDE4 inhibitor
• PDE4: (Phosphodiesterase 4)
• AMPc g AMP g h inflammatory cytokines
J Drugs Dermatol. 2016;15(4):390-396.

14. Front. Pharmacol. 2018 (Oct) 9:1048

15. Crisaborole: i pruritus
Acta Derm Venereol 2018; 98: 484–489

16. Biotherapeutical Agents

17. Curr Allergy Asthma Rep (2016) 16:70

18. Ann Allergy Asthma Immunol 120 (2018) 34-41.
AD: Biological Agents

19. AD: Biological Agents
• Dupilumab
• Human monoclonal antibody
• Anti IL-4Rα (IL-4 & IL-13 receptor )
• FDA: adults with moderate or severe AD
• Initial Dose = 600 mg SC
• Maintenance Dose = 300 mg SC every 2 weeks
N Engl J Med 2016; 375 (24): 2335 – 48.

20. J Allergy Clin Immunol 2018; In Press
§ Dupilumab:
§ i dysregulated genes,
i cellular and molecular
cutaneous markers of
inflammation

21. J Allergy Clin Immunol 2018; In Press
Dupilumab: i Proinflammatory cytokines

22. J Allergy Clin Immunol 2018; In Press
Dupilumab: i Epidermal Thickness

23. § Dupilumab:
§ i Gene expression of:
Th2 Th1 Th17
J Allergy Clin Immunol 2018; In Press

24. J Allergy Clin Immunol 2018;141:858-66
• IL-31:
• Expressed in many tissues and involved mainly in Th2-weighted
inflammation
• Strongly linked with chronic pruritic skin disorders
• Broad spectrum of action as a proinflammatory and
immunomodulatory cytokine
• Monoclonal antibodies anti IL-31RA:
• Nemolizumab (human) Lokivetmab (canine)

25. J Allergy Clin Immunol 2018;142:1121-30

26. Biotherapeutic Agents
Requirements for its use:
• Know the endotype
• Know the biomarker
• Personalized Medicine

27. Expert Rev Clin Immunol. 2018 Jan;14(1):61-68
§ Lack of double-blind controlled randomized studies including a
significant number of patients
§ At least 3 criteria should be fulfilled:
§ IgE sensitization to aeroallergens must be proven
§ Exposure to aeroallergens induces AD flare-ups
§ Physician must choose a standardized product for AIT

28. § Efficacy of AIT is under investigation in patients with allergic (extrinsic)
atopic dermatitis
§ Combination of biological therapeutics with allergen-specific
immunotherapy may enhance immunomodulation
Italian Journal of Pediatrics (2018) 44:80

29. • Exciting times in atopic dermatitis
• Increased disease understanding
• Improving patient’s Tx & quality of life

30. drortegamartell@prodigy.net.mx
Thank you for your attention / Grazie per la tua attenzione