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Atopic dermatitis 2018 - Dr. Ortega Martell

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Atopic dermatitis 2018

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Atopic dermatitis 2018 - Dr. Ortega Martell

  1. 1. Atopic Dermatitis 2018 José Antonio Ortega Martell, M.D. Hidalgo State University, México World Allergy Organization drortegamartell@prodigy.net.mx
  2. 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. 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. 4. Patophysiology Therapeutic options Atopic Dermatitis Advances 2018
  5. 5. Patophysiology Atopic Dermatitis Advances 2018
  6. 6. Ann Allergy Asthma Immunol 120 (2018) 34-41. AD: Pathophysiology Skin Barrier Immune System Systemic involvement
  7. 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. 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. 9. IL-31 • Receptors in: • Keratinocytes (ii Barrier) • Nerve endings (hh Pruritus) J Allergy Clin Immunol 2017;140:633-43
  10. 10. Therapeutic options Atopic Dermatitis Advances 2018
  11. 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. 12. * Crisaborole * Dupilumab 12 more Biologic agents 6 small molecule inhibitors 2019 * Nemolizumab
  13. 13. Crisaborole: PDE4 inhibitor • PDE4: (Phosphodiesterase 4) •  AMPc g AMP g h inflammatory cytokines J Drugs Dermatol. 2016;15(4):390-396.
  14. 14. Front. Pharmacol. 2018 (Oct) 9:1048
  15. 15. Crisaborole: i pruritus Acta Derm Venereol 2018; 98: 484–489
  16. 16. Biotherapeutical Agents
  17. 17. Curr Allergy Asthma Rep (2016) 16:70
  18. 18. Ann Allergy Asthma Immunol 120 (2018) 34-41. AD: Biological Agents
  19. 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. 20. J Allergy Clin Immunol 2018; In Press §  Dupilumab: §  i dysregulated genes, i cellular and molecular cutaneous markers of inflammation
  21. 21. J Allergy Clin Immunol 2018; In Press Dupilumab: i Proinflammatory cytokines
  22. 22. J Allergy Clin Immunol 2018; In Press Dupilumab: i Epidermal Thickness
  23. 23. § Dupilumab: §  i Gene expression of: Th2 Th1 Th17 J Allergy Clin Immunol 2018; In Press
  24. 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. 25. J Allergy Clin Immunol 2018;142:1121-30
  26. 26. Biotherapeutic Agents Requirements for its use: •  Know the endotype •  Know the biomarker •  Personalized Medicine
  27. 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. 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. 29. • Exciting times in atopic dermatitis • Increased disease understanding • Improving patient’s Tx & quality of life
  30. 30. drortegamartell@prodigy.net.mx Thank you for your attention / Grazie per la tua attenzione

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