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Updated treatment of atopic dermatitis Prof. Ortega Martell

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Updated treatment of atopic dermatitis

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Updated treatment of atopic dermatitis Prof. Ortega Martell

  1. 1. Updated Treatment of Atopic Dermatitis 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. Breakfast Seminar: Objectives • To review some of the main pathophysiologic mechanisms involved in AD including skin barrier defect and immune dysregulation • To review the role of emollients, anti-inflammatory agents, wet wrap therapy and immune-directed targets for biologic therapy
  5. 5. AD: Pathophysiology
  6. 6. Ann Allergy Asthma Immunol 120 (2018) 34-41. Skin Barrier Immune System Systemic involvement
  7. 7. Dual theory: outsiden inside https://www.atopicdermatitisexposed.com/ Skin barrier Failure Immune system Failure
  8. 8. • Hypothesis: “outside g inside” 1.  Skin barrier defect 2.  Allergen sensitization / microbe invasion 3.  Immune system activation g inflammation • Supporting evidence: • Genetic factors in severe AD • Example: Filaggrin gene mutations Allergy Asthma Immunol Res. 2018 May; 10(3): 207–215.
  9. 9. • Hypothesis: “inside g outside” 1.  Immune system control failure (iTreg) 2.  Response: hTh2 g hTh1, hTh17, hTh22 3.  Pro-Inflammatory cytokines g skin damage • Supporting evidence: • Genetic factors in severe AD (gen FOXP3) • T lymphocytes: h even in non-lesional skin Allergy Asthma Immunol Res. 2018 May; 10(3): 207–215.
  10. 10. Skin Barrier Defect Unbalanced Immune System
  11. 11. 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
  12. 12. Th2 Lymphocyte pattern ü  IL-4 u  STAT6 / GATA3 v  IL-4 v  IL-13 v  IL-5 v  IL-9
  13. 13. 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
  14. 14. J Allergy Clin Immunol 2007;120:150-5. Th2 cytokines g i Filaggrin production
  15. 15. J Allergy Clin Immunol 2016;138:336-49
  16. 16. IL-31 • Receptors in: • Keratinocytes (ii Barrier) • Nerve endings (hh Pruritus) J Allergy Clin Immunol 2017;140:633-43
  17. 17. AD and allergic diseases • Asthma, Allergic Rhinitis, Food Allergy
  18. 18. J Allergy Clin Immunol 2016;137:998-1010
  19. 19. J Allergy Clin Immunol 2017;139:1723-34 •  Eczema •  Food allergy •  Asthma •  Rhinitis ISSN 0091-6749 V O L U M E 1 3 9 N O . 6 J U N E 2 0 1 7 www.jacionline.org THE JOURNAL OF AllergyAND Clinical Immunology CURRENT PERSPECTIVES Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases Calpain-14 and its association with eosinophilic esophagitis Autoimmune chronic spontaneous urticaria: What we know and what we do not know PARADIGMS AND PERSPECTIVES Thunderstorm-related asthma attacks CLINICAL REVIEWS Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march MECHANISMS OF ALLERGIC DISEASES Phenotypic and genetic aspects of epithelial barrier function in asthmatic patients AN OFFICIAL JOURNAL OF
  20. 20. AD: Treatment options
  21. 21. AD: clinical diagnosis ü  Pruritus ü  Eczema •  Xerosis •  Atopy •  IgE hhh Essential for Diagnosis Very common
  22. 22. Differential Diagnosis •  Contact Dermatitis •  Seborrhoeic Dermatitis •  Scabies •  Psoriasis •  Ichthyosis •  Photosensibility •  Skin Lymphoma •  Primary I.D. •  More causes of erythrodermia …
  23. 23. Ann Allergy Asthma Immunol 120 (2018) 23-33. •  9m old boy, Eczema since 2m •  Staph aureus Cellulitis, Tx with i.v. clindamycin, Met PDN •  IgE (+) egg, milk, peanut, soy, elimination: no improvement •  SCORAD = 57 •  Wet wraps, emolient, cephalexin, topical steroids, TCI •  IgG = < 75 mg/dL, IgE = 593 IU/ml CD19 = 49%, IgD+CD27+B = 3.7%
  24. 24. Ann Allergy Asthma Immunol 120 (2018) 23-33. • Transient hypogammaglobulinemia of infancy
  25. 25. 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
  26. 26. Evaluate g better Treatment •  Find myths and barriers •  Find common triggers •  Investigate sleep disturbance •  Psychological affectation Success in Tx Quality of life Br J Dermatol 2017, 177 (5): 1316 – 1321.
  27. 27. AD: Main Treatment Goals •  Prevent exacerbations 1 •  Tx to comorbidities 2 •  Tx to complications 3 •  Minimal adverse effects 4 •  Improve quality of life 5 J Am Acad Dermatol 2016, 74 (3): 491-8.
  28. 28. Treatment options • Non pharmacological: • Emolients • Skin care • Baths, Wet wraps • Topical agents: • Steroids, calcineurin inhibitors • Antimicrobial agents, Crisaborole J Am Acad Dermatol 2014, 70(2): 338 – 351.
  29. 29. Recommendations for patients with AD
  30. 30. AD: Bleach baths and Wet wraps i Staphylococcus aureus, Malassezia … Variable results
  31. 31. Before After Infection with meticilin resistant Staphylococcus aureus (MRSA) Ann Allergy Asthma Immunol 120 (2018) 23-33.
  32. 32. Wet wrap therapy Before After Ann Allergy Asthma Immunol 120 (2018) 23-33.
  33. 33. Ann Allergy Asthma Immunol 120 (2018) 23-33. Wet Wrap Therapy: g H2O g emolient g TCS g wet g dry
  34. 34. Topical calcineurin inhibitors (Tacrolimus, Pimecrolimus) Indirect calcineurin inhibitors (Cyclosporin) Topical steroids (multilevel-effect) PDE4 Inhibitors (h AMPc) (i NFAT, NFκB) (Crisaborole)
  35. 35. Crisaborole: PDE4 inhibitor • PDE4: (Phosphodiesterase 4) •  AMPc g AMP g h inflammatory cytokines J Drugs Dermatol. 2016;15(4):390-396.
  36. 36. Front. Pharmacol. 2018 (Oct) 9:1048
  37. 37. Crisaborole: mild – moderate AD • Significant improvement in Tx group
  38. 38. Ann Allergy Asthma Immunol 120 (2018) 10-22. Therapeutic options in Atopic Dermatitis
  39. 39. • Non lesional: • Skin care • Trigger avoidance • Mild AD: • Skin care • Antiseptic • Trigger avoidance • Rescue: • TCS (TCI, CSB) Ann Allergy Asthma Immunol 120 (2018) 10-22.
  40. 40. • Moderate AD: • TCS, TCI, CSB • Severe AD: ü  Refer to specialist • Phototherapy • Dupilumab • Immunosuppressant • Wet wrap therapy • Rescue: • TCS, TCI, CSB … Ann Allergy Asthma Immunol 120 (2018) 10-22.
  41. 41. AD: mild g moderate Ann Allergy Asthma Immunol 120 (2018) 10-22.
  42. 42. AD: moderate g severe Ann Allergy Asthma Immunol 120 (2018) 10-22.
  43. 43. Immunotherapy: Ag – specific J Allergy Clin Immunol 2016;138:1541-7
  44. 44. Immunotherapy: Ag – specific J Allergy Clin Immunol 2016;138:1541-7
  45. 45. J Allergy Clin Immunol 2013;132:110-7
  46. 46. J Allergy Clin Immunol 2013;132:110-7
  47. 47. Biotherapeutical Agents
  48. 48. J Allergy Clin Immunol 2017;139:S65-76
  49. 49. J Allergy Clin Immunol 2017;139:S65-76
  50. 50. Ann Allergy Asthma Immunol 120 (2018) 34-41. AD: Biological Agents
  51. 51. 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.
  52. 52. J Allergy Clin Immunol 2017;139:S65-76 Blocking IL-4 / IL-13 •  h Filaggrin expression •  h Defensin production •  i CC-Chemokine synthesis •  i IgE production •  i Type 2 response (Th2, ILC2)
  53. 53. J Allergy Clin Immunol 2017;139:S65-76 Therapy with Dupilumab
  54. 54. Dupilumab 16 weeks: moderate – severe AD • Clinical improvement in Dupilumab group N Engl J Med 2016; 375 (24): 2335 – 48.
  55. 55. Dupilumab 52 weeks: moderate – severe AD • Clinical improvement in Dupilumab group N Engl J Med 2016; 375 (24): 2335 – 48.
  56. 56. New Agents in the pipeline •  Anti IL-31 •  Anti IL-13 •  Anti IL-13 Clinical Issues in Atopic Dermatitis. Lisa A. Beck. AAAAI-WAO Meeting. Orlando, Fl. 2018
  57. 57. Biotherapeutic Agents Requirements for its use: •  Know the endotype •  Know the biomarker •  Personalized Medicine
  58. 58. • Exciting times in atopic dermatitis • Increased disease understanding • Improving patient’s Tx & quality of life
  59. 59. drortegamartell@prodigy.net.mx Thank you for your attention / Grazie per la tua attenzione

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