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Stevens johnson syndrome & toxic epidermal necrolysis

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Stevens johnson syndrome & toxic epidermal necrolysis
Presented by Jintana Chataroopwijit, MD.
September23, 2016

Published in: Health & Medicine
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Stevens johnson syndrome & toxic epidermal necrolysis

  1. 1. STEVENS-JOHNSON SYNDROME TOXIC EPIDERMAL NECROLYSIS Jintana Chataroopwijit 23 September 2016
  2. 2. INTRODUCTION ➤ Severe cutaneous adverse reaction (SCAR) ➤ Immune-complex-mediated hypersensitivity complex
  3. 3. CLASSIFICATION Body surface area detachment 1. Steven-Johnson syndrome : less than 10% 2. Overlapping Steven-Johnson syndrome/toxic epidermal necrolysis 3. Toxic epidermal necrolysis : more than 30%
  4. 4. EPIDERMIOLGY ➤ Steven-Johnson syndrome : 1-6 cases per million per year ➤ Toxic epidermal necrolysis : 1-2 cases per million per year ➤ Primarily male, AIDS patients Autoimmunity Review 7 (2008) 598-608
  5. 5. INCIDENCE
  6. 6. ETIOLOGY ➤ Drug-induced ➤ Infectious ➤ Malignancy related ➤ Idiopathic International Journal of Pharmacology Reasearch volume4 Issue4 (2014
  7. 7. ETIOLOGY : DRUG-INDUCED Autoimmunity Review 7 (2008) 598-608
  8. 8. Alden score
  9. 9. ETIOLOGY : INFECTIOUS International Journal of Pharmacology Reasearch volume4 Issue4 (2014) ➤ Herpes simplex virus ➤ AIDS ➤ Coxsackie viral infection ➤ Influenza ➤ Hepatitis ➤ Mumps ➤ Epstein-Barr virus ➤ Enteroviruses ➤ Group A beta-hemolytic streptococci ➤ Diphteria ➤ Brucellosis ➤ Lymphogranuloma venereum ➤ Mycobacteria ➤ Mycoplasma pneumoniae ➤ Rickettsial infections ➤ Tularemia ➤ Typhoid
  10. 10. GENETIC SUSCEPTIBILITY J Allergy Clin Immonol (2012) vol.136 no.2
  11. 11. GENETIC SUSCEPTIBILITY J Allergy Clin Immonol (2012) vol.136 no.2
  12. 12. ETIOLOGY ➤ Malignancy related ➤ Photo-induced ➤ Post vaccination ➤ Idiopathic Autoimmunity Review 7 (2008) 598-608
  13. 13. PATHOGENESIS ➤ Not fully understood ➤ Immune-mediated Autoimmunity Review 7 (2008) 598-608
  14. 14. IMMUNOHISTOCHEMICAL CHARACTERISTICS ➤ Detection of activated T cell in lesion skin ➤ Predominance of CD4+ T cell in dermis and CD8+ in epidermis Autoimmunity Review 7 (2008) 598-608
  15. 15. HISTOLOGY OF DISEASE
  16. 16. PATHOGENESIS
  17. 17. J Allergy Clin Immonol (2012) vol.136 no.2
  18. 18. IMMUNOPATHOLOGY ➤ Two pathways leading to apoptosis cell death ➤ Ligation of Fas and FasL ➤ Release of Perforin and GranzymeB Autoimmunity Review 7 (2008) 598-608
  19. 19. FAS/FAS LIGAND ➤ Fas ➤ Skin homeostasis ➤ Expression in normal keratinocyte at basal membrane and first suprabasal cell layer ➤ In TEN : stain positive for FasL in perivascular and junctional dermis in skin-infiltrating lymphocyte ➤ Ligation of Fas on keratinocyte by FasL on T cell --> keratinocyte apoptosis Autoimmunity Review 7 (2008) 598-608
  20. 20. FAS/FAS LIGAND ➤ Jurket cell ➤ Express high level of Fas ➤ Highly sensitive to Fas-induced apoptosis Autoimmunity Review 7 (2008) 598-608
  21. 21. FAS/FAS LIGAND ➤ Soluble FasL (sFasL) ➤ Proteolytic processing membrane-bound form of FasL ➤ Level increasing in early but return to baseline levels after progression creases ➤ Not specific for SJS/TEN but also in other drug-induced cutaneous eruption, some inflammatory skin disease and several autoimmune disease ➤ Unclear role Autoimmunity Review 7 (2008) 598-608
  22. 22. FAS/FAS LIGAND ➤ Sera from TEN patients can induce apoptosis in normal human keratinocytes and could be almost completely inhibited by antiFasL mAb ➤ IVIG : blocking Fas activity Autoimmunity Review 7 (2008) 598-608
  23. 23. PERFORIN/GRANZYME B ➤ Blister fluid in TEN ➤ CD8+ lymphocyte ➤ Markers of NK cells or cytotoxic T ➤ Able to lyse autologous keratinocyte in the presence of causative drug Autoimmunity Review 7 (2008) 598-608
  24. 24. PERFORIN/GRANZYME B ➤ Upregulation of MHC class I and induced MHC class II expression ➤ Elevation CD8+ lymphocyte in PBMC and declined to below control levels after systemic high dose conventional treatment ➤ Elevation of mRNA expression of perforin and granzyme B in PBMC : severity of disease Autoimmunity Review 7 (2008) 598-608
  25. 25. PERFORIN/GRANZYME B ➤ Drug-specific CTL ➤ Incresed expression of Perforin and Granzyme B on epidermal CD8 T cell ➤ Induced an influx of CD4+ T cell into epidermis ➤ Keratinocyte apoptosis Autoimmunity Review 7 (2008) 598-608
  26. 26. CYTOKINE DYSREGULATION ➤ Specimen from biopsy : express elevated levels of IFN- gamma, TNF-alpha, IL-5, IL-6, IL-10 and IL-13 ➤ Blister fluid : high concentration of IFN-gamma, TNF-alpha, IL-6, IL-13 and IL-18(induce IFN-gamma) Autoimmunity Review 7 (2008) 598-608
  27. 27. CYTOKINE DYSREGULATION ➤ IFN-gamma, TNF-alpha and IL-1beta along with IL-15 can enhance surface expression of FasL on human keratinocyte ➤ Upregulation adhesion molecules --> recruitment of lymphocyte to the skin ➤ Elabolation of type I cytokine profile ( IFN-gamma and TNF- alpha --> major trigger keratinocyte apoptosis Autoimmunity Review 7 (2008) 598-608
  28. 28. CLINICAL CHARACTERISTICS ➤ Influenza-like symptoms : 1-14 days ➤ Fever ➤ Cough ➤ Myalgias ➤ Arthralgias ➤ Malaise Autoimmunity Review 7 (2008) 598-608
  29. 29. CLINICAL CHARACTERISTICS : SKIN LESION ➤ Flat, irregular, atypical target lesions or diffuse purpuric macules with frequently necrotic center ➤ Mostly trunk and face, also neck and proximal extremities ➤ Positive Nickolsky sign ➤ Reepithelialization usually begins after a few days and complete within 2-3 weeks Autoimmunity Review 7 (2008) 598-608
  30. 30. CLINICAL MANIFESTRATION
  31. 31. SIMILARITIES IN CLINICAL PRESENTATION Journal of Rare Disease 2010 , 5:39 International Journal of Pharmacology Reasearch volume4 Issue4 (2014)
  32. 32. CLINICAL CHARACTERISTICS ➤ Erythematous, painful erosion : Buccal mucosa, ocular and genital mucosa ➤ Ocular involvement ➤ Acute conjunctivitis ➤ Eyelid edema and crusting to conjunctival memebrane or pseudomembrane ➤ Cornea erosions ➤ Cicratizing symblepharon ➤ Conjunctival fornix foreshortening ➤ Corneal ulcer Autoimmunity Review 7 (2008) 598-608
  33. 33. TREATMENT
  34. 34. FOUNDAMENTAL INTERDISCIPLINARY TREATMENT Autoimmunity Review 7 (2008) 598-608
  35. 35. DRUG THERAPY ➤ Intravenous immunoglobulin ➤ Anti-Fas potential of pooled human intravenous immunoglobulin ➤ Suggested dose : more than 2 g/kg ➤ One study showed that each 1 g/kg increase in IVIG = 4.2 fold in TEN patient survival Harr and French Ophanet Journal of Rare Diseases 2010, 5:39
  36. 36. Harr and French Ophanet Journal of Rare Diseases 2010, 5:39
  37. 37. Harr and French Ophanet Journal of Rare Diseases 2010, 5:39
  38. 38. Harr and French Ophanet Journal of Rare Diseases 2010, 5:39
  39. 39. DRUG THERAPY ➤ Systemic steriod : controversy ➤ Thalidomide (anti TNF alpha) : higher mortality ➤ TNF antagonist : infliximab, etanercept ➤ Ciclosporin (CsA) : may be useful ➤ Cyclophosphamide (CPP) ➤ Plasmapheresis/plasma exchange Harr and French Ophanet Journal of Rare Diseases 2010, 5:39
  40. 40. ALLERGOLOGICAL TESTING ➤ Detailed drug history ➤ Patch testing : low sensitivity ➤ Lymphocyte transformation test (LTT) : very low sensitivity ➤ Up regulation of CD69 on T-lymphocytes two days after lymphocyte stimulation in vitro Autoimmunity Review 7 (2008) 598-608
  41. 41. MORTALITY
  42. 42. MORTALITY

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