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Tens ppt


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Tens ppt

  1. 1. Toxic Epidermal Necrolysis (TEN) <ul><ul><li> is a rare, potentially fatal, adverse drug reaction characterized by tenderness and erythema of the skin and mucosa, and extensive mucocutaneous exfoliation. </li></ul></ul><ul><ul><ul><ul><li>This exfoliation is due to extensive death of keratinocytes via apoptosis. </li></ul></ul></ul></ul><ul><ul><li>Incidence: 0.4 to 1.2 cases per million per year. </li></ul></ul>
  2. 2. Spectrum of Drug Reactions: SJS to TEN <ul><ul><ul><li>Spectrum of adverse cutaneous drug reactions with increasing severity and extent of epidermal detachment associated with increased mortality. </li></ul></ul></ul><ul><ul><ul><ul><li>SJS : < 10% BSA; 1-5% mortality </li></ul></ul></ul></ul><ul><ul><ul><ul><li>SJS-TEN overlap : 10-30% BSA </li></ul></ul></ul></ul><ul><ul><ul><ul><li>TEN : > 30% skin detachment; 25-35% mortality . </li></ul></ul></ul></ul>
  3. 3. Causative Agents <ul><ul><ul><li>More than 100 different drugs have been associated with TEN. </li></ul></ul></ul><ul><ul><ul><li>Most frequently incriminated drugs: </li></ul></ul></ul><ul><ul><ul><ul><li>Antibiotics (quinolones, aminopenicillins, tetracyclines, cephalosporins, imidazole antifungal agents) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>NSAIDS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Anticonvulsants </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Allopurinol </li></ul></ul></ul></ul>
  4. 4. Clinical Features Figure 22.4 Cutaneous features of toxic epidermal necrolysis (TEN). A Characteristic dusky-red color of the early macular eruption in TEN. Lesions with this color often progress to full-blown necrolytic lesions with dermo-epidermal detachment. B Positive Nikolsky sign: epidermal detachment reproduced by mechanical pressure on an area of erythematous skin.
  5. 5. Clinical Features Figure 22.5 Clinical features of toxic epidermal necrolysis (TEN). A Detachment of large sheets of necrolytic epidermis (&gt;30% body surface area), leading to extensive areas of denuded skin. B Hemorrhagic crusts with mucosal involvement. C Epidermal detachment of palmar skin.
  6. 6. Treatment <ul><ul><ul><li>Optimal medical management requires early diagnosis, immediate discontinuation of the causative drug(s), and supportive care. </li></ul></ul></ul><ul><ul><ul><li>Careful daily wound care, hydration, and nutritional support are essential, and preferably, done in an ICU. </li></ul></ul></ul><ul><ul><ul><li>No specific treatments for TEN have met evidence-based medicine standards of acceptance. </li></ul></ul></ul><ul><ul><ul><li>The use of corticosteroids is controversial and they may even increase mortality. </li></ul></ul></ul>
  7. 7. Pathophysiology <ul><ul><ul><li>Exfoliation in TEN is due to extensive keratinocyte cell death via apotosis. </li></ul></ul></ul><ul><ul><ul><li>Apotosis is mediated by interaction of the death receptor Fas and its ligand, FasL (CD95L). </li></ul></ul></ul><ul><ul><ul><ul><li>Increased FasL expression in TEN. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>The molecular mechanism by which culprit drugs up-regulate keratinocyte FasL expression in TEN is currently unknown. </li></ul></ul></ul></ul><ul><ul><ul><li>FasL activity can be blocked with monoclonal Abs that interfere with the interaction of Fas and FasL  rationale for molecular strategies to treat TEN. </li></ul></ul></ul>
  8. 9. Fas-mediated Keratinocyte Apoptosis in TEN and Potential Mechanism of Inhibition by IVIG <ul><li>In 1998, it was reported that IVIG contains Abs that are able to block the binding of FasL to Fas, thus inhibiting Fas-mediated keratinocyte apoptosis in vitro. </li></ul>(French et al., 2006)
  9. 10. Histology Figure 22.1 Histology of toxic epidermal necrolysis (TEN). A Histology of an early-stage lesion of TEN. Arrows: apoptotic keratinocytes. B Histology of a late-stage lesion of TEN featuring separation of the epidermis from the dermis, and full-thickness necrosis of the epidermis.