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. Clinical Features Figure 22.5 Clinical features of toxic epidermal necrolysis (TEN). A Detachment of large sheets of necrolytic epidermis (>30% body surface area), leading to extensive areas of denuded skin. B Hemorrhagic crusts with mucosal involvement. C Epidermal detachment of palmar skin.
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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.
Hinweis der Redaktion
This exfoliation is due to extensive death of keratinocytes ( the main cell type of the epidermis ) via apoptosis. [TEN has a low incidence of 0.4 to 1.2 cases per million per year.]
Stevens-Johnson syndrome and TEN are considered to be part of a spectrum of adverse cutaneous drug reactions with increasing severity and extent of skin detachment. [STOP] The continuum ranges from Stevens-Johnsons with less than 10% of body surface area affected to Stevens-Johnsons-TEN overlap with 10-30% of body surface area affected to TEN with greater than 30% skin detachment. The severity of epidermal detachment is tightly correlated with the observed rate of mortality: 1-5% in SJS versus 25-35% in TEN.
What causes TEN? The medications most frequently incriminated as causes of TEN are antibiotics, NSAIDs, antiepileptics, and allopurinol.
On the left, you can see the characteristic dusky-red color of the early macular lesions in TEN. The image on the right demonstrates a positive Nikolsky sign: epidermal detachment reproduced by mechanical pressure on an area of intact skin.
Here you can see detachment of large sheets of necrolytic epidermis, leading to extensive areas of denuded skin. You can also appreciate hemorrhagic crusts with mucosal involvement. Epidermal detachment of palmar skin.
Supportive care is similar to that performed for severe burns and is aimed at limiting hypovolemia, electrolyte imbalance, renal insufficiency, and sepsis . No specific treatments for TEN have met evidence-based medicine standards of acceptance BECAUSE OF THE LOW PREVALENCE OF TEN. A few cases have been treated with cyclosporine, cyclophosphamide, plasmapheresis, and N-acetylcysteine and have shown promising results. The use of steroids is controversial and SOME REPORTS SUGGEST THAT THEY MAY EVEN increase mortality (secondary to increased risk of septicemia).
On to pathophysiology… THIS apotosis is mediated by interaction of the death receptor Fas and its ligand, FasLigand (FasL or CD95L). IT HAS BEEN SHOWN that there is increased FasLigand expression in TEN. IT HAS BEEN SHOWN that FasLigand activity…
The bottom figure represents the epidermis during TEN. It shows the anti-Fas antibodies in IVIG (represented by red circles) inhibiting apoptosis by blocking the Fas Receptor. Fas-mediated keratinocyte apoptosis in TEN and the potential mechanism of inhibition by IVIG: (A) shows normal epidermis. (B) shows TEN with induction of keratinocyte FasLigand expression and interaction with the Fas Receptor at the cell surface, leading to keratinocyte apoptosis. (C) shows the epidermis during TEN treated by IVIG and predicted inhibition of apoptosis by blockade of the Fas Receptor by anti-Fas Ab in IVIG.
Key histologic features include necrotic keratinocytes, separation of the epidermis from the dermis, and full-thickness epidermal necrosis shows histology of an early-stage lesion of TEN. The arrows point towards apoptotic keratinocytes (in the basal and immediate suprabasal layers of the epidermis – the histologic correlate of the dusky-gray color that is a warning sign of pending full-blown epidermal necrolysis and detachment). (B) shows histology of a late-stage lesion of TEN featuring separation of the epidermis from the dermis, and full-thickness necrosis of the epidermis. There is a sparse perivascular infilitrate composed primarily of lymphocytes. Histology is useful in distinguishing TEN from Staph Scalded Skin Syndrome (SSSS). TEN results in full-thickness epidermal necrolysis, whereas Staph Scalded Skin Syndrome shows a subcorneal split with a normal underlying epidermis; subcorneal blister with cleavage located in the granular layer of the epidermis. Bachot N, Revuz J, Roujeau JC. Intraveous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol . 2003;139:33-6. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz P, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol . 2000;115:149-53. Brown KM, Silver GM, Halerz M, Walaszek P, Sandroni A, Gamelli RL. Toxic epidermal necrolysis: does immunoglobulin make a difference? J Burn Care Rehabil. 2004;25:81-8. French LE, Trent JT, Kerdel FA. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome: our current understanding. International Immunopharmacology . 2006;6:543-549. Herbert AA, Bogle MA. Intravenous immunoglobulin prophylaxis for recurrent Stevens-Johnson syndrome. J Am Acad Dermatol . 2004;50:286-8. Metry DW, Jung P, Levy ML. Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature. Pediatrics . 2003;112:1430-1436. Prins C, Kerdel FA, Padilla S, et al. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Arch Dermatol . 2003;139:26-32. Prins C, Vittorio C, Padilla S, et al. Effect of high-dose intravenous immunoglobulin therapy in Stevens-Johnson syndrome: a retrospective, multicenter study. Dermatology . 2003;207:96-99. Shortt R, Gomez M, Mittman N, Cartotto R. Intraveous immunoglobulin does not improve outcome in toxic epidermal necrolysis. J Burn Care Rehabil . 2004;25:246-55. Trent JT, Kirsner RS, Romanelli P, Kerdel FA. Analysis of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis using SCORTEN: The University of Miami experience. Arch Dermatol . 2003;139:39-43. Trent JT, Kirsner RS, Romanelli P, Kerdel FA. Use of SCORTEN to accurately predict mortality in patients with toxic epidermal necrolysis in the United States. Arch Dermatol . Jul 2004;140(7):890-2. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998;282:490-3. Yeung CK, Lam LK, Chan HH. The timing of intravenous immunoglobulin therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis. Clinical Experimental Dermatology . 2005;30:578-602.