Skip to main content

Advertisement

SpringerLink
Log in

Severe cutaneous adverse reactions: emergency approach to non-burn epidermolytic syndromes

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Introduction

Although severe cutaneous adverse reactions (SCARs), such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are rare, they are associated with considerable morbidity and mortality.

Methods

The current knowledge regarding background, differential diagnoses, critical care and implications for inter-hospital emergency medical service (EMS) transport of these patients is discussed.

Conclusion

SCAR patients will substantially benefit from early interdisciplinary care and thorough consideration of complications during EMS transport and intensive care treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Spies M, Vogt PM, Herndon DN (2003) Toxic epidermal necrolysis. A case for the burn intensive care unit. Chirurg 74:452–460

    Article  PubMed  CAS  Google Scholar 

  2. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC (1993) Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 129:92–96

    Article  PubMed  CAS  Google Scholar 

  3. Arndt KA (1970) The sign of Pyotr Vasilyewich Nikolsky. N Engl J Med 282:1154–1155

    PubMed  CAS  Google Scholar 

  4. Assier H, Bastuji-Garin S, Revuz J, Roujeau JC (1995) Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 131:539–543

    Article  PubMed  CAS  Google Scholar 

  5. Rzany B, Hering O, Mockenhaupt M, Schröder W, Goerttler E, Ring J, Schöpf E (1996) Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 135:6–11

    Article  PubMed  CAS  Google Scholar 

  6. Lyell A (1956) Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 68:355–361

    Article  PubMed  CAS  Google Scholar 

  7. Iwatsuki K, Yamasaki O, Morizane S, Oono T (2006) Staphylococcal cutaneous infections: invasion, evasion and aggression. J Dermatol Sci 42:203–214

    Article  PubMed  CAS  Google Scholar 

  8. Mutasim DF (2003) Autoimmune bullous dermatoses in the elderly: diagnosis and management. Drugs Aging 20:663–681

    Article  PubMed  Google Scholar 

  9. Mockenhaupt M, Norgauer J (2002) Cutaneous adverse drug reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis. Allergy Clin Immunol Int 14:143–150

    Article  Google Scholar 

  10. Rzany B, Mockenhaupt M, Baur S, Schröder W, Stocker U, Mueller J, Holländer N, Bruppacher R, Schöpf E (1996) Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson Syndrome, and toxic epidermal necrolysis in Germany (1990–1992): structure and results of a population-based registry. J Clin Epidemiol 49:769–777

    Article  PubMed  CAS  Google Scholar 

  11. Mockenhaupt M, Idzko M, Grosber M, Schöpf E, Norgauer J (2005) Epidemiology of staphylococcal scalded skin syndrome in Germany. J Invest Dermatol 125:700–703

    Article  Google Scholar 

  12. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P (2000) SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 115:149–153

    Article  PubMed  CAS  Google Scholar 

  13. Dorafshar AH, Dickie SR, Cohn AB, Aycock JK, O′Connor A, Tung A, Gottlieb LJ (2008) Antishear therapy for toxic epidermal necrolysis: an alternative treatment approach. Plast Reconstr Surg 122:154–160

    Article  PubMed  CAS  Google Scholar 

  14. Guegan S, Bastuji-Garin S, Pszepczynska-Guigne E, Roujeau JC, Revuz J (2006) Performance of the SCORTEN during the first 5 days of hospitalization to predict the prognosis of epidermal necrolyse. J Invest Dermatol 126:272–276

    Article  PubMed  CAS  Google Scholar 

  15. Vaishampayan SS, Das AL, Verma R (2008) SCORTEN: does it need modification? Indian J Dermatol Venereol Leprol 74:35–37

    Article  PubMed  CAS  Google Scholar 

  16. Hague JS, Goulding JM, Long TM, Gee BC (2007) Respiratory involvement in toxic epidermal necrolysis portends a poor prognosis that may not be reflected in SCORTEN. Br J Dermatol 157:1294–1296

    Article  PubMed  CAS  Google Scholar 

  17. Patel GK, Finlay AY (2003) Staphylococcal scalded skin syndrome: diagnosis and management. Am J Clin Dermatol 4:165–175

    Article  PubMed  Google Scholar 

  18. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128:35–44

    Article  PubMed  CAS  Google Scholar 

  19. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, Naldi L, Dunant A, Viboud C, Roujeau JC, EuroSCAR Study Group (2008) Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 58:25–32

    Article  PubMed  Google Scholar 

  20. Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP, Martin E, Kaufman DW, Maison P (2009) Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics 123:e297–e304

    Article  PubMed  Google Scholar 

  21. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, Chin SW, Chiou CC, Chu SC, Ho HC, Yang CH, Lu CF, Wu JY, Liao YD, Chen YT (2008) Granulysin is a key mediator for disseminated keratinocyte death in Stevens–Johnson syndrome and toxic epidermal necrolysis. Nat Med 14:1343–1350

    Google Scholar 

  22. Paquet P, Pierard GE (2007) Toxic epidermal necrolysis: revisiting the tentative link between early apoptosis and late necrosis (review). Int J Mol Med 19:3–10

    PubMed  CAS  Google Scholar 

  23. Khalili B, Bahna SL (2006) Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis. Ann Allergy Asthma Immunol 97:272–280

    Article  PubMed  CAS  Google Scholar 

  24. Abe R (2008) Toxic epidermal necrolysis and Stevens-Johnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. J Dermatol Sci 52:151–159

    Article  PubMed  CAS  Google Scholar 

  25. Chung WH, Hung SI, Chen YT (2007) Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 7:317–323

    Article  PubMed  CAS  Google Scholar 

  26. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, Naldi L, Bouwes Bavinck JN, Sidoroff A, de Toma C, Schumacher M, Roujeau JC, Hovnanian A, Mockenhaupt M, RegiSCAR study Group (2008) A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18:99–107

    Article  PubMed  CAS  Google Scholar 

  27. Goyal S, Gupta P, Ryanl CM, Kazlas M, Noviski N, Sheridan RL (2009) Toxic epidermal necrolysis in children: medical, surgical, and ophthalmologic considerations. J Burn Care Res 30:437–439

    Article  PubMed  Google Scholar 

  28. Hughey LC (2007) Fever and erythema in the emergency room. Semin Cutan Med Surg 26:133–138

    Article  PubMed  CAS  Google Scholar 

  29. McGee E, Munster A (1998) Toxic epidermal necrolysis syndrome: mortality rate reduced with early referral to regional burn center. Plast Reconstr Surg 102:118

    Google Scholar 

  30. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Study Group (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377

    Article  PubMed  CAS  Google Scholar 

  31. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60

    Article  PubMed  Google Scholar 

  32. Schummer W (2009) Central venous pressure validity, informative value and correct measurement. Anaesthesist 58:499–505

    Article  PubMed  CAS  Google Scholar 

  33. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, Doctor A, Davis A, Duff J, Dugas MA, Duncan A, Evans B, Feldman J, Felmet K, Fisher G, Frankel L, Jeffries H, Greenwald B, Gutierrez J, Hall M, Han YY, Hanson J, Hazelzet J, Hernan L, Kiff J, Kissoon N, Kon A, Irazuzta J, Lin J, Lorts A, Mariscalco M, Mehta R, Nadel S, Nguyen T, Nicholson C, Peters M, Okhuysen-Cawley R, Poulton T, Relves M, Rodriguez A, Rozenfeld R, Schnitzler E, Shanley T, Kache S, Skippen P, Torres A, von Dessauer B, Weingarten J, Yeh T, Zaritsky A, Stojadinovic B, Zimmerman J, Zuckerberg A (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688

    Article  PubMed  Google Scholar 

  34. Pruitt BN Jr (1987) Burn treatment for the unburned. JAMA 257:2207–2208

    Article  PubMed  Google Scholar 

  35. Oda J, Yamashita K, Inoue T, Harunari N, Ode Y, Mega K, Aoki Y, Noborio M, Ueyama M (2006) Resuscitation fluid volume and abdominal compartment syndrome in patients with major burns. Burns 32:151–154

    Article  PubMed  Google Scholar 

  36. Daugherty EL, Liang Hongyan, Taichman D, Hansen-Flaschen J, Fuchs BD (2007) Abdominal compartment syndrome is common in medical intensive care unit patients receiving large-volume resuscitation. J Intensive Care Med 22:294–299

    Article  PubMed  Google Scholar 

  37. Mullens W, Abrahams Z, Francis GS, Taylor DO, Starling RC, Tang WH (2008) Prompt reduction in intra-abdominal pressure following large-volume mechanical fluid removal improves renal insufficiency in refractory decompensated heart failure. J Card Fail 14:508–514

    Article  PubMed  Google Scholar 

  38. Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, Taylor DO, Tang WH (2008) Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol 52:200–207

    Article  PubMed  CAS  Google Scholar 

  39. Roujeau JC, Chosidow O, Saiag P, Guillauma JC (1990) Toxic epidermal necrolysis (Lyell syndrome). J Am Acad Dermatol 23:1039–1058

    Article  PubMed  CAS  Google Scholar 

  40. Gandhi M, Kowal-Vern A, An G, Hanumadass M (2008) Blister fluid composition in a pediatric patient with toxic epidermal necrolysis. J Burn Care Res 29:671–675

    Article  PubMed  Google Scholar 

  41. Lehnhardt M, Jafari HJ, Druecke D, Steinstraesser L, Steinau HU, Klatte W, Schwake R, Homann HH (2005) A qualitative and quantitative analysis of protein loss in human burn wounds. Burns 31:159–167

    Article  PubMed  CAS  Google Scholar 

  42. Boldt J, Papsdorf M (2008) Fluid management in burn patients: results from a European survey—more questions than answers. Burns 34:323–328

    Article  Google Scholar 

  43. Venkatesh B, Gough J, Ralston DR, Muller M, Pegg S (2004) Protein losing enteropathy in critically ill adult patients with burns: a preliminary report. Intensive Care Med 30:162–166

    Article  PubMed  Google Scholar 

  44. Perel P, Roberts I (2007) Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 17:CD000567

    Google Scholar 

  45. Spirt MJ (2004) Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther 26:197–213

    Article  PubMed  Google Scholar 

  46. Kvasnicka J, Rezac J, Svejda J, Duchkova H, Kaze F, Zalud P, Richter J (1979) Disseminated intravascular coagulation associated with toxic epidermal necrolysis (Lyell’s syndrome). Br J Dermatol 100:551–558

    Article  PubMed  CAS  Google Scholar 

  47. Pottier P, Hardouin JB, Lejeune S, Jolliet P, Gillet B, Planchon B (2009) Immobilization and the risk of venous thromboembolism. A meta-analysis on epidemiological studies. Thromb Res 124:468–476

    Article  PubMed  CAS  Google Scholar 

  48. Ballard J, Edelman L, Saffle J, Sheridan R, Kagan R, Bracco D, Cancio L, Cairns B, Baker R, Fillari B, Wibbenmeyer L, Voight D, Palmieri T, Greenhalgh D, Kemalyan N, Caruso D, Multicenter Trials Group, American Burn Association (2008) Positive fungal cultures in burn patients: a multicenter review. J Burn Care Res 29:213–221

    PubMed  Google Scholar 

  49. Halebian PH, Corder VJ, Madden MR, Finklestein JL, Shires GT (1986) Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg 204:503–512

    Article  PubMed  CAS  Google Scholar 

  50. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M (2008) Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR study. J Am Acad Dermatol 58:33–40

    Article  PubMed  Google Scholar 

  51. Guibal F, Bastuji-Garin S, Chosidow O, Saiag P, Revuz J, Roujeau JC (1995) Characteristics of toxic epidermal necrolysis in patients undergoing long-term glucocorticoid therapy. Arch Dermatol 131:669–672

    Article  PubMed  CAS  Google Scholar 

  52. Bahna SL, Khalili B (2007) New concepts in the management of adverse drug reactions. Allergy Asthma Proc 28:517–524

    Article  PubMed  CAS  Google Scholar 

  53. Fernandez AP, Kerdel FA (2007) The use of i.v. IG therapy in dermatology. Dermatol Ther 20:288–305

    Article  PubMed  Google Scholar 

  54. Bachot N, Revuz J, Roujeau JC (2003) Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol 139:33–36

    Article  PubMed  CAS  Google Scholar 

  55. Mittmann N, Chan B, Knowles S, Cosentino L, Shear N (2006) Intravenous immunoglobulin use in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome. Am J Clin Dermatol 7:359–368

    Article  PubMed  Google Scholar 

  56. Faye O, Roujeau JC (2005) Treatment of epidermal necrolysis with high-dose intravenous immunoglobulins (IV Ig): clinical experience to date. Drugs 65:2085–2090

    Article  PubMed  CAS  Google Scholar 

  57. Whitaker IS, Prowse S, Potokar TS (2008) A critical evaluation of the use of Biobrane as a biologic skin substitute: a versatile tool for the plastic and reconstructive surgeon. Ann Plast Surg 60:333–337

    Article  PubMed  CAS  Google Scholar 

  58. Boorboor P, Vogt PM, Bechara FG, Alkandari Q, Aust M, Gohritz A, Spies M (2008) Toxic epidermal necrolysis: use of Biobrane or skin coverage reduces pain, improves mobilisation and decreases infection in elderly patients. Burns 34:487–492

    Article  PubMed  CAS  Google Scholar 

  59. Dalli RL, Kumar R, Kennedy P, Maitz P, Lee S, Johnson R (2007) Toxic epidermal necrolysis/Stevens-Johnson syndrome: current trends in management. ANZ J Surg 77:671–676

    Article  PubMed  Google Scholar 

  60. Ryan DW (1995) The fluidised bed. Intensive Care Med 21:270–276

    Article  PubMed  CAS  Google Scholar 

  61. Hsiao CT, Lin LJ, Shiao CJ, Hsiao KY, Chen IC (2008) Hemorrhagic bullae are not only skin deep. Am J Emerg Med 26:316–319

    Article  PubMed  Google Scholar 

  62. Lebargy F, Wolkenstein P, Gisselbrecht M, Lange F, Fleury-Feith J, Delclaux C, Roupie E, Revuz J, Roujeau JC (1997) Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study. Intensive Care Med 23:1237–1244

    Article  PubMed  CAS  Google Scholar 

  63. Jäckel R, Fuchs M, Raff T, Wiedemann B (2002) Drug-induced toxic epidermal necrolysis with involvement of the intestinal and respiratory tract. A case report. Anaesthesist 51:815–819

    Article  PubMed  Google Scholar 

  64. Fine JD, Johnson LB, Weiner M, Suchindran C (2007) Tracheolaryngeal complications of inherited epidermolysis bullosa: cumulative experience of the national epidermolysis bullosa registry. Laryngoscope 117:1652–1660

    Article  PubMed  Google Scholar 

  65. Windfuhr JP, Schloendorff G, Baburi D, Kremer B (2008) Life-threatening posttonsillectomy hemorrhage. Laryngoscope 118:1389–1394

    Article  PubMed  Google Scholar 

  66. Riazi S, Karkouti K, Heggie J (2006) Case report: management of life-threatening oropharyngeal bleeding with recombinant factor VIIa. Can J Anaesth 53:881–884

    Article  PubMed  Google Scholar 

  67. Kluger E (1998) Fatal outcome in allopurinol hypersensitivity syndrome. Ugeskr Laeger 160:1179–1180

    PubMed  CAS  Google Scholar 

  68. Garza A, Waldman AJ, Mamel J (2005) A case of toxic epidermal necrolysis with involvement of the GI tract after systemic contrast agent application at cardiac catheterization. Gastrointest Endosc 62:638–642

    Article  PubMed  Google Scholar 

  69. Krejci V, Hiltebrand LB, Sigurdsson GH (2006) Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med 34:1456–1463

    Article  PubMed  CAS  Google Scholar 

  70. Lamblin V, Favory R, Boulo M, Mathieu D (2006) Microcirculatory alterations induced by sedation in intensive care patients. Effects of midazolam alone and in association with sufentanil. Crit Care 10:R176

    Article  PubMed  Google Scholar 

  71. Gregory DG (2008) The ophthalmologic management of acute Stevens-Johnson syndrome. Ocul Surf 6:87–95

    PubMed  Google Scholar 

  72. Lasudry J (2007) The pathology of ocular syndromes caused by toxicity. Bull Soc Belge Ophtalmol 304:155–178

    PubMed  Google Scholar 

  73. Chang YS, Huang FC, Tseng SH, Hsu CK, HO CL, Sheu HM (2007) Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea 26:123–129

    Article  PubMed  Google Scholar 

  74. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC (2000) Toxic epidermal necrolysis and Stevens-Johnson syndrome. Does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 136:323–327

    Article  PubMed  CAS  Google Scholar 

  75. Stern RS (2000) Improving the outcome of patients with toxic epidermal necrolysis and Stevens-Johnson syndrome. Arch Dermatol 136:410

    Article  PubMed  CAS  Google Scholar 

  76. Mockenhaupt M (2009) Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges 7:142–163

    PubMed  Google Scholar 

  77. Poloczek S, Madler C (2000) Transport of intensive care patients. Anaesthesist 49:480–491

    Article  PubMed  CAS  Google Scholar 

  78. Warren J, Fromm RE Jr, Orr RA, Rotello LC, Horst HM, American College of Critical Care Medicine (2004) Guidelines for the inter- and intrahospital transport of critically ill patients. Crit Care Med 32:256–262

    Article  PubMed  Google Scholar 

  79. Bork K (2005) Pruritus precipitated by hydroxyethyl starch: a review. Br J Dermatol 152:3–12

    Article  PubMed  CAS  Google Scholar 

  80. Holland NJ, Sandhu GS, Ghufoor K, Frosh A (2001) The Foley catheter in the management of epistaxis. Int J Clin Pract 55:14–15

    PubMed  CAS  Google Scholar 

  81. Danzl D (2002) Hypothermia. Semin Respir Crit Care Med 23:57–68

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Plastic and Hand Surgery, Burn Trauma Center, Bergmannstrost Hospital, Merseburger Str. 165, 06112, Halle/Saale, Germany

    Manuel Florian Struck, Beate Reichelt & Michael Steen

  2. Department of Anaesthesiology, Intensive Care and Emergency Medicine, Bergmannstrost Hospital, Halle/Saale, Germany

    Peter Hilbert

  3. Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, University Medical Center, Freiburg, Germany

    Maja Mockenhaupt

Authors
  1. Manuel Florian Struck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Hilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maja Mockenhaupt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beate Reichelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Steen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manuel Florian Struck.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Struck, M.F., Hilbert, P., Mockenhaupt, M. et al. Severe cutaneous adverse reactions: emergency approach to non-burn epidermolytic syndromes. Intensive Care Med 36, 22–32 (2010). https://doi.org/10.1007/s00134-009-1659-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-009-1659-1

Keywords

Search

Navigation