Advertisement

Allergo Journal

, Volume 28, Issue 8, pp 16–34 | Cite as

Schwere Hautreaktionen: klinisches Bild, Epidemiologie, Ätiologie, Pathogenese und Therapie

  • Maren Paulmann
  • Maja MockenhauptEmail author
Übersicht
  • 37 Downloads

Zusammenfassung

Hintergrund

Schwere Hautreaktionen, meist infolge von Medikamenteneinnahme, sind sehr selten und können mit einer hohen Letalität einhergehen. Eine geeignete Therapie, um die Letalität zu senken, ist erstrebenswert.

Methoden

Die aktuellen Veröffentlichungen zu dieser Thematik wurden gesichtet und bewertet.

Ergebnisse

Bei den selbstlimitierenden Erkrankungen akute generalisierte exanthematische Pustulose (AGEP) und generalisiertes bullöses fixes Arzneiexanthem (GBFDE) gibt es keine klare Indikation für eine systemische immunmodulierende Therapie, der Goldstandard ist die supportive Therapie. Bei „drug reaction with eosinophilia and systemic symptoms“ (DRESS) ist die Situation weniger eindeutig, doch werden systemische Glukokortikosteroide vor allem bei ausgeprägter Organbeteiligung empfohlen. Diese geht mit Komplikationen und häufig auch einer Virusreaktivierung einher, welche die Abheilung verzögern kann. Die Datenlage bei Stevens-Johnson-Syndrom (SJS)/Toxisch epidermaler Nekrolyse (TEN) ist kontrovers für verschiedene immunmodulierende Therapien. Aktuelle Publikationen präferieren eine Steroid-Pulstherapie, den Tumornekrosefaktor(TNF)-α-Inhibitor Etanercept sowie den Calcineurin-Inhibitor Cyclosporin A, wobei letztgenannter den vielversprechendsten Ansatz darstellt.

Schlussfolgerung

Die Seltenheit und Unvorhersehbarkeit der Reaktionen machen eine randomisierte doppelblinde Therapiestudie extrem schwierig. Mithilfe von Metaanalysen kann eine Tendenz in der Anwendung von systemischen Therapieoptionen herausgearbeitet werden. Für alle Krankheitsbilder stellt die supportive Therapie immer noch die wichtigste Behandlungsstrategie dar.

Schlüsselwörter

AGEP Cyclosporin A DRESS GBFDE Glukokortikosteroide SJS/TEN 

Abkürzungen

AGEP

Akute generalisierte exanthematische Pustulos

ANA

Antinukleärer Antikörper

CMV

Cytomegalievirus

DIHS

Drug-induced hypersensitivity syndrome

DRESS

Drug reaction with eosinophilia and systemic symptoms

EBV

Epstein-Barr-Virus

EEM

Erythema exsudativum multiforme

EEMM

Erythema exsudativum multiforme majus

GBFDE

Generalisiertes bullöses fixes Arzneiexanthem

HHV-6

Humanes Herpesvirus Typ 6

Ig

Immunglobulin

IL

Interleukin

IVIG

Intravenöse Immunglobuline

KG

Körpergewicht

KI

Konfidenzintervall

KOF

Körperoberfläche

NSAR

Nicht steroidale Antirheumatika

OR

Odds Ratio

PCR

Polymerase chain reaction

SCORTEN

Severity-of-illness score for TEN

SJS

Stevens-Johnson-Syndrom

SSSS

Staphylococcal scalded skin syndrome

Teffs

Effektor-T-Zellen

TEN

Toxisch epidermale Nekrolyse

Th

T-Helferzelle

TNF

Tumornekrosefaktor

Treg

Regulatorische T-Zelle

Literatur

  1. 1.
    Mockenhaupt M, Roujeau JC. Epidermal Necrolysis (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis). In: Kang S, Amagai M, Bruckner A, Enk AH, Margolis DJ, McMichael AJ, Orringer JS, editors. Fitzpatrick’s Dermatology, 9. edition. New York: McGraw Hill Education; 2019. p. 733–48Google Scholar
  2. 2.
    Rzany B, Mockenhaupt M, Baur S, Schröder W, Stocker U, Mueller J et al. 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 1996;49:769–73CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP) — a clinical reaction pattern. J Cutan Pathol 2001;28:113–9CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 2007;156:609–11CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hotz C, Valeyrie-Allanore L, Haddad C, Bouvresse S, Ortonne N, Duong TA et al. Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. Br J Dermatol 2013;169:1223–32CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Burrows NP, Russell Jones RR. Pustular drug eruptions: a histopathological spectrum. Histopathology 1993;22:569–73CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Halevy S, Kardaun SH, Davidovici B, Wechsler J, EuroSCAR and RegiSCAR study group. The spectrum of histopathological features in acute generalized exanthematous pustulosis: a study of 102 cases. Br J Dermatol 2010;163:1245–52CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 2013;169:1071–80CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 1996;15:250–7CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kano Y, Ishida T, Hirahara K, Shiohara T. Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am 2010;94:743–59CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chi MH, Hui RCY, Yang CH, Lin JY, Lin YT, Ho HC et al. Histopathological analysis and clinical correlation of drug reaction with eosinophilia and systemic symptoms (DRESS). Br J Dermatol 2014;170:866–73CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ortonne N, Valeyrie-Allanore L, Bastuji-Garin S, Wechsler J, de Feraudy S, Duong T-A et al. Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study. Br J Dermatol 2015;173:50–8CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 2007;156:1083–4CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Paulmann M, Mockenhaupt M. Schwere arzneimittelinduzierte Hautreaktionen: Klinik, Diagnostik, Ätiologie und Therapie. J Dtsch Dermatol Ges 2015;13:625–45PubMedPubMedCentralGoogle Scholar
  15. 15.
    Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau J-C, SCAR Study Group. Severe Cutaneous Adverse Reactions. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol 2002;138:1019–24CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92–6CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rzany B, Hering O, Mockenhaupt M, Schröder W, Goerttler E, Ring J et al. Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme majus, Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 1996;135:6–11CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ziemer M, Mockenhaupt M. Severe Drug-Induced Skin Reactions: Clinical Pattern, Diagnostics and Therapy. Skin Biopsy - Perspectives 2011;  https://doi.org/10.5772/22335Google Scholar
  19. 19.
    Cho YT, Lin JW, Chen YC, Chang CY, Hsiao CH, Chung WH et al. Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features. J Am Acad Dermatol 2014;70:539–48CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Paulmann M, Mockenhaupt M. Unfreiwillige Reexposition: Generalisiertes bullöses fixes Arzneiexanthem bei 2 älteren Patientinnen. Hautarzt 2017;68:59–63CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lipowicz S, Sekula P, Ingen-Housz-Oro S, Liss Y, Sassolas B, Dunant A et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 2013;168:726–32CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sidoroff A, Dunant A, Viboud C, Halevy S, Bouwes Bavinck JN, Naldi L et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007;157:989–96CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chang SL, Huang YH, Yang CH, Hu S, Hong HS. Clinical manifestations and characteristics of patients with acute generalized exanthematous pustulosis in Asia. Acta Derm Venereol 2008;88:363–5PubMedPubMedCentralGoogle Scholar
  24. 24.
    Davidovici B, Dodiuk-Gad R, Rozenman D, Halevy S, Israeli RegiSCAR Network. Profile of acute generalized exanthematous pustulosis in Israel during 2002–2005: results of the RegiSCAR Study. Isr Med Assoc J IMAJ 2008;10:410–2PubMedPubMedCentralGoogle Scholar
  25. 25.
    Alniemi DT, Wetter DA, Bridges AG, El-Azhary RA, Davis MDP, Camilleri MJ et al. Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013. Int J Dermatol 2017;56:405–14CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Brockow K, Ardern-Jones MR, Mockenhaupt M, Aberer W, Barbaud A, Caubet JC et al. EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity. Allergy 2019;74:14–27CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol 1991;127:1333–8CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Davidovici BB, Pavel D, Cagnano E, Rozenman D, Halevy S, EuroSCAR, RegiSCAR study group. Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases. J Am Acad Dermatol 2006;55:525–9CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Pennisi RS. Acute generalised exanthematous pustulosis induced by the herbal remedy Ginkgo biloba. Med J Aust 2006;184:583–4CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int Off J Jpn Soc Allergol 2006;55:1–8CrossRefGoogle Scholar
  31. 31.
    Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases. Arch Dermatol 2010;146:1373–9CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Paulmann M, Mockenhaupt M. Fever in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric Cases: Laboratory Work-up and Antibiotic Therapy. Pediatr Infect Dis J 2017;36:513–5CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 2008;128:35–44CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Quirke KP, Beck A, Gamelli RL, Mosier MJ. A 15-year review of pediatric toxic epidermal necrolysis. J Burn Care Res Off Publ Am Burn Assoc 2015;36:130–6CrossRefGoogle Scholar
  35. 35.
    Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP et al. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics 2009;123:e297–304CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kauppinen K, Stubb S. Fixed eruptions: causative drugs and challenge tests. Br J Dermatol 1985;112:575–8CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    de Argila D, Angeles Gonzalo M, Rovira I. Carbamazepine-induced fixed drug eruption. Allergy 1997;52:1039CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Baird BJ, De Villez RL. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol 1988;27:170–4CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dharamsi FM, Michener MD, Dharamsi JW. Bullous fixed drug eruption masquerading as recurrent Stevens Johnson syndrome. J Emerg Med 2015;48:551–4CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Schmid S, Kuechler PC, Britschgi M, Steiner UC, Yawalkar N, Limat A et al. Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol 2002;161:2079–86CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Navarini AA, Valeyrie-Allanore L, Setta-Kaffetzi N, Barker JN, Capon F, Creamer D et al. Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis. J Invest Dermatol 2013;133:1904–7CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Feldmeyer L, Heidemeyer K, Yawalkar N. Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy. Int J Mol Sci 2016 Jul 27;17(8). pii:E1214CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Musette P, Janela B. New Insights into Drug Reaction with Eosinophilia and Systemic Symptoms Pathophysiology. Front Med 2017;4:179CrossRefGoogle Scholar
  44. 44.
    Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DIHS) / drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019. Allergology International 2019;68:301–8CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005;102:4134–9CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    White KD, Abe R, Ardern-Jones M, Beachkofsky T, Bouchard C, Carleton B et al. SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation. J Allergy Clin Immunol Pract 2018;6:38–69CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med 2008;14:1343–50CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Su SC, Mockenhaupt M, Wolkenstein P, Dunant A, Le Gouvello S, Chen CB et al. Interleukin-15 Is Associated with Severity and Mortality in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. J Invest Dermatol 2017;137:1065–73CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H et al. A marker for Stevens-Johnson syndrome...: ethnicity matters. Pharmacogenomics J 2006;6:265–8CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogent Genomics 2008;18:99–107CrossRefGoogle Scholar
  52. 52.
    Roujeau JC, Dunant A, Mockenhaupt M. Epidermal necrolysis, ocular complications, and „cold medicines“. J Allergy Clin Immunol Pract 2018;6:703–4CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Genin E, Schumacher M, Roujeau J, Naldi L, Liß Y, Kazma R et al. Genome-Wide Association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe. Orphanet J Rare Dis 2011;6:52CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Chen Z, Liew D, Kwan P. Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions. Neurology; 83:2077–84Google Scholar
  55. 55.
    Shiohara T, Mizukawa Y, Teraki Y. Pathophysiology of fixed drug eruption: the role of skin-resident T cells. Curr Opin Allergy Clin Immunol 2002;2:317–23CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Shiohara T, Mizukawa Y. Fixed drug eruption: a disease mediated by selfinflicted responses of intraepidermal T cells. Eur J Dermatol 2007;17:201–8PubMedPubMedCentralGoogle Scholar
  57. 57.
    Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J 2002;8:5PubMedPubMedCentralGoogle Scholar
  58. 58.
    Uhara H, Saiki M, Kawachi S, Ashida A, Oguchi S, Okuyama R. Clinical course of drug-induced hypersensitivity syndrome treated without systemic corticosteroids. J Eur Acad Dermatol Venereol JEADV 2013;27:722–6CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ushigome Y, Kano Y, Ishida T, Hirahara K, Shiohara T. Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol 2013;68:721–8CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Cho YT, Chu CY. Treatments for Severe Cutaneous Adverse Reactions. J Immunol Res 2017:1503709Google Scholar
  61. 61.
    Funck-Brentano E, Duong T-A, Bouvresse S, Bagot M, Wolkenstein P et al. Therapeutic management of DRESS: a retrospective study of 38 cases. J Am Acad Dermatol 2015;72:246–52CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Tohyama M, Hashimoto K, Yasukawa M, Kimura H, Horikawa T, Nakajima K et al. Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol 2007;157:934–40CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016;174:1194–227CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Dorafshar AH, Dickie SR, Cohn AB, Aycock JK, O’Connor A, Tung A et al. Antishear therapy for toxic epidermal necrolysis: an alternative treatment approach. Plast Reconstr Surg 2008;122:154–60CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? J Burn Care Res Off Publ Am Burn Assoc 2010;31:100–4CrossRefGoogle Scholar
  66. 66.
    Kreymann KG, Berger MM, Deutz NEP, Hiesmayr M, Jolliet P, Kazandjiev G et al. ESPEN Guidelines on Enteral Nutrition: Intensive care. Clin Nutr Edinb Scotl 2006;25:210–23CrossRefGoogle Scholar
  67. 67.
    Chronopoulos A, Mockenhaupt M, Pleyer U. Okuläre Beteiligung bei Stevens-Johnson-Syndrom und Toxisch epidermale Nekrolyse. Klin Monbl Augenheilkd 2012; 229:534–9CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000;115:149–53CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Halebian PH, Corder VJ, Madden MR, Finklestein JL, Shires GT. Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg 1986;204:503–12CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. Acta Derm Venereol 2007;87:144–8CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Zimmermann S, Sekula P, Venhoff M, Motschall E, Knaus J, Schumacher M et al. Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis. JAMA Dermatol 2017;153:514–22CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hirahara K, Kano Y, Sato Y, Horie C, Okazaki A, Ishida T et al. Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis: clinical evaluation and analysis of biomarkers. J Am Acad Dermatol 2013;69:496–8CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Araki Y, Sotozono C, Inatomi T, Ueta M, Yokoi N, Ueda E et al. Successful treatment of Stevens-Johnson syndrome with steroid pulse therapy at disease onset. Am J Ophthalmol 2009;147:1004–11, 1011.e1CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Schneck J, Fagot J-P, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. 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 2008;58:33–40CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    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;282:490–3CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    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;139:39–43PubMedPubMedCentralGoogle Scholar
  77. 77.
    Bachot N, Revuz J, Roujeau JC. Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol 2003;139:33–6CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Shortt R, Gomez M, Mittman N, Cartotto R. Intravenous immunoglobulin does not improve outcome in toxic epidermal necrolysis. J Burn Care Rehabil 2004;25: 246–55CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Faye O, Roujeau JC. Treatment of epidermal necrolysis with high-dose intravenous immunoglobulins (IVIG). Clinical experience to date. Drugs 2005;65:2085–90CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Lee HY, Lim YL, Thirumoorthy T, Pang SM. The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre. Br J Dermatol 2013;169:1304–9CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol 2012;167:424–32CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Valeyrie-Allanore L, Wolkenstein P, Brochard L, Ortonne N, Maître B, Revuz J et al. Open trial of ciclosporin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 2010;163:847–53CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Arévalo JM, Lorente JA, González-Herrada C, Jiménez-Reyes J. Treatment of toxic epidermal necrolysis with cyclosporin A. J Trauma 2000;48:473–8CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Kirchhof MG, Miliszewski MA, Sikora S, Papp A, Dutz JP. Retrospective review of Stevens-Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. J Am Acad Dermatol 2014;71:941–7CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Singh GK, Chatterjee M, Verma R. Cyclosporine in Stevens Johnson syndrome and toxic epidermal necrolysis and retrospective comparison with systemic corticosteroid. Indian J Dermatol Venereol Leprol 2013;79:686–2CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    González-Herrada C, Rodríguez-Martín S, Cachafeiro L, Lerma V, González O, Lorente JA et al. Cyclosporine Use in Epidermal Necrolysis Is Associated with an Important Mortality Reduction: Evidence from Three Different Approaches. J Invest Dermatol 2017;137:2092–100CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    St John J, Ratushny V, Liu KJ, Bach DQ, Badri O, Gracey LE et al. Successful Use of Cyclosporin A for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Three Children. Pediatr Dermatol 2017;34:540–6CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Roujeau JC, Mockenhaupt M, Guillaume JC, Revuz J. New evidence supporting cyclosporine efficacy in epidermal necrolysis. J Invest Dermatol 2017;137:2047–9CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Wolkenstein P, Latarjet J, Roujeau JC, et al (1998) Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet Lond Engl 352:1586–9CrossRefGoogle Scholar
  90. 90.
    Kreft B, Wohlrab J, Bramsiepe I, Eismann R, Winkler M, Marsch WC. Etoricoxib-induced toxic epidermal necrolysis: successful treatment with infliximab. J Dermatol 2010;37:904–6CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol 2014;71:278–83CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Wang CW, Yang LY, Chen CB, Ho HC, Hung SI, Yang CH et al. Randomized, controlled trial of TNF-? antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest 2018;128:985–6CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Narita YM, Hirahara K, Mizukawa Y, Kano Y, Shiohara T. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: Is cytokine expression analysis useful in predicting its therapeutic efficacy?. J Dermatol 2011;38:236–45CrossRefGoogle Scholar
  94. 94.
    Giudice G, Maggio G, Bufano L, Memeo G, Vestita M. Management of Toxic Epidermal Necrolysis with Plasmapheresis and Cyclosporine A: Our 10 Years’ Experience. Plast Reconstr Surg Glob Open 2017;5:e1221CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Yang CW, Cho YT, Chen KL, Chen YC, Song HL, Chu CY. Long-term Sequelae of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. Acta Derm Venereol 2016;96:525–9CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Paulmann M, Kremmler C, Sekula P, Valeyrie-Allanore L, Naldi L, Kardaun S, Mockenhaupt M for the RegiSCAR Group (2016) Long-term sequelae in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis: a 5-year analysis. Clin Transl Allergy 2016, 6(Suppl 3):31 (P34); DOI  https://doi.org/10.1186/s13601-016-0121-z; https://ctajournal.biomedcentral.com/track/pdf/10.1186/s13601-016-0121-z; Allergy (Journal of the European Academy of Allergy and Clinical Immunology (EAACI)), link BioMedCentral platform 3PubMedCentralGoogle Scholar
  97. 97.
    Kauppinen K. Cutaneous reactions to drugs. With special reference to severe bullous mucocutaneous eruptions and sulphonamides. A clinical study. Acta Derm Venereol Suppl (Stockh) 1972;68:1–89Google Scholar
  98. 98.
    Barbaud A, Collet E, Milpied B. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. B J Dermatol 2013;3:555–62CrossRefGoogle Scholar
  99. 99.
    Ardern-Jones M, Mockenhaupt M. Making a diagnosis in severe cutaneous drug reactions. Curr Opn Allergy Clin Immunol 2019;19:283–93CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Dokumentationszentrum schwerer Hautreaktionen, Klinik für Dermatologie und VenerologieUniversitätsklinikum FreiburgFreiburgDeutschland
  2. 2.Dokumentationszentrum schwerer Hautreaktionen, Klinik für Dermatologie und VenerologieMedizinische Fakultät und Universitätsklinikum FreiburgFreiburgDeutschland

Personalised recommendations