Skip to main content
SpringerLink
Log in

Toxic Epidermal Necrolysis in Patients Receiving Anticonvulsants and Cranial Irradiation: A Risk to Consider

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Toxic epidermal necrolysis (TEN) is an infrequent disease but with a high mortality rate. It is a mucocutaneous reaction resulting from hypersensitivity to a variety of agents including most anticonvulsants. Many patients with primary or metastatic intracranial tumours receive anticonvulsants for seizure prophylaxis despite their efficacy not having been clearly demonstrated. Moreover, several cases have been reported in the literature in which serious adverse drug reactions such as TEN and Stevens–Johnson syndrome (SJS) have occurred following anticonvulsants exposure. In some of these cases the effect of radiation therapy and the tapering of steroid dose on the pathogenesis of these reactions have been highlighted. We report, here, a case of TEN that appeared in a patient receiving phenytoin, and shortly after the end of cranial and thoracic irradiation therapy for brain metastases of non-small cell lung cancer. Clinical considerations about diagnosis of SJS and TEN are presented. The use of prophylactic anticonvulsants is also discussed as well as a review of the literature.

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.

Similar content being viewed by others

References

  1. Lyell A: Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 68: 355-361, 1956

    Google Scholar 

  2. Revuz J, Penso D, Roujeau JC, Guillaume JC, Payne CR, Wechsler J, Touraine R: Toxic epidermal necrolysis: clinical findings and prognosis factors in 87 patients. Arch Dermatol 123: 1160-1165, 1987

    Google Scholar 

  3. Egan CA, Grant WJ, Morris SE, Saffle JR, Zone JJ: Plasmapheresis as an adjunct treatment in toxic epidermal necrolysis. J Am Acad Dermatol 40: 458-461, 1999

    Google Scholar 

  4. Renfro L, Grant-Kels JM, Daman LA: Drug-induced toxic epidermal necrolysis treated with cyclosporin. Int J Dermatol 28(7): 441-444, 1989

    Google Scholar 

  5. Heng MC, Allen SG: Efficacy of cyclophosphamide in toxic epidermal necrolysis. Clinical and pathophysiologic aspects. J Am Acad Dermatol 25: 778-786, 1991

    Google Scholar 

  6. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, Auquier A, Bastuji-Garin S, Correia O, Locati F, Mockenhaupt M, Paoletti C, Shapiro S, F.R.C.P. (E), Shear N, Schöp E, Kaufman DW: Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 333: 1600-1607, 1995

    Google Scholar 

  7. Schlienger RG, Shear NH: Antiepileptic drug hypersensitivity syndrome. Epilepsia 39(Suppl 7): S3-S7, 1998

    Google Scholar 

  8. Tennis P, Stern RS: Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49: 542-546, 1997

    Google Scholar 

  9. Stern RS, Chan HL: Usefulness of case report literature in determining drugs responsible for toxic epidermal necrolysis. J Am Acad Dermatol 21: 317-322, 1989

    Google Scholar 

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

    Google Scholar 

  11. Rzany B, Correia O, Kelly JP, Naldi L, Auquier A, Stern R: Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis during first weeks of antiepileptic therapy: a case-control study. Study Group of the International Case-Control study on Severe Cutaneous Adverse Reactions. Lancet 353: 2190-2194, 1999

    Google Scholar 

  12. Mattson RH, Cramer JA, Collins JF: Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalised tonic-clonic seizures in adults. N Engl J Med 327: 765-771, 1992

    Google Scholar 

  13. Guberman AH, Besag FM, Brodie MJ, Dooley JM, Duchowny MS, Pellock JM, Richens A, Stern RS, Trevathan E: Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 40: 985-991, 1999

    Google Scholar 

  14. Yalcin B, Karaduman A: Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. J Am Acad Dermatol 43(5 Pt 2): 898-899, 2000

    Google Scholar 

  15. Duncan KO, Tigelaar RE, Bolognia JL: Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital. J Am Acad Dermatol 40: 493-496, 1999

    Google Scholar 

  16. Borg M, Probert J, Zwi L: Is phenytoin contraindicated in patients receiving cranial irradiation? Australas Radiol 39: 42-46, 1995

    Google Scholar 

  17. Cockey G, Amann S, Reents S, Lynch J: Stevens-Johnson syndrome resulting from whole-brain radiation and phenytoin. Am J Clin Oncol 19(1): 32-34, 1996

    Google Scholar 

  18. Delattre J, Safai B, Posner J: Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 38: 194-198, 1988

    Google Scholar 

  19. Hong-Xuan K, Delattre J, Poisson M: Stevens-Johnson syndrome in a patient receiving cranial irradiation and carbamazepine. Neurology 40: 1144-1145, 1990

    Google Scholar 

  20. Janinis J, Panagos G, Panousaki A, Skarlos D, Athamasiou E, Karpasitis N, Pirounaki M: Stevens-Johnson syndrome and epidermal necrolysis after administration of sodium phenytoin and cranial irradiation. Eur J Cancer 29A(3): 478-479, 1993

    Google Scholar 

  21. Maiche A, Teerenhovi L: Stevens-Johnson syndrome in patients receiving radiation therapy. Lancet 2(8445): 45, 1985

    Google Scholar 

  22. Rowe JE, Pina J, Sau P, Samlaska C, James W: Toxic epidermal necrolysis associated with diphenylhydantoin and cranial irradiation. Int J Dermatol 30: 747-749, 1991

    Google Scholar 

  23. Romero Maldonado N, Sendra Tello J, Raboso Garcia-Baquero E, Harto Castano A: Anticonvulsant hypersensitivity syndrome with fatal outcome. Eur J Dermatol 12: 503-505, 2002

    Google Scholar 

  24. Khafaga YM, Jamshed A, Allam AA, Mourad WA, Ezzat A, Al Eisa A, Gray AJ, Schultz H: Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy. Acta Oncol 38: 111-116, 1999

    Google Scholar 

  25. Micali G, Linthicum K, Han N, West DP: Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies. Pharmacotherapy 19: 223-227, 1999

    Google Scholar 

  26. Errani A, Reggiani M, Schianchi S, Staffa M: Toxic epidermal necrolysis induced by barbiturates and radiotherapy. Br J Dermatol 131: 586-587, 1994

    Google Scholar 

  27. Mamon HJ, Wen PY, Burns AC, Loeffler JS: Allergic skin reactions to anticonvulsant medications in patients receiving cranial irradiation therapy. Epilepsia 40: 341-344, 1999

    Google Scholar 

  28. Trent JT, Bowes LE, Romanilli P, Kerdel FA: Toxic epidermal necrolysis of the scalp following anticonvulsants use and cranial irradiation. J Cutan Med Surg 5: 475-478, 2001

    Google Scholar 

  29. Eralp Y, Aydiner A, Tas F, Saip P, Topuz E: Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation. Am J Clin Oncol 24: 347-350, 2001

    Google Scholar 

  30. Wen PY, Marks PW: Medical management of patients with brain tumors. Curr Opin Oncol 14: 299-307, 2002

    Google Scholar 

  31. Cohen N, Strauss G, Lew R, Silver D, Recht L: Should prophylactic anti-convulsants be administered to patients with newly-diagnosed cerebral metastasis? A retrospective analysis. J Clin Oncol 6: 1621-1624, 1988

    Google Scholar 

  32. Byrne TN, Cascino TC, Posner JB: Brain metastases from melanoma. J Neurooncol 1: 313-317, 1983

    Google Scholar 

  33. Glantz MJ, Cole BF, Friedberg MH, Lathi E, Choy H, Furie K, Akerley W, Wahlberg L, Lekos A, Louis S: A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology 46(4): 985-991, 1996

    Google Scholar 

  34. North JB, Penhall RK, Hanieh A, Frewin DB, Taylor WB: Phenytoin and postoperative epilepsy. A double-blind study. J Neurosurg 58: 672-677, 1983

    Google Scholar 

  35. Forsyth PA, Weaver S, Fulton D, Brasher PM, Sutherland G, Stewart D, Hagen NA, Barnes P, Cairncross JG, DeAngelis LM: Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci 30: 106-112, 2003

    Google Scholar 

  36. De Santis A, Villani R, Sinisi M, Stocchetti N, Perucca E: Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Epilepsia 43: 175-182, 2002

    Google Scholar 

  37. Foy PM, Chadwick DW, Rajgopalan N, Johnson AL, Shaw MD: Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy? J Neurol Neurosurg Psychiat. 55: 753-757, 1992

    Google Scholar 

  38. Franceschetti S, Binelli S, Casazza M, Lodrini S, Panzica F, Pluchino F, Solero CL, Avanzini G: Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir (Wien) 103: 47-51, 1990

    Google Scholar 

  39. Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, Grossman SA, Cairncross JG: Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 54: 1886-1893, 2000

    Google Scholar 

  40. Kuijlen JM, Teernstra OP, Kessels AG, Herpers MJ, Beuls EA: Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis. Seizure 5: 291-298, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Oncología Médica, Hospital Universitario Son Dureta, Palma de Mallorca, Islas Baleares, Spain

    David Aguiar, Roberto Pazo, Ignacio Durán, Josefa Terrasa, Antonio Arrivi, Herminio Manzano, Javier Martín & Julio Rifá

Authors
  1. David Aguiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Pazo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ignacio Durán
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Josefa Terrasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Arrivi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Herminio Manzano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Julio Rifá
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aguiar, D., Pazo, R., Durán, I. et al. Toxic Epidermal Necrolysis in Patients Receiving Anticonvulsants and Cranial Irradiation: A Risk to Consider. J Neurooncol 66, 345–350 (2004). https://doi.org/10.1023/B:NEON.0000014538.31561.bc

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEON.0000014538.31561.bc

Search

Navigation