Zusammenfassung
Hintergrund: Arzneimittelinduzierte Hautreaktionen werden auch im Kindesalter häufig beobachtet
und äußern sich meist in Form makulopapulöser oder urtikarieller Exantheme. Schwere
bullöse Arzneimittelreaktionen im Sinne eines Stevens-Johnson-Syndroms (SJS) oder
einer toxischen epidermalen Nekrolyse (TEN) werden jährlich bei etwa vier Fällen auf
eine Million Einwohner beobachtet, darunter auch Kinder. Antiepileptika, insbesondere
auch Carbamazepin, zählen zu den häufig auslösenden Medikamenten. Fallbericht: Ein 10 5/12 Jahre alter dunkelhäutiger Junge zeigte sechs Wochen nach Beginn einer Carbamazepin-Therapie
eine blasige Ablösung der Epidermis von mehr als einem Drittel der Körperoberfläche.
Innerhalb weniger Stunden bildete sich eine lebensbedrohliche systemische Entzündungsreaktion
mit akutem Lungenversagen aus. Der Krankheitsverlauf wurde durch eine bakterielle
Sepsis, bilaterale Thrombosen der Iliakalvenen und eine Symblepharon-Entwicklung an
den Augen kompliziert. Die Hauterkrankung heilte mit ausgeprägten Pigmentstörungen
ab.
Wir berichten über die differenzialdiagnostischen und therapeutischen Besonderheiten
der TEN und geben einen Überblick über die Literatur.
Abstract
Background: Drug-related skin reactions often present as macular, maculopapular or urticarial
rashes. Severe drug eruptions are rare, with life-threatening events occurring in
about 4 per one million persons a year. In pediatric patients the estimated incidence
of Stevens-Johnsons-syndrome (SJS) and toxic epidermal necrolysis (TEN) is even lower.
They are often caused by antiepileptic drugs like carbamazepine. Case Report: A 10 5/12 year old boy of dark complexion suddenly developed a severe bullous skin disease
six weeks after starting carbamazepine therapy due to focal epilepsy. Within few hours
a life-threatening systemic inflammatory reaction occurred with subsequent respiratory
failure. The clinical course was complicated by bacterial sepsis, bilateral thrombosis
of the external iliacal veins and bilateral ocular symblephara. The skin healed with
considerable pigmentary disturbance. We report the differential diagnostic and therapeutical
features of toxic epidermal necrolysis and give a review of the literature.
Schlüsselwörter
Toxische epidermale Nekrolyse - Blasenbildung - arzneimittelinduzierte Hautreaktion
- Carbamazepin
Key words
Toxic epidermal necrolysis - carbamazepine - blister formation - drug-induced skin
reaction
Literatur
- 1
Bachot N, Roujeau J-C.
Physiopathology and treatment of severe drug eruptions.
Curr Opin Allergy Clin Immunol.
2001;
1
293-298
- 2
Bastuji-Garin S, Rzany B, Stern R S, Shear N, Naldi L, Roujeau J-C.
Clinical classification of cases of Toxic Epidermal Necrolysis, Stevens-Johnson-Syndrome,
and Erythema multiforme.
Arch Dermatol.
1993;
129
92-96
- 3 Brady H R, Brenner B M. Acute Prenal Failure. In: Harrison's Priciples of internal
medicine. 13th ed. McGraw-Hill 1994
- 4
Brettle R P.
Erythema multiforme syndrome associated with varicella.
N Engl J Med.
1981;
305
1472-1473
- 5
Chan H L, Stern R S, Arndt K A, Langlois J, Jick S S, Jick H, Walker A M.
The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal
necrolysis. A population-based study with particular reference to reactions caused
by drugs among outpatients.
Arch Dermatol.
1990;
126
43-47
- 6
Dietrich A, Kawakubo Y, Rzany B, Mockenhaupt M, Simon J C, Schopf E.
Low N-acetylating capacity in patients with Stevens-Johnson syndrome and toxic epidermal
necrolysis.
Exp Dermatol.
1995;
4
313-316
- 7 Doose H. Epilepsien im Kindesalter. 11. Aufl Hamburg Desition 1998
- 8
Forman R, Koren G, Shear N H.
Erythema multiforme, Stevens-Johnson-Syndrome and toxic epidermal necrolysis in children:
a review of 10 years' experience.
Drug Saf.
2002;
25
965-972
- 9
Fournier S, Bastuji-Garin S, Mentec H, Revuz J, Roujeau J C.
Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection.
Eur J Clin Microbiol Infect Dis.
1995;
14
558-559
- 10
Garcia-Doval I, LeCleach L, Bocquet H, Otero X L, Roujeau J C.
Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of
causative drugs decrease the risk of death?.
Arch Dermatol.
2000;
136
323-327
- 11
Ghislain P D, Roujeau J -C.
Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis
and hypersensitivity syndrome.
Dermatol Online J.
2002;
8
5
- 12
Guillaume J C, Roujeau J C, Revuz J, Penso D, Touraine R.
The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyell's syndrome).
Arch Dermatol.
1987;
123
1166-1170
- 13
Halebian P H, Corder V J, Madden M R, Finklestein J L, Shires G T.
Improved burn center survival of patients with toxic epidermal necrolysis managed
without corticosteroids.
Ann Surg.
1986;
204
503-512
- 14
Hanakawa Y, Schechter N M, Lin C, Garza L, Li H, Yamaguchi T, Fudaba Y, Nishifuji K,
Sugai M, Amagai M, Stanley J R.
Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded
skin syndrome.
J Clin Invest.
2002;
110
53-60
- 15
Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y,
Nagata S.
The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate
apoptosis.
Cell.
1991;
66
233-243
- 16
Kauppinen K.
Cutaneous reactions to drugs with special reference to severe bullous mucocutaneous
eruptions and sulphonamides.
Acta Derm Venereol.
1972;
68 (Suppl)
1-89
- 17
Laibson P R.
Current concepts and techniques in corneal transplantation.
Curr Opin Ophthalmol.
2002;
13
220-223
- 18
Leititis J U, Burghard R, Rietschel E, Rieger C H, Brandis M.
Stevens-Johnson syndrome during an immunosuppressive therapy with cyclophosphamide
and prednisone.
Klin Padiatr.
1985;
197
441-442
- 19 Majumdar S, Mockenhaupt M, Roujeau J, Townshend A. Interventions for toxic epidermal
necrolysis (Cochrane Review). Cochrane Database Syst Rev 2002; 4: CD001435
- 20
Mockenhaupt M, Norgauer J.
Schwere arzneimittelinduzierte Hautreaktionen.
Allergologie.
2001;
24
419-432
- 21
Nassif A, Bensussan A, Dorothee G, Mami-Chouaib F, Bachot N, Bagot M, Boumsell L,
Roujeau J C.
Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal
necrolysis.
J Invest Dermatol.
2002;
118
728-733
- 22
Peng Y Z, Yuan Z Q, Xiao G X.
Effects of early enteral feeding on the prevention of enterogenic infection in severely
burned patients.
Burns.
2001;
27
145-149
- 23
Prandota J.
Important role of prodromal viral infections responsible for inhibition of xenobiotic
metabolizing enzymes in the pathomechanism of idiopathic Reye's syndrome, Stevens-Johnson
syndrome, autoimmune hepatitis, and hepatotoxicity of the therapeutic doses of acetaminophen
used in genetically predisposed persons.
Am J Ther.
2002;
9
149-156
- 24
Prins C, Kerdel F A, Padilla R S, Hunziker T, Chimenti S, Viard I, Mauri D N, Flynn K,
Trent J, Margolis D J, Saurat J H, French L E.
Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins.
Arch Dermatol.
2003;
139
26-32
- 25
Revuz J, Penso D, Roujeau J C, Guillaume J C, Payne C R, Wechsler J, Touraine R.
Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients.
Arch Dermatol.
1987;
123
1160-1165
- 26
Roujeau J-C, Kelly J P, Naldi L, Rzany B, Stern R S, Anderson T, Auquier A, Bastuji-Garin S,
Correia O, Locati F, Mockenhaupt M, Paoletti C, Shapiro S, Shear N, Schöpf E, Kaufman D W.
Medication Use and the Risk of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis.
N Engl J Med.
1995;
333
1600-1608
- 27 Roujeau J-C . Treatment of SJS and TEN in Skin Reactions to Drugs. In: Kauppinen
K, Alanko K, Hannuksela M, Maibach H (eds). Boca Raton USA CRC Press LLC 1998; 141-149
- 28
Rzany B, Correia O, Kelly J P, 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.
1999;
353
2190-2194
- 29
Rzany B, Hering O, Mockenhaupt M, Schroder W, Goerttler E, Ring J, Schopf E.
Histopathological and epidemiological characteristics of patients with erythema exudativum
multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Br J Dermatol.
1996;
135
6-11
- 30
Rzany B, Schmitt H, Schopf E.
Toxic epidermal necrolysis in patients receiving glucocorticosteroids.
Acta Derm Venereol.
1991;
71
171-172
- 31
Spies M, Sanford A P, Aili Low J F, Wolf S E, Herndon D N.
Treatment of extensive toxic epidermal necrolysis in children.
Pediatrics.
2001;
108
1162-1168
- 32
Tristani-Firouzi P, Petersen M J, Saffle J R, Morris S E, Zone J J.
Treatment of toxic epidermal necrolysis with intravenous immunoglobulin in children.
J Am Acad Dermatol.
2002;
47
548-552
- 33
van der Meer J B, Schuttelaar M L, Toth G G, Kardaun S H, Beerthuizen G, de Jong M C,
Jonkman M F, Nieuwenhuis P.
Successful dexamethasone pulse therapy in a toxic epidermal necrolysis (TEN) patient
featuring recurrent TEN to oxazepam.
Clin Exp Dermatol.
2001;
26
654-656
- 34
Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat J H,
Tschopp J, French L E.
Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous
immunoglobulin.
Science.
1998;
282
490-493
- 35
Wilkins J, Morrison L, White C R.
Oculocutaneous manifestations of the erythema multiforme/Stevens-Johnson/toxic epidermal
necrolysis spectrum.
Dermatol Clin.
1992;
10
571-582
- 36
Wolkenstein P, Carriere V, Charue D, Bastuji-Garin S, Revuz J, Roujeau J C, Beaune P,
Bagot M.
A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal
necrolysis and Stevens-Johnson syndrome.
Pharmacogenetics.
1995;
5
255-258
- 37
Wolkenstein P, Chosidow O, Flechet M L, Robbiola O, Paul M, Dume L, Revuz J, Roujeau J C.
Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson
syndrome and toxic epidermal necrolysis.
Contact Dermatitis.
1996;
35
234-236
- 38
Wolkenstein P, Latarjet J, Roujeau J C, Duguet C, Boudeau S, Vaillant L, Maignan M,
Schuhmacher M H, Milpied B, Pilorget A, Bocquet H, Brun-Buisson C, Revuz J.
Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis.
Lancet 1998;.
14;
352
1586-1589
- 39
Wolkenstein P, Revuz J.
Toxic epidermal necrolysis.
Dermatol Clin.
2000;
18
485-495
Dr. Johannes Wirbelauer
Pädiatrische Intensivmedizin
Universitäts-Kinderklinik
Josef-Schneider-Straße 2
97080 Würzburg
Phone: +49-9 31-20 12 77 28
Fax: +49-9 31-20 12 72 42
Email: wirbelauer_j@klinik.uni-wuerzburg.de
