Data-Médicos
Dermagic/Express  No. 2-(88)
09 Febrero 2.000  09 February 2.000

~Necrolisis epidermica toxica  ~
~Toxic epidermal necrolysis ~

EDITORIAL ESPANOL
=================
Hola amigos de la red, DERMAGIC de nuevo con ustedes, el tema de hoy: LA
NECROLISIS EPIDERMICA TOXICA, o SINDROME DE LYELL. Nosotros que hacemos
los tratamientos a los pacientes y sus diversas enfermedades
dermatologicas estamos expuestos a que se nos presente esta temible
patologia, Una simple "pastilla" antiinflamatoria , ovulo vaginal ,
anticonvulsivante , vacunas , etc REALMENTE cualquier medicamento PUEDE
desencadenar la necrolisis epidermica TOXICA es una real verdad,  y LO
PEOR es que muchas veces, el estado alergico es TOTALMENTE DESCONOCIDO.
De modo que siempre hay que interrogar bien al paciente sobre posibles
alergias, hacer una buena historia, pero aun haciendolo, hay que contar
con un poco de BUENA SUERTE. Porque en muchos casos  el sindrome de
LYELL se presenta de imprevisto NO EXISTIENDO ningun antecedente. Asi
que  esperemos no tener nunca que vivir esta experiencia.
Espero que disfruten estas 71 referencias.

Saludos a todos !!!

Dr. Jose Lapenta R.,,,

EDITORIAL ENGLISH
=================
Hello friends of the net, DERMAGIC again with you, today's topic: THE
TOXIC EPIDERMAL NECROLYSIS or  LYELL'S SYNDROME . We that make the
treatments to the patients and their diverse illnesses dermatologics are
exposed to this terrible pathology, A simple anti- inflammatory " pill
",  vaginal suppository,  anticonvulsant, vaccines, etc,  any medication
can REALLY cause the TOXIC epidermal  necrolysis, its a real true, and
THE worst thing is that many times, the allergic state is COMPLETELY
UNKNOWN.  So that it is always necessary to interrogate the patient well
on possible allergies, to make a good history, but even making it, it is
necessary to count with some GOOD LUCK. Because in many cases the
LYELL'S syndrome  is presented ACCIDENTALLY,
NOT EXISTING any antecedent. So let us hope to never have to live this
experience.
I hope they enjoy these 71 references.

Greetings to ALL,  !!
Dr. Jose Lapenta R.,,,
===================================================================
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
===================================================================
1.) Management of severe toxic epidermal necrolysis in children.
2.) Toxic epidermal necrolysis following morbilli-parotitis-rubella
vaccination.
3.) Acute myocardial infarction following toxic epidermal necrolysis?
4.) Fulminant toxic epidermal necrolysis induced by trovafloxacin.
5.) Thalidomide-induced toxic epidermal necrolysis.
6.) Skin coverage with Biobrane biomaterial for the treatment of
patients with toxic epidermal necrolysis.
7.) Captopril-induced toxic epidermal necrolysis and agranulocytosis
successfully treated with granulocyte colony-stimulating factor.
8.) Epidermal calprotectin in drug-induced toxic epidermal necrolysis.
9.) Toxic epidermal necrolysis and graft vs. host disease: a clinical
spectrum but a diagnostic dilemma.
10.) Dermatological adverse effects with the antimalarial drug
mefloquine:a review of 74 published case reports.
11.) Toxic epidermal necrolysis in acquired immunodeficiency syndrome
treated with intravenous gammaglobulin.
12.) Clinical manifestations and outcomes in 17 cases of Stevens-Johnson
syndrome and toxic epidermal necrolysis.
13.) Treatment issues in the care of patients with toxic epidermal
necrolysis.
14.) [Erythema multiforme. A heterogeneous pathologic phenotype].
15.) Blister fluid cytokines in cutaneous inflammatory bullous
disorders.
16.) 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.
17.) Toxic epidermal necrolysis occurring as a consequence of treatment
with foscarnet.
18.) Progressive bronchial obstruction associated with toxic epidermal
necrolysis.
19.) Would cyclosporin A be beneficial to mitigate drug-induced toxic
epidermal necrolysis?
20.) Regulatory function of factor-XIIIa-positive dendrocytes in
incipient toxic epidermal necrolysis and graft-versus-host reaction. A
hypothesis.
21.) A study of the efficacy of plasmapheresis for the treatment of drug
induced toxic epidermal necrolysis.
22.) Lyell syndrome and Stevens-Johnson syndrome caused by lamotrigine].

23.) Plasmapheresis as an adjunct treatment in toxic epidermal
necrolysis.
24.) Biological skin covers in treatment of two cases of the Lyell's
syndrome.
25.) Hypopharyngeal stenosis and dysphagia complicating toxic epidermal
necrolysis.
26.) Soluble fractions of tumor necrosis factor-alpha, interleukin-6 and
of
their receptors in toxic epidermal necrolysis: a comparison with
second-degree burns.
27.) Randomised comparison of thalidomide versus placebo in toxic
epidermal necrolysis.
28.) [Ocular manifestations and sequelae of Lyell syndrome caused by
sulfadoxine-pyrimethamine in Cameroon].
29.) Fatal toxic epidermal necrolysis associated with use of terconazole
vaginal suppository.
30.) Lamotrigine-induced severe cutaneous adverse reactions.
31.) Cotrimoxazole induced toxic epidermal necrolysis in a suspected
caseof Pneumocystis carinii pneumonia with human immuno deficiency virus
infection.
32.) Inhibition of toxic epidermal necrolysis by blockade of CD95 with
human intravenous immunoglobulin.
33.) Toxic epidermal necrolysis with severe gastrointestinal mucosal
cell death: a patient who excreted long tubes of dead intestinal
epithelium.
34.) Toxic epidermal necrolysis syndrome: mortality rate reduced with
early referral to regional burn center.
35.) Gelatinases in drug-induced toxic epidermal necrolysis.
36.) Case report: oxaprozin and fatal toxic epidermal necrolysis.
37.)[Undesired drug effects after taking chlormezanone (Muscle
Trancopal) with lethal results].
38.) Treatment of the cutaneous involvement in Stevens-Johnson syndrome
and toxic epidermal necrolysis with silver nitrate-impregnated
dressings.
39.) Oral manifestations of toxic epidermal necrolysis (TEN) in patients
with AIDS: report of five cases.
40.) Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal
necrolysis in northeastern Malaysia.
41.) Toxic epidermal necrolysis associated with treatment for preterm
labor.
42.) [A case of Lyell's syndrome caused by carbamazepine].
43.) [Toxic epidermal necrolysis after the use of intermediate dose of
cytosine arabinoside].
44.) Toxic epidermal necrolysis in a burn patient complicated by acute
pancreatitis.
45.) Vulvovaginal involvement in toxic epidermal necrolysis: a
retrospective study of 40 cases.
46.) Toxic epidermal necrolysis: an analysis of referral patterns and
steroid usage.
47.) Toxic epidermal necrolysis syndrome versus mycosis fungoides.
48.) Toxic epidermal necrolysis.
49.) Heterotopic ossification as a complication of toxic epidermal
necrolysis.
50.) Methotrexate-induced toxic epidermal necrolysis in a patient with
psoriasis.
51.) Nutrition requirements in patients with toxic epidermal necrolysis.

52.) Photo-induced toxic epidermal necrolysis caused by clobazam.
53.) Cyclophosphamide in the treatment of toxic epidermal necrolysis.
54.) Recombinant granulocyte colony-stimulating factor in the management
of toxic epidermal necrolysis.
55.) 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.
56.) Apoptosis as a mechanism of keratinocyte death in toxic epidermal
necrolysis.
57.) Experience with toxic epidermal necrolysis treated in a burn
center.
58.) Medication use and the risk of Stevens-Johnson syndrome or toxic
epidermal necrolysis [see comments]
59.) Analysis of the acute ophthalmic manifestations of the erythema
multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease
spectrum.
60.) Use of Biobrane in the treatment of toxic epidermal necrolysis.
61.) Metabolic predisposition to cutaneous adverse drug reactions. Role
in
toxic epidermal necrolysis caused by sulfonamides and anticonvulsants.
62.) Epidemiologic approaches to the study of toxic epidermal
necrolysis.
63.) The spectrum of Stevens-Johnson syndrome and toxic epidermal
necrolysis: a clinical classification.
64.) Macrophages and tumor necrosis factor alpha in toxic epidermal
necrolysis [see comments]
65.)Investigation of mechanisms in toxic epidermal necrolysis induced by
carbamazepine.
66.) Histopathological and epidemiological characteristics of patients
with erythema exudativum multiforme major, Stevens-Johnson syndrome and
toxic epidermal necrolysis.
67.) Management of severe toxic epidermal necrolysis in children.
68.) Vulvovaginal sequelae in toxic epidermal necrolysis.
69.) Patch testing in severe cutaneous adverse drug reactions, including
Stevens-Johnson syndrome and toxic epidermal necrolysis.
70.) Characteristics of toxic epidermal necrolysis in patients
undergoing long-term glucocorticoid therapy [see comments]
71.) Burn center care for patients with toxic epidermal necrolysis [see
comments]
============================================================
============================================================
1.) Management of severe toxic epidermal necrolysis in children.
============================================================
J Burn Care Rehabil 1999 Nov-Dec;20(6):497-500
Sheridan RL, Weber JM, Schulz JT, Ryan CM, Low HM, Tompkins RG
Shriners Burns Hospital and Department of Surgery, Massachusetts General

Hospital and Harvard Medical School, Boston 02114, USA.
[email protected]

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme

that results in extensive epidermal sloughing; the condition is
associated
with a mortality of up to 70%. From 1991 to 1998, 10 children with
severe
toxic epidermal necrolysis were referred to a regional pediatric burn
facility. Wounds were managed with strategy involving prevention of
wound
desiccation and superinfection, including the frequent use of biologic
wound coverings. Children unable to guard their airway because of
extensive
oropharyngeal involvement were prophylactically intubated. Enteral
nutrition was stressed. Steroids were not used and antibiotics were
administered to managed specific foci of infection only. The 2 boys and
8
girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years)

and sloughed surface area of 76+/-6% of the body surface (range 50 to
95%).
Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2

children), and viral syndrome or unknown agents (2 children) were felt
to
have triggered the syndrome. Six children (60%) required intubation for
an
average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal
involvement
occurred in 9 (90%) and ocular involvement in 9 (90%). Although
infectious
complications were common (2 pneumonias, 2 urinary infections, 1
bacteremia, 2 central line infections, and 2 candidemias), all children
survived after lengths of stay in the burn unit averaging 19+/-3 (range
6
to 40) days. The most common long-term morbidity was keratitis sicca (2
children, 20%), finger nail deformities (3 children, 30%), and
variegated
skin pigment changes (5 children, 50%). Although having both a cutaneous

and visceral wound that predispose them to infectious complications,
most
children with TEN will survive if managed with a strategy emphasizing
biologic wound closure, intensive nutritional support, and early
detection
and treatment of septic foci. Burn units have the resource set required
to
manage severe TEN and early referral of such children may have a
favorable
impact on survival.

============================================================
2.) Toxic epidermal necrolysis following morbilli-parotitis-rubella
vaccination.
============================================================
J Eur Acad Dermatol Venereol 1999 Jul;13(1):59-61

Dobrosavljevic D, Milinkovic MV, Nikolic MM
Institute of Dermatology, University Clinical Centre, Belgrade,
Yugoslavia.

We present the first reported case of toxic epidermal necrolysis (TEN)
caused by morbilli-parotitis-rubella (MPR) vaccine. A 13-year-old girl
developed TEN 7 days after she received live, attenuated, triple MPR
vaccine. The history of drug intake and any illness was negative. At
admission the patient was acutely ill with high fever. The whole body
was
erythematous. The epidermis was wrinkled and the Nikolsky sign was
positive. Numerous erosions were present on the lips and genital region.
On
the seventh day of illness, the eruption involved 80% of the skin.
Systemic
corticosteroid therapy was not employed. The skin and mucosal defects
completely epithelized by the end of the third week of illness. Mild
keratoconjunctivitis sicca remained because of permanent cup cell
damage.

============================================================
3.) Acute myocardial infarction following toxic epidermal necrolysis?
============================================================
Clin Exp Dermatol 1999 Sep;24(5):375-8

Hirakawa S, Ohtsu T, Ojima Y, Kouchi H, Uchida S, Kanzaki H, Arata J
Department of Dermatology, Okayama University Medical School, Japan.
[email protected]

We describe a 29-year-old woman with rheumatoid arthritis who suffered
an
acute myocardial infarction 70 days after an initial presentation with
toxic epidermal necrolysis (TEN). The trigger for the TEN was probably
an
over-the-counter anti-influenza treatment containing tipepidine
hibenzate.
Although the patient had familial hypercholesterolemia, we believe that
thrombocytosis, induced by the inflammatory response and metabolic
stress
resulting from the TEN, may also have played a significant role in the
pathogenesis of the myocardial infarction. Although TEN manifests itself

principally as a skin disease, the potential for systemic morbidity,
including cardiovascular abnormalities, should also be remembered.

============================================================
4.) Fulminant toxic epidermal necrolysis induced by trovafloxacin.
============================================================
Arch Intern Med 1999 Oct 11;159(18):2225

Matthews MR, Caruso DM, Phillips BJ, Csontos LG
Publication Types:
Letter
============================================================

============================================================
5.) Thalidomide-induced toxic epidermal necrolysis.
============================================================
Pharmacotherapy 1999 Oct;19(10):1177-80

Horowitz SB, Stirling AL
College of Pharmacy and Allied Health Professions, St. John's
University,
Jamaica, New York 11439, USA.

Toxic epidermal necrolysis (TEN) is a severe dermatologic disorder
associated with mortality of up to 30%. Withdrawal of the causative
agent
is crucial in its management. Although thalidomide-induced dermatologic
disorders rarely were reported before thalidomide was administered to
patients positive for the human immunodeficiency virus, hypersensitivity

reactions including rash are the agent's major dose-limiting toxicities
in
this population. As it is prescribed for other immunosuppressed
patients,
such as those with malignancies, the frequency of dermatologic reactions

(including TEN) may increase. A 62-year-old woman developed TEN after
approximately 5 weeks of thalidomide therapy for the treatment of a
glioblastoma.

============================================================
6.) Skin coverage with Biobrane biomaterial for the treatment of
patients
with toxic epidermal necrolysis.
============================================================
J Burn Care Rehabil 1999 Sep-Oct;20(5):406-10

Arevalo JM, Lorente JA
Servicio de Cirugia Plastica, Hospital Universitario de Getafe, Madrid,
Spain.

Toxic epidermal necrolysis (TEN) is an exfoliative skin disorder that
may
involve a large body surface area and mucosal surfaces. The microscopic
changes that occur with this condition are similar to those that occur
with
superficial dermal burns, such as dermal detachment from the underlying
dermis. Complications of TEN are related to the loss of the epithelial
skin
barrier and include pain, fluid and electrolyte loss, and an increased
risk
of sepsis. The treatment of a patient with TEN is best accomplished in a

burn unit, where expert treatment of these complications can be
provided.
Medical treatment includes the administration of immunosuppressive
therapy
and the discontinuation of any previous corticosteroid treatment.
Surgical
management includes the debridement of necrotic areas. In this article,
the
surgical management of 8 consecutive patients with TEN who were admitted
to
the intensive care burn unit at the Hospital Universitario de Getafe in
Madrid, Spain, from 1996 to 1998 is described. These patients were
treated
with extensive early debridement of necrotic skin areas followed by
wound
coverage with Biobrane (Dow B. Hickam, Inc, Sugarland, Tex), a temporary

semisynthetic skin substitute. Skin coverage with this material
decreases
pain and fluid loss, and it possibly facilitates epithelization and
decreases the risk of sepsis, without adverse side effects. This
semisynthetic material meets some standards of an ideal skin substitute:
it
is easy to use, provides several beneficial physiologic effects, and
improves patients' comfort. In the 8 cases of patients with TEN that
were
studied, the use of Biobrane skin substitute for the coverage of massive

areas of detached skin was found to be an important aspect of treatment.
 
 

============================================================
7.) Captopril-induced toxic epidermal necrolysis and agranulocytosis
successfully treated with granulocyte colony-stimulating factor.
============================================================
South Med J 1999 Sep;92(9):918-20

Winfred RI, Nanda S, Horvath G, Elnicki M
Department of Medicine, West Virginia University School of Medicine,
Morgantown 26505-9214, USA.

Captopril-induced bone marrow suppression is rare, except in certain
high-risk patient populations. Severe exfoliative rashes have also been
associated with captopril, but a combined presentation of toxic
epidermal
necrolysis and agranulocytosis has not been previously described. We
report
an unusual case of captopril-induced toxic epidermal necrolysis with
agranulocytosis in a patient with no known risk factors. The bone marrow

suppression was successfully treated using granulocyte
colony-stimulating
factor (G-CSF), and the white blood cell (WBC) count recovered within 3
days after starting therapy. This case underscores the early experience
with captopril, which showed a strong correlation between high doses
used
to treat hypertension and bone marrow suppression.

============================================================
8.) Epidermal calprotectin in drug-induced toxic epidermal necrolysis.
============================================================
J Cutan Pathol 1999 Jul;26(6):301-5

Paquet P, Pierard GE
Department of Dermatopathology, University of Liege, CHU Sart Tilman,
Belgium.

Calcium ions (Ca++) in excess alter cell viability. Their potential role
in
drug-induced toxic epidermal necrolysis (TEN) was investigated. Thirteen

TEN patients were biopsied at the site of early bullous lesions and on
clinically normal-looking skin at least 2 cm distant from blisters.
Immunohistochemistry was applied using the mouse monoclonal antibody Mac

387 recognizing the cytosolic protein complex L1 (calprotectin). The L1
antigen is a calcium-binding protein expressed by human granulocytes,
monocytes-macrophages and injured epidermis, but not by normal epidermis

and other cells harboured in the skin. The majority (8/13) of TEN
samples
from apparently non-involved skin expressed the L1 antigen in a
patch-like
pattern inside the epidermis where inflammatory cells were scant or
absent.
As assessed by computerized image analysis of TEN bullous skin, the
intensity of the L1 expression in the epidermis was not statistically
correlated with the amount of the infiltrating inflammatory cells (Mac
387+
macrophages, UCLH1 + T lymphocytes and Factor XIIIa+ dendrocytes)
present
in the dermis and in the epidermis. Such findings suggest a key role for

keratinocytes in the production of the L1 calcium-binding complex. As
the
L1 complex formation is a calcium-dependent process, one of the first
biological events in TEN could be a dramatic increase in keratinocytes
intracellular Ca++ concentration following damage by the involved drug
metabolites. The ultimate toxic cell dysregulation would result from the

disturbance in the intracellular Ca++ homeostasis.

============================================================
9.) Toxic epidermal necrolysis and graft vs. host disease: a clinical
spectrum but a diagnostic dilemma.
============================================================
Clin Exp Dermatol 1999 Jul;24(4):260-2

Stone N, Sheerin S, Burge S
Department of Dermatology, Stoke Mandeville Hosptial, Aylesbury, UK.

We describe a 53-year-old man who developed partial and full thickness
skin
loss associated with pyrexia, diarrhoea, liver, renal and bone marrow
failure, during treatment for an aggressive B cell lymphoblastic
lymphoma.
The clinical features and histology were compatible with both toxic
epidermal necrolysis and graft vs. host disease, causing a diagnostic
and
therapeutic dilemma. We discuss the possibility that methotrexate was
the
causative drug, with review of its cutaneous side-effects.
Histologically
our patient demonstrated the sparse dermal infiltrate with full
thickness
epidermal necrosis typical of toxic epidermal necrolysis and graft vs.
host
disease. We discuss this finding with respect to the pathogenesis of
toxic
epidermal necrolysis.

============================================================
10.) Dermatological adverse effects with the antimalarial drug
mefloquine:
a review of 74 published case reports.
============================================================
Clin Exp Dermatol 1999 Jul;24(4):249-54

Smith HR, Croft AM, Black MM
St. John's Institute of Dermatology, St Thomas' Hospital, London UK.

Mefloquine is a relatively new antimalarial drug which has been
associated
with a wide variety of adverse effects, including skin reactions. In
order
to evaluate the range and frequency of mefloquine's dermatological
effects,
we searched the scientific literature for published case reports of such

effects. We found 74 case reports, published between the years 1983 and
1997. Pruritus and maculopapular rash are the dermatological effects
most
commonly associated with mefloquine: their approximate frequency is
4-10%
for pruritus, and up to 30% for nonspecific maculopapular rash. Adverse
effects associated less commonly with mefloquine include urticaria,
facial
lesions and cutaneous vasculitis. One case of Stevens-Johnson syndrome
and
one fatal case of toxic epidermal necrolysis occurred. Appropriate
primary
studies of mefloquine use should be carried out to elucidate the
epidemiology and aetiology of dermatological and other adverse effects
of
the drug.

============================================================
11.) Toxic epidermal necrolysis in acquired immunodeficiency syndrome
treated with intravenous gammaglobulin.
============================================================
Australas J Dermatol 1999 Aug;40(3):153-7

Phan TG, Wong RC, Crotty K, Adelstein S
Department of Clinical Immunology, Royal Prince Alfred Hospital,
Camperdown, New South Wales, Australia. [email protected]

A 31-year-old man with the acquired immunodeficiency syndrome who
developed
toxic epidermal necrolysis (TEN) was successfully treated with
intravenous
immunoglobulin. He presented with a widespread, blistering skin rash,
extensive mucosal ulceration, high-grade fever and pancytopaenia.
Nevirapine, a non-nucleoside reverse transcriptase inhibitor, was
suspected
as the culprit drug, although the patient had been taking this
medication
for 6 months. The patient also demonstrated an increased number of
gamma/delta (gamma delta) T cells that decreased concomitantly with his
clinical improvement. This correlation has not been described in TEN
previously and may be of pathophysiological significance.

============================================================
12.) Clinical manifestations and outcomes in 17 cases of Stevens-Johnson

syndrome and toxic epidermal necrolysis.
============================================================
Australas J Dermatol 1999 Aug;40(3):131-4

Wong KC, Kennedy PJ, Lee S
Concord Repatriation General Hospital, Sydney, New South Wales,
Australia.

The clinical features and outcomes of 17 patients with Stevens-Johnson
syndrome (SJS) or toxic epidermal necrolysis (TEN) were retrospectively
reviewed. There were 11 males and six females with an average age of
61.5
years. Ten patients with SJS (seven males, three females) and seven
patients with TEN (four males, three females) were identified.
Antibiotics,
mainly beta-lactams, were the most common cause of SJS/TEN in this
series.
The mean skin loss in TEN was 45.7% total body surface area in contrast
to
the lesser skin loss (< 10%) observed in three patients with SJS.
Complications included septicaemia, pneumonia and multi-organ failure,
mainly in the TEN group. Two patients died from TEN-related
complications
and one patient with SJS died from unrelated causes. Ocular involvement
and
skin pigmentary changes represented the most significant long-term
sequelae.

============================================================
13.) Treatment issues in the care of patients with toxic epidermal
necrolysis.
============================================================
Burns 1999 Aug;25(5):439-42

Smoot EC 3rd
University of Tennessee at Memphis, Department of Surgery, USA.

A review of current medical literature is presented to summarize
treatment
issues of ongoing controversy in the care of patients with toxic
epidermal
necrolysis. Terminology for the disease spectrum may be confusing and is

discussed. Steroid treatment recommendations from the allergy and
immunology literature are contrasted with burn center findings for
optimal
treatment. Issues of when to stop offending trigger medications, the
value
of a diagnostic biopsy, timing of hospitalization and the importance of
prospective organ system monitoring are addressed.

============================================================
14.) [Erythema multiforme. A heterogeneous pathologic phenotype].
============================================================
Minerva Stomatol 1999 May;48(5):217-26
Carrozzo M, Togliatto M, Gandolfo S
Dipartimento di Fisiopatologia Clinica, Universita degli Studi, Torino.
[email protected]

The term Erythema Multiforme (EM) include actually a wide range of
clinical
expressions, from exclusive oral erosions (Oral EM) to mucocutaneous
lesions (EM Minor), sometimes with severe involvement of multiple
mucosal
membrane (EM major, Stevens-Johnson syndrome [SJS]) or with involvement
of
a large area of the total body surface (toxic epidermal necrolysis
[TEN]).
However, this terminology is not worldwide accepted and often the
various
clinical categories show some overlapping features. Among the great
number
of suspected etiological factors, herpes simplex virus is involved in
many
cases of EM minor whereas SJS and TEN are caused in 80% of cases by
systemic drugs, mainly by anticonvulsivants, sulfonamides, nonsteroidal
anti-inflammatory drugs and antibiotics. Several oral EM seem
idiopathic,
but data on this topic are very few. There is no specific or consistent
microscopic and immunopathologic pattern of EM and the diagnosis should
be
done by excluding other similar diseases. The treatment include the use
of
antivirals for EM minor, mainly if recurrent, and of immunosuppressants
(especially systemic corticosteroids) for SJS. TEN patients require
adequate supportive care and often they have to be treated in emergency
departments. Finally, patients with exclusive oral lesions may be
treated
with both topical and systemical corticosteroids.

============================================================
15.) Blister fluid cytokines in cutaneous inflammatory bullous
disorders.
============================================================
Acta Derm Venereol 1999 Jul;79(4):288-90

Rhodes LE, Hashim IA, McLaughlin PJ, Friedmann PS
Department of Dermatology, University of Liverpool, UK.

Cytokines are important regulators of immune and inflammatory reactions
in
the skin, and may contribute to inflammatory blister induction. We
examined
the profiles of interleukin-6 (IL-6) and tumour necrosis factor-alpha
(TNF-alpha) in fluid of spontaneous blisters in the immune-based
inflammatory disorders bullous pemphigoid (8 patients), allergic contact

dermatitis (5 patients) and toxic epidermal necrolysis (5 patients).
These
were compared with levels in 9 patients with burns, i.e. inflammatory
blisters of non-immune aetiology, and 4 patients with blisters of
physical
origin. Very high levels of IL-6 were found in bullous pemphigoid and
toxic
epidermal necrolysis (p<0.001) compared with non-inflammatory and burn
blisters. TNF-alpha levels were high in bullous pemphigoid and burns,
but
undetectable in non-inflammatory blisters. The pattern in bullous
pemphigoid (very high IL-6, high TNF-alpha) differed substantially from
toxic epidermal necrolysis (very high IL-6, low TNF-alpha), while burns
and
allergic contact dermatitis showed lesser elevation of both cytokines.
Hence, differences in cytokine profiles were identified, although the
relevance to underlying pathomechanisms is uncertain.

============================================================
16.) 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 Jun 26;353(9171):2190-4

Rzany B, Correia O, Kelly JP, Naldi L, Auquier A, Stern R
Department of Dermatology, Fakultat fur Klinische Medizin Mannheim der
Universitat Heidelberg, Mannheim, Germany.
[email protected]

BACKGROUND: There is still controversy about whether all antiepileptic
drugs are associated with the severe cutaneous reactions Stevens-Johnson

syndrome (SJS) and toxic epidermal necrolysis (TEN). We have studied the

role of antiepileptic drugs in SJS and TEN, taking into account
potential
cofactors that might confound or modify the risk. METHODS: The
case-control
study in France, Italy, Germany, and Portugal identified cases of
SJS/TEN
that developed when the patient was not in hospital and were validated
by
an expert committee. Controls were patients admitted to the same
hospital
as the case for an acute illness or an elective procedure. FINDINGS: 73
(21%) of the 352 SJS/TEN cases and 28 (2%) of the 1579 controls reported

intake of antiepileptic drugs. Among the 73 exposed SJS and TEN
patients,
36 reported intake of phenobarbital, 14 of phenytoin, 21 of
carbamazepine,
13 of valproic acid, and three of lamotrigine. Risk was highest in the
first 8 weeks after onset of treatment. For individual antiepileptic
drugs
the univariate relative risk of SJS/TEN for 8 weeks or less of use was
57
(95% CI 16-360; multivariate risk 59 [12-302]) for phenobarbital; 91
(26-infinity) for phenytoin; 120 (34-infinity) for carbamazepine; 25
(5.6-infinity) for lamotrigine, and 24 (5.9-infinity) for valproic acid.

The result for valproic acid was based on four case users, all of whom
reported concurrent use of other associate drugs. The univariate
relative
risk for more than 8 weeks of use was 6.2 (2.4-17.0; multivariate risk
2.1
[0.5-9.3]) for phenobarbital, 1.2 (0-5.4) for phenytoin, 0.4 (0.02-2.1)
for
carbamazepine, and 7.0 (2.4-21.0; multivariate risk 2.0 [0.3-15.0]) for
valproic acid. INTERPRETATION: SJS and TEN are associated with
short-term
therapy with phenytoin, phenobarbital, and carbamazepine. The
association
with valproic acid seems to be confounded by concomitant short-term
therapy
with other causal drugs. Lamotrigine also has the potential for severe
skin
reactions. The period of increased risk is largely confined to the first
8
weeks of treatment.

============================================================
17.) Toxic epidermal necrolysis occurring as a consequence of treatment
with foscarnet.
============================================================
Cutis 1999 Jun;63(6):333-5

Wharton JR, Laughlin C, Cockerell CJ
Department of Dermatology, University of Arkansas Medical Center, Little

Rock, USA.

Toxic epidermal necrolysis (TEN) has been shown to occur following
administration of many different medications. Recently, we observed a
patient who sustained a severe case of TEN shortly following the
administration of foscarnet. Since this agent has not been previously
associated with this complication, we report the first case of TEN
occurring secondary to treatment with foscarnet.

============================================================
18.) Progressive bronchial obstruction associated with toxic epidermal
necrolysis.
============================================================
Respirology 1999 Mar;4(1):93-5

Minamihaba O, Nakamura H, Sata M, Inage M, Shirakabe M, Tanida H, Osada
Y,
Kondo S, Tomoike H
First Department of Internal Medicine, Yamagata University School of
Medicine, Japan.

Toxic epidermal necrolysis (TEN) is an acute life-threatening condition,

characterized by erosion of the mucous membranes, extensive detachment
of
the epidermis, and severe constitutional symptoms. Pulmonary
complications
of TEN are reported as rare, but are one of the most common causes of
death. Our report focuses on an unusual case of toxic epidermal
necrolysis
which showed multiple bronchial obliteration during the chronic phase of

the disease. Biopsied tissue of the obliterated bronchi demonstrated
non-specific granulation. To improve the obliterated ventilatory
function,
we tried to reopen the bronchial obliteration using a balloon catheter
under the guidance of fibreoptic bronchoscopy, however rapid restenosis
of
the bronchi ensued.

============================================================
19.) Would cyclosporin A be beneficial to mitigate drug-induced toxic
epidermal necrolysis?
============================================================
Dermatology 1999;198(2):198-202

Paquet P, Pierard GE
Department of Dermatopathology, University of Liege, Belgium.
[email protected]

Drug-induced toxic epidermal necrolysis (TEN) is a rare life-threatening

disease whose mortality remains high. The treatment of the disease is
badly
settled. Several kinds of drugs have been tested, including systemic
corticosteroids, cyclophosphamide, pentoxifylline and thalidomide, but
without any clear-cut outcome. Cyclosporin A (CsA) has many inhibitory
effects on the main cell populations involved in TEN (T lymphocytes,
macrophages and keratinocytes). CsA could also act on tumor necrosis
factor
alpha metabolism, a cytokine which is important in TEN epidermal
destruction. Moreover, apoptosis is the mechanism leading to
keratinocyte
death and CsA has antiapoptotic properties. CsA has already been used
successfully on a limited series of TEN patients. We have reviewed the
potential theoretical useful effects of CsA in TEN. We conclude that CsA

could be a good candidate to reverse TEN progression.

============================================================
20.) Regulatory function of factor-XIIIa-positive dendrocytes in
incipient
toxic epidermal necrolysis and graft-versus-host reaction. A hypothesis.

============================================================
Dermatology 1999;198(2):184-6

Hermanns-Le T, Paquet P, Pierard-Franchimont C, Arrese JE, Pierard GE
Department of Dermatopathology, University Medical Center of Liege,
Belgium.

BACKGROUND: Lymphocyte-poor graft-versus-host-reaction (GVHR) and toxic
epidermal necrolysis (TEN) share some histological resemblance. In both
diseases, factor-XIIIa-positive dendrocytes show some morphological
changes, probably as a response to altered cytokine environment.
OBJECTIVE:
To study the ultrastructural aspect of boosted dendrocytes in GVHR and
TEN.
METHODS: Sixty GVHR and 25 TEN lesions were examined using
immunohistochemistry. Among them, 6 dendrocyte-rich cases of each
disease
were studied by electron microscopy. RESULTS: Dendrocyte activation with

enlarged endoplasmic reticulum, and collagen fiber and mast cell granule

phagocytosis were evidenced in both diseases. Depletion in dendrocytes
was
only encountered in a few GVHR cases exhibiting specifically a sclerotic

aspect in the superficial dermis. CONCLUSION: Factor-XIIIa-positive
dendrocytes probably play a role in the regulation of the connective
tissue
remodeling that may accompany epidermal destruction.

============================================================
21.) A study of the efficacy of plasmapheresis for the treatment of drug

induced toxic epidermal necrolysis.
============================================================
Ther Apher 1998 May;2(2):153-6

Yamada H, Takamori K, Yaguchi H, Ogawa H
Department of Dermatology, International Goodwill Hospital, Yokohama,
Japan.

The efficacy of plasmapheresis for the treatment of toxic epidermal
necrolysis (TEN) in our patient and related reports in the literature
were
examined. The patient, a 41-year-old female, was diagnosed as having
drug
(Sedes-G [isopropylantipyrin, arylisopropylacetoureid, and
phenacetinum])
induced TEN. Upon admission to our hospital, extensive corticostroid
therapy was initiated. After 6 days, because more than 90% of the
patient's
body surface was affected by TEN, it was concluded that the patient was
unresponsive to corticosteroid therapy. Double filtration plasmapheresis

(DFPP) was therefore begun. After 2 sessions of DFPP, extensive
reepithelialization rapidly occurred, and after 3 sessions of DFPP, the
improvement was dramatic. The patient's condition had almost healed
during
1 month's hospitalization. It has been reported in the literature that
22
patients with drug induced TEN have been treated with plasmapheresis.
The
mortality rate of 23 patients, including our patient, was 17.4%. The
rate
of effectiveness of plasmapheresis on drug induced TEN is 82.6%. It
appears
that some kind of necrolytic factors were removed by the plasmapheresis.

This suggests that plasmapheresis may be an effective treatment for drug

induced TEN.

============================================================
22.) Lyell syndrome and Stevens-Johnson syndrome caused by lamotrigine].

============================================================
Ann Dermatol Venereol 1999 Jan;126(1):46-8
 

Bocquet H, Farmer M, Bressieux JM, Barzegar C, Jullien M, Soto B,
Roujeau
JC, Revuz J
Service de dermatologie, Hopital Henri Mondor, Creteil.

BACKGROUND: Lamotrigine is a new anticonvulsant belonging to the
triazine
family. Several cases of Stevens-Johnson syndrome (SJS) and toxic
epidermal
necrolysis (TEN) have been described in patients taking this drug. We
report 2 cases in children attending the same hospital. CASE REPORTS:
Two
children, aged 9 and 13 years, developed SJS and TEN respectively, 3 and
28
days after lamotrigine was added to their usual anticonvulsant regimen.
In
both cases, outcome was favorable despite major decline in psychomotor
capacity in one. In the first case, chronological attributability was
plausible for lamotrigine and doubtful for sodium valproate, clonazepam
and
hydrocortisone. In the second case, chronological attributability was
probable for amoxicillin, plausible for lamotrigine and doubtful for
sodium
valproate, but the numerous previous absorptions of amoxicillin made
lamotrigine more suspect. DISCUSSION: The risk of Steven-Johnson
syndrome
and toxic epidermal necrolysis is high with lamotrigine with an
estimated
frequency of 1/1000. This risk is probably higher than with other
anticonvulsants. Associating lamotrigine with sodium valproate increases

the frequency of adverse skin reactions.

============================================================
23.) Plasmapheresis as an adjunct treatment in toxic epidermal
necrolysis.
============================================================
J Am Acad Dermatol 1999 Mar;40(3):458-61

Egan CA, Grant WJ, Morris SE, Saffle JR, Zone JJ
Salt Lake City Veterans Affairs Medical Center, Department of
Dermatology,
University of Utah School of Medicine, USA.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, progressive
disease characterized by the sudden onset of skin necrosis. It is
frequently associated with systemic involvement and has a high rate of
morbidity and mortality. Standard therapy includes meticulous wound
care,
fluid replacement, and nutritional support in an intensive care setting.

OBJECTIVE: We evaluated the outcomes of patients treated in a burn unit
for
TEN over a 9-year period and compared the outcomes of a subset of
patients
treated with plasmapheresis with those managed by conventional means.
METHODS: The records of 16 patients with a diagnosis of TEN obtained
from a
computerized database were reviewed. Parameters recorded included extent
of
body surface area involvement and number of mucous membranes involved at

admission, complications such as sepsis or need for mechanical
ventilation,
length of stay, and disposition. RESULTS: Sixteen patients were included
in
this study. Ten were treated with conventional support measures alone.
Six
were treated with plasmapheresis. The average age was 42.4 years; the
male/female ratio was 1:2.2. Sulfamethoxazole/trimethoprim was
implicated
in causation in 6 patients. The average extent of involvement on
admission
in all patients was 51.5% total body surface area. The average length of

stay in all patients was 14.8 days. Eight patients (50%) were discharged

home, 4 (25%) were discharged to a rehabilitation facility, and 4 (25%)
died (2 of sepsis, 2 of cardiopulmonary arrest). None of the
plasmapheresis-treated patients died. CONCLUSION: Plasmapheresis is a
safe
intervention in extremely ill TEN patients and may reduce the mortality
in
this severe disease. Prospective studies are needed to further define
its
usefulness.

============================================================
24.) Biological skin covers in treatment of two cases of the Lyell's
syndrome.
============================================================
Ann Transplant 1997;2(1):45-8

Klein L, Mericka P, Strakova H, Jebavy L, Nozickova M, Blaha M, Talabova
Z,
Hosek F
Dept. of Plastic Surgery and Burns Treatment, Teaching Hospital Purkinje

Military Medical Academy. [email protected]

The treatment of two cases of toxic epidermal necrolysis (Lyell's
syndrome)
is described. Although some features were common for both ones (young
men
practically of the same age, reaction after using the same drug) the
clinical course of illness was very different. Spontaneous
epithelisation
of partial-thickness lesions and definitive healing under the xenografts
in
one patient and full-thickness skin-loss on 12% of body surface with
severe
septic complications requiring application of cultured keratinocytes
and/or
skin autografting in the other patient were the main differences. The
interdisciplinary approach using a burns treatment protocol in
non-burned
patient including the close co-operation with the tissue bank in
preparing
different types of biological covers has been applied.

============================================================
25.) Hypopharyngeal stenosis and dysphagia complicating toxic epidermal
necrolysis.
============================================================
Arch Otolaryngol Head Neck Surg 1998 Dec;124(12):1375-6

Barrera JE, Meyers AD, Hartford EC
Department of Otolaryngology-Head and Neck Surgery, University of
Colorado
Health Sciences Center, Denver, USA.

Toxic epidermal necrolysis is a severe dermatologic disorder clinically
characterized by the acute onset of erythema and tenderness of the skin.

Destruction of the epidermal barrier results in significant morbidity
and
mortality. Large erosions of mucous membrane, including the mouth and
oral
mucosa, are typical of toxic epidermal necrolysis. After ingesting
naproxen
sodium (Aleve) and aspirin, a previously healthy 43-year-old woman
developed toxic epidermal necrolysis that resulted in hypopharyngeal
stenosis complicated by dysphagia and recurrent aspiration.

============================================================
26.) Soluble fractions of tumor necrosis factor-alpha, interleukin-6 and
of
their receptors in toxic epidermal necrolysis: a comparison with
second-degree burns.
============================================================
Int J Mol Med 1998 Feb;1(2):459-62

Paquet P, Pierard GE
Department of Dermatopathology, University of Liege, Liege, Belgium.

Drug-induced toxic epidermal necrolysis (TEN) is a rare bullous disease
characterized by severe epidermal necrosis and sloughing. Soluble
TNF-alpha(sTNF-alpha), soluble IL-6 (sIL-6) and their reactive soluble
receptors (sTNF-Rp55 or-R1, sTNF-Rp75 or-R2, sIL-6R) were quantified in
blister fluid and serum of 6 TEN patients and 13 cases of second-degree
burn. The amounts of sTNF-alpha, sTNF-R1 and sTNF-R2 were significantly
higher in TEN blisters than in burns reflecting the probable involvement
of
the TNF-alpha system in the specific pathomechanism of TEN. The ratio
sTNF-alpha/sTNF-R2 was significantly lower in TEN blisters than in
burns.
The concentrations of sTNF-R2 in TEN blisters and serums were
significantly
greater than those of sTNF-R1. This suggests a potential important role
for
sTNF-R2 in TEN by enhancing the cytotoxic effect of TNF-alpha. In
addition,
both sTNF-R1 and sTNF-R2 were significantly more abundant in TEN
blisters
than in serums, indicating that the TNF-alpha processing was mainly a
local
event in the TEN skin. No significant difference could be established
for
sIL-6 and sIL-6R between TEN and burns. Although a role for IL-6 cannot
be
ruled out, its production has no specific characteristics in TEN
compared
to burns.

============================================================
27.) Randomised comparison of thalidomide versus placebo in toxic
epidermal
necrolysis.
============================================================
Lancet 1998 Nov 14;352(9140):1586-9

Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vaillant L,
Maignan M, Schuhmacher MH, Milpied B, Pilorget A, Bocquet H,
Brun-Buisson
C, Revuz J
Department of Dermatology, Hopital Henri-Mondor, University Paris XII,
Creteil, France.

BACKGROUND: Toxic epidermal necrolysis (TEN) is associated with a 30%
death
rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in
the
pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha
action.
We did a double-blind, randomised, placebo-controlled study of
thalidomide
in TEN. METHODS: The patients received a 5-day course of thalidomide 400
mg
daily or placebo. The main endpoint was the progression of skin
detachment
after day 7. Secondary endpoints were the severity of the disease,
evaluated with the simplified acute physiology score (SAPS), and the
mortality. TNF-alpha and interleukin 6 were measured. FINDINGS: The
study
was stopped because there was excess mortality in the thalidomide
group--ten of 12 patients died compared with three of ten in the placebo

group (Fisher's exact test with Katz's approximation, relative
risk=2.78,
p=0.03). After adjustment for SAPS, mortality remained significantly
higher
in the thalidomide group than in the placebo group (exact logistic
regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma
TNF-alpha concentration was higher in the thalidomide group than the
placebo group on day 2, though the difference was not significant
(Wilcoxon
rank-sum test p=0.07). INTERPRETATION: Even though few patients were
included, our data suggest that thalidomide is detrimental in TEN,
possibly
because of a paradoxical enhancement of TNF-alpha production.

============================================================
28.) [Ocular manifestations and sequelae of Lyell syndrome caused by
sulfadoxine-pyrimethamine in Cameroon].
============================================================
J Fr Ophtalmol 1998 Jan;21(1):72-7
 

Moussala M, Binam F, Nkam M, Kouda Zeh A, Bengono G
Departement d'Ophtalmologie, Faculte de Medecine et des Sciences
Biomedicales, Universite de Yaounde I, Cameroun.

We report a Lyell syndrome secondary to anti-malarial treatment with
sulfadoxine-pyrimethamine. Eye lesions predominated: symblepharon and
corneal opacification. Desinsertion of conjunctival synechias was
performed
by ophthalmologists. There were corneal opacities and fibro-vascular
veil
on the two eyes. A keratoprosthesis was done on one eye. It is very
likely
that the incidence of this syndrome will increase mainly because of two
factors. The continuous increase of plasmodii resistance to chloroquine
hence the more frequent use of sulfonamides for the treatment of
malaria;
secondly, sulfonamides are used in the treatment and prevention of
opportunistic infections in AIDS patients. It is important for
ophthalmologists in tropical areas to be aware of Lyell's syndrome so
that
proper and early management may be undertaken.

============================================================
29.) Fatal toxic epidermal necrolysis associated with use of terconazole

vaginal suppository.
============================================================
J Cutan Med Surg 1998 Oct;3(2):85-7

Searles GE, Tredget EE, Lin AN
Division of Dermatology and Cutaneous Sciences, University of Alberta,
Canada.
============================================================
============================================================
30.)Lamotrigine-induced severe cutaneous adverse reactions.
============================================================
Epilepsia 1998;39 Suppl 7:S22-6

Schlienger RG, Shapiro LE, Shear NH
Division of Clinical Pharmacology, Sunnybrook Health Science Centre,
University of Toronto, Ontario, Canada.

PURPOSE: We systematically reviewed and analyzed published and
unpublished
cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis
(TEN) associated with lamotrigine (LTG) therapy to identify
characteristics
of these reactions. METHODS: We performed a MEDLINE search (January 1985
to
April 1998) and citation tracking for published reports. In addition,
reports were requested from the Uppsala Monitoring Centre of the World
Health Organization (WHO). Published and WHO cases of LTG-associated SJS
or
TEN were included if the causal relationship was assessed as either
possible, probable, or definite. RESULTS: We identified a total of 57
cases
(43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published.
Cases
in the SJS group were significantly younger than in the TEN group (21
years
vs. 31 years). The median time to onset (17 days for SJS and TEN) and
the
median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not
differ
significantly. Concomitant use of valproate (VPA) was reported in 74% of

the SJS cases and 64% of the TEN cases. In three cases, TEN was the
cutaneous manifestation of the antiepileptic drug hypersensitivity
syndrome
(AHS). CONCLUSIONS: The main features of severe cutaneous drug
reactions,
such as dosage, onset, and concomitant VPA use, do not differ in
patients
with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous
manifestations of LTG-induced AHS. Further epidemiologic studies are
needed
to identify the incidence of severe LTG-induced cutaneous adverse
reactions
and the relative risk compared with other AEDs.

============================================================
31.) Cotrimoxazole induced toxic epidermal necrolysis in a suspected
case
of Pneumocystis carinii pneumonia with human immuno deficiency virus
infection.
============================================================
Indian J Chest Dis Allied Sci 1998 Apr-Jun;40(2):125-9

Arora VK, Venubabu K
Department of Tuberculosis and Chest Diseases, J.I.P.M.E.R., Hospital,
Pondicherry.

Toxic epidermal necrolysis due to trimethoprim sulphamethoxazole therapy
in
a subject of HIV with suspected pneumocystis carinii pneumonia, is
reported, because of its rarity in Indian conditions. Patient showed
excellent recovery on corticosteroid therapy.

============================================================
32.) Inhibition of toxic epidermal necrolysis by blockade of CD95 with
human intravenous immunoglobulin.
============================================================
Science 1998 Oct 16;282(5388):490-3

Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker
T,
Saurat JH, Tschopp J, French LE
Department of Dermatology, Geneva University Medical School, CH-1211
Geneva
4, Switzerland.

Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse
drug
reaction in which keratinocytes die and large sections of epidermis
separate from the dermis. Keratinocytes normally express the death
receptor
Fas (CD95); those from TEN patients were found to express lytically
active
Fas ligand (FasL). Antibodies present in pooled human intravenous
immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro.
In
a pilot study, 10 consecutive individuals with clinically and
histologically confirmed TEN were treated with IVIG; disease progression

was rapidly reversed and the outcome was favorable in all cases. Thus,
Fas-FasL interactions are directly involved in the epidermal necrolysis
of
TEN, and IVIG may be an effective treatment.

============================================================
33.) Toxic epidermal necrolysis with severe gastrointestinal mucosal
cell
death: a patient who excreted long tubes of dead intestinal epithelium.
============================================================
J Dermatol 1998 Aug;25(8):533-8

Sugimoto Y, Mizutani H, Sato T, Kawamura N, Ohkouchi K, Shimizu M
Department of Dermatology, Mie University, Faculty of Medicine, Japan.

TEN is a severe inflammatory disease which is characterized by
generalized
epithelial destruction. The epidermis is the most common target of TEN,
however, any epithelium can be involved. We report a toxic epidermal
necrolysis (TEN) patient who excreted long tubes of dead intestinal
epithelium. Epidermal keratinocytes and intestinal epithelium were found
to
undergo extensive apoptosis by TUNEL method. Drugs were speculated as
the
causative agents for this case, the causative drug has not been
identified.
In contrast to marked improvement of cutaneous manifestation and hepatic

function by methyl prednisolone pulse therapy, the gastrointestinal
symptoms did not respond to therapies, and the patient died by heart
failure. Present case suggested a pathogenetic mechanism targeting
antigens
commonly expressed on the gastrointestinal epithelium and epidermis.

============================================================
34.) Toxic epidermal necrolysis syndrome: mortality rate reduced with
early
referral to regional burn center.
============================================================
Plast Reconstr Surg 1998 Sep;102(4):1018-22

McGee T, Munster A
Baltimore Regional Burn Center at Johns Hopkins Bayview Medical Center,
MD
21224, USA.

Toxic epidermal necrolysis syndrome is an uncommon, acute,
life-threatening
disorder that involves sloughing of skin at the dermal-epidermal
junction
with associated mucositis. Between 1985 and 1995, 36 patients were
treated
for toxic epidermal necrolysis syndrome, at the Baltimore Regional Burn
Center. A retrospective chart analysis was performed to discover
significant determinants of mortality. Ninety-seven percent of the
patients
(35 of 36) were referred from outside institutions after an average of
6.3
+/- 0.8 days. Analysis of the data shows that patients who survived had
been referred 7.5 days earlier than nonsurvivors (4.0 +/- 0.5 days
versus
11.5 +/- 1.4 days, p < 0.001). When the patients were separated into two

groups on the basis of time of referral, those referred "early" (< or =
7
days) had a mortality rate of 4 percent (1 of 24) versus 83 percent (10
of
12) for those referred "late" (> 7 days) (p < 0.001). Data were
available
from transferring institutions for 21 of the 36 patients. Analysis of
the
microbiologic data from these 21 patients revealed bacteremia, and
subsequent death occurred in 100 percent (6 of 6) of the patients
referred
with positive cultures, whereas bacteremia developed in only 33 percent
(5
of 15) of the patients referred with negative cultures, for a mortality
rate of 7 percent (1 of 15). In addition, 86 percent (6 of 7) of the
patients who were referred late (> 7 days) had positive cultures on
referral. The current trend toward prolonged treatment in outside
facilities before referral to a burn center is detrimental to the care
of
patients with toxic epidermal necrolysis syndrome. The overall rate of
bacteremia, septicemia, and mortality is significantly reduced with
early
(< or = 7 days) referral to a regional burn center.

============================================================
35.) Gelatinases in drug-induced toxic epidermal necrolysis.
============================================================
Eur J Clin Invest 1998 Jul;28(7):528-32

Paquet P, Nusgens BV, Pierard GE, Lapiere CM
Department of Dermatopathology, University of Liege, Belgium.

BACKGROUND: The matrix metalloproteinases (MMPs) MMP2 and MMP9 play a
significant role in epidermal detachment, inflammation and
re-epithelialization. We have evaluated their activity in toxic
epidermal
necrolysis (TEN). DESIGN: The level and pattern of activity of MMP2 and
MMP9 were investigated by measuring the degradation of 3H-labelled
gelatin
and by zymography in blister fluid from six TEN patients and compared
the
results with three other blistering conditions: bullous pemphigoid (n =
6),
second-degree burn (n = 13) or suction blister (n = 3). RESULTS: A
higher
amount of MMP2 was found in TEN blister fluid with the constant presence
of
a significantly larger proportion of the activated forms of MMP2, a
particular feature of TEN, than the other blistering diseases studied.
CONCLUSION: This study emphasizes the potential role of MMP2 in the
specific inflammatory reaction and reparation process in TEN skin.

============================================================
36.) Case report: oxaprozin and fatal toxic epidermal necrolysis.
============================================================
J Burn Care Rehabil 1998 Jul-Aug;19(4):321-3

Paul CN, Voigt DW, Clyne KE, Hansen SL
Burn and Wound Center, Saint Elizabeth Community Health Center, Lincoln,

Nebraska 68510, USA.

We have presented a case of fulminating TEN with a fatal outcome. We
believe there is strong probability that the TEN was caused by a
propionic
acid NSAID oxaprozin. This is the first reported case of TEN related to
this particular agent. Toxic epidermal necrolysis has been reported with

all types of NSAIDs. It appears from this case that switching from one
class of nonsteroidal anti-inflammatories to another is not always
without
risk. Despite the class of nonsteroidal anti-inflammatory agent used,
the
possibility of systemic reaction cannot be excluded.

============================================================
37.)[Undesired drug effects after taking chlormezanone (Muscle
Trancopal)
with lethal results].
============================================================
Dtsch Med Wochenschr 1998 Jul 10;123(28-29):866-70

von Boxberg C, Breidenbach K, Hohler H, Kobberling J
Medizinische Klinik, Ferdinand-Sauerbruch-Klinikum, Wuppertal.

HISTORY AND CLINICAL FINDINGS: A 34-year-old woman was admitted for
treatment of toxic epidermolysis of the skin and mucosa. 16 days
previously
she had started to take chlormezanone (Muskel Trancopal) and some other
medications for pain in the shoulder and neck. On admission she had a
fever
of 39 degrees C and, in addition to the epidermolysis, diffuse abdominal

pain on pressure and blood-streaked stool. INVESTIGATIONS: Liver enzyme
activities (GOT 979 U/I, GPT 1496 U/I, gamma GT 201 U/I) alkaline
phosphatase 515 U/I), bilirubin (3.9 mg/dl) and pancreatic enzyme
activities were raised. Sonography was nondiagnostic, computed
tomography
demonstrated only a small amount of ascites. TREATMENT AND COURSE: The
epidermolytic lesions, cholestatic hepatitis and pancreatitis markedly
regressed under aseptic wound treatment, antibiotics and parenteral
nutrition. Persistent blood-streaked stools and bilateral pneumonia with

progressive respiratory failure developed. Despite intensive medical
care
the patient died after 14 days from protracted sepsis with multi-organ
failure. Autopsy additionally revealed adult respiratory distress
syndrome
and complete loss of colonic mucosa. CONCLUSION: The severe course of a
toxic epidermal necrosis with fatal outcome is the first such case
reported
in Germany that very probably was caused by chlormezanone. 4 weeks after

this case was reported to the German Doctors' Drug Commission, the
manufacturers of the drug withdrew it from the market.

============================================================
38.) Treatment of the cutaneous involvement in Stevens-Johnson syndrome
and
toxic epidermal necrolysis with silver nitrate-impregnated dressings.
============================================================
Arch Dermatol 1998 Jul;134(7):877-9

Lehrer-Bell KA, Kirsner RS, Tallman PG, Kerdel FA
Publication Types:
Letter
============================================================

============================================================
39.) Oral manifestations of toxic epidermal necrolysis (TEN) in patients

with AIDS: report of five cases.
============================================================
Oral Dis 1998 Jun;4(2):90-4

Schmidt-Westhausen A, Grunewald T, Reichart PA, Pohle HD
Abteilung fur Oralchirurgie und zahnarztliche Rontgenologie,
Universitatsklinikum Charite, Humboldt Universitat zu Berlin, Germany.

OBJECTIVE: To describe oral findings in HIV-infected individuals with
toxic
epidermal necrolysis (TEN). PATIENTS: In a retrospective study over a 10

year period the medical histories of 931 hospitalised HIV-infected
patients
were reviewed for the occurrence of TEN. RESULTS: Five cases of TEN were

diagnosed (three men, two women; median age: 41 years; median CD4+ T
lymphocyte count: 20/microliter). Four patients had been treated with
biweekly pyrimethamine/sulfadoxine for prophylaxis against Pneumocystis
carinii pneumonia and toxoplasmosis. In one patient flucloxacillin was
administered. Signs of TEN with cutaneous epidermolysis occurred and
patients showed oral lesions characterized as oropharyngeal blisters and

bullae on the palate, buccal mucosa, tongue and floor of the mouth
initially. Antibiotics and corticosteroids were administered; none of
the
patients died. CONCLUSION: Longacting sulfonamides and antibiotics have
been implicated as the cause of severe mucocutaneous reactions. Since
rash
and oral blisters may be the first signs of TEN in patients receiving
these
it is mandatory to follow up these patients closely to detect oral or
cutaneous changes indicating the development of TEN.

============================================================
40.) Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal
necrolysis in northeastern Malaysia.
============================================================
Int J Dermatol 1998 Jul;37(7):520-3

Kamaliah MD, Zainal D, Mokhtar N, Nazmi N
Department of Medicine, School of Medical Sciences, Hospital University
Science Malaysia, Kubang Kerian, Kota Bharu, Kelantan, Malaysia.

BACKGROUND: Previous studies have reported that drugs and infections are

common causes of erythema multiforme (EM) and Stevens-Johnson syndrome
(SJS). Toxic epidermal necrolysis (TEN) is mainly related to drugs. No
study has been conducted in Kelantan, the northeastern state of
Malaysia,
to assess these cutaneous reactions. METHODS: A retrospective study of
all
hospitalized cases of EM, SJS, and TEN was conducted covering an 8-year
period from 1987 to 1994. RESULTS: There were four cases (13.8%) of EM,
22
cases (75.9%) of SJS, and three cases (10.3%) of TEN. Drugs as a
definitive
cause was observed in one case (25%) of EM, 12 cases (54.5%) of SJS, and

two cases (66.7%) of TEN. Drugs as a probable cause was observed in
seven
cases (31.8%) of SJS and one case (33.3%) of TEN. The male to female
ratio
was equal in EM and SJS. Antiepileptics were the commonest culprits,
followed by antibiotics. One patient died of SJS and one patient died of

TEN, giving mortality rates of 4.5% and 33.5% respectively. Fever was
noted
in 18 patients (62.1%). Leukocytosis was noted in 10 patients (34.5%),
and
nine patients (31.0%) had elevated liver transaminase enzymes. No
significant correlation was noted between these biochemical changes and
cutaneous eruption. Secondary infections were observed in 11 patients
(37.9%): Staphylococcus aureus was the commonest isolated organism.
CONCLUSIONS: This study shows that drugs remain the commonest culprit in

SJS and TEN. Despite adequate treatment, the mortality rate remains
high,
especially in TEN. These findings are similar to those of other reported

studies.

============================================================
41.) Toxic epidermal necrolysis associated with treatment for preterm
labor.
============================================================
Dermatology 1998;196(4):461-2

Claessens N, Delbeke L, Lambert J, Matthieu L, Lafaire C, Van Marck E
Department of Dermatology, Universitair Ziekenhuis Antwerpen, Belgium.
[email protected]

We report a 29-year-old pregnant woman who developed toxic epidermal
necrolysis at 29 weeks of gestation after administration of ritodrine,
indomethacin and betamethasone. Toxic epidermal necrolysis is an
unreported
side effect of this widely used combination of medications. Since toxic
epidermal necrolysis is a potentially fatal disease, awareness of a
possible association is warranted.

============================================================
42.) [A case of Lyell's syndrome caused by carbamazepine].
============================================================
Wiad Lek 1995 Jan-Jun;48(1-12):154-6

Urbanowski S, Gwiezdzinski Z, Rybakowski J
Katedry i Kliniki Dermatologii Ak. Med., Bydgoszczy.

A case is described of Lyell syndrome in a female patient with
schizoaffective psychosis which developed several days after addition of

carbamazepine to the psychotropic treatment used. After withdrawal of
the
drug and three weeks of treatment with prednisone in dose 60 mg daily,
antibiotic therapy and intensive dermatological-nursing care, full
remission of skin lesions and oral mucosa lesions was obtained.

============================================================
43.) [Toxic epidermal necrolysis after the use of intermediate dose of
cytosine arabinoside].
============================================================
Rev Assoc Med Bras 1998 Jan-Mar;44(1):53-5
 

Figueiredo MS, Yamamoto M, Kerbauy J
Departamento de Medicina, Universidade Federal de Sao Paulo-Escola
Paulista
de Medicina.

Toxic epidermal necrolysis is a drug-induced dermatologic disease
related
to Lyell syndrome, erythema multiforme and Stevens-Johnson syndrome.
PURPOSE: To report a fatal case of toxic epidermal necrolysis owing to
intermediate dose of cytarabine. CASE REPORT: A 16 year-old female
patient
with acute lymphocytic leukemia (LLA-L1) treated with the Protocol of
the
Brazilian Group for Treatment of Leukemia of Childwood (GBTLI-85-AR). On

the second day after the administration of intermediate dose of
cytarabine
(1.5 g/m2 i.v. every 12 hours for 3 days), she presented bullous lesions
in
the left buttock that disseminated envolving to necrosis, sepsis, and
death
on the 13th day. CONCLUSION: Cytarabine is frequently associated with
dermatologic toxicity but, until now, there is no other case of toxic
epidermal necrolysis described.

============================================================
44.) Toxic epidermal necrolysis in a burn patient complicated by acute
pancreatitis.
============================================================
Burns 1998 Mar;24(2):181-3

Coetzer M, van der Merwe AE, Warren BL
Department of Surgery, University of Stellenbosch, Tygerberg Hospital,
Republic of South Africa.

This report concerns a previously healthy patient who presented with 8%
total body surface area burn wounds to his face and neck. Even though
his
burn wounds healed quickly, his course was complicated by the
development
of toxic epidermal necrolysis affecting 60% total body surface area due
to
a drug reaction. During the recovery period he subsequently developed
jaundice and pancreatitis -- a rare and interesting course that is not
well
described in the literature.

============================================================
45.) Vulvovaginal involvement in toxic epidermal necrolysis: a
retrospective study of 40 cases.
============================================================
Obstet Gynecol 1998 Feb;91(2):283-7   (ISSN: 0029-7844)

Meneux E; Wolkenstein P; Haddad B; Roujeau JC; Revuz J; Paniel BJ [Find
other articles with these Authors]
Department of Obstetrics and Gynecology, Centre Hospitalier
Intercommunal
de Creteil, France.

OBJECTIVE: To determine the incidence, features, and surgical treatment
of
vulvovaginal lesions in toxic epidermal necrolysis. METHODS: Acute
genital
lesions were studied retrospectively in 40 women hospitalized for toxic
epidermal necrolysis in a dermatologic intensive care unit. A
questionnaire
was sent to evaluate sequelae and their effects on sexual activity.
Examination and surgical treatment were proposed to patients with
symptomatic sequelae. RESULTS: Twenty-eight of the 40 patients reported
genital lesions during the acute phase of toxic epidermal necrolysis. No

specific treatment was carried out during the acute period. Sequelae
were
observed in five cases, of which three involved the lower genital tract
and
two the vulva exclusively. The two patients with exclusive vulval
involvement did not attempt any sexual activity. The other three
patients
with both vulval and vaginal lesions were unable to have normal sexual
intercourse. Two of the three patients were treated surgically. One
patient
succeeded in having intercourse, but surgery failed to relieve
dyspareunia.
CONCLUSION: Genital involvement is frequent during toxic epidermal
necrolysis but rarely leads to symptomatic sequelae. Surgery for
synechiae
is sometimes necessary to recover sexual activity because the
vulvovaginal
canal is stenotic. Because of the partial effect on pain relief after
surgery, a preventive approach should be tried.

============================================================
46.) Toxic epidermal necrolysis: an analysis of referral patterns and
steroid usage.
============================================================
J Burn Care Rehabil 1997 Nov-Dec;18(6):520-4   (ISSN: 0273-8481)

Engelhardt SL; Schurr MJ; Helgerson RB [Find other articles with these
Authors]
Department of Surgery, University of Wisconsin Hospital, Madison 53792,
USA.

Toxic epidermal necrolysis (TEN) is an exfoliative disorder associated
with
epidermal slough and systemic toxicity. As of 1986, the literature has
advocated early burn center transfer and has rejected the use of
steroids.
We questioned whether therapy for TEN has changed to reflect these
concepts. All cases of TEN referred to our tertiary burn center since
1988
were reviewed. The history was evaluated for steroid usage and timing of

burn center transfer. Drug exposures, septic complications, and deaths
were
noted. Statistics are expressed as mean +/- SD. Fourteen cases of TEN
were
identified. Transfer was delayed more than 2 days in 10 (72%) instances.

Mean delay was 4.4 +/- 2.7 days. Half received steroids. There were
three
deaths (21%). Pneumonia developed in five patients (36%), urinary tract
infections developed in three (21%) patients, seven (50%) patients
required
intubation, and three (21%) required hemodialysis. No differences in
mortality rates or infectious complications were noted in patients who
received steroids or who were transferred late. Septic complications
occur
frequently in TEN. Delay in transfer and initiation of steroids at
referring institutions are common. Early burn center referral and
avoidance
of steroids needs to be reiterated at the level of the referring
physician.

============================================================
47.) Toxic epidermal necrolysis syndrome versus mycosis fungoides.
============================================================
J Burn Care Rehabil 1997 Sep-Oct;18(5):421-3   (ISSN: 0273-8481)

Speron S; Gamelli R [Find other articles with these Authors]
Department of Surgery, Loyola University Medical Center, Maywood, IL
60153,
USA.

We present a case in which our patient was first seen with biopsy and
histologically confirmed toxic epidermal necrolysis syndrome (TENS).
Subsequent to recovery and discharge from the hospital, the patient
reappeared within 2 months of her discharge with a rash over her neck
and
back, with a central area of superficial breakdown. Biopsy results
confirmed this lesion to be mycosis fungoides, not a recurrent case of
TENS. Given the time lag between these two clinical courses, it is easy
to
speculate that this patient only had one disease entity, which we failed
to
diagnose on initial presentation. Once the skin becomes manifest with
mycosis fungoides, the lesions are those typically beginning as an
erythrodermic rash, it then progresses to indurated and infiltrated
purple
plaques. These symptoms may be confused with TENS, particularly in a
patient with a preexisting diagnosis of TENS. It is critical that
histologic confirmation of the clinical diagnosis be confirmed so that
the
treatment of the patient can be correctly instituted.

============================================================
48.) Toxic epidermal necrolysis.
============================================================

J Burn Care Rehabil 1997 Sep-Oct;18(5):417-20   (ISSN: 0273-8481)

Murphy JT; Purdue GF; Hunt JL [Find other articles with these Authors]
Department of Surgery, University of Texas, Southwestern Medical Center,

Dallas 75235-9031, USA.

Toxic epidermal necrolysis (TEN) is a poorly understood and devastating
condition. It is usually diagnosed in a primary care setting. Treatment
of
severe cases by burn care personnel is usually by referral. In this
review,
we report excessive mortality rates associated with prolonged use of
systemic steroid therapy and delayed referral (more than 1 week from
diagnosis). Forty-four consecutive patients admitted to a regional burn
center with the diagnosis of TEN over a 14-year period, (0.7% of all
admissions) were included. Precipitating factors were identified in 30
cases. Twenty-one patients had known prehospital allergy conditions
directly related to the inciting agent. The mean age of this population
was
44.9 years, and the mean total body surface area (TBSA) injury was
52.4%.
Eighty-four and one-half percent of all patients with TEN were admitted
to
the ICU. Twenty-four patients required ventilator support. Overall
mortality rate was 36%. Nonsurviving patients had a mean age of 61.6
years,
compared to 35.3 years for survivors. Nonsurvivors had a mean TBSA of
64.4%, survivors had a mean TBSA of 44%. TEN, although a nonthermal
injury,
is best managed by personnel experienced in the care of severe thermal
injuries. Despite the availability of this expertise, delayed transfer
of
severe presentations continues to contribute to exceptionally high
morbidity and mortality rates.

============================================================
49.) Heterotopic ossification as a complication of toxic epidermal
necrolysis.
============================================================
Arch Phys Med Rehabil 1997 Jul;78(7):774-6   (ISSN: 0003-9993)
Gibson CJ; Poduri KR [Find other articles with these Authors]
Department of Physical Medicine and Rehabilitation, School of Medicine
and
Dentistry, University of Rochester, NY, USA.

The development of heterotopic ossification (HO) as a complication of
toxic
epidermal necrolysis (TEN) has not been previously reported. TEN, also
known as Lyell's syndrome, is a rare but serious skin disorder that
typically occurs after the administration of drugs, especially
sulfonamides, barbiturates, phenytoin, and nonsteroidal
anti-inflammatory
agents. TEN is characterized by the development of large fluid-filled
bullae with separation of large sheets of skin. Complications of TEN can

include extensive denudation of skin with dehydration and electrolyte
abnormalities, gastrointestinal hemorrhage, acute tubular necrosis,
secondary infection of denuded skin, pneumonia, bacterial
conjunctivitis,
keratitis, and septic infarcts of internal organs. We report a case of
HO
in a patient with TEN after treatment with
trimethoprim-sulfamethoxazole. A
49-year-old man developed an erythematous rash, bullae, fever, and
extensive skin loss consistent with a diagnosis of TEN. He was intubated

for complications of TEN (pneumonia) and maintained on bed rest for
several
weeks. In addition, he developed HO that resulted in multiple joint
contractures. He was treated with aggressive range of motion by physical

therapy, surgical resection of the HO followed by radiation to both
elbows,
right hip, and right knee. Postoperative outpatient rehabilitation
enabled
improved function in his mobility and activities of daily living. HO is
known to occur after spinal cord and brain injuries and burns. It has
not
been reported to occur after TEN. Our experience with this case suggests

that HO may merit inclusion into the list of complications of TEN.

============================================================
50.) Methotrexate-induced toxic epidermal necrolysis in a patient with
psoriasis.
============================================================

J Am Acad Dermatol 1997 May;36(5 Pt 2):815-8   (ISSN: 0190-9622)

Primka EJ 3rd; Camisa C [Find other articles with these Authors]
Cleveland Clinic Foundation, Department of Dermatology, OH, USA.

We describe a fatal case of low-dose methotrexate (MTX) toxicity in a
patient with psoriasis, emphasizing the factors that exacerbate MTX
toxicity and presenting rescue techniques. The patient had a toxic
epidermal necrolysis-like condition. MTX cutaneous reactions ranging
from
toxic epidermal necrolysis to specific ulcerations have been described.
The
use of granulocyte colony stimulating factor for leukopenia associated
with
MTX toxicity is discussed.

============================================================
51.) Nutrition requirements in patients with toxic epidermal necrolysis.

============================================================

Nutr Clin Pract 1997 Apr;12(2):81-4   (ISSN: 0884-5336)

Coss-Bu JA; Jefferson LS; Levy ML; Walding D; David Y; Klish WJ [Find
other
articles with these Authors]
Department of Pediatrics, Baylor College of Medicine, Houston, Texas,
USA.

Patients with toxic epidermal necrolysis, a severe, exfoliative skin
disorder, have clinical features similar to those of partial-thickness
burn
patients. The literature suggests that they also have similar
nutritional
requirements. We report two patients diagnosed with toxic epidermal
necrolysis on mechanical ventilation, in whom resting energy expenditure

and respiratory quotient were measured by indirect calorimetry. The
patients were treated using standard burn protocols. Nitrogen balance
was
calculated by measuring total urinary nitrogen in urine samples obtained

over 24 hours. These measurements were done while the patients were on
mechanical ventilation and receiving total parenteral nutrition. As in
burn
patients, early in their course the two patients had resting energy
expenditure values twice that predicted. After 12 days of
hospitalization,
nitrogen balance was negative in patient 1 and positive in patient 2.
Energy and protein requirements appear to have been related to the
amount
of body surface affected.
 

============================================================
52.) Photo-induced toxic epidermal necrolysis caused by clobazam.
============================================================
Br J Dermatol 1996 Dec;135(6):999-1002   (ISSN: 0007-0963)

Redondo P; Vicente J; Espana A; Subira ML; De Felipe I; Quintanilla E
[Find
other articles with these Authors]
Department of Dermatology, University Clinic of Navarra, School of
Medicine, Pamplona, Spain.

Toxic epidermal necrolysis (TEN) is a life-threatening disease, the
pathogenesis of which remains largely unknown. We describe a 23-year-old

woman under treatment with clobazam who developed lesions of TEN in
light-exposed areas. Patch and photopatch tests with clobazam were
negative. The cellular phenotype and cytokines were studied in blister
fluid. The cellular infiltrate was composed mainly of T lymphocytes with
a
predominant cytotoxic phenotype. There was an increase in the level of
tumour necrosis factor (TNF)-alpha in blister fluid compared with the
control (a patient with bullous pemphigoid).

============================================================
53.) Cyclophosphamide in the treatment of toxic epidermal necrolysis.
============================================================

South Med J 1996 Oct;89(10):1001-3   (ISSN: 0038-4348)

Frangogiannis NG; Boridy I; Mazhar M; Mathews R; Gangopadhyay S; Cate T
[Find other articles with these Authors]
Department of Internal Medicine, Baylor College of Medicine, Houston, TX

77030, USA.

A patient with non-small cell lung carcinoma and recent radiotherapy for

brain metastases developed toxic epidermal necrolysis (TEN) shortly
after
therapy with phenytoin was initiated for a seizure. Exfoliation
progressed
to involve 90% of her body surface despite treatment with high-dose
corticosteroids for 5 days, but sloughing and systemic toxicity ceased
within 2 days of initiating therapy with intravenous cyclophosphamide
(300
mg/day). Reepithelialization rapidly followed. This experience and the
reports of others suggest that intravenous cyclophosphamide is helpful
in
the treatment of TEN.
 

============================================================
54.) Recombinant granulocyte colony-stimulating factor in the management
of
toxic epidermal necrolysis.
============================================================

Br J Dermatol 1996 Aug;135(2):305-6   (ISSN: 0007-0963)

Goulden V; Goodfield MJ [Find other articles with these Authors]
Dermatology Department, Leeds General Infirmary, U.K.

We report a 7-year-old girl with extensive toxic epidermal necrolysis
(TEN)
and neutropenia who was successfully treated using recombinant
granulocyte
colony-stimulating factor. Our patient had extensive epidermal loss and
neutropenia, both indicators of a poor prognosis, but none the less made
a
rapid and complete recovery.

============================================================
55.) 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 Jul;49(7):769-73   (ISSN: 0895-4356)

Rzany B; Mockenhaupt M; Baur S; Schroder W; Stocker U; Mueller J;
Hollander
N; Bruppacher R; Schopf E [Find other articles with these Authors]
Department of Dermatology, University of Freiburg, Germany.

The severe skin reactions erythema exsudativum multiforme majus (EEM
with
mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic
epidermal necrolysis (TEN) are difficult to study as they are very rare
diseases with an incidence of about two cases per 1 million inhabitants
per
year. We report on the structure of a registry with the aim of
ascertaining
all hospitalized cases of EEMM, SJS, and TEN in western Germany and
Berlin.
The registry is structured as an intensive reporting system, regularly
contacting more than 1500 departments including 100% of the burn units
(n =
34), departments of pediatrics (n = 241), departments of dermatology (n
=
106), and 100% of all internal medicine departments in hospitals with
intensive care facilities or with more than 200 beds (n = 1161). With a
coverage rate up to 95% based on the number of responding departments
between April 1, 1990 and December 31, 1992, from a total of 767
reported
cases 353 patients with EEMM, SJS, and TEN were finally included in the
registry. Most of these patients were directly reported to the registry;

only 2.54% (9 of 353) were primarily registered by the German
spontaneous
reporting systems. Assuming an average population of 64.5 million for
western Germany and Berlin an incidence up to 1.89 per 1 million
inhabitants per year could be calculated for SJS and TEN.

============================================================
56.) Apoptosis as a mechanism of keratinocyte death in toxic epidermal
necrolysis.
============================================================

Br J Dermatol 1996 Apr;134(4):710-4   (ISSN: 0007-0963)

Paul C; Wolkenstein P; Adle H; Wechsler J; Garchon HJ; Revuz J; Roujeau
JC
[Find other articles with these Authors]
Department of Dermatology, Hopital Henri Mondor, Creteil, France.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are
life-threatening diseases characterized by extensive epidermal
destruction.
The aim of our study was to investigate apoptosis in keratinocytes of
patients with TEN and TEN/SJS overlap syndrome. Keratinocytes from TEN
patients were found to undergo extensive apoptosis. These results
suggest
that cell destruction in TEN occurs as a result of apoptosis. Our
findings
suggest that apoptosis inhibitory agents may play an important part in
the
therapeutic strategy of TEN.

============================================================
57.) Experience with toxic epidermal necrolysis treated in a burn
center.
============================================================

J Burn Care Rehabil 1996 Jan-Feb;17(1):30-3   (ISSN: 0273-8481)

Yarbrough DR 3rd [Find other articles with this Author]
Department of Surgery, Medical University of South Carolina, Charleston
29425, USA.

Toxic epidermal necrolysis syndrome is one of several clinically
similar,
severe acute, exfoliative skin disorders that have become of increasing
interest to burn surgeons in recent years. Recognition of a clinical
course
similar to extensive second-degree burns has resulted in the development
of
treatment protocols that are best carried out in a burn unit by
personnel
experienced in critical care techniques, the management of extensive
cutaneous injuries, fluid and electrolyte derangements, and intensive
nutritional support of critically ill patients. Current evidence
suggests
that in most instances toxic epidermal necrolysis syndrome is a CD8
lymphocyte-mediated reaction triggered by exposure to certain drugs. The

target organs of the immune reaction are skin and mucous membranes.
Appropriate management of the extensive skin wounds and the nutritional
and
critical care support afforded by treatment in burn units appears to
have
contributed significantly to the increasing survival of patients with
this
devastating and potentially lethal illness.

============================================================
58.) Medication use and the risk of Stevens-Johnson syndrome or toxic
epidermal necrolysis [see comments]
============================================================

N Engl J Med 1995 Dec 14;333(24):1600-7   (ISSN: 0028-4793)

Roujeau JC; Kelly JP; Naldi L; Rzany B; Stern RS; Anderson T; Auquier A;

Bastuji-Garin S; Correia O; Locati F; et al [Find other articles with
these
Authors]
Department of Dermatology, Universite Paris XII, Creteil, France.

BACKGROUND. Toxic epidermal necrolysis and Stevens-Johnson syndrome are
rare, life-threatening, drug-induced cutaneous reactions. We conducted a

case-control study to quantify the risks associated with the use of
specific drugs. METHODS. Data were obtained through surveillance
networks
in France, Germany, Italy, and Portugal. Drug use before the onset of
disease was compared in 245 people who were hospitalized because of
toxic
epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients
hospitalized for other reasons (controls). Crude relative risks were
calculated and adjusted for confounding by multivariate methods when
numbers were large enough. RESULTS. Among drugs usually used for short
periods, the risks were increased for trimethoprim-sulfamethoxazole and
other sulfonamide antibiotics (crude relative risk, 172; 95 percent
confidence interval, 75 to 396), chlormezanone (crude relative risk, 62;
21
to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18),
quinolones (multivariate relative risk, 10; 2.6 to 38), and
cephalosporins
(multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the
multivariate relative risk was 0.6 (95 percent confidence interval, 0.2
to
1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs
usually used for months or years, the increased risk was confined
largely
to the first two months of treatment, when crude relative risks were as
follows: carbamazepine, 90 (95 percent confidence interval, 19 to
infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to
infinity);
valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal
antiinflammatory
drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and
corticosteroids, 54 (23 to 124). For many drugs, including thiazide
diuretics and oral hypoglycemic agents, there was no significant
increase
in risk. CONCLUSIONS. The use of antibacterial sulfonamides,
anticonvulsant
agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids
is
associated with large increases in the risk of Stevens-Johnson syndrome
or
toxic epidermal necrolysis. But for none of the drugs does the excess
risk
exceed five cases per million users per week.

============================================================
59.) Analysis of the acute ophthalmic manifestations of the erythema
multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease
spectrum.
============================================================
Ophthalmology 1995 Nov;102(11):1669-76   (ISSN: 0161-6420)

Power WJ; Ghoraishi M; Merayo-Lloves J; Neves RA; Foster CS [Find other
articles with these Authors]
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston

02114, USA.

PURPOSE: To evaluate the epidemiology, possible etiologic factors,
complications encountered, and treatment administered to a group of
patients with ocular involvement in the erythema
multiforme/Stevens-Johnson
syndrome/toxic epidermal necrolysis disease spectrum who were seen at
two
large tertiary referral centers over a 34-year period. METHODS: Hospital

records from 1960 to 1994 at the Massachusetts General Hospital and
Shriners Hospital for Crippled Children were reviewed for patients with
erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal
necrolysis. Only patients fulfilling specific clinical diagnostic
criteria
and those who received a diagnosis by a dermatologist were included in
the
review. RESULTS: A total of 366 patients with erythema multiforme,
Stevens-Johnson syndrome, or toxic epidermal necrolysis were identified.

Drugs were the most commonly identified etiologic factor in all three
conditions: sulfonamides were the most frequently identified agents.
Eighty-nine patients (24%) had ocular manifestations at the time of
their
acute hospital stay. Ocular involvement was seen in 9% of patients with
erythema multiforme, in 69% with Stevens-Johnson syndrome, and in 50%
with
toxic epidermal necrolysis. The ocular problems were more severe in
patients with both Stevens-Johnson syndrome and toxic epidermal
necrolysis.
There was no significant difference between the number of patients who
were
treated with systemic steroids and those who were not (P = 0.42).
CONCLUSIONS: The erythema multiforme/Stevens-Johnson syndrome/toxic
epidermal necrolysis disease spectrum remains an important cause of
severe
visual loss in a significant number of patients. Systemic steroids used
during the acute phase of the disease appear to have no effect on the
development of ocular manifestations. Studies on the acute
immunopathogenic
mechanisms occurring in these disease are warranted if more effective
therapies are to be found.

============================================================
60.) Use of Biobrane in the treatment of toxic epidermal necrolysis.
============================================================

J Burn Care Rehabil 1995 May-Jun;16(3 Pt 1):324-7; discussion 327-8
(ISSN: 0273-8481)

Kucan JO [Find other articles with this Author]
Institute for Plastic Surgery, Southern Illinois University,
Springfield,
IL 62702, USA.

Toxic epidermal necrolysis syndrome is an exfoliative dermatologic
disorder
of unknown origin resulting in the loss of epidermis in a sheetlike
fashion
at the dermoepidermal junction. The resulting wound renders the patient
vulnerable to potential septic complications, fluid and protein losses,
and
severe pain. During the past decade treatment of toxic epidermal
necrolysis
syndrome has incorporated the basic tenets of burn care: appropriate
fluid
resuscitation, nutritional support, infection surveillance and
treatment,
and optimal care of the open wound. Biobrane, a readily available and
effective biosynthetic skin substitute, has been successfully used in
the
treatment of toxic epidermal necrolysis syndrome and provides a safe and

reliable method to achieve wound closure. Its successful use requires a
thorough understanding of application and removal techniques. Once
adherent, it avoids the cost and pain associated with repeated dressing
changes.

============================================================
61.) Metabolic predisposition to cutaneous adverse drug reactions. Role
in
toxic epidermal necrolysis caused by sulfonamides and anticonvulsants.
============================================================
Arch Dermatol 1995 May;131(5):544-51   (ISSN: 0003-987X)

Wolkenstein P; Charue D; Laurent P; Revuz J; Roujeau JC; Bagot M [Find
other articles with these Authors]
Department of Dermatology, Hopital Henri-Mondor, Creteil, France.

BACKGROUND AND DESIGN: Cutaneous adverse drug reactions (ADRs) have been

hypothesized to have a metabolic basis. Our aim was to identify
detoxification defects involved in toxic epidermal necrolysis and other
severe cutaneous ADRs. Lymphoid cells of 33 patients with cutaneous ADRs

were challenged with reactive metabolites generated from drugs by a
microsomal oxidation system. To be precise in the detoxification defect
involved in sulfonamide and anticonvulsant reactions, we challenged
lymphoid cells from 11 patients (seven patients with sulfonamide ADRs
and
four patients with anticonvulsants ADRs) to menadione and formaldehyde.
Menadione induces toxic effects by oxygen species; formaldehyde is
detoxified by aldehyde dehydrogenase, oxidase, and reductase. RESULTS:
When
the culprit drug was a sulfonamide or an anticonvulsant (used in 13 and
13
patients, respectively), the toxic effects of culprit drug-reactive
metabolites toward patients' lymphoid cells were higher than toward
controls'. First-degree relatives of four patients with sulfonamide- and

phenobarbital-induced toxic epidermal necrolysis were also tested. In
each
family, a relative was more susceptible to culprit drug-reactive
metabolites than were controls. After incubation with menadione, or
formaldehyde, no difference in toxicity was found between patients' and
controls' lymphoid cells. CONCLUSIONS: Toxic epidermal necrolysis and
other
severe cutaneous ADRs to sulfonamides and anticonvulsant drugs may be
linked to a highly specific defect in the detoxification of culprit
drug-reactive metabolites. Our results suggest that this defect is
constitutional and inherited and does not involve oxygen free radicals
and/or aldehyde detoxification pathways.

============================================================
62.) Epidemiologic approaches to the study of toxic epidermal
necrolysis.
============================================================
J Invest Dermatol 1994 Jun;102(6):31S-33S   (ISSN: 0022-202X)

Kaufman DW [Find other articles with this Author]
Slone Epidemiology Unit, Boston University School of Medicine,
Massachusetts.

The appropriate epidemiologic strategy for studying the etiology of
toxic
epidermal necrolysis is determined by the characteristics of the
disease,
particularly its rarity and the fact that it is caused by numerous
drugs.
Although information about drugs as risk factors can in principal be
obtained from case reports and experimental studies, the former are
subject
to bias and the latter are impractical because toxic epidermal
necrolysis
is so rare. Cohort studies are also impractical because of the rarity of

the outcome. An automated database, even if based on a large population,

can only yield valid results if it is used as the starting point for a
case-control study that includes access to the subjects and to the
medical
records for information to confirm the diagnosis. A population-based
case
registry can provide a large enough and well-documented series of cases,

but does not allow for the valid estimation of risks because it lacks a
comparison series. This leaves a case-control study as the only strategy

that is both practical and valid. An ongoing international case-control
study of toxic epidermal necrolysis and Stevens-Johnson syndrome in
relation to the use of drugs is described. Data collection has proceeded
in
France, Italy, Germany, and Portugal. The study in Germany is conducted
within a population-based case registry, and the study in Portugal is
also
population based; this will allow for the estimation of absolute risks.
Data on demographic factors and medical history, a detailed history of
drug
use in the month before hospital admission, and various other factors
are
collected by interview of the cases and hospital controls. Cases are
confirmed in an independent review process in which the diagnoses, and
classification along a spectrum of Stevens-Johnson syndrome and toxic
epidermal necrolysis, are determined without knowledge of drug use. As
of
June, 1993, 459 cases and 1299 controls have been enrolled. At the
scheduled end of data collection in 1995, the projected totals are 691
cases and 1956 controls. These large numbers will allow for the detailed

evaluation of even relatively uncommonly used drugs, for the evaluation
of
more commonly used drugs in relation to subtypes of toxic epidermal
necrolysis/Stevens-Johnson syndrome, and for the comparison of results
between countries.

============================================================
63.) The spectrum of Stevens-Johnson syndrome and toxic epidermal
necrolysis: a clinical classification.
============================================================
J Invest Dermatol 1994 Jun;102(6):28S-30S   (ISSN: 0022-202X)

Roujeau JC [Find other articles with this Author]
Paris XII University, France.

The nosology of severe bullous erythema multiforme (EM), Stevens-Johnson

syndrome (SJS), and toxic epidermal necrolysis (TEN) remains
controversial.
To conduct a prospective case-control study of the etiologic factors of
these diseases, we needed to define criteria for classifying the cases.
After having reviewed photographs of the skin lesions of more than 200
patients, an international group of dermatologists proposed a
classification based on the pattern of "EM-like lesions" (categorized as

typical targets, raised or flat atypical targets, and purpuric macules)
and
on the extent of epidermal detachment. The "consensus" classification in

five categories was as follows: bullous erythema multiforme, detachment
below 10% of the body surface area (BSA) plus localized typical targets
or
raised atypical targets; SJS, detachment below 10% of the BSA plus
widespread erythematous or purpuric macules or flat atypical targets;
overlap SJSTEN, detachment between 10% and 30% of the BSA plus
widespread
purpuric macules or flat atypical targets; TEN with spots, detachment
above
30% of the BSA plus wide-spread purpuric macules or flat atypical
targets;
TEN without spots, detachment above 10% of the BSA with large epidermal
sheets and without any purpuric macules or target. Whether all five
categories proposed represent distinct etiopathologic entities will
require
further epidemiologic and laboratory investigations.

============================================================
64.) Macrophages and tumor necrosis factor alpha in toxic epidermal
necrolysis [see comments]
============================================================
Arch Dermatol 1994 May;130(5):605-8   (ISSN: 0003-987X)

Paquet P; Nikkels A; Arrese JE; Vanderkelen A; Pierard GE [Find other
articles with these Authors]
Department of Dermatopathology, University of Liege, Belgium.

BACKGROUND: We studied the immunopathologic characteristics of five
cases
of toxic epidermal necrolysis by using a large panel of antibodies.
OBSERVATIONS: The pattern and amount of the inflammatory cell infiltrate

varied according to the stage of the disease. The main constant feature
was
the prominent involvement of the monocyte-macrophage lineage, including
factor XIIIa+HLA-DR+ dendrocytes and CD68+ Mac 387+ macrophages, before
and
during the epidermal necrosis. The number of CD4+ and CD8+ lymphocytes
was
comparatively small. This was associated with a dense labeling of the
epidermis for tumor necrosis factor alpha. CONCLUSIONS: Cells of the
monocyte-macrophage lineage largely outnumber lymphocytes in the lesions
of
toxic epidermal necrolysis. Tumor necrosis factor alpha is likely a
major
cytokine that is responsible for necrosis.

============================================================
65.)Investigation of mechanisms in toxic epidermal necrolysis induced by

carbamazepine.
============================================================

Arch Dermatol 1994 May;130(5):598-604   (ISSN: 0003-987X)

Friedmann PS; Strickland I; Pirmohamed M; Park BK [Find other articles
with
these Authors]
Department of Dermatology, Liverpool University, England.

BACKGROUND: Erythema multiforme and toxic epidermal necrolysis can occur
as
serious and even life-threatening adverse drug reactions. The underlying

mechanisms are unknown, but evidence suggests that affected individuals
may
have impaired capacity to detoxify reactive intermediate drug
metabolites.
Such intermediates may be directly toxic or may react with host tissues
to
form antigens, evoking an immune response. We describe our investigation
of
a patient with carbamazepine-induced erythema multiforme and toxic
epidermal necrolysis. The inflammatory infiltrate was examined
immunocytochemically in lesional skin specimens from the patient, in the

patient's patch test response to carbamazepine, and in lesional skin
specimens from five other patients with drug-induced erythema
multiforme.
The patient's lymphocytes were examined both for susceptibility to
cytotoxic damage by liver microsome-induced carbamazepine metabolites
and
for proliferative responses to native carbamazepine, which might
indicate
cell-mediated immune sensitization. OBSERVATIONS: Lesions of toxic
epidermal necrolysis were more florid, but findings were essentially
similar in all the skin samples examined. In the dermis there were CD14+

macrophages, CD1a+ Langerhans cells, and CD3+ CD45RO+ T cells. The
CD4-CD8
T-cell ratio was 2:1, and 10% of the T cells were CD25+, suggesting
activation by recent encounter with antigen. The epidermis contained
CD14+
macrophages and T cells, but the CD8+ cells out-numbered the CD4+ cells.
Up
to 25% of the T cells were CD25+. Lymphocyte proliferation was not
induced
by native carbamazepine, but the patient's lymphocytes were
significantly
more susceptible to cytotoxic killing by liver microsome-induced
carbamazepine intermediates. CONCLUSIONS: The inflammatory reaction in
skin
affected by erythema multiforme and toxic epidermal necrolysis was rich
in
CD8+ T cells, suggesting an immune cytotoxic reaction. The patient
appeared
to have a reduced capacity to detoxify reactive intermediates. This,
together with the lack of lymphocyte response to native drug but a
positive
patch test response, suggests that the immune response may be directed
at
drug-modified epidermal cells.

============================================================
66.) Histopathological and epidemiological characteristics of patients
with
erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic

epidermal necrolysis.
============================================================
Br J Dermatol 1996 Jul;135(1):6-11   (ISSN: 0007-0963)

Rzany B; Hering O; Mockenhaupt M; Schroder W; Goerttler E; Ring J;
Schopf E
[Find other articles with these Authors]
Department of Dermatology, University of Freiburg, Germany.

The clinical and histopathological classification of erythema exudativum

multiforme major (EEMM), Stevens-Johnson syndrome (SJS) and toxic
epidermal
necrolysis (TEN) are difficult, due to the lack of clear-cut criteria.
Based on a new clinical classification, 149 of 219 (68%)
histopathological
specimens, from a total of 534 patients with EEMM, SJS and TEN, have
been
reviewed. A comparison was made with the clinical picture, and any past
history of infection or drug intake. All patients had been included in
the
German Registry of Severe Skin Reactions between April 1990 and December

1993. No differences could be found between the biopsies examined and
the
total number of histopathological specimens, concerning clinical
diagnosis,
gender and age. Sections from 28 of 149 specimens were not diagnostic or

were too old to be properly evaluated. In nine cases, other diagnoses
were
proposed. One hundred and eleven of the histological slides with the
diagnosis of EEMM (n = 16), SJS (n = 34) and TEN (n = 61), were
classified
as epidermal type of erythema multiforme. In these 111 slides, necrotic
keratinocytes could be found, ranging from individual cells to confluent

epidermal necrosis. The epidermo-dermal junction showed changes ranging
from vacuolar alteration up to subepidermal blisters. The dermal
infiltrate
was superficial and mostly perivascular. It was sparse in SJS and TEN,
and
more pronounced in EEMM. Oedema in the papillary dermis was evident
occasionally in all clinical groups. In 59 of 111 cases (53%), at least
one
eosinophil was present in the dermis. In 11 of 111 (10%), more than 10
eosinophils per field could be seen. Eosinophils were less common in the

patients with the most severe forms of TEN, in whom there was detachment
of
more than 30% of the skin surface area. No differences in the history
for
drug intake, or for infection with Mycoplasma pneumoniae, herpes simplex

and other organisms, could be detected between patients with or without
eosinophils in their skin sections. This dermatopathological study of
patients with EEMM, SJS and TEN indicates that the epidermal type of
erythema multiforme is the pathological correlate for these diseases.

============================================================
67.) Management of severe toxic epidermal necrolysis in children.
============================================================
J Burn Care Rehabil 1999 Nov;20(6):497-500   (ISSN: 0273-8481)

Sheridan RL [Find other articles with this Author]
Shriners Burns Hospital and Department of Surgery, Massachusetts General

Hospital and Harvard Medical School, Boston 02114, USA.
[email protected].

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme

that results in extensive epidermal sloughing; the condition is
associated
with a mortality of up to 70%. From 1991 to 1998, 10 children with
severe
toxic epidermal necrolysis were referred to a regional pediatric burn
facility. Wounds were managed with strategy involving prevention of
wound
desiccation and superinfection, including the frequent use of biologic
wound coverings. Children unable to guard their airway because of
extensive
oropharyngeal involvement were prophylactically intubated. Enteral
nutrition was stressed. Steroids were not used and antibiotics were
administered to managed specific foci of infection only. The 2 boys and
8
girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years)

and sloughed surface area of 76+/-6% of the body surface (range 50 to
95%).
Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2

children), and viral syndrome or unknown agents (2 children) were felt
to
have triggered the syndrome. Six children (60%) required intubation for
an
average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal
involvement
occurred in 9 (90%) and ocular involvement in 9 (90%). Although
infectious
complications were common (2 pneumonias, 2 urinary infections, 1
bacteremia, 2 central line infections, and 2 candidemias), all children
survived after lengths of stay in the burn unit averaging 19+/-3 (range
6
to 40) days. The most common long-term morbidity was keratitis sicca (2
children, 20%), finger nail deformities (3 children, 30%), and
variegated
skin pigment changes (5 children, 50%). Although having both a cutaneous

and visceral wound that predispose them to infectious complications,
most
children with TEN will survive if managed with a strategy emphasizing
biologic wound closure, intensive nutritional support, and early
detection
and treatment of septic foci. Burn units have the resource set required
to
manage severe TEN and early referral of such children may have a
favorable
impact on survival.
============================================================
68.) Vulvovaginal sequelae in toxic epidermal necrolysis.
============================================================
J Reprod Med 1997 Mar;42(3):153-6   (ISSN: 0024-7758)

Meneux E; Paniel BJ; Pouget F; Revuz J; Roujeau JC; Wolkenstein P [Find
other articles with these Authors]
Department of Gynecology, Centre Hopitalier Intercommunal, Creteil,
France.

OBJECTIVE: To evaluate the incidence of vulvar lesions during the acute
and
healing periods in toxic epidermal necrolysis (TEN), to describe the
clinical aspects and functional consequences, and to evaluate surgical
treatment. STUDY DESIGN: During the acute period in 40 patients,
cutaneous
and mucous lesions were described on the day of hospitalization and
daily
thereafter. To evaluate the healing period, a questionnaire was sent to
the
same 40 patients to obtain information on symptomatology after the acute

period, anatomic modifications, and the quality of sexual and other
genital
activity. RESULTS: During the acute period, genital lesions were present
in
28 of the 40 patients studied (70%). In 24/28 (89%) the lesions were
vulvar
only, and in 3/28 (11%) they were vulvovaginal. In one case vaginal
involvement could not be proven because the patient was a virgin. During

the healing period, sequelae occurred in 5 of the 40 patients (12.5%):
four
cases were known since the patients had visited the Department of
Gynecology because of secondary effects, and one case was detected by
the
questionnaire. The symptoms occurred during hospitalization in 1 case,
at
the end of the second month in 2, at the 12th month in 1 and unknown in
1.
The site was the vulva in all five cases and was the vulva and vagina in

three. Again, the virgin could not be examined. The average interval
between secondary effects and the original gynecologic visit was 7
months
(3-12). The sequelae were treated surgically in two of the five affected

patients: on the vulva, nymphoplasty, posthectomy and median
perineotomy;
in the vagina, sharp and blunt dissection, with use of a soft mold. The
first patient had a recurrence six months after surgery, and the second
had
no recurrence but has been unable to engage in intercourse. CONCLUSION:
From our study of the involvement of the vulva and vagina during TEN and

the sequelae, it is clear that detection from the questionnaire was
insufficient. Some women can have synechiae without functional sequelae,

and others can have minor involvement with important psychological
repercussions. A prospective study with systematic examination of the
vulvovaginal area and systematic follow-up for at least one year is
needed.
For therapy, a lubricant gel (perhaps topical steroids) could be useful.

Placing a soft mold in the vagina as soon as possible, though difficult,

and keeping it there until complete healing occurs can lead to
infection.
It is not clear that use of a mold would promote healing or be
tolerated.
Intercourse immediately after the acute period would be helpful but
probably would not be welcome to the patients. However useful, a
prospective survey would be difficult because it would entail many years
of
study.

============================================================
69.) Patch testing in severe cutaneous adverse drug reactions, including

Stevens-Johnson syndrome and toxic epidermal necrolysis.
============================================================
Contact Dermatitis 1996 Oct;35(4):234-6   (ISSN: 0105-1873)

Wolkenstein P; Chosidow O; Flechet ML; Robbiola O; Paul M; Dume L; Revuz
J;
Roujeau JC [Find other articles with these Authors]
Department of Dermatology, Hopital Henri-Mondor, Creteil, France.

Patch testing may help to assess the culpability of a drug in an adverse

reaction. Our aim was to study patch testing in severe cutaneous adverse

drug reactions (ADRs) (Stevens-Johnson syndrome/toxic epidermal
necrolysis
(SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and other
cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had
SJS/TEN, 14 AGEP, and 23 other cutaneous ADRs. Patients were patch
tested
with the suspect drug, and with a standard series of drugs. 2 patients
among the 22 SJS/TEN cases had a relevant positive test. 7 patients
among
the 14 AGEP cases had a relevant positive test. 6 patients among the 23
other cutaneous ADRs had a relevant positive test. Our results suggest
that
patch testing has a weak sensitivity in SJS/TEN and is not appropriate
in
these diseases. Patch testing seems more adapted to other cutaneous
ADRs,
such as AGEP, in which the proportion of positive patch tests was
significantly higher (p < 0.02). Nevertheless, the difference of
sensitivity of patch testing in SJS/ TEN, AGEP or other cutaneous ADRs
could be linked not only to the clinical type of eruption, but also to
the
different spectrum of culprit drugs in each type of eruption.

============================================================
70.) Characteristics of toxic epidermal necrolysis in patients
undergoing
long-term glucocorticoid therapy [see comments]
============================================================

Arch Dermatol 1995 Jun;131(6):669-72   (ISSN: 0003-987X)

Guibal F; Bastuji-Garin S; Chosidow O; Saiag P; Revuz J; Roujeau JC
[Find
other articles with these Authors]
Department of Dermatology, Hopital Henri Mondor, Universite Paris XII,
Creteil, France.

BACKGROUND AND DESIGN: The usefulness of steroid therapy in toxic
epidermal
necrolysis (TEN) remains controversial. Up to 5% of the TEN cases occur
in
patients who undergo long-term steroid therapy. We, thus, looked for the

potential effect of long-term glucocorticosteroid therapy before the
onset
of TEN on altering the progression of the disease. The records of 179
patients were reviewed. The characteristics of the 13 patients who were
undergoing long-term glucocorticosteroid therapy were compared with
those
of 166 other patients with TEN. The following parameters were studied:
age,
mortality, delay between the introduction of the suspect drug and the
onset
of TEN, length of hospital stay, body surface area involved, time
elapsed
between the first symptom of TEN and hospital admission, number of
medications taken by the patients before the onset of TEN, lymphocyte
count, granulocyte count, platelet count, glycemia, serum aspartate
aminotransferase level, and total disease duration. RESULTS: Patients
who
were undergoing long-term glucocorticosteroid therapy differed from
other
patients with TEN in the administration of more drugs, longer delay
between
the introduction of the suspect drug and the onset of TEN, and a longer
time elapsed between the first symptom of TEN and hospital admission. We

observed no differences for the other parameters that were studied.
CONCLUSION: Our study shows that long-term steroid therapy may delay the

onset of TEN, but it does not halt its progression.

============================================================
71.) Burn center care for patients with toxic epidermal necrolysis [see
comments]
============================================================
J Am Coll Surg 1995 Mar;180(3):273-8   (ISSN: 1072-7515)

Kelemen JJ 3rd; Cioffi WG; McManus WF; Mason AD Jr; Pruitt BA Jr [Find
other articles with these Authors]
Department of General Surgery, Brooke Army Medical Center, Sam Houston,
Texas.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life threatening
exfoliative disorder that is most commonly precipitated by the
administration of a medication. Efforts to reduce morbidity and improve
survival have brought into question the use of corticosteroids and
recommend the transfer of patients to a burn center to facilitate wound
care. STUDY DESIGN: This study evaluated the correlation of measures of
disease severity and impact of treatment strategies on morbidity and
mortality in patients with TEN. The records of all patients with TEN
admitted to the United States Army Institute of Surgical Research during
a
12 year period were reviewed. Patient characteristics, etiologic agents,

time to referral of patients to the burn center, corticosteroid therapy,

and other demographic features were studied. Univariate and multivariate

analyses were used to determine the significance of these factors with
respect to outcome. RESULTS: The sulfonamides and phenytoin were the
most
frequently identified etiologic agents. Patients at the extremes of age
had
a higher mortality rate. The period of hospitalization was longer in
patients transferred to the burn center more than seven days after skin
slough. Percent of epidermalysis, white blood cell count nadir, and
corticosteroid administration for more than 48 hours were independently
associated with mortality. CONCLUSIONS: These data indicate that the
sulfonamides and phenytoin are the most common etiologic agents,
expeditious transfer to a burn center reduces morbidity, and
corticosteroid
administration dramatically increases mortality.

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