REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES

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A.- Multidisciplinary Treatment in Toxic Epidermal Necrolysis (2023).

B.- Treating Toxic Epidermal Necrolysis With Systemic Immunomodulating Therapies: A Systematic Review and Network Meta-Analysis (2021).

C.- Plasmapheresis for Refractory Toxic Epidermal Necrolysis Unresponsive to Conventional Therapy: A Case Report and Literature Review (2025).

D.- Recent Developments in the Research of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Pathogenesis, Diagnosis and Treatment (2025).

E.- Systemic Interventions for Treatment of Stevens-Johnson Syndrome/­Toxic Epidermal Necrolysis: Summary of a Cochrane Review (2022).

F.- Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis (2022).

G.- Tumor necrosis factor alpha inhibitors in the treatment of toxic epidermal necrolysis (2018).

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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]

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1.) Management of severe toxic epidermal necrolysis in children.

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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. sheridan.robert@mgh.harvard.edu

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.

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2.) Toxic epidermal necrolysis following morbilli-parotitis-rubella vaccination.

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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.

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3.) Acute myocardial infarction following toxic epidermal necrolysis?

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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.

gme08027@med.okayama-u.ac.jp

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.

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4.) Fulminant toxic epidermal necrolysis induced by trovafloxacin.

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Arch Intern Med 1999 Oct 11;159(18):2225

Matthews MR, Caruso DM, Phillips BJ, Csontos LG

Publication Types:

Letter

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5.) Thalidomide-induced toxic epidermal necrolysis.

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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.

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6.) Skin coverage with Biobrane biomaterial for the treatment of patients with toxic epidermal necrolysis.

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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.    

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7.) Captopril-induced toxic epidermal necrolysis and agranulocytosis successfully treated with granulocyte colony-stimulating factor.

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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.

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8.) Epidermal calprotectin in drug-induced toxic epidermal necrolysis.

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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.

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9.) Toxic epidermal necrolysis and graft vs. host disease: a clinical spectrum but a diagnostic dilemma.

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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.

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10.) Dermatological adverse effects with the antimalarial drug mefloquine: a review of 74 published case reports.

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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.

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11.) Toxic epidermal necrolysis in acquired immunodeficiency syndrome treated with intravenous gammaglobulin.

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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. tri@immu.rpa.cs.nsw.gov.au

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.

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12.) Clinical manifestations and outcomes in 17 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis.

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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.

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13.) Treatment issues in the care of patients with toxic epidermal necrolysis.

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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.

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14.) [Erythema multiforme. A heterogeneous pathologic phenotype].

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Minerva Stomatol 1999 May;48(5):217-26

Carrozzo M, Togliatto M, Gandolfo S

Dipartimento di Fisiopatologia Clinica, Universita degli Studi, Torino.

Mcarro@tin.it

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.

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15.) Blister fluid cytokines in cutaneous inflammatory bullous

disorders.

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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.

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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.

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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.

berthold.rzany@haut.ma.uni-heidelberg.de

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.

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17.) Toxic epidermal necrolysis occurring as a consequence of treatment with foscarnet.

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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.

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18.) Progressive bronchial obstruction associated with toxic epidermal necrolysis.

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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.

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19.) Would cyclosporin A be beneficial to mitigate drug-induced toxic epidermal necrolysis?

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Dermatology 1999;198(2):198-202

Paquet P, Pierard GE

Department of Dermatopathology, University of Liege, Belgium.

Gerald.Pierard@ulg.ac.be

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.

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

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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.

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21.) A study of the efficacy of plasmapheresis for the treatment of drug induced toxic epidermal necrolysis.

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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.

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

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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.

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23.) Plasmapheresis as an adjunct treatment in toxic epidermal necrolysis.

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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.

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24.) Biological skin covers in treatment of two cases of the Lyell's syndrome.

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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. ferko@pmf.pmfhk.cz

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.

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25.) Hypopharyngeal stenosis and dysphagia complicating toxic epidermal necrolysis.

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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.

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26.) Soluble fractions of tumor necrosis factor-alpha, interleukin-6 and of their receptors in toxic epidermal necrolysis: a comparison with second-degree burns.

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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.

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27.) Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis.

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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.

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28.) [Ocular manifestations and sequelae of Lyell syndrome caused by sulfadoxine-pyrimethamine in Cameroon].

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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.

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

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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.

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30.)Lamotrigine-induced severe cutaneous adverse reactions.

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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.

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31.) Cotrimoxazole induced toxic epidermal necrolysis in a suspected case of Pneumocystis carinii pneumonia with human immuno deficiency virus infection.

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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.

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32.) Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.

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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.

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33.) Toxic epidermal necrolysis with severe gastrointestinal mucosal cell death: a patient who excreted long tubes of dead intestinal epithelium.

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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.

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34.) Toxic epidermal necrolysis syndrome: mortality rate reduced with early referral to regional burn center.

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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.

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35.) Gelatinases in drug-induced toxic epidermal necrolysis.

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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.

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36.) Case report: oxaprozin and fatal toxic epidermal necrolysis.

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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.

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37.)[Undesired drug effects after taking chlormezanone (Muscle Trancopal) with lethal results].

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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.

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38.) Treatment of the cutaneous involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis with silver nitrate-impregnated dressings.

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Arch Dermatol 1998 Jul;134(7):877-9

Lehrer-Bell KA, Kirsner RS, Tallman PG, Kerdel FA

Publication Types:

Letter

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39.) Oral manifestations of toxic epidermal necrolysis (TEN) in patients with AIDS: report of five cases.

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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.

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40.) Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in northeastern Malaysia.

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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.

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41.) Toxic epidermal necrolysis associated with treatment for preterm labor.

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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.

Dockx@IBM.net

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.

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42.) [A case of Lyell's syndrome caused by carbamazepine].

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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.

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43.) [Toxic epidermal necrolysis after the use of intermediate dose of cytosine arabinoside].

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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.

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44.) Toxic epidermal necrolysis in a burn patient complicated by acute pancreatitis.

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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.

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45.) Vulvovaginal involvement in toxic epidermal necrolysis: a retrospective study of 40 cases.

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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.

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46.) Toxic epidermal necrolysis: an analysis of referral patterns and steroid usage.

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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.

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47.) Toxic epidermal necrolysis syndrome versus mycosis fungoides.

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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.

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48.) Toxic epidermal necrolysis.

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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.

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49.) Heterotopic ossification as a complication of toxic epidermal necrolysis.

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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.

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

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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.

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

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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.  

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52.) Photo-induced toxic epidermal necrolysis caused by clobazam.

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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).

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

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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.  

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

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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.

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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.

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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.

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

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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.

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

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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.

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

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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.

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59.) Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum.

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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.

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

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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.

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61.) Metabolic predisposition to cutaneous adverse drug reactions. Role in toxic epidermal necrolysis caused by sulfonamides and anticonvulsants.

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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.

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62.) Epidemiologic approaches to the study of toxic epidermal necrolysis.

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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.

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63.) The spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis: a clinical classification.

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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.

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64.) Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis [see comments]

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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.

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

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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.

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

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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 dermato pathological study of patients with EEMM, SJS and TEN indicates that the epidermal type of erythema multiforme is the pathological correlate for these diseases.

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67.) Management of severe toxic epidermal necrolysis in children.

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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.

sheridan.robert@mgh.harvard.edu.

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.

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68.) Vulvovaginal sequelae in toxic epidermal necrolysis.

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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.

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

Stevens-Johnson syndrome and toxic epidermal necrolysis.

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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.

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

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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.

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71.) Burn center care for patients with toxic epidermal necrolysis [see comments]

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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 epidermolysis, 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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DATA-MÉDICOS/DERMAGIC-EXPRESS No 2-(88)  09/02/2000 DR. JOSÉ LAPENTA R. 

UPDATED 13 JULY 2025

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Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.025

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.025

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