CLINICAL AND COMMUNITY STUDIES ETUDES CLINIQUES ET COMMUNAUTAIRES

Toxic epidermal necrolysis: a burn-centre challenge Walter Peters, PhD, MD, FRCSC; Jawed Zaidi, MD, FRCS (Ire); Leith Douglas, MD, FRCSC Objective: To describe the clinical features and outcome of patients with toxic epidermal necrolysis. Design: Case series. Setting: Ross Tilley Burn Centre, Wellesley Hospital, Toronto. Patients: Ten patients (seven women) with toxic epidermal necrolysis referred to the centre from 1984 to 1990. Intervention: Biobrane (Winthrop Pharmaceuticals, New York) was applied to all raw surfaces after the epidermis had been completely separated. It was not removed until the epidermis had regenerated. Main results: The age of the patients varied from 27 to 90 (mean 45) years. The proportion of body surface area involved was 20% to 95% (mean 58.5%). Nine of the patients had received steroids and antibiotics prophylactically before being referred to the burn centre; the steroids were immediately tapered and the antibiotics withdrawn unless there was a specific infection. Urinary tract infection developed in seven patients, respiratory failure in six and systemic sepsis in six. All of the patients ultimately required antibiotics for treatment of systemic infections. Two patients died; both had severe illness before the onset of the toxic epidermal necrolysis. Biobrane provided a marked reduction in pain, eliminated the need for further dressings and allowed early, aggressive physiotherapy. The wounds healed completely within 14 to 21 days, with no significant scarring or need for skin grafting. Conclusions: The use of a temporary skin substitute is recommended for the treatment of toxic epidermal necrolysis. There is no indication for prophylactic steroid or antibiotic therapy; indeed, such therapy is probably contraindicated.

Objectif: Decrire les caracteristiques cliniques et l'issue de cas d'erythrodermie bulleuse avec epidermolyse. Conception: Serie de cas. Contexte: Centre des bruiles Ross Tilley, H6pital Wellesley, Toronto. Patients: Dix patients (sept femmes) atteints d'erythrodermie bulleuse avec epidermolyse envoyes au centre de 1984 a 1990. Intervention: On a applique de la Biobrane (Winthrop Pharmaceuticals, New York) sur toutes les surfaces a vif apres detachement complet de l'epiderme. La Biobrane n'a ete enlevee qu'apres la regeneration de l'epiderme. Principaux resultats: L'age des patients variait de 27 a 90 ans (age moyen de 45 ans). La proportion de la surface du corps atteinte variait de 20 % a 95 % (moyenne de 58,5 %). On avait administre des steroides et des antibiotiques par mesure prophylactique a neuf des patients avant de les transferer au centre des bruiles. On a reduit sur-le-champ les steroides et sevre les patients des antibiotiques sauf dans les cas d'infection specifique. From the Ross Tilley Burn Centre, Wellesley Hospital, Toronto, Ont., and the Division of Plastic Surgery, University of Toronto, Toronto, Ont.

Reprint requests to: Dr. Walter Peters, Ste. 224, Turner Wing, Wellesley Hospital, 160 Wellesley St. E, Toronto, ON M4Y IJ3 -

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Sept patients ont ete victimes d'infection des voies urinaires, six, d'insuffisance respiratoire et six, de septicemie generalisee. Tous les patients ont fini par avoir besoin d'antibiotiques a cause d'infections generalisees. Deux patients sont decedes: tous deux souffraient d'une maladie grave avant I'apparition de I'erythrodermie bulleuse avec epidermolyse. La Biobrane a reduit considerablement la douleur, supprime la necessite d'appliquer d'autres pansements et a permis d'administrer rapidement au patient une physiotherapie agressive. Les plaies se sont cicatrisees rapidement dans les 14 a 21 jours sans que les patients presentent de cicatrices importantes ou aient besoin de greffes de peau. Conclusions: On recommande d'utiliser un substitut cutane temporaire pour traiter les cas d'erythrodermie bulleuse avec epidermolyse. Rien n'indique qu'il soit recommande d'administrer des steroides ou des antibiotiques comme mesure prophylactique et il se pourrait meme qu'une telle therapie soit contre-indiquee.

T oxic epidermal necrolysis (TEN) was first described in 1956, by Lyell,l as an acute, generalized, sheet-like loss of epidermis resembling a scald burn. Histologic studies have shown that the plane of separation occurs at the epidermaldermal junction.2'3 TEN is distinct from a milder form of epidermal loss known as Staphylococcus scalded skin syndrome, which is caused by a staphylococcal toxin and is characterized by a separation site high in the epidermis.2'3 Over the years TEN has been described as a variant of erythema multiforme major, erythema multiforme exudativum, acute disseminated epidermal necrolysis, Lyell's disease and Stevens-Johnson syndrome.2'3 Although the exact cause of TEN is unknown it is usually associated with the ingestion of certain drugs. In some patients the condition may be part of a generalized systemic process or the result of a respiratory tract infection; in such cases the drugs may be incidental in the overall disease process. There is current agreement that steroid prophylaxis and systemic or topical antibiotic therapy are not effective and appear to be contraindicated.3-6 During the course of TEN, however, the development of pneumonia, sepsis and urinary tract infection may necessitate antibiotic therapy. The mortality rates in previous reports'-7 have varied from 75% to 100%. Because of the overwhelming problems with wound care and the subsequent potential for multisystem involvement it is generally agreed that patients with TEN are best managed in a formal burn centre. We describe 10 such patients referred to our burn centre and provide a treatment protocol.

Patients and methods We retrospectively reviewed the charts of all patients with TEN admitted to the Ross Tilley Burn Centre, Toronto, from 1984 to 1990. The criteria for inclusion were (a) presentation with the clinical characteristics of TEN and (b) confirmation of an epidermal-dermal cleavage plane on histologic analysis. The patients were evaluated according to dis1478

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ease progression, outcome.

complications, suspected cause and

Since regular dressing changes to exposed, raw skin surfaces are very painful for the patient and time-consuming for the nursing staff we investigated a more effective method of wound care. Biobrane (Winthrop Pharmaceuticals, New York), a temporary skin substitute,8 was applied to all raw surfaces after the epidermis had completely separated. In all cases the Biobrane was left intact until the epidermis had regenerated; thus, further dressing changes were avoided. We used a standardized wound treatment protocol,7 which is based on the hypothesis that the epidermal separation leaves denuded dermis with intact skin appendages. The dermis is completely viable and, if meticulously protected, will regenerate the epithelium in about 14 days without infection or scarring. The associated conjunctivitis and mucositis will also resolve if the eyes are protected, if the patient is well nourished and if sepsis is prevented. Our treatment protocol included the following steps. * Intravenous fluid resuscitation: the amount is usually considerably smaller than that given to patients with a comparable burn injury. * Early enteral feeding, usually through a small nasogastric tube, because of painful swallowing. * Use of an air-fluid bed (Clinitron bed; Support Systems International, Toronto). Such a bed eliminates the need for frequent, painful repositioning. * Complete avoidance of steroids. If their administration was started at the referring hospital the dose would be tapered. * Use of a narcotic for pain. * Avoidance of catheters since they could produce pain and erosion because of mucosal involvement. * Use of systemic antibiotic therapy for specific infections but not for prophylaxis. Topical antibiotic therapy is not used. * Meticulous eye care daily. A glass rod is used LE ler JUIN 1991

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to break down conjunctival synechiae in order to prevent subsequent tissue adhesions. 0 Meticulous wound care. Jelonet (Smith & Nephew Inc., Lachine, Que.) and moist saline gauze dressings are applied once daily. When most of the involved epidermal surface has sloughed off, usually 3 to 4 days after the onset of TEN, the patient is taken to the operating room and given a general anesthetic. All of the epidermis is then removed, and the wounds are vigorously washed with saline and a rough cloth. Biobrane is stretched under tension and stapled in place over all raw surfaces. The patient is then transferred to the intensive care area in the burn centre. The Biobrane is inspected daily; any collection of fluid is gently expressed. In most cases the Biobrane is left intact until the epidermis has regenerated, usually within 2 weeks. Ordinarily no other dressings are required.

illness preceded the onset of TEN, but no specific drug was found to be the cause. Eight of the patients survived, their in-hospital stay lasting 12 to 170 (mean 35) days. Of the remaining two patients one was 68 years old and had pre-existing chronic renal failure, diabetes mellitus and hypertension; he died on day 3. The other

Results During the study period 10 patients (7 women) were admitted to the burn centre for treatment of TEN. The age varied from 27 to 90 (mean 45) years. The proportion of body surface area involved varied from 20% to 95% (mean 58.5%). Nine of the patients had received steroids and antibiotics prophylactically before being referred to the burn centre. The steroids were immediately tapered on admission to our unit, and the antibiotics were stopped unless there was a specific infection. The condition frequently involved a prodrome phase, with fever, malaise and pharyngitis. Areas of erythema then developed and progressed to discrete papular lesions (Fig. 1). Over the next 1 to 3 days blisters and bullae formed over large areas of the skin (Fig. 2). These areas subsequently sloughed off (Fig. 3). During this critical phase wound care was particularly difficult, and the patients were extremely uncomfortable with pain. The mucous membranes of the mouth and eyes (Fig. 4), the oropharynx, the genitals and the rectum were eroded. Urinary tract infection developed in seven patients and necessitated antibiotic therapy. Respiratory failure occurred in six patients, all of whom required mechanical ventilation and antibiotics for pneumonia. A pneumothorax developed in one patient, who required the insertion of a chest tube. Systemic sepsis, confirmed by means of blood culture, occurred in six patients. Candidemia was detected in one patient and responded to systemic amphotericin therapy. A drug was strongly suspected as the cause in nine of the cases: amoxicillin in two cases, phenytoin in two, carbamazepine in one, chlorambucil in one, co-trimoxazole in one, erythromycin in one and etretinate in one. In the remaining case a flu-like JUNE 1, 1991

Fig. 1: Areas of erythema progressing to papular lesions in early stages of toxic epidermal necrolysis.

Fig. 2: Blisters and bullae form over large areas of skin during next 1 to 3 days.

Fig. 3: Entire surface of involved areas sloughs off. CAN MED ASSOC J 1991; 144 (11)

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patient was 74 years old and had widespread lymphoma, for which he was receiving chemotherapy; he died on day 4. As soon as the Biobrane was applied (Fig. 5) the pain and discomfort were markedly decreased. The patients were then able to undergo aggressive physiotherapy without further delay. The wounds healed completely, usually within 14 to 21 days after the onset of TEN. None of the patients required skin grafting. There was no significant scarring.

Discussion The survival rate of 80% in this series compares favourably with the rates in other series.'-7 The two patients who died had severe pre-existing illness. The use of xenografts (pigskin) has previously been described for temporary wound coverage in patients with TEN.7 We found that Biobrane was particularly effective: it markedly reduced the pain, eliminated the need for further dressings and in general facilitated healing. There appears to be no indication for the prophylactic use of steroids and antibiotics in cases of TEN.3-6 Such use is probably contraindicated: the antibiotic therapy would tend to promote the emergence of resistant organisms, and the steroid therapy may exacerbate any subsequent infection.3-6 Fig. 4: Mucous membranes of mouth (top) and eye (bottom) are eroded.

References 1. Lyell A: Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br JDermatol 1956; 68: 355-361 2. Idem: A review of toxic epidermal necrolysis in Britain. Br J Dermatol 1967; 79: 662-671 3. Rasmussen J: Toxic epidermal necrolysis. Med Clin North Am 1980; 64: 901-920 4. Halebian PH, Corder V, Herndon D et al: A burn centre experience with toxic epidermal necrolysis. J Burn Care Rehabil 1983; 4: 176-183 5. Halebian PH, Madden MR, Finkelstein JL et al: Improved burn centre survival of patients with toxic epidermal necrolysis managed without glucocorticoids. Ann Surg 1986; 204: 503512 6. Westly ED, Wechsler HL: Toxic epidermal necrolysis granulocytic leukopenia as a prognostic indicator. Arch Dermatol 1984; 120: 721-726 7. Heimback DM, Engrav LH, Marvin JA et al: Toxic epidermal necrolysis - a step forward in treatment. JAMA 1987; 257:

Fig. 5: Under general anesthesia temporay skin substitute is applied after debridement and is left intact until epidermis has regenerated.

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2171-2175 8. Phillips LG, Robson MC, Smith DJ et al: Uses and abuses of a biosynthetic dressing for partial skin thickness burns. Burns 1989; 15: 254-256

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Toxic epidermal necrolysis: a burn-centre challenge.

To describe the clinical features and outcome of patients with toxic epidermal necrolysis...
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