Annals of Burns and Fire Disasters - vol. XI - n. 4 - December 1998

LYELL'S SYNDROME MANAGEMENT IN A BURN UNIT.
COVERAGE WITH CRYOPRESERVED ALLOGRAFT

Garcia Bernal F.J., Torrero V., Regalado J., Ferdinandez Samaniego F., Gabilondo F. J.

Department of Plastic and Reconstructive Surgery and Burn Centre, Cruces Hospital, Bilbao, Spain

SUMMARY. Eight cases of Lyell's syndrome or toxic epidermal necrolysis are described that have been managed in the Cruces Hospital Burn Centre in the last five years. The therapeutic approach to the patients is presented, describing the methodology of the systemic treatment and the disease's cutaneous manifestations. Along with the general treatment scheme, the topical care of the cutaneous manifestations is presented. Cryopreserved allografts obtained from our skin bank were used as a skin coverage tool.

Introduction

Clinically, Lyell's syndrome and the StevensJohnson syndrome or toxic epidermal necrolysis are a severe form of exfoliative den-natitis accompanied by systemic changes that share certain clinical and anatornopathological aspects with the disorders caused by intermediate second-degree burns.
In most cases a pharmacological aetiology is present. Other factors indicated as aetiological factors in Lyell's syndrome are micro-organisms, food, and other elements exerting an antigenic action.
In the therapeutic approach, fluid loss replacement and restoration of the dermoepidermic barrier are priorities, as well as an infection control policy by means of isolation of the patient. For these reasons, in our experience, such patients could benefit from management in a burns unit.

Clinical picture

The cutaneous manifestations of Lyell's syndrome begin as a pruriginous erythema and mild discomfort in the face and upper thorax, which extend through the extremities within a few days. The erythema turns into a bullous, exfoliative lesion that is macroscopically similar to a superficial second-degree scald burn. When there are no complications, this cutaneous affection tends towards spontaneous wound healing in less than two weeks, with no scarring.
In its severest forms, the cutaneous affection covers 100% of the body surface. Characteristically the palms and soles are affected.
The oral, ophthalmic, urogenital and rectal mucosae are typically affected. Perioral crusting may impair oral nutritional support. Oropharyngeal involvement causes a troublesome cough. Haernaternesis and melaeria are occasionally seen secondary to intra-oral, oesophageal, gastric or intestinal mucosal haemorrhages. The gastrointestinal tract mucosa may be affected at any level, with manifestations such as rectal bleeding and proctalgia occasionally being present.
Urogenital mucosa involvement causes dysuria and itching. Ophthalmic mucosa involvement may produce photophobia, conjunctivitis and synechia, which compromise the integrity of visual function.
The syndrome is characteristically accompanied by fever and severe pain.
Nikolsky's sign, or skin exfoliation with minimal trauma, although not specific, is often found when we examine these patients.

Histopathology

The final diagnosis is always defined by skin biopsy. The histological study reveals an eosinophilic necrosis with subepidermal blisters with a den-noepidermal exfoliation level. There is a minimal inflammatory response and immunofluorescence tests are negative.

Practical approach to treatment

Treatment of the condition has three primary goals:

1. haemodynarnic stability
2. pain management
3. infection control policy

With regard to this last goal, it is our opinion that isolation of the patient in a burns unit greatly improves infection control as well as guaranteeing adequate skin coverage.
The management protocol consists of: 

• monitoring of various parameters used in burn patients: pulse rate, arterial pressure, body temperature, central venous pressure, percentage of oxygen-haemoglobin saturation, urine output, etc.
• laboratory tests to cheek fluid requirements
• periodic surface cultures of the regions affected and blood cultures if there is fever above 38.5 °C (101.3 °F) 
• management of the patient on an air-fluidized bed in order to avoid decubitus ulcers and to obtain an adequate temperature and humidity state
• intravenous access through a central line for fluid therapy
• enteral nutrition if oral feeding is impaired, or parenteral feeding if mucosal damage is present
• intravenous narcotics for pain control, such as morphine 0. 1 rng/kg/24 h
• oral antiacids for gastric stress ulcer prophylaxis no empirical antibiotherapy is indicated, either systemic or topic. If any infectious process is present, a specific therapy is applied by means of cultures and antibiograms
• we do not indicate steroid therapy, in the light of numerous articles that have found a relationship between a higher mortality rate and the initiation of this therapy
• the management of the wound is performed under sedation and analgesia, with Midazolam and Fentanyl, in adequate doses, in relation to the patient's body weight. Skin cultures are taken, loose devitalized epidermis and blisters are removed, and the resulting wound is covered with cryopreserved allografts if the damaged skin exceeds 15% of the body surface

Wound management

First of all a calculation is made of the affected surface area, reckoning that 1% equals 150-180 cm². It is advisable to calculate the injured area periodically, as the initial erythema may develop into exfoliative lesions, thus becoming an injured area susceptible to coverage.
The cryopreserved allografts proceed from our skin bank and are unfrozen by immersion in warm water (Fig. 1).

Fig. 1 - Allografts from skin bank unfrozen by water- immersion.

The allografts are applied on the de-epithelialized areas using an aseptic technique. For fixation of the allografts we employ a xerofonn and soft gauze dressing (Figs. 2, 3).

Fig. 2 - Allograft placed on sterile gauze before application on skin. Fig. 3 - Allografts applied under aseptic conditions on, deepithelialized skin, using only xeroform gauze without any fixation system.

The use of an airfluidized bed (Fig. 4) is advised for the patient's comfort and in order to facilitate wound epithelialization.
The external dressings are changed periodically in relation to clinical evaluations. The allografts remain attached to their bed until they peel off after about 10-12 days, by which time the epithelial layers have been restored. If there is any sign of infection, the allografts must be removed and replaced.

Fig. 4 - Air-fluidized bed to facilitate wound epithelialization.

Case reports

Case 1.
45-yr-old man, twice operated for detachment of the retina. Admitted to the burn unit after a one-week history of itching, 38 °C fever, and a cutaneous rash involving 90% of the total body surface area (TBSA), as well as involvement of mucosal surfaces (Figs. 5a, b). Skin biopsy confirmed Lyell's syndrome. Treatment consisted of fluid infusion, use of an air-fluidized bed, morphine, and enteral and parenteral support. On the third day after admission the exfoliative skin was removed and the resulting wound covered with cryopreserved allografts. Epithelial regeneration was complete, without any sequelae, two weeks after admission.

Fig. 5a - Case 1. Exfoliative disorder all over body surface. Fig. 5b - Case 1. Epidermal exfoliation.

Case 2.
35-yr-old man, HIV-positive, suffering from Pneumocystis carinii, cerebral toxoplasmosis, oral mycosis, genital herpes, and tuberculosis. After a seizure episode the patient was treated with phenytoin. 24 h later he began to present itching, fever, a skin rash involving 90% TBS, and a severe mucosal affection. General measures of patient management were adopted and on the fifth day after admission the wound was covered with cryopreserved allografts. Eight days later the skin was completely regenerated (Figs. 6a, b, c, d, e, f). Skin biopsy diagnosis indicated Lyell's syndrome.

Fig. 6a - Case 2. Positive Nikol sky's sign. Fig. 6b - Case 2. Allografting.

Fig. 6d - Case 2. Exfoliation of skin and positive Nikolsky's sign. Fig. 6e - Case 2. Allografting. Fig. 6f - Case 2. Restitutio ad integrum of skin.

Case 3.
72-yr-old man treated with diuretics, digitalis and allopurinol. Referred 8 days' history of fever and progressive exfoliative skin disorder affecting 70% TBSA, as well as Nikolsky's sign and severe mucosal damage. 48 h after admission and administration of general care measures, allografts were applied for wound coverage. Wound healing was complete in seven days. Lyell's syndrome confirmed by skin biopsy.

Case 4.
44-yr-old male, HIV-positive in terminal phase, with bronchopulmonary source of sepsis. When treatment with ceftriaxone was initiated, the patient developed fever, itching, and a cutaneous exanthema on the face, which in 48 h became a generalized exfoliative skin disorder with mucosal involvement, the palms and soles also being injured. The patient died three days after admission, before skin coverage could be performed. Skin biopsy confirmed the diagnosis.

Case 5.
35-yr-old male, HIV-positive, with herpes zoster, brain tumour, and oesophageal candidiasis. Treated with phenytoin after a seizure episode. A few hours later generalized itching developed, together with fever and a blistering skin reaction on the face, extending to the trunk and extremities. Within 48 h the skin disorder had become general with a positive Nikolsky's sign. The patient died as a consequence of multi-organic dysfunction. Skin biopsy indicated Lyell's syndrome.

Case 6.
4-yr-old schoolboy, suffering from fever, itching and a skin rash after trimethoprim - sulphamethoxazole treatment for a bronchopulmonary process. Within 24 h the rash, which was first limited to the face, extended to the upper extremities, chest, palms, and soles, along with mucosal damage. The above-described treatment was established and allografts were applied. Skin regeneration was complete in 10 days and the patient was moved to the paediatric area for treatment of the bronchopulmonary process. Skin biopsy confirmed the diagnosis.

Case 7.
9-yr-old boy treated with carbamazepine for seizures. After a few h, onset of fever and cutaneous rash in the face. After 48 h the rash became an exfoliative dermatitis in nearly 100% TBSA with severe mucosal damage. After debridement of the blisters the wound was covered with cryopreserved allografts. Skin completely regenerated 14 days after admission. Skin biopsy was positive for Lyell's syndrome.

Case 8.
44-yr-old woman admitted to the burns unit suffering from itching, fever, and a facial rash which progressively extended to the upper extremities and trunk, with severe mucosal damage. TBSA affected was 45%. The patient had been treated with Ampicillin for an oropharyngeal affection. Treated as described above, without skin allograft for the wound. Skin regeneration was complete in 10 days. The patient suffered the complication of gastrointestinal bleeding and sepsis due to Acinetobacter baumanii. Discharged from hospital 22 days after admission. Skin biopsy positive for Lyell's syndrome.

Discussion

Toxic epidermal necrolysis is mainly a severe mucocutaneous exfoliative reaction that requires systemic treatment along with several topical measures. It is essential in the diagnosis phase to search for the drug intake antecedent. Cutaneous isolation measures, control of infection, and the management of cutaneous coverage improve the symptoms and facilitate evolution of the injuries towards epithelialization. Mucosal hygienic measures are of fundamental importance to increase the patient's comfort and to prevent the appearance of complications and sequelae. Steroid therapy is not administered in our burn centre, in line with the experience of other clinicians. The empirical administration of systemic or topical antibiotics is not indicated, unless there is a concomitant infectious process, in which case a specific antibiotic is used, as indicated by the cultures and antibiograms. For wound coverage we employ a biological skin substitute, cryopreserved allograft, in order to prevent infection, diminish pain, and prevent fluid losses, thus contributing to homeostasis.

Conclusions

Lyell's syndrome is a severe disease with a high mortality rate in which systemic treatment, along with meticulous cutaneous management, is essential. Considering the syndrome's clinical features, Lyell's syndrome patients would benefit from the management of their pathology in a burn centre/unit.
In our experience, the cryopreserved allograft is an ideal tool to promote recovery of the cutaneous barrier because it helps to diminish fluid losses, the intensity of inflammation, pain, and the risks of infection.

RESUME. Les Auteurs présentent huit cas du syndrome de Lyell ou la nécrolyse épidermique toxique qui ont été traités dans le Centre des Brûlures de l'Hôpital Cruces (Bilbao, Espagne) dans les derniers cinq ans. Ils présentent l'approche thérapeutique employée pour les patients, avec une description de la méthodologie du traitement systémique et des manifestations cutanées de la maladie. Ils présentent en outre le plan général du traitement et les soins topiques pour les manifestations cutanées. Pour la couverture de la peau ils ont utilisé des allogreffes obtenues dans leur banque de la peau.

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