Annals of*the MBC - vol. 5 - n' 3 - September 1992


Pousa F., Valero J., Vazquez-Barro A., Trincado S.

Burns Unit, Juan Canalejo Hospital, La Coruha, Spain

SUMMARY. Three cases of Stevens-Johnson syndrome are described. This syndrome is characterized by extensive loss of tffe epidermis and other complications. The cutaneous lesions are similar to second-degree burns in their development, and they benefit from temporary coverage with cryopreserved allografts, as may be performed in a Burns Centre.

Burns Units are referral centres for the treatment of patients suffering from considerable cutaneous loss(1,2), sometimes aetiologically distinct from burns, such as those caused by disseminated intravascular coagulation, traumatic avulsions and exfoliative dermAtitis complaints, among which the Stevens-Johnson syndrome (S.J.S.) is significant.
S.J.S. has an acute, self-limiting systemic clinical setting characterized by extensive and painful loss of the epidermis with skin, mucous membrane and corneal involvement, accompanied by general symptoms such as tachycardia and fever (3). Nutritional requirements are augmented, as are fluid losses via the lesioned skin.
The cutaneous lesions, equivalent to seconddegree burns in their development and treatment (1,4), benefit from the provision of a suitable temporary coverage with cryopreserved allografts (2).

Case reports
Case 1
A 17-year-old female, weighing 56 kg, presented an exfoliative dermatitis affecting 95% of the total body surface. The clinical setting had started ten days previously with a reddish macular exanthem in areas exposed to light (face, neck and hands). On these exanthematic lesions vesicles with a serous content appeared which developed into blisters, leading to an extensive loss of epidermis. There was no past history of drug taking, viral infection or recent vaccinations. On admission, besides the cutaneous lesions, there were also severe lesions of the oral, conjunctival and vaginal mucous membranes and a temperature of 40 'C. High doses of corticosteroids and systemic prophylactic antibiotics were administered. Analysis showed granulocytopenia-derived leukopenia and slight normocytic/normochromic anaemia. Haemocultures were methicil lin -resistant Staphylococcus aureus positive; cutaneous cultures obtained from wounds in the trunk and extremities were Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae and enterococcus positive. A pre-admittance biopsy of skin from the affected areas showed the existence of subepidermic vesicles with a necrotic epidermis ceiling and a denuded, festinated papillary dermis floor, with perivascular distribution of mononuelear inflammatory infiltration, all characteristic of S.J.S.
Treatment was based on gradual elimination of the corticosteroids, initiation of prophylaxis of the stress ulcers with oral sucralphate, and nutritional support with oral supplements. Empiric treatment of the sepsis with aztreonam and vancomycin was effective and unmodified thereafter.
Among other steps taken were the removal of a central venous catheter, substituted by a peripheral catheter, and the removal of the bandages. Zinc sulphate was applied topically. The cutaneous lesions of the rear trunk and upper extremities worsened 72 hours after admission, necessitating surgery under general anaesthesia for the debridement and coverage of extensive areas with cryopreserved allografts, maintaining exposure after the operation. The general condition improved, as did granulocyte recounts as leukopenia disappeared. Eight days after surgery the trunk and extremities were epithelialized. The patient was released 11 days after surgery.

Case 2
A 7-year-old female, weighing 28 kg, was admitted five days after the onset of a generalized maculovesicular exanthem which began on the thorax and abdomen and extended to the face and extremities, affecting 65% TBSA. The lesions were accompanied by fever, but no other systemic symptoms, and slight irritation of oral, vaginal and rectal mucosae and ocular conjunctivae. Treatment with methylprednisolone, total parenteral nutrition via the right subclavian artery and antibiotic prophylaxis with cefotaxime and cloxacillin had been started on admittance to hospital before transfer to this Unit. Analysis showed severe leukopenia but apart from the temperature nothing indicated sepsis. Biopsy of skin from the aftected areas confirmed the clinical diagnosis. The corticosterolds were gradually eliminated and the prophylactic antibiotherapy suspended. Total parenteral nutrition was suspended and the central catheter removed, being replaced by oral dietetic supplements. Topical therapy consisted of debridement of the aftected areas and coverage using cryopreserved allografts. The cutaneous lesions and leukopenia reacted favourably and the patient was released 15 days after admission.

Case 3
A 75-year-old man developed an exfoliative dermatitis 10 days after taking allopurinol for hyperuricaemia; 64% TI1SA was involved, mainly on the limbs and thorax. The oral mucosa and the cornea were also involved. He was transferred to the Burns Unit five days after developing the rash, with a treatment based on prophylactic antibiotics, steroids an parenteral nutrition.
After admission the steroids were gradually withdrawn, the antibiotics were removed, prophylaxis of the stress ulcers with sucralphate was performed, the central venous catheter was replaced by a peripheral one and nutritional support was given with oral supplements.
A skin biopsy specimen taken to determine the level of epidermal separation showed necrosis of the upper 4 to 5 epidermal cell layers, with cleavage occurring mainly at the suprabasal epidermal layer.
The wounds were treated initially with zinc sulphate, and 24 hours after admission with debridement and coverage with cryopreserved allograft under general exposure after the surgical operation.
Fifteen days after admission, when the areas of skin loss were completely re-epithelialized, the patient developed pneumonia and urinary infection. Empiric antibiotic treatment was initiated (imipenem and tobramycin). The infections were caused by Pseudomonas aeruginosa. The patient died of pulmonary failure 30 days after admission. anaesthesia, maintaining

The Stevens-Johnson syndrome is an acute, self-limiting systemic process characterised by painful, extensive loss of the epidermis affecting the skin, mucous membranes and corneas (5), accompanied by systemic symptoms such as fever and tachycardia (2,3,6,7). In 1957 Lyell related this clinical setting to exposure to several drugs such as the sulphonamides, phenobarbital, diphenylhydantoin, penicillin G sodium and penicillin G potassium, exposure to a staphylococcal toxin and also exanthematic viral diseases and their vaccines, no aetiological factors being found in 27% of cases (5,6,7).
In 1967 Koblenzer defined as a different entity the previously denominated Staphylococcic Syndrome (Scalded Skin Syndrome) (6), based on the fact that the location of the bullae was not in the dermoepidermal junction, as in cases of S.J.S., but in the upper layer of the epidermis(5,8). Mortality is lower (3% approximately) in the Staphylococcic Syndrome thanks to the efficacy of the antistaphylococcics (1,3,4,5,6,7,9).
S.J.S. is a severe form of erythema multiforme which most frequently affects children and young adults. Patients may present a prodromal period, characterized by fever, malaise and pharyngitis before eryt ema, although in severe cases these prodromes may be absent, as in the cases we report. Erythema usually appears on the lips and face as a diffuse redness or as dark papules with a red margin. 24 to 48 hours later blisters appear, and we observe a positive Nicholsky's sign and a temperature of 38-40 'C, with systemic toxic reactions, conjunctivitis and involvement of oral, vaginal, digestive and upper airway mucous membranes. Renal involvement develops in more than 50% of patients, usually due to hypovolaemia which causes acute tubular necrosis, but occasionally to progressive membranous glomerulonephritis or membranoproliferativeness, even several years after the acute episode (4,6,8, 10). It was difficult to ascertain if there was severe renal dysfunction in our patients, owing to their late admission. Pneumonia is common but can be treated successfully by conventional means (3,6).
If the patient lives, epithelialization from skin appendages is achieved in 10 to 28 days, but in some cases there are scars, contractures, oesophageal, urethral or vaginal strictures, permanent loss of nails or intestinal pneumatosis (7,11).
The patients we report were admitted to the Burn Unit as the complications deriving from the cutaneous lesions are similar to those of extensive second-degree burns, i.e. massive hydroelectrolytic loss, breakdown of thermic regulation, increase in catabolism, and the abolition of cutaneous antimicrobial protection. Although there is great fluid loss, resuscitation is less important than in the case of bums, perhaps due to the fact that there is no intense oedema secondary to the release of acute phase reactants, as occurs in burns.
The late admission of the cases reported is normal, given the difficulties of making medical personnel aware of the need to refer cases early in order to avoid lesion contamination, and to facilitate adequate coverage as soon as possible (1). Patients are admitted 5-6 days after the first symptoms, with extensive exfoliative lesions, frequently septic, and undergoing corticosteroid treatment. On admission central venous catheters are removed and replaced by peripheral ones, in order to reduce the risk of sepsis by catheter (3,4). Blood, catheter and wound cultures and lesion biopsies provide an accurate diagnosis.
Although for years high doses of corticosteroids have been used to check the progress of cutaneous lesions, to improve systemic toxicity signs and symptoms and to reduce temperature, it is now generally held that their use is erroneous as gastrointestinal ulcerations, Candida albicans and polymicrobial gram-negative septicaemia occur less frequently when they are not used. For this reason they are gradually suspended on admission to our unit.
Topical therapy consists of the application of zinc sulphate up to the time of coverage with cryopreserved allografts, although there are no studies which rigorously uphold its use. We do not believe in the use of gentamicin and other topical antibiotics because of the resistance and absorption risk which they present (4,6), or in the use of commercial preparations with polyethylene glycol, such as nitrofurazone, proved to be toxic when used for extensive burns. Perhaps the most used chemotherapeutic treatment in Bums Units is silver sulphadiazine, as it is easy to apply and has few sideeffects. It is not advisable in these cases, however, due to its relationship with the onset of the illness (8,12). Some authors recommend bandages soaked in silver nitrate 0.5%. These do not produce allergic reactions and do not inhibit epithelialization, but they can cause severe hyponatraemia if used extensively. They are also inconvenient, as they stain bedding and must be changed every 12 hours (2).
Fundamental to this discussion is the restriction in the use of the prophylactic antimicrobials even in the presence of leukopenia (3). Granulocytopenia causes leukopenia and its persistence leads to 'an elevated risk of infection, which is not well understood (2,4,5,6,7). It is thought that the greater incidence of septic complications in S.J.S. than in burns is perhaps due to the immunological defect, the involvement of mucous membranes, leukopenia, and epidermic necrosis.
Treatment includes measures normally taken in Burns Unit, such as nutritional support and dietetic supplements per os in order to avoid nasogastric tubes (1,3,7).
The treatment most specifically related to a Burns Unit with access to a skin bank was, for these patients, the use of cryopreserved allografts. At the present time, this is the closest to the ideal coverage available, as it reduces pain, hydroelectrolytic cutaneous losses and bacterial multiplication, improving thermoregulation and promoting reepithelialization (1,5). It is applied under general anaesthesia, avoiding endotracheal intubation so as not to increase damage to the upper airways which are often involved in the syndrome, after an operative debridement to slough-detached epithelium. If this biological dressing is unavailable, amnion or porcine cutaneous xenografts or skin substitutes may be used (1,3,7,8,13).
Two of these cases healed well, even though affected in more than 50% T13SA, which, together with the afore-mentioned granulocytopenia, would indicate a poor prognosis (5,10,12); with the exception of evident scars on the trunk of one patient, severe after-eflects were not seen at subsequen~ check-ups.
In conclusion, Burns Units provide specially trained personnel for topical care, intensive monitorization and the most aseptic environment possible, thereby of necessity improving results with S.J.S. patients.

RESUME. Les autevrs décrivent trois cas du syndrome de Stevens-Johnson, qui est charactérisé par la perte étendue de 1'&piderme et d'autres complications. Les 1ésions cutanées sont semblables aux brOlures du second degré dans leur développement, et elles bénéficient d'une couverture momentanée avec des allogreffes cryopréservées, qui peut &tre effectuée chez un centre de brùlés.


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