eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Treatment & Medication
Updated: Feb 20, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Recurrent EM minor is typically related to episodes of recurrent herpes simplexvirus infection and can be prevented by continuing use of antiviral agents.
Patients with Stevens-Johnson syndrome/toxic epidermal necrolysis should be treated in an ICU or burn unit under the coordinated care of an ICU team and consultants. Hospitalization should be considered for patients with an initially benign presentation of Stevens-Johnson syndrome because predicting which patients will progress to more severe manifestations or toxic epidermal necrolysis is not possible. The broad principles of management are fluid replacement, nutritional supplementation, sterile technique, and wound care. Studies have shown that early care by or transport to a burn center significantly reduces the mortality rate.
- Fluid replacement: Fluid rehydration is essential because epidermal loss results in massive fluid shifts and dehydration.
- Nutritional supplementation: Aggressive nutritional support should be initiated because protein losses through denuded skin are massive, predisposing the patient to complications and retardation of reepithelialization.
- Sterile technique
- Epidermal loss predisposes patients to infection and sepsis.
- Sterile technique is essential to prevent complications from endogenous and exogenous sources.
- Silver sulfadiazine must be avoided because sulfonamides are a frequent inciting drug in toxic epidermal necrolysis.
- Broad-spectrum prophylactic antibiotics are not recommended.
- Wound care
- Debridement of all necrotic epidermis with replacement by using biologic dressings, such as collagen-based substitutes or porcine xenografts, is recommended.
- Some physicians use biologic dressings only on denuded skin, leaving necrotic intact epidermis in place.
- Adhesive tapes should be avoided because further skin loss may occur at the site of application.
- Oral care and application of antiseptics may be necessary.
- Consultation with an ophthalmologist is essential.
- Frequently applied eye drops may be necessary with daily blunt disruption of synechiae.
- Eye drops must not contain sulfonamides because they are frequently implicated in toxic epidermal necrolysis.
- Other supportive treatment
- Because epidermal slough leads to massive heat loss, the environmental temperature should be increased to 30-32°C.
- Heated antiseptic baths, heat shields, infrared lamps, and air-fluidized beds may decrease heat losses.
- As a caveat, air-fluidized beds can pose an evaporative effect, and fluid status should be corrected prior to use.
Consultations
- Obtain an early consultation with a dermatologist because the prognosis and the course differ markedly for toxic epidermal necrolysis/Stevens-Johnson syndrome and other diseases in the differential diagnosis.
- Consultation with an ophthalmologist is essential because early lesions may be subclinical.
- Consultation with a pulmonologist is prudent because interstitial edema may be evident on chest radiographs prior to the appearance of clinical symptoms.
- Consultation with a GI specialist is appropriate in cases of suspected involvement of the GI tract.
Medication
The first step in medical treatment is withdrawal of causative drugs. Retrospective studies have indicated that early withdrawal decreases the mortality rate.9 Implicated medications are listed above (see Causes).
The use of corticosteroids in the management of the Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum is one of the most controversial areas in dermatology. Administration early in the course of disease has been advocated, but multiple retrospective studies demonstrate no benefit or higher rates of morbidity and mortality related to sepsis. This risk is probably proportional to the area of sloughed skin.
Halebian et al advised against the use of steroids based on 2 open nonrandomized prospective studies of corticosteroids in 30 patients admitted to a burn unit with Stevens-Johnson syndrome or toxic epidermal necrolysis.10 Fifteen patients received corticosteroids and 15 did not. The groups were statistically similar in terms of age, morbid days before burn center admission, and the amount of skin sloughed. Thirty-three percent of the steroid group survived versus 66% of the nonsteroid group (P = .057). Sepsis occurred with similar frequency in both groups, but 91% of those in the steroid group died versus 56% of those in the infected nonsteroid group.
Steroids are suggested to predispose patients to gram-negative sepsis by impairing host resistance and ultimately leading to late clinical recognition of sepsis by suppression of symptoms. Because multiple studies, albeit uncontrolled, have demonstrated a higher morbidity and mortality in patients receiving corticosteroids, most authorities do not recommend their use.
A number of studies support the use of IVIG in the treatment of toxic epidermal necrolysis. Viard et al suggested that apoptotic cell death occurs via activation of a cell-surface death receptor.4 In vitro, target cell death was blocked by a receptor-ligand blocking antibody and by antibodies present in pooled human IVIG. An open trial of IVIG in 10 patients with toxic epidermal necrolysis resulted in a halt of progression within 24-48 hours, with no mortality.
Since 2000, a number of case reports and 8 noncontrolled clinical studies containing 9 or more patients have analyzed the efficacy of IVIG in toxic epidermal necrolysis. Some studies have not demonstrated a therapeutic benefit, while others have shown decreased mortality.11,12,13 Six of the 8 studies suggested a benefit of IVIG at doses greater than 2 g/kg. Schneck J et al published a retrospective study of patients from France and Germany enrolled in EuroSCAR, a case-control study of risk factors. Neither IVIG or corticosteroids decreased mortality when compared with supportive care alone.14
Given the potentially fatal nature of toxic epidermal necrolysis and the ethical issues involved, a randomized controlled trial will likely never be performed. Given the suggestion of a therapeutic benefit, many centers are incorporating IVIG into their treatment protocols. At University Hospital at Stony Brook, New York, Stevens-Johnson syndrome/toxic epidermal necrolysis patients are treated with a dosage of 1g/kg/d for 4 consecutive days.
An open study from the trauma literature demonstrated the efficacy of cyclosporine. Arevalo et al presented 11 patients admitted consecutively to a burn unit, with toxic epidermal necrolysis involving a large BSA (83% ± 17%).15 Each received cyclosporine 3 mg/kg/d enterally every 12 hours. This group was compared to a series of 6 historical control subjects treated with cyclophosphamide and corticosteroids. The time from the onset of skin signs to arrest of disease progression and to complete reepithelialization was significantly shorter in the cyclosporine group. All patients in the cyclosporine group survived versus 50% surviving in the cyclophosphamide group. Given a mortality rate of approximately 30% in patients not infected with HIV with toxic epidermal necrolysis, cyclosporine may prove to be a life-saving therapy, but randomized controlled trials are needed to make definitive recommendations.
Cyclophosphamide, N- acetylcysteine, and monoclonal antibodies directed against cytokines have been used in isolated case reports and small uncontrolled studies. Thalidomide has been shown to have a deleterious effect on patients' outcomes.16
Only early transfer to and care in a burn unit has been demonstrated to decrease mortality. Coupled with early withdrawal of offending agents, this intervention is the best treatment that can be offered at this time.
Immune globulins
These agents are used to improve clinical and immunologic aspects of the disease. They may decrease autoantibody production, and they may increase solubilization and removal of immune complexes.
Immune globulin intravenous (Gamimune, Gammar-P, Sandoglobulin, Gammagard S/D)
IVIG may block target cell death by a receptor-ligand blocking antibody and by antibodies present in pooled human immunoglobin.
Adult
1 g/kg/d IV for 3 d
Pediatric
Not established
Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity; IgA deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Immunosuppressants
These agents inhibit key factors in the immune system responsible for immune reactions.
Cyclosporine (Sandimmune, Neoral)
May block production of pathogenic antibodies.
Adult
2.5-5 mg/kg/d PO in divided doses
Pediatric
Administer as in adults
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; methylprednisolone and cyclosporine mutually inhibit one another, resulting in increased plasma levels of each drug
Documented hypersensitivity; uncontrolled hypertension or malignancies
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
More on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
| Overview: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
| Differential Diagnoses & Workup: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
 Treatment & Medication: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
| Follow-up: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
| Multimedia: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
| References |
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References
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Inachi S, Mizutani H, Shimizu M. Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson syndrome. Contribution of perforin-positive cell infiltration. Arch Dermatol. Jul 1997;133(7):845-9. [Medline].
Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science. Oct 16 1998;282(5388):490-3. [Medline].
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Further Reading
Keywords
Stevens-Johnson syndrome, Stevens Johnson syndrome, toxic epidermal necrolysis, SJS, TEN
