eMedicine Specialties > Ophthalmology > Dermatologic Disorders
Stevens-Johnson Syndrome: Treatment & Medication
Updated: Dec 18, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Supportive systemic therapy: Management of patients with SJS is usually provided in ICUs or burn centers. No specific treatment of SJS exists; therefore, most patients are treated symptomatically. In principal, the symptomatic treatment of patients with SJS does not differ from the treatment of patients with extensive burns.
- Fluid management is provided by macromolecules and saline solutions during the first 24 hours. Phosphate salts are necessary in the presence of hypophosphatemia. The amount of fluids required in patients with SJS is usually less than in those patients with burns covering the same body surface area.
- After the second day of hospitalization, oral intake of fluids provided by nasogastric tube is often begun, so that intravenous fluids can be tapered progressively and discontinued, usually in 2 weeks.
- Massive parenteral nutrition is necessary as soon as possible to replace the protein loss and to promote healing of cutaneous lesions.
- Intravenous insulin therapy may be required because of impaired glycoregulation.
- Patients with SJS are at a high risk of infection. Sterile handling and/or reverse-isolation nursing techniques are essential to decrease the risk of nosocomial infection.
- Cultures of blood, catheters, gastric tubes, and urinary tubes must be performed regularly.
- Because of the association between SJS and sulfonamides, avoid the use of silver sulfadiazine, which is commonly used in burn units; instead, use another antiseptic, such as 0.5% silver nitrate or 0.05% chlorhexidine, to paint and bathe the affected skin areas.
- Prophylactic systemic antibiotics are not recommended.
- The diagnosis of sepsis is difficult. Carefully consider the decision to administer systemic antibiotics. The first signs of infection are an increase in the number of bacteria cultured from the skin, a sudden drop in fever, and deterioration of the patient's condition, indicating the need for antibiotic therapy. The choice of antibiotic usually is based on the bacteria present on the skin. Because of impaired pharmacokinetics, similar to that present in burn patients, the administration of high doses may be required to reach therapeutic levels. Monitoring the serum levels is necessary to adjust the dosage.
- Environmental temperature raised to 30-32°C reduces caloric loss through the skin. Fluidized air beds are recommended if a large portion of the skin on the patient's backside is involved. Heat shields and infrared lamps are used to help reduce heat loss.
- Anticoagulation with heparin for the duration of hospitalization is recommended. Antacids reduce the incidence of gastric bleeding.
- Pulmonary care includes aerosols, bronchial aspiration, and physical therapy. Tranquilizers are used to the extent limited by respiratory status.
- Several skin care approaches have been described. Extensive debridement of nonviable epidermis, followed by immediate cover with biologic dressings, such as porcine cutaneous xenografts, cryopreserved cutaneous allografts, and amnion- or collagen-based skin substitutes, are among the recommended treatments. Leaving the involved epidermis that has not yet peeled off in place and using biologic dressings only on raw dermis also has been recommended. Skin allotransplantation reduces pain, minimizes fluid loss, improves heat control, and prevents bacterial infection. Hyperbaric oxygen also can improve healing.
- Immunomodulatory therapy: SJS is a rare disorder with relatively high mortality and morbidity rates. To date, because of a lack of consensus on the proposed therapeutic modalities, intensive supportive management and withdrawal of the offending drug remain the criterion standard. For any intervention, a prospective randomized controlled trial would be the most appropriate step to validate its use. However, a large number of patients are required to reach statistical significance. Furthermore, for ethical reasons, withdrawal of a potentially life-saving therapy for the sake of randomization with a placebo control is not possible.
- Several therapeutic modalities have been advocated for the treatment of SJS based on the current, yet incomplete, understanding of its pathogenetic mechanisms. Plasmapheresis, immunosuppressive therapy, and intravenous immunoglobulin (IVIg) have been used with variably successful results.
- The safety of systemic corticosteroids in the treatment of SJS is an issue that has been raised and is based on a few case series; in those reports, systemic corticosteroids were administered too late in the course of the disease, in inappropriately low doses, and for a very long duration that actually impaired the healing process and increased the risk of sepsis. The currently advocated approach for corticosteroid use suggests the early use of short-term (4-7 d), high-dose intravenous corticosteroids.12
- The role of other immunosuppressive therapy, that is, cyclosporine, azathioprine, or cyclophosphamide, in the acute phase is less popular, particularly since such medication typically takes weeks to begin to influence immunological reactions. Cyclophosphamide has been reported to be the culprit drug that induced SJS in one instance.13 Nevertheless, the role of cyclosporine in the treatment of the acute phase of SJS has been revisited, and, indeed, it showed encouraging results.5 Also, immunosuppressive therapy may play a pivotal role in the management of the chronic ocular surface inflammation that can take place later on in selected cases.
- The rational for the use of IVIg is the most appealing. Based on in vitro and clinical data, IVIg can block the Fas receptors on the surface of the keratinocytes, thus interfering with the Fas-Fas ligand mediated apoptosis.14 Encouraging results were reported when IVIg was used in high doses very early in the course of the disease and for a short period. Unfortunately, there is no consensus with regard to either the dose or the duration of treatment with IVIg.3
- Interestingly, few studies have addressed the effect of systemic steroids or IVIg on either the development or the outcome of ocular manifestations in SJS and TEN. Neither treatment appeared to have an effect on the ocular outcome in patients in two reports.15,1
Surgical Care
- Treatment of acute ocular manifestations
- Treatment of acute ocular manifestations usually begins with aggressive lubrication of the ocular surface.
- As inflammation and cicatricial changes ensue, most ophthalmologists use topical steroids, antibiotics, and symblepharon lysis.
- In case of exposure keratopathy, tarsorrhaphy may be required.
- Maintenance of ocular integrity can be achieved through the use of amniotic membrane grafting, adhesive glues, lamellar grafts, and penetrating keratoplasty, either in the acute phase or in subsequent, follow-up care.
- Visual rehabilitation in patients with visual impairment can be considered once the eye has been quiet for at least 3 months.
- Treatment of chronic ocular manifestations
- In the case of mild chronic superficial keratopathy, long-term lubrication may be sufficient. In addition to lubrication, some patients may require a cosmetically acceptable long-term lateral tarsorrhaphy. The visual rehabilitation in patients with severe ocular involvement, resulting in profound dry eye syndrome with posterior lid margin keratinization, limbal stem cell deficiency, persistent epithelial defects with subsequent corneal neovascularization, and frank corneal opacity with surface conjunctivalization and keratinization, is difficult and often frustrating for both the patient and the physician. A close, usually long-term, relationship between the patient and the physician needs to be established to achieve the best possible result.
- The removal of keratinized plaques from the posterior lid margins, along with mucous membrane grafting and/or amniotic membrane grafting, is usually the first step and one of the most important determining factors in the future success of corneal surgeries. Preferably, a skilled oculoplastic surgeon with specific experience on patients with SJS should perform this procedure.
- Subsequently, limbal stem cell transplantation and amniotic membrane grafting with superficial keratectomy removing conjunctivalized or keratinized ocular surface can follow. Patients with persistent corneal opacity require lamellar or penetrating keratoplasty in the next step, but each exposure to alloantigenic material increases the odds of tissue rejection. Therefore, the author’s advice is to strive for major, if not perfect, resurrection of the useful vision, rather than perform allografts of both eyes and keratoplasties.
- To preserve corneal clarity after the visual reconstruction, the long-term use of gas permeable scleral contact lenses may be necessary to protect the ocular surface. Long-term management frequently involves the treatment of trichitic lashes and/or eyelid margin repair for distichiasis or entropion. If the ocular surface repeatedly fails to heal upon multiple surgical interventions, keratoprosthesis may be considered as a last resort.
Medication
The goal of pharmacotherapy is to reduce morbidity and to prevent complications. For persistent or recurrent ocular inflammation, patients may benefit from short-term systemic corticosteroids and/or long-term immunosuppressive therapy, which may reduce severity of conjunctivitis and improve prognosis quod visum by reducing damage to ocular surface.
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.
Prednisone (Deltasone)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
5-60 mg/d PO; dose may be adjusted according to the severity of the condition and response
Pediatric
1-2 mg/kg/d PO; dose can be divided and given 1-2 times daily
Coadministration with estrogens may decrease prednisone clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections
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
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; administer appropriate antimicrobial coverage concomitantly if infectious causes are contemplated; if no clinical improvement or if disease progression does not stop within 48 h, increase dose or switch to another corticosteroid; if still no effect on arresting disease progression in 72 h, discontinue use; total treatment duration should be limited to <1 wk; if withdrawal results in reactivation of disease, reinstitute treatment with later tapering
Methylprednisolone (Solu-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
10-250 mg IV, may be repeated q4-6h as necessary; total dose usually does not exceed 1.5 g/24 h
Pediatric
0.5-2 mg/kg/d; dose can be individualized according to the severity of the disease
Coadministration with digoxin, may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug; reduced dose may be required in patients on cyclophosphamide
Documented hypersensitivity; viral, fungal, or tubercular skin infections
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
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; administer appropriate antimicrobial coverage concomitantly if infectious causes are contemplated; if no clinical improvement or if disease progression does not stop within 48 h, increase dose; if still no effect on arresting disease progression in 72 h, discontinue use; total treatment duration should be limited to <1 wk; if withdrawal results in reactivation of disease, reinstitute treatment with later tapering
Immunosuppressants
Inhibit key factors of the immune system, reducing overall immune activity.
Cyclosporine (Sandimmune, Neoral)
Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease for a variety of organs.
For children and adults, base dosing on ideal body weight.
Adult
Initial: 14-18 mg/kg/d PO 4-12 h before organ transplantation
Maintenance: 5-15 mg/kg/d PO qd or divided bid
Pediatric
Administer as in adults
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer
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 enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of immune cells.
Adult
500-750 mg/m2 PO
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
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)
Neutralize circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Adult
2 g/kg IV over 2-5 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 if deficient, 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
More on Stevens-Johnson Syndrome |
| Overview: Stevens-Johnson Syndrome |
| Differential Diagnoses & Workup: Stevens-Johnson Syndrome |
 Treatment & Medication: Stevens-Johnson Syndrome |
| Follow-up: Stevens-Johnson Syndrome |
| Multimedia: Stevens-Johnson Syndrome |
| References |
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References
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Further Reading
Keywords
SJS, toxic epidermal necrolysis, TEN, erythema multiforme, EM, erythema multiforme minor, von Hebra, erythema multiforme major, EMM
