Management of Stevens Johnsons Syndrome and Toxic Epidermal Necrolysis

Diagnosis

TEN  and SJS are characterized by:

·       Typically, the disease process begins with influenza-like symptoms which are a part of a 1- to 14-day prodrome during which fever, sore throat; chills, headache, and malaise may be present.

·       Mucocutaneous lesions develop abruptly. The rash can begin as macules that develop into papules, vesicles, bullae, or confluent erythema. Characteristic skin lesions are flat, irregular, atypical target lesions or diffuse purpuric macules that frequently have necrotic centers (particularly in TEN) and tend to coalesce over the course of time.

·       In TEN, loss of epidermis is often sheet-like with a frequently positive Nikolsky sign (in which there is lateral displacement of the necrotic epidermis in response to slight pressure). As a result of cell death in the basal layer and stratum spinosum, the epidermis detaches from the dermis, giving rise to flaccid blisters. Although minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, gastrointestinal, and lower respiratory tract mucous membranes may develop in the course of the illness. Gastrointestinal and respiratory involvement may progress to necrosis.

·       Ocular involvement is seen in many patients with typical manifestations.

The physician is responsible for the early recognition of the reaction and the withdrawal of all potentially responsible drugs, especially those introduced within 1 month from the reaction.

Even if SJS or TEN is primarily diagnosed clinically, the diagnosis should be confirmed through histopathology. Histopathology classically shows widespread keratinocyte apoptosis and full-thickness epidermal necrosis and detachment, whereas the underlying dermis is not greatly altered and the epidermidis is infiltrated by activated lymphocytes, mainly CD8 cells, and macrophage.

The differential diagnosis of SJS or TEN includes a variety of skin reactions such as erythema multiforme (EM) major and atypical EM major, acute generalized erythematous pustulosis, intermediate burns, generalized fixed bullous drug eruption, staphylococcal scalded skin syndrome, edematous erythroderma, bullous pemphigoid, paraneoplastic pemphigus, exfoliative dermatitis, and acute graft-versus-host disease.

Erythema multiforme (EM) presents as initial target-like lesions characterized by an erythematous raised and palpable rim surrounding a gray center, whereas lesions of the SJS/TEN group are flat. In addition to these clinical and etiologic differences, EM and SJS/TEN can be distinguished histologically.

Treatment

No treatment modality has been established as standard for patients with SJS/TEN. Obviously, withdrawal of the suspected offending agent is critically important.
Immunoglobulin: A therapy with intravenous immunoglobulin (IVIG) was adopted on the basis of the identification of the mechanism of keratinocytes apoptosis in SJS/TEN. Nevertheless, at present, there is no strong evidence supporting IVIG administration in these patients.
Corticosteroids: The use of corticosteroids is controversial. A retrospective comparative study reported that combination therapy with corticosteroid and IVIG shows a tendency to reduce the mortality rate in comparison with the administration of corticosteroids alone.
Further studies are needed to determine the true efficacy of other agents such as tumor necrosis factor-α inhibitors, cyclosporine, cyclophosphamide, plasmapheresis and thalidomide.
Treatment, therefore, is primarily supportive and symptomatic and is similar to the therapy for burn patients.
Optimal treatment of SJS/TEN involves a multidisciplinary approach.

·       Fluid replacement must be initiated using macromolecules or saline solutions. Early and continuous enteral nutrition reduces the risk of stress ulcer and enterogenic infection. Total parenteral nutrition should be started in patients with hemodynamic instability or who are unable to take food.

·       Control of infection is crucial in the management of these patients because the high mortality is mostly attributed to bacterial sepsis; however, antibiotic use is generally reserved for the presence of documented infections or signs of sepsis.

·        Given that the majority of patients have ocular involvement, an ophthalmologist often is needed to assess and minimize the risk of infection ocular damage with treatments including topical lubricants-antibiotics and steroid drops.

·       Also, treatment of multiorgan damage, and prevention of further systemic complications. Special attention to airway and hemodynamic stability and pain control.

http://journals.lww.com/drug-monitoring/Fulltext/2010/12000/Stevens_Johnson_Syndrome_and_Toxic_Epidermal.1.aspx?WT.mc_id=EMxj15x20101206xL3