Toxic Epidermal Necrolysis (TEN) Treatment & Management

Updated: Jun 07, 2022
  • Author: Samantha P Jellinek-Cohen, PharmD, BCPS (AQ-ID); Chief Editor: Michael Stuart Bronze, MD  more...
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Approach Considerations

Management of toxic epidermal necrolysis (TEN) requires prompt recognition of the disorder and withdrawal of all potential causative agents. The mainstay of treatment is supportive care until the epithelium regenerates. Supportive measures include isolation, fluid and electrolyte balance, nutritional support, pain management, and protective dressings. Early transfer of patients to a burn or intensive care unit has been shown to reduce the risk of infection, mortality rate, and length of hospitalization.

Withdraw the offending agent, if one is identified, as soon as possible. One observational study showed a reduction in mortality from 26% to 5% when the implicated drugs with short elimination half-lives were withdrawn no later than the day the blisters or erosions first developed.

No controlled prospective treatment studies or generally accepted guidelines exist. In 1991, Avakian and colleagues published the University of Florida treatment protocol for toxic epidermal necrolysis. [48] In 2007, these guidelines were revised by Fromowitz and colleagues. [49] The guidelines are as follows:

Monitor fluids and electrolytes. Administer fluids and titrate based on central venous pressure and urine output; on average, 3-4 L are needed in patients with 50% of the body surface area affected.

An ophthalmologic examination early is desirable, preferably by an ophthalmologist. [50, 37]


Prehospital Care

Prehospital care for patients with TEN is similar to that for patients with burns. Supplement with oxygen by face-mask as needed; do not perform prophylactic tracheal intubation. Prevent hypothermia with rewarming devices and blankets.

In severe TEN, the barrier function of the skin is compromised. Thus, contamination and evaporation must be minimized. The patient should be treated similarly to one with extensive burns, that is, with the application of sterile coverings. Fluid and pulmonary status must be carefully monitored.


Emergency Department Care

For the emergency physician, the two most important elements in the treatment of TEN are discontinuation of the offending drug and admission to a burn unit. [51] Evidence suggests that rapid institution of these two measures is associated with a more favorable prognosis. [52, 53]

Emergency department care should be directed toward the following:

  • Maintaining fluid and electrolyte homeostasis

  • Mitigating temperature loss-the patient’s room should be heated to a temperature of 25OC-28 OC. [54]

  • Providing adequate analgesia

  • Preventing secondary infection

Aggressive fluid and electrolyte management, pain control, and meticulous skin care are important. Fluid resuscitation with crystalloids should follow standard guidelines used for burn patients. However, patients with TEN typically require less aggressive fluid replacement than that of burn patients because of less severe microvascular injury.

A goal of resuscitation should be to maintain sufficient mean arterial blood pressure (ABP >65 mm Hg), central venous pressure (CVP 8-12 mm Hg), and central oxygenation (Svco2 >70%) for adequate tissue perfusion and renal perfusion. [30] Fluid management should be based on the physiologic endpoint of urine output of 0.5-1 mL/kg/h. [51]

Patients with extensive skin involvement require reverse isolation and a sterile environment. Areas of skin erosion should be covered with nonadherent protective dressings such as petrolatum gauze. Respiratory distress may result from mucosal sloughing and edema and may necessitate endotracheal intubation and ventilation.


Supportive Systemic Therapy

Due to the need for large volume fluid resuscitation and to allow for intravenous medication administration, a large bore intravenous catheter should be placed on a nonerythematous portion of the patient’s body.

The patient should be placed in a heated environment to enhance reepithelialization. However, this may enhance water losses, and appropriate hydration must be maintained. Institute a bed warmer.

Saline applied to skin hourly is important, and then emollients are smeared. Chlorhexidine solution is used to bathe the patient's skin. Chlorhexidine mouthwash is administered 4 times a day, and white petrolatum is administered to the lips. Rinse the patient’s mouth frequently and apply a topical anesthetic or spray for buccal pain.

Provide daily physical therapy for range-of-motion exercises.

Place a Foley catheter and nasogastric tube only when needed. A urinary catheter should be placed in patients with urogenital involvement to decrease the risk of both infection and added injury. [54]

Energy requirements for patients with TEN must be carefully calculated and nutritional support provided. Protein loss can be significant. [33] Enteral nutrition through a nasogastric or naso jejnual tube is preferred to parenteral nutrition when oral mucosal involvement is severe, at 20-25 kcal/kg/day.

Patients with mucosal vulnerability may have severe bleeding complications. Coagulation factors and blood counts should be held within the normal ranges, and transfusion of red cells, platelets, and plasma products should be considered when necessary. [30]

Ocular complications are common and can be debilitating. Early consultation with an ophthalmologist is recommended to assess and minimize the risk of ocular damage. Treatments with topical lubricants/antibiotics and steroid drops are often needed.

Wound care

Meticulous wound care is necessary to prevent secondary infection. Debate continues in the literature regarding whether or not to debride the wounds associated with toxic epidermal necrolysis. To date, no conclusive evidence supports early, late, or no debridement of the wounds. Cutaneous lesions heal in approximately 2 weeks; mucosal membrane lesions take longer.

If debridement of necrotic and desquamation areas is chosen, it is performed with the patient under general anesthesia. Apply porcine xenografts to involved areas.

Provide hydrotherapy (whirlpool) twice a day. Repair and replace porcine xenografts. Apply Kerlix dressings soaked in silver nitrate 0.5% to involved areas after each whirlpool session.

Collagen dressings have been found to inhibit the action of metalloproteinases and encourage wound healing through deposition and organization of freshly formed fibers and granulation tissue in the wound bed, creating a good environment for wound healing. [55]

Pharmacologic therapies

Emergence of resistance precludes the use of prophylactic antibiotics. Bacterial sampling of skin lesions should be performed the first day and every 48 hours. Indicators for antibiotic treatment include increased number of bacteria cultured from the skin with selection of a single strain, sudden decrease in temperature, or deterioration of the patient's condition.

Empiric antimicrobial therapy should include broad-spectrum antimicrobials that cover gram-negative, gram-positive, and anaerobic organisms. Staphylococcus aureus is the main bacteria present during the first days, with gram-negative strains appearing later. If staphylococcal infection is involved, administer an appropriate antistaphylococcal agent (ie, nafcillin/oxacillin for methicillin-sensitive organisms or vancomycin for methicillin-resistant organisms).

Provide pain relief with patient-controlled analgesia (PCA). Opiate analgesics for skin pain and anxiety are essential for comforting patients. Hydroxyzine may be used to relieve the intense pruritus that may occur when reepithelialization begins.

Patients remain nonambulatory until skin begins to heal. Until that time, anticoagulant therapy is imperative. Heparin is indicated for prophylaxis of thromboembolic events.

Apply chloramphenicol ointment to prevent infection. Silver sulfadiazine should be avoided because it is a sulfonamide derivative and may precipitate TEN. Silver compounds not utilizing sulfadiazine or other sulfa medications should be used because they assist in wound healing and prevent infection and bacterial growth.

No specific treatment modality has been proven effective, including the following:

  • Plasmapheresis

  • Corticosteroids

  • Cyclophosphamide

  • Cyclosporine

  • Tumor necrosis factor–alpha (TNF-alpha) inhibitors

  • Intravenous immune globulin (IVIg) [10, 56]

Multiple studies of these modalities have been completed, and multiple studies are ongoing. Completed studies have shown that either the risk of the medication outweighs the benefit or the data are inconclusive to support its utilization. Therefore, there is a significant need for randomized control studies to further evaluate potential treatment modalities in TEN.

Corticosteroids are commonly used to control progression of TEN, but this is highly controversial. In some studies, corticosteroids have increased the incidence of mortality.

Consider the use of plasmapheresis, if available, daily for 3 days. Although prospective randomized studies have not been performed, limited data suggest that plasmapheresis may enhance elimination of the drug or offending agent or inflammatory mediators such as cytokines and should be considered. [57]

Anti–TNF-α treatment has been reported to rapidly resolve skin lesions due to TEN. TNF-α is strongly expressed in keratinocytes and macrophages of lesional skin, and high concentrations are found in cutaneous blister fluid.

Sucrose-depleted IVIg 1 g/kg/d (infused over 4 h) for 3 days may be beneficial if started within 48-72 hours of bulla onset. If more than 72 hours have elapsed since the onset of bulla but TEN is still actively progressing, with new lesions, IVIg may still be useful.

TEN patients with neutropenia tend to have a poor prognosis due to their increased risk of developing an infection. In these patients, granulocyte colony-stimulating factor may be beneficial. [58]

Menstrual suppression may reduce the risk of vaginal adenosis and endometriosis and can be considered in patients with severe genital mucosal involvement. Topical estrogen has been shown to promote healing in other vulvular dermatoses and burns and should be considered as adjuvant therapy. [59]



Most patients with TEN require specialized care under the direction of a team of physicians with experience in handling this disorder. Burn-unit care represents an option worthy of serious consideration.

Required consultations may include the following:

  • A dermatologist is consulted to identify and to confirm the diagnosis of TEN

  • A plastic surgeon is consulted to debride areas of skin necrosis, as indicated

  • • An ophthalmologist is consulted for assisting in the evaluation and possible  treatment of ocular manifestations and preventing long-term sequelae, with consideration for surgical interventions including amniotic membrane transplantation [60, 50, 37]  
  • An internal medicine specialist is consulted to assist in patient treatment

  • Consultation with a respiratory medicine specialist may be important, since respiratory mucosa may slough; establishment of pulmonary toilet may be advisable

  • Otolaryngologic or urologic consultation may be helpful in patients with significant mucous membrane involvement of those areas.



Parenteral nutrition or nutrition provided enterally via a soft-fine bore nasogastric tube is usually needed. Start total parenteral nutrition in patients unable to take nourishment. Early and continuous enteral nutrition reduces the risk of stress ulcers, reduces bacterial translocation and enterogenic infection, and allows earlier discontinuation of venous lines. [61]



Encourage mobilization. Involve physiotherapy for mobilization, those needing respiratory support and in those who are immobile and in need of passive exercises. [62]



There are currently no guidelines to prevent or minimize the risk of re-exposure in patients diagnosed with TEN. In the inpatient setting, when a diagnosis is made, the medical record should be updated to reflect the diagnosis in the allergies section with the severity categorized as critical. Prior to discharge, the diagnosis and implicated drugs/classes should be discussed with the patient and a plan for preventing re-exposure should be developed. The diagnosis should be communicated to the patient’s pharmacy and physicians. Medical identification jewelry should be obtained which include the brand and generic names of the allergen. Family members of TEN patients may be susceptible to the same drugs and should be counseled to avoid these medications when possible. [58, 63]


Long-Term Monitoring

Long-term gynecology care is recommended.

Pulmonary function tests performed during the usual follow-up display abnormalities presenting mainly as asymptomatic diffusion impairment, with a risk proportional to BSA involvement.