SKINIPEDIA - Skin Diseases: Toxic Epidermal Necrolysis

Skin Diseases and Conditions: Toxic Epidermal Necrolysis

A STUDY by Author: Victor Cohen, PharmD, Clinical Pharmacy Manager, Department of Emergency Medicine, Maimonides Medical Center, Assistant Professor, Division of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University

Medical Care

Management of toxic epidermal necrolysis (TEN) requires prompt detection, withdrawal of all potential causative agents, evaluation, and largely supportive care. Early transfer of patients with toxic epidermal necrolysis to a burn or intensive care unit has been shown to reduce the risk of infection, mortality rate, and length of hospitalization. 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.¹⁰ In 2007, these guidelines were revised by Fromowitz and colleagues.¹¹ 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. 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.

Nonpharmacological measures and therapies include the following:

• Withdraw all unnecessary medications.
• Withdraw the offending agent 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study showed a reduction in mortality from 26% to 5% when the implicated drugs with short elimination half-lives were withdrawn no later than the day the blisters or erosions first developed.
• Provide daily physical therapy for range-of-motion exercises.
• Place a central or intravenous line in areas of uninvolved skin.
• Consider the use of plasmapheresis, if available, daily for 3 days. Plasmapheresis may enhance elimination of the drug or offending agent or inflammatory mediators such as cytokines and should be considered.¹²
• Under general anesthesia, necrotic and desquamation areas are débrided within a few hours of admission.
• Apply porcine xenografts to involved areas.
• Irrigate the eyes every hour.
• 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.
• Administer Peridex mouthwash 4 times a day and white petrolatum to lips.
• Rinse the patient’s mouth frequently and apply a topical anesthetic or spray for buccal pain. Cyclophosphamide and cyclosporine have been used with some success, but no randomized controlled studies have been performed.
• Place the patient in a heated environment to enhance reepithelialization. However, this may enhance water losses, and appropriate hydration must be maintained. Institute a bed warmer.
• Place a Foley catheter and nasogastric tube only when needed.
• Consider blood transfusions when hematological complications, such as marked anemia, are evident.

Pharmacological therapies include the following:

• Start systemic antibiotics for documented infection or signs of sepsis.
• Emergence of resistance precludes the use of prophylactic antibiotics. Empiric antimicrobial therapy should include broad-spectrum antimicrobials that cover gram-negative, gram-positive, and anaerobic organisms. 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 when reepithelialization begins because intense pruritus may occur.
• Corticosteroids are commonly used to cease progression, but this is highly controversial. In some studies, corticosteroids have increased the incidence of mortality.
• Patients remain nonambulatory until skin begins to heal. Until that time, anticoagulant therapy is imperative. Heparin is indicated for prophylaxis of thromboembolic events.
• Saline applied to skin hourly is important, and then emollients are smeared.
• Chlorhexidine solution is used to bathe the patient's skin.
• Apply chloramphenicol ointment to prevent infection. Avoid use of silver sulfadiazine cream. Silvadene cream is a sulfa medication, a category of drugs often implicated as a cause of toxic epidermal necrolysis.
• If within 48-72 hours of bulla onset, use sucrose-depleted intravenous immunoglobulin 1 g/kg/d (infused over 4 h) for 3 days. If more than 72 hours have elapsed since the onset of bulla but the patient is still actively progressing with new lesions, intravenous immunoglobulin may still be useful.

Consultations

• Most patients with toxic epidermal necrolysis require specialized care under the direction of physicians with experience in handling this disorder. Burn-unit care represents an option worthy of serious consideration.
• A dermatologist is consulted to identify and to confirm toxic epidermal necrolysis.
• A plastic surgeon is consulted to débride areas of skin necrosis, as indicated.
• An ophthalmologist is consulted to prevent conjunctival-corneal adhesions, especially if vision is threatened. Ophthalmological complications are common and may require long-term treatment with corticosteroids.
• 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.

Toxic Epidermal Necrolysis Study - Medication - Part V is here

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