Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder

characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and
mucous membranes, resulting in exfoliation and possible sepsis and/or death (see the image
below). Mucous membrane involvement can result in gastrointestinal hemorrhage, respiratory
failure, ocular abnormalities, and genitourinary complications. TEN is most commonly drug
induced. However, the disorder has other potential etiologies, including infection, malignancy,
and vaccinations (see Etiology). TEN is idiosyncratic, and its occurrence is not easily predicted.

Some authors believe that Stevens-Johnson syndrome (SJS; also known as erythema multiforme
major) is a manifestation of the same process involved in TEN, with the latter involving more
extensive necrotic epidermal detachment. TEN involves more than 30% of the body surface,
whereas SJS involves less than 10% (see Differentials).

A classification system, based largely on the extent of epidermal detachment and morphology of
the skin lesions, aids in differentiating opposite spectrums of the same disease entity.[1] This
system comprises the following:

TEN with spots

TEN without spots

Overlap Stevens-Johnson syndrome and TEN (SJS-TEN)

TEN with spots is defined as widespread, irregularly shaped erythematous or purpuric macules
with blistering that occurs on all or part of the macule. Blisters become more confluent and result
in detachment of the epidermis and erosions on greater than 30% of the body surface area.
Mucosal surfaces are usually involved.

TEN without spots is defined as widespread, large areas of erythema with no discrete lesions.
Epidermal detachment is greater than 10% of the body surface area. Mucosal surfaces are usually
involved.

Overlap Stevens-Johnson syndrome and TEN (SJS-TEN) is characterized by widespread,

irregularly shaped erythematous or purpuric macules with blistering that occurs on all or part of
the macule. Blisters become confluent and result in detachment of the epidermis and erosions on
10-29% of the body surface area.

TEN is a clinical diagnosis, confirmed by histopathologic analysis of lesional skin (see Clinical
and Workup). The mainstay of treatment is supportive care until the epithelium regenerates.
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 (see Treatment).

Historical background
Alan Lyell provided an early description of TEN in 1956, describing the condition as "an
eruption resembling scalding of the skin."[2] This dermatologic condition is characterized by
extensive epidermal loss suggestive of severe scalding. In that same year, Lang and Walker
reported a case of TEN.[3] The disorder was originally described by Debre et al in 1939 in French
as l'erythrodermie bulleuses avec epidermolyse.[4]

Lyell later reclassified the conditions of 2 of his patients as having staphylococcal scalded skin
syndrome,[5] which is due to Staphylococcus aureus infection rather than to a probable drug
hypersensitivity-type reaction. Histopathologic analysis of the skin remains the main tool for
discrimination between the two conditions.

Patient education

Patients who have had TEN must be counseled regarding the likely causative medication or
agent, and they must be advised to avoid these medications and those of the same or similar
classes in the future. Cross-reactivity may occur with agents that chemically resemble the
causative agent. Patients must call a pharmacist whenever they start a new prescription.

Genetic factors are suspected in drug-induced blistering disorders, and blood relatives of the
patient also should not use the suspected drug.

For patient education information, see the Skin, Hair, and Nails Center, as well as Life-
Threatening Skin Rashes.

Pathophysiology

The pathophysiology of TEN has not been fully elucidated; however, various theories have
received wide acceptance. TEN is believed to be an immune-related cytotoxic reaction aimed at
destroying keratinocytes that express a foreign antigen.

TEN mimics a hypersensitivity reaction, with its characteristic delayed reaction to an initial
exposure and an increasingly rapid reaction with repeated exposure.

The widespread epidermolysis and blistering of TEN results from keratinocyte apoptosisan
organized series of biochemical reactions leading to cell changes and cell death.[6] However, the
number of inflammatory T cells in the skin of patients with TEN is variable and perhaps too low
to explain the widespread destruction.[7]

There is evidence supporting several immunopathologic pathways leading to keratinocyte

apoptosis in TEN, including the following:

Fas ligand activation on keratinocyte membranes leading to death receptormediated apoptosis

[8]
 Release of destructive proteins (perforin and granzyme B) from cytotoxic T lymphocytes (CTLs)
generated from an interaction with cells expressing major histocompatability complex (MHC)
class I [9]

Overproduction of T cell and/or macrophage-derived cytokines (interferon- [INF-], tumor

necrosis factor- [TNF-], and various interleukins) [10, 11]

Drug-induced secretion of granulysin from CTLs, natural killer cells, and natural killer T cells [12]

Precisely how the inciting agent triggers the proposed pathways is yet to be elucidated.

TEN can be induced by drugs or infection or can be idiopathic. Medications are the major
precipitating cause. Numerous medications have been implicated,[13] including antibiotics,
antiepileptic drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), ampicillin, allopurinol,
corticosteroids (topical and systemic), and the antiretroviral drugs nevirapine and abacavir.[14, 15]

Antibacterial drugs associated with TEN include the following:

Sulfonamides (4.5 cases per million users per week)

Chloramphenicol

Macrolides (eg, erythromycin)

Penicillins

Quinolones (eg, ciprofloxacin, [16] trovafloxacin [17] )

Anticonvulsants associated with TEN include the following:

Phenobarbital

Phenytoin [18]

Carbamazepine

Valproic acid

Lamotrigine

TEN in patients taking anticonvulsants has most often been reported within 2 months of starting
the drug. However, some cases associated with long-term use have been reported.

NSAIDs associated with TEN include the following:

 Phenylbutazone and oxybutazone - Implicated most commonly, although they are no
longer available in the United States

Oxicams (eg, piroxicam, tenoxicam) - Implicated more often than other NSAIDs

Ibuprofen

Indomethacin

Sulindac

Tolmetin

With allopurinol, risk is not constant over time. Patients have a 5.5 relative risk. However, during
the first 2 months of therapy, the relative risk is 52, and the long-term therapy risk is 0.5.

No laboratory test is able to confirm a specific drug etiology. A causal link is suggested when
TEN occurs during the first 4 weeks of medication therapy, usually between 1 and 3 weeks.
Drugs with longer half-lives and those with circulating active metabolites may result in more
fulminant disease.

Infectious agents (ie, Mycoplasma pneumoniae, herpes virus, hepatitis A), immunizations, and
bone marrow or solid organ transplantation have also been associated with TEN.

Epidemiology

In the United States, the annual frequency of TEN is reported to be 0.22-1.23 cases per 100,000
population. In the HIV-positive population, the incidence of TEN increases to 1 case per
thousand per year.[19]

Worldwide, the average annual incidence of TEN is 0.4-1.3 cases per million population.[20] In
1992, the cumulative incidence of TEN and SJS in Germany was 1.9 cases per million
population. A French survey of dermatologists and health care facilities reported an annual
incidence of 1 case per million population.

Race-, sex-, and age-related demographics

A genetic predilection toward carbamazepine-induced TEN has been observed in HLA-B*1502

positive Han Chinese patients.[21] The US Food and Drug Administration recommends screening
for the HLA-B*1502 allele before initiating carbamazepine in patients of Asian ancestry.[22]

For unclear reasons, TEN appears to have a predilection for females. The female-to-male ratio is
1.5:1.[23]
TEN may occur in all age groups; however, the mean age of patients with TEN is reported to be
between 46 and 63 years. Infection is more commonly implicated as an etiology in children,
whereas medication exposure is more common in adults. Elderly persons may be at greater risk
because of their tendency to use multiple medications.

Prognosis

The estimated mortality associated with TEN varies widely in different reports, from 10-70%.
Outcome depends in part on the quality of care and the rapidity with which treatment is initiated.

Septicemia and multisystem organ failure are the primary causes of death. Epithelial loss results
in vulnerability to bacterial and fungal infections. Sloughing of stratified epithelium of mucosal
membranes can result in GI hemorrhage, respiratory failure, ocular abnormalities, and
genitourinary lesions. Significant fluid loss from extensive skin exfoliation and an inability to
tolerate oral intake can lead to hypovolemia, acute tubular necrosis, and shock.

Age, extent of epidermal involvement, and serum urea level are said to be the most important
prognostic factors in TEN.[24] Mortality rates in children are much lower than in adults.[25] Elderly
patients have a poor prognosis.

Other negative prognostic factors include the following:

Elevated blood urea nitrogen (BUN) and serum creatinine levels

Respiratory failure

Multiple drugs

Thrombocytopenia

Lymphopenia

Neutropenia

Leukopenia

Sepsis

Severity-of-illness score

A severity-of-illness score that estimates the risk of death in TEN (SCORTEN) has been
developed and validated.[26] Each of the following independent prognostic factors is given a score
of 1:

Age >40 years

 Heart rate >120 beats per minute

Cancer or hematologic malignancy

Involved body surface area >10%

Blood urea nitrogen level >10 mmol/L (28 mg/dL)

Serum bicarbonate level < 20 mmol/L (20 mEq/L)

Blood glucose level >14 mmol/L (252 mg/dL)

The number of positive criteria and the corresponding mortality rates are as follows:

0: 1 to 3%

2: 12%

3: 35%

4: 58%

5 or more: 90%

Sequelae

Major sequelae are generally limited to the affected organ systems (ie, the skin and mucosal
membranes).

Cutaneous sequelae of TEN include the following:

Changes in skin pigment (hypopigmentation or hyperpigmentation; sun exposure must be

avoided for several months because ultraviolet light can worsen hyperpigmentation; sunblock is
recommended)

Nail loss and nail dystrophy

Hypohidrosis (inability to sweat)

Scarring, alopecia, and hypertrophic scarring

Dermal desiccation, causing deep dermal wounds

Chronic xerostomia

Esophageal strictures
 Vulvovaginal synechiae

Phimosis

Chronic erosion of the mouth and genitalia

Ocular complications generally result from abnormal keratinization of the tarsal conjunctiva. A
Sjogrenlike syndrome with decreased lacrimal secretion causes dry eye and predisposes to
corneal abrasions and corneal scarring with neovascularization. In addition, patients have been
reported to have palpebral synechiae, entropion, or symblepharon (adhesion of the eyelids).[27]

A study by Power and colleagues found that 50% of patients with TEN developed ocular
complications.[28] Patients treated with steroids fared no better than those treated without steroids.
Therefore, TEN remains a common cause of visual loss in a significant number of patients.
Ultimately, 5-9% of patients can become blind as a result of some of these complications.

Patients with toxic epidermal necrolysis (TEN) may describe an influenzalike prodrome
characterized by the following:

Malaise

Rash

Fever

Cough

Arthralgia

Myalgia

Rhinitis

Headache

Anorexia

Nausea and vomiting, with or without diarrhea

Other prodromal signs and symptoms include conjunctivitis (32%), pharyngitis (25%), and
pruritus (28%). The prodrome typically lasts from 1 day to as long as 3 weeks.

The cutaneous eruption begins as a poorly defined, erythematous macular rash with purpuric
centers. Over a period of hours to days, the rash coalesces to form flaccid blisters and sheetlike
epidermal detachment. The lesions predominate on the torso and face, sparing the scalp. Pain at
the site of the skin lesions is often the predominating symptom and is often out of proportion to
physical findings in early disease.

Mucous membrane erosions (seen in 90% of cases) generally precede the skin lesions by 1-3
days. The most frequently affected mucosal membrane is the oropharynx, followed by the eyes
and genitalia. Oral cavity involvement typically presents as a sore or burning sensation. Intake
may be limited because of pain associated with the oropharyngeal lesions.

Ocular manifestations range from acute conjunctivitis to corneal erosions and ulcers. Genital
involvement may result in painful urination. Other mucosal surfaces such as the esophagus,
intestinal tract, or respiratory epithelium may be affected. Bronchial epithelial sloughing may
result in dyspnea and hypoxemia.

Most cases of TEN are drug induced, typically occurring within 1-3 weeks of therapy initiation
and rarely occurring after more than 8 weeks. Therefore, a detailed medication history, focusing
on medications that have been recently started, is a vital component of the patient's history.

More than 220 different medications have been suggested. The most commonly implicated
agents include the following:

Sulfonamide antibiotics

Antiepileptic drugs

Oxicam nonsteroidal anti-inflammatory drugs

Allopurinol

Nevirapine

Abacavir

Lamotrigine

Fewer than 5% of patients report no history of medication use.

Physical Examination

Vital signs in toxic epidermal necrolysis may include hyperpyrexia, hypotension secondary to
hypovolemia, and tachycardia.

Skin examination

Skin lesions begin as painful/burning, warm, erythematous, morbilliform macules that are
initially discrete. They begin symmetrically on the face and thorax before spreading to the entire
body. The skin lesions coalesce and fill with fluid-producing large, flaccid blisters. The
epidermis sloughs in sheets, leaving a characteristic moist, denuded dermis (see images below).
Conjunctivitis and denudation and erosions of other mucous membranes precede epidermal
necrolysis

A positive Nikolsky sign is evident when the application of slight lateral pressure to the
epidermal surface results in the epidermis easily separating from its underlying surface.

The usual course is an intense erythema that progresses rapidly to epidermolysis and stops within
2-3 days. Dermatologic recovery typically takes 1-3 weeks, with mucosal lesions taking longer.
Rarely, necrolysis recurs in areas that began to heal.

Involvement of the oral mucosa results in edema and erythema, followed by blistering. Ruptured
blisters may form extensive hemorrhagic erosions with grayish white pseudomembranes or
shallow aphthouslike ulcers. Hemorrhagic crusting of the lips is a common finding (as seen in
the image below).

Ocular involvement varies in severity and can result in mild inflammation, conjunctival erosion,
purulent exudates, or pseudomembrane formation.

Involvement of respiratory epithelium may result in bronchial hypersecretion, hypoxemia,

interstitial infiltrates, pulmonary edema, bacterial pneumonia, or bronchiolitis obliterans.
 Complications

Numerous complications of TEN can arise as a result of the widespread cutaneous and mucosal
membrane inflammation and necrosis. Stomatitis and mucositis, which are painful and hinder
oral intake, can place patients at risk for dehydration and malnutrition.

Epithelial loss predisposes to septicemia (Pseudomonas aeruginosa, Staphylococcus aureus,

gram-negative species, and Candida albicans). Renal hypoperfusion, acute tubular necrosis, and
renal insufficiency may develop subsequent to septic shock.

Ulceration of various mucosal membranes may result in pain, scarring, and stricture formation.
Affected surfaces include oral, ocular, and urogenital mucosa. Barrera and colleagues reported a
case of hypopharyngeal stenosis and dysphagia with recurrent aspiration.[29] Miscellaneous
complications include hypovolemia, massive gut bleeding, and pulmonary emboli.

Mild-to-severe eye complications can occur, such as the following:

Lid edema

Persistent dry eyes

Chronic photosensitivity

Conjunctivitis

Keratitis
 Conjunctival fornix foreshortening

Ectropion or entropion with subsequent trichiasis

Symblepharon

Corneal ulceration and scarring

Blindness

Pulmonary complications may occur. Mucous retention and sloughing of tracheobronchial

mucosa may occur, with aspiration of mucosal debris. Pneumonia and pneumonitis are common
and sometimes fatal complications of TEN. Pulmonary embolism and acute respiratory distress
syndrome (ARDS) have also been reported.

GI hemorrhage results from intestinal inflammation.

Diagnostic Considerations

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered to be a
single disease entity differing in severity. There is debate whether TEN and SJS are part of a
spectrum of disorders including erythema multiforme major (EMM); however, it is widely
accepted that SJS and TEN are distinct entities differing in etiology, clinical manifestations,
histopathology, treatment, and prognosis.

EMM is characterized by typical target lesions (at least 3 concentric rings) with or without blister
formation in a symmetric, predominantly acral distribution. In contrast, the skin lesions of SJS
and TEN are predominately central (trunk and face), consisting of blisters that arise on
erythematous or purpuric macules and involve 2 or more mucosal surfaces.

Histopathologic examination is necessary in differentiating these disorders from other severe

bullous skin diseases, including the following[30] :

Staphylococcal scalded skin syndrome

Toxic shock syndrome

Phototoxic skin reactions

Drug reaction with eosinophilia

Acute generalized exanthematous pustulosis

Paraneoplastic pemphigus
TEN and SJS are characterized by apoptotic keratinocyte cell death in the epidermis with
dermal-epidermal separation that results in bullae formation.

Other problems to be considered in the differential diagnosis of TEN include the following:

Cauterization burns

Caustic agents

Drug reaction with eosinophilia

Generalized bullous fixed eruption

Kerosene and paraffin burns

Differential Diagnoses

Acute Conjunctivitis

Chemical Burns

Exfoliative Dermatitis

Hypersensitivity Vasculitis

Pemphigus Vulgaris

Pseudoporphyria

Staphylococcal Scalded Skin Syndrome

Toxic Shock Syndrome

Approach Considerations

TEN is a clinical diagnosis, confirmed by histopathologic analysis of lesional skin. Early

involvement of a dermatologist and dermatopathologist is recommended. Skin biopsy, harvested
at the earliest possible stage, is important in establishing an accurate diagnosis and directing
specific therapeutic modalities.

Necrotic keratinocytes with full-thickness epithelial necrosis and detachment is consistent with
the diagnosis of TEN. Perivascular and scattered lymphocytic infiltration of the dermis is
sometimes demonstrated, although the underlying dermis is not greatly altered.
No definitive or specific emergent laboratory tests are indicated for TEN. Basic laboratory tests
may be helpful in planning symptomatic or supportive therapy. Surveillance cultures of blood,
skin, and urine should be obtained.

Imaging studies are not indicated for the diagnosis of TEN. Chest radiography should be
performed in the setting of respiratory distress because tracheobronchial inflammation may
predispose to diffuse interstitial pulmonary disease or pneumonia.

Blood Studies

Hematology studies include the following:

Complete blood count (CBC) and differential

Circulating immune complexes

Erythrocyte sedimentation rate

Leukopenia is common, whether a result of TEN itself or of bacteremia, as is a normochromic

normocytic anemia. Eosinophilia may be present. Less often, thrombocytopenia, neutropenia,
and bandemia may occur. Neutropenia is an unfavorable prognostic sign.

In the acute phase, there are transient decreases of peripheral CD4+ T lymphocytes and reduced
allogeneic and natural killer cell cytotoxicity, which returns to normal in 7-10 days.

Coagulation studies may include prothrombin time/international normalized ratio (INR) and
activated partial thromboplastin time.

Chemistry to assess fluid and electrolyte losses include the following:

Albumin

Blood urea nitrogen

Total protein

As toxic epidermal necrolysis progresses, multiple organs are affected, causing other
abnormalities in laboratory test results. Diffuse skin involvement may cause significant fluid loss
and electrolyte abnormalities.

Biopsy

A skin biopsy specimen must be obtained. In experienced hands, a frozen section specimen
expedites matters. Results are very useful in differentiating TEN from other dermatologic
disorders.
Histologically, TEN is characterized by full-thickness epidermal necrosis with little evidence of
epidermal or dermal inflammation. Epidermal detachment and sloughing may be evident.
Satellite cell necrosis may be visible early, progressing to extensive eosinophilic necrosis.

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.[31] In 2007, these guidelines were revised by Fromowitz and colleagues.[32]
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.

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.[33] Evidence suggests that
rapid institution of these two measures is associated with a more favorable prognosis.[34, 35]

Emergency department care should be directed toward the following:

Maintaining fluid and electrolyte homeostasis

Mitigating temperature loss

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.[23] Fluid management should be based on the
physiologic endpoint of urine output of 0.5-1 mL/kg/h.[33]

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

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 patients 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.

Energy requirements for patients with TEN must be carefully calculated and nutritional support
provided. Protein loss can be significant.[25]

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.[23]

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.

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. phylococcus 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 factoralpha (TNF-alpha) inhibitors

Intravenous immune globulin (IVIg) [6, 36]

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.[37]

AntiTNF- treatment has been reported to rapidly resolve skin lesions due to TEN. TNF- 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.

Consultations

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 treatment of ocular manifestations and

preventing long-term sequelae

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.

Medication Summary

The goals of pharmacotherapy in toxic epidermal necrolysis (TEN) are to reduce morbidity and
to prevent complications. No specific treatment modality has been proven effective, but agents
such as crystalloids, antibiotics, antihistamines, anticoagulants, analgesics, and antiseptic agents
are important for supportive care. Use of corticosteroids is controversial.

Crystalloids

Class Summary

Fluid resuscitation is critical in TEN. In cases of acute skin failure, insensible losses may be
enormous, and repletion of water loss is essential.

Isotonic sodium chloride 0.9%

Patients with TEN are at serious risk of dehydration, which may complicate their condition. For
example, water losses in a hypercatabolic state result in hypoalbuminemia and reduced renal
perfusion. This leads to acute renal failure; therefore, maintaining intravascular volume is
paramount. The rate of intravenous repletion should be titrated based on urine output or central
venous pressure.

Antibiotics

Class Summary
Patients with TEN lose their epidermis, a major barrier to invading organisms. If patients become
infected, morbidity is enhanced. Staphylococcus aureus is the main bacteria present during the
first days, with gram-negative strains appearing later.

Case reports of Klebsiella species,[38] Escherichia coli, and Pseudomonas species recovered from
patients with TEN have created concern about the possible polymicrobial nature of sepsis
associated with this condition. Therefore, good gram-negative coverage may be necessary.

View full drug information

Nafcillin

Nafcillin covers most common skin organisms (eg, Staphylococcus, Streptococcus). If patient
has allergy to penicillin or if methicillin-resistant S aureus (MRSA) is present on skin culture,
use vancomycin.

View full drug information

Gentamicin

Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in

combination with both an agent against gram-positive organisms and one that covers anaerobes.
Third-generation cephalosporins, such as ceftazidime, and others with good gram-negative
coverage are suitable alternatives. Adjust dose based on renal insufficiency.

Antihistamines

Class Summary

Hydroxyzine may be used when reepithelialization begins because intense pruritus may occur.

View full drug information

Hydroxyzine (Vistaril)

Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in

subcortical region of the central nervous system.

Anticoagulants

Class Summary

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

Heparin augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. It
does not actively lyse thrombus but is able to inhibit further thrombogenesis. Heparin prevents
reaccumulation of clot after spontaneous fibrinolysis. It is indicated for the prevention of
thromboembolic events.

Analgesics

Class Summary

Opiate analgesics are important to alleviate pain and anxiety associated with TEN. Much like
treatment of a second-degree burn, the pain must not be ignored.

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Morphine sulfate (Duramorph, Astramorph, MS Contin)

Morphine is the drug of choice for pain in patients with TEN. In case of allergy or intolerability,
meperidine or fentanyl may be used.

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Fentanyl Citrate ( Fentora, Abastral, Duragesic)

A synthetic opioid analgesic that is primarily a mu receptor agonist, fentanyl is 50-100 times
more potent than morphine. It has short duration of action (1-2 h) and minimal cardiovascular
effects, such as hypotension. Respiratory depression is uncommon, but this effect lasts longer
than its analgesic effect. Fentanyl is frequently used in patient-controlled analgesia for relief of
pain. Unlike morphine, fentanyl is not commonly associated with histamine release.

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Meperidine (Demerol)

Meperidine is a synthetic opioid narcotic analgesic indicated for the relief of severe pain. This
analgesic has multiple actions similar to those of morphine. However, meperidine may produce
less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic
doses of morphine.
Antiseptics

Class Summary

These agents inhibit growth of gram-positive and gram-negative bacteria.

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Chlorhexidine gluconate (PerioGard, Peridex, Hibiclens, Avagard)

Chlorhexidine binds to negatively charged bacterial cell walls and extramicrobial complexes. It
has bacteriostatic and bactericidal effects.

Topical Anesthetics

Class Summary

Topical anesthetics can be applied to mucous membranes, especially buccal, to relieve pain.

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Benzocaine (Americaine, Anbesol, Chiggerex Plus)

Benzocaine inhibits neuronal membrane depolarization, blocking nerve impulses. It provides oral
or mucosal anesthesia, thereby controlling pain.

Corticosteroids

Class Summary

While corticosteroids may be used, their use is highly controversial. Although high-dose
corticosteroids used early in the course of TEN (within 24-48 hours of onset) may halt the
progression of the reaction, many experts believe that corticosteroids should not be used because
they predispose patients to infection, mask early signs of sepsis, encourage GI bleeding, and
impair or delay wound healing.

If corticosteroids are used, the initial high dose is titrated down as quickly as possible and
tapered off, usually over 7-10 days.

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Dexamethasone (Baycadron)
Dexamethasone decreases inflammation by suppressing migration of polymorphonuclear
leukocytes and reducing capillary permeability. Other corticosteroids, such as
methylprednisolone, prednisone, and hydrocortisone, also may be used.

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Methylprednisolone (Solu-Medrol, Medrol, A-Methapred)

Methylprednisolone is a highly potent synthetic glucocorticoid that causes diverse metabolic

effects and modifies the body's immune responses to various stimuli.

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Prednisone

Prednisone, a synthetic glucocorticoid analog, acts as a potent immunosuppressant. It May

inhibit cyclooxygenase, which, in turn, inhibits prostaglandin biosynthesis. These effects may
result in analgesic, antipyretic, and anti-inflammatory activities.

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Hydrocortisone (A-Hydrocort, Solu-Cortef, Cortef)

Hydrocortisone elicits anti-inflammatory properties and causes profound and varied metabolic
effects. This agent modifies the body's immune response to diverse stimuli.