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Toxic Epidermal Necrolysis, Emergency Medicine

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Toxic Epidermal Necrolysis, Emergency Medicine

Basics

Description

Chest radiograph should be obtained ‚

There are no established treatment regimens; however, there are several suggested guidelines: ‚

All patients with suspected TEN should be admitted to a burn unit (if burn unit is unavailable and transfer is not possible, then admit to ICU) ‚

  • One of the most fulminant and potentially fatal of all dermatologic disorders
  • Skin sloughing at the dermal " “epidermal interface results in the equivalent of a 2nd-degree burn
  • Can affect up to 100% of total body surface area (BSA)
  • May extend to involve:GI mucosaRespiratory mucosaGenitourinary/renal epithelium
  • Mechanism unclear, research indicates immunologic, cytotoxic, and delayed hypersensitivity may be involved as well as genetic susceptibility
  • Current classification system proposes 3 categories within the spectrum of Stevens " “Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), distinct from erythema multiforme major and based on percentage of total BSA:SJS: <10% of BSASJS " “TEN overlap syndrome: 10 " “30% of BSATEN: >30% of BSA, can affect up to 100% BSA
  • More common in older patients and immunocompromised patients
  • Mortality rate is about 30%, usually due to secondary sepsis from Staphylococcus aureus and Pseudomonas aeruginosa
  • Synonym(s):Lyell syndromeFixed drug necrolysisEpidermolysis necroticans combustiformisEpidermolysis bullosa
  • GI mucosa
  • Respiratory mucosa
  • Genitourinary/renal epithelium
  • SJS: <10% of BSA
  • SJS " “TEN overlap syndrome: 10 " “30% of BSA
  • TEN: >30% of BSA, can affect up to 100% BSA
  • Lyell syndrome
  • Fixed drug necrolysis
  • Epidermolysis necroticans combustiformis
  • Epidermolysis bullosa

Etiology

  • Dose-independent drug reactions are the usual cause of TEN:Drugs introduced within previous 1 " “3 wk are most likely candidatesFrequently implicated drugs include:Sulfonamide and PCN antibioticsAnticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine)NSAIDs (oxicams, pyrazoles, sulindac),AllopurinolCorticosteroidsAntiretroviral drugs
  • Other rare causes: Infections, graft-versus-host disease, vaccinations, idiopathic cases (combined <4%)
  • Drugs introduced within previous 1 " “3 wk are most likely candidates
  • Frequently implicated drugs include:Sulfonamide and PCN antibioticsAnticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine)NSAIDs (oxicams, pyrazoles, sulindac),AllopurinolCorticosteroidsAntiretroviral drugs
  • Sulfonamide and PCN antibiotics
  • Anticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine)
  • NSAIDs (oxicams, pyrazoles, sulindac),
  • Allopurinol
  • Corticosteroids
  • Antiretroviral drugs

Diagnosis

Signs and Symptoms

  • Prodrome: Influenza like, one to several days of fever, malaise, pruritus, cutaneous tenderness, erythema, anorexia, myalgias, arthralgias
  • Mucous membranes are commonly affected 1 " “3 days before skin lesions appear (oropharynx, eyes, genitalia, anus, esophageal and intestinal mucosae, respiratory epithelium) leading to conjunctivitis, esophagitis, pharyngitis, GI bleeding, vomiting, diarrhea, dysuria, cough, dyspnea
  • Skin:Rash usually begins on face (scalp usually spared) and trunk as erythematous macules, irregular target-like bullae, or diffuse, ill-defined erythema; initially may have pain at sites out of proportion to examWidespread epidermolysis, denuding of skin surfaces, flaccid bullae, and sheet-like sloughing of epidermis generally progress over 3 " “4 days but can progress rapidly over hoursNikolsky sign: With lateral pressure, the skin denudes and sloughs from separation of epidermis from dermis
  • Mucous membranes involved in >90% of cases, initial swelling and erythema followed by blistering and ulceration
  • Ocular lesions (pseudomembranes, synechiae or adhesions, keratitis, corneal erosions)
  • Rash usually begins on face (scalp usually spared) and trunk as erythematous macules, irregular target-like bullae, or diffuse, ill-defined erythema; initially may have pain at sites out of proportion to exam
  • Widespread epidermolysis, denuding of skin surfaces, flaccid bullae, and sheet-like sloughing of epidermis generally progress over 3 " “4 days but can progress rapidly over hours
  • Nikolsky sign: With lateral pressure, the skin denudes and sloughs from separation of epidermis from dermis

Essential Workup

  • Diagnosis is made clinically:Based on history and characteristic skin and mucous membrane lesions
  • Based on history and characteristic skin and mucous membrane lesions

Diagnosis Tests & Interpretation

  • No confirmatory lab tests exist
  • CBC: Normocytic anemia, leukocytosis, lymphopenia/neutropenia, and thrombocytopenia may be present
  • ESR may be elevated as a result of systemic inflammation
  • Serum chemistry: Electrolyte derangements if extensive fluid losses:Prerenal azotemiaSerum bicarbonate <20 associated with 40 ƒ — higher mortality
  • LFTs: Elevated transaminases, low total protein and albumin
  • UA may show hematuria (urethral " “mucosal erosion, glomerulonephritis) or casts (acute tubular necrosis)
  • Wound/skin cultures and blood cultures
  • Serum granulysin (an implicated cytotoxin)
  • Prerenal azotemia
  • Serum bicarbonate <20 associated with 40 ƒ — higher mortality
  • Severity of illness score for TEN (SCORTEN): Each risk factor earns 1 point, a higher score means a poorer prognosis:Age >40 yrMalignancyTachycardia >120/minInitial percentage of epidermal detachment >10%BUN >27 mg/dLSerum glucose level >252 mg/dLSerum bicarbonate level <20 mEq/L
  • Biopsy may be performed by consulting dermatologist to rule out autoimmune bullous diseases, staphylococcal scalded skin syndrome, and other diagnoses:Results not immediately available to ED physician
  • Age >40 yr
  • Malignancy
  • Tachycardia >120/min
  • Initial percentage of epidermal detachment >10%
  • BUN >27 mg/dL
  • Serum glucose level >252 mg/dL
  • Serum bicarbonate level <20 mEq/L
  • Results not immediately available to ED physician

Differential Diagnosis

  • Stevens-Johnson syndrome (SJS)
  • Erythema multiforme major (EMM):Differentiation of SJS/TEN from EMM:Immunopathologically distinctEtiology: SJS/TEN is mainly drug-induced, mechanism uncertain; EMM both infection and drug-induced, mechanism type IV hypersensitivityLesions:TEN: Widely distributed, mainly on the trunk and face, nonspecific, target-like lesions that often are confluent and too numerous to count, then desquamationEMM: Limited in number, symmetric and acral distribution, typical target type (at least 3 concentric rings) with or without blistersPrognosis: EMM is usually benign; recurrence of disease is common (30%)
  • Staphylococcal scalded skin syndrome (SSSS):Differentiation of TEN from SSSS:Age: TEN: Primarily adults (but may occur in children); SSSS: Primarily affects childrenEtiology:TEN most often represents an idiosyncratic, drug-induced, dose-independent reaction and hence does not require treatment with antibioticsSSSS results from infection and requires antibioticsPain: TEN, painful; SSSS, painlessMucous membranes: Involved with TEN; spared with SSSSSkin cleavage: Dermal " “epidermal junction in TEN; intraepidermally in SSSS (both can produce a positive Nikolsky sign)
  • Autoimmune bullous diseases (pemphigus vulgaris, bullous pemphigoid)
  • Scarlet fever
  • Toxic shock syndrome
  • Chemical or thermal scalds
  • Hypersensitivity vasculitis
  • Kawasaki syndrome
  • Differentiation of SJS/TEN from EMM:
  • Immunopathologically distinct
  • Etiology: SJS/TEN is mainly drug-induced, mechanism uncertain; EMM both infection and drug-induced, mechanism type IV hypersensitivity
  • Lesions:TEN: Widely distributed, mainly on the trunk and face, nonspecific, target-like lesions that often are confluent and too numerous to count, then desquamationEMM: Limited in number, symmetric and acral distribution, typical target type (at least 3 concentric rings) with or without blisters
  • Prognosis: EMM is usually benign; recurrence of disease is common (30%)
  • TEN: Widely distributed, mainly on the trunk and face, nonspecific, target-like lesions that often are confluent and too numerous to count, then desquamation
  • EMM: Limited in number, symmetric and acral distribution, typical target type (at least 3 concentric rings) with or without blisters
  • Differentiation of TEN from SSSS:
  • Age: TEN: Primarily adults (but may occur in children); SSSS: Primarily affects children
  • Etiology:TEN most often represents an idiosyncratic, drug-induced, dose-independent reaction and hence does not require treatment with antibioticsSSSS results from infection and requires antibiotics
  • Pain: TEN, painful; SSSS, painless
  • Mucous membranes: Involved with TEN; spared with SSSS
  • Skin cleavage: Dermal " “epidermal junction in TEN; intraepidermally in SSSS (both can produce a positive Nikolsky sign)
  • TEN most often represents an idiosyncratic, drug-induced, dose-independent reaction and hence does not require treatment with antibiotics
  • SSSS results from infection and requires antibiotics

Treatment

Pre-Hospital

  • Transport to facility with burn center
  • Care during transport should be gentle to avoid skin trauma
  • IV catheter should be avoided for short transport if hemodynamically stable (more sterile conditions in ED)
  • Avoid using adhesive materials

Initial Stabilization/Therapy

  • If intubation or nasogastric tube is required, gentle technique must be used to minimize mucosal damage
  • Meticulous sterile technique
  • Peripheral IV line is preferred over central line to decrease risk of sepsis
  • Cardiac monitor, pulse oximeter, nasogastric tube, Foley catheter

Ed Treatment/Procedures

  • Identify and stop any causative medication
  • Aggressive fluid resuscitation and electrolyte management as in burn care (Parkland formula):Urine output should target a rate of 0.5 " “1 mL/kg/hr.
  • Warming measures and frequent core temperature evaluation are important
  • If available, cover with biologic dressings (e.g., Biobrane):Reduces pain, decreases caloric and evaporative losses, and facilitates healing
  • Antibiotic drops for eyes
  • Petroleum jelly application to lips
  • Prevention of peptic stress ulcers
  • Topical antibiotics, including silver nitrate, are unproven but may be applied with the exception of silver sulfadiazine (sulfonamide derivative).
  • Timely admission to burn unit/ICU
  • Ophthalmology consultation is required for eye involvement (evaluation and removal of pseudomembranes and adhesions)
  • Urine output should target a rate of 0.5 " “1 mL/kg/hr.
  • Reduces pain, decreases caloric and evaporative losses, and facilitates healing

Medication

  • Pain should be controlled with IV opiates
  • Antibiotics should be used when documented signs of sepsis are present or for sudden deterioration in the clinical setting; coverage should include gram-positive, gram-negative (including P. aeruginosa), and aerobic organisms
  • Antihistamines can be used for pruritus
  • Anticoagulation should be considered while patients are nonambulatory for prevention of thromboembolic events
  • Systemic corticosteroids continue to be controversial:Retrospective studies show no benefit and suggest greater risk of death from infection
  • IVIG should be started 48 " “72 hr after bulla formation but can be helpful after 72 hr
  • The following experimental therapies are under investigation:PlasmapheresisCyclosporineCyclophosphamideN-acetylcysteineAnti-TNF-α antibodies (i.e., Infliximab) but Thalidomide contraindicated (harm shown)
  • Retrospective studies show no benefit and suggest greater risk of death from infection
  • Plasmapheresis
  • Cyclosporine
  • Cyclophosphamide
  • N-acetylcysteine
  • Anti-TNF-α antibodies (i.e., Infliximab) but Thalidomide contraindicated (harm shown)

Follow-Up

Disposition

  • Transfer to facility with burn unit has been shown to improve patient outcome
  • Dermatology should be called to help confirm the diagnosis
  • Ophthalmology should be called to evaluate and prevent corneal ulcerations and adhesions
  • Surgery or plastic surgery should evaluate the need for wound debridement.
  • Respiratory therapy should initiate pulmonary toilet in the setting of pulmonary mucosal sloughing.

Pearls and Pitfalls

  • Burn units and ICUs offer the best management settings
  • Remember to educate patients on medications (including combinations, medications, and structurally similar medications)
  • Aggressive fluid hydration is essential

Additional Reading

  • Downey ‚ A, Jackson ‚ C, Harun ‚ N, et al. Toxic epidermal necrolysis: Review of pathogenesis and management. J Am Acad Dermatol. 2012;66:995 " “1003.
  • Fernando ‚ SL. The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53:165 " “171.
  • Fujita ‚ Y, Yoshioka ‚ N, Abe ‚ R, et al. Rapid immunochromatographic test for serum granulysin is useful for the prediction of Stevens " “Johnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol. 2011;65:65 " “68.
  • Gerull ‚ R, Nelle ‚ M, Schaible ‚ T. Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review. Crit Care Med. 2011;39:1521 " “1532.
  • Iwai ‚ S, Sueki ‚ H, Watanabe ‚ H, et al. Distinguishing between erythema multiforme major and Stevens " “Johnson syndrome/toxic epidermal necrolysis immunopathologically. J Dermatol. 2012;39:781 " “786.
  • Yeong ‚ EK, Lee ‚ CH, Hu ‚ FC, et al. Serum bicarbonate as a marker to predict mortality in toxic epidermal necrolysis. J Intensive Care Med. 2011;26:250 " “254.

See Also (Topic, Algorithm, Electronic Media Element)

Codes

ICD9

  • 695.14 Stevens-Johnson syndrome-toxic epidermal necrolysis overlap syndrome
  • 695.15 Toxic epidermal necrolysis

ICD10

  • L51.2 Toxic epidermal necrolysis [Lyell]
  • L51.3 Stevens-Johnson synd-tox epdrml necrolysis overlap syndrome

SNOMED

  • 23067006 Lyells toxic epidermal necrolysis, subepidermal type (disorder)
  • 403215006 Toxic epidermal necrolysis - erythema multiforme overlap syndrome (disorder)
  • 402744003 toxic epidermal necrolysis due to drug (disorder)
  • 403214005 Toxic epidermal necrolysis associated with infection (disorder)
  • 402359006 Toxic epidermal necrolysis due to graft-versus-host disease (disorder)