Rosen & Barkin's 5-Minute Emergency Medicine Consult (720 page)

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

DIAGNOSIS

• 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 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
    
• 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)
  

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

• 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 azotemia
    
  • Serum bicarbonate <20 associated with 40× 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)
  

Chest radiograph should be obtained

• Severity of illness score for TEN (SCORTEN): Each risk factor earns 1 point, a higher score means a poorer prognosis:
  
  • 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
    
• 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
    

• Stevens-Johnson syndrome (SJS)
  
• Erythema multiforme major (EMM):
  
  • 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 desquamation
      
    • EMM: 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%)
    
• Staphylococcal scalded skin syndrome (SSSS):
  
  • 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 antibiotics
      
    • SSSS 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)
    
• Autoimmune bullous diseases (pemphigus vulgaris, bullous pemphigoid)
  
• Scarlet fever
  
• Toxic shock syndrome
  
• Chemical or thermal scalds
  
• Hypersensitivity vasculitis
  
• Kawasaki syndrome
  

TREATMENT

• 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
  

• 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
  

• 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)
  

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

• 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:
  
  • Plasmapheresis
    
  • Cyclosporine
    
  • Cyclophosphamide
    
  • N-acetylcysteine
    
  • Anti-TNF-α antibodies (i.e., Infliximab) but Thalidomide contraindicated (harm shown)
    

FOLLOW-UP

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)

• 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 débridement.
  
• Respiratory therapy should initiate pulmonary toilet in the setting of pulmonary mucosal sloughing.
  

• 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
  

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