Basics
Description
- 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 mucosa
- Respiratory mucosa
- Genitourinary/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 BSA
- SJS " “TEN overlap syndrome: 10 " “30% of BSA
- TEN: >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 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 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
Signs and Symptoms
History
- 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
Physical Exam
- 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)
Essential Workup
- Diagnosis is made clinically:
- Based on history and characteristic skin and mucous membrane lesions
Diagnosis Tests & Interpretation
Lab
- 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 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)
Imaging
Chest radiograph should be obtained ‚
Diagnostic Procedures/Surgery
- 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
Differential Diagnosis
- 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
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)
Medication
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
Disposition
Admission Criteria
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) ‚
Issues for Referral
- 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)
Burns ‚
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)