Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric Population

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric Population

By Stephen Alerhand, MD
EM Resident Physician
Icahn School of Medicine at Mount Sinai

Edited by Alex Koyfman, MD

 

Definition

  • Widespread epidermal necrosis and detachment, with mucocutaneous complications in ~90% 1
Condition % Body surface area showing skin detachment
SJS <10%
SJS/TEN overlap 10-30%
TEN >30%
      Variants of same disease along spectrum

 

Incidence 2-5

  • 2-7 cases per million people per year
  • SJS: 1-7 cases
  • TEN: 0.4-1.5 cases
    • M=F in children 6

 

Etiology

  • TEN triggered by medications or URI in 74%-94% of cases 7-9
  • Medications 10-12
    • Sulfa Abx, Phenobarbital, Lamotrigine, Carbamazepine, NSAIDS, Allopurinol
    • Within first 8 weeks of starting medication
    • Greater risk with higher doses 13 and rapid introduction 12, 14
    • Symptoms not clearly attributed to a drug by ALDEN (algorithm of drug causality for EN) in 20-25% of cases (higher for children) 15
      • Potentially offending drug scored by 6 parameters:
        • Time delay from drug administration to reaction onset
        • Probability of drug presence in body
        • Prior history of exposure to same drug, regardless of reaction
        • Presence of drug beyond progression phase
        • Drug notoriety as cause of SJS/TEN
        • Presence or absence of other etiologies
      • Infection 16-21
        • Mycoplasma pneumoniae, Cytomegalovirus infections, Herpesvirus, Hep A
        • More common for children than medications 22
      • Predisposing conditions 23-29
        • HIV (100-fold higher risk), malignancy, SLE, radiotherapy, collagen vascular disease, UV light, genetic, underlying immunologic disease

 

Clinical course

  • Fever, flu-like symptoms 1-3 weeks after starting drug
    • Malaise, myalgia, arthralgia, dysphagia, photophobia, conjunctival itching/burning
  • Skin and mucosal involvement 1-3 days later
    • Macules with purpuric centers a large blisters, vesicles, bullae a epidermal detachment with Nikolsky’s sign 3-5 days later a large denuded areas
      • Start on face and thorax, then spread symmetrically
        • Scalp, palms, soles rarely involved
      • Tender to touch, skin pain out of proportion to findings
    • Re-epithelization begins 1 week after onset, takes up to 3 weeks; faster in children 30

SJS:TEN pic 1

SJS:TEN pic 2

SJS:TEN pic 3

 

Mucosal and other complications

  • Large wound area leads to severe pain, massive fluid and protein loss, electrolyte imbalances, bleeding, evaporative heat loss with subsequent hypothermia, insulin resistance, hypercatabolic state, infection and bacteremia, hypovolemic shock with renal failure, multiple organ dysfunction
  • High risk for bacterial infection
    • Main cause of death is sepsis, most often by Staph aureus and Pseudomonas aeroginosa
    • Greater with BSA >30% and WBC >10 31
  • Ophthalmologic
    • Up to 30% of surviving children 32
    • Acute stage within 2-6 weeks of drug onset
    • Most commonly severe conjunctivitis with purulent discharge; swollen and erythematous eyelids, suppurative keratitis, endophthalmitis, pain and photophobia
    • Most severe: long-term vision loss from chronic corneal inflammation

SJS:TEN pic 4

  • Pulmonary
    • PNA, interstitial pneumonitis
    • Risk of ARDS
    • Mechanical ventilation in 25% 33, associated with higher mortality 34
  • GI
    • Diarrhea, melena, small bowel ulcerations, colonic perforation, small bowel intussusception, stenosis, strictures, stomatitis
  • Skin
    • Long-term hyper-/hypopigmentation in virtually all children tends to fade partially fade with time
    • Hypertrophic changes, scarring
  • Urogenital
    • Urethritis

 

Diagnosis

  • Confirmation by skin biopsy 35-36
    • Apoptosis, necrosis, and vacuolization of keratinocytes
    • Dermo-epidermal detachment
    • Lymphocytic infiltration of perivascular regions

SJS:TEN pic 5

  • Patch testing, pin prick, intradermal injection lack sensitivity for predicting SJS/TEN 37
  • Lab abnormalities
    • Anemia, lymphopenia
    • Neutropenia in 1/3 of cases, with poor prognosis 7
    • Hypoalbuminemia, electrolyte imbalance, increased BUN, increased glucose

 

Management

  • Withdrawal of drug
    • Reduces mortality and improves prognosis
      • In 10-year observational study of 113 patients, there was better prognosis (outcome measure: no death before hospital discharge) by odds ratio 0.69 (about 30%) for each day before blister development that drug was withdrawn. 38
      • In retrospective study of 19 patients, 21% mortality vs. the predicted mortalities by APACHE II (22%) and SCORTEN (30%) 39
    • Drugs with long half-lives had increased risk of death (odds ratio 4.9), independent of drug withdrawal 38
  • Supportive care
    • Wound care 40
      • Debride wounds, moisture-retentive ointments and/or topical Abx to improve barrier function and prevent bacterial infection, non-adherent monocrystalline gauze materials containing silver, whirlpool therapy, anti-shear wound care, fluidized air beds, copper sulfate
    • Fluid and electrolyte management
      • Increased water loss from denuded dermis
      • Volume loss ~1/3 less than that for burn victims 41
    • Nutritional support
      • Early oral feeding 7
      • High-calorie requirements similar to those in burn injury 42-43
    • Temperature management
      • Temp increased up to 30-32 deg Celsius to prevent excessive caloric expenditures from epidermal loss 1
    • Ocular care
      • Early baseline Ophtho consult
      • Cleaning of eye lids, daily lubrication
      • Daily Erythromycin drops to prevent infection, corticosteroid drops to reduce inflammation 44
    • Pain control
    • Pulmonary toilet
    • Monitoring and treatment of super-infections
      • Sterile handling, antiseptic solutions
      • Repeated cultures q48h of skin, blood, catheters, gastric, urinary tubes
      • Signs of infection: visible changes in skin lesions, increase in quantity of cultured bacteria, sudden decrease in temp, general deterioration
      • No prophylactic abx; can cause emergence of resistant bacteria and negatively impact survival 45

 

Therapies

  • No established therapies
    • No randomized prospective trials due to rarity of condition and ethical considerations; few studies and minimal standardization to this point
    • Conflicting data in children 46, 48
  • IVIg 47, 49-52
  • Corticosteroids 53-59

 

Prognosis/Triage

  • SCORTEN (severity-of-illness score) 60
    • Validated for adults and children combined on days 1 and 3 of hospitalization 61-62
      • Not yet validated for children specifically

SJS:TEN pic 6

SJS:TEN pic 7

Kaplan-Meier Analysis of survival of patients with TEN based upon SCORTEN score, calculated within 24 hours of hospital admission.

Adapted with permission from: Guegan, S, Bastuji-Garin, S, Poszepczynska-Guigne, E, et al. J Invest Dermatol 2006, 126:272.

 

  • Transfer to non-specialized wards: 63
    • Limited skin involvement, SCORTEN score 0-1, non-rapidly progressive disease
  • Transfer to ICU or burn unit: 63
    • More severe disease, SCORTEN >= 2
    • Retrospective review of 199 patients showed mortality of 32% with early ICU/burn unit transfer vs 51% with transfer after 1 week 64
    • Longer hospital stay if transferred to burn unit after 1 week 66
  • Negative prognostic factors: hypernatremia 67, increased BUN, neutropenia, thrombocytopenia, visceral involvement, delayed presentation 8, 45, 68

 

Mortality (from large RegiSCAR study) 69

  • SJS: 10%
  • TEN: >30%
  • 23% mortality at 6 weeks, 34% at 1 year
  • Slightly lower mortality when a drug was identified as the cause
  • Major prognostic factor for death within 90 days only: disease severity
    • Beyond 90 days: serious comorbidities and age
  • Lower for children
  • Major causes of death: sepsis, ARDS, multiple organ failure

 

Recurrence

  • May occur with drug re-exposure
  • In a retrospective study of 55 cases, 10 children had recurrence between 2 months and 7 years after first episode, 3 had multiple recurrences, and 1 died 70
  • Recurrence of such rare event suggests long-lasting vulnerability and genetic predisposition

 

ED Pearls

  • Be on guard for alerting signs:
    • Skin tenderness, blistering, mucositis, and fever >100.4
  • If such early signs even minimally present, find out whether “notorious” drugs were initiated within past 2 months:
    • Sulfa Abx, Phenobarbital, Lamotrigine, Carbamazepine, NSAIDS, Allopurinol
  • Withdraw all non-essential medications immediately
  • Strongly consider transfer to burn unit or ICU, or at very least make a consult
  • Early Ophtho consult to prevent common and long-lasting sequelae
  • Watch for super-infection: visible changes in skin lesions, increase in quantity of bacteria cultured, sudden decrease in temp, general deterioration
  • Recurrence of such a rare condition suggests future risk
    • Educate about future avoidance, allergy passport

 

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