Introduction

Stevens-Johnson syndrome (SJS) is a rare, but serious and potentially fatal skin disorder. It is an immune-complex mediated hypersensitivity reaction. The term toxic epidermal necrolysis (TEN) was previously be believed to be a different disorder, but is now considered to be part of the same spectrum as SJS, although TEN is more severe.

In SJS and TEN there is “sheet-like” skin loss, almost always caused by a drug reaction. About 10% of cases of SJS and 30% of TEN are fatal.

The mechanism is not understood.

Epidemiology and Aetiology

  • A complication of medication
  • Incidence of about 1-2 in a million per year
  • F>M
  • 100x more common in patients with HIV
  • Genetic factors predispose an individual to getting SJS / TEN
  • More than 200 medications are known to cause SJS / TEN
    • More common in drugs with long half lives
    • Usually oral or IV drugs, only very rare with topical formations
    • in about 20% of cases no drug can be identified as the cause
  • Associated drugs include:
    • Sulfonamides –¬†cotrimoxazole
    • Beta-lactase –¬†penicillins, cephalosporins
    • Anti-convulsants –¬†lamotrigine, carbamazepine, phenytoin, phenobarbitone
    • Paracetamol
    • Allopurinol
    • NSAIDs –¬†typically the -oxicam varieties
  • About 20% of cases are due to infection, or rarely vaccination

Presentation

  • Time of presentation from starting drug is variable
    • Within first week with antibiotics
    • Can be several months for anticonvulsants
    • For most drugs it is between 3-30 days from commencement of the medication
  • Prodromal illness
    • Fever
    • Sore throat, difficulty swallowing
    • URTI symptoms – runny nose, cough
    • Conjunctivitis
    • Myalgia, joint pain
  • Skin lesions
    • Can be very variable at first, and may include target lesions, Manuela, generalised erythema and blistering
    • As the disease progresses, affected patches of skin merge into large “sheets” of skin which are then shed
    • Underneath this, the dermis is exposed
  • Niklosky sign
    • Refers to the appearance of blisters and erythema when the skin is gently rubbed
  • Mucosal involvement
    • Eyes
    • Lips / mouth – often severe
    • Pharynx and oesophagus – can prevent eating and drinking
    • Genitals
    • Respiratory tract – causing cough and respiratory distress
    • GI tracts – causing diarrhoea

Patients are often severely systemically unwell. There may also be internal organ involvements – including lungs, liver, kidneys, bone marrow and joints

Stephens-John Syndrome

Stephens-John Syndrome. Image from DermnetNZ and used in accordance with the licensing requirements of Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (New Zealand).

Diagnosis

Diagnosis is clinical. The severity of the disease is classified by the percentage of skin detachment:

  • SJS
    • <10% body surface area (BSA) skin detachment
    • Widespread erythematous or purpuric macules or flat atypical targets
  • Overlap SJS / TEN
    • 10 – 30% BSA skin detachment
    • Widespread erythematous or purpuric macules or flat atypical targets
  • TEN
    • >30% BSA skin detachment
    • Widespread purpuric macules or flat atypical targets
    • OR
    • >10% BSA detachment with no macules and large epidermal sheets

As the disease progresses, the classification may change

SCORTEN

SCORTEN is an illness severity score used in SJS and TEN. Score is associated with mortality. One point is given for each criteria:

  • Age >40
  • Known malignancy (of any type)
  • HR >120
  • Percentage of skin detachment at presentation >10%
  • Urea >10 mmol/L
  • Glucose >14 mmol/L
  • Bicarb <20mmol/L

Mortality risk based on SCORTEN score:

  • 0 or 1 – 3% mortality
  • 2 – 12%
  • 3 – 35%
  • 4 – 58%
  • 5 or more – 90%

Patients with a SCOTEN score of >3 should be managed in ICU

An alternative scoring system known as ABCD-10 is also in use

Investigation

  • Serum granulysin
    • Can be detected the in the first few days when the true character of the rash is not known and can predict SJS
  • Skin biopsy
    • Often used to confirm the diagnosis
    • Differentials include Scalded skin syndrome, and in the early stages, erythema multiforme
    • Histology shows full thickness epidermal necorsis with minimal inflammation
    • Immunofluorescence is negative – indicating lack of antibody deposition
  • Bloods
    • For U+Es to assess electrolyte loss
    • FBC – anaemia is common
    • Neutropenia is a poor prognostic sign
    • LFTs – raised in 30% of cases
      • 10% of cases develop a full blown hepatitis
    • Proteinuria – occurs in about 505 of patients

Patch testing is NOT useful to attempt to identify the causative drug

Management

There is no specific treatment that can alter the underlying course of the disease. Treatment is focussing on treating the cause (if infective), and supporting the end organ dysfunction. Many patients end up in intensive care.

Principles of management:

  • Cease any drugs that may be implicated
  • Treat any underlying infections
  • IV fluid therapy with electrolyte replacement
  • Analgesia
  • Skin lesions are managed as burns
  • Anaesthetic mouthwashes
  • Eye care
    • Ophthalmology assessment
    • Antibiotics +/- steroid eye drops
  • Treat any secondary infections
  • Immunomodulating therapies
    • Use of steroids is controversial – no proven benefit
    • There may be some benefit from pulsed doses
    • Other drugs may be considered – such as cyclosporin, monoclonal antibodies (anti-TNF-alpha)

Complications

  • Multiple organ failure
    • Liver
    • Lungs
    • Kidney
  • Dehydration
  • Malnutrition
  • VTE
  • Bowel perforation
  • Secondary skin infection and scarring
  • Eye complications – such as uveitis, corneal ulceration
    • Sign impairment occurs in up to 10% of patients
  • Vaginal stenosis / penile scarring

Prognosis

  • Mortality:
    • 10% for SJS
    • 30% for TEN
    • Mortality is typically due to systemic infection and / or multi-organ failure
  • Long term complications include:
    • Hyperhidrosis
    • Hair loss
    • Heat and cold sensitivity
    • Scarring
    • Altered skin pigmentation
  • Vaginal, urethral and anal strictures
  • Sight impairment

References

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