SOE 215: Stevens Johnson Syndrome

Introduction

A 24 year-old man, presents to the emergency department with a widespread erythematous rash covering his trunk and face. He has recently been diagnosed with epilepsy and started on lamotrigine. The admitting team are concerned that this could be Stevens Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN) and ask for a critical care review…

Question No. 2

Q: What is Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)? What is the difference between the two?

Answer No. 2

SJS and TEN are severe muco-cutaneous reactions characterized by erythema, extensive epidermal necrosis, and widespread bullous epidermal detachment. They are most commonly triggered by drugs and affect all age groups
Widespread skin loss from these conditions leads to ‘acute skin failure’ which is comparable with any other major organ dysfunction
Although rare, these conditions have high mortality rates, long critical care stays, and are associated with significant chronic morbidity
SJS and TEN are variants of the same disease spectrum, but distinguished chiefly by severity:
- SJS is the less severe form, affecting <10% total body surface area (TBSA)
- TEN is more severe and affects >30% TBSA
- Cases which affect 10–30% are referred to as SJS/TEN overlap.
In total, 90% of cases involve mucous membranes of the mouth, eyes, and genital tract.

Question No. 3

Q: How common is SJS / TEN?

Answer No. 3

This rare condition has an annual estimated incidence of 0.4–1.2 cases per million

Question No. 4

Q: What is the prognosis in SJS / TEN?

Answer No. 4

The overall mortality rate for SJS is 10%, but increases to 30–50% in TEN
The main cause of in-hospital mortality is multi-organ failure from sepsis

Question No. 5

Q: What are the pathological mechanisms underlying SJS / TEN?

Answer No. 5

Characterized histologically by keratinocyte apoptosis and separation of the epidermis from the dermis at the dermo-epidermal junction (black arrows)
Leads to extensive epidermal destruction
Proposed mediators are:
- Cytokines including fas-fas ligand and tumour necrosis factor alpha
- Direct toxic effect of drug triggering an immune reaction involving CD8+ lymphocytes

Question No. 6

Q: How does SJS / TEN present?

Answer No. 6

Usually presents with prodrome for 2–3 days of fever, flu-like illness and malaise
Features can be described as those affecting: the skin, mucous membranes (involvement is characteristic of SJS / TEN) and extra-cutaneous sites

Skin

Initial Phase:

Erythematous, dusky red, flat macules
Lesions symmetrically distributed on face, trunk and limbs

Late Phase:

Lesion coalesce to form flaccid blisters
Epidermal detachment

Mucous Membranes

Eyelid oedema, redness and discharge
Buccal erosive haemorrhagic lesions, white pseudomembranous crust
Crust on lips
Genital erosive haemorrhagic lesions, painful urination

Extracutaneous Sites

Respiratory Tract: Respiratory distress
GI Tract: Nausea, diarrhoea, malabsorption, colonic perforation
Renal Tract: Proteinuria, haematuria

Question No. 7

Q: What is the differential diagnosis for SJS / TEN?

Answer No. 7

Erythema multiforme major
Acute generalized erythematous pustulosis
Intermediate burns
Generalized Fixed Bullous Drug Eruption
Staphylococcal Scalded Skin Syndrome
Edematous erythroderma
Bullous pemphigoid
Paraneoplastic pemphigus
Linear IgA Bullous Dermatosis
Lupus erythematosus
Exfoliative dermatitis

Question No. 8

Q: How do you work up the patient with suspected SJS / TEN?

Answer No. 8

Usually presents with prodrome for 2–3 days of fever, flu-like illness and malaise
Features can be described as those affecting: the skin, mucous membranes (involvement is characteristic of SJS / TEN) and extra-cutaneous sites

Skin

Initial Phase:

Erythematous, dusky red, flat macules
Lesions symmetrically distributed on face, trunk and limbs

Late Phase:

Lesion coalesce to form flaccid blisters
Epidermal detachment

Mucous Membranes

Eyelid oedema, redness and discharge
Buccal erosive haemorrhagic lesions, white pseudomembranous crust
Crust on lips
Genital erosive haemorrhagic lesions, painful urination

Extracutaneous Sites

Respiratory Tract: Respiratory distress
GI Tract: Nausea, diarrhoea, malabsorption, colonic perforation
Renal Tract: Proteinuria, haematuria

Question No. 9

Q: Which score can be used to assess prognosis in SJS / TEN?

Answer No. 9

The SCORTEN is a validated scoring system to predict mortality
This should be scored within 24 hours of admission.
- Age >40
- Malignancy
- Initial area greater >10%
- Heart rate >120
- Serum urea >10
- Serum glucose >14
- Serum bicarbonate <20

Score

Predicted Mortality (%)

0-1

3.2

2

12.1

3

35.3

4

58.3

5 or more

90

Question No. 10

Q: What is the management of SJS / TEN?

Answer No. 10

Key Principles

Early recognition and withdrawal of offending agents
Multidisciplinary supportive care in burns centre
Strict infection control as per BAD guidelines

Initial Resuscitation & Supportive Care

ABC approach treating abnormalities as found:
- May require intubation if significant airway involvement
- Careful fluid assessment and resuscitation with ongoing maintenance
- IV access through non-lesioned skin, regularly replace
Maintenance fluids calculated with Parkland formula or more restrictive variant
Multimodal analgesia with opiate sparing agents
Multidisciplinary approach towards supportive care:
- Strict asepsis, nurse in side room
- Regular infection surveillance
- Attention to thromboprophylaxis

Specific Management

Withdraw offending agent and treat underlying cause
Management of skin lesions:
- Regularly cleanse wounds and intact skin by irrigation
- Apply emollients and topical antimicrobial
- Leave detached epidermis in situ
- Necrotic lesions may need surgical debridement and skin grafting
Careful MDT approach to management of ocular, oral, genital and respiratory tract lesions:
- Vigilant care of eyes with lubricants and drops
Experimental treatment - centre dependent:
- IVIG
- Ciclosporin
- Corticosteroids (generally not recommended)

Monitoring, Referral & Deposition

Skin area >10% should be managed in a burns centre or medical ICU
Senior MDT approach:
- Burns surgeon
- Dermatologist
- Ophthalmologist

Question No. 11

Q: Would you give corticosteroids to this patient?

Answer No. 11

Corticosteroids

Although widely trialled shown to have no significant beneficial effect at best, and at worst be harmful, with some small studies reporting increased mortality with steroid use
Summary of current evidence has been produced but Law et al
They are currently not recommended for routine treatment

Law et al.

R

Question No. 12

Q: Which other therapies have been used in the management of SJS / TEN and what is the evidence for their efficacy?

Answer No. 12

Intravenous Immunoglobulin (IVIg)

Proposed mechanism of action is antagonization of fas-fas ligand activity
No controlled studies have been performed with current evidence conflicted on its efficacy
A summary of current evidence has been produced by French et al
Despite this the use of IVIg is considered as a ‘Red’ indication for short term use by the department of Health Guidelines - considered the highest priority because of a risk to life without treatment

Ciclosporin

Proposed mechanism of action is suppressant of T-cell function reducing keratinocyte apoptosis
Data is scarce and of poor quality limiting recommendations

French et al.

R

Question No. 13

Q: How should skin be managed in SJS/TEN?

Answer No. 13

Skin should be handled gently with limitation of trauma
Conservative approach generally standard of care:
- Necrotic loose tissue removed
- Blisters pierced and loose dermis left in place to act as a biological dressing
- Wounds and intact skin cleansed regularly
- Regular application of emollient to whole skin and topical antibacterial to sloughy areas only
- Non-adhesive antibacterial dressing used to cover lesions
Surgical debridement may be indicated, particularly if:
- Local sepsis / subepidermal pus
- Extensive epidermal detachment

Question No. 14

Q: How should mucosal lesions (ocular/ oral /genital / respiratory) be managed in SJS/TEN?

Answer No. 14

Treatment of Eye Involvement

Early ophthalmology review and review daily thereafter during acute illness
Frequent application of lubrication (hyaluronate or carmellose eye drops 2 hourly)
Corticosteroid drops (dexamethasone 0.1% twice a day) may reduce damage
If evidence of ulceration topical antibiotic prophylaxis should be used (e.g. moxifloxacin drops four times a day)

Treatment of Mouth Involvement

Manage lips with soft white soft paraffin ointment every 2 hours
Clean the mouth daily with an oral sponge
Use regular mouthwashes:
- Anti-inflammatory: rinse or spray containing benzydamine hydrochloride every three hours
- Anti-septic: rinse containing chlorhexidine twice a day
- Corticosteroid: mouthwash (e.g. betamethasone sodium phosphate) four times a day

Treatment of Urogenital Involvement

Daily review is required during the acute illness
Corticosteroid cream should be administered to involved but non-eroded surfaces
Gynaecology review recommended for females to consider need for vaginal dilators

Treatment of Airway Involvement

Mechanical ventilation may be required if pulmonary infiltrates and respiratory failure develops
Fibreoptic bronchoscopy is useful to washout of necrotic bronchial epithelium

Question No. 15

Q: How can infection be prevented in SJS /TEN?

Answer No. 15

Wounds should be handled in a sterile manner whenever possible
Antimicrobial solutions for disinfection recommended
Use of bowel management systems may prevent wound soiling
No evidence for prophylactic use of antibiotics
Frequent wound swabs should be sent for surveillance and to guide antimicrobial therapy

Question No. 16

Q: How should fluid replacement be managed for patients with SJS/TEN?

Answer No. 16

Traditionally patients have been managed as burns patients:
- Parkland formula applied for involvement >15%
- Can result in overaggressive fluid replacement and related complications
Alternative regime of 2 mL/kg/ body weight / % BSA epidermal detachment / 24 hours has been suggested
Should be guided by urine output, lactate and other markers of tissue perfusion

Question No. 17

Q: Which patients with SJS / TEN should be referred to the regional centre? What are the benefits of transfer?

Answer No. 17

Transfer to a regional burns centre should be considered for patients with:
1. TEN (>30% BSA epidermal loss)
  and
2. Evidence of any one of:
  - Clinical deterioration
  - extension of epidermal detachment,
  - sub-epidermal pus,
  - local sepsis,
  - wound conversion and/or delayed healing.
Transfer to a burns centre allows:
- Supportive care provided by an experienced multidisciplinary team
- Surgical intervention to allow debridement of necrotic or infected tissue