Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis | Simple Revision Notes for Medical Students

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are dermatological emergencies, characterised by skin and mucosal loss. Though quite rare, they can be fatal.

Classification

SJS/TEN are thought to be variants of a single condition. They occur most commonly secondary to medications and as they’re variants of each other, they exist on a spectrum, based on the extent of skin surface area that gets affected.

<10%: Stevens Johnson Syndrome
10-30%: SJS/TEN overlap
>30%: Toxic epidermal necrolysis

Pathophysiology

The unfortunate thing about SJS/TEN is that they occur very unpredictably, and although quite rare they can be severe and sometimes fatal.

The precise underlying mechanism isn’t fully understood, but the basic flow is this – the immune system metabolises a drug, and there is an improper immune reaction to this drug resulting in death of keratinocytes (the major component of the epidermis). This death of keratinocytes causes the epidermis to detach from the underlying skin, resulting in the clinical manifestations of SJS/TEN.

One proposed theory for what causes the keratinocyte death is that there is a T-cell mediated reaction whereby cytotoxic T cells and NK cells result in cell death of keratinocytes via release of granulysin which is a cytolytic protein (we know this as granulysin is found in the blisters of SJS/TEN, and its concentration relates to the severity of the disease).

Another theory is that there is a cell receptor called Fas which, when it binds its ligand (the Fas ligand), it results in cell death of the keratinocyte.

There are also some genes associated with SJS/TEN, so some people can have a genetic predisposition to it.

Causes

Drug reactions account for the majority of SJS/TEN reactions (75%), with non-drug reactions thought to account for 25% of the underlying aetiology.

Antibiotics: They cause the vast majority of these types of skin reactions
- Sulfonamides: Co-trimoxazole
- Penicillins
- Cephalosporins
Allopurinol
Anti-epileptic drugs
- Lamotrigine
- Carbamazepine
- Phenytoin
Paracetamol
NSAIDs
Antiretrovirals e.g. Nevirapine
Non-drug
- Infections
- Graft-vs-host disease
- Vaccines

Clinical Features

Prodromal Illness: This usually manifests like a flu-like illness:

Fever
Coryzal symptoms
Sore eyes
Sore throat
General malaise

Acute Illness: The prodrome is followed by acute onset of a painful rash which starts on the trunk. It then extends to affect the face/limbs.

Skin Manifestations

Erythema
Macules: Flat, red spots which coalesce to form flaccid blisters
Flaccid blisters: These slough off to expose the underlying dermis, which appears red and oozing.
Target Lesions
Nikolsky Sign positive: Gentle rubbing of the skin causes blisters and erosions of the skin
Pain: Patients will naturally be quite distressed and in pain given the widespread involvement
Secondary Infection of the Skin

Other Mucosal Involvement

Ocular: Conjunctivitis, Anterior uveitis, corneal ulceration. Red, photophobic eyes.
Oral: Mouth ulceration, stomatitis, blistering
Respiratory: Sloughing of the bronchial epithelium resulting in cough, respiratory distress, and pneumonia
Genitourinary: Urethritis, vaginal adhesions
Gastrointestinal: Dysphagia, diarrhoea, urethritis

SCORTEN

SCORTEN is a severity scoring system for TEN which predicts mortality rates. It can also be used for SJS.

It scales 7 risk factors for high mortality:

Age
Concurrent malignancy
Heart rate
Serum BUN
Serum bicarbonate
Serum glucose
Detached/compromised body surface

A score of 0-1 is associated with a mortality of 3.2%, whilst a score of 5 with a mortality of >90%.

Differential Diagnosis

Erythema multiforme: A self-limiting inflammatory condition usually triggered by herpes simplex. Lesions are usually raised. Mucosal and ocular involvement alongside blisters are less common
Staphylococcal scalded skin syndrome: Mucosal involvement doesn’t occur, and also commonly affects children

Management

Conservative

Analgesia: Pain can be very severe so adequately controlling pain is important
Identify underlying cause: If a drug is thought to be the likely causative factor, stopping the medication
Nutrition and Fluid Management
Thermoregulation: The skin’s thermoregulation becomes disrupted so ensuring the patient is kept warm
Monitor for infection: Swabs can be taken
Dressings
Ophthalmology involvement: Due to eye involvement, it’s important to involve the ophthalmologists