Steven Johnson Syndrome / Toxic Epidermal Necrolysis

Question 1

What is Stevens-Johnson syndrome and Toxic epidermal necrolysis (TEN)?

Answer 1

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) => variants of the same condition.

SJS/TEN is a rare, acute and potentially fatal skin reaction with sheet-like skin and mucosal loss.
=> nearly always caused by medications.

Question 2

Who is at risk of SJS/TEN?

What genetics factors increase the risk?

Which drugs increase the risk?

What is the most common drug assoc. with SJS/TEN?

Answer 2

1. Anyone on medication can develop SJS/TEN unpredictably
2. Females > Males (only v slightly)
3. 100x more common in HIV
4. Genetic factors:
   => HLA associations in some races to anticonvulsants and allopurinol

=> Polymorphisms e.g. CYP2C coding for cytochrome P450 in patients reacting to anticonvulsants

5. > 200 medications associated with SJS/TEN
6. Most common drugs that cause SJS/TEN = antibiotics
7. Other drugs include:
   => Sulfonamides: cotrimoxazole

=> Beta-lactam: penicillins, cephalosporins

=> Anti-convulsants: lamotrigine, carbamazepine, phenytoin, phenobarbitone

=> Allopurinol

=> Paracetamol/acetaminophen

=> NSAIDs

Question 3

What are the clinical features of SJS/TEN?

Answer 3

Usually develops within the first week of antibiotic therapy but up to 2 months after starting an anticonvulsant.

Prodromal illness: non-specific, flu-like illness. Symptoms include:
=> Fever > 39 C
=> Sore throat, difficulty swallowing
=> Runny nose and cough
=> Sore red eyes, conjunctivitis
=> General aches and pains.

Followed by an abrupt onset of a tender/painful red skin rash starting on the trunk and extending rapidly over hours to days onto the face and limbs
=> rarely affects scalp, palms or soles

The skin lesions may be:

=> Macules — flat, red and diffuse (measles-like spots) or purple (purpuric) spots

=> Diffuse erythema
=> Erythema multiforme
=> Flaccid blisters (TENS)

The blisters merge to form sheets of skin detachment, exposing red, oozing dermis.

Nikolsky sign +ve in areas of skin redness.
=> meaning blisters and erosions appear when skin is rubbed gently

Mucosal involvement is prominent and severe. At least 2 mucosal surfaces are affected including:

=> Eyes (conjunctivitis, less often corneal ulceration, anterior uveitis) — red, sore, sticky, photosensitive eyes

=> Lips/mouth (cheilitis, stomatitis) — red crusted lips, painful mouth ulcers

=> Pharynx, oesophagus - difficulty eating

=> Genital area and urinary tract - erosions, ulcers, urinary retention

=> Upper respiratory tract (trachea and bronchi) - cough & respiratory distress

=> Gastrointestinal tract -diarrhoea

Question 4

What are the complications of SJS/TEN?

Answer 4

Fatal => complications in the acute phase
=> mortality rate = 10% for SJS and 30% for TEN

During the acute phase, potentially fatal complications include:

=> Dehydration and acute malnutrition

=> Infection of skin, mucous membranes, lungs (pneumonia), septicaemia (blood poisoning)

=> Acute respiratory distress syndrome

=> Gastrointestinal ulceration, perforation and intussusception

=> Shock and multiple organ failure including kidney failure

=> Thromboembolism and disseminated intravascular coagulopathy

Question 5

How is SJS/TEN diagnosed?

Answer 5

SJS/TEN = clinical diagnosis and classified based on the skin surface area detached

1. Stevens-Johnson Syndrome
   => Skin detachment <10% of body surface area
   => Widespread erythematous or purpuric macules
2. Overlap SJS/TEN
   => Detachment between 10% and 30% of body surface area
   => Widespread purpuric macules or flat atypical targets
3. TEN with spots
   => Detachment >30% of body surface area
   => Widespread purpuric macules or flat atypical targets
4. TEN without spots
   => Detachment of >10% of body surface area
   => Large epidermal sheets and no purpuric macules

Question 6

What investigations are carried out in SJS/TEN?

Answer 6

Raised serum Granulysin in the first few days of drug eruption = predictive of SJS/TEN

Skin biopsy
=> confirms clinical diagnosis
=> excludes staphylococcal scalded skin syndrome (SSSS) + other generalised rashes with blisters

Histopathology:
=> keratinocyte necrosis (death of skin cells)

=> full thickness epidermal/epithelial necrosis (death of an entire layer of skin)

=> minimal inflammation (very mild lymphocytic infiltrate of the superficial dermis)

=> Direct immunofluorescence test on skin biopsy = negative, indicating disease is not due to deposition of antibodies in the skin.

Blood tests
=> essential for fluid and nutrients replacement

i. Anaemia
ii. Leucopenia + lymphopenia (90%)
iii. Neutropenia (bad prognostic sign)
iv. LFT: Mildly raised liver enzymes + 10% develop overt hepatitis
v. Mild proteinuria (50%)

Question 7

What is SCORTEN?

Answer 7

SCORTEN = illness severity score to predict mortality in SJS and TEN cases.

One point is scored for each of the seven criteria present at the time of admission.

Age >40 years

Presence of malignancy (cancer)

Heart rate >120

Initial percentage of epidermal detachment >10%

Serum urea level >10 mmol/L

Serum glucose level >14 mmol/L

Serum bicarbonate level <20 mmol/L

The risk of dying from SJS/TEN depends on the score
SCORTEN 0-1 = >3.2%
SCORTEN 2  = >12.1%
SCORTEN 3 = >35.3%
SCORTEN 4 = >58.3%
SCORTEN 5 or more = >90%

*In 2019, a new prediction model was proposed, the ABCD-10.

A: age over 50years (1pts)

B: bicarbonate level <20 mmol/L (1pts)

C: cancer present and active (2pts)

D: dialysis prior to admission (3pts)

10: epidermal detachment ≥ 10% body surface area on admission (1pts)

Question 8

What are the differential diagnosis for SJS/TEN?

Answer 8

Other severe cutaneous adverse reactions (SCARs) to drugs e.g. drug hypersensitivity syndrome

Staphylococcal scalded skin syndrome and toxic shock syndrome

Erythema multiforme

Mycoplasma infections

Bullous systemic lupus erythematosus

Paraneoplastic pemphigus

Question 9

What is the treatment for SJS/TEN?

Answer 9

Cessation of causative drug

Manage in dermatology / burns unit

Short term dexamethasone pulse therapy

Nutrition + fluid (crystalloid) replacement IV

Temperature maintenance

Pain relief