Derm: Toxic Epidermal Necrolysis: Free MSRA Podcast

⚕️ FREE MSRA PODCAST – Toxic Epidermal Necrolysis
🎧 A clear, high-yield breakdown of this life-threatening blistering skin emergency – perfect for exam prep and rapid clinical recognition.

🧠 Key Learning Points

📌 Definition
• Toxic Epidermal Necrolysis (TEN) is a rare, severe mucocutaneous reaction, typically to medications, characterised by widespread epidermal necrosis and detachment affecting >30% of the body surface area.
• It’s the most extreme form of the SJS/TEN spectrum.

📌 Causes & Risk Factors
• Drugs are the most common trigger (90%+):
– Antibiotics (esp. sulphonamides)
– Anticonvulsants (e.g. carbamazepine, lamotrigine)
– NSAIDs (oxicam class)
– Allopurinol
• Other triggers:
– Mycoplasma pneumoniae, HSV
– HLA-B*1502 allele (esp. in East Asian populations)
– HIV, SLE, malignancy
– Recent vaccination or transplant

📌 Pathophysiology
• A delayed hypersensitivity reaction (Type IV)
• Immune activation → cytotoxic T cells release granulysin and perforin, destroying keratinocytes
• Results in full-thickness epidermal necrosis

📌 Symptoms
• Prodrome: flu-like illness (fever, sore throat, conjunctivitis)
• Mucosal involvement early (eyes, mouth, genitals)
• Rapidly spreading erythematous macules, then blisters and sloughing
• Positive Nikolsky’s sign – skin peels with lateral pressure
💡 Mnemonic: "Fever + Fragile skin + Facial mucosa"

📌 Differential Diagnosis
• Stevens-Johnson syndrome (SJS) – less skin involved
• Staphylococcal scalded skin syndrome (SSSS)
• Bullous pemphigoid / pemphigus vulgaris
• Burns
• Erythroderma, Toxic shock syndrome, Erythema multiforme

📌 Diagnosis
• Clinical diagnosis based on history and skin signs
• Skin biopsy: shows full-thickness epidermal necrosis
• Bloods: FBC, U&Es, LFTs, CRP – assess severity
• Cultures: screen for secondary infection
• Rule out SSSS and autoimmune blistering with biopsy + DIF
🧠 No specific blood test confirms TEN

📌 Management
• Stop causative drug immediately
• Admit to burns/ICU unit
• Supportive care:
– Fluid/electrolyte replacement
– Nutritional support (often NG feeds)
– Temperature regulation
– Skin care: non-adhesive dressings, barrier nursing
– Pain relief
• Controversial pharmacological therapies:
– IVIG, cyclosporin, TNF-α inhibitors (limited evidence)
– Steroids: debated
• Multidisciplinary care: dermatology, critical care, ophthalmology

📌 Complications
• Sepsis, pneumonia, renal failure, DIC
• Ocular complications (dry eye, scarring, blindness)
• Esophageal strictures, urogenital stenosis, joint contractures
• Psychological trauma, chronic pain

📌 Prognosis
• High mortality (up to 30–50%)
• SCORTEN score predicts mortality:
– Score ≥5 → ~90% mortality
• Prognosis depends on:
– BSA involvement
– Age, comorbidities
– Speed of recogniti

Episode Transcript

(00:00):
Welcome back to the Deep Dive. We're tackling a really critical
topic today based on the material you shared.
A true medical emergency. That's right, we're focusing on
toxic epidermal necrolysis or 10.
Now for anyone revising say for the MSR A, this is high yield
stuff. It's severe, it's dramatic and

(00:20):
even though it's rare, you absolutely need to recognise it.
It's life threatening. OK, so our mission here is
really to break down the key info.
Make it clear, make it spic. Right, let's dive in then.
Toxic epidermal necrolysis. What?
What is it fundamentally? OK, so 10 is defined as a severe
acute reaction affecting the skin and crucially, the mucous
membranes. Think widespread cell death.

(00:43):
Cell death. Yeah, necrosis.
It causes the outer layer of theskin, the epidermis, to detach
from the underlying dermis. And this isn't just a small
patch, it can be really extensive over large areas of
the body. Plus the mucous membranes, eyes,
mouth, airway, genitals, they'rehit too.
Wow. And like we said, definitely a
life threatening emergency, not just a bad rash.
OK, that sounds incredibly serious.

(01:03):
Skin literally detaching. What sets something like this
off? What's the the aetiology?
So the vast majority of cases the trigger is a severe adverse
drug reaction. It's not a predictable side
effect, more like a an idiosyncratic hypersensitivity
reaction, really severe. Any particular drugs we should,
you know, have on our radar? Yes, definitely.

(01:26):
The sources highlight a few key groups.
Antibiotics, especially sulfonamides, are high up there.
Then you've got anticonvulsants and as aids like your ibuprofen,
naproxen and allopurinol which is used for gout.
Those come up frequently, Antiretrovirals too, and some
others, but those first few are sort of the classic offenders.
Is it always drugs or can other things trigger Tenon?

(01:47):
Drugs are definitely the main culprit far and away, but the
material does mention infectionscan sometimes be a trigger,
though it's less common. Like what kind of infections?
Things like Mycoplasma pneumonia, that bacterial
pneumonia, and certain herpes virus infections are listed as
possible non drug causes. OK.
So whether it's a drug or maybe an infection, what's actually

(02:08):
happening in the body? You mentioned hypersensitivity.
Yeah, the pathophysiology, it's essentially an immune complex
mediated hypersensitivity reaction.
The idea is the body reacts probably to toxic metabolites
from processing certain drugs. Toxic metabolites.
Right. And these metabolites somehow
trigger this massive immune response.

(02:31):
Which then attacks the skin. Exactly.
It gets quite cellular. The material mentions cytotoxic
T lymphocytes. These are immune cells get
activated inappropriately, right?
And along with molecules like granzyme B, fast cell and
granulosin, they basically attack the keratinocytes.
The main skin cells you mean? Precisely the main cells making
up the epidermis. So you get this huge wave of

(02:52):
programmed cell death necrosis in those skin cells.
OK. So the immune systems kind of
like attacking the body's own skin structures that's.
A good way to put it, yeah, the immune system goes haywire and
targets the skin and mucous membrane cells, causing them to
die off and detach like the walls crumbling as we sort of
discussed. Makes sense.
OK, so knowing the triggers and the mechanism, who's more likely

(03:13):
to get this? Are there specific risk factors?
There are. The sources list several things.
A big one is a history of previous adverse drug reactions.
If you've reacted badly before, the risk of a severe reaction
like 10 might be higher. And obviously taking one of
those high risk drugs we mentioned.
Yes, exposure to those specific drug classes is a key risk

(03:35):
factor, but beyond that, things like recent immunizations or
having had a bone marrow or organ transplant are mentioned.
Certain infections to like mycoplasma or HIV can increase
susceptibility. What about underlying conditions
or or genetics? Yeah, both conditions like SLE,
systemic lupus erythematosus andalso malignancy are listed as

(03:55):
increasing risk and genetics. Definitely there's specific
mention of the HLA B for five O 2 allele.
HLA B45O2 What's the story there?
Well, this particular genetic variant is found more often in
certain ethnic groups, particularly people of East
Asian descent, and carrying thisallele dramatically increases
the risk of 10 if exposed to certain drugs, especially some

(04:18):
anticonvulsants like carbamazepine.
It really shows how it's often amix of the trigger, like the
drug, and the person's genetic makeup.
That genetic link is crucial, especially for tailoring
prescribing potentially. OK, so 10 looks dramatic.
What else could it be confused with?
What are the main differential diagnosis?
Yeah, this is super important because you need to rule things

(04:38):
out quickly. Basically anything causing
widespread blisters or skin peeling.
The list is quite long. Go on staphylococcal scalded
skin syndrome. SSSS, especially in kids that
talks and mediated though burns obviously.
Chemical thermal bullous and pedigo.
Another skin infection. Then autoimmune blistering
diseases like pemphicus or pemphigoid.

(04:59):
But the sources say they're usually much slower to develop
than 10. Slower onset, right?
Yeah. Genetic conditions like
epidermolysis bullosa SLE itselfcan have severe skin
manifestations. Scarlet fever is mentioned, but
it causes peeling desquimation without the blisters the the
bullet. That's a key distinction.
Ah, no bullet. Good point.
Other severe drug eruptions erythema haltiform, which is on

(05:21):
the same spectrum but generally less severe.
Skin detachment, bullets, lichenplanus, toxic shock syndrome,
again toxin mediated, and then general widespread redness and
peeling conditions like erythroderma.
A lot to consider. Definitely need careful
assessment. Thankfully you said it's rare.
How rare are we talking? Very rare, yes.
The estimate is about one to twocases per million people per

(05:44):
year globally. It is noted as being a bit more
common in older people, possiblyjust because they tend to be on
more medications, right? Makes sense.
OK, so rare, but devastating when you do suspect he and what
does the patient actually look like?
How does it typically present? It often starts quite subtly,
which makes early diagnosis tricky.
There's usually a prodrome phase, maybe two or three days.

(06:06):
Feels like a bad flu. Flu like.
Yeah, fever, maybe some upper respiratory symptoms, sore
throat, feeling generally unwell, achy joints and muscles,
maybe some itching and importantly, conductivitis, red
sore eyes. So really nonspecific at first.
Exactly. But a key feature mentioned in
about 90% of cases is early mucous membrane involvement.

(06:27):
Sore mouth, sore eyes, genital discomfort, sometimes before the
skin rash really kicks off. That's a red flag.
And then the skin changes. Yes, and it happens fast.
A red painful rash appears, often starting on the face or
the upper body, then spreading quickly.
Blisters or bulai form in these red areas.
Then these blisters merge and the top layer of skin starts to

(06:50):
Slough off, detach and sheets. It's often described as looking
like a severe burn because it's so painful and the skin loss is
so extensive. And how is the patient
systemically? Very unwell, typically running a
high fever, hyperpyraxia. They can quickly become
dehydrated because of the fluid loss through the damaged skin
leading to low blood pressure, high heart rate.
It's like a major burn injury interms of fluid loss and risk.

(07:11):
Is there that specific sign Nikolski's?
Yes, positive Nicosia sign is a classic finding.
If you apply gentle rubbing or sideways pressure on seemingly
normal skin near a blistered area, the top layer just shears
off. It shows how fragile that
epidermal dermal junction is, right?
OK, let's try a quick scenario. Say a patient started a new
antibiotic a week ago. They felt rough for a couple of

(07:33):
days. Fever, really sore eyes and
mouth. Now they've got this incredibly
painful red rash spreading over their chest and back, large
blisters forming, and you noticerubbing their arm gently causes
the skin to peel right off. Yeah, that's a textbook picture.
The drug exposure, the prodrome,the crucial mucous membrane
signs early on, then the rapid, painful, blistering rash, often

(07:55):
starting centrally. And that positive Nikolski's,
that pattern screams 10 or SGS 10.
Spectrum needs urgent action. Absolutely.
So high suspicion. What tests do you actually do?
Well, the diagnosis is mainly clinical.
It rests heavily on the history,especially that drug history and
the physical exam findings. There's no single blood test
that says yes. This is 10.

(08:16):
But you still need labs right? For management.
Absolutely critical. You need baseline bloods and
ongoing monitoring. Full blood count.
Urea and electrolytes are vital to track hydration, kidney
function, albumin. Protein levels can drop
significantly. Urine tests too.
Checking for protein, for instance.
And what about confirming the diagnosis or ruling out those
differentials? Screening for infection is key,
so blood, urine, skin cultures and a skin biopsy can be really

(08:40):
helpful. It won't prove 10 on its own
maybe, but it shows that characteristic full thickness
epidermal necrosis and helps differentiate it from things
like SSSS or autoimmune blistering diseases.
OK. And the material mentioned
Stevens Johnson syndrome, SJS being related.
Yes, SJS and 10 are viewed as the same disease process, just

(09:00):
on a spectrum of severity. The distinction is made based on
the percentage of body surface area the BSA that has skin
detachment. The sources don't specify the
exact cut offs here, but basically less detachment is
SJS. More extensive detachment pushes
it into SJS. 10 overlap or full blown 10.
Got it. So clinical diagnosis,
supportive tests, how do we manage it?

(09:21):
What's the approach say in the UK?
Management is all about speed and intensity.
First step, immediate hospital mission, ideally straight to a
specialised unit. Like a burns unit?
Exactly, a burns unit or maybe adermatology ICU if available.
They have the expertise in managing large areas of skin
loss and critical illness. And the absolute first thing you
do. Stop the suspected causative
drug immediately. That's priority number one.

(09:44):
Then it's all about intensive supportive care and preventing
complications, especially infection.
This is ICU level care. Is there anything
pharmacologically to like stop the reaction itself?
This is where it gets a bit controversial.
According to the sources, intravenous immunoglobulin IVI
is mentioned as a first line pharmacological option.

(10:07):
OK. IVI anything else?
Other drugs like cyclosporine, maybe cyclophosphamide are
mentioned, but importantly the material highlights that
systemic steroids, IVID, cyclosporine, even TNF alpha
inhibitors, they're all still considered controversial
treatments. OK, so no magic bullet drug.
Not really a universally agreed one.
Well, things like plasmapheresisor drugs like infliximab or

(10:28):
attainercept have been considered or used.
There's a lack of definitive evidence from large trials.
So the cornerstone remains stopping the trigger and
aggressive supportive care. Right.
Tell me more about that supportive care.
What does it actually involve? It's incredibly detailed, very
similar to managing major burns.You've got massive fluid loss,
so meticulous fluid and electrolyte replacement is
viable. Infection controls huge.

(10:51):
That lost skin barrier means a massive risk of sepsis, so
barrier nursing, careful monitoring, maybe prophylactic
antibiotics. So that's also debated.
And nutrition. And skin care.
Yeah, nutritional support is key.
Often needing tube feeding if the mouth is badly affected and
the skin care is intensive. Gentle cleaning, maybe some
debridement of dead skin, special non adherent dressings,

(11:13):
emollients trying to prevent shearing forces on the fragile
healing skin. It takes a whole
multidisciplinary team. Sounds incredibly challenging.
Given all that, what's the outlook?
What's the prognosis? It's serious.
TIN has a high mortality rate. The outcome really depends on
factors like how much skin it's involved, the BSA, the patient's
age, any other underlying healthproblems, and crucially, how

(11:36):
quickly they get to that specialised care.
Is there a way to quantify that risk?
Yes, the Scort and scale is usedfor exactly that.
It predicts mortality risk basedon several clinical factors.
The natures are quite sobering. How sobering.
A score of 01 gives about a 3% mortality risk.
Score 2 it jumps to 12%. Score 3 is over 35%, Score 4 is

(11:57):
nearly 60%, and if the score is five or more, the mortality risk
is estimated at 90%. Wow, that really brings home the
severity it does. And for those who do survive,
are there lasting effects? Yes, definitely.
Surviving the acute phase is often just the beginning.
Long term complications are common and absolutely vital.
Survivors must avoid the offending drug forever, and it

(12:19):
needs to be clearly documented everywhere in their records.
What sort of long term problems are we talking?
About they can be really widespread because it hits
mucous membranes too. In the acute phase.
Besides sepsis, you worry about pneumonia, respiratory failure,
dehydration, shock, organ failure, blood.
Clots the immediate dangers, butlong term.
Long term eye problems are a major concern.

(12:39):
Severe dry eyes, scarring, even blindness, joint contractures
from immobility, nail loss or abnormalities, persistent mouth
problems, swallowing difficulties from esophageal
strictures, GI bleeding, genitalissues like themosis in men or
gynaecological problems. And the skin itself, does it
heal OK? Often it heals with pigment

(13:00):
changes, patches of lighter or darker skin.
Scarring can happen, especially if there was infection.
Increased sun sensitivity is common, and of course there's
the huge psychological toll of having gone through something so
traumatic. It really is a devastating
condition top to bottom. Absolutely.
This deep dive really underlinesthat 10, while rare, demands
immediate recognition, stopping the drug and getting the patient

(13:22):
to intensive, specialist supportive care.
The potential for severe complications, both immediate
and long term, just highlights why being vigilant about drug
reactions and recognising those early signs is so vital.
A really important overview. Thank you for walking us through
that complex picture so clearly.Happy to help, it's crucial
information and. Thank you for tuning in to this
deep dive. For more free MSRA revision

(13:45):
resources, you can visit fremessra.com and for the full
Premium Revision Toolkit, check out Pass throughout sra.com.