00:01
Welcome. The topic for this talk is erythema
multiforme,
which is a very interesting lesion with a
very characteristic rash.
00:10
So erythema multiforme or EM is a targetoid
lesion.
00:16
And this is not named after a certain
department store chain in the United
States, but rather is based on the fact that
it looks like a big bullseye.
00:25
And there may or may not be systemic
symptoms,
but the characteristic lesions are what kind
of give this this entity
its particular designation.
00:35
The epidemiology of this is it's not all that
common.
00:39
So a global incidence of maybe 2 million
cases annually,
given that there are 7 billion people or so
on the planet,
it's kind of 1 in 2000.
00:48
So not that common, but you will encounter it
probably at some point or another in
your careers. It is more common in young
adults,
typically less than 30 years of age,
men greater than women,
for reasons that are not clear to me.
01:01
And maybe one of you out there has a better
idea.
01:04
So with regard to pathophysiology,
the vast majority of cases of erythema
multiforme, 90% or more are going to be
infectious.
01:14
Leading the charge is going to be viral
infections and in particular those associated
with herpes simplex virus type 1 or 2.
01:22
They are going to be maybe up to 50% of all
the causes of erythema
multiforme. So keep that in mind.
01:29
Epstein-barr virus can do this and certainly
other viruses as well.
01:33
In other categories bacterial infections.
01:35
And you see a list there of potential
bacterial infections can also be a cause
for erythema multiforme.
01:44
Similar targetoid lesions also occur in Lyme
disease.
01:48
Borrelia infections, which are more common,
as you're probably aware,
in the northeastern United States.
01:54
On clinical grounds alone,
you can't really distinguish erythema
multiforme versus the targetoid lesion that
occurs
with Lyme disease, although the Lyme disease
tends to be single lesions and
erythema multiforme tend to be multiple
lesions.
02:11
But on clinical grounds can't tell them
apart,
and you need to keep that in your
differential as well with target lesions.
02:19
Fungal causes can also be involved with
erythema
multiforme, although typically less
frequently.
02:26
Of the noninfectious causes,
we have three general categories,
and one is going to be drugs.
02:31
And there's a panoply of drugs that can be
associated with erythema multiforme.
02:37
Secondly, malignancy occult malignancies,
particularly leukemias and lymphomas
are certainly a possibility.
02:44
And if you rule out everything else that
rises to the top of your differential.
02:49
And then finally, a variety of autoimmune
diseases,
inflammatory diseases not otherwise
specified,
including sarcoid, lupus,
polyarteritis nodosa that lead to
kind of a systemic pro-inflammatory state
that can also manifest with the targetoid
lesions that we see in erythema multiforme.
03:08
Erythema multiforme is characterized or
classified as either minor or major
based on the presence or absence of one,
mucosal lesions,
two, systemic symptoms.
03:18
So systemic symptoms would be fever,
night sweats,
weight loss, joint and muscle aches and
pains,
that sort of thing. If you just have the rash
it's a erythema multiforme
minor. Add the other ones on top and now
you're into major category.
03:34
What's going on? So remember I said HSV was
the most common infectious cause about
50% of the cases. And what is happening is
that the the
keratinocytes are infected with
HSV. HSV is now driving the production of
various
antigens, various viral proteins that can be
expressed and then
subsequently recognized on the surface of the
keratinocytes.
04:00
And then you have HSV-specific helper T
cells,
typically of a Th1 phenotype.
04:06
So they're going to be driving the production
of certain pro-inflammatory cytokines such as
interferon gamma. The upregulation of those
pro-inflammatory
cytokines and chemokines drives the
subsequent recruitment of inflammatory
cells, NK cells, CD8 cells,
other
additional CD4 positive T cells,
and macrophages that will then
in turn cause keratinocyte damage via all
those mechanisms.
04:33
So we have kind of a infection recognized by
host,
recruitment of inflammatory cells and then
damage to the infected cells.
04:44
And that's how we're getting the targetoid
lesions of erythema multiforme.
04:49
The clinical presentation.
04:50
Well again like most things in dermatology or
dermatopathology
it's by inspection. So it will be,
the lesions will typically begin
as erythematous that is to say red flat
macules that
over 3 to 5 days as we recruit more
inflammatory cells convert into
papules and eventually the targetoid lesions.
05:12
And these are typically 1 to Three
centimeters in diameter,
so they're pretty big and not easy to miss
provided you actually
look for them. They tend to be symmetrical
and a peripheral
distribution on extensor surfaces.
05:28
So kind of like that. And like that there's a
centripetal spread.
05:32
So they start trunk and then they go out to
the periphery and they tend to be quite itchy
or pruritic. The mucosal lesions are very
painful.
05:42
They are erosions and ulcers within the mouth
and on the lips.
05:47
You can also get involvement around the eyes
so the ocular mucosa and then the genital
mucosa and anus. They usually erythema
multiforme,
as the immune system responds and then we get
the counter-regulatory mechanisms.
06:01
We typically get spontaneous resolution
within about a month.
06:04
And there are no long term sequelae,
although the lesions can recur because
again if infection is a major driving force,
if you get reinfected,
yes, you can go through that cycle again
entirely.
06:17
How are we going to diagnose this?
Well, it's the clinical presentation.
06:22
It's how they look. We can also,
since we know that 90% of these are going
to be due to some infectious entity,
we can do serologic testing to try to
identify that in patients who also have
respiratory symptoms,
you want to look for certain mycobacteria.
06:36
But in patients who have and the most common
one being HSV herpes
simplex virus, you want to look for that and
particularly if it's recurrent,
that tends to be the major player in
recurrent erythema multiforme.
06:51
The biopsy somewhat nonspecific.
06:54
A lot of things look like this.
06:56
So it's the biopsy per se is not going to
nail the diagnosis.
06:59
But it will rule out some other things.
07:02
And what you're going to see is damage to the
epithelium.
07:05
And that's represented as kind of vacuolated
and degenerated keratinocytes
at the Dermoepidermal junction.
07:12
You're also going to see some dermal
inflammatory infiltrate mononuclear
cells. You may also see vascular congestion
vascular dilation as
well as edema within the dermis,
but again somewhat of a nonspecific
picture. How do we manage it?
Well, as I said before,
it's mostly self-limiting and doesn't
typically require treatment.
07:35
However, if there's recurrent disease,
we may want to
consider getting rid of the causative agent,
particularly infectious agents.
07:44
Symptomatic therapy. When it's really itchy
or involves the mouth,
we can give topical corticosteroids or oral
antihistamines to kind of lessen
those itchiness. And then we can give
anesthetic
mouthwash for oral lesions and for recurrent
erythema multiforme
that you get over and over and over again.
08:05
You may want to give continuous acyclovir
therapy for the
virus for six months as a suppressive
therapy.
08:13
With that covered we targeted a very
characteristic lesion
and talked about it from beginning to end.
08:20
Thanks.
The lecture Erythema Multiforme: Pathophysiology by Richard Mitchell, MD, PhD is from the course Inflammatory Lesions of the Skin.
What is the most common infectious cause of erythema multiforme?
What feature distinguishes erythema multiforme major from minor?
How do the skin lesions of erythema multiforme typically evolve?
Which treatment is most appropriate for recurrent HSV-induced erythema multiforme?
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