All right. Next, let's move on to
urticaria and angioedema.
Urticaria, ultimately, is caused by mast cell
activation in the superficial dermis.
Mast cells, when they degranulate,
which is why it's very pruritic, and they
release a variety of vasodilators.
And that's what causes the localized swelling
and these classic raised flat lesions.
There's 2 main ways in which mast
cell activation occurs.
There's the IgE-mediated type
and then the non-IgE
mediated type. Let's talk about IgE first.
So, the IgE-mediated type
is essentially a type
1 immediate allergic reaction in which
the patient has previously been
exposed to some trigger, has
and those antibodies are now binding
to mast cells in the skin.
When that patient is then re-exposed
to that allergen,
the IgE immediately recognizes it,
triggers the mast cell,
and massive degranulation
occurs very readily.
The most common allergens
or drugs, like beta-lactams,
food allergies can do this, insect
bites like from Hymenoptera,
mosquitoes, etc., infections
like viruses, mycoplasma, and parasites. What
you'll typically see on physical exam
is a very asymmetric
distribution of lesions,
and they are abrupt in onset, intensely
pruritic -- again, due to all that histamine --
with very well demarcated, flat,
with central pallor. Next up, we're
going to talk about the
non-immune mediated causes of urticaria.
Essentially, mast cells are still involved,
but IgE is not part of the equation.
So specific medications can do this. NSAIDs,
particularly, COX inhibitors,
can block prostaglandin synthesis, which
allows mast cells to degranulate.
Opioids and vancomycin actually directly
stimulate mast cell activation in
And then ACE inhibitors are acting via
inhibition of kinin metabolism.
In addition, there are some physical
conditions that can lead to urticaria to form
in susceptible hosts. Certain
physical stimuli, like cold,
vibration, or pressure, can lead
to urticaria's emergence.
I should just add that there are some
less common associated
chronic conditions that can cause this.
Things like urticarial vasculitis,
mastocytosis, and a variety
of autoimmune diseases.
Now, in general, urticaria are self-limited.
The lesions only last for a few hours.
And while flushing and
fatigue and headache are not uncommon
with a simple urticarial reaction,
I do want you to be on the lookout for
more severe symptoms, like
throat tightness, bronchospasm,
nausea or vomiting.
That may be an indication of a more severe
reaction, such as, for example,
angioedema. Angioedema, by
definition, is localized
edema of soft tissue and mucosal tissues.
Now, it can occur in isolation, or it
may occur with urticaria or
potentially with anaphylaxis. It may
actually be life-threatening.
Patients experience throat tightness,
hoarseness, nausea, vomiting, diarrhea,
crampy abdominal pain, and you can see
a good picture of it here on the right.
Now, you might be wondering
why this tends to afflict
the face and the lips and the oral tissues.
Keep in mind that those are the
loosest tissues in your body.
So while this lesion, this process may be
happening in all the skin in the body,
it's these loose connective tissues
around the lips, the
face, the tongue, the throat, and the genitalia
that can cause these complications.
The mechanism is 1 of 2 different ways.
It can be mast cell-mediated,
which means mast
cell degranulation within the
deeper dermis through
mechanisms that are similar
to urticarial lesions.
Or it can be bradykinin-mediated,
which means it's not going
to require any mast cells whatsoever.
Bradykinin, when it's released,
increases vascular permeability. It's
an inflammatory mediator
just causes vasogenic edema.
Incidentally, if there's no mast cells
involved, it's going to be less
itchy because you don't have mast cells
degranulating histamine at the same time.
The most common cause of
is ACE inhibitors because they directly
inhibit bradykinin degradation.
Angioedema, if it's mast cell-mediated,
is going to be immediate.
In contrast, if it's bradykinin-mediated
by an ACE inhibitor,
patients often report being on ACE
inhibitors for months to years
before developing angioedema,
and it's still not clear exactly
why that's the case and what precipitates
the angioedema reaction.
All right. Having talked about
urticaria and angioedema,
the next logical extension is to briefly
Anaphylaxis is a severe type
1 hypersensitivity reaction. Patients are
going to present with pruritus,
urticaria, angioedema, laryngeal edema,
wheezing, and nausea and vomiting. It's
essentially mediated through the same
pathways that urticaria and
angioedema can be caused by.
Just want to briefly mention
fixed drug eruption.
This is a situation where a patient
ingests a medication,
develops a specific rash, say,
erythematous plaque on their left thigh.
If they don't take that medication again
for a while, and then they take it again,
strangely enough, they will develop the same
erythematous plaque in exactly
the same location.
That's essentially a fixed drug
eruption that will happen
predictably every time they're
exposed to that medication.
We've already spoken at some length
about erythema multiforme,
Stevens-Johnson syndrome, and
toxic epidermal necrolysis.
So let's now talk about DRESS and DHS.