00:00
Alright, 3 more to go. Now, the ANCA-associated small vessel vasculitides, which is all the ones
we've got left, they actually have a lot of things in common so let's compare and contrast them
Okay, so again, this slide is going to cover all the things that are common to all of the
ANCA-associated vasculitides. First off, they are called small vessel but again as I mentioned
before, they do have some medium vessel involvement as well. You're going to see systemic symptoms
with these diseases typically fevers, maybe weight loss, maybe malaise and there may be a prodrome
of weeks to months before you start to see symptoms. In fact, with EGPA, eosinophilic granulomatosis
with polyangiitis, it could be a few years before you start to see these more fulminant
presentations. It may involve the kidneys and they often do, you're going to see a rapidly
progressive, crescentic, pauci-immune glomerulonephritis. And on skin biopsy similar to what
you saw with PAN, you're going to see subcutaneous nodules but you may see also granulomatous
lesions as well. On exam, you're going to have maculo-papular erythematous rash, you may have some
palpable purpura, and you may also find livedo reticularis. You're going to start to see some
commonalities between all the different vasculitides and it's going to be difficult to tease them
apart but we're going to do our best to get through it all. When you look at the lung exam,
on chest x-ray, or on physical exam, you'll find pleural effusions, nodules, opacities, and you
may also see alveolar hemorrhage but perhaps not as common as you might see it in polyarteritis
nodosa. Other manifestations include the cardiovascular system where you might see heart
failure or pericarditis, gastrointestinal system, again mesenteric ischemia, and also you could
find mononeuritis multiplex just like we saw with PAN. With ANCA-associated vasculitides, you
can have fairly quick life threatening organ involvement that will progress somewhat rapidly
over time. It's actually most often the cardiac manifestations that are the most lethal
manifestations of the vasculitides. In addition, you're going to find a high ESR and high CRP but
these are kind of generic inflammatory markers. Now, we've had this image here on the right
for all this time. We may as well talk about it. Right? So the image on the left p-ANCA, the p
stands for perinuclear and that means that essentially there are anti-bodies that are surrounding
the nucleus that are lighting up. It turns out that the p in perinuclear refers to myeloperoxidase
as well. That's the enzyme which was later identified to be the protein that's floating around
the nucleus. What's difficult to see in that slide on the bottom left is that there's a larger cell
around that ring around the nucleus. So, that antibody is lighting up just around the nucleus.
02:53
In contrast, if you look at the picture on the right, c stands for cytoplasmic and that means
that the protein that's being highlighted there is actually diffusely spread throughout the
cytoplasm rather than being just around the nucleus and you can see the nucleus is vaguely
highlighted there on the right but it's the entire cell that is being lit up. So that's what
perinuclear versus cytoplasmic ANCA-associated proteins refer to. For c-ANCA, the specific
protein that's highlighted is called proteinase 3. Now we have to make a very key point here.
03:25
Importantly, not all ANCA-associated vasculitis is ANCA-positive. Now that doesn't confuse
you, you're not paying attention. I just said that not all ANCA-associated vasculitis is associated
with a positive ANCA. I know. These are basically cases in which everything looks like a typical
ANCA-associated vasculitis with a classic ANCA-associated vasculitis story, classic symptoms,
classic biopsy findings but the actual serum ANCA testing is negative. Go figure. Alright, so now
that we've talked about that common things about the 3 ANCA-associated vasculitides, let's
talk about how to tease them apart. We'll start with GPA, granulomatosis with polyangiitis.
04:17
The characteristic feature of this one, which used to be called Wegner's, is ENT involvement;
ear, nose, and throat involvement. 90% of such patients will have necrotizing lesions of the
nasopharynx, this classic saddle-nose deformity which you can see here, otitis media interestingly
enough, sinusitis, hemoptysis, the entire part of the ENT system can be involved here. In addition,
such patients are very likely to have renal involvement and that's a crescentic glomerulonephritis,
and these patients 90% of them will be c-ANCA positive and again they're staining for PR3,
proteinase 3, here. In contrast, this is microscopic polyangiitis. In many ways, microscopic
polyangiitis is very similar to granulomatosis with polyangiitis except, you guessed it, it doesn't
have granulomas on biopsy. Otherwise, very similar presentation, similar pathology, and the
other difference is it's ANCA positivity is instead on the perinuclear side with evidence of MPO
staining 70% of the time. Next up is eosinophilic granulomatosis with polyangiitis which is
definitely distinct from those other 2 types. This is going to have more of a pulmonary involvement
type of picture rather than all that ENT involvement with the necrotizing features. These folks
are going to have asthma oftentimes for a decade or more before the onset of more of the
systemic symptoms. They will have some sinus symptoms. So, rhinosinusitis, nasal polyps,
maybe serous otitis media but you're not going to see those destructive symptoms like the
saddle-nose deformity, that sort of thing with EGPA. Most importantly, this is the most
significant finding is lots of eosinophils. Whether you're going to have peripheral eosinophilia
with eosinophil counts in the 10-15% range or if you perform biopsies or a broncho-alveolar
lavage, you're going to find eosinophils in places you don't normally find them in great numbers.
06:16
In EGPA, in terms of it's ANCA positivity, this is one of the ones that is not always associated
with a positive ANCA, in fact only about 40% of cases of EGPA will have a positive ANCA. When
When it is positive, more often than not it is a p-ANCA type of picture staining for MPO. Okay,
so that was all of our vasculitides that we've had in our differential diagnoses. So now that
we've looked at all of them, let's look back at our patient and the diagnostic work-up that's
underway. Alright, let's start to jump into our data now that we've looked at every item on our
differential diagnoses. Okay, so I'm seeing right off the bat we have a little bit of an anemia
with a low hemoglobin, slightly elevated white blood cell count but there is a significant finding
with 13% eosinophils up there in the top right and I want that to trigger a flag, you should be
thinking about EGPA as soon as you start to see peripheral eosinophilia. Creatinine of 1 is also
important. That's going to really make our likelihood of having GPA, MPA, or ATGBM disease
considerably less and of course the accompanying negative urinalysis supports that as well.
07:25
Those conditions usually have renal involvement. Next up, the IGE level, we hadn't talked about
that before but that's one of the lab tests that can be associated with EGPA. The p-ANCA,
we've talked about the different ANCA positivities here, p-ANCA is one of the ones that is more
likely with EGPA, either way the fact that this person's ANCA positive should definitely take
PAN off of our list. Next up, looking at the x-ray findings, yes we clearly have some pulmonary
involvement, that could go for and against the couple different conditions but the big finding is
the bronchoalveolar lavage, 40% eosinophils. Typically you'll only have a few percent of eosinophils
present on a BAL, if any at all. So that is strongly supporting our diagnosis of EGPA. Lastly,
we'll probably going to perform a skin biopsy in such a patient and in this case we would find a
necrotizing vasculitis with eosinophilic infiltration and perivascular necrotizing granulomas.
08:27
This is a slam dunk for EGPA. So, have we made our diagnosis? Let's revisit some of the salient
features of our H&P to just review a few things.