Case 3: Baseline Characteristics
In this video, Craig Gordon, MD, nephrologist at Tufts Medical Center and associate professor of medicine at Tufts University School of Medicine, discusses the baseline characteristics in this case of ANCA-associated vasculitis:
Editor’s note: The following is an automatically generated transcript of the above video.
“Let's get started with a patient. So this is a 66-year-old woman with osteopenia, recurrent sinusitis, GERD, and hypertension. She presents to the emergency department with joint swelling, rash, and ankle swelling. And there her exam reveals a petechial rash, one plus lower extremity edema, and her exam is otherwise unremarkable. Her serum creatinine is elevated at 2.5 milligrams per deciliter and her baseline is 0.7. So this is a true major decline in GFR. Her urinalysis reveals three plus blood and two plus protein and review of her urine sediment shows multiple dysmorphic as well as non-dysmorphic red blood cells and several RBC casts.
And as we often do in clinical practice, a series of serological tests were sent for the workup of glomerular disease. But as I'm sure most, if not all of you, know that this is really an urgent situation and we're not going to want to wait for those results. So given the hematuria, proteinuria, and the presumptive increase in creatinine that is thought to be acute, the patient is managed for presumed rapidly progressive glomerulonephritis or RPGN, and she's treated with pulse IV methylprednisolone and she gets a three day course of this.
Somewhere in these first three days in the hospital, she undergoes a kidney biopsy. That biopsy reveals a necrotizing and crescentic glomerulonephritis. And in particular, more than 50% of glomeruli revealed cellular and/or fibrocellular crescents. On the immunofluorescent microscopy, no deposits were seen making this a pauci-immune glomerulonephritis. And subsequently, several days later, her anti-PR3 titers return positive at 340 with a C-ANCA titer of 1:320. And the remainder of her serology is most notably the anti-GBM, but also ANA complements and many others turn negative. And I'll come back to my point about anti-GBM a little bit later in the talk.
So the diagnosis was a crescentic pauci-immune ANCA-associated vasculitis and given the PR3 positivity and C-ANCA positivity, very likely granulomatosis with polyangiitis or GPA. So let's take look at the clinical presentations of the different forms of ANCA-associated vasculitis. And this is a table from the KDIGO guidelines in 2024, which highlights some of the organ systems involved in the three major classifications of ANCA-associated vasculitis. So the first of these is microscopic polyangiitis. The case we're probably dealing with today is granulomatosis with polyangiitis or GPA, formerly known as Wegener's. And the third version of ANCA-associated vasculitis is eosinophilic granulomatosis with polyangiitis, which was formerly Churg-Strauss.
I'm going to focus really on the first two columns just to highlight that skin involvement is common, but in about 40% of individuals will have cutaneous involvement. Kidney involvement in MPA and GPA is virtually in everyone, 80 or 90%. And pulmonary involvement tends to be more notable in GPA as well as the well-described ear, nose, and throat manifestations. But these are not universal features and certainly you can have ear, nose, and throat and pulmonary involvement in microscopic polyangiitis and absolutely can have cases of GPA without these.
So let's turn to the biopsy for a second before we turn to management. So the KDIGO, as I mentioned, recently about six months ago, published a update to the chapter on ANCA-associated vasculitis as part of the 2024 clinical practice guideline on ANCA-associated vasculitis. This was an update to the earlier 2021 practice guideline on glomerular disease. And KDIGO will continue to update chapters from that as evidence arises. So that should be a clue that there's going to be some new important things we've learned about treatment of ANCA-associated vasculitis in the slides to come.
As you can see here, a biopsy that shows greater than 50% globally sclerotic glomeruli would be labeled a sclerotic class. And this is probably someone where treatment might cause more harm than good. Those with greater than 50% normal glomeruli are considered focal class by our colleagues from pathology. And those with greater than 50% cellular crescents are considered crescentic class. And there can also be mixed classifications. And I think this information is relevant just to sort of think about how aggressive we want to be in treatment versus having the wisdom to not be too aggressive in the wrong circumstance.”