In this lecture, we will discuss granulomatosis with polyangiitis which used to be called
Wegener's syndrome and Goodpasture syndrome. These are both rheumatologic conditions
that affect both the kidneys and the lungs. So, let’s start with granulomatosis with polyangiitis.
This is an autoimmune vasculitis. It primarily affects medium-sized blood vessels of both the lungs
and the kidneys. It’s a rare condition. I’ve only made this diagnosis once in children.
So, there are constitutional, pulmonary, and renal symptoms that I’d like to cover. First, constitutional,
these patients may have fatigue, fever, malaise. They may develop anorexia or weight loss
like any other autoimmune condition. These patients will have pulmonary symptoms. They focus primarily
around the pulmonary hemorrhage. These patients will be found to be coughing up blood.
Any time a child is coughing up blood, you know something is very wrong. This is one of those conditions
that can cause it. Their cough will be bloody. On X-ray, you may see pulmonary nodules.
Those pulmonary nodules are commonly seen in this disease. Additionally, patients will have renal findings
and in particular, hematuria. So, they’ll be coughing up blood and they’ll be peeing out blood.
They may also have proteinuria as well. This renal disease can result in hypertension and renal failure.
In addition to these classic findings, there are a few other findings you should know about.
These patients may have chronic otitis media. They may get destruction of the cartilage of the nose
resulting in a saddle nose deformity. Those might show up on your exam. So, let’s talk about testing
for this disease. The hallmark test for a patient where you suspect granulomatosis with polyangiitis
is the c-ANCA. Of course, they may have other findings too like elevated inflammatory markers
or urine and blood on the urinalysis or nodules on their chest X-ray. But the c-ANCA is positive
in more than 80% of these patients. Let’s pause for a moment and remember what ANCA is.
ANCA is an antinuclear antigen, which antibody, which is found in neutrophils and monocytes
in patients with autoimmune vasculitis. When we look for this antibody, we may see it in the cytoplasm
which is a c-ANCA or in a perinuclear pattern which is a p-ANCA. You can see that the cytoplasm
in the p-ANCA positive patient is not lighting up and the perinuclear region is not lighting up
in the c-ANCA positive patient. c-ANCA is classically seen in Wegener's. p-Anca is seen in other
autoimmune conditions. So, let’s look at these two. c-ANCA is classic in inflammatory bowel disease.
It may be seen in primary sclerosing cholangitis
or eosinophilic granulomatosis with polyangiitis
which we used to call Churg-Strauss syndrome.
It can be seen in granulomatosis with polyangiitis or cystic fibrosis.
Likewise, the p-ANCA is sometimes seen in IBD, is seen in drug vasculitis, and may be seen
in autoimmune hepatitis. So basically, when we see these patterns, there are certain diseases
that tend to fit in one or the other or perhaps both conditions like inflammatory bowel disease.
So, let’s shift gears now to Goodpasture syndrome which is also an autoimmune disease that affects
the lungs and the kidney. In this case, the antibodies are directed against basement membrane proteins.
These antibodies cause inflammation along those basement membranes. That in turn is primarily
found in both lung and kidney. So these patients, just like patients with polyangiitis are going to have
a constitutional, a pulmonary, and a renal finding. Their constitutional symptoms are usually fever and malaise.
Their pulmonary symptoms include cough, again hemoptysis, and again respiratory distress.
Their renal findings are more likely to be proteinuria with generalized edema or hypertension resulting.
So, in patients with Goodpasture syndrome, we are going to do serum testing for the anti-glomerular
basement membrane auto antibody. So basically, it’s looking for antibodies that are bound
to the basement membrane. In patients who end up with a renal biopsy for what is presumed to be
nephrotic syndrome, we may pick up the evidence of Goodpasture syndrome. Basically on biopsy,
anti-GBM antibodies will show up with a linear deposition on immunofluorescent staining.
Here, you can see such a case. This is a glomerulus that is lighting up with the basement membrane
being the target of this antibody response. The treatment of Goodpasture is important because these patients
can get very sick. We usually start with steroids as a way of controlling the autoimmune response.
Patients may end up on cyclophosphamide and may benefit from rituximab. We will do plasmapheresis for any
patient who has hematemesis or a non-responsive renal disease. Those patients have the worst prognosis.
So, that’s my brief summary of these two diseases that are autoimmune affecting the lungs
and the kidneys. Sometimes people get confused. I’m hoping that by presenting them side by side,
you can see these key differences. Thanks for your time.