Welcome back, Clinical Problem Solvers! In this post we’ll dive deeper into our illness script for Granulomatosis with Polyangiitis (GPA).
Overview & Pathophysiology
All vasculitides are characterized by blood vessel inflammation, and we can group them by the size of the affected vessels. Here’s our working schema (to be featured on a future episode):
GPA is a small vessel vasculitis, and one of the three ANCA-associated vasculitides. The other two are microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
A 70-year-old man with COPD presented with subacute pleuritic chest pain and dyspnea. A CXR showed a left upper lobe consolidation, and he was treated with antibiotics for presumed community-acquired pneumonia. However, the patient continued to be symptomatic and he returned for further evaluation.
A CT Chest showed multifocal cavitary lung nodules. His infectious workup was unremarkable and ANCA serologies returned positive for c-ANCA/PR3. A lung biopsy demonstrated necrotizing granulomatous inflammation, and a diagnosis of GPA was made.
We often think of GPA as a pulmonary-renal syndrome, but, while many patients develop renal complications, a much smaller percentage present with them.
It’s important to remember that GPA is a systemic illness with a variety of manifestations across multiple organ systems. The tempo of these symptoms can range from a smoldering subacute illness to a fulminant acute presentation over a few days.
Let’s review some of the most common signs and symptoms of GPA, so that we know when to bring it into our DDx.
Ear, Nose, and Throat
The upper airway structures are the most commonly involved organs in GPA. Findings include recurrent sinusitis, recurrent otitis, and bloody or purulent nasal discharge.
In Episode 24, Dr. Sarah Goglin taught us that sinus symptoms can be an early finding, and it is not uncommon for patients to be treated for recurrent bacterial sinusitis many times before a diagnosis of GPA is made.
GPA can also cause destruction of the nasal bones and cartilage, leading to the characteristic saddle-nose deformity seen here:
(Source: Saddle Nose Deformity (NEJM))
Lower Respiratory Tract
Both the airways and pulmonary parenchyma can be involved in GPA with a wide range of manifestations, ranging from dyspnea or pleurisy (as in our case) to catastrophic respiratory involvement with diffuse alveolar hemorrhage.
As Dr. Goglin explained, GPA is really the only rheumatologic disease that causes cavitary lung nodules. This finding, especially when refractory to antibiotics, warrants consideration of GPA, in addition to the many associated infections.
Renal complications are common in GPA, and include an active urine sediment (hematuria, proteinuria, and RBC casts), intrarenal acute kidney injury, and even rapidly progressive glomerulonephritis and renal failure. Kidney biopsy will often show a pauci-immune glomerulonephritis.
The most common skin finding will be a leukocytoclastic vasculitis with purpura that will occasionally be necrotic or ulcerated, as seen here:
(Source: Robert A. Briggaman via Small Vessel Vasculitis from NEJM)
Common neurologic manifestations of GPA include mononeuritis multiplex (i.e. a neuropathy affecting two or more noncontiguous nerves) and cranial neuropathies.
GPA is endlessly fascinating, and there is far more to this disease than what we covered here! Some of our favorite articles on the topic are listed below.
- Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis
- Small Vessel Vasculitis- NEJM
- Clinical Problem Solving Case: The Right Frame
- Pulmonary Wegener’s Granulomatosis: A Clinical and Imaging Study of 77 Cases
- The Pulmonary Vasculitides