Correct!
5. All of the above.
Our patient underwent treatment with high-dose steroids and plasmapheresis. She stabilized without further bleeding after transfusion and steadily improved throughout her hospital course.
Granulomatous polyangitis (GPA, formerly Wegner’s granulomatosis) and microscopic polyangitis (MPA) have traditionally been considered different clinical entities in part based upon their distinct antibody profiles. GPA is traditionally associated with proteinase 3 (PR3) antibodies (c-ANCA) and MPA is associated with myeloperoxidase (MPO) antibody positivity (p-ANCA). However, 20% of patients with GPA or MPA have the alternate ANCA. Recently there has been more difficulty in clinically distinguishing these ANCA-associated vasculitides based on serologic, histologic or clinical markers (2). Traditionally, GPA has been more frequently associated with pulmonary disease however there is significant overlap in clinical and histologic findings in both of these diseases.
Classically GPA involves both upper (chronic sinusitis, subglottic stenosis, and granulomatous nasal or paranasal inflammation) and lower respiratory tracts whereas MPA traditionally involves only the lower respiratory tract (3). Tracheobronchial disease is almost exclusive to patients with GPA though it’s important to note that GPA is based on a histologic classification rather than serologic. Tracheobronchial disease symptoms can include hoarseness, cough, dyspnea, stridor, wheezing, bronchiectasis and blood from supraglottic airways. Lower tract symptoms can include pleuritis, pleural effusions, pulmonary arterial hypertension, pulmonary fibrosis as well as pulmonary nodules and infiltrates. Lung nodules or infiltrates are apparent in 85% of patients with GPA (4).
Diffuse alveolar hemorrhage (DAH) is reported in 25-55% of patients with MPA and only 5% of patients with GPA. It has been seen as the presenting problem at diagnosis, mostly in MPA and increases mortality. In the acute setting 30% of patients do not survive an episode of DAH. In survivors of an episode of DAH their 1-year and 5-year survival is reduced to 82% and 68% respectively (5). Alveolar hemorrhage is the main cause of hospitalization and hospital ICU admission in cases of ANCA-associated vasculitis with pulmonary complications.
The mainstay of treatment for pulmonary disease from ANCA-associated vasculitides is glucocorticoid therapy and immune modulation. Induction is achieved with glucocorticoids. Azathioprine and methotrexate are commonly used to maintain remission, but recently there have been studies suggesting a role for Rituximab therapy. Plasma exchange has been recommended in critical situations with severe renal or pulmonary disease (6). By removing circulating ANCAs it is thought to decrease the autoimmune response and blunt further organ damage.
ANCA-associated vasculitides overlap significantly and cannot be distinguished based on their serologic markers alone. Our patient had a diagnosis of granulomatosis with polyangiitis clinically but had serologic markers of microscopic polyangiitis. The degree of pulmonary disease that can be associated with either disease process can be diverse and understanding the significant overlap between the two disease processes with regards to their pulmonary involvement is needed to appropriately recognize the possible pulmonary manifestations, regardless of the serologic diagnosis.
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