Pulmonary Vasculitis
Vasculitis is primarily associated
with inflammatio and necrosis of blood vessels, and includes a number of rare
conditions (vasculitides) with high untreated mortality. Pulmonary
vasculitis commonly occurs with systemic vasculitis, and may cause wheeze,
hypoxaemia, pulmonary infiltrates masses, necrotizing lesions and/or alveolar
haemorrhage. Vasculitis may be secondary to systemic collagen vascular
disease such as rheumatoid arthritis, scleroderma or systemic
lupus erythematosus (SLE) or may be primary vasculitides that
involve pulmonary blood vessels (Wegener’s granulomatosis, Churg–Strauss
syndrome, microscopic polyangiitis, lymphomatoid granulomatosis and angiitis).
Anti-glomerular basement membrane disease (Goodpasture’s syndrome) has a
similar clinical presentation to pulmonary vasculitis.
Most primary vasculitides involve
neutrophil infiltratio into the lung interstitium, with consequent vascular
damage by fibrinoi necrosis; capillary rupture can lead to alveolar
haemorrhage. Autoantibodies against components of the cytoplasm of granulocytes
and neutrophils, antineutrophil cytoplasmic antibodies (ANCA),
are diagnostic markers for vasculitis and may be part of the pathology. These
are differentially characterized by neutrophil staining: cytoplasmic (c-ANCA)
and perinuclear (p-ANCA), which are largely synonymous with PR3-ANCA (targeting
peroxidase-3), and MPO-ANCA (targeting myeloperoxidase), respectively (Table
1).
Collagen vascular diseases
Rheumatoid arthritis may cause vasculitis and pulmonary hypertension
(Chapter 27); however, this is far less frequent than pleural disease
(Chapter 32) or diffuse parenchymal disease (Chapter 30). Patients may develop Caplan’s
syndrome as a result of dust inhalation (e.g. coal dust) (Chapter 33). Limited
cutaneous scleroderma often spares lung parenchyma and causes pulmonary
hypertension by direct involvement of pulmonary arterioles. While not common, pulmonary
capillaritis causing alveolar haemorrhage secondary to SLE is a devastating
complication with a high mortality rate. Patients generally have a pre-existing
diagnosis of SLE, usually with renal involvement. Rarely, SLE may cause
pulmonary hypertension by direct involvement of the pulmonary vasculature.
Clinically, this is indistinguishable from pulmonary arterial hypertension (Chapter
27).
Vasculitides
Wegener’s granulomatosis (WG) is a systemic vasculitis that predominantly
involves the upper and lower respiratory systems and the renal glomeruli.
Vascular inflammatio may involve arterioles, capillaries and venules. Patients
are generally aged 40-60 years and present with upper respiratory symptoms,
usually involving the sinuses (sinusitis) or nasopharynx (ulcers, septal
perforation, saddle nose deformity). Radiographic abnormalities in the chest
are common, mostly as nodules or masses, often with cavitation (Fig. 29a), but
they may appear as parenchymal infiltrates Renal disease is usual and consists
of glomerulonephritis with haematuria, proteinuria and red blood cell casts.
Necrotizing granulomas (chronically inflame tissue masses characterized
by multinucleate giant cells) are seen in the lungs (Fig. 29b), nasopharynx and
kidneys. WG may also involve the ears (otitis media), eyes (conjunctivitis,
uveitis), heart (coronary arteries), peripheral nervous system, skin or joints.
PR3-ANCA has a 60-90% sensitivity and more than 90% specificit for WG.
Churg–Strauss syndrome (allergic granulomatosis and angiitis)
is a medium/small vessel granulomatous vasculitis of the lung, skin, heart, nervous
system and kidney. It is probably the second most common pulmonary vasculitis
after WG. Most patients have a history of allergic rhinitis and/or asthma and
peripheral eosinophilia that may predate the vasculitis by up to a decade.
Patients will present with worsening asthma, fever, malaise, subcutaneous
tender nodules, mononeuritis multiplex and radiographic infiltrates There may
also be pericarditis, abdominal pain and glomerulonephritis. Radiographic
abnormalities are most often patchy, feeting infiltrates but may include
cavitating nodules or masses, interstitial infiltrate or pleural effusions. CT
scans may show ground glass opacities or peribronchial thickening. Lung biopsy
shows perivascular granulomatous inflammation small artery and vein vasculitis,
prominent eosinophils and necrosis. The diagnosis may be made without biopsy in
the presence of asthma, eosinophilia, migratory pulmonary infiltrate and
neuropathy. Both PR3-ANCA and MPO-ANCA may be positive. Treatment: most
patients respond to corticosteroids. Cyclophosphamide or azathioprine may be
added in resistant cases (suppress immune system). Patients who respond to
therapy seldom relapse. Patients with an onset of asthma immediately before or
concurrent with vasculitis have a poorer prognosis. Overall, survival is more
than 70%, with increased mortality due to cardiac, central nervous system
(CNS), renal or gastrointestinal involvement.
Microscopic polyangiitis has microscopic similarities to WG and polyarteritis
nodosa. In contrast to WG, MPA does not involve the nasopharynx and sinuses and
is usually associated with MPO-ANCA rather than PR3-ANCA. It is often seen in
patients with hepatitis B or C infection. Treatment with corticosteroids
and cyclophosphamide substantially reduces mortality.
Goodpasture’s syndrome is a facet of antiglomerular basement membrane
(GBM) disease, when antibodies (linear IgG) are deposited on the basement
membranes of the alveoli and glomerulus, causing damage to collagen and
consequent alveolar haemorrhage and glomerulonephritis, respectively. Alveolar
haemorrhage occurs predominantly in smokers, or after recent respiratory
infections that alter alveolar permeability. Patients present with rapidly
progressive glomerulonephritis, haemoptysis, anaemia and diffuse alveolar
infiltrate on radiographs. In contrast to the primary vasculitides, prolonged
systemic symptoms are uncommon. Pulmonary function testing demonstrates
elevated DLco from extravasated haemoglobin in the lung.
Diagnosis requires demonstration of anti-GBM antibodies in serum or linear IgG
in glomerular or alveolar basement membranes. Both PR3-ANCA and MPO-ANCA may be
positive. Treatment: patients with Good-pasture's syndrome should be
treated with high-dose corticosteroids, cyclophosphamide and sometimes
plasmapheresis. Therapy may control alveolar haemorrhage, but pulmonary and
renal function may not recover.
Lymphomatoid granulomatosis is a systemic vasculitis of lungs, kidneys, CNS
and skin. It is strongly associated with, and may be a late complication of, Epstein–Barr
virus infection. It behaves like an indolent lymphoproliferative disease
and may transform into a B-cell lymphoma. Patients typically have fever,
malaise, cough, dyspnoea and a papular rash. Radiographic abnormalities usually
consist of multiple lower lobe nodular densities. Lung biopsy shows
angiocentric/angiodestructive mixed cell infiltratio with lymphocytes, plasma
cells and atypical lymphocytes. Vascular occlusion and necrosis are common. Treatment:
Lymphomatoid granulomatosis is considered to be a lymphoproliferative
disorder and is treated with chemotherapy and corticosteroids. Without
treatment, the disease progresses and is usually fatal.
