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).
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.