Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg- Strauss syndrome (CSS) are small to medium -vessel vasculitides that, because of their frequent association with antineutrophil cytoplasmic antibodies (ANCA), are usually referred to as ANCA-associated systemic vasculitides (AASV).

These diseases are challenging to diagnose and to treat. The diagnosis of AASV is made on the basis of clinical findings, biopsy of the involved organ and the presence of ANCA in the serum.

Lung disease is a very common and important clinical feature of AASV.

Vasculitis in the lung usually involves the small vessels -arteries, capillaries and venules.

Distinguishing the ANCA-associated vasculitides from other forms of vasculitis or nonvasculitic processes (such as infection) can be particularly difficult. 

ANCA are associated with small sized vessel vasculitis ; one subtype is an antibody against myeloperoxidase (MPO), which stains in a perinuclear pattern (P-ANCA) indirect immunofluorescence (IIF) using a neutrophil substrate, and the other subtype is an antibody against proteinase-3(PR-3), which stains in a diffuse granular cytoplasmic pattern ANCA by IIF. PR-3 ANCA is more specific in Wegener's granulomatosis than the other primary vasculitides.  MPO-ANCA can be found in microscopic polyangiitis (MPA), Churg Strauss Syndromes(CSS)

Capillaritis with severe pulmonary hemorrhage may be seen in all three diseases or as isolated single organ disease.

Of the other causes of small vessel vasculitis of the lungs SLE is the most frequent. Alveolar hemorrhage may be the presenting manifestations and is usually associated with glomerulonephritis. Immune complexes are present in the lungs with a granular distribution.

Less commonly, pulmonary capillaritis has been reported in patients with polymyositis and occasionally in the other collagen vascular diseases.

Pulmonary disease is uncommon in Henoch-Schonlein purpura and in the vasculitis of cryoglobulinanemia.

In Goodpasture’s syndrome primary capillaritis is associated with linear deposition of IgG and complement along the basement membrane.

The dual circulation of the lung may be one reason why the response to the systemic vasculitic disorders is unique, providing a spectrum of diseases different to that seen in other organs. Eg. The classical lesions of polyarteritis nodosa, which is a disease of systemic muscular arteritis, are very rarely seen in the lungs; whereas certain diseases such as Wegener’s granulomatosis typically involve the lower respiratory tract.

Recent classifications separate the types of vasculitis according to vessel size and type of immune response involved.

With rare exceptions, those that involve the lung cause disease of the small vessels - small muscular arteries, arterioles, capillaries, and venules.  Some types of small vessel vasculitis in the lung are also frequently associated with glomerulonephritis, producing the "pulmonary-renal" syndromes.

Very rarely the elastic pulmonary arteries may be involved by giant cell arteritis or Takayasu arteritis.

In addition to small vessel disease, Behcet’s syndrome typically produces aneurysms of the large elastic pulmonary arteries.

The interpretation of biopsy material requires detailed information of the clinical, radiological and serological findings.

 

Respiratory system involvement in antineutrophil cytoplasmic-associated systemic vasculitides: clinical, pathological, radiological and therapeutic considerations.Drugs R D. 2007;8(1):25-42. Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg- Strauss syndrome (CSS) are small-vessel vasculitides that, because of their frequent association with antineutrophil cytoplasmic antibodies (ANCA), are usually referred to as ANCA-associated systemic vasculitides (AASV). The diagnosis of AASV is made on the basis of clinical findings, biopsy of an involved organ and the presence of ANCA in the serum. Lung disease is a very common and important clinical feature of AASV. In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules, frequently cavitated, and masses are the most common findings on chest radiography. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar haemorrhage as a result of alveolar capillaritis is the most frequent manifestation of respiratory involvement, and is clinically expressed as haemoptysis, respiratory distress and anaemia. However, diffuse alveolar haemorrhage may also be subclinical and should be suspected when a chest radiograph demonstrates new unexplained bilateral alveolar infiltrates in the context of falling haemoglobin levels. Normal and high-resolution CT have a higher sensitivity than chest radiography for demonstrating airway, parenchymal and pleural lesions. However, many of these radiological findings are nonspecific and, therefore, their interpretation must take into account all clinical, laboratory and pathological data. Therapy of AASV is commonly divided into two phases: an initial 'remission induction' phase, in which more intensive immunosuppressant therapy is used to control disease activity, and a 'maintenance' phase, which uses less intensive therapy, for maintaining disease remission while lowering the risk of adverse effects of immunosuppressant drugs. In patients with AASV refractory to standard therapy with corticosteroids and oral cyclophosphamide, new therapeutic options are now available. Recurrence of pulmonary symptoms suggesting a flare indicates the need for a careful search for an opportunistic lung infection or iatrogenic pulmonary complications. In conclusion, involvement of the respiratory system is a very common and important organ manifestation of AASV. Respiratory system involvement comprises a wide spectrum of clinical features and radiological findings, and because of its frequency and prognostic significance, a complete assessment of the respiratory system should be included in the work-up of all patients with AASV. Respiratory system involvement in systemic vasculitides.Clin Exp Rheumatol. 2006 Mar-Apr;24(2 Suppl 41):S48-59. The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar hemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with hemoptysis, respiratory distress and anemia. However, DAH may be subclinical and has to be suspected when chest radiograph demonstrates new unexplained bilateral alveolar infiltrates, in the face of falling hemoglobin levels. In giant cell arteritis, the most frequent respiratory symptom is cough, usually non-productive, persistent, and responsive to corticosteroids. In Takayasu arteritis, pulmonary involvement is frequently subclinical and detectable by non-invasive techniques. Pulmonary involvement is rare in polyarteritis nodosa, Kawasaki disease, Henoch-Schonlein purpura and cryoglobulinemic vasculitis.In conclusion, the involvement of the respiratory system is a very common and important feature of AASV, whereas is less frequent in other SV. It comprises a wide spectrum of clinical features and radiological findings, and may have a prognostic significance. The assessment of the respiratory system should be included in the work-up of all patients with SV, especially of those with AASV. Immune mediated intra-alveolar haemorrhage in the adult.Rev Mal Respir. 2006 Feb;23(1 Suppl):3S61-73. INTRODUCTION: The diagnosis of diffuse intra-alveolar haemorrhage (DAH) is suggested by the combination of haemoptysis, anaemia and pulmonary infiltrates. Broncho-alveolar lavage produces macroscopically haemorrhagic fluid and/or haemosiderin laden macrophages. The diagnostic approach should allow distinction between immune mediated and other causes on account of the therapeutic implications. BACKGROUND: The main immunological causes are small and medium vessel vasculitis (Wegener's granulomatosis, microscopic polyangeitis), lupus and Goodpasture's syndrome. Other immune disorders are only rarely involved. The association of DAH with an acute glomerulonephritis, indicating the pulmonary-renal syndrome, extra-thoracic involvement and immunological abnormalities suggest an immune aetiology. Immunosuppressant treatment should be started as soon as possible with corticosteroids often combined with intravenous cyclophosphamide. Plasmapharesis is indicated for Goodpasture's syndrome and poorly responding lupus. Aggravating factors such as hypervolaemia and disorders of haemostasis should be searched for and treated. Hospital mortality is close to 20%. VIEWPOINT AND CONCLUSION: Immune mediated DAH is a disorder whose rarity justifies the establishment of a national registry with the aim of developing standardised diagnostic and therapeutic strategies. Update in the diagnosis and management of pulmonary vasculitis.Chest. 2006 Feb;129(2):452-65. The term vasculitis encompasses a number of distinct clinicopathologic disease entities, each of which is characterized pathologically by cellular inflammation and destruction of the blood vessel wall, and clinically by the types and locations of the affected vessels. While multiple classification schemes have been proposed to categorize and simplify the approach to these diseases, ultimately their diagnosis rests on the identification of particular patterns of clinical, radiologic, laboratory, and pathologic features. While lung involvement is most commonly seen with the primary idiopathic, small-vessel or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides of Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, one should remember that medium-vessel vasculitis (ie, classic polyarteritis nodosa), large-vessel vasculitis (ie, Takayasu arteritis), primary immune complex-mediated vasculitis (ie, Goodpasture syndrome), and secondary vasculitis (ie, systemic lupus erythematosus) can all affect the lung. However, for the purpose of this review, we will focus on the ANCA-associated vasculitides. Diagnosis and treatment of primary small vessel vasculitis with involvement of lungs. Zhonghua Jie He He Hu Xi Za Zhi. 1999 Jun;22(6):347-50. OBJECTIVE: To investigate the clinical characteristics of primary small vessel vasculitis with involvement of lungs. METHODS: 13 cases of primary small vessel vasculitis with involvement of lungs from 1993 to 1998 were analyzed retrospectively. RESULTS: Among 13 cases 7 were microscopic polyangiitis (MPA) and 6 were Wegener granulomatosis (WG). The ages of onset were from 17 to 68 years old with average age 48.8 years old. 69%(9/13) were ANCA positive, among them 100%(7/7) MPA were ANCA positive (6/7 were P-ANCA positive, 1/7 was C-ANCA positive), while 33%(2/6) WG were ANCA positive (one case of P-ANCA and another case of C-ANCA was positive respectively). The major symptoms of respiratory system included hemoptasis 69% (9/13), dyspnea 23%(3/13), dry cough 15%(2/13) and chest pain 15%(2/13). The chest x-rays showed multiple patchy shadows in both lungs were mainly found in MPA (3/7) and single or multiple masses or nodular shadows were mainly found in WG (5/6) with or without cavity formation. The appearance of lungs in MPA 71% (5/7) had been explained as "pulmonary infection" and that of WG had been explained as "primary lung cancer or metastatic carcinoma". Symptoms of respiratory system might occur before (3/5) or after (2/5) occurrence of acute renal failure. The treatments with corticosteroid and CTX were effective in these cases, in particularly, pulmonary lesions improved obviously. CONCLUSIONS: It is very difficult to make diagnosis of primary small vessel vasculitis with involvement of lungs and this should be paid more attention. ANCA detection is very useful in diagnosis of MPA. Corticosteroid and CTX are most effective in treating these diseases. Pulmonary vasculitis.Semin Respir Crit Care Med. 2004 Oct;25(5):483-9. This review summarizes the radiological manifestations of the vasculitides of proven or presumed immunologic origin in which the inflammatory reaction is directed primarily against the vessel wall. These include Wegener's granulomatosis, Churg-Strauss syndrome, Takayasu's arteritis, Behcet's syndrome, Goodpasture's syndrome, and microscopic polyangiitis. Chest radiography is used routinely in the initial evaluation and follow-up of these patients. The radiographic findings however are nonspecific and need to be interpreted together with the clinical findings. Computed tomography (CT) plays an increasingly important role in the assessment of patients with vasculitis and, in the proper clinical context, allows a confident diagnosis of some of these entities. Magnetic resonance imaging and positron emission tomography play a limited role. The characteristic imaging manifestations of the various vasculitides are reviewed and illustrated. Pathology of pulmonary vasculitis.Semin Respir Crit Care Med. 2004 Oct;25(5):475-82. There are three major vasculitis syndromes that affect the lung: Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The pathology of pulmonary vasculitis is complicated because it requires correlation with clinical, laboratory, and radiological features; there is overlap in some histological features among the vasculitis syndromes; biopsies early in the course of disease or after therapy may show atypical or incomplete histological features; the differential diagnosis is complex and includes infection that should not be treated with corticosteriods or immunosupressive agents; and few pathologists have much experience with these cases. Major histological features of necrosis, granulomatous inflammation, and vasculitis characterize WG. The inflammatory consolidation consists of a mixture of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and eosinophils. Necrosis may take the form of neutrophil microabscesses or geographic necrosis. Granulomas may take several forms, including scattered or loose clusters of giant cells, palisading histiocytes or giant cells lining the border of geographic necrosis or microabscesses, and palisading microgranulomas. Sarcoidal granulomas are very rare. CSS may show eosinophilic pneumonia, allergic granulomas, and eosinophilic vasculitis. Asthmatic bronchitis may also be present. Biopsies from CSS patients are rare because this syndrome is usually diagnosed clinically. Microscopic polyangiitis demonstrates neutrophilic capillaritis and diffuse alveolar hemorrhage.