Asthma with eosinophilia is a near-universal finding in EGPA that often presents several years prior to the diagnosis of vasculitis. Asthma that is steroid-dependent or refractory to standard medical therapy can suggest the diagnosis.
Systemic vasculitis can cause nonspecific constitutional symptoms such as fever, weakness, and weight loss. In addition, the kidneys, nervous system, and skin are also common target organs in all AAV. When renal failure and microscopic hematuria are seen, a microscopic examination of urine should be performed to look for red blood cell casts. Notably, there are many other causes of RPGN that have no lung involvement.
Mononeuritis multiplex, defined by the presence of peripheral nerve abnormalities in 2 or more distributions, is suggestive of small-vessel vasculitis. Other nervous system abnormalities include paresthesias, weakness, pain, and functional deficiencies such as foot drop.
Mononeuritis multiplex is also typically found in the medium-vessel vasculitis, polyarterteritis nodosa PAN. It should be noted that PAN does not cause pulmonary vasculitis. Palpable purpura is a finding of non-blanching purplish discolorations that signify a cutaneous vasculitis. It is a nonspecific finding, as it can be associated with AAV, as well as drug reactions, cryoglobulinemia, infections, rheumatologic disorders, and malignancy.
The syndrome is characterized by a combination of upper and lower respiratory tract disease along with renal disease. The presence of ulcerating or destructive lesions is highly suggestive. EGPA is characterized by a classic triad of asthma, eosinophilia, and necrotizing vasculitis. The presence of asthma, peripheral blood eosinophilia with elevated IgE levels, pulmonary eosinophilia in BAL fluid, and the presence of eosinophils in tissue, make it unique amongst AAV, and also make it difficult to identify as a manifestation of vasculitis. In contrast to GPA with its classic upper airway findings and cavitary lesions and EGPA with its asthma and ground glass opacities, MPA does not have features that distinguish it from other AAV aside from its very high rate of renal involvement.
Signs and symptoms of vasculitis can overlap significantly with other conditions, including infection, malignancy, connective tissue disease, drug toxicity, and venous thromboembolic disease.
DAH has myriad etiologies, and pulmonary capillaritis suggestive of vasculitis must be differentiated from diffuse alveolar damage and bland hemorrhage e. The etiology of AAV, like most other autoimmune diseases, is not known. Additionally, evaluation for connective tissue disease should take place, with antinuclear antibodies, rheumatoid factor, and disease-specific antibodies e. Goodpasture disease, which is an autoimmune disorder against glomerular basement membrane, can also present with the combination of DAH and RPGN, so in the proper clinical setting, sending anti-glomerular basement membrane antibodies should also be considered.
Our understanding of the role that ANCA testing plays in the diagnosis of vasculitis has advanced immensely since the s. Immunofluorescent staining of ethanol-fixed neutrophils shows a diffuse pattern in the cytoplasm of patients with GPA cytoplasmic pattern, or c-ANCA , while a perinuclear pattern is most commonly noted in patients with MPA and pauci-immune glomerulonephritis perinuclear pattern, or p-ANCA. Imaging studies in pulmonary vasculitis are fairly non-specific. DAH must be diagnosed via bronchoscopy in these cases.
GPA can also present with pulmonary nodules and cavities seen on imaging. These opacities will typically be seen in different areas of the lung on serial imaging. Pulmonary vasculitis can also result in pulmonary fibrosis, but this is rare overall. Bronchoscopy plays several important roles in the diagnosis of pulmonary vasculitis, including evaluation for DAH, malignancy, infection, and eosinophilia and assessing for ulcerative and stenotic upper airway and endobronchial disease. Lower respiratory samples can be obtained by BAL and should be sent for culture, cytology, and cell count with differential.
Endobronchial or transbronchial biopsies can be helpful in excluding infections and malignancy, but the small size of the acquired tissue specimen limits diagnostic accuracy.
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- Systemic Vasculitis.
- Systemic Vasculitis.
- Imaging Features.
Transbronchial biopsies should not be performed in patients with severe DAH or respiratory failure, owing to a high complication rate. However, tissue biopsy is often necessary to diagnose vasculitis definitively. EGPA is further distinguished by the presence of eosinophils in tissue specimens.
What is Vasculitis?
The skin and sinuses, which are often involved, are frequently the most accessible biopsy sites. Percutaneous renal biopsy is performed in the setting of acute glomerulonephritis. The histopathologic finding of a segmental, necrotizing glomerulonephritis is highly suggestive of vasculitis.
Immunofluorescence should be performed to evaluate for immune-deposition that would suggest immune-complex mediated vasculitis e. The absence of immune deposits defines pauci-immune glomerulonephritis, which in the right clinical setting, is consistent with AAV. However, this requires general anesthesia and is the most invasive modality of biopsy; it is also generally contraindicated in patients with severe DAH or respiratory failure.
Tissue should be evaluated by conventional histopathology for evidence of vasculitis, such as vascular necrosis with neutrophilic infiltration of the capillary walls, granulomas or eosinophilic components. Stains to detect acid-fast bacilli and fungi should also be performed. Cytology from BAL can be helpful if the differential includes malignancy. Therapy for pulmonary vasculitis requires immunosuppressive treatment with corticosteroids and cytotoxic immunosuppressive agents, with escalating intensity based on disease severity.
As RTX carries with it less long-term concerns for cancer risk, we believe it should be the induction agent of choice. Initial induction therapy is geared toward achieving remission, and should be followed by maintenance therapy. If CYC is used as induction, a maintenance regimen of either azathioprine or methotrexate should be administered once remission is achieved. If RTX is used as induction, it is less clear that a maintenance regimen is needed, but retreatment with RTX in month intervals is reasonable, or azathioprine or methotrexate may be considered 6 months after induction.
Survival has improved significantly compared to older data. The most recent survival data comes from the longitudinal follow-up for the studies demonstrating efficacy of RTX as an induction agent for AAV. It should be noted that all of the patients in the second study had RPGN, which worsens the prognosis significantly. Longitudinal monitoring of patients with AAV requires careful evaluation for disease relapse and complications of therapy. The clinician must be cautious that signs or symptoms consistent with a flare of vasculitis may also represent signs of infection or drug toxicity.
In addition, the incidence of venous thromboembolic disease in patients with AAV is several times higher than the general population, so it should be considered in the differential diagnosis of a disease flare. A comprehensive knowledge of the possible etiologies is necessary because vasculitis can be primary or secondary to another autoimmune disease or can be associated with other precipitants such as drugs, infections or malignancy. The prevalence of coronary arteritis among patients with systemic vasculitis is largely unknown because of the relative rarity of these conditions as well as a lack of standardized prospective imaging studies systematically evaluating the coronary vasculature.
Furthermore, involvement of the subepicardial coronary microcirculation may result in symptoms of myocarditis or cardiomyopathy but these blood vessels are below the detection of conventional coronary angiography as well as non-invasive cardiac imaging modalities. The clinical, laboratory and physical examination features of the primary systemic vasculitides are quite diverse and can have significant overlap.
CNS Vasculitis - Rheumatology Advisor
The more common findings associated with some of these conditions are highlighted in Table 1. Isolated coronary arteritis without any other systemic symptomatology is considered extremely rare.
Download Table 1 as PDF. However, because patients with coronary arteritis may present acutely with cardiac ischemic symptoms, it may not be feasible in such circumstances to investigate for symptoms suggestive of systemic vasculitis prior to proceeding to emergent coronary reperfusion. Although there are no specific features on conventional coronary angiography that are diagnostic of coronary arteritis certain features may be suggestive. For example, tapered smooth narrowing has been described in cases of giant cell arteritis GCA with coronary involvement.
While evaluation of the lumen with conventional coronary angiography aids in understanding the coronary anatomical abnormalities, it is insufficient to assess for inflammation or thickening of the coronary artery wall or to identify extra-coronary arterial abnormalities. Since isolated coronary arteritis is rarely seen without other arterial or systemic findings present, computed tomography CT or magnetic resonance MR angiography should be considered in patients with suspicion for, or diagnosis of, coronary arteritis.
In patients with large GCA and Takayasu's arteritis , medium PAN or variable Behcet's disease vessel vasculitis, evaluation with non-invasive angiography of the chest, abdomen, and pelvis is strongly recommended. For patients with concern for small vessel vasculitis i. The above modalities are also beneficial in assessing for diseases that result in luminal narrowing from periarterial soft tissue thickening or extrinsic compression as can be seen in Immunoglobuin G4 IgG4 -related disease or more rare conditions such as Erdheim-Chester disease.
Nuclear medicine myocardial perfusion studies can assist in determining myocardial viability but cannot distinguish between reduced perfusion from vasculitic or atherosclerotic etiology. Data regarding interventions in patients with coronary arteritis, regardless of the etiology, are limited to case reports and retrospective cohort studies.