Vasculitis
Vasculitis is a group of diseases characterized by inflammatory changes in the walls of blood vessels. Vascular inflammation can lead to destruction of blood vessels, so it is sometimes called necrotizing vasculitis. Vasculitis encompasses a wide range of diseases, including primary vasculitis, accompanied by or secondary to other diseases; the invading blood vessels can be predominantly arterial, but can also involve arterioles, venules, and capillaries at the same time. It can be a disease in which small vessels are the main targets of invasion, or it can be a disease in which larger vessels are the main targets. Pulmonary vasculitis, as the name implies, is a vasculitis in which the blood vessels of the lungs are invaded. Some pulmonary vasculitides are rare and difficult to diagnose, and should be given sufficient clinical attention. 1994 in the United States ChapelHill meeting from six different countries, different centers, different professional scholars after careful discussion, a series of primary vasculitis naming and classification criteria were summarized, the Chapel Hill meeting also discussed the non-granulomatous small vessel vasculitides involved in upper or lower respiratory tract, with or without necrotizing glomerulonephritis, and in the absence of anti-renal basement membrane antibodies or immune complexes, and suggested that the diagnosis of this group of diseases should be based on a single diagnosis of respiratory microscopic polyangiitis (microscopic polyarteritis), because the pulmonary vasculitis in these patients is predominantly necrotizing alveolar capillaritis.
Etiology
The etiology of pulmonary vasculitis is not clear.Shortly after the Chapel Hill meeting, Lie proposed a new classification.Because this classification criterion is more concise and practical, the clinical features of various pulmonary vasculitides will be briefly described.
1. Primary vasculitis disease
(1) Affecting large, medium, and small vessels: ① Takayasu’s vasculitis. ② Giant cell (temporal) arteritis. ③Central nervous system limited vasculitis.
(2) Affecting medium and small blood vessels: ①Polyarteritis nodosa. (2) Affecting medium and small vessels: ① Nodular polyarteritis. Wegener’s granuloma.
(3) Mainly affecting small vessels: ① Microscopic polyangiitis. ②Allergic purpura. Leukocytoclastic vasculitis of the skin.
(4) Others: ① Behçet’s syndrome. Burger’s disease. Cogan’s syndrome. (4) Others: (1) Behçet’s syndrome. (2) Burger’s disease.
2. Secondary vasculitis
(1) Infectious vasculitis.
(2) Vasculitis secondary to connective tissue disease.
(3) Drug-induced (allergic) vasculitis.
(4) Secondary to mixed primary cryoglobulinemia.
(5) Vasculitis associated with cancer.
(6) Urticarial hypocomplementemic vasculitis.
(7) Post-transplant vasculitis.
(8) Pseudovasculitis syndromes (mucocele, endocarditis, Sneddon’s syndrome).
Epidemiology
Pulmonary vasculitis is not common in the clinic, more common in connective tissue disease to Wegener’s granulomatosis, for example, to 1967, the literature of various countries reported 200 cases, Peking Union Medical College Hospital to 1999, only found more than 20 cases, and the prevalence of many diseases is still not clear.
Pulmonary vasculitis can be found in all age groups, but some specific diseases have age and gender tendency. For example, allergic purpura is more common in young children; granulomatous vasculitis is more common in middle-aged and elderly people aged 50-60 years; and vasculitis secondary to connective tissue disease is more common in women of childbearing age. wegener’s granulomatosis and Churg-Strauss syndrome account for the majority of male patients.
Pathogenesis
Pulmonary vasculitis is characterized by an inflammatory reaction in the vascular wall, which often extends throughout the entire vascular wall and is often centered on blood vessels, while perivascular tissues may also be involved, with the exception of bronchocentric granulomatous disease. Small, medium, and large arterioles may be involved, and capillary inflammation may also occur. Inflammation is often accompanied by fibrinoid necrosis, intimal hyperplasia and perivascular fibrosis. Thus pulmonary vasculitis can lead to occlusive vasculopathy due to occlusion of blood vessels. The inflammatory response cells are neutrophils, normal or abnormal lymphocytes, eosinophils, monocytes, macrophages, histiocytes, plasma cells, and multinucleated giant cells, and tend to be a mixture of components. If the neutrophils are predominant, it is the manifestation of leukocyte fragmentation vasculitis; if the lymphocytes are predominant, it is the main manifestation of granulomatous vasculitis. However, the number of infiltrating inflammatory cell types varies from vasculitis to vasculitis at different stages of the disease. For example, after the acute phase of leukocytoclastic vasculitis, a large number of lymphocyte infiltration may also occur, whereas in the late phase of granulomatous vasculitis, inflammatory cells may be predominantly monocytes, histiocytes, and multinucleated giant cells rather than lymphocytes.
Although the clinicopathologic manifestations of pulmonary vasculitis can vary, there is a common immunopathology. Over the past decade, studies have found that antineutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of vasculitis.
ANCA include two major categories:
1. C-ANCA (cytoplasmic staining pattern of ANCA) binds mainly to proteinase 3 (PR3) in primary granules in neutrophils, monocytes and immature macrophages. During alcohol fixation, the primary granules are ruptured and PR3 is released, and because of its weak charge, indirect immunofluorescence staining shows a rough granule-like intracytoplasmic staining pattern.
2. P-ANCA (perinuclear staining pattern of ANCA), mainly for serine proteases such as myeloperoxidase (MPO), elastase, lactoferrin and other components of the particles, which are mostly positively charged, and are released with the rupture of the particles in indirect immunofluorescence staining. In indirect immunofluorescence staining, as the particles rupture and release, they easily bind to the negatively charged nucleus and exhibit a perinuclear phenotype, from which P-ANCA gets its name. C-ANCA for PR3 has been found to be detected in the sera of many patients with active Wegener’s granulomatosis with high specificity, and the titer of C-ANCA in some of the patients was positively correlated with the disease activity. In contrast, P-ANCA against MPO is more frequent in systemic necrotizing vasculitis including Churg-Strauss syndrome, microscopic polyangiitis, and idiopathic and drug-induced glomerulonephritis. Atypical P-ANCA for other components is seen in many diseases such as inflammatory bowel disease, inflammatory liver disease, connective tissue disease, chronic infections, HIV infection, rheumatoid arthritis, and even in a small percentage of normal subjects. Sometimes, ANA may also show a similar staining phenotype to P-ANCA in indirect immunofluorescence staining, which is mistaken for P-ANCA positivity. Therefore, when evaluating a positive P-ANCA result, it is important to analyze it in relation to the antigen it is directed against and the clinical presentation. In many cases, atypical P-ANCA only suggests the presence of a chronic inflammatory response and is not specific for the diagnosis of vasculitis.
Most ANCA antigens are used by neutrophils as bactericidal components of the host defense response. However, it is not well understood why an immune response is generated against these autoantigens and what role infection plays in this. It is true that recurrent bacterial infections can lead to exacerbation of vasculitis, and that nasal S. aureus carriage in patients with vasculitis can lead to recurrence of vasculitis. There is evidence that cotrimoxazole is effective in the treatment of limited Wegener’s granulomatosis and that it reduces flares in patients with multisystem involvement.
There are several hypotheses for the pathogenesis of ANCA in vasculitis. One theory suggests that some proinflammatory factors such as IL-1, TGF-β, TNF, or pathogenic components can stimulate neutrophils, leading to the translocation of some components of the cytoplasmic granules to the cell surface, where they become targets of ANCA attack. These cytokines also lead to overexpression of adhesion factors by endothelial cells.ANCA can also induce the release of reactive oxygen radicals and lysosomal enzymes from neutrophils, leading to localized endothelial cell damage. These neutrophils can cross damaged endothelial cells and accumulate around blood vessels. It has also been suggested that vascular endothelial cells themselves can express ANCA antigens.
In conclusion, ANCA can prompt neutrophils to adhere to vascular endothelial cells, indirectly leading to endothelial cell damage and promoting neutrophil migration into perivascular tissues.
In addition, some studies have shown that the formation and deposition of pathogenic immune complexes are also an important cause of vascular inflammation. Other mechanisms such as direct infection of endothelial cells, the presence of anti-endothelial cell antibodies, and HLA-dependent T cell-mediated endothelial cell injury are also involved in the pathogenesis of vasculitis. Differences in the type of endothelial cell response, immunopathologic mechanisms, and vascular characteristics result in clinically distinct vasculitis syndromes.
Symptoms
Systemic symptoms of pulmonary vasculitis include fever, malaise, arthralgia, and skin lesions, especially in patients with systemic vasculitis and connective tissue disease. Symptoms such as dyspnea and cough may be seen in granulomatous vasculitis, and hemoptysis may be seen in Wegener’s granuloma and lymphomatoid granuloma, especially in patients with pulmonary aneurysm or diffuse capillaritis. churg-Strauss syndrome is often accompanied by recurrent episodes of dyspnea and asthma.
1. affecting large, medium and small blood vessels
(1) Temporal arteritis Also known as giant cell arteritis.
(2) Multiple aortitis Also known as Takayasu’s disease.
Involvement of the pulmonary arteries is more common and has been reported in up to 50% of cases. It may be accompanied by pulmonary hypertension and may present with significant clinical manifestations such as hemoptysis and chest pain. Some studies have shown that even in patients without obvious pulmonary symptoms, pulmonary biopsy and angiography also show pulmonary artery involvement.
2. Mainly affecting medium and small vessels
(1) Nodular polyarteritis is a systemic disease involving multiple systems. The main pathological manifestations are neutrophilic infiltration of small and medium-sized muscular arteries, accompanied by endothelial hyperplasia, fibrinoid necrosis, vascular occlusion, and aneurysm formation, which results in ischemia and infarction of the affected tissues. Joint muscle, hepatic and mesenteric vessels, testes, peripheral nervous system, and kidneys are more commonly involved. Opinions have differed as to whether the lungs and their blood vessels are involved. The current majority opinion is that polyarteritis nodosa rarely involves the lungs. Therefore, if there is evidence of pulmonary vascular involvement, care should be taken to differentiate it from microscopic polyangiitis, Churg-Strauss syndrome, and Wegener’s granulomatosis.
(2) Churg-Strauss syndrome is also known as allergic granulomatous vasculitis. It is named because it was first reported by Churg and Strauss in 1951. It is a systemic disease characterized by asthma, eosinophilia and granulomatous vasculitis, and is more common in middle-aged men with a history of asthma and asthma symptoms. The lungs, peripheral nerves, heart, and skin are more commonly involved. Kidney involvement is rare and mild in foreign countries. Churg-Strauss syndrome lung manifestations in addition to asthma manifestations, but also cough, hemoptysis, chest imaging can be seen flaky infiltration shadow or nodular shadow.Churg-Strauss do not treat progress very quickly. Aggressive adrenocorticotropic hormone combined with immunosuppressive therapy is effective.
(3) Wegener’s granuloma was first reported by Wegener, hence its name. Its clinical manifestations are mainly necrotizing granulomatous vasculitis and glomerulonephritis in the upper and lower respiratory tracts, and it can also involve the eyes, ears, heart, skin, joints, and the peripheral and central nervous systems. If only the upper and lower respiratory tract are involved without renal involvement, it is called limited Wegener’s granulomatosis. The etiology of Wegener’s granuloma is unknown, but Wegener’s granuloma is often associated with hypergammaglobulinemia and ANCA positivity, and is effective in response to cytotoxic drug therapy, suggesting that an immune mechanism is involved in the pathogenesis of the disease.Wegener’s granuloma can develop at any age, but it is more common in middle-aged males. Lung lesions can be mild or severe and can be fatal. 2/3 of patients may present with chest X-ray abnormalities, either unilateral or bilateral. The main manifestations are infiltrative shadows or nodules in the lungs, some of which are accompanied by cavity formation. Due to bronchial lesions can cause pulmonary atelectasis, pleural thickening and pleural effusion can also occur. Pathologic biopsy often shows necrosis of lung tissue with granulomatous inflammation, infiltrating cells including neutrophils, lymphocytes, plasma cells, eosinophils, and histiocytes, and vascular inflammation that can lead to vascular obstruction and infarction; one-third of the patients may present with hemoptysis due to pulmonary capillaritis. In addition, some patients may develop interstitial fibrosis, acute and chronic bronchitis, occlusive bronchitis and so on. Numerous clinical studies have shown that ANCA, especially C-ANCA against PR3, although also seen in other vasculitides, can be seen in more than 80% of Wegener’s granulomatosis cases, and the persistently high density often suggests the disease is active, and its titer can also be decreased with the remission of the disease, which can be used as an important indicator to monitor the disease activity of Wegener’s granulomatosis. With the application of cytotoxic drugs, especially cyclophosphamide, the mortality rate of Wegener’s granulomatosis has been significantly reduced. The dosage of cyclophosphamide is usually 1-2mg/(kg-d), or 2-4mg/(kg-d) every other day, and it is often used in combination with corticosteroids. The duration of treatment should be at least 1 year, and the dosage can be gradually reduced later. Maintenance methotrexate has been reported. Cotrimoxazole can be added to some patients who have infection triggers or are prone to recurrence, and some studies have shown that it can reduce recurrence.
3. Mainly affecting small vessels
(1) Microscopic polyangiitis Microscopic polyangiitis is a separate form of vasculitis that one separates from polyarteritis nodosa. Its clinical manifestation is necrotizing inflammation of small arteries, veins, and capillaries, mainly involving the kidneys, skin, and lungs, and most often accompanied by ANCA positivity. There is no or little deposition of immune components in the affected vessels. Involved vessels may show fibrinoid necrosis and infiltration of polymorphonuclear leukocytes and monocytes, which may be accompanied by thrombosis. The kidneys show focal segmental glomerulonephritis, sometimes with crescent formation, and the lungs show necrotizing pulmonary capillaritis with few immunoglobulin and complement deposits. The disease is common in middle-aged and elderly people, and is slightly more common in men. The onset of the disease is often accompanied by malaise, weight loss, fever, arthralgia and other systemic symptoms. Renal involvement is common, manifested as proteinuria, hematuria or cellular tubular pattern; many patients manifested as rapidly progressive glomerulonephritis.
(2) Anaphylactic purpura, also known as Henoch-Schënlein purpura. It is a leukocyte-crushing vasculitis, which is common in children and also in adults. It is a leukocyte-crushing vasculitis. It is often accompanied by an antecedent infection of the upper respiratory tract, followed by purpura of the buttocks and lower extremities, arthritis, and abdominal pain, and in some patients, microscopic hematuria and glomerulonephritis may also occur. Respiratory tract involvement is relatively rare, may be manifested as alveolar hemorrhage and periportal flaky infiltration shadow, serum IgA can be elevated, tissue biopsy immunofluorescence can also be seen IgA deposition.
4. Behçet’s syndrome
Behçet’s syndrome can involve both large and small blood vessels, both arteries and veins. Its main clinical manifestations are recurrent painful oral ulcers, perineal ulcers, which may be accompanied by arthralgia, erythema nodosum or pustular papules, thrombophlebitis of the lower extremity veins, and uveitis, and it may also involve the gastrointestinal tract, cardiovascular, neurological system, kidneys and lungs. Patients with active disease
Positive pinprick reaction may occur. IgG and complement deposits may be seen at the site of involvement, and 10% of patients may have pulmonary involvement with recurrent episodes of pneumonia and hemoptysis, sometimes with fatal hemoptysis. The cause of hemoptysis may be due to pulmonary small vessel vasculitis or bronchial vein rupture, or due to ruptured pulmonary aneurysm or arteriovenous fistula. Behçet’s syndrome should be treated with aggressive immunosuppressive therapy if there is involvement of vital organs such as the eyes, nervous system, gastrointestinal tract, and lungs. Disease activity hemoptysis surgical treatment is not effective, easy to recurrence or the emergence of new aneurysms.
5. Vasculitis secondary to connective tissue disease
(1) Systemic lupus erythematosus Systemic lupus erythematosus lung involvement is mainly manifested as pleurisy, pleural effusion, but also may appear as pulmonary atelectasis, acute lupus vasculitis, diffuse interstitial lung lesions and vasculitis. Pulmonary vasculitis is primarily a leukocyte-crushing vasculitis that may be accompanied by fibrinoid necrosis, but the exact incidence in lupus erythematosus has been reported to vary. Some patients may develop pulmonary hypertension, which is mostly mild-moderate.
(2) Rheumatoid arthritis: In addition to joint involvement, vasculitis may also occur. Lung involvement often manifests as pleurisy or pleural effusion, nodules in the lungs, interstitial lung lesions, and some patients may develop pulmonary vasculitis and pulmonary hypertension, but the incidence is low.
(3) Systemic sclerosis The main clinical manifestations are sclerosis of the fingertips and sclerosis of the skin of the trunk and limbs. Patients are often accompanied by obvious Raynaud’s phenomenon and pulmonary interstitial lesions pulmonary arterial hypertension, small arteries and fine arterial intimal hyperplasia, centripetal fibrosis resulting in small arterial stenosis and occlusion. However, inflammatory cell infiltration and fibrinoid necrosis are uncommon. Therefore, strictly speaking, it cannot be called vasculitis. Hormone and immunosuppressant therapy is mostly ineffective.
(4) Desiccation syndrome is an autoimmune disease characterized by epithelial involvement of exocrine glands. Foreign and domestic epidemiological data show that dry syndrome is not a rare disease, there are views that it is called autoimmune epitheliitis, because it can not only affect the salivary glands caused by dry mouth and dry eyes, but also can involve the renal tubular epithelium caused by renal tubular acidosis, the involvement of hepatic and biliary epithelium, pancreatic epithelium and gastrointestinal glands caused by gastrointestinal symptoms, and involvement of the lungs and fine bronchial epithelium caused by interstitial pulmonary fibrosis and pulmonary arterial hypertension. Dry syndrome vasculitis and hypergammaglobulinemia are also important pathogenic mechanisms of interstitial fibrosis and pulmonary hypertension. Treatment emphasizes the use of active corticosteroid and immunosuppressive therapy in the early stage of interstitial lung disease.
6. Cryoglobulinemia
Repeated episodes of purpura, arthralgia and involvement of kidney and other internal organs, accompanied by increased serum cryoglobulin content and positive rheumatoid factor are the clinical features of this disease. Leukocyte infiltrative vasculitis with immunoglobulin and complement deposits in the vessel wall is the histologic feature. The lungs may also be affected, often with diffuse interstitial infiltration, and the pulmonary vessels also show the inflammatory changes described above.
7. Other episodic pulmonary vasculitis
All of these disorders are predominantly pulmonary and may also present with pulmonary vasculitis.
(1) Lymphangiomatoid granulomatosis is a granulomatous disease centered on blood vessels, in which the lungs are invaded without exception, as first described by Liebow et al. in 1972. The histomorphology is characterized by destructive infiltrative lesions centered on blood vessels in the upper and lower respiratory tracts, skin, and central nervous system. The infiltrating cells are mainly lymphoblasts, plasma cells, histiocytes, and atypical large lymphocytes containing abnormal karyorrhexis and forming granulomatous lesions. Untreated lymphomatoid granulomas generally deteriorate rapidly and most eventually die from central nervous system lesions. About half of the patients may remit with cyclophosphamide and corticosteroid therapy, with an average survival of 4 years, and will progress to angiocentric T-cell lymphoma when treatment fails. However, there can be benign types, the latter mainly manifested as polymorphic lymphocytic infiltration of vasculitis and granuloma formation, with little tissue necrosis, and the response to treatment is good, which was once called “lymphocytic vasculitis and granulomatous disease”.
(2) Necrotizing nodular disease-like granulomatosis was first reported by Liebow in 1973. Its histologic features are granulomatous lesions fused in the lungs, which are similar in morphology to nodular disease, but are accompanied by necrotizing granulomatous vasculitis of the pulmonary arteries and veins, and about half of the patients are not accompanied by enlarged hilar lymph nodes, which is different from typical nodular disease. The prognosis of this disease is good, and it often resolves spontaneously. It is possible that this disease is a variant of nodular disease.
(3) Bronchocentric granulomatosis, clinical symptoms may include fever, malaise, cough, asthma, etc., eosinophil count can be increased, chest X-ray shows infiltrative or nodular shadows, and pulmonary atelectasis can also occur, unlike other systemic vasculitis diseases, there is no multiorgan involvement, and half of the patients are related to the exposure of Aspergillus or other fungi; the lungs are centered on the bronchi, and infiltration of the small airways is destroyed by lymphocytes and plasma cells, with the bronchi as the center. Infiltration destroys small airways, granuloma formation is the basic histologic change, and small arteries and veins near the lesion may be invaded, thus pulmonary vasculitis is a secondary pathologic process. The prognosis is good and it can resolve spontaneously, requiring only symptomatic treatment, and corticosteroid therapy only if symptoms are severe.
Signs and symptoms
Signs are associated with organ involvement. For example, leukocytoclastic vasculitis is characterized by a more pronounced rash and ulcers, and joint deformities suggest the presence of rheumatoid arthritis. Nasal and upper respiratory tract ulcers may indicate the presence of wegener’s granulomas or lymphomatoid granulomas. In the former case, ptosis, keratitis and uveitis may also be present. Behçet’s syndrome is most often associated with painful oral and perineal ulcers and uveitis. Nodular polyarteritis and Churg-Strauss syndrome often present with peripheral nerve involvement, while giant cell arteritis may present early with signs of central nerve involvement. Signs in the lungs also vary depending on the degree of lesion invasion. Complications: Pulmonary vasculitis can be complicated by multisystem and multiorgan damage.
Examination
1. Laboratory examination
Positive cellular anemia, thrombocytosis, increased polyclonal r-globulin, decreased albumin level, increased ESR, increased CRP, and liver enzyme abnormalities are often seen, which suggest an acute phase reaction to inflammation.
2. Other auxiliary examinations
Angiography shows irregular lumen, narrowing and occlusion of the lumen, and tumor-like dilatation of the lumen. In addition to the ultrasound diagnosis of cardiovascular disease, imaging can also find thickening of the vessel wall, lumen narrowing and other lesions. X-ray imaging can also detect thickening of the vessel wall and narrowing of the lumen. Magnetic resonance imaging can also detect thickening of the vessel wall and narrowing of the lumen.
Diagnosis
In all vasculitides, there are some skin lesions, generalized and musculoskeletal symptoms, and abnormalities in the inflammatory response on laboratory tests. The presence of these abnormalities should be noted to exclude vasculitis. Systemic symptoms of vasculitis include fever, anorexia, weight loss, and malaise. Muscle and joint symptoms include rheumatic polymyalgia-like symptoms, arthralgia or arthritis, myalgia, and peripheral neuropathy.
Laboratory tests often show normocytic anemia, thrombocytosis, decreased albumin levels, increased polyclonal r-globulin, increased ESR, increased CRP, and liver enzyme abnormalities, all of which are suggestive of an acute phase reaction to inflammation. To diagnose vasculitis, first of all, we need to have a full understanding of the different clinical manifestations of vasculitis, combined with the clinical, laboratory, histopathological or angiographic abnormalities of specific patients to diagnose, and pay attention to the differential diagnosis with some secondary vasculitis. The definitive diagnosis of vasculitis requires biopsy or angiography. These tests should be performed whenever possible to clarify the diagnosis of vasculitis. Once vasculitis is diagnosed, long-term treatment is often required, and the medications used to treat it have many toxic side effects.
In general, biopsies should be performed on symptomatic and easily accessible sites, while blind biopsies of asymptomatic sites such as muscles, testes or nerves have a lower positive rate. Skin, muscle, nasal mucosa, and temporal artery biopsies are well tolerated and easy to obtain. Despite the lack of specificity for confirming the diagnosis of a particular vasculitis skin biopsy, the combination of clinical, laboratory, and radiologic manifestations can often lead to a diagnosis of vasculitis. Testicular involvement is uncommon and testicular biopsy requires general anesthesia, which is sometimes difficult for patients to accept. Peroneal nerve biopsy is helpful if the patient has clinical signs of neuropathy or abnormal electromyography and nerve conduction velocity measurements, but biopsy often has sequelae of localized sensory deficits in the distal lower extremities. Percutaneous renal biopsy is not dangerous, but there are few manifestations of vasculitis. Its most common histopathologic manifestation is focal segmental necrotizing glomerulonephritis. For the diagnosis of pulmonary vasculitis, transbronchoscopic lung biopsy is not highly positive and open or thoracoscopic lung biopsy should be performed.
For suspected vasculitis without a suitable biopsy site, angiography should be performed. Angiography of vasculitis typically shows segmental arterial stenosis, sometimes with saccular aneurysm-like dilatation and occlusion. Usually abdominal angiography is used, but sometimes angiographic abnormalities can be seen despite the absence of abdominal manifestations, and abnormalities can be seen in the kidneys, liver, and mesenteric vasculature. The presence of a saccular aneurysm on angiography is often severe. Effective treatment can reverse the angiographic abnormalities. However, angiographic specificity is low, and many vasculitides and secondary vasculitides can cause similar angiographic abnormalities, such as polyarteritis nodosa, Wegener’s granulomatosis, Churg-Strauss syndrome, vasculitides in rheumatoid arthritis and systemic lupus erythematosus, and leukoaraiosis. In addition, some other diseases, such as left atrial mucocele, bacterial endocarditis, thrombotic thrombocytopenic purpura, abdominal tuberculosis, arterial entrapment, tumors, and pancreatitis can cause angiographic abnormalities. In giant cell arteritis, aortitis, Buerger’s disease, the angiography has certain characteristics, the distribution of the affected vessels is different and there is no saccular aneurysm.
Differential diagnosis
1. Infectious vasculitis
Many different pathogenic infections can cause vasculitis-like manifestations, including bacterial (e.g. streptococcus, staphylococcus, salmonella, yersinia, mycobacteria, pseudomonas, etc.), fungal, rickettsial, Burkholderia cepacia, and viral infections (e.g. hepatitis A, B, C viruses, cytomegalovirus, EBV, herpes zoster virus, HIV, etc.), which can be easily differentiated from other infectious diseases according to their clinical manifestations and the corresponding laboratory tests. Most of them can be easily identified. Hypersensitivity vasculitis caused by infectious diseases is often characterized by skin lesions.
2. Tumor or connective tissue disease secondary vasculitis
When patients present with vasculitis-like manifestations (especially skin lesions), and if they are accompanied by hepatosplenomegaly, lymphadenopathy, cytopenia, or abnormalities in peripheral blood smears, it is important to exclude the possibility of vasculitis secondary to tumor. Lymphomas, leukemias, and non-benign tumors with hyperplasia of the reticuloendothelial system are prone to this presentation, while solid tumors are relatively rare. In addition, some connective tissue diseases may also present with secondary vasculitis, such as rheumatoid arthritis, dry syndrome, and systemic lupus erythematosus.
Treatment
The treatment of pulmonary vasculitis is mostly the same, regardless of its etiology or whether it is confined to the lungs or is part of a systemic disease, and glucocorticoids and cyclophosphamide remain the mainstay of therapy.
Glucocorticoids can be given orally with prednisone (prednisone) or intravenously with methylprednisolone (methylprednisolone) for 3 to 5 days, then changed to the above dose of prednisone (prednisone) orally, and later tapered to discontinuation over 2 to 6 months, depending on response to therapy. Cyclophosphamide is usually given orally for 6 to 12 months and then tapered off over several months. Cyclophosphamide may be administered intravenously to patients who require mechanical ventilation for respiratory failure. Pneumocystis carinii pneumonia can occur in approximately 20% of patients on this regimen; therefore, prophylactic use of sulfamethoxazole/metronidazole (SMZco) is recommended for 3 days per week. Prolonged cyclophosphamide regimens tend to have a concomitant increase in the incidence of its side effects, such as infections, hemorrhagic cystitis, bladder tumors, and bone marrow suppression.
Azathioprine and methotrexate are indicated for those who cannot tolerate cyclophosphamide, but there are only a few data on their long-term efficacy. Plasma exchange is recommended for patients who do not respond to cytotoxic and immunosuppressive drugs. It has been shown to be effective in Good-Pasture syndrome, particularly in those with diffuse alveolar hemorrhage, but its efficacy in systemic vasculitis is uncertain, and data must continue to be accumulated to observe its efficacy.
IVIG has been tried in patients with classic WG, but results have been inconsistent.
Other measures such as human monoclonal antibodies against specific lymphocyte subpopulations have been tried in patients with WG who are refractory or intolerant to conventional therapy.
LYG hormones and immunosuppressive agents may be tried, often with poor response, and limited lesions may be treated with radiotherapy or surgical resection.
Prognosis.
The prognosis of pulmonary vasculitis is related to the different disease types. Generally CSS, NSG and BG have a better prognosis, and WG survival is significantly prolonged by hormone + CTX treatment, but LYG is difficult to treat and has a poor prognosis.
Prevention
Long-term use of immunosuppressive drugs, need to be alert to lung infection.