Allergic vasculitis and granulomatous disease
Introduction
Introduction to allergic vasculitis and granulomatosis Allergic vasculitis and granulomatosis, ie allergic granuloma (AG), is also called allergic granulomatosis or allergic granulomatous vasculitis. It is an autoimmune granulomatous vasculitis characterized by intrapulmonary and systemic small vessel inflammation, extravascular granuloma and hypereosinophilic cytosis. It is asthma, eosinophilia and blood vessels. External granuloma formation is characterized by vascular inflammatory diseases. The lesions mainly involve small and medium arteries, but also affect the skin, heart, gastrointestinal tract, liver and other organs. basic knowledge The proportion of illness: 0.0074% Susceptible people: no specific population Mode of infection: non-infectious Complications: optic neuritis congestive heart failure
Cause
Causes of allergic vasculitis and granulomatosis
Autoantigen (60%):
The pathogenesis of this disease is not very clear, dust particles, avian antigens and autoantigens may be the main cause of this disease. Animal experiments and clinical studies have proved that CSS is caused by immune pathogenesis, immune complex mediated Type III allergies, IgE-mediated type I allergies, and sensitized T cell-mediated type IV allergies may be involved in the pathological process of the disease, and the entry of organic antigens in the body directly activates the complement bypass pathway, thereby enabling C3 cleaves into C3b and chemokine C3a, which induces the release of lysosomal enzymes from macrophages in vivo, which further cleaves complement to produce more chemotactic complement products C3a, C5a and C5,6,7 As well as C3b with a variety of biological functions, C3b further supplements its own consumption and activates macrophages to form an inflammatory "magnification feedback loop" that explains the formation of pulmonary and systemic granulomatous vasculitis. Animal experiments have found that macrophages phagocytose antigenic substances that enter the body, releasing themselves with lysosomal enzymes, which promote the cleavage of C3 and other complement components. Produces more chemokines (C3a, C5a, C5, 6, 7) and C3b, factor B in the complement activation pathway, interacts with C3b, and further cleaves complement C3 while sensitizing B lymphocytes Mature is the secretion of antibodies to plasma cells, which increases the number of antibodies.
Pathogenesis:
The basic features of the pathological changes of allergic granuloma are vasculitis and extravascular necrotic granuloma, often accompanied by eosinophil infiltration, vasculitis can be granulomatous or non-granulomatous, arteriovenous can be simultaneously Involved, necrotic inflammatory changes usually occur in the small arteries and venules in the affected tissues, and extravascular granuloma formation and fibrinoid necrosis are found in about 50% of cases. Typical granuloma diameter is about 1 cm or more. Large, often located in the vicinity of small arteries or veins, epithelioid tissue cells are radially distributed around the central necrotic area, while a large number of eosinophils are seen in the central necrotic area, and other inflammatory cells such as polymorphonuclear nucleus are also visible in the granuloma. Infiltration of leukocytes and lymphocytes, but in small quantities, phagocytic cells and giant cells are more common in chronic injury, eosinophil infiltration in the early stage of the disease, and infiltration of eosinophils in the healing phase is significantly reduced, necrotic Vasculitis, granuloma and eosinophil infiltration are rarely seen simultaneously in the same biopsy specimen.
In the lungs, the pathological manifestations of allergic granuloma are mainly necrotic vasculitis and eosinophilic pneumonia-like changes. Vasculitis can involve arteries and veins. It is characterized by granuloma formation and giant cell infiltration of the vessel wall. In some cases, infiltration of transmural eosinophils and histiocytes is sometimes seen, and extravascular granulomas are more common.
Vasculitis and granuloma changes can also be seen in the heart, gastrointestinal tract, liver, spleen, lymph nodes, kidney and urinary tract, etc. There are a large number of eosinophils in the central necrotic area, and other inflammatory cells can be seen in the granuloma. Polymorphonuclear leukocytes and lymphocytes infiltrate, but the number is small, phagocytic cells and giant cells are more common in the chronic injury period, eosinophil infiltration in the early stage of the disease is obvious, and the infiltration of eosinophils is significantly reduced in the healing stage. Necrotizing vasculitis, granuloma and eosinophil infiltration are rarely seen in the same biopsy specimen.
In the lungs, the pathological manifestations of allergic granuloma are mainly necrotic vasculitis and eosinophilic pneumonia-like changes. Vasculitis can involve arteries and veins. It is characterized by granuloma formation and giant cell infiltration of the vessel wall. In some cases, infiltration of transmural eosinophils and histiocytes is sometimes seen, and extravascular granulomas are more common.
Vasculitis and granuloma changes can also be found in the heart, gastrointestinal tract, liver, spleen, lymph nodes, kidneys and urinary tract.
Prevention
Allergic vasculitis and granulomatosis prevention
Primary prevention
(1) Strengthen nutrition and enhance physical fitness.
(2) Prevent and control infection and improve autoimmune function.
(3) Avoid wind and cold, avoid excessive fatigue, avoid alcohol and tobacco, and avoid spicy food.
2. Secondary prevention
Early diagnosis, understanding of infection, good clinical observation, early detection of damage to various systems, early treatment, mainly to control lung infection.
3. Three levels of prevention
Pay attention to lung, kidney, heart and skin lesions, and pay attention to the occurrence of secondary Staphylococcus aureus infection, use drugs carefully to prevent the occurrence of allergies. The application of traditional Chinese medicine may have the effects of regulating immunity, clearing away heat and detoxifying, promoting blood circulation and removing blood stasis.
Complication
Allergic vasculitis and granulomatosis complications Complications optic neuritis congestive heart failure
The most common cranial neuropathy is ischemic optic neuritis. When the heart is involved, it can manifest as congestive heart failure, severe heart failure, etc. When the lesion invades the liver or the greater omentum, it often forms abdomen mass.
Symptom
Symptoms of allergic vasculitis and granulomatosis Common symptoms Decreased appetite, diarrhea, abdominal pain, lymph node enlargement, hot ecchymosis, proteinuria, relaxation, hot nasal congestion
The disease is a rare systemic rheumatism, often episodes, can occur once every two or three months to several years, patients with acute attacks may have fever, anemia, weight loss, general malaise and loss of appetite, sometimes fever Some patients have arthritis or joint pain, but almost all patients have pulmonary symptoms as the main clinical manifestations.
1. Staging of the disease Lanham et al. divided the development of Churg-Strauss syndrome into three phases:
1 The first stage is the prodromal period, which can last for several years (generally more than 10 years, sometimes up to 30 years), mainly manifested as allergic rhinitis and nasal polyps, often accompanied by asthma.
2 The second stage is characterized by eosinophilia in the peripheral blood and eosinophil infiltration of the affected tissue. It is often characterized by chronic eosinophilic pneumonia or eosinophilic gastroenteritis. Remission and recurrence often alternate between years.
3 The third stage is the systemic vasculitis stage. Clinically, not every case is developed in accordance with this stage. In general, systemic vasculitis occurs after several years of asthma attacks (average about 3 years), and asthma appears. The prognosis of vasculitis soon after is poor.
2. Respiratory system performance
(1) allergic rhinitis: allergic rhinitis is seen in most patients, is the most common initial symptoms of Churg-Strauss syndrome, in addition, often accompanied by recurrent sinusitis, paranasal sinusitis and nasal polyps, the main symptoms are Nasal congestion, discharge of purulent or bloody secretions, obstruction of breathing when the polyps are severe, nasal mucosa can be granular brittle crusting, common granuloma of nasal mucosa biopsy, often accompanied by eosinophil infiltration, but vasculitis is rare.
(2) Asthma: Asthma is one of the most important and prominent clinical manifestations of Churg-Strauss syndrome. It is almost common in all patients. Compared with common asthma, it is usually older and often begins to appear after 35 years old. Before the onset of vasculitis, asthma is generally more severe and frequent, but asthma can be alleviated after the appearance of vasculitis. There is no significant correlation between the severity of asthma attacks and the degree of systemic vasculitis.
(3) Infiltration of the lungs: Invasive lesions of the lungs generally appear in the second stage of the disease, which can be accompanied by asthma and eosinophilia, which is similar to the clinical manifestations of eosinophilic pneumonia. Intrapulmonary infiltration Radiological manifestations are diverse, often short-lived, rapidly disappearing, patchy, marginal irregularities, diffuse distribution, no distribution of lung or lung segments, and sometimes pulmonary interstitial infiltration And bilateral diffuse nodular infiltration, but rarely formed cavities, 25% to 50% of patients with pleural infiltration, manifested as pleural effusion and pleural friction, but generally appear later, sometimes also visible hilar The lymph nodes are swollen.
3. Skin performance
About 2/3 of the patients have skin damage, which also reflects the characteristics of allergic granuloma with small blood vessel involvement, mainly as various rashes, such as erythema papular rash similar to polymorphic erythema, hemorrhagic A rash (defect or ecchymosis), about half of the patients may have cyanosis of the skin, the rash is more common in the extremities, especially the elbow extension, followed by the (toe), 30% of patients may have subcutaneous nodules, Occurs in the scalp and extremities, it is different from the nodules in other diseases, histopathological changes are specific, often manifested as a typical case of Churg-Strauss syndrome, the skin of the network is also more common .
4. Neurological performance
The neurological manifestations of Churg-Strauss syndrome are mainly peripheral nerve involvement, often manifested as multiple mononeuritis, the incidence rate is 63% to 75%, and the symptoms of motor and paresthesia are asymmetric, mainly found in the lower limbs. In particular, the sciatic nerve and its temporal and temporal branches are most commonly involved. The phrenic nerve, ulnar nerve and median nerve are generally less involved. Multiple mononeuritis can be gradually restored without treatment, and can be completely recovered without treatment. Residual sequelae, peripheral nerve involvement in the late stage of the disease, paresthesia is more common than dyskinesia, the disease is less involved in the central nervous system, the most common cranial neuropathy is ischemic optic neuritis.
5. Cardiac performance
Allergic granuloma often has heart involvement and is one of the leading causes of death. It can be manifested as congestive heart failure, severe heart failure, etc. Lanham et al reported that 50% of patients may have ECG abnormalities, 25 % of patients develop congestive heart failure, and pathology is mainly characterized by granuloma formation and coronary vasculitis.
6. Digestive system performance
17% to 62% of allergic granulomatosis patients may have gastrointestinal symptoms, including abdominal pain, diarrhea and gastrointestinal bleeding, which may occur due to mesenteric vasculitis (more common) and eosinophilic tract of the intestinal wall Cell infiltration (less common), a large number of eosinophil infiltration can be expressed as eosinophilic gastroenteritis, some patients with submucosal eosinophil infiltration accompanied by granuloma formation, can appear nodular mass, oppression of the stomach Intestinal, causing gastrointestinal obstruction, eosinophils can also invade the serosa, causing peritonitis, manifested as ascites, containing a large number of eosinophils, with certain characteristics, colon involvement is rare, manifested as ileocecal and A multiple ulcer with a descending colon, often forming abdomen mass when the lesion invades the liver or the greater omentum.
7. Kidney performance
About 16% to 80% of patients have kidney involvement, and allergic granuloma kidneys are relatively lightly damaged. The clinical manifestations are microscopic hematuria and/or proteinuria, sometimes self-resolving, but a few can also develop into Severe renal insufficiency requires dialysis treatment. The renal pathology of allergic granuloma is mainly characterized by focal segmental necrotic glomerulonephritis, which may have crescent formation, and other manifestations of renal vasculitis, kidney. Interstitial eosinophil infiltration and granuloma formation.
8. Joint and muscle performance
20% to 51% of patients have polyarticular pain and arthritis. Arthritis usually occurs during vasculitis. Joints can be affected in any part of the joint. It is characterized by migratory joint pain and myalgia is also very common. Leg muscles, spasmodic pain, gastrocnemius tendon pain is often one of the early manifestations of allergic granulomatous vasculitis.
The diagnosis of AG is usually based on typical clinical and laboratory data. The history of asthma after middle age, or asthma with allergic rhinitis and high eosinophilia, multiple mononeuritis, pulmonary infiltration , heart damage, gastrocnemius pain or spasm, as well as the clinical manifestations of skin changes, it is generally not difficult to diagnose this disease.
Lanham et al.: a history of repeated asthma for several years, peripheral blood eosinophils 1.5 × 109 / L; systemic vasculitis involving two or more extrapulmonary organs; increased erythrocyte sedimentation rate, ANCA positive; biopsy A large amount of eosinophil infiltration can confirm the disease.
Examine
Examination of allergic vasculitis and granulomatosis
1. General examination: almost all active CSS are accompanied by varying degrees of anemia and erythrocyte sedimentation rate, and white blood cell reduction may occur. Anemia and leukopenia may be related to autoimmune reaction, and 95% of patients may exceed eosinophils. 10%, the absolute number of the average is 12.9 × 109 / L, when asthma patients with eosinophils above 1.5 × 109 / L, should consider the possibility of this disease, but should be repeated at least 3 times, and exclude drugs And other interference factors.
2. Immunological examination: 75% of patients have elevated serum IgE. The incidence of almost all patients is not directly related to HBsAg. 60% to 70% of patients have positive serum ANCA, and P-ANCA and C-ANCA have the same clinical significance.
3. Imaging examination: chest X-ray examination of CSS patients may have a transient lung infiltration shadow, and the early stage of the disease may be characterized by double-middle-lower lung reticulum changes. With the development of the disease, patchy or large pieces may appear. Shadows, sometimes lung shadows can be migratory, mesenteric artery and renal angiography are usually normal.
4. Histological examination: Biopsy of any affected organ or tissue in the skin, lungs and kidneys shows an angiogenic granuloma-like change in the affected area, accompanied by eosinophil infiltration, which is important for the diagnosis of this disease. value.
Diagnosis
Diagnosis and differentiation of allergic vasculitis and granulomatosis
Diagnostic criteria
1. The 1990 American College of Rheumatology AG classification criteria (Table 2), with a sensitivity of 85% and a specificity of 99.7%, we applied this standard as a clinical application.
If you meet 4 or more of the above 6 criteria, you can diagnose it as CSS.
2. Diagnostic criteria
(1) Asthma: A history of asthma or a diffuse high-pitched voice during exhalation.
(2) Eosinophilia, which is greater than 10% of the white blood cell differential count.
(3) Single or multiple neuropathy: single neuropathy caused by systemic vasculitis, multiple single or multiple neuropathy (ie, glove/sock-like distribution).
(4) Non-fixed intrapulmonary infiltration, migratory or transient pulmonary infiltration caused by systemic vasculitis on X-ray films.
(5) Paranasal sinus lesions, history of acute or chronic paranasal sinus pain or tenderness, blurred paranasal sinus on X-ray films.
(6) extravascular eosinophil infiltration: pathology showed arterial, micro-arterial, venules peripheral eosinophil infiltration.
Four or more of the above six criteria can be diagnosed.
So far, the diagnosis of allergic granuloma is mainly based on the combination of clinical and pathological, most of the patients are in the middle age, often have a history of asthma for several years, in addition to asthma, such as allergic rhinitis and eosinophilia And other systemic lesions such as single or multiple mononeuritis, pulmonary infiltration, myocardial lesions, etc. should consider the possibility of Churg-Strauss syndrome, if there is asthma, eosinophilia and multiple mononeuritis Symptoms, as well as the presence of high titers of anti-myeloperoxidase antibodies or perinuclear anti-neutrophil cytoplasmic antibodies in serum, are highly suggestive of the diagnosis of Churg-Strauss syndrome.
Differential diagnosis
Allergic granuloma should be differentiated from other systemic vasculitis and should be differentiated from certain diseases with peripheral blood eosinophilia as well as bronchial asthma or asthmatic bronchitis.
Nodular polyarteritis
Many clinical manifestations of the third stage of allergic granuloma (systemic vasculitis stage) are similar to nodular polyarteritis. In the past, allergic granuloma was summarized in nodular polyarteritis, both Systemic necrotizing vasculitis has extensive tissue and organ involvement, and pathological findings are similar, but nodular polyarteritis has no history of asthma and allergy, no eosinophilia, and the identification is not difficult. The polymorphic polyarteritis is not completely consistent with the susceptible parts of allergic granuloma. Allergic granuloma often affects the peripheral nerve and heart. Although glomerulonephritis is also common, it is mild and rarely resembles a knot. Renal failure occurs in the same way as polyarteritis. Nodular polyarteritis usually does not invade the lungs, and allergic granulomatous lung involvement is common. In addition, nodular polyarteritis is often associated with hepatitis B virus infection. Allergic granuloma does not have this feature.
2. Wegener granulomatosis
Wegener's granulomatosis and allergic granuloma are not very difficult to distinguish clinically. Wegener's granulomatosis has no history of asthma and allergies, and there are few eosinophilia, allergic granulation. The lesions of the upper respiratory tract are generally non-necrotic, while the Wegener granulomatosis is more common. In addition, the difference between allergic granuloma and Wegener's granulomatous disease is: allergic granulation Swelling kidney damage is often milder than Wegener's granulomatosis, and there is very little renal failure, but Wegener's granulomatosis is common, and the pathological manifestations are also significantly different. Patients with allergic granuloma Skin lesions are more common than Wegener's granulomatosis. Allergic granulomatosis is easy to invade the heart. Wegener's granulomatosis is rare. In addition, anti-neutrophil cytoplasmic antibodies are an important differential diagnosis tool: Plasma neutrophil cytoplasmic antibodies and/or anti-protease-3 antibodies are specific immunological indicators of Wegener's granulomatosis, while neutrophil cytoplasmic antibodies in allergic granulomas are often nuclear Peripheral or anti-myeloperoxidase Positive.
3. Hypereosinophilic syndrome (hypereosinophilic syndrome)
Persistent eosinophilia in peripheral blood and bone marrow, characterized by diffuse infiltration of organ eosinophils, which has many similarities with allergic granulomas, both of which are systemic diseases. With elevated peripheral blood eosinophils and eosinophilic infiltration, it can be expressed as Loftier syndrome, eosinophilic gastroenteritis and other secondary changes, but compared with allergic granuloma, high hobby Acidic granulocyte syndrome has more obvious eosinophilia, and often has myocardial intimal fibrosis, no history of asthma and allergic disease. High eosinophilic syndrome can often be accompanied by diffuse central nervous system damage, liver and spleen. And systemic lymphadenopathy, thromboembolism and thrombocytopenia, and allergic granuloma signs rarely occur, tissue biopsy of high eosinophilic syndrome without vasculitis and granuloma, hormone therapy effect Not good.
4. Chronic eosinophilic pneumonia
Chronic eosinophilic pneumonia is common in women and is characterized by elevated peripheral blood eosinophils, persistent infiltration in the lungs, distribution at the edge of the lung, but no involvement of extrapulmonary tissue, pathologically no vasculitis and granuloma Performance.
5. Both PAN AG and PAN belong to vasculitis, which is mainly caused by small arteries. It can also involve venules. Two-thirds of the patients can affect the kidneys, but AG is mainly affected by lung and kidney. There is also a clinical manifestation characterized by asthma, and PAN lacks this feature. Glucocorticoid and immunosuppressive therapy can achieve the desired relief effect of CSS, and PAN has a poor response to this treatment.
6. Wegener granuloma
The pathological changes were necrotizing granuloma of the upper respiratory tract and/or lung, glomerulonephritis and systemic arterioles, venous vasculitis, only a small amount of eosinophil infiltration was observed in histopathology, and no asthma occurred in the patient. In the end, he died of uremia, and the disease often has no progressive granuloma and renal insufficiency of the upper respiratory tract and kidney. It is only a recurrent asthma caused by transient pulmonary infiltration, and Wegner's granuloma is mainly It is positive for P-ANCA, and AG is mainly positive for C-ANCA.
7. Chronic eosinophilic pneumonia
The disease is more common in women, generally does not involve extrapulmonary organs and tissues, and has no histological features of granuloma and vasculitis, and is easily differentiated from AG.
8. Idiopathic eosinophilia syndrome
The histological features of this disease and AG are blood, bone marrow and other multiple organs, multi-system eosinophil infiltration, and eosinophils in the blood are higher than AG, and can be accompanied by typical myocardial fibrosis However, there is often no asthma attack and no histological features of vasculitis and granuloma.
9. Allergic pulmonary aspergillosis with eosinophilia
The disease can significantly increase serum IgE, pathogens can be found in the sputum, skin allergy test is positive, combined with other clinical and chest X-ray examination, it is not difficult to identify with AG.
