polyarteritis nodosa
Introduction
Introduction to nodular polyarteritis Nodular polyarteritis, also known as polyarteritis, or nodular arteritis, is a necrotizing vascular inflammatory disease involving the small and medium arteries. Nodular polyarteritis can affect any organ of the human body, but It is most common in the skin, joints, peripheral nerves, gastrointestinal tract and kidneys. The severity of the lesion varies greatly from person to person. Nodular polyarteritis can also be combined with other diseases such as rheumatoid arthritis, Sjogren's syndrome, etc. According to the size of the affected vessels, it is divided into classic nodular polyarteritis and Minimal polyarteritis, the former invades the middle arteries and their branches, the latter involves small arteries and venules, characterized by small and medium arterial necrotizing, non-granulomatous vasculitis, because vascular injury does not only involve the outer layer of the arterial wall Rather, it may involve necrotizing arteritis in all layers of the arterial wall, eventually leading to multiple aneurysms, thrombosis or infarction. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious complication:
Cause
Cause of nodular polyarteritis
Virus infection (30%):
A part of nodular polyarteritis (about 1/3) is associated with hepatitis B virus infection. With the application of hepatitis B vaccine, patients with nodular polyarteritis associated with hepatitis B infection are gradually decreasing, causing knots. Other causes of polyarteritis may be human immunodeficiency virus infection, cytomegalovirus infection, paravirus B19, etc., but there is no direct evidence that these factors can cause nodular polyarteritis, the blood vessel wall of experimental animals. Various antigens are sensitized to the subendothelial glassy necrosis. The mechanism is that the immune complex (IC) deposits on the blood vessel wall, which activates complement to cause inflammation, activates the complement component to attract polymorphonuclear leukocytes to release the immune complex at the phagocytic deposition. Enzymes damage the arterial wall. The development of IC arteritis is related to the persistence of IC, size and genetic quality. The virus grows in the intima of the blood vessels. Localization can also cause arteritis, such as cytomegalovirus and rubella virus. The disease can also be caused by high blood pressure caused by drugs and high blood pressure caused by unilateral nephrectomy.
Vascular injury (25%):
1. The mechanism of vascular injury in nodular polyarteritis is not well understood. Some of the nodular polyarteritis associated with hepatitis B virus infection, hepatitis B virus antigen-induced immune complexes can activate complement, induction and activation. Granulocytes cause local vascular inflammation damage.
(1) Cytokines play an important role in the pathogenesis of nodular polyarteritis. Peripheral serum in patients with nodular polyarteritis, interferon-, interleukin-2, -tumor necrosis factor, interleukin The levels of -1 and so on were significantly elevated, and they induced the expression of adhesion molecules (LFA-1, ICAM-1 and ELAM-1), which made neutrophils easy to contact with vascular endothelial cells and induced vascular endothelial cells. In addition, anti-vascular endothelial cell antibodies are often detected in the serum of patients with nodular polyarteritis. Anti-endothelial cell antibodies can directly act on the surface of vascular endothelial cells, and mediate vascular endothelial damage through antibody-dependent cytotoxicity.
(2) Immunohistochemical studies have found that a large number of macrophages and T lymphocytes (mainly CD4) infiltrate in the inflammation site of patients with nodular polyarteritis. These T cells express a large number of lymphocyte activation markers, such as IL-2. HLA-DR antigens, etc., suggest that T cell-mediated immune mechanisms play a role in the pathogenesis of nodular polyarteritis.
Neither cytokines, anti-endothelial cells nor T-cell-mediated immune mechanisms are characteristic of nodular polyarteritis, but also in other systemic vasculitis such as Wegener's granulomatosis, Churg-Strauss syndrome.
Necrotic injury (25%):
(1) The pathology of nodular polyarteritis is generally characterized by focal vascular necrotic inflammatory lesions in the middle and small muscle arteries, rarely involving small arteries and venules, and lesions occurring in vascular bifurcation At any point, the arteries of any part of the body can be affected, but usually the lung and spleen arteries are rarely involved. The characteristics of vascular inflammation in the acute phase are mainly fibrinoid necrosis and infiltration of various cells. The infiltrating cells are mainly polymorphic nuclei. White blood cells, lymphocytes and eosinophils, the structure of the normal blood vessel wall is completely destroyed (Fig. 1), and aneurysms and thrombosis are also seen.
(2) Another characteristic of the pathological changes of nodular polyarteritis is that the same patient's active lesions and healed vascular injuries can exist simultaneously (Fig. 2). It is difficult to determine the involvement of different organs because in many studies. The source of the patients varies greatly. In the autopsy case report, the kidney and heart involvement of the patients with nodular polyarteritis accounted for about 70%, the liver and gastrointestinal involvement accounted for about 50%, and the peripheral nerve involvement accounted for 50%. Mesenteric involvement accounts for 30%, skeletal muscle involvement accounts for 30%, central nervous system involvement accounts for 10%, and skin involvement rates vary widely (from 2% to 50%) (Figures 3, 4).
Prevention
Nodular polyarteritis prevention
First, primary prevention
1. Avoid indoor over-cooling or overheating, and the temperature should be appropriate.
2. Anti-infection, enhance physical fitness, improve autoimmune function, regular life, and comfortable mood.
3. Strong nutrition, avoid alcohol and spicy stimulating items, and avoid fat and savory products.
Second, secondary prevention
Phase 1 diagnosis, phase 2 comprehensive treatment.
Third and third level prevention
At present, there is no specific drug for this disease. Traditional Chinese medicine treatment can regulate immunity, clear away heat and detoxify, promote blood circulation and remove blood stasis, and often work.
Complication
Nodular polyarteritis complications Complication
Common complications of this disease:
1. Arrhythmia.
2. Intestinal bleeding perforation.
3. Acute oliguric renal failure.
Symptom
Nodular polyarteritis symptoms common symptoms dyspnea vascular atrophic leukoplakia visual disorder reticular plaque systemic vasculitis corneal ulcer jaundice arrhythmia fatigue visual field defect
Both men and women can be ill, more common in men, due to a variety of tissue organs can be involved, clinical manifestations are complex and diverse, early stage of the disease with atypical systemic symptoms is more common, can also be a system or organ as the main performance, The disease is generally divided into skin type and system type.
(a) skin type : skin lesions are confined to the skin, characterized by nodules and common, generally 0.5 ~ 1.0cm size, solid, single or multiple, arranged along the superficial artery or irregularly gathered near the blood vessels, Rose red, bright red or near normal skin color, can be freely pushed or adhered to the skin, with tenderness, necrosis can form ulcers in the center of the nodules, the edges are not Liu, often there are reticular bluish spots, wheal, blisters and purpura, etc. It occurs in the calf and forearm, torso, face, scalp and earlobe. It occurs on both sides but is asymmetrical. The skin lesions can also be pleomorphic. Generally, there is no systemic symptoms, or it may be accompanied by low fever, joint pain, and muscle. Pain and other discomfort, benign process, a seizure.
(B) system type : acute or insidious onset, often irregular fever, fatigue, joint pain, myalgia, signs of physical and other symptoms of general discomfort.
1. Renal lesions are the most common, may have proteinuria, hematuria, a small number of nephrotic syndrome manifestations, severe renal function damage can occur when the renal arterioles are extensively affected, intrarenal aneurysm rupture or severe renal colic can occur due to infarction And a large number of hematuria, hypertension is more common, sometimes the only clinical manifestations, high blood pressure increased kidney damage, uremia is one of the main causes of death.
2. Digestive system: affected with different parts of the lesions, abdominal pain is the most common, vomiting, blood in the stool, etc., such as small aneurysm rupture can cause digestive tract or abdominal bleeding, manifested as severe abdominal pain, signs of peritonitis, liver involvement There may be jaundice, upper abdominal pain, elevated transaminase, and hepatitis C virus infection in patients with chronic active hepatitis. When the gallbladder and pancreas are involved, they may show symptoms of acute cystitis and acute pancreatitis.
3. Cardiovascular system: It is also more common, except for renal hypertension, which can affect the heart, mainly due to coronary artery disease, angina pectoris, severe myocardial infarction, heart failure, various arrhythmias can occur, to the room Sexual tachycardia is common, and heart failure is one of the major causes of death in this disease.
4. The nervous system: This system is commonly involved. In the progressive PAN, the nervous system symptoms appear earlier, especially peripheral neuropathy, which is caused by vasculitis of the nutritional nerve. The incidence of this disease can reach 50% to 70%. And can be the initial manifestation of the disease, the most typical is polyneuritis, characterized by pain or paresthesia along the nerve pathway, sudden onset, both upper and lower limbs can be involved, often asymmetry, can also affect motor function Central nervous system lesions are rare, manifested as severe headache, epilepsy, hemiplegia, coma, insanity or subarachnoid hemorrhage, etc., the above symptoms often indicate poor prognosis, the special symptoms of peripheral nerves are due to the involvement of the phrenic nerve The wrist is drooping, the median neuropathy cannot raise the thumb, and the foot is drooping caused by the involvement of the phrenic nerve.
5. The respiratory system PAN has fewer lungs than other vasculitis. The respiratory symptoms are mainly chest pain, cough, asthma, dyspnea and hemoptysis. The arteritis of the lungs and/or trachea can cause obstruction, infarction and intrapulmonary hemorrhage. Or hemorrhagic pleural effusion, pneumonia or pneumothorax may occur, pulmonary hypertension is rare.
6. Eye manifestations The incidence of eye symptoms is 10% to 20%, including optic atrophy, retinal detachment, optic disc edema, central retinal artery occlusion, uveitis, diffuse choroiditis, iritis, scleritis, scleral perforation Necrosis and subconjunctival hemorrhage, high blood pressure can also cause retinal artery disease, symptoms include visual impairment, sudden loss of vision (often unilateral), diplopia and blind spots, in addition to hypertensive arteriolar changes, fundus hemorrhage And exudation, visual field defects, conjunctivitis, conjunctival edema and corneal ulcers.
7. Skeletal muscle system muscles, joint pain is common, limb pain is due to neuropathy, ischemia or vascular damage in muscle fibers, joint pain can be migratory, severe gastrocnemius pain is more common, muscle biopsy can suggest this disease.
8. Testicular male patients may have orchitis or epididymitis, testicular pain is a common symptom, and even can cause testicular shrinkage, Dahl et al reported that 86% of patients with testicular tissue have pathological features of nodular polyarteritis.
9. Restricted type accounts for about 10% of PAN, also known as skin-type nodular arteritis (CPN). The cause is unknown. The incidence of men and women is equal. The age of onset is 5 to 68 years old. This type only affects skin, joints, muscles and individual. There are peripheral neuropathy, no visceral involvement, clinically many chronic recurrent benign processes, laboratory tests in addition to increased erythrocyte sedimentation rate, skin biopsy can make a diagnosis, skin tissue immunofluorescence can be seen IgM and C3 precipitation, individual cases HBV antigen positive A small number of cases exist simultaneously with arteritis. The clinical can be relieved spontaneously or after hormone therapy. Non-hormonal antipyretic analgesics are effective in some patients, and a few patients respond to sulfapyridine treatment.
10. Kidney performance: The kidney is the most important "target" organ of the disease, 80% to 90% have different degrees of renal damage, most patients have mild clinical manifestations, moderate proteinuria, microscopic or gross hematuria, red blood cell tubular urine, a few It is characterized by nephrotic syndrome. In severe cases, renal failure occurs. If it develops rapidly, it will enter uremia for several weeks or several months. More than half of the patients may die from renal failure.
Renal infarction or hemangioma rupture caused by renal arteritis is also an important clinical manifestation of nodular polyarteritis. The area of renal infarction is large, which can lead to ischemic necrosis of the renal cortex and cause hypertension. If the infarct size is small, clinical Completely asymptomatic, hematuria of necrotizing glomerulonephritis is mostly painless. If there is a large amount of gross hematuria with hypochondriac pain and rib angle tenderness, retroperitoneal and perirenal hemorrhage due to renal infarction or aneurysm rupture should be considered. Renal angiography is helpful for diagnosis and emergency surgical exploration if necessary.
In PAN, renal angiography suggests that approximately 1/3 of patients have intrarenal arterial hemangioma and/or renal infarction, combined with systemic symptoms, and skin or neuromuscular biopsy to determine the diagnosis. Patients with suspected and PAN have kidneys. Injury, renal angiography should be performed before renal puncture. If there is renal microangioma, renal puncture can not be performed.
When the renal tubular injury occurs, it can show the dysfunction of urine concentration and dilution. The patient has polyuria and does not respond to diuretic hormone. The ureter can cause spasm, infarction, and enlarge the renal pelvis.
The course of the disease depends on the organs involved, the severity varies, the severe ones develop rapidly, and even die. There are also relief and seizures that alternate and appear to be cured for many years.
Examine
Examination of nodular polyarteritis
Nodular polyarteritis is not specific in laboratory examination. There are positive pigmentation anemia in blood routine examination, total white blood cells and neutrophils are often increased, and the number of platelets is not significantly changed. Urinary protein can be seen in urine examination. Microscopic hematuria or gross hematuria can also occur in cell type, granule tube type and waxy tube type. When renal function is abnormal, serum creatinine can be increased and creatinine clearance rate can be decreased.
In addition, it often manifests as increased erythrocyte sedimentation rate, increased C-reactive protein, decreased albumin levels, increased globulin, decreased total complement and complement C3 levels, etc. Low complementemia is commonly seen in patients with secondary polyarteritis, rheumatoid factor. It can be positive and often accompanied by cryoglobulinemia. Antinuclear antibodies are not as common as rheumatoid factors, and are often low titer positive. Antineutrophil cytoplasmic antibodies are generally negative.
About 7% to 54% of patients with nodular polyarteritis are positive for hepatitis B virus surface antigen, although with the increase in the use of hepatitis B vaccine, patients with nodular polyarteritis associated with hepatitis B infection have been significantly reduced, but all nodules Hepatitis B antigen and antibody tests should be performed in patients with polyarteritis. Typical nodular polyarteritis usually occurs in the first 6 months of hepatitis B infection. Hepatitis C infection is also associated with nodular polyarteritis, especially It is closely related to patients with both cryoglobulinemia and hypocomplementemia.
Angiography often finds small aneurysms and segmental stenosis in the middle and large arteries of the kidneys, liver, mesentery and other internal organs. Although the formation of small aneurysms is not a characteristic change of nodular polyarteritis, it is very common. In contrast, aneurysms are rarely found in anti-neutrophil-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis), and angiography is useful when other findings are not abnormal. The diagnostic tool, visceral angiography of nodular polyarteritis, shows segmental stenosis and aneurysm formation.
Diagnosis
Diagnosis and differential diagnosis of nodular polyarteritis
diagnosis
1. The clinical manifestations of nodular polyarteritis are different, and early diagnosis is not easy. Most patients have systemic manifestations such as fatigue, fever and weight loss, such as skin damage, peripheral neuropathy and kidney disease. Systemic involvement is highly suggestive of the diagnosis of nodular polyarteritis. Rheumatoid polymyalgia syndrome or oligoarthritis involving large joints may also be an early clinical manifestation of nodular polyarteritis, suggesting nodular polyarteritis Some of the key clinical manifestations of diagnosis are:
(1) Systemic manifestations: fever, chills, fatigue, weight loss, general discomfort.
(2) joint pain or myalgia.
(3) Multiple organ involvement.
1 skin damage (purpura, reticular epidermis, necrotizing damage, extremity necrosis).
2 peripheral neuropathy (multiple single neuritis).
3 abnormal urine sediment, high blood pressure.
4 abdominal pain.
Although the diagnosis of nodular polyarteritis is mainly based on clinical manifestations, biopsy and angiography are important criteria for the diagnosis of nodular polyarteritis:
1 biopsy: if the pathology confirmed that there is a small, arterial necrotizing vasculitis suggests the possibility of the disease, but no specificity, the positive rate of biopsy is related to the site of the material, in the organs and tissues with corresponding symptoms and signs, the positive rate Relatively high.
2 angiography: also no specificity, but can indicate the presence of systemic vasculitis.
2. In 1990, the American College of Rheumatology proposed a classification criteria for nodular polyarteritis (Table 1). In 1994, the International Conference on Vasculitis held in Chapel Hill, USA, proposed the definition criteria for nodular polyarteritis, namely: , necrotizing inflammation of small arteries, no arterioles, involvement of capillaries and venules, no glomerulonephritis, currently clinically based on these two criteria to diagnose nodular polyarteritis, many scholars believe that Chapel Hill meeting The standard is relatively narrow. According to this standard, the incidence of nodular polyarteritis is very low, so its clinical applicability requires further study.
3. In 1990, the US ACR classification (diagnosis) standard for PAN was confirmed by three or more of the following criteria:
(1) Weight loss 4kg, except for diet or other factors.
(2) reticular bluish spots: spots or reticular spots on the limbs or trunk.
(3) Testicular pain or tenderness: except due to infection, trauma or other causes.
(4) Myalgia, weakness or tenderness of the lower extremities, diffuse myalgia (except for the shoulder muscles and hip belt muscles) and muscle weakness or lower limb muscle tenderness.
(5) Single neuropathy or polyneuropathy.
(6) Diastolic blood pressure 12.0 kPa (90 mmHg).
(7) Creatinine, elevated urea nitrogen: serum creatinine 132.7 mol / L (1.5 mg / dl) or blood urea nitrogen 14.3 mmol / L (40 mg / dl).
(8) Hepatitis B virus: HBsAg or HbsAb was detected in serum.
(9) Angiographic abnormalities: including visceral aneurysms or obstruction, except for arteriosclerosis.
(10) Small and medium arterial biopsy: pathology shows granulocyte and/or mononuclear cell infiltration in the arterial wall.
Differential diagnosis
1. Nodular polyarteritis and microscopic polyangiitis, Wegener's granulomatosis and other types of systemic vasculitis such as Churg-Strauss syndrome have many similar clinical manifestations, requiring differential diagnosis, microscopic microvascular The main difference between inflammation and nodular polyarteritis is the presence or absence of arterioles, venules or capillary involvement. When these small blood vessels are involved, even if there is a moderately large arterial injury, the diagnosis should be Considering microscopic vasculitis under the microscope, in addition, microscopic vascular glomerular involvement is one of its characteristic manifestations, while nodular polyarteritis is generally free of glomerular lesions. Wegener's granuloma is a kind of Middle and small vascular involvement of necrotizing vasculitis, but can also involve tiny blood vessels, pathological manifestations of granuloma formation characteristic changes, and nodular polyarteritis generally no granuloma formation, in addition, in Wegener granulation Most of the swelling is cytoplasmic anti-neutrophil cytoplasmic antibody positive, while nodular polyarteritis is generally negative for anti-neutrophil cytoplasmic antibodies, Churg-Strauss syndrome is a small blood Tube-related necrotizing vasculitis, its pathological changes also have the characteristics of granuloma formation, characterized by eosinophilia and asthma in the clinic and anti-neutrophil cytoplasmic antibodies are often positive, these characteristics are easy to Nodular polyarteritis was identified.
2. In addition, many diseases such as cholesterol embolism, sepsis, infective endocarditis, left atrial myxoma and tumor have similar clinical manifestations with nodular polyarteritis and must be differentiated.
