OVERVIEW
Polyarteritis nodosa (PAN) is a necrotizing vasculitis characterized by inflammatory exudation and proliferation of medium-sized or small arteries forming segmental nodules. It occurs at the bifurcation of blood vessels and leads to microaneurysm formation, thrombosis, aneurysm rupture and hemorrhage, and organ infarction, most commonly involving the skin, joints, and peripheral nerves, and may involve all organs of the body. The disease can occur at any age, with 40-60 years old being the most common, and the ratio of male to female incidence is about (2-3):1.
Etiology
The exact etiology of PAN is unknown, and may be related to viral and bacterial infections, especially hepatitis B virus (HBV) infection and drugs, injection serum, etc. Immunopathologic mechanisms play an important role in the disease. The etiology can be categorized into two groups: one group of PAN etiology is still unclear; the other group of about 1/3 PAN occurs with HBV infection. The mechanism of vascular injury is not completely clear. HBV-associated PAN is due to HBV antigen-induced immune complexes that can activate complement, inducing and activating neutrophils to cause local vascular inflammatory injury. Cytokines (e.g., α-interferon, interleukin-2, tumor necrosis factor-α, etc.) can induce the expression of adhesion molecules, which make neutrophils susceptible to contact with endothelial cells and induce vascular endothelial injury. Anti-vascular endothelial cell antibodies can act directly on the surface of the vascular endothelium and mediate endothelial damage, and T-cell-mediated immune mechanisms also play a role in the pathogenesis of PAN.
Symptoms
PAN is a systemic disease with variable onset, complex clinical manifestations, and multiple organ damage.
1. Systemic symptoms
Irregular fever, malaise, headache, excessive sweating, weight loss, muscle pain, limb pain, abdominal pain, arthralgia, etc.
2. Skin
20% to 30% of patients with skin damage, typically manifested as painful erythematous subcutaneous nodules along the superficial arterial line or irregularly aggregated in the proximal part of the blood vessels, red in color, with tenderness, most common in the lower limbs, but also purpura, reticular cyanosis, ischemic changes in the distal fingers (toes) or ulcers. If not accompanied by visceral arterial damage is called cutaneous PAN, the prognosis is better.
3. Nervous system
Involvement of peripheral nerves is common, accounting for about 60% of cases, manifested as multiple mononeuritis and/or polyneuritis, peripheral neuritis may appear suddenly, and many of them are the first symptoms of PAN. Central nervous system involvement accounts for about 40% of cases, which may manifest as diffuse or limited unilateral brain or multiple parts of the brain and brainstem with functional abnormalities, convulsions, consciousness disorders, and cerebrovascular accidents.
4. Skeletal and muscular system
About 1/3 of the patients with skeletal muscle and blood vessel involvement have muscle pain with constant site, mostly in gastrocnemius muscle, half of the patients have arthralgia, and a few have obvious arthritic changes.
5. Urinary system
Kidney is the most frequently involved target organ of PAN, and about 30% to 60% of patients present with renal involvement. It is often manifested as hypertension and azotemia; acute necrotizing vasculitis of renal artery in PAN can lead to thrombosis and renal infarction, thus causing acute renal failure; inflammation and secondary fibrosis of periureteral vessels can lead to unilateral or bilateral ureteral stenosis.
6. Digestive system
Involvement of the digestive system is suggestive of a more severe disease and is seen in about 50% of patients. Symptoms vary depending on the location and severity of the vasculitis. In the case of large superior mesenteric artery embolization, there may be vascular infarction, intestinal obstruction, intussusception, intestinal wall hematoma, and in severe cases, intestinal perforation or peritonitis. Inflammation, ulceration, and bleeding of the gastrointestinal tract may occur with involvement of medium and small arteries. When it occurs in the biliary tract, pancreas and liver, the damage can be inflammation and necrosis of the gallbladder, pancreas and liver, which is manifested as abdominal cramps, nausea, vomiting, intestinal bleeding, peritonitis and shock.
7. Others
The incidence of heart damage is about 36%～65%, which is one of the main causes of death; PAN can also involve testes and epididymis, with an incidence of about 30%, and ovaries can also be involved, which is mainly characterized by pain.
Examination
1. Peripheral blood test
Anemia, increased white blood cell count, increased sedimentation rate, increased C-reactive protein (CRP), increased serum immunoglobulin, rheumatoid factor, antinuclear antibody and HBV antigen may be positive. Measurement of plasma β-thromboglobulin and factor VIII-associated antigen can help to follow up the efficacy of treatment and reflect the degree of vasculitis activity.
2. Urine routine examination
Urine routine can see proteinuria, tubular urine, hematuria.
3. Angiography
The liver, kidney, cerebral arteries, mesenteric arteries and coronary arteries may show aneurysmal dilatation or vascular occlusion. Magnetic resonance angiography can confirm the lesions of the above vessels.
Diagnosis
Currently, the classification criteria of the American College of Rheumatology (ACR) in 1990 are used: ① weight loss ≥4 kg (not caused by dieting or other reasons); ② reticular cyanosis (limbs and trunk); ③ testicular pain and/or tenderness (not caused by infection, trauma, or other reasons); ④ myalgia, malaise, or tenderness of the lower extremities; ⑤ polyneuritis mononeuronica or polyneuritis; ⑥ diastolic blood pressure ≥90 mm Hg; ⑦ blood urea nitrogen ＞400 mg/kg; ⑦ blood urea nitrogen ＞400 mg/kg. Urea nitrogen >400mg/L or creatinine >15mg/L (non-renal factors); ⑧ Positive serum hepatitis B virus markers (HBsAg or HBsAb); ⑨ Aneurysm or vascular occlusion on arteriography (except for atherosclerosis, fibromuscular dysplasia, or other non-inflammatory lesions); ⑩ Neutrophilic and monocytic infiltration of the wall of the small and medium-sized arteries on biopsy.
PAN is diagnosed if at least 3 of the above 10 are positive.
PAN should be considered in patients with unexplained fever, abdominal pain, renal failure, hypertension, suspected nephritis, cardiac disease with eosinophilia, arthralgia, and rapidly progressive hypertension, etc. Systemic disease with unexplained symmetric or asymmetric involvement of the major nerve trunks should also be considered to exclude PAN.
Differential diagnosis
The clinical manifestations of this disease are complex and need to be differentiated from various infectious diseases, such as infective endocarditis, primary peritonitis, cholecystitis, pancreatitis, visceral perforation, peptic ulcer, glomerulonephritis, coronary artery disease, polyneuritis, malignant tumors, and vasculitis secondary to connective tissue diseases. Typical PAN should also be differentiated from the following diseases: ① microscopic polyangiitis: the disease is dominated by small vessel involvement, with the kidney and lungs as the main target organs, peripheral nerves are less frequently involved, angiography is not abnormal, and 50% to 80% of the patients are positive for anti-neutrophil cytoplasmic antibody, which is diagnosed by histopathological examination; ② eosinophilic granulomatous polyangiitis: the lesion involves the small- and medium-caliber muscular arterioles, and pulmonary vascular involvement is common. Eosinophilic granulomatous polyangiitis: the lesions involve small and medium caliber muscular arteries, pulmonary vascular involvement is common, with granuloma formation inside and outside the blood vessels, peripheral blood eosinophilia, eosinophilic infiltration of the lesion tissues, and history of bronchial asthma or chronic respiratory diseases; renal involvement is characterized by necrotizing glomerulonephritis, and 2/3 of the patients are positive for anti-neutrophil cytoplasmic antibody.
Treatment
1. Glucocorticoid
Glucocorticoid is the drug of choice for the treatment of this disease. Early high-dose medication can effectively improve the symptoms and alleviate the condition. In mild cases without visceral insufficiency, prednisone can be used orally, and the dosage can be gradually reduced after controlling the symptoms and maintaining the treatment, and attention should be paid to the adverse reactions caused by glucocorticosteroids during the period of taking the drug.
2. Immunosuppressant
If the effect of glucocorticoid control is not good, can be combined with immunosuppressive therapy, usually preferred cyclophosphamide or azathioprine oral. In severe patients with aneurysm, cyclophosphamide should be injected intravenously, and methotrexate, cyclosporine, mycophenolate mofetil can also be used. During the use of drugs, attention should be paid to the detection of blood routine, urine routine and liver and kidney function, pay attention to the side effects of drugs.
3. Drugs for hepatitis B virus infected patients
People with HBV replication can use small-dose glucocorticosteroids and mycophenolate mofetil if necessary, but emphasize the use of antiviral drugs at the same time.
4. Immunoglobulin and plasma exchange
Patients with severe PAN can be treated with shock therapy using high-dose gammaglobulin intravenous infusion or plasma exchange. Both require concomitant use of hormones and immunosuppressants.
Prognosis
The prognosis for untreated PAN is extremely poor, with a 5-year survival rate of only 13%. Common causes of death include cardiac, renal, or other vital organ failure, gastrointestinal complications, or aneurysm rupture. The prognosis of the disease varies widely. Some patients may present with a mild clinical course without severe comorbidities, while others die due to the development of severe multisystem damage. After aggressive treatment with hormones and immunosuppressive agents, the 5-year survival rate of patients significantly increases up to 80%.
Prevention
Infections should be actively prevented and treated, such as good vaccination against hepatitis B, which can effectively prevent hepatitis B virus infection; actively preventing and treating respiratory infectious diseases, such as pharyngitis and tonsillitis, in order to minimize the occurrence of this disease.