Polyarteritis nodosa (PAN) is a necrotizing vasculitis that affects medium- and small-sized arteries. The estimated annual incidence ranges from 0 to 8 per 1,000,000 people, and the prevalence is approximately 31 per 1,000,000. Men are more frequently affected than women, with a peak onset age of 40–50 years.
Etiology
The cause of PAN remains unknown. A combination of genetic predisposition and viral infections is associated with the disease. Past studies have indicated that infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV may be linked to its onset. However, with the widespread use of hepatitis B vaccination, HBV-related PAN has become increasingly rare, now accounting for less than 5% of PAN cases.
Pathology
PAN is characterized by segmental, transmural necrotizing vasculitis of medium- and small-sized arteries, with a predilection for arterial bifurcations. Any organ's arteries may be involved, although the pulmonary arteries are infrequently affected. In the acute phase, vascular injury manifests as fibrinoid necrosis and infiltration by various inflammatory cells, leading to complete disruption of the normal vascular wall structure, aneurysm formation, and thrombosis.
Clinical Manifestations
The disease can be classified into systemic and single-organ forms. Among the single-organ forms, the skin-limited type is the most common. Systemic PAN includes both idiopathic cases and HBV-related cases. The clinical manifestations of PAN are highly variable. Systemic PAN may cause severe, widespread multi-organ involvement in some patients, with rapid disease progression. In contrast, single-organ PAN is confined to the affected organ.
Systemic PAN
General Symptoms
Fever, general malaise, weight loss, and joint or muscle pain are the most common systemic symptoms, present in 90% of patients.
Systemic Symptoms
Clinical manifestations vary depending on the organs and systems involved.
Nervous System
This is the most frequently affected system in PAN, occurring in 36–72% of patients. Peripheral nerve involvement is predominant, with occasional vascular involvement of the brain. Peripheral nerve involvement may present as mononeuritis multiplex or polyneuropathy, with symptoms such as wrist drop, foot drop, numbness in the hands and feet, and abnormal limb sensory perception.
Renal Involvement
Renal damage occurs in 30–60% of patients to varying degrees, although the glomeruli themselves are rarely affected. Involvement of the renal arcuate arteries can cause elevated serum creatinine levels, hypertension, hematuria, and proteinuria. Lesions in the renal vasculature may lead to multiple areas of infarction in the kidney.
Gastrointestinal System
Nearly 40% of patients exhibit gastrointestinal symptoms, including diarrhea, nausea, vomiting, abdominal pain, gastrointestinal bleeding, bowel ischemia, infarction, perforation, and abnormal liver function.
Reproductive System
Testicular pain, induration, and swelling occur in 20% of patients. However, autopsy findings reveal that 80% of male patients show epididymal and testicular involvement.
Other Manifestations
Ocular involvement may include conjunctivitis, keratitis, uveitis, and occasionally retinal vasculitis, leading to symptoms such as blurred vision, double vision, progressive visual loss, or even blindness. Peripheral vascular involvement can result in intermittent claudication, gangrene, and ulceration in the extremities. Cardiac involvement may manifest as cardiac enlargement, arrhythmias, angina, myocardial infarction, or heart failure.
Cutaneous PAN
Cutaneous PAN is rare and occurs most frequently in women over the age of 40. The most common presentations include skin ulcers, livedo reticularis, subcutaneous nodules, atrophie blanche, and purpura. Lesions are often found on the lower limbs, but the upper limbs and trunk may also be affected. Recurrence is common.
Auxiliary Examinations
Laboratory Tests
Laboratory findings are generally non-specific. Mild anemia, slight increases in leukocyte and platelet counts, and the presence of proteinuria and hematuria in urinalysis may be observed. Additional findings may include elevated erythrocyte sedimentation rate (ESR), increased C-reactive protein (CRP), decreased albumin levels, and elevated globulin levels. Negative antineutrophil cytoplasmic antibodies (ANCA) are typically noted, and patients with hepatitis B-related PAN may present with positive HBsAg.
Angiography
Angiographic findings typically show microaneurysms and segmental stenosis in medium- and small-sized arteries of the kidneys, liver, mesentery, and other visceral organs as well as the lower limbs. The characteristic angiographic finding of PAN includes the "string-of-beads" appearance due to alternating areas of arterial dilation and stenosis, which is diagnostically specific.
Pathology
Histopathological examination of biopsy specimens taken from affected organs may confirm the diagnosis. Findings include inflammatory cell infiltration of the muscular arterial walls, fibrinoid necrosis of the vessel walls, destruction of elastic fibers, narrowing of the vessels, or aneurysm formation.
Diagnosis
The clinical manifestations of PAN are highly variable and lack specificity, making early diagnosis challenging. Suspicious cases often require early pathological biopsy and vascular imaging for confirmation. The 1990 American College of Rheumatology (ACR) classification criteria for PAN are frequently referenced. These include the following:
- Weight Loss: Unexplained weight loss occurring at the onset of the disease, unrelated to diet or other factors.
- Livedo Reticularis: Appearance of mottled or net-like discoloration on the limbs or trunk.
- Testicular Pain or Tenderness: Pain or tenderness in the testicles not caused by infection, trauma, or other factors.
- Myalgia, Weakness, or Leg Tenderness: Diffuse muscle pain (excluding shoulder or pelvic girdle muscles), muscle weakness, or tenderness in the calf muscles.
- Mononeuropathy or Polyneuropathy: Symptoms of mononeuritis multiplex, multiple mononeuropathies, or polyneuropathy.
- Diastolic Blood Pressure ≥90 mmHg: The presence of hypertension with diastolic pressure ≥90 mmHg.
- Elevated Blood Urea Nitrogen (BUN) or Creatinine: BUN levels ≥14.3 mmol/L or serum creatinine levels ≥133 μmol/L, excluding dehydration or obstruction.
- Hepatitis B Virus: Positive HBsAg or HBsAb.
- Abnormal Angiography: Findings of visceral artery occlusion or aneurysm, excluding other causes.
- Medium- or Small-Vessel Biopsy: Evidence of arterial wall infiltration by neutrophils or a combination of neutrophils and mononuclear cells.
A classification of PAN requires the presence of at least three of the ten criteria, while excluding vasculitis associated with other connective tissue diseases or ANCA-associated vasculitis.
Treatment
In idiopathic systemic PAN without organ damage to the nervous system, kidney, or heart in patients under 65 years of age, monotherapy with glucocorticoids is typically sufficient. For cases with organ damage, a combination of glucocorticoids (e.g., prednisone at 1 mg/kg daily or an equivalent dose) and immunosuppressants, with cyclophosphamide as the first choice, is required. Following disease remission, a maintenance treatment using other immunosuppressants, such as azathioprine or methotrexate, can be initiated.
For hepatitis B-related systemic PAN, which tends to present more severe symptoms and pronounced neurological involvement compared to idiopathic PAN, antiviral therapy should be combined with glucocorticoids. Antiviral therapy is typically administered for 6–12 months. In cases where organ involvement due to vasculitis is poorly controlled, the addition of immunosuppressive agents may be necessary.
Prognosis
The prognosis of systemic PAN depends on whether visceral and central nervous system involvement is present and the severity of the disease. Untreated cases have a poor prognosis, with a five-year survival rate of less than 15%. The majority of deaths occur during the first year after disease onset. With timely and appropriate treatment, the five-year survival rate improves dramatically to 83%.