Polyarteritis Nodosa (PAN) is a rare systemic necrotizing vasculitis that primarily affects medium-sized muscular arteries. It leads to vessel inflammation, resulting in damage to the vessel wall and subsequent organ ischemia and infarction. This condition is characterized by segmental transmural inflammation of the arterial wall.
Histological Features
The hallmark of PAN is the presence of focal, segmental, and transmural inflammation of the affected arteries. Histologically, the inflammatory infiltrate is composed of
neutrophils, eosinophils, and mononuclear cells. The inflammation leads to fibrinoid necrosis of the vessel wall, which is a key histopathological finding. As the disease progresses, the inflammation can cause aneurysmal dilatation and rupture of the arteries.
Stages of Inflammation
PAN exhibits different stages of inflammation within the same artery. Early lesions show an acute inflammatory response with neutrophilic infiltration and fibrinoid necrosis. In the chronic phase, the inflammation is replaced by
fibrosis and
thrombosis. This results in the thickening of the vessel wall and narrowing of the lumen, leading to reduced blood flow.
Pathogenesis
The exact cause of PAN is unknown, but it is believed to be an immune-mediated process. Immune complexes and autoantibodies likely play a role in the pathogenesis. The involvement of hepatitis B virus (HBV) infection has been noted in some cases, suggesting an infectious trigger for the autoimmune response. The immune complexes deposit in the vessel walls, triggering an inflammatory response that leads to vascular damage.
Clinical Manifestations
The clinical manifestations of PAN are varied and depend on the organs involved. Common symptoms include fever, weight loss, hypertension, and myalgia. Organ-specific symptoms may include renal impairment due to
glomerulonephritis, gastrointestinal symptoms from mesenteric artery involvement, and neurological deficits due to peripheral nerve inflammation. Skin lesions such as nodules, ulcers, and livedo reticularis are also common.
Diagnosis
The diagnosis of PAN is based on clinical criteria, laboratory findings, and histopathological examination. A biopsy of an affected artery is the gold standard for diagnosis. Imaging studies such as angiography can also aid in identifying characteristic aneurysms and stenoses in medium-sized arteries. Laboratory tests may show elevated inflammatory markers, but specific tests for PAN are lacking.
Treatment
Treatment of PAN involves immunosuppressive therapy to control the inflammatory process.
Corticosteroids are the mainstay of treatment, often combined with other immunosuppressive agents such as cyclophosphamide. In cases associated with HBV infection, antiviral therapy is also recommended. Early diagnosis and treatment are crucial to prevent irreversible organ damage.
Prognosis
The prognosis of PAN varies depending on the extent of organ involvement and the timeliness of treatment. Untreated PAN can be fatal due to complications such as renal failure, myocardial infarction, and gastrointestinal perforation. With appropriate treatment, the prognosis has significantly improved, with many patients achieving remission.
Research and Future Directions
Ongoing research aims to better understand the pathogenesis of PAN and to identify novel therapeutic targets. The role of genetic factors, environmental triggers, and immune mechanisms continues to be explored. Advances in imaging techniques and biomarkers may also improve the early diagnosis and monitoring of disease activity.
