Polyarteritis Nodosa

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Definition

Classic polyarteritis nodosa (PAN) is a multisystem, necrotizing vasculitis of small and medium-sized muscular arteries in which involvement of the renal and visceral arteries is characteristic. PAN does not involve pulmonary arteries, although bronchial vessels may be involved; granulomas, significant eosinophilia, and an allergic diathesis are not part of the classic syndrome. The term microscopic polyangiitis (microscopic polyarteritis) discribes the necrotizing vasculitis with few or no immune complexes (pauci-immune) affecting small vessels (capillaries, venules, or arterioles). Since necrotizing arteritis involving small and medium-sized arteries may also be present, it shares features with classic PAN except that glomerulonephritis is very common in microscopic polyangiitis, and pulmonary capillaritis often occurs.

Incidence And Prevalence

Pan is an uncommon disorder. The mean age at onset in reports of PAN is 48 years, and the male-to-female ratio is 1.6:1.

Pathophysiology And Pathogenesis

The vascular lesion in classic PAN is a necrotizing inflammation of small and medium-sized muscular arteries. The lesions are segmental and tend to involve bifurcations and branchings of arteries. They may spread circumferentially to involve adjacent veins. However, involvement of venules is not seen in classic PAN and, if present, suggests microscopic polyangiitis or the polyangiitis overlap syndrome (see below). In the acute stages of disease, polymorphonuclear neutrophils infiltrate all layers of the vessel wall and perivascular areas, which results in intimal proliferation and degeneration of the vessel wall. Mononuclear cells infiltrate the area as the lesions progress to the subacute and chronic stages. Fibrinoid necrosis of the vessels ensues with compromise of the lumen, thrombosis, infarction of the tissues supplied by the involved vessel, and, in some cases, hemorrhage. As the lesions heal, there is collagen deposition, which may lead to further occlusion of the vessel lumen. Aneurysmal dilatations up to 1 cm in size along the involved arteries are characteristic of classic PAN. Granulomas and substantial eosinophilia with eosinophilic tissue infiltrations are not characteristically found and suggest allergic angiitis and granulomatosis (see below). online canadian pharmacy

Multiple organ systems are involved, and the clinicopathologic findings reflect the degree and location of vessel involvement and the resulting ischemic changes. As mentioned above, pulmonary arteries are not involved in classic PAN, and bronchial artery involvement is uncommon, whereas pulmonary capillaritis occurs frequently in microscopic polyangiitis. The pathology in the kidney in classic PAN is predominantly that of arteritis without glomerulonephritis. In contrast, glomerulonephritis is very common in microscopic polyangiitis. In patients with significant hypertension, typical pathologic features of glomerulosclerosis may be seen alone or superimposed on lesions of glomerulonephritis. In addition, pathologic sequelae of hypertension may be found elsewhere in the body. online canadian pharmacy

The presence of hepatitis B antigenemia in approximately 20 to 30 percent of patients with systemic vasculitis, particularly of the classic PAN type, together with the isolation of circulating immune complexes composed of hepatitis B antigen and immunoglobulin, and the demonstration by immunofluorescence of hepatitis B antigen, IgM, and complement in the blood vessel walls, strongly suggest the role of immunologic phenomena in the pathogenesis of this disease. Hepatitis C infection has been reported in approximately 5 percent of patients with PAN; however, its pathogenic role in the vasculitis is unclear at present. Hairy cell leukemia can be associated with classic PAN; the pathogenic mechanisms of this association are unclear.

Clinical And Laboratory Manifestations

Nonspecific signs and symptoms are the hallmarks of classic PAN. Fever, weight loss, and malaise are present in over one-half of cases. Patients usually present with vague symptoms such as weakness, malaise, headache, abdominal pain, and myalgias. Specific complaints related to the vascular involvement within a particular organ system also may dominate the presenting clinical picture as well as the entire course of the illness. In classic PAN, renal involvement most commonly manifests as ischemic changes in the glomeruli, whereas in microscopic polyangiitis glomerulonephritis is the predominant renal lesion. Hypertension may be related to both the renal polyarteritis and the glomerulitis and may dominate the clinical picture. Classic PAN may involve any organ system. Generic Cialis Soft

There are no diagnostic serologic tests for classic PAN. In over 75 percent of patients, the leukocyte count is elevated with a predominance of neutrophils. Eosinophilia is seen only rarely and, when present at high levels, suggests the diagnosis of allergic angiitis and granulomatosis. The anemia of chronic disease may be seen, and an elevated erythrocyte sedimentation rate (ESR) is almost always present. Other common laboratory findings reflect the particular organ involved. Hypergammaglobulinemia may be present, and up to 30 percent of patients have a positive test for hepatitis B surface antigen. Positive ANCA titers (usually of the p-ANCA type) are found in variable percentages of patients with classic PAN. Microscopic polyangiitis is strongly associated with ANCA that are usually of the p-ANCA type, but c-ANCA have also been reported. In contrast, the ANCA in Wegener’s granulomatosis (see below) are almost always of the c-ANCA type, which can be helpful in distinguishing Wegener’s granulomatosis from microscopic polyangiitis when both present with a pulmonary-renal syndrome. Arteriograms may demonstrate characteristic abnormalities such as aneurysms in the small and medium-sized muscular arteries of the kidneys and abdominal viscera. online drug store

Diagnosis

The diagnosis of classic PAN is based on the demonstration of characteristic findings of vasculitis on biopsy material of involved organs. In the absence of easily accessible tissue for biopsy, the angiographic demonstration of involved vessels, particularly in the form of aneurysms of small and medium-sized arteries in the renal, hepatic, and visceral vasculature, is sufficient to make the diagnosis. Aneurysms of vessels are not pathognomonic of classic PAN; furthermore, aneurysms need not always be present, and angiographic findings may be limited to stenotic segments and obliteration of vessels. Biopsy of symptomatic organs such as nodular skin lesions, painful testes, and muscle groups provides the highest diagnostic yields, while blind biopsy of asymptomatic organs is frequently negative. The presence of small vessel vasculitis, particularly in the setting of glomerulonephritis and pulmonary capillaritis distinguishes microscopic polyangiitis from classic PAN. Viagra Oral Jelly

Prognosis

The prognosis of untreated classic PAN as well as that of microscopic polyangiitis is extremely poor. The usual clinical course is characterized either by fulminant deterioration or by relentless progression associated with intermittent acute flare-ups. Death usually results from renal failure; from gastrointestinal complications, particularly bowel infarcts and perforation; and from cardiovascular causes. Intractable hypertension often compounds dysfunction in other organ systems, such as the kidneys, heart, and central nervous system, leading to additional late morbidity and mortality. The 5-year survival rate of untreated patients has been reported to be 13 percent, while glucocorticoid treatment may increase this figure to over 40 percent. Brand Levitra online

Treatment

Extremely favorable therapeutic results have been reported in classic PAN with the combination of prednisone, 1 mg/kg per day, and cyclophosphamide, 2 mg/kg per day. This regimen has been reported to result in up to a 90 percent long-term remission rate even following the discontinuation of therapy. In addition, long-term remissions have been reported in PAN associated with hepatitis B virus antigenemia using the antiviral agent vidarabine in combination with plasma exchange with and without glucocorticoids. Favorable results have also been reported in the treatment of PAN related to hepatitis B virus with IFN alpha and plasma exchange. Careful attention to the treatment of hypertension can lessen the acute and late morbidity and mortality associated with renal, cardiac, and central nervous system complications of PAN. The treatment regimen for microscopic polyangiitis is similar to that for classic PAN, particularly if glomerulonephritis is present.