Although immunological factors are thought to be central in the pathogenesis of most vasculitic syndromes, a uniform mechanism for all syndromes is not accepted. Clinical and/or experimental data suggests circulating immune complexes as the etiology for several of the vasculitic syndromes. Identification of vascular lesions and identification of immune complexes in the blood and tissues helps to make the diagnosis. However identification of immune complexes in vascular lesions depends on the timing of the biopsy relative to the phase of the disease.[1] Additional support for immune complex etiology is supported by identification of hepatitis B and C antigen in some cases.[1]

A second group of vascular syndromes bears little resemblance to immune complex disease vasculitis. This group is more likely to have a cell mediated etiology, and includes giant cell arteritis, Takayasu's arteritis, Wegener's granulomatosis, and Lymphoid granulomatosis.

The clinical presentation of PAN is related to organ systems involved but includes constitutional symptoms such as malaise, weakness, fever, and weight loss. Overall PAN is clinically rare, and the incidences unknown. PAN peaks in the fourth to fifth decades but it can be seen at any age. The male to female ratio is 2-3:1.

The kidney is involved in 75-80% of cases and is the most common organ involved. Patients present with painless hematuria, hypertension, and rising BUN and serum creatinine. Renal failure may be responsible for death in up to 50% of the patients.[1] Ruptured arterial aneurysms may result in bleeding, leading to subcapsular or perinephric hemorrhage.

Cardiac involvement can be seen in as high as 80% patients of patients. Congestive heart failure is the most common presentation. Involvement of the coronary arteries may lead to ischemia and infarction and conduction abnormalities are rare.

GI involvement with PAN is stated to be as high as 50% of patients.[2] Patients can present with intestinal angina, and may progress to bowel infarction. If ischemia is limited to the mucosa or submucosa, mucosal ulceration and bleeding may occur. With transmural ischemia, infarction may occur and progress to perforation. Liver involvement can result in hepatic hematomas and infarction.

Musculoskeletal involvement can mimic rheumatoid arthritis when it presents as a systemic polyarthritis with elevated ESR and rheumatoid factor. Differentiation generally is based on profound constitutional symptoms in the presence of a non-erosive arthritis in PAN. Muscle involvement can mimic simple myalgias or a proximal myopathy like polymyositis, although dramatic muscle weakness of polymyositis is rare in PAN.

CNS involvement is reported to be seen in 25% of patients and may present with cognitive impairment, altered mental status, seizures, strokes, and hemorrhage. Peripheral presentations may include mononeuritis multiplex with symmetric sensory glove and stocking distributions. New mononeuritis multiplex in the absence of diabetes or trauma should be considered evidence of a necrotizing vasculitis until proven differently.[3]

Skin involvement in polyarteritis nodosa is rare and may present with nonspecific vascular rashes or subcutaneous nodules. These nodules may be quite painful and display necrotizing vasculitis of the muscular arteries on biopsy. Ocular involvement manifests as hemorrhages, conjunctivitis, iritis, and retinal detachments. Orchitis occurs in 10-15% of male patients. When present, it is an excellent source of diagnostic biopsy material.

Laboratory diagnosis in PAN is often nonspecific. The diagnosis is often based on pathologic evidence of necrotizing vasculitis or angiographic evidence of multiple microaneurysms of medium and small arteries such as in the kidneys, coronary vessels, and mesenteric arteries. In the presence of high clinical suspicion with elevated ESR, elevated WBC and anemia but absence of obvious target organ involvement in the abdomen, abdominal angiography is the diagnostic mode of choice. 70-80% of all patients with PAN will have positive abdominal arteriograms consistent with arteritis.[1] 70% of the positive arteriograms demonstrate multiple microaneurysms. Nonspecific radiographic changes of vasculitis include abrupt changes in arterial caliber with arterial narrowing, arterial cutoff, and infarcts such as in the cortex of the kidney.

Biopsies for pathology should be directed at the clinically suspected involved target organs. Blind biopsies of muscle, kidney and testicles in the absence of symptoms is generally not productive. Therapy has markedly improved the 5-year survival from 10-15% in untreated patients to 80% in patients treated with steroids and cyclophosphamide.[1] Treatment is long-term to control the disease, in the order of years in some cases.

References:
1. Calabrese LH, Hoffman GS, Clough JD. Systemic Vasculitis in Peripheral
Vascular Disease. PP 380-405. Ed by Young JR, Olin JW and Bartholomew JR.
Mosby-year Book, Inc. St. Louis, MO, 1996.

2. Reuter SR and Redman HC. Vascular disease in gastrointestinal angiography.
PP 91-93. W.B. Saunders Company, Philadelphia, PA, 1977.

3. Cupps TR, Fauci AS. The vasculitides. Chapter 4: Systemic necrotizing vasculitis
of the polyarteritis nodosa group. W.B. Saunders Co., Philadelphia, 1981.

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