Determining Disease Activity Biomarkers in Individuals With Polyarteritis Nodosa

Longitudinal Protocol of Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a rare immune system disorder that causes swelling and damage to small- and medium-sized blood vessels in the body. In order to properly treat this disease, it is critical that the level of disease activity can be determined over the course of the disease. The purpose of this study is to determine new biological markers, or biomarkers, that may be used to assess the severity of disease in people with PAN.

PAN, also known as systemic necrotic vasculitis, was the first recognized form of primary systemic vasculitis. PAN causes the inflammation of small- to medium-sized blood vessels, especially those supplying the nerves, skin, kidneys, gastrointestinal tract, heart, eye, and genitals. Unlike another form of vasculitis called microscopic polyangiitis, PAN does not usually cause glomerulonephritis, a type of kidney disease, or vasculitis in the very smallest blood vessels (arterioles, capillaries, and venules). There are no radiographic or serologic tests that can reliably measure disease activity in PAN. Currently, clinicians must rely on patients' symptoms, signs, laboratory tests, and imaging to guide treatment decisions, but such data are rarely consistently reliable in determining PAN disease activity. This study will use new scientific methods to discover new biomarkers that can be used to monitor disease activity in PAN patients. These biomarkers may be used to help direct clinical care for PAN patients and assist in future drug development.

Study visits will occur monthly for the first year, then every 3 months thereafter for the remainder of the study. Blood and urine collection will occur at every visit. A physical exam and medical and medication history will occur every 3 months; also, participants will be asked to complete several questionnaires to assess disease activity, health status, and tobacco, alcohol, and drug use. Participants may have additional study visits if a disease flare or disease-related complications occur during the study.

Inclusion Criteria:

• Parent or guardian willing to provide informed consent, if applicable
• Diagnosis of vasculitis
• Diagnosis of PAN, meeting at least 1 major criterion and 1 minor criterion OR 2 major criteria of the following adapted American College of Rheumatology (ACR) criteria that fall under the diagnosis of PAN and that are not explained by other causes:

MAJOR CRITERIA

1. Arteriographic abnormality
2. Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
3. Mononeuropathy or polyneuropathy

MINOR CRITERIA

1. Weight loss of more than 4 kg (8.8 lbs)
2. Livedo reticularis, cutaneous ulcerations, or skin nodules
3. Testicular pain or tenderness
4. Myalgias
5. Diastolic blood pressure greater than 90 mm Hg
6. Elevated blood urea nitrogen (BUN) or serum creatinine levels
7. Ischemic abdominal pain

Exclusion Criteria:

• Microscopic polyangiitis
• Granulomatosis with polyangiitis(Wegener's)
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
• Takayasu's arteritis
• Giant cell arteritis
• Cogan's syndrome
• Behcet's disease
• Sarcoidosis
• Kawasaki disease
• Cryoglobulinemic vasculitis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Mixed connective tissue disease or any overlap autoimmune syndrome
• Presence of antiproteinase 3 or antimyeloperoxidase antineutrophil cytoplasmic antibodies (ANCA)
• Glomeronephritis
• Alveolar hemorrhage
• Hepatitis B, hepatitis C, or HIV infection
• Any other infectious form of medium vessel vasculitis
• Isolated cutaneous PAN