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Study Description

The purpose of this study is to identify genes that increase the risk of developing vasculitis, a group of severe diseases that feature inflammation of blood vessels. Better methods are needed to recruit patients with these rare diseases into cohorts of adequate size for high-quality genetics studies, and the existing infrastructure of the Vasculitis Clinical Research Consortium (VCRC) provides the means for such recruitment. Results of these studies will provide vasculitis researchers with insight into the causes of these diseases and generate new ideas for diagnostic tests and therapies, and will be of great interest to the larger communities of researchers investigating vasculitis and other autoimmune, inflammatory, and vascular diseases. This study will enhance the VCRC Data and Specimen Repository.

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Study Inclusion/Exclusion Criteria

Inclusion criteria for Giant Cell Arteritis:

A total of 300 patients with GCA will be enrolled in the VCRC study cohort. Enrollment will be sequential and patients will have disease in various stages and of different duration.

Patients will have a diagnosis of GA, according to the American College of Rheumatology (ACR) criteria for classification of GCA, meeting at least 2 of the following 5 remaining criteria at the time of diagnosis of GCA.

Age at disease onset >50 years (required)

  1. New onset or new type of localized pain in the head
  2. Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)
  3. ESR of >40 mm in the first hour by the Westergren method
  4. Abnormal artery biopsy (i.e. temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear giant cells)
  5. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else.

Exclusion criteria for Giant Cell Arteritis:

  1. Not applicable

Inclusion criteria for Takayasu's Arteritis:

A total of 200 patients with TAK will be enrolled in the VCRC study cohort. Enrollment will be sequential and patients will have disease in various stages and of different duration.

An adaptation of the American College of Rheumatology (ACR) criteria will be used for the diagnosis of TAK. At the time of inclusion, criterion #6, listed below, must be met (arteriogram abnormalities compatible with TAK, including conventional dye angiography or MR angiography or CT angiography), in addition to at least two of the other criteria listed below (#1 through #5). The criteria will have an additional degree of rigor in that arteriographic abnormalities will be essential for inclusion. Angiographic demonstration of features of TAK was not a requirement of the original criteria.

Adapted American College of Rheumatology (ACR) criteria

  1. Age at disease onset <50 years
  2. Claudication of extremities
  3. Decreased brachial artery pulse (one or both arteries)
  4. Blood pressure difference of >10 mm Hg between the arms
  5. Bruit over subclavian arteries or aorta
  6. Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography)

Exclusion criteria for Takayasu's Arteritis

  1. Arteriographic lesions that could be entirely due to atherosclerosis
  2. Fibromuscular dysplasia
  3. Cogan's syndrome
  4. Behcet's disease
  5. Sarcoidosis
  6. Kawasaki disease
  7. Giant cell arteritis (large vessel vasculitis and >50 years old)
  8. Syphilis or other infectious forms of large vessel vasculitis

Inclusion criteria for Polyarteritis Nodosa

A total of 100 patients with PAN will be enrolled in the VCRC study cohort. Enrollment will be sequential and patients will have disease in various stages and of different duration.

An adaption of the American College of Rheumatology criteria will be used for the diagnosis of PAN. At the time of inclusion, one major and one minor criteria OR two major criteria OR isolated cutaneous PAN must be met. These criteria are meant to help more specifically classify the patient's diagnosis.

College of Rheumatology (ACR) criteria

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 (not explained by other causes) felt by investigator to be due to vasculitis

  1. Weight loss > 4 kg
  2. Livedo reticularis cutaneous ulcerations, or skin nodules
  3. Testicular pain or tenderness
  4. Myalgias
  5. Diastolic blood pressure > 90 mm Hg
  6. Elevated BUN or serum creatinine levels
  7. Ischemic abdominal pain

Isolated cutaneous Polyarteritis Nodosa

  1. Biopsy-proven cutaneous PAN

Exclusion criteria for Polyarteritis Nodosa

  1. Microscopic polyangiitis
  2. Granulomatosis with polyangiitis (Wegener's)
  3. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
  4. Takayasu's arteritis
  5. Giant cell arteritis
  6. Cogan's syndrome
  7. Behcet's disease
  8. Sarcoidosis
  9. Kawasaki disease
  10. Cryoglobulinemic vasculitis
  11. Systemic lupus erythematosus
  12. Rheumatoid arthritis
  13. Mixed connective tissue disease or any overlap autoimmune syndrome
  14. Presence of anti-proteinase 3 or anti-myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA)
  15. Glomerulonephritis
  16. Alveolar hemorrhage
  17. Hepatitis B, hepatitis C, HIV infection
  18. Any other infectious form of medium vessel vasculitis

Inclusion criteria for Granulomatosis with Polyangiitis (Wegener's) and Microscopic Polyangiitis

A total of 500 patients with AAV will be enrolled in the VCRC study cohort. Enrollment will be sequential and patients will have disease in various stages and of different duration.

A participant will be said to have GPA and/or MPA by meeting at least 2 of the 5 modified American College of Rheumatology (ACR) criteria for classification of GPA OR any of the criteria of the Chapel Hill Consensus Conference Definition of Microscopic Polyangiitis Granulomatosis.

Widely accepted diagnostic criteria- as opposed to classification criteria or definitions- have not yet been developed for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The Wegener's Granulomatosis Etanercept Trial employed a modification of the American College of Rheumatology (ACR) Criteria for the classification of GPA in its eligibility criteria. These criteria are shown below:

Modified ACR Criteria for the Classification of Granulomatosis with Polyangiitis. Among a group of patients with various forms of systemic vasculitis, the presence of at least two of the first four criteria is associated with a sensitivity of the criteria, the investigators added a fifth criteria- ANCA positivity- and indicated that patients should have at least 2 of the 5 modified criteria in order to qualify for enrollment.

  1. Nasal or oral inflammation: painful or painless oral ulcers or purulent or bloody nasal discharge
  2. Abnormal chest radiograph: nodules, fixed infiltrates, or cavities
  3. Urinary sediment: microhematuria or red cell casts inflammation on biopsy: granulomatous inflammation within the wall of an artery or in the perivascular area
  4. ANCA positivity by enzyme immunoassay for either PR3- or MPO-ANCA

MPA was not included among the diseases for which the ACR developed Classification Criteria in 1990. In 1994, however, the Chapel Hill International Consensus Conference developed a definition for MPA. This definition is shown below.

Chapel Hill Consensus Conference Definition of Microscopic Polyangiitis

  1. Necrotizing vasculitis with few or no immune deposits affects small vessels (i.e., capillaries, venules, or arterioles).
  2. Necrotizing arteritis involving small and medium-sized arteries may be present.
  3. Necrotizing glomerulonephritis is very common.
  4. Pulmonary capillaritis often occurs.

Exclusion criteria for Granulomatosis with Polyangiitis (Wegener's) and Microscopic Polyangiitis

  1. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
  2. Takayasu's arteritis
  3. Giant cell arteritis
  4. Polyarteritis nodosa
  5. Cogan's syndrome
  6. Behcet's disease
  7. Sarcoidosis
  8. Kawasaki disease
  9. Tuberculosis or atypical mycobacterial infections
  10. Deep fungal infections
  11. Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics AAV
  12. Cryoglobulinemic vasculitis
  13. Systemic lupus erythematosus
  14. Rheumatoid arthritis
  15. Mixed connective tissue disease or any overlap autoimmune syndrome

Inclusion criteria of Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
A total of 200 patients with EGPA will be enrolled in the VCRC study cohort. Enrollment will be sequential and patients will have disease in various stages and of different duration.

An adaptation of the American College of Rheumatology (ACR) criteria will be used for the diagnosis of EGPA. At the time of inclusion, patients must have documented evidence of 4 of the following 6.

Adapted American College of Rheumatology (ACR) criteria

  1. Asthma
  2. Peak peripheral blood eosinophilia of >10% of total BC
  3. Peripheral neuropathy attributable to vasculitis
  4. Transient pulmonary infiltrates on chest imaging studies
  5. Paranasal sinus abnormalities or nasal polyposis
  6. Eosinophilic inflammation on tissue biopsy

If patients have 4 of the above 6 criteria but lack clear-cut documentation of small vessel vasculitis, they are also eligible for enrollment.

Exclusion criteria for Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

  1. Granulomatosis with polyangiitis (Wegener's)
  2. Microscopic polyangiitis
  3. Drug-induced vasculitis
  4. Hypereosinophilic syndrome
  5. Sarcoidosis
  6. Infectious forms of vasculitis
  7. Takayasu's arteritis
  8. Giant cell arteritis
  9. Cogan's syndrome
  10. Behcet's disease
  11. Kawasaki disease
  12. Cryoglobulinemic vasculitis
  13. Systemic lupus erythematosus
  14. Rheumatoid arthritis
  15. Mixed connective tissue disease or any overlap autoimmune syndrome

General Exclusion Criteria

  • Inability to give informed consent and to sign the consent form
  • Enrolled in VCRC protocols 5502, 5503, 5504, 5505, 5506, 5522, or 5523
  • Unwilling to provide blood for DNA collection

Study History

  • Study Activated October 8, 2010
  • First Accrual October 25, 2010

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Diseases/Traits Related to Study (MESH terms)
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