One-Time DNA Study for Vasculitis

The systemic vasculitides comprise several inflammatory diseases of blood vessels, usually
arteries, which may cause systemic, multi-organ disease that can result in substantial
morbidity and increased mortality. Each type of vasculitis is a rare ("orphan") disease.
However, taken together, vasculitis affects tens of thousands of Americans and is responsible
for substantial morbidity and mortality and almost one billion dollars per year in hospital
care alone. While the vasculitides share the trait of vascular inflammation, the unique
disease phenotypes, clinical courses, differences in prognoses, and responses to therapy
suggest that important differences exist in pathogenesis. The Vasculitis Clinical Research
Consortium (VCRC) currently focuses on 6 specific types of vasculitis that were selected to
represent a balance between unmet medical and scientific needs, prevalence in North America,
feasibility of study, and an interest in studying a spectrum of small, medium, and large
vessel vasculitides.

The great majority of published studies on the genetics of vasculitis have used modest-sized
cohorts that are only suitable for investigation of a few candidate genes at a time, or to
detect large effect sizes, so that replicated findings are highly skewed to the HLA region.
Larger and more ambitious genetic studies in vasculitis are expected to generate numerous
hypotheses for translational research in gene expression, biochemistry, and molecular
pathology.

A one-time collection of clinical data and DNA would substantially increase the sample sizes
for genetic association studies in all six vasculitides studied in the VCRC. Many patients
are seen at participating VCRC centers but do not enroll in the Longitudinal Studies. These
patients often are interested in participating in research studies but cannot return
frequently for visits, usually due to distance from the VCRC centers. This approach would be
particularly useful for the rarer forms of vasculitis under study (Takayasu's Arteritis
(TAK), Polyarteritis Nodosa (PAN), eosinophilic granulomatosis with polyangiitis
(Churg-Strauss) (EGPA) and also for Giant Cell Arteritis (GCA), since elderly patients have
been particularly likely to decline participation in the Longitudinal Studies due to travel
constraints.

Inclusion Criteria:

1. Diagnostic criteria for Giant Cell Arteritis 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 >40mm 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 cell infiltration or granulomatous inflammation,
usually with multinucleated giant cells)

5. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else

Inclusion Criteria:

2. Diagnostic criteria for Takayasu's Arteritis

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 >10mm 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)

Inclusion Criteria:

3. Diagnostic criteria for Polyarteritis Nodosa Major criteria (not explained by other
causes) felt by investigator to be due to vasculitis

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

Inclusion Criteria:

4. Diagnostic criteria for Granulomatosis with Polyangiitis (Wegener's) (GPA) and
Microscopic Polyangitis (MPA)

- Diagnosis of GPA or MPA. Widely accepted diagnostic criteria, as opposed to
classification criteria or definitions, have not been developed for GPA & MPA.

- For diagnosis of GPA meets at least 2 of the following 5 modified ACR criteria:

1. Nasal or oral inflammation with oral ulcers or nasal discharge with pus or blood

2. Abnormal chest radiograph with nodules, fixed infiltrates, or cavities

3. Urinary sediment with microhematuria or red cell casts

4. Granulomatous inflammation within the wall of an artery or in the perivascular
area on biopsy

5. Antineutrophil cytoplasmic antibody (ANCA) positive by enzyme immunoassay for
either PR3- or MPO-ANCA

- For diagnosis of MPA, meets the Chapel Hill Consensus Conference Definition for MPA:

1. Necrotizing vasculitis, with few or no immune deposits, that affects small
vessels (i.e., capillaries, venules, arterioles)

2. Necrotizing arteritis involving small- and medium-sized arteries may be present

3. Necrotizing glomerulonephritis is very common

4. Pulmonary capillaritis often occurs

Inclusion Criteria:

5. Diagnostic criteria for Eosinophilic Granulomatosis with Polyangiitis
(Churg-Strauss)

1. Asthma

2. Peak peripheral blood eosinophilia of >10% of total WBC

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 clearcut documentation of
small vessel vasculitis, they are also eligible for enrollment.

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