Vasculitis

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Vasculitis

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Inflammation and damage to blood vessels.

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Vascuiltis can cause:

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Lumen compromise and ischemia of distal tissues.

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Vasculitis Pathophysiology

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Immunopathogenic mechanisms thought to be due to certain antigenic stimuli.

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Primary Vasculitic Syndromes

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Wegener's Granulomatosis
Churg-Strauss Syndrome
Polyarteritis Nodosa
Microscopic Polyangiitis.
Giant Cell Arteritis
Takayasu's Arteritis
Henoch-Schonlein Purpura
Idiopathic Cutaneous Vasc
Essential Mixed Cryoglobulinemia
Behcet's Syndrome
Isolated CNS Vasc.
Cogan's Syndrome
Kawasaki DIsease

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Vasculitic Mnemonic

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WG
CSS
PAN
MPA
GCA
TAKA
Henoch
IdioCut
EssMixed
Bechets
CNS
Cogan
Kawasaki

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Vasculitides

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Presence of inflammatory leukocytes in vessel walls with reactive damage to mural structures.

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Effects of vasculitis

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Loss of vessel integrity leading to bleeding. Lumen compromise with ischemia and necrosis distally.

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Vasculitis Classification

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Large vessel V.
Takayasu Arteritis
Giant Cell Arteritis
Medium vessel V.
PAN
Kawasaki Disease
Primary CNS
Small vessel V.
Churg
Wegeners
Mycroscopic Polyarteritis
Henoch-Schonlein Purpura
Essential Cryoglobulinemic V.
Hypersensivity V.
V. Secondary to CTD
V. Secondary to viral infection.

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Vasculitis Mortality Timing related to cause.

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Early due to disease.
Late due to complications of therapy.

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Takayasu Arteritis

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Aorta and large branches. Inflammation may be localized of involve entire vessel.

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Giant Cell Arteritis [Temporal arteritis.]

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Large and medium-sized vessels. Usually cranial branches of arteries originating from aortic arch.

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Polyarteritis Nodosa

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Systemic necrotizing v affecting small and medium-sized muscular arteries.

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Kawasaki Disease

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Arteritis of large, medium and small arteries, particular coronary system. Usually in children and in association with mucocutaneous lymph hode syndrome.

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Primary Central Nervous System V.

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Medium and small arteries over diffuse area of CNS. Without symptomatic involvement of extracranial vessels.

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Churg-Strauss V. [Allergic granulomatosis and angiitis]

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V of medium and small muscular arteries, often found with vascular and extravascular granulmoatosis. Classically involves lung and skin.

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Wegeners G.

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Systemic v. ov medium and small arteries as well as venules and arterioles. Granulomatous inflamation of upper and lower respiratory tracts, necrotizing pauci-immune GNP. Usually assocated with ANCA.

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Microscopic Polyarteritis [or polyangiitis]

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capillaries, venules or arterioles. Associated with ANCA and part of WG clinical spectrum.

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Henoch-Schonlein Purpura

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IgA containing immune complex deposition. Small vessel inflammation esp. postcapillary venules. Hyersensitivity vasculitis.

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Essential Cryoglobulinemic Vasculitis

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Cryoglobulins [mixture of Ig and Complement] that precipitate in cold and dissolve upon rewarming. Usu. due to Hep C inf. CG deposited in walls of small vessles.

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Hypersenstivity V

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Small Vessels. Due to known or suspected substence. Palpable petechiae or purpura major finding. Leukocytoclastic vasculitis on biopsy mostly postcapillary venules.

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CTD-related Vasculitis

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SLE, RA, relapsing polychondritis, BEhcet's, and otherCTD. Small muscular arteries, arterioles and venules. Propensity to affect certain organs related to specific CTD.

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Virus-related V.

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Medium/small vessels. Hep B and C related usually, but occ HIV, CMV, EBV, Parovirus B19. Probably immune-complex related. Presentation MB similar to PAN or MicroPoly. Treatment consists of anti-viral, not anti-inflammatory regimens.

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Vasculitis Clinical Approach

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Systemic symptoms with single or multi-organ dysfunction. Fatigue, weakness, rever, arthralgias, abdominal pain, HTN, renal insufficiency [with active sediment], and neurological dysfunction.

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Leukocytoclastic Vasculitis Overview LCCV

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Leukocytoclastic vasculitis (LCV), also known as hypersensitivity vasculitis and hypersensitivity angiitis, is a histopathologic term commonly used to denote a small-vessel vasculitis (see image shown below). Leukocytoclastic vasculitis has many causes, but no cause is identified in up to 50% of patients with this condition.

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Leukocytoclastic Vasculitis affected areas of the body.

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Leukocytoclastic vasculitis may be localized to the skin or may manifest in other organs. The internal organs affected most commonly include the joints, the gastrointestinal tract, and the kidneys. The prognosis is good in the absence of internal involvement.

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LCCV pathophysiology

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Circulating immune complexes were once believed to be the cause of leukocytoclastic vasculitis. Although immune complexes are involved in the pathogenesis of leukocytoclastic vasculitis, other autoantibodies such as antineutrophil cytoplasmic antibody (ANCA), other inflammatory mediators, and local factors that involve the endothelial cells and adhesion molecules play an important role. However, the exact mechanisms remain unknown.

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LCCV Demographics

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Whites>Blacks
Men=Women
Any age [HSP in kids]

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Possible LCCV Systemic Symptoms

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The physician should elicit information from the patient about possible systemic manifestations. Questions should be directed at evaluating for fever, arthralgia, arthritis, myalgia, abdominal pain, diarrhea, hematochezia, cough, hemoptysis, sinusitis, paresthesia, weakness, and hematuria.

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Mo co presentation small vessel vasculitis

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Palpable purpura is the most common presentation of small-vessel vasculitis.
Lesions are usually round and 1-3 mm.
They may coalesce to form plaques; in some instances, they may ulcerate.
Palpable purpura is most common on the legs, but any surface can be involved. In some cases, the purpuric lesions are barely palpable.

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LCCV Hives

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Urticarial lesions may develop in some patients with leukocytoclastic vasculitis (LCV); in rare cases, this type of lesion predates the purpuric lesions.
The urticarial lesions are of a different character than typical urticaria. They tend to be of longer duration (often >24 h) and tend to resolve with some residual pigmentation or ecchymosis, as depicted below. Patients experience more burning than itching.

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LCCV Hives 2

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Urticarial vasculitis. Lesions differ from routine hives in that they last longer (often >24 h), are less pruritic, and often resolve with a bruise or residual pigmentation.

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Hypocomplimentemic LCCV variation.

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Patients with hypocomplementemic urticarial vasculitis may develop chronic obstructive pulmonary disease, and a careful examination of the heart and lungs is warranted.

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LCCV Ulceration

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Ulceration is more common in vasculitis that affects larger vessels, but it may complicate intense purpura.

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Causes of LCCV

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One third and one are idiopathic.
The remainder have various identifiable causes.
Drugs that can cause cutaneous vasculitis are antibiotics, particularly beta-lactam drugs, nonsteroidal anti-inflammatory drugs, and diuretics. However, almost all drugs are potential causes.

Foreign proteins such as streptokinase, those found in vaccines, and those used in monoclonal antibody therapy can be associated with a serum sickness syndrome with leukocytoclastic vasculitis.

Infections may be associated with vasculitis.
Upper respiratory tract infections, particularly with beta-hemolytic streptococci, and viral hepatitis are implicated most often.
HIV infection is also associated with some cases of cutaneous vasculitis.
Leukocytoclastic vasculitis may also be seen with bacterial endocarditis.
Occasionally, ascertaining whether a drug or an infection is responsible for LCCV is hard due to LCCV postdating insult.

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Causes of LCCV 2

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Foods or food additives may cause vasculitis.
Hepatitis C is a regularly recognized cause of vasculitis, probably through the presence of cryoglobulins; however, in the past, hepatitis B was implicated in some cases of vasculitis.
Collagen-vascular diseases account for 10-15% of vasculitis cases.
In particular, rheumatoid arthritis, Sjögren syndrome, and lupus erythematosus may have an associated vasculitis.
In many cases, the presence of vasculitis denotes active disease.
Inflammatory bowel disease, ulcerative colitis, and Crohn disease may be associated with cutaneous vasculitis.
Malignancy accounts for less than 1% of cases of cutaneous vasculitis.
Perhaps lymphoproliferative diseases are more common, particularly hairy cell leukemia; however, any type of tumor at any site may be related to cutaneous vasculitis.
Effective tumor therapy has led to an apparent cure of the vasculitis in some patients.

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LCCV DiffDX

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Amyloidosis, AA (Inflammatory)
ITP
Antiphospholipid Syndrome
Meningococcemia
Atrial Myxoma
Scurvy
Behcet Disease
Wegener Granulomatosis

Other Problems to Be Considered
Hypersensitivity vasculitis
ITP
Polyangiitis overlap syndrome
Thrombocytopenia

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LCCV Basic Lab

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CBC, ESR, CMP, UA

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LCCV in-depth labs

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Antinuclear antibody, ANCA (cytoplasmic ANCA [cANCA], perinuclear ANCA [pANCA], atypical ANCA), and rheumatoid factor, should be obtained in patients without an obvious cause of their disease. A recent study has linked IgA-type antiphospholipid antibodies with Henoch Schönlein purpura in adult patients.2

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LCCV w/suspected lupus erythematosus and patients with urticarial vasculitis labs:

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Complement levels may be obtained, including total hemolytic complement (CH100 or CH50), C3 levels, and C4 levels.

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LCCV w/o cause ID further labs:

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Paraproteins should include serum protein electrophoresis, cryoglobulins, and hepatitis C antibody.
Hepatitis B was associated with vasculitis in the past; however, it appears that the association may have occurred by virtue of coinfection with hepatitis C (previously termed non-A/non-B hepatitis).
Cryoglobulins may be present in patients with leukocytoclastic vasculitis, especially in association with infections (hepatitis C, bacterial endocarditis). Results for rheumatoid factor are often positive in patients with cryoglobulinemia.
HIV also.

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LCCV + Murmur work-up:

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Blood Culturs and ECHO

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Radiographic LCCV Studies

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CXR, visceral angiography if indicated.

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Hypocomplementemic urticarial vasculitis additional study:

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PFT

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LCCV Histology

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Skin biopsy reveals the presence of vascular and perivascular infiltration of polymorphonuclear leukocytes with formation of nuclear dust (leukocytoclasis), extravasation of erythrocytes, and fibrinoid necrosis of the vessel walls (see image below). This process is dynamic, and biopsy of a lesion performed too early or too late in its evolution may not reveal these findings. The presence of eosinophils has been correlated with drug-associated disease.

Immunofluorescent staining may reveal immunoglobulins (eg, immunoglobulin G, immunoglobulin M) and complement components (eg, C3, C4) deposited on the skin basement membrane, suggesting immune complex deposition. In Henoch-Schönlein purpura, IgA deposits may be found.

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LCCV Treatment

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1. Leg elevation/stockings.
2. Treat identifiable cause.
3. Colchicine/dapsone if cutaneous lesions.
4. If visceral involvement: high-dose steroids w/ w/o immunosuppressant.
5. Patients with either severe or debilitating disease might also be treated with biologic agents such as rituximab or intravenous immunoglobulin

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LCCV Consultations

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Rheumatologist
Dermatologist
Nephrologist
Gastroenterologist or hepatologist
Immunologist or allergist
Pulmonologist

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Rituximab in LCCV

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Stone et al (2010) conducted a multicenter, randomized, double-blind trial comparing rituximab (375 mg/m2/wk for 4 wk) with cyclophosphamide (2 mg/kg/d) in the treatment of ANCA-associated vasculitis. Prednisone was gradually tapered downward; the primary endpoint was remission of disease without use of prednisone at 6 months. The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 67% of the rituximab group compared with 42% of the cyclophosphamide group reached the primary end point (P =0.01).4

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Colchicine in LCCV

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Has effects against neutrophils, which probably are involved in the pathogenesis of cutaneous vasculitis. Has been demonstrated to be steroid sparing in open-label studies. The only double-blind, placebo-controlled trial failed to demonstrate efficacy; however, the study had several methodological errors

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Dapsone in LCCV

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anti-inflammatory properties

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Cyclophosphamide (Cytoxan, Neosar) in LCCV

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Useful in life-threatening cases of vasculitis. Patients with only skin disease generally should not be treated with this agent. Useful in patients with polyarteritis nodosa, Wegener granulomatosis, and Churg-Strauss syndrome. Alkylating agent that depresses T-cell and B-cell function.

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Azathioprine (Imuran) in LCCV

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Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

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Methotrexate (Rheumatrex, Folex PFS) in LCCV

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Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.

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Mycophenolate (CellCept) in LCCV

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Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.
Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (MMF, CellCept) is a prodrug that, once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (MPA, Myfortic) is an enteric-coated product that delivers the active moiety.

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Rituximab (Rituxan) in LCCV

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Antibody genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Antibody is an IgG1-kappa immunoglobulin that contains murine light- and heavy-chain variable region sequences and human constant region sequences.

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Mononeuritis Multiplex [asymmetric polyneuropathy]

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Suggestive of vasculitis. DM only other cause of this problem in developed countries.

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Palpable Purpura in V.

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If alone likely LCCV or hypersensitive v. If with organ involvement likely HSP or microscopic polyarteritis.

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V. with GNP and pulmonary involemement.

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Suggests Wegeners or MicroPoly. May also be anti-GBM disease. Also, PE, infection and SLE.

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Cytopathological Mechanisms in V.

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Immune complex:
HSP
V with CVD.
Serum Sickness
Hep C ess mixed cryo
Hep B PAN
ANCA Production types:
Wegeners
Churg
Micro-Poly
Pathologic T-lympho Resonose with granule formation
GCA
Taka
Wegeners
Churg