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VasculitisI. Introduction
A. Definition - "vasculitis" encompasses a group of clinicopathologic entities marked by inflammation and necrosis of blood vessels.
1.Different vasculitides are differentiated by pathologic and clinical findings and if known, etiological factors.
II. Clinical vasculitides
A. PAN
1. Necrotizing panarteritis of small to medium sized arteries.
2. Pathology.
a. Inflammatory infiltrate contains PMN, lymphocytes and eosinophils, fibrinoid necrosis, disruption of elastic lamina.
b. Vessel occlusion, thrombosis.
c. Lesions are segmental and at different stages of development.
d. Lesions at arterial bifurcations, microaneurysms.
e. Healed lesions - proliferation of fibrous tissue, endothelial cells, fibrosis.
3. Clinical features.
a. Uncommon disease.
b. M:F, 2:1. May occur at any age but peak age is 40-60 yrs.
c. Systemic symptoms - fever, malaise, arthralgias, myalgias, wt loss.
d. Renal disease - 70%, vasculitis, glomerulonephritis.
(1) Hypertension, renal insufficiency.
e. Peripheral neuropathy - 50-70%, mononeuritis multiplex, asymmetric sensorimotor neuropathy (often becomes symmetric later in illness).
f. Skin - 50%, palpable purpura, ulcerations, livedo reticularis, digital ischemia.
g. Joints - 50%, arthralgias/arthritis, nondeforming, asymmetric, lower extremities.
h. Liver - 50%, chronic HBsAg carrier, occasionally hepatitis.
i. GI - 25%, nausea, vomiting, abdominal pain, bleeding, ischemia.
j. Lungs- 10%, infiltrates.
k. Occasionally clinical involvement of CNS, heart, eyes and testes.
4. Laboratory findings - anemia, leukocytosis, elevated ESR, UA with proteinuria cells, hypoalbuminemia, hypergammaglobulinemia, hypocomplementemia, HBsAg+ (up to 50%).
5.Rheumatoid vasculitis.
a. Usually occurs in patients with tong standing, severe RA.
b. Pathology is similar to PAN.
c. Similar clinical presentation to PAN except renal disease unusual.
(1) Digital infarcts and leg ulcers common.
6. PAN associated with hairy cell leukemia.
B. Leukocytoclastic (hypersensitivity) vasculitides.
1. Heterogeneous group of disorders involving small vessels - arterioles, capillaries and especially venules.
2. Pathology shows vasculitis with inflammatory infiltrate consisting predominantly of PMN and fibrinoid necrosis.
3. Lesions are all at same stage consistent with acute exposure to antigen (hypersensitivity).
4. Skin involvement is characteristic - palpable purpura, macules, papules, ulcers, vesicles, bullae, urticaria, erythema multiforme, nodules, dived reticularis, a. Skin involvement typically in dependents regions.
5. Less frequently other organs involved -joints, kidneys, GI tract, lungs.
6. Heart and CNS rarely involved.
7. Types of leukocytoclastic vasculitides.
a. Serum sickness.
(1) Etiology - drugs (penicillin, sulfa), heterologous serum, virus (hepatitis B).
(2) 7-10 days after exposure - fever, urticaria, arthralgias/arthritis, lymphadenopathy.
(3) Usually clears in 3 weeks. Occasionally disseminated vasculitis with renal involvement.
b. Henoch-Schönlein purpura.
(1) Nonthrombocytopenic purpura.
(2) Organ involvement- skin, joints, GI, kidneys.
(3) Renal involvement - hematuria, rarely GN, IgA nephropathy.
c. Essential mixed cryoglobulinemia with vasculitis.
(1) Polyclonal IgG and monoclonal or polyclonal rheumatoid factor.
(2) Often associated with HBsAg+ or coccidioidin antigen+.
(3) Organ involvement - skin (palpable purpura of lower extremities), joints, peripheral neuropathy, kidneys (GN), myopathy.
d. Hypocomplementemic vasculitis.
(1) Recurrent urticarial rash tasting24-48 hrs.
(2) Sometimes associated with fever, arthralgias, abdominal pain.
(3) Occasionally renal involvement- hematuria, proteinuria, RBC casts.
(4) All serologic tests normal except hypocomplementemia.
e. Leukocytoclastic vasculitis associated with other diseases cells.
3. This disease is probably the same as infantile polyarteritis.
4. Clinical manifestations include fever, conjunctivitis, oropharyngeal inflammation, edema of hands and feet, morbilliform rash over trunk, cervical lymphadenopathy, thrombocytosis, cardiac involvement.
a. Coronary artery aneurysms and thrombosis - most common cause of morbidity and mortality.
b. Rarely GI and CNS involvement.
H. Giant cell arteritis.
1. Granulomatous vasculitis of medium to large arteries, especially the superficial temporal arteries.
2. Pathology.
a. Arteries that originate from the aortic arch are most commonly involved - superficial temporal, vertebral and ophthalmic arteries.
b. Involvement is patchy.
c. Mild disease - focal lymphocytic infiltration and intimal thickening.
(1) Lymphocytic infiltration may be localized to internal or external elastic lamina or adventitia.
d. Severe disease - panarteritis with lymphocytic infiltrate, multinucleated giant cells, necrosis, disruption of elastic lamina.
(1) Granulomas may be present.
3. Clinical features.
a. Systemic symptoms - 50%, fever, malaise, weight loss.
b. PMR-39%.
c. Synovitis- 15%.
d. Headache - 68%.
e. Jaw claudication - 45%. Tongue or limb - 10%.
f. Visual symptoms.
(1) Transient- 16%.
(2) Permanent visual toss - 14%, generally occurs early but not initial manifestation.
g. CNS symptoms- 15%, CVA.
h. Superficial temporal artery signs.
(1) Tender artery - 27%.
(2) Decreased pulse - 46%.
(3) Swollen artery - 23%.
4.Laboratory findings - elevated ESR (often >100 mm/hr), anemia, thrombocytosis, hypoalbuminemia, elevated alkaline phosphatase and occasionally other LFTs, negative serology.
I. Miscellaneous vasculitides.
1. Isolated CNS vasculitis - rare disorder involving granulomatous inflammation of intracerebral arteries.
a. Headaches and variable mental status and neurologic problems in the absence of systemic disease.
2. Thromboangiitis obliterans (Buerger's disease) -obliterative disease of small to medium arteries and veins of extremities (upper >lower) most commonly seen in male smokers, a. Raynaud's phenomenon, claudications, infarctions, thrombophlebitis.
3. Behcet's disease -perivascular inflammation of small vessels, necrosis maybe present but not fibrinoid necrosis.
a. Recurrent aphthous stomatitis.
b. Genital aphthous ulcers.
c. Uveitis.
d. Synovitis.
e. Cutaneous vasculitis.
f. Meningoencephalitis.
g. Presence of 3 of the above 6 fulfills diagnostic criteria for Behcet's disease.
h. Others - phlebitis, arteritis, inflammatory bowel disease, pericarditis.
4.Erythema nodosum - venulitis with panniculitis. Tender, warm, erythematous nodules over lower extremities. Fever, arthralgias. Often associated with underlying illness.
III. Diagnosis and evaluation of patients with vasculitis.
A. Making diagnosis.
1. H + P- clinical findings.
2. Laboratory tests are usually of minimal diagnosis because they are usually nonspecific.
a. CBC and ESR may show evidence of chronic disease and inflammation.
b. ANA is usually negative. RF is positive in essential mixed cryoglobulinemia and sometimes Wegener' s granulomatosis.
c. ANCA
d. Immune complexes and complement studies show evidence of immune complex disease.
e. Cryoglobulins may be present in any vasculitis but especially essential mixed cryoglobulinemia
f. Test for specific antigens - HBsAg may be present in PAN or essential mixed cryoglobulinemia.
g. Tests to rule out underlying disease, especially with leukocytoclastic vasculitis.
3. Pathologic confirmation.
a. Tissue biopsy.
(1) Skin - leukocytoclastic vasculitis, PAN.
(2) Lung, nasopharynx, paranasal sinuses - Wegener's granulomatosis, allergic angiitis and granulomatosis.
(3) Kidney- Henoch-Schönlein purpura, PAN.
(4) Peripheral nerve - PAN.
(5) Muscle - PAN.
(6) Testicle - PAN.
(7) Artery - giant cell arteritis.
b. Angiogram.
(1) Celiac, superior mesenteric and renal - PAN.
(2) Aortic arch - Takayasu's arteritis.
(3) Intracerebral - isolated CNS vasculitis.
4. Determine extent of disease.
a. H+P.
b. Laboratory tests - liver and renal function tests, urinalysis, chest x-ray, angiogram, biopsy.
IV. Treatment
A Treatment is dependent on severity of disease and organ involvement, not necessarily diagnosis.
B. Mild disease may need no treatment or only symptomatic treatment.
C. With more severe disease and significant organ involvement, more aggressive treatment is required.
D. Treatment of primary vasculitides.
1. Primary vasculitis.
a. Suppress inflammation - corticosteroids, possibly colchicine.
(1) For severe organ involvement start I mg/kg/day in divided doses.
b. Suppress immune system- cytotoxic agents.
(1) Cyclophosphamide is drug of choice.
(a) Start at 1-2 mg/kg/day PO Increase by 25 mg/day every 2 weeks until clinical response or WBC below 3000.
(b) For fulminant disease start 4 mg/kg/day PC) or IV for 3 days then 1-2 mg/kg/day PO
(c) Monthly IV pulse cyctophasphamide may be a tesstoxic alternative.
(d)Continue for 1 year after remission induced.
(2)Azathioprine 1-2 mg/kg/day.
(3)Methotrexate may be used as a steroid sparing agent.
(4)When cytotoxic agents in full effect may taper corticosteroids.
c. Remove immune complexes - plasmapheresis.
d. Dapsone may be useful in cutaneous vasculitis.
e. Bactrim may be useful in Wegener's granulomatosis.
2. Secondary vasculitis.
a. Remove inciting antigen if possible and observe,
b. Treat underlying disorder.
c. Treat symptomatically - may require corticosteroids or cytotoxic agents.
E. Treatment of organ involvement.
1. Systemic symptoms- NSAIDs, corticosteroids.
2. Skin disease- observe, corticosteroids, dapsone, colchicine.
a. Urticaria- antihistamines.
3. Lungs - corticosteroids, for severe involvement add cyclophosphamide.
4. Kidneys, severe involvement - cyclophosphamide plus corticosteroids.
5. CNS - cyclophosphamide plus corticosteroids.
6. Peripheral nerves - corticosteroids.
F. Specific diseases.
1. Severe PAN - cyclophosphamide plus corticosteroids.
2. Wegener's granulomatosis - cyclophosphamide plus corticosteroids.
3. Giant cell arteritis - corticosteroids. 4. Behcet's disease-chlorambucil.
V. Classification of vasculitides
Fauci, 1978
Revised Lei Classification, 1993
Polyarteritis group
Polyarteritis nodosa
Mucocutaneous lymph node syndrome
Allergic angiitis and granulomatosis
Overlap of PAN and allergic angiitis
Hypersensitivity vasculitis
Serum sickness
Henoch-Schönlein purpura
Essential mixed cryoglobulinemia
Hypocomplementemic vasculitis
Vasculitis with connective tissue disease
Vasculitis with
chronic inflammatory disease
Vasculitis with malignancy
Wegener' granulomatosis
Lymphomatoid granulomatosis
Arteritis of large arteries
Giant cell arteritis
Takayasu's arteritis
Large artery arteritis with
SA, polychondritis, Cogan's syndrome Isolated vasculitis of CNS (granulomatous)
Thromboangiitis obliterans (Buerger's disease)
Affecting large and medium sized vessels
Takayasu's arteritis
Giant cell arteritis
Isolated angiitis of the CNS
Affecting medium and small sized arteries
Polyarteritis nodosa
Allergic angitis and granulomatosis
Wegener's granulomatosis
Affecting small sized vessels
Microscopic polyangiitis
Henoch-Schönlein purpura
Cutaneous leukocytoclastic angiitis
Miscellaneous conditions
Buerger's disease Cogan's syndrome
Mucocutaneous lymph node syndrome
Secondary Vasculitides
Infection related vasculitis
Vasculitis with connective tissue disease
Drug hypersensitivity related vasculitis
Essential mixed cryoglobulinemia
Vasculitis with malignancy Hypocomplementemic vasculitis
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