eMedicine Specialties > Pediatrics: General Medicine > Rheumatology
Vasculitis and Thrombophlebitis: Differential Diagnoses & Workup
Updated: Nov 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Differential Diagnoses
Other Problems to Be Considered
Atrial myxoma
Atrial thrombus
Cogan syndrome
Erythema nodosum
Lemierre syndrome
Mucha-Habermann syndrome
Panniculitis
Rheumatoid vasculitis
Thrombophlebitis
Glomerulonephritis
Workup
Laboratory Studies
Laboratory studies in patients with vasculitis, thrombophlebitis, or both may reveal the following:
- CBC count reveals normochromic normocytic anemia of chronic disease; leukocytosis and thrombocytosis reflect inflammation as acute phase reactants. Serum complement is similarly elevated, except in the entity of hypocomplementemic urticarial vasculitis.
- The Westergren sedimentation rate is elevated.
- The findings on a comprehensive metabolic profile depend on organ involvement. BUN, creatinine, and transaminase levels may be elevated. Hypoalbuminemia may be present (suggesting chronicity of illness or protein loss).
- Antineutrophil cytoplasmic antibody (ANCA) findings may include the following:
- Central or cytoplasmic ANCAs (c-ANCAs) are associated with Wegener granulomatosis. Confirmatory enzyme-linked immunosorbent assay (ELISA) for antiproteinase 3 (anti-PR3) findings are usually positive. c-ANCA findings may be positive in microscopic polyangiitis (MPA); anti-PR3 findings are often negative.
- Perinculear ANCAs (p-ANCAs) are associated with MPA, inflammatory bowel disease, polyarteritis nodosa, and crescentic glomerulonephritis. ELISA for myeloperoxidase is positive. p-ANCAs are also directed against other antigens, including elastase and lactoferrin. In contrast, more than 90% of c-ANCAs are directed against PR3.
- The data issued from the University of North Carolina Chapel Hill laboratory concerning their ANCA reports indicate that for MPA, 40% of patients are c-ANCA (anti-PR3) positive, 50% are p-ANCA (anti-MPO) positive, and 10% are ANCA negative. This is compared with Wegener granulomatosis, in which 75% of patients are c-ANCA positive, 20% are p-ANCA positive, and 5% are ANCA negative. In Churg-Strauss syndrome, 10% of patients are c-ANCA positive, 60% are p-ANCA positive, and 30% are ANCA negative. Patients with necrotizing and crescentic glomerulonephritis have positive c-ANCA findings in 20% of cases, positive p-ANCA findings in 70% of cases, and negative ANCA findings in 10% of cases.
- ANCA is considered pathogenic by many; however, as many as 20% of patients with limited Wegener granulomatosis have negative ANCA findings. In patients with severe disease, virtually all have positive c-ANCA findings when their disease is active. Following ANCA titers has not been helpful, but a patient who has been seronegative who then becomes ANCA positive should be monitored very closely for disease flare.
- c-ANCAs and p-ANCAs are identified by the difference in fluorescent pattern on indirect immunofluorescence due to ethanol fixation; this difference does not occur with formaldehyde fixation of the slide. The indirect immunofluorescence method is widely regarded as the best assay for ANCAs. Confirmatory ELISA may be performed to identify the antigen to which these antibodies are directed.
- Antiendothelial cell antibodies (AECAs) may be elevated.
- Hepatitis is associated with polyarteritis nodosa and cryoglobulinemia; serology may indicate prior or current infection.
- Antinuclear antibody (ANA) findings are rarely positive.
- Rheumatoid factor (by latex fixation) is always elevated in mixed cryoglobulinemia.
- Angiotensin-converting enzyme levels may be elevated in sarcoid vasculitis (or with any pulmonary granulomatous involvement).
- Factor VIII-related antigen, also called von Willebrand factor antigen (vWFAG), is a marker of endothelial cell activation. It may be elevated.
- ELISA is used to screen for the presence of anticardiolipin antibody; antiphosphoserine, antiphosphoglycerol, antiphosphatidic acid, antiphosphoinositol, and antiphosphoethanolamine assays are also available.
- Activated partial thromboplastin time (aPTT) is prolonged in the presence of lupus anticoagulant/antiphospholipid antibody.
- Using lupus anticoagulant, various studies reveal functional antibody to phospholipid; aPTT, kaolin clotting time, dilute Russell viper venom time, and hexagonal phase phospholipid test are common assays. Clotting factor deficiencies correct with the addition of small amounts of normal plasma; a 4:1 (patient-to-normal ratio) mix may be needed to distinguish between factor deficiencies and low-level lupus anticoagulants.
- Other markers for hypercoagulability include protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin gene mutation G20210A, methylene tetrahydrofolate reductase (MTHFR) mutation, and homocystinemia, which are all cumulative risk factors for thrombosis.
Imaging Studies
- Chest radiography is used to screen for pulmonary infiltrates or consolidations in Wegener granulomatosis and MPA. Look for hilar adenopathy, which suggests pulmonary sarcoidosis.
- Sinus CT scanning is used to look for thickening or opacification as evidence of upper airway disease in Wegener granulomatosis.
- Angiography or magnetic resonance angiography (MRA) may reveal long areas of stenosis or aneurysm formation; bruits or symptoms of ischemia should guide the site of imaging study. Studies of children with primary CNS vasculitis (PCNSV) revealed that MRA identified nearly as many lesions as angiography, which is the criterion standard. As a noninvasive modality, MRA should be considered first. If the MRA is negative and examination of spinal fluid is suggestive, angiography should be obtained.
- Ultrasonography may be useful in identifying subclavian artery disease. Ultrasonographic duplex Doppler studies can be used to identify venous thromboses of the extremities.
- Head CT scanning or MRI is performed as needed for patients with confusion, mental status changes, and focal neurologic findings. Results may show hemorrhage, ischemia, and collateral formation (eg, moyamoya).
- Short tau inversion recovery (STIR) MRI images of tender muscles can reveal edema of proximal musculature in patients suspected of dermatomyositis or who have the characteristic malar and heliotrope rash, shawl sign, Gottron sign, or Gottron papules.
- Imaging can be used to noninvasively follow disease activity; progression may occur even with normal clinical and laboratory indices.
Other Tests
- Electromyography may be useful in evaluating patients with peripheral neurologic involvement, such as mononeuritis multiplex.
Procedures
- Vasculitis may be difficulty to demonstrate, even on biopsy. Skip lesions may lead to a false-negative finding.
- Renal biopsy findings may show focal segmental glomerulonephritis or crescentic lesions. Immunofluorescence may demonstrate immune deposition, suggestive of lupus, or a pauci-immune pattern, suggesting MPA. Immunoglobulin A (IgA) deposits support a diagnosis of Henoch-Schönlein purpura.
- Skin biopsy findings may be used to identify vasculitis, but findings are not specific beyond leukocytoclastic vasculitis (eg, nondiagnostic for a specific vasculitis syndrome). Sural nerve biopsy is usually nondiagnostic in a patient without peripheral nerve findings. In asymptomatic systems, blind biopsy has a very low yield.
- Lung biopsy is useful in Wegener granulomatosis, Churg-Strauss syndrome, and sarcoidosis.
- Conjunctival biopsy and sinus biopsy are useful in Wegener granulomatosis and sarcoidosis.
- Testicular biopsy can be helpful in polyarteritis nodosa.
- Muscle biopsy can be helpful in polyarteritis nodosa, especially if the muscle is bright on STIR MRI images.
Histologic Findings
Leukocytoclastic vasculitis observed in Henoch-Schönlein purpura, polyarteritis nodosa, and Wegener granulomatosis is characterized by focal segmental necrotizing full-thickness lesions of varying stages in small vessels. Fibrinoid necrosis is present. The cellular infiltrate is predominantly polymorphonuclear neutrophils. Lymphocytes and eosinophils may be present. Histologically, leukocytoclastic vasculitis is indistinguishable from MPA; indirect immunofluorescence may distinguish pauci-immune lesions of MPA.
- Henoch-Schönlein purpura is associated with a leukocytoclastic vasculitis with IgA immune deposits.
- In Churg-Strauss disease, leukocytoclastic vasculitis, eosinophilic tissue infiltrate, and extravascular granuloma are present.
- Takayasu disease is characterized by granulomatous destruction of the aorta and branches.
- In Wegener granulomatosis, both leukocytoclastic and granulomatous vasculitis occur.
Staging
- Wegener granulomatosis patients are divided into patients with limited disease and patients with organ-threatening disease. These divisions determine treatment strategies.
More on Vasculitis and Thrombophlebitis |
| Overview: Vasculitis and Thrombophlebitis |
 Differential Diagnoses & Workup: Vasculitis and Thrombophlebitis |
| Treatment & Medication: Vasculitis and Thrombophlebitis |
| Follow-up: Vasculitis and Thrombophlebitis |
| Multimedia: Vasculitis and Thrombophlebitis |
| References |
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Further Reading
Keywords
vasculitis, thrombophlebitis, superficial venous thrombosis, Henoch-Schönlein purpura, Kawasaki disease, infantile polyarteritis nodosa, polyarteritis nodosa, Takayasu's arteritis, Takayasu arteritis, temporal arteritis, Wegener granulomatosis, treatment, diagnosis, symptoms
