Laboratory Studies
The evaluation of a patient with leukocytoclastic vasculitis (LCV) serves two purposes. The first is determining the presence of systemic disease. The second is identifying an associated disorder, which can provide prognostic information. [36]
Although no standard protocol has been established, testing in all adult patients with LCV should include the following:
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Complete blood cell count
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Erythrocyte sedimentation rate or C-reactive protein level
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Urinalysis
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Blood chemistry panel, with careful assessment of kidney function
Serologic studies, such as 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. One study has linked IgA-type antiphospholipid antibodies with Henoch-Schönlein purpura in adult patients. [37]
In patients with suspected systemic lupus erythematosus or urticarial vasculitis, complement levels should be obtained, including total hemolytic complement (CH100 or CH50), C3 levels, and C4 levels. Patients with hypocomplementemic urticarial vasculitis syndrome, and less commonly in those with systemic lupus erythematosus, often have circulating anti-C1q antibodies with concomitant low levels of C1q. [38]
In patients without an identified etiology, laboratory analysis should include serum protein electrophoresis with immunofixation to assess for paraproteinemia, cryoglobulins, and hepatitis C antibody. Hepatitis B was previously thought to be associated with LCV; however, the association appears to have occurred by virtue of coinfection with hepatitis C. Cryoglobulins may be present in patients with LCV, especially in association with infections (hepatitis C, bacterial endocarditis). Results for rheumatoid factor are often positive in patients with cryoglobulinemia. Immunofixation electrophoresis is useful to identify subtle paraproteinemia that has been reported in some patients with leukocytoclastic vasculitis.
The following studies may also be appropriate:
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Patients with fever and/or a heart murmur should undergo cardiac ultrasonography and blood cultures to assess for endocarditis.
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HIV testing should be performed in patients at high risk and in patients with an otherwise unidentifiable cause of LCV.
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If the peripheral blood smear result is abnormal, obtaining bone marrow may be useful [39]
Whether patients with LCV need to be tested for malignancy is controversial. In general, the authors believe that such testing should be performed only in the presence of suggestive symptoms or findings. [40] However, in older adults with LCV who have not been screened for colorectal cancer, stool guaiac testing or fecal immunochemical testing (FIT) should be performed.
Imaging Studies
Chest radiography is part of the routine evaluation for LCV in patients with respiratory symptoms.
Visceral angiography may be indicated in patients with a history of abdominal pain, melena, hematochezia, hematuria, or kidney involvement.
Other Tests
Pulmonary function tests should be obtained in patients with hypocomplementemic urticarial vasculitis syndrome (HUVS) to assess for chronic obstructive pulmonary disease.
Ocular examination should be performed in patients with HUVS to assess for episcleritis and uveitis.
Procedures
A skin biopsy of a relatively new lesion should be performed in most adult patients with suspected leukocytoclastic vasculitis (LCV). The diagnostic yield is higher when skin biopsy is performed in the first 24 to 48 hours after onset of LCV. [41] Children with suspected LCV are often not forced to endure biopsy for humanitarian reasons.
If the cause of LCV is relatively clear, such as a new medication exposure or recent infection, postponement of biopsy may be considered. If the lesions resolve within several weeks, biopsy may not be necessary.
Muscle, nerve, or visceral organ biopsy may be warranted in patients with severe vasculitic syndromes; however, most patients with LCV of the skin do not require such tests.
If Henoch-Schönlein purpura is suspected, direct immunofluorescence (DIF) microscopy should be performed to assess for perivascular deposition of IgA. In confirming Henoch-Schönlein purpura by cutaneous biopsy, a kidney biopsy may be avoided in some patients. Biopsy for DIF should be performed within 24-48 hours of the appearance of a lesion.
Histologic Findings
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 the evolution of LCV may not reveal these findings. The presence of eosinophils has been correlated with drug-associated disease. Neutrophilia has been associated with severe bacterial infections. [42]
The picture of leukocytoclastic vasculitis is a pattern that can occur in any vasculitic syndrome but may also occur in nonvasculitic diseases such as neutrophilic dermatoses, at the base of an ulcer, or in some insect bite-reactions. Careful clinical-pathologic correlation is necessary.
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-predominant deposits may be found.
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Hypersensitivity vasculitis.
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Henoch-Schönlein purpura.
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Histopathology of leukocytoclastic vasculitis.
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Urticarial vasculitis. Lesions differ from routine urticaria (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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Erythema elevatum diutinum, a rare cutaneous vasculitis.
