Leukocytoclastic Vasculitis

I. Problem/Condition.

Vasculitis describes inflammation in and around blood vessels and can manifest in any organ system. The classification of vasculitis is made based on the size of the involved blood vessels. Small vessels of the arterial or venous systems in addition to medium and large-caliber vessels deeper in the subcutis or arteries themselves can be affected. Vasculitis can be idiopathic or secondary to drugs, infections, neoplastic processes or other autoimmune connective tissue diseases. Diagnostic clues on skin exam may reflect the size of the vessels involved. Often, the dermatologist is consulted to aid in diagnosis, work-up and management.

When small post-capillary vessels are involved, the clinical presentation is often palpable non-blanching purpura or petechiae. (See Figure 1). As small to medium sized vessels are affected, the lesions will be larger and can even present as purple net-like lesions, necrotic deeper nodules or ulcerations in the skin and subcutaneous tissue (See Figure 2). Regardless of the vessel size, the cutaneous lesions are palpable and purpuric appearing (See Figure 3).

Leukocytoclastic Vasculitis due to Raptiva
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Leukocytoclastic vasculitis (LCV) is an inflammatory process primarily involving the small vessels in the skin. It is a pathologic diagnosis, NOT a disease. It usually presents as an acute process that resolves spontaneously in about 90% of patients within several weeks to months. Approximately 10% will go on to have a more chronic course. Systemic symptoms occur in 5-25% of patients and may include arthritis, genitourinary, gastrointestinal, or neurologic involvement. Presence of systemic symptoms should prompt further work up for associated systemic disease, as discussed below. LCV can affect males and females equally and is more common in adults, but children can be affected as well. It is a general classification of small vessel vasculitis that is seen histopathologically, but there are several specific sub-types, which will be further discussed.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

Epidemiologically, the causes of LCV can be broken down into the following broad categories:

Idiopathic (~50%)
Infection (15-20%)
Inflammation (15-20%)
Drug (10-15%), e.g., penicillins

A common rash seen with LCV is palpable purpura on dependent areas of the bilateral lower extremities. However, the differential diagnosis of the different types of rashes associated with LCV is broad, and includes the following: urticaria, urticarial vasculitis, arthropod bites, morbilliform drug eruption, erythema multiforme, urticaria, scurvy, amyloidosis, antiphospholipid antibody syndrome, cryoglobulinemia, capillaritis, trauma, thrombocytopenia, platelet dysfunction, viral exanthems, infectious emboli, Sweet’s syndrome, granulomatous dermatitis, and coagulopathies. In patients with history of cocaine abuse, levamisole-induced vasculitis should also be considered.

B. Describe a diagnostic approach/method to the patient with this problem.

Work-up should include complete blood count (CBC) with differential, erythrocyte sedimentation rate, comprehensive metabolic panel, and urinalysis. Where appropriate, screen for infections as an etiology. It is important to review drug history, exposures to drugs or infectious agents, thorough evaluation of the skin, history and histopathologic review of the specimens. History and symptoms may also help guide the clinician in working a patient up with leukocytoclastic vasculitis. In up to 50% of patients an underlying cause may not be identified.

Depending on clinical scenario, the workup for specific causes of LCV may include the following (this is a partial list):

Infection workup: antistreptolysin (ASO) titer, CBC with differential, skin biopsy for AFB/fungal/bacterial cultures, PPD or Quantiferon-gold; even if no risk factors consider hepatitis, HIV
Inflammatory workup: cryoglobulins, rheumatoid factor, ANCAs, ANA, C3, C4; consider anti-SSA/Ro, anti-SSB/La, IgA if in differential diagnosis
Consider cancer screening if appropriate (e.g., stool guiaic, chest X-ray)

1. Historical information important in the diagnosis of this problem.

It is thought that leukocytoclastic vasculitis is a reaction pattern to other underlying conditions in most cases. It results from circulating immune complexes and inflammatory mediators which affect endothelial cells leading to upregulation of adhesion molecules and recruitment of inflammatory cells. The endothelial linings of vessels are damaged resulting in edema, inflammation, and extravasation of erythrocytes, which is clinically reflected in the patient. Direct immunofluorescence typically demonstrates deposition of C3, IgM, IgA, IgG and fibrin in a granular perivascular pattern.

Because it is most commonly a reaction pattern, there are many underlying associations linked with this eruption. Recognizing the clinical presentation may guide the physician to narrowing down the possible etiologic agents. In general, medications may be a trigger for leukocytoclastic vasculitis and may include NSAIDs, penicillins, anti-thyroid agents, quinolones, anti-TNF agents and leukotriene inhibitors.

Infections with bacteria and viruses can be seen in association with LCV. Such agents may be ß-hemolytic streptococci, mycobacterial infections, mycoplasma, rickettsiae, hepatitis C and B, HIV, and Parvovirus B19. Finally, inflammatory or autoimmune disorders and neoplasms may trigger the small vessel vasculitis. These can include lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, myeloproliferative disorders, lymphoproliferative disorders, and plasma cell dyscrasias.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Leukocytoclastic vasculitis typically presents in dependent areas of the skin 7-10 days after exposure to the inciting event. The lesions may be asymptomatic or associated with burning, pruritus, or pain. Lesions most commonly include nonblanching palpable purpura or erythematous macules or papules that can vary in size from a few millimeters to several centimeters, but lesions may also be urticarial, vesicular, targetoid or bullous. Postinflammatory hyperpigmentation may persist for several months. LCV may be accompanied by other systemic symptoms such as fever, arthralgias, myalgias and weight loss.

While non-specific systemic symptoms may accompany small vessel vasculitis, some signs may be suggestive of more widespread involvement and are more concerning such as involvement of the GI tract, kidneys, nerves, lungs or heart. Involvement of such organ systems should prompt immediate consultation of the appropriate specialist so that appropriate therapies will be initiated with minimal mortality to the patient.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Complete blood count, biochemistry profile with liver and renal function, erythrocyte sedimentation rate, and urinalysis are useful in excluding other vasculitides and determining the presence of systemic disease or associated disorder, which may be causing the vasculitis.

Histopathology of classic leukocytoclastic vasculitis depends on the lesion that is biopsied. Newer lesions (less than 48 hours old) typically have a perivascular neutrophilic infiltrate that can be seen within the vessel wall. Edema from endothelial cell damage, fibrinoid necrosis of the vessel wall, extravasation of erythrocytes and karyorrhexis of neutrophils is also observed. In older lesions, a mononuclear infiltrate may be seen.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

N/A

III. Management while the Diagnostic Process is Proceeding.

A. Management of Clinical Problem Leukocytoclastic Vasculitis.

Treatment is dependent on the underlying process that may be triggering the eruption. Skin biopsy can give clues to underlying process and aids in treatment options as targeted therapy. Treatment of the underlying condition or discontinuation of the offending agent is the first step in addressing leukocytoclastic vasculitis usually without further intervention and resolution of the eruption. Skin targeted therapies for mild disease include topical steroids, supportive care, and topical calcineurin inhibitors.

Depending on the underlying etiology and in more chronic or severe disease, initiation of systemic steroidal tapers with the addition of steroid-sparing agents such as colchicine, dapsone, methotrexate, mycophenolate mofetil, azathioprine or cyclophosphamide usually results in control of the eruption with minimal side effects of long-term steroid use.

IV. What's the evidence?

Fiorentino,, David, F.. “Cutaneous Vasculitis.”. Journal of the American Academy of Dermatology.. vol. 48. 2003. pp. 311-40.

Chen, KR,, Carlson, JA.. “Clinical approach to cutaneous vasculitis.”. Am J Clin Dermatol.. vol. 9. 2008. pp. 71-92.

Sunderkötter, C,, Bonsmann, G,, Sindrilaru, A,, Luger, T.. “Management of leukocytoclastic vasculitis.”. J Dermatolog Treat.. vol. 16. 2005. pp. 193-206.

Jorizzo,, Joseph,. “Cutaneous Small-Vessel Vasculitis.”. Journal of the American Academy of Dermatology.. vol. Volume 39,. 1998. pp. 667-690.

Bolognia,, Jean,. .

Iglesias-Gamarra,, Antonio,. “Small-Vessel Vasculitis. Current Rheumatology Reports.”. vol. Volume 9. 2007. pp. 304-311.

Einhorn, J,, Levis, JT.. “Dermatologic Diagnosis: Leukocytoclastic Vasculitis.”. . vol. 19. 2015. pp. 77-78.

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