Leukocytoclastic Vasculitis

Leukocytoclastic vasculitis (LCV) is a histopathologic description of when vasculitis occurs in the small vessels of the skin or organs due to inflammation caused by neutrophils with leukocytoclasia.¹

Epidemiology

There is significant confusion around the naming of leukocytoclastic vasculitis. It is often misused as a descriptor of a specific disease or type of vasculitis, when in fact it is a histopathologic phenomenon that occurs with many different diseases. For example, leukocytoclastic vasculitis is sometimes mistakenly used as a label for the diseases it commonly coincides with, such as cutaneous small-vessel vasculitis and cutaneous leukocytoclastic angiitis. While leukocytoclastic vasculitis can be present in systemic diseases, it most often manifests cutaneously.¹

Since leukocytoclastic vasculitis is poorly defined, it is difficult to estimate the incidence and prevalence. Biopsy-proven leukocytoclastic vasculitis occurs with an estimated incidence of 4.5 per 100,000 person-years in the United States.¹ Research estimates the prevalence in different locations to range from 2.7 to 29.7 per million.¹

The incidence of leukocytoclastic vasculitis seems to be evenly distributed across different ages and genders. However, some studies have suggested it may be marginally more common among men and older adults.^1,2

Leukocytoclastic Vasculitis Diagnosis & Presentation

Since leukocytoclastic vasculitis typically has cutaneous involvement, the most common clinical presentation develops on the skin as palpable purpura that often arise quickly (over the course of a couple hours), and tend to predominantly affect the lower body, particularly the lower legs.³ The leukocytoclastic vasculitis palpable purpura may coalesce into a larger rash and the affected skin may be painful and itchy or asymptomatic. The lesions tend to fade into hyperpigmented scars after two to three weeks. Patients can also develop urticarial lesions (hives) that may persist for over 24 hours.⁴

The diagnostic process is dependent on symptoms because there is no standardized procedure. A skin biopsy can be used to determine whether cutaneous symptoms are due to leukocytoclastic vasculitis. However, knowing the histopathology of the lesions does not reveal the underlying causes or whether there is systemic involvement. A comprehensive and thorough diagnostic work-up is necessary to form a valuable diagnosis.¹

Etiologies or underlying systemic involvement are identifiable in roughly half of patients.¹ Idiopathic leukocytoclastic vasculitis represents the other half.⁶ Below are the causes or diseases that may be associated with LCV⁷:

• ANCA-associated vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis)
• Immune complex vasculitis (cryoglobulinemic vasculitis, IgA-vasculitis or Henoch–Schonlein purpura, hypocomplementemic urticarial vasculitis)
• Vasculitis associated with systemic diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, sarcoidosis)
• Vasculitis associated with probable etiology (drugs, infection, sepsis, neoplasms)

Diagnostic Workup

The diagnostic workup for leukocytoclastic vasculitis does not follow a uniform series of steps. If the skin biopsy indicates a diagnosis of leukocytoclastic vasculitis, the goal is to determine whether there is systemic involvement and identify the potential causes. Different steps of the workup may or may not be necessary depending on the specifics of the case and what they signify.^1,6

A skin biopsy should be performed in almost all cases of suspected cutaneous vasculitis. A sample can be obtained through a punch biopsy (most typical) or wedge biopsy. When possible, sampling should occur within 48 hours after the rash appears.¹

Medical history

• Medication and health history to help inform the patient’s risk of having systemic disease and to identify potential triggers, such as drugs, underlying conditions, and recent infections
• Symptoms and signs of systemic disease (abdominal pain, stool changes, blood in stool, coughing, coughing blood, trouble breathing, blood in urine, sinusitis, tingling, joint issues)

Physical exam & laboratory tests (depending on symptoms and signs

Blood tests

• Complete blood count
• Erythrocyte sedimentation rate
• A comprehensive metabolic panel
• Antinuclear antibody (ANA)
• Rheumatoid factor
• Antineutrophil cytoplasmic antibodies (ANCA)
• Complement levels
• Cryoglobulins
• Hepatitis B and C tests
• HIV test

Differential Diagnosis

If a skin biopsy does not indicate leukocytoclastic vasculitis, consider these differential diagnoses¹:

• Vessel wall abnormalities with inflammation or vessel damage from clots, including on-LCV vasculitis, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, emboli, pigmented purpuric dermatosis, and Gardner–Diamond syndrome
• Vessel wall abnormalities without inflammation, including scurvy, Ehlers–Danlos syndrome, solar purpura, steroid purpura, amyloidosis and trauma
• Other vessel abnormalities, including platelet dysfunction disorders, thrombocytopenia, and clotting factor defects

Leukocytoclastic Vasculitis Management

The management and treatment of leukocytoclastic vasculitis is dependent on the causes or triggers and whether there is systemic involvement.

Nonpharmacotherapy

For cutaneous leukocytoclastic vasculitis, the treatment is largely focused on symptom management. Providers should direct all patients with leukocytoclastic cutaneous vasculitis to elevate the affected areas, utilize compression socks, and minimize walking or standing.⁶

In most cases, the episodes are acute and resolve on their own—especially if they are due to a medication. However, some patients may experience recurrent episodes that follow different patterns with flare-ups that are occasional, intermittent, or constant. Recurrence is more likely if the trigger is unknown. Eliminating the trigger will often prevent recurrence in cases with an identifiable cause.

Pharmacotherapy

Pharmacological interventions can be used for cutaneous leukocytoclastic vasculitis when necessary. However, the protocol and dosages vary depending on the extent of the condition and the specific needs of the patient. Corticosteroids are the standard pharmacological option for skin-limited leukocytoclastic vasculitis. For long term management, colchicine may be an option. Dapsone, hydroxychloroquine, and nonsteroidal anti-inflammatory drugs (NSAIDs) may also be considered based on limited evidence.⁶

Corticosteroids are also the standard option for cases with systemic involvement and may be used with or without immunosuppressants, including azathioprine and methotrexate. Plasma-exchange or rituximab may be an option for more severe cases.⁶

Monitoring Leukocytoclastic Vasculitis Side Effects

Since the management of leukocytoclastic vasculitisdepends on the underlying causes and severity, providers should balance the risks of pharmacological interventions with the necessity and benefits of treatment. Treatment selection must be made in the context of contraindications and potential side effects.

For example, corticosteroids should only be used for leukocytoclastic cutaneous vasculitis when necessary and for short periods due to the substantial side effect profile and the potential for adrenal dependence. Corticosteroid therapy should also not be discontinued abruptly because of the risk of rebound. Patients who experience a rebound or do not respond well to corticosteroids may need to transition to other medications, such as colchicine or dapsone. However, these drugs also come with side effects. Gastrointestinal upset is common in patients taking colchicine while dapsone can cause a wide range of adverse effects, including anemia.⁶

References

1. Fraticelli P, Benfaremo D, Gabrielli A. Diagnosis and management of leukocytoclastic vasculitis. Intern Emerg Med. 2021;16(4):831-841. doi:10.1007/s11739-021-02688-x

2. Arora A, Wetter DA, Gonzalez-Santiago TM, Davis MD, Lohse CM. Incidence of leukocytoclastic vasculitis, 1996 to 2010: A population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2014;89(11):1515-1524. doi:10.1016/j.mayocp.2014.04.015

3. Leukocytoclastic Vasculitis. American Osteopathic College of Dermatology. Accessed June 22, 2022.

5. Hypersensitivity vasculitis. US National Library of Medicine (MedlinePlus). Reviewed May 2, 2021. Accessed June 22, 2022.

4. Gota C. Overview of cutaneous small vessel vasculitis. UpToDate. Updated July 30, 2020. Accessed June 22, 2022.

6. Fett N. Management of adults with idiopathic cutaneous small vessel vasculitis. UpToDate. Updated November 11, 2021. Accessed June 22, 2022.

7. Pagnoux C. Leukocytoclastic vasculitis. Rheumatology Advisor. Accessed June 22, 2022.

Author Bio

Serena McNiff is a journalist covering health and science. Her work has appeared on HealthDay, CNBC, WebMD, U.S. News, and more.