Clinical Reference / Therapeutic Strategies / Leukocytoclastic Vasculitis

Leukocytoclastic Vasculitis


Key Points

  • Leukocytoclastic vasculitis (LCV) represents inflammation of small vessels in the skin stemming from immune complex deposition.
  • Clinically, LCV presents with an eruption of palpable monomorphous purpuric papules, which may have central vesicles or pustules and may coalesce into larger plaques. It favors dependent areas of the body.
  • In approximately 50% of cases, cutaneous LCV is caused by medications, drugs (cocaine), infection (such as hepatitis, streptococcal infection), autoimmune disease, or malignancy.
  • The therapeutic strategy is to search for an etiology, then treat the underlying disorder.

Introduction

Leukocytoclastic vasculitis (LCV) represents inflammation of small vessels in the skin stemming from immune complex deposition. It is sometimes associated with skin pruritus or tenderness. Clinically, LCV presents with an eruption of palpable monomorphous purpuric papules, which may have central vesicles or pustules and may coalesce into larger plaques. The presentation is typically symmetric and affects dependent areas of the body (lower extremities in an ambulatory patient, sacrum and buttocks in a hospitalized patient). In approximately 50% of cases, cutaneous LCV is caused by medications, drugs (cocaine), infection (such as hepatitis, streptococcal infection), autoimmune disease, or malignancy. In rare cases, LCV will present in the setting of a syndrome such as Henoch-Schönlein purpura (HSP), typified by the triad of cutaneous LCV (IgA deposition), arthritis, and gastrointestinal involvement in which the skin lesions predominantly affect the lower extremities and buttocks.

The therapeutic strategy is to treat the underlying disorder. Most cases of cutaneous LCV will require no or only brief courses of immunosuppressive therapy so, if symptoms persist, the concern for a systemic vasculitis should be diagnostically evaluated. Cutaneous LCV may be associated with internal organ involvement, especially of small vessels of the brain, lungs, kidney, and gastrointestinal system, and the morphology and severity of the skin disease do not predict such involvement. Therefore, systemic small vessel vasculitis must be evaluated in every patient presenting with LCV. Treatment may be required for systemic disease even when skin lesions are mild.

Differential Diagnosis 

Venous stasis

Persistent pigmented purpuric dermatitis

Treatment

First-line therapy: The first-line therapy for LCV is to search for an underlying cause (and treat if necessary). The second aim is to suppress or control cutaneous lesions and symptoms, as skin lesions may be pruritic or painful. Because cutaneous LCV is a self-limited and a benign disorder in most cases, one should be certain that the therapy employed is not more dangerous than the disease.

A diagnostic evaluation should be targeted to the patient’s symptoms. A detailed review of systems should be performed and notable findings pursued by diagnostic testing for:

  • kidney, brain, GI, joint involvement
  • autoimmune disease
  • malignancy
  • infection (streptococcal, hepatitis)
  • medication or drugs as a cause

 First steps

  • For skin pruritus: Treat with antihistamines; a combination of hydroxyzine 25-50 mg three or four times daily is occasionally useful. If the patient responds to this regimen, it may be continued as long as necessary. Non-sedating antihistamines (loratadine, fexofenadine, cetirizine) may be used if the first-generation agents are not tolerated.
  • For cutaneous ulcers or bullae: Treat with mid-potency topical corticosteroids such as triamcinolone 0.1% ointment and emollients such as petrolatum. Non-healing wounds benefit from semi-occlusive dressings with gentle compression.
  • For skin tenderness: Treatment with an nonsteroidal anti-inflammatory medication such as ibuprofen may be helpful for symptomatic lesions if there is no concern for kidney or GI involvement.

Subsequent steps

  • No treatment; wait 2-3 weeks for spontaneous resolution. This approach is acceptable if the lesions cause limited symptoms and there is no evidence of internal organ involvement.
  • Treat with prednisone 1-2 mg/kg daily for 4-7 days. If the patient responds, taper prednisone over a 14-day period.
  • Treat with colchicine 0.6 mg one or two tablets twice daily as tolerated.
  • Treat with dapsone 50 mg twice daily and increase the dose up to 100 mg twice daily if required.
  • Dapsone and colchicine may be combined for enhanced efficacy, to minimize toxicity from either medication (hemolysis and diarrhea, respectively).
  • Hydroxychloroquine 200 mg twice daily, azathioprine 50-100 mg daily, or methotrexate 10-25 mg weekly may be used as steroid-sparing agents. These agents are used for mild, persistent, but not rapidly progressive disease.
  • If a steroid-sparing immunosuppressive agent is needed for aggressive disease, the two favored agents would be mycophenolate mofetil and, in severe cases, cyclophosphamide.

Pitfalls

  • Do not overlook a treatable, underlying cause. Each patient must be fully evaluated, and any potential causative drugs must be eliminated.
  • Evaluate for systemic involvement, especially renal (e.g., urinalysis with microscopic evaluation of urine sediment) and gastrointestinal (e.g., stool guaiac).
  • Dapsone will induce some drop in the hematocrit. This will be enhanced in persons with low levels of G6PD, so this must be assayed before starting this agent.
  • The major error in management is to use low levels of immunosuppressive therapies (especially systemic steroids) for a prolonged period, which causes significant complications. The preferred approach is early aggressive treatment to induce a remission then maintenance with lower toxicity agents.

When to refer to a dermatologist

  • When the diagnosis of palpable purpura is not clear.
  • For skin biopsy of lesions to confirm the diagnosis. A biopsy for direct immunofluorescence (which reveals deposition at cutaneous superficial dermal vessels), in addition to biopsies for hematoxylin and eosin staining, may be helpful.
  • For management of erosive or bullous skin lesions of LCV, especially if severe or extensive.

Case 1

  • 40-year-old female admitted to the hospital for wound infection following a right knee surgery indicated for anterior and posterior cruciate ligament and meniscal tear, performed one week ago. Upon admission, she is noted to have a symmetric eruption of palpable purpuric papules and small pustules on the arms and legs, which she states has been present for two days
  • No significant past medical history and she takes no medications except for an opiate-based pain medication for her knee surgery
  • Review of systems is notable only for recent fevers in association with the rash

Initial evaluation

  • Tired-appearing female
  • Low-grade fever is noted
  • Scattered purpuric macules, papules and small pustules on the arms and legs; no mucosal lesions noted. The surgical site on the right knee appears erythematous, warm, with purulent drainage
  • Diagnosis: Favor LCV due to medication (opiates) versus wound infection
  • A surgical wound bacterial swab is performed which reveals streptococcal infection
  • A skin biopsy is performed to confirm the diagnosis of LCV. She is started on topical triamcinolone 0.1% ointment twice daily and hydroxyzine 25 mg at bedtime to help with skin pruritus
  • Concern for systemic involvement and/or underlying systemic disorder prompts stool guaiac testing, urinalysis with microscopy and blood test for BUN and creatinine clearance, erythrocyte sedimentation rate, ASO and complete blood count with differential. All were normal except for a slight leukocytosis with neutrophilia and positive ASO titer, suggestive of streptococcal wound infection. She is started on systemic antibiotics
  • Her opiate-based pain medication is discontinued and she is switched to ibuprofen once her kidney function tests returned normal
  • Follow-up in 1 week

Follow-up evaluation

  • The rash is resolving and she reports no new lesions. Her surgical site appears improved now without evidence of infection. She is recommended to complete her course of systemic antibiotics for the streptococcal infection and to continue the topical corticosteroids and antihistamines for symptomatic relief
  • Follow-up at 4 weeks (resolved)

Podjasek JO, Wetter DA, Pittelkow MR, Wada DA. (2012). Cutaneous small-vessel vasculitis associated with solid organ malignancies: the Mayo Clinic experience, 1996 to 2009, JAAD, 66(2):e55-65.

Ting TV. (2014). Diagnosis and management of cutaneous vasculitis in children, Ped Clin North Amer, 61(2):321-346.