Leukocytoclastic Vasculitis Overview

Leukocytoclastic Vasculitis

• A vasculitic process primarily affecting the dermal post capillary venules and small arterioles
• Histopathologic description of small vessel vasculitis
• Affects all age groups, but most common in adults (90%)
• Mild female predominance

Etiology of Leukocytoclastic Vasculitis

• Idiopathic: Represents the largest proportion of cases (45-55%)
• Drugs: A significant factor in 10-15% of cases
  • Cardiovascular medications: Thiazides, Hydralazine
  • Antibiotics: Beta Lactams (penicillins, cephalosporins), Quinolones, Macrolides
  • Others: NSAIDs, Allopurinol, Propylthiouracil
• Infections: Account for 15-20% of cases
• Inflammatory Disorders: Represent 15-20% of cases
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)
  • Sjogren syndrome
• Neoplasms: Less common (2-5% of cases)
  • Multiple myeloma, Plasma cell dyscrasias
  • Hairy cell leukemia
  • Myelodysplasia

Histopathology

• Characterized by:
  • Neutrophilic infiltration in and around the vessel wall
  • Leukocytoclasis: Degranulation and fragmentation of neutrophils leading to nuclear dust
  • Fibrinoid necrosis (fibrin deposition in and around vessel walls)
  • Damage to the vessel wall and surrounding tissue

Pathogenesis

• Mediated by immune complex deposition

Clinical Features

• Cutaneous lesions are mostly asymptomatic
• Itching, burning, or pain may be present
• Associated symptoms: Fever, arthralgia, myalgia
• History of: New medications, changes in medication dosage, IV drug use, transfusions, travel history
• Complete review of symptoms to rule out other systemic vasculitides

Palpable Purpura

• Raised (palpable) lesions, red to purple in color (2-5 mm in size)
• Raised appearance and erythema due to the inflammatory response in the skin
• Prominent involvement of lower limbs, dependent sites with fewer lesions on proximal sites
• Why does Small Vessel Vasculitis favor the lower legs?
  • Stasis: Gravity pooling and slow blood flow in the lower limbs
  • This leads to deposition of inflammatory mediators in blood vessels
  • Prolonged standing exacerbates venous hypertension, increasing blood leakage in purpura.
• Other lesion types:
  • Urticarial: Edematous pink papules or plaques, resolving with dusky patches
  • Targetoid: Bull's eye-like appearance
• Residual post-inflammatory hyperpigmentation may persist for months.

Prognosis

• 90% of patients have spontaneous resolution of cutaneous lesions within several weeks.
• 10% experience chronic or recurrent lesions

Investigations

• Skin biopsy:
  • Punch biopsy (4 mm or longer) from the center of a fresh lesion, ideally within 48 hours of onset
  • Separate lesion for direct immunofluorescence testing
  • Cultures for bacterial, fungal, and mycobacterial infections if suspected
  • Histology shows neutrophil infiltrate into post-capillary venules, leukocytoclasis, fibrinoid necrosis.
• Direct Immunofluorescence Test (DIF):
  • Demonstrates deposits of C3, IgM, or IgG in a granular pattern within the vessel wall (80% of CSSV cases)
  • Immunoglobulin deposition highest (100%) in skin lesions ≤ 48 hours
  • DIF negative, only C3 detected in lesions present ≥ 72 hours
  • IgA positivity suggests Henoch-Schoenlein purpura
• Evaluation for Therapy and Disease Activity:
  • Inflammatory markers: CRP, ESR may be elevated
  • CBC with differential count, blood sugar, RFT, LFT for therapy purposes
• Evaluation to Rule Out Other Differentials:
  • ANA (Antinuclear Antibodies)
  • Rheumatoid factor
  • Anti-streptolysin-O
  • HBV, HBC serology
  • Montoux test for tuberculosis
  • HIV test
  • Antiphospholipid antibodies
• Evaluation to Rule Out Systemic Involvement:
  • Stool for occult blood
  • Chest X-ray, pulmonary function tests
  • Visceral angiography, ECHO to look for systemic vasculitides

Treatment

• Often self-limiting

• Triggering agent (infection, drug) should be identified and treated or removed

• Minimize stasis: Compression hosiery, elevation of dependent areas

• Antihistamines or anti-inflammatory drugs may reduce symptoms

• Bullae or ulcers: Short course of steroids

• Prednisolone: Initial dose 0.5-1 mg/kg, tapered over 6 weeks based on response

• Recurrent episodes/persistent and severe disease:

  • Colchicine: 0.6 mg twice daily orally
  • Dapsone: Initially 5 mg/day, increased by 50 mg weekly until 150-200 mg reached or effect is achieved

• Refractory to Above Therapies:

  • Cytotoxic agents: Azathioprine (1-2 mg/kg per day), Methotrexate (15-25 mg per week)

Approach to Vasculitis

• Identify the vessel involved:
  • Large vessels: Giant cell arteritis, Takayasu disease
  • Medium vessels: Polyarteritis nodosa (PAN), Kawasaki disease
  • Small vessels:
    • Granulomatous: Wegener's granulomatosis, Churg-Strauss syndrome
    • Non-granulomatous: Henoch-Schonlein purpura, Urticarial vasculitis, Leukocytoclastic vasculitis

Small Vessel Vasculitis (Immune Complex Vasculitis)

• Henoch-Schönlein Purpura:
  • IgA mediated vasculitis affecting small vessels of skin, GI tract, kidneys, and joints
  • Peak age: 4-6 years
  • Classic tetrad:
    • Palpable purpura
    • Abdominal pain
    • Haematuria
    • Arthritis
  • Skin and renal biopsy: Leukocytoclastic vasculitis with IgA deposition
  • Lab studies: Mild leukocytosis, elevated IgA level
• Urticarial Vasculitis:
  • Variant of cutaneous small vessel vasculitis
  • Erythematous wheals resembling urticaria, but histologically show changes of LCV
  • Clinical features:
    • Annular wheals lasting more than 24 hours
    • Pain and burning sensation rather than itching
    • Hyperpigmentation on resolution
    • Systemic symptoms and signs
• Cryoglobulinemic Vasculitis:
  • Immune mediated small vessel vasculitis characterized by abnormal immunoglobulin proteins in the body
  • Types:
    • Type 1: Single monoclonal immunoglobulin (IgM)
    • Type 2: Mixed cryoglobulinemia with monoclonal rheumatoid factor
    • Type 3: Mixed polyclonal rheumatoid factor
  • Clinical features: Meltzer's triad:
    • Purpura
    • Arthralgia
    • Weakness

Small Vessel Vasculitis (ANCA Associated)

• Granulomatosis with Polyangiitis (GPA):
  • Synonym: Wegener's granulomatosis
  • Classic triad:
    • Systemic small vessel vasculitis
    • Necrotizing granulomatous inflammation of upper and lower respiratory tracts
    • Glomerulonephritis
  • Clinical features:
    • Cutaneous: Palpable purpura, pyoderma granulomatosum ulcers, tender subcutaneous nodules
    • Respiratory tract: Purulent sinus discharge, otitis media, saddle nose deformity, cavitary lung lesions
    • Renal: Glomerulonephritis
• Eosinophilic Granulomatosis with Polyangiitis (EGPA):
  • Synonym: Churg-Strauss syndrome
  • Small vessel autoimmune vasculitis leading to necrosis
  • Clinical features:
    • Presence of 4 or more of the following:
      • History of bronchial asthma
      • Eosinophilia greater than 10% of peripheral blood
      • Paranasal sinusitis
      • Pulmonary infiltrates
      • Mononeuritis multiplex or polyneuropathy
      • Histology: Vasculitis with extravascular eosinophils
  • Investigations:
    • Biopsy: Eosinophilic infiltration of tissue, extravascular granulomas, vasculitis
    • Peripheral blood eosinophilia is a requisite for diagnosis
    • Inflammatory markers, IgE elevated

Medium Vessel Vasculitis

• Polyarteritis Nodosa (PAN):
  • Inflammatory necrotizing vasculitis affecting medium-sized arteries, preferentially at vessel bifurcations
  • Affects multiple systems: Skin, joints, gut, kidneys, but lungs are usually spared.
  • Classification:
    • Cutaneous: Livedo reticularis (does not blanch with pressure), ulcerations, splinter hemorrhages (near malleoli, calf digital ischemia)
    • Extracutaneous: Unexplained weight loss, arthralgia, abdominal pain, hypertension
• Kawasaki Disease:
  • Synonym: Mucocutaneous lymph node syndrome
  • Acute febrile illness with inflammation of medium-sized blood vessels, particularly coronary arteries
  • Clinical features:
    • Fever (102-104°F)
    • Erythematous rash
    • Oral signs: Strawberry tongue, cracked lips
    • Eye signs: Redness of bulbar conjunctiva
    • Lymphadenopathy

Large Vessel Vasculitis

• Giant Cell Vasculitis (Temporal Arteritis):
  • Synonym: Temporal arteritis or granulomatous arteritis
  • Inflammatory vasculopathy affecting large-sized arteries, common in older individuals
  • Classification: 3 of the 5 criteria must be present:
    • Age at onset greater than 50 years
    • New onset of headache
    • Temporal artery abnormality
    • Elevated ESR (≥ 50 mm/h)
    • Biopsy findings: Vasculitis with predominant mononuclear cell inflammation and granulomatous inflammation containing multinucleated giant cells.
• Takayasu Arteritis:
  • Chronic granulomatous vasculitis primarily involving the aorta and its branches, including pulmonary and coronary arteries
  • Age of onset: 40 years or younger
  • Clinical features:
    • Claudication of the extremities
    • Decreased pulsation of one or both brachial arteries
    • Difference of at least 10 mmHg in systolic blood pressure between arms
    • Bruit over one or both subclavian arteries or the abdominal aorta
    • Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia, or other causes.

This quiz covers the fundamental aspects of leukocytoclastic vasculitis, including its etiology, histopathologic features, and demographics. It emphasizes the role of drugs, infections, inflammatory disorders, and neoplasms in its development. Ideal for medical students or healthcare professionals looking to deepen their understanding of this condition.