What is the initial workup and treatment approach for a patient presenting with suspected cutaneous vasculitis?

Workup for Cutaneous Vasculitis

For suspected cutaneous vasculitis, obtain a skin biopsy from the most tender, reddish or purpuric lesion extending to the subcutis, along with targeted laboratory testing including urinalysis with microscopy, ANCA serology (MPO and PR3 by ELISA), complete blood count, comprehensive metabolic panel, inflammatory markers (ESR/CRP), and direct immunofluorescence to distinguish primary from secondary causes and guide treatment. 1, 2, 3, 4

Initial Clinical Assessment

Key Historical Features to Elicit

• Drug exposure history is critical, as approximately 50% of cutaneous vasculitis cases are drug-related 5
• Infection symptoms including recent upper respiratory infections, chronic sinusitis, or systemic infections (10% of cases) 5
• Constitutional symptoms such as fever, malaise, joint pain, or weight loss suggesting systemic involvement 4, 6
• Organ-specific symptoms including hematuria, hemoptysis, peripheral neuropathy (mononeuritis multiplex), or respiratory tract symptoms (nasal crusting, chronic sinusitis) 1, 2, 6

Physical Examination Findings

• Palpable purpura is the hallmark of small-vessel cutaneous vasculitis 4, 7, 8
• Distribution and depth of lesions: superficial dermal involvement presents as palpable purpura or infiltrated erythema, while deep dermal/subcutaneous involvement manifests as nodular erythema, livedo racemosa, deep ulcers, or digital gangrene 4
• Coexistence of pan-dermal and subcutaneous lesions suggests connective tissue disease, ANCA-associated vasculitis, Behçet disease, or malignancy-associated vasculitis 4

Essential Laboratory Workup

First-Tier Laboratory Tests

• Urinalysis with microscopy looking specifically for dysmorphic red blood cells, red cell casts, and proteinuria indicating glomerulonephritis 1, 2, 3
• Complete blood count to assess for anemia, leukocytosis, thrombocytosis, or cytopenias 2
• Comprehensive metabolic panel including serum creatinine to evaluate renal function 2, 3
• Inflammatory markers (ESR and CRP) are elevated in most cases, though 10% of ANCA-associated vasculitis patients have normal values 1, 2

ANCA Testing Protocol

• Both MPO-ANCA and PR3-ANCA by antigen-specific immunoassay (ELISA) are the gold standard, not indirect immunofluorescence alone 1, 3
• Approximately 90% of small-vessel vasculitis patients have ANCA directed against MPO or PR3 1
• Important caveat: About 10% of true ANCA-associated vasculitis patients are persistently ANCA-negative, requiring tissue biopsy for diagnosis 1, 3

Additional Serologic Testing

• Antinuclear antibodies (ANA) to evaluate for connective tissue diseases that can present with secondary vasculitis 2
• Cryoglobulin levels if clinical suspicion exists 5
• Hepatitis B and C serology as these infections can trigger vasculitis 5
• Anti-streptolysin O titer if post-infectious etiology suspected 5

Tissue Biopsy Strategy

Optimal Biopsy Technique

• Biopsy from the most tender, reddish or purpuric lesional skin extending to the subcutis is essential for diagnostic yield 4
• Serial sections are often required to identify the main vasculitic lesion 4
• The diagnostic yield of biopsies demonstrating vasculitis is over 70%, varying by organ sampled 3

Direct Immunofluorescence

• Concomitant biopsy for direct immunofluorescence distinguishes IgA-associated vasculitis (Henoch-Schönlein purpura) from IgG/IgM-associated vasculitis, which has prognostic significance 4
• In one study, 73.9% of patients who underwent direct immunofluorescence had positive findings for vasculitis 5

Age-Specific Diagnostic Considerations

Children vs. Adults

• In children, 99% of cutaneous vasculitis is primary (Henoch-Schönlein purpura in 89%, hypersensitivity vasculitis in 11%), allowing for a simpler diagnostic workup 8
• In adults, only 70% have primary cutaneous vasculitis, with 13% having systemic necrotizing vasculitis and 17% having secondary vasculitis from connective tissue disease, infection, or malignancy 8
• Adults require more extensive workup given the higher likelihood of serious underlying systemic disease 8

Critical Red Flags Requiring Urgent Evaluation

Indicators of Systemic Vasculitis

• Rapidly declining renal function (serum creatinine >4 mg/dL or >354 μmol/L) 9, 2
• Pulmonary-renal syndrome with alveolar hemorrhage affects 10% of ANCA-associated vasculitis patients and increases mortality risk 1, 3
• Peripheral neuropathy (mononeuritis multiplex) 1, 2
• Upper/lower respiratory tract involvement with sinusitis, nasal crusting, or pulmonary infiltrates 1, 2

When to Start Treatment Before Biopsy

• If clinical presentation is compatible with ANCA-associated vasculitis and MPO-ANCA or PR3-ANCA is positive, do not delay immunosuppressive therapy while waiting for biopsy, especially in rapidly deteriorating patients 9, 1, 2
• Biopsy should be performed soon after starting treatment when feasible to confirm diagnosis and provide prognostic information 9

Differential Diagnosis to Exclude

Vasculitis Mimics (Pseudovasculitis)

• Thrombotic disorders including antiphospholipid antibody syndrome must be excluded 4, 7
• Infections can closely mimic small-vessel vasculitis, particularly bacterial endocarditis 8
• Malignancies can present with cutaneous vasculitis as the initial manifestation 8

Secondary Causes

• Connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome) 1, 8
• Severe bacterial infections, especially endocarditis (4 cases in one series) 8
• IgG4-related disease can mimic vasculitis 1

Common Pitfalls to Avoid

• Do not rely on ANA positivity alone for vasculitis diagnosis; positive ANA with negative MPO-ANCA and PR3-ANCA does not confirm vasculitis 1
• Do not assume normal inflammatory markers exclude vasculitis, as 10% of ANCA-associated vasculitis patients have normal ESR and CRP 1
• Do not perform superficial biopsies; extend to subcutis to capture deeper vessel involvement 4
• Do not use indirect immunofluorescence alone for ANCA testing; antigen-specific immunoassays are required 1, 3
• Follow-up is essential as cutaneous manifestations may be the initial presentation of serious systemic involvement that develops later 5

Referral Considerations

All patients with suspected ANCA-associated vasculitis should be managed at centers with vasculitis expertise to ensure optimal diagnostic services and treatment outcomes 9, 2, 3