What is the appropriate work‑up and management for a patient with a skin biopsy showing vascular stasis, negative ANCA, positive ANA and dry‑eye symptoms suggesting Sjögren’s syndrome versus cutaneous vasculitis?

Work-up and Management of Venous Stasis with Positive ANA and Dry-Eye Symptoms

Given that your skin biopsy showed venous stasis (not vasculitis) and ANCA is negative, this patient does not have cutaneous vasculitis but rather likely has primary Sjögren's syndrome with venous insufficiency as a separate condition. 1

Diagnostic Clarification

The key distinction here is that venous stasis on biopsy indicates chronic venous insufficiency, not active vasculitis—these are fundamentally different pathologic processes. 2 True cutaneous vasculitis would show leukocytoclastic vasculitis (neutrophilic infiltration of vessel walls with fibrinoid necrosis) or necrotizing vasculitis on histology. 2, 1

What the Positive ANA Means in This Context

• A positive ANA with dry-eye symptoms strongly suggests Sjögren's syndrome, which has an 88% prevalence of ANA positivity. 1
• The negative ANCA effectively rules out ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis). 2, 3
• Sjögren's syndrome can present with cutaneous vasculitis in 9-16% of cases, but your patient's biopsy showed venous stasis, not vasculitis. 1, 4

Required Work-up for Suspected Sjögren's Syndrome

Confirm Sjögren's Syndrome Diagnosis

Obtain the following objective tests to meet European Community Study Group criteria (need 4 or more criteria): 1, 4

• Schirmer test for objective ocular dryness (≤5 mm wetting in 5 minutes) 1
• Unstimulated salivary flow rate (≤1.5 mL in 15 minutes) 1
• Minor salivary gland biopsy from lower lip showing focal lymphocytic sialadenitis (focus score ≥1 focus per 4 mm²)—this is the gold standard histologic confirmation 1, 4
• Anti-Ro/SS-A and Anti-La/SS-B antibodies by ELISA—present in 70% and 43% respectively of primary Sjögren's patients 1
• Rheumatoid factor—positive in 78% of Sjögren's patients with vasculitis 1

Assess for Extraglandular Manifestations

Screen for systemic involvement that occurs more frequently when ANA is positive: 1

• Urinalysis for microscopic hematuria, red cell casts, and proteinuria to detect renal involvement (10% prevalence in Sjögren's with vasculitis) 5, 1
• Comprehensive metabolic panel including creatinine to assess kidney function 6
• Neurologic examination for peripheral neuropathy (31% prevalence in Sjögren's with vasculitis versus 4% without) 1, 7
• Cryoglobulin testing—critical because cryoglobulinemic vasculitis in Sjögren's carries 12% mortality 1
• Complete blood count, complement levels (C3, C4), and immunoglobulin levels 1

Rule Out Concurrent ANCA-Associated Vasculitis

Although ANCA is negative, be aware that 11% of primary Sjögren's patients can have ANCA positivity (usually pANCA/MPO-ANCA), which when present is associated with cutaneous vasculitis, peripheral neuropathy, and Raynaud's phenomenon. 7, 8 Your patient's negative ANCA makes this unlikely but does not completely exclude it if clinical suspicion remains high.

Management Strategy

For Venous Stasis (The Actual Biopsy Finding)

Treat the venous insufficiency with:

• Compression therapy (20-30 mmHg graduated compression stockings)
• Leg elevation
• Treatment of any underlying venous disease
• This is a vascular mechanical problem, not an autoimmune vasculitis requiring immunosuppression

For Sjögren's Syndrome (If Confirmed)

Symptomatic management for sicca symptoms: 2

• Artificial tears and lubricating eye ointments for dry eyes
• Saliva substitutes and cholinergic agonists (pilocarpine or cevimeline) for xerostomia
• Hydroxychloroquine may help with arthralgias and fatigue

Immunosuppression is NOT indicated unless true vasculitis or severe organ involvement develops: 1

• Small-vessel leukocytoclastic vasculitis in Sjögren's can be treated with low-dose glucocorticoids (prednisone 0.5-1 mg/kg/day) 5, 4
• Life-threatening cryoglobulinemic vasculitis requires cyclophosphamide or rituximab plus high-dose glucocorticoids 5, 9

Critical Pitfalls to Avoid

• Do not treat venous stasis with immunosuppression—this would expose the patient to serious infection risk without benefit, as venous stasis is a hemodynamic problem, not an inflammatory vasculitis. 2
• Do not rely on ANCA titers to guide treatment decisions—structured clinical assessment of organ involvement should inform therapy, not antibody levels. 2, 9
• Do not assume all skin lesions in Sjögren's are vasculitis—only 9-16% of primary Sjögren's patients develop true cutaneous vasculitis, and biopsy is essential to distinguish this from other dermatologic conditions. 1, 4
• If true vasculitis were present and refractory, refer to a specialized vasculitis center—these patients require expert multidisciplinary management. 2, 9, 6

When to Obtain Repeat Biopsy

If new purpuric, urticarial, or necrotic skin lesions develop, obtain a deep skin biopsy reaching medium-sized vessels to capture potential vasculitis. 2 A superficial punch biopsy may miss the diagnosis. 2