What is the differential diagnosis for a 66-year-old patient with leukocytoclastic vasculitis, scalp pruritus, and pneumonia?

Differential Diagnosis of Leukocytoclastic Vasculitis with Scalp Pruritus and Pneumonia in a 66-Year-Old Patient

In a 66-year-old patient presenting with leukocytoclastic vasculitis, scalp pruritus, and pneumonia, the primary differential diagnosis is Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly Churg-Strauss syndrome), which characteristically presents with asthma/respiratory involvement, eosinophilia, and small-vessel vasculitis affecting multiple organ systems. 1, 2

Primary Systemic Vasculitic Syndromes to Consider

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• EGPA is the most likely diagnosis given the triad of respiratory disease (pneumonia), vasculitis, and the patient's age (median age 40-50 years, but occurs in older adults). 1
• The European League Against Rheumatism notes that EGPA requires marked peripheral eosinophilia (usually >1500 cells/μl or >10%), and 26-48% of patients are p-ANCA positive, increasing to 75% with renal involvement. 1
• MPO-ANCA-positive patients more frequently exhibit peripheral neuropathy, glomerulonephritis, and purpura (due to small vessel vasculitis), while MPO-ANCA-negative patients more commonly have myocardial, respiratory, and gastrointestinal involvement. 1, 2
• The scalp pruritus may represent eosinophilic infiltration or vasculitic involvement of the scalp. 1
• Critical diagnostic workup includes: peripheral eosinophil count, p-ANCA/MPO-ANCA testing, chest CT, assessment for asthma or allergic rhinitis history, and evaluation for cardiac, renal, gastrointestinal, and peripheral nerve involvement. 1

Granulomatosis with Polyangiitis (GPA, formerly Wegener's)

• GPA presents with necrotizing granulomatous lesions and systemic vasculitis, strongly associated with C-ANCA/PR3-ANCA (84-85% positive). 2
• Pulmonary involvement manifests as infiltrates, nodules, or cavitations on imaging, which could explain the pneumonia presentation. 2
• The American College of Rheumatology recommends C-ANCA/PR3-ANCA testing in all suspected ANCA-associated vasculitis. 2

Microscopic Polyangiitis (MPA)

• MPA shows small vessel vasculitis without granulomas, typically MPO-ANCA positive, with frequent renal and pulmonary involvement. 2
• Distinguished from GPA by absence of granulomatous inflammation on biopsy. 2

Secondary Causes of Leukocytoclastic Vasculitis

Drug-Induced Vasculitis

• Penicillins, cephalosporins, sulfonamides, phenytoin, and allopurinol can trigger leukocytoclastic vasculitis by acting as haptens and stimulating an immune response. 3
• Obtain detailed medication history documenting all drugs taken in the preceding 2 months, as drug discontinuation is usually resolutive with favorable prognosis. 4, 5

Infection-Associated Vasculitis

• The Infectious Diseases Society of America recommends screening for Hepatitis B and C, HIV, and post-herpes zoster granulomatous vasculitis in all cases of suspected vasculitis. 2
• Group A Streptococcus and other bacterial infections can trigger vasculitis. 3
• Given the pneumonia, consider whether the pulmonary process is infectious (bacterial, viral, fungal) or vasculitic. 6

Connective Tissue Disease-Associated Vasculitis

• Rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, and other connective tissue diseases can present with cutaneous vasculitis and pulmonary involvement. 2, 5, 7
• The American College of Rheumatology notes that coexistence of pan-dermal small-vessel vasculitis and subcutaneous muscular-vessel vasculitis usually indicates connective tissue disease or ANCA-associated vasculitis. 7

Cryoglobulinemic Vasculitis

• Associated with hepatitis C infection, presents with palpable purpura and can have pulmonary involvement. 5
• Cryoglobulins should be tested repeatedly as levels fluctuate, and temporary negativity does not exclude mixed cryoglobulinemia. 2

IgA Vasculitis (Henoch-Schönlein Purpura)

• More common in children but can occur in adults, characterized by IgA deposition on direct immunofluorescence. 5, 7
• Typically presents with palpable purpura, abdominal pain, arthralgia, and renal involvement. 8

Malignancy-Associated Vasculitis

• Lung cancer can present with radiographic findings mimicking pneumonia, particularly in older smokers, and can be associated with paraneoplastic vasculitis. 6, 7
• The American College of Rheumatology notes that malignancy-associated vasculitis often shows coexistence of pan-dermal small-vessel vasculitis and subcutaneous muscular-vessel vasculitis. 7

Non-Infectious Pulmonary Mimics

Organizing Pneumonia (Cryptogenic Organizing Pneumonia/COP)

• A common non-infectious mimic of pneumonia that can be associated with connective tissue disease. 6

Allergic Bronchopulmonary Aspergillosis

• The European Respiratory Society identifies this as a hypersensitivity disorder with pulmonary infiltrates and eosinophilia. 2
• Part of the differential diagnostic workup recommended by the EGPA Consensus Task Force includes specific IgE and IgG for Aspergillus species and search for Aspergillus in sputum/bronchoalveolar lavage fluid. 1

Essential Diagnostic Workup

Immediate Laboratory Testing

• Complete blood count with differential (looking for eosinophilia >1500 cells/μl, neutrophilic leukocytosis, or lymphopenia). 1, 3
• ANCA testing: Both MPO-ANCA (p-ANCA) and PR3-ANCA (c-ANCA) by ELISA, as MPO-ANCA is more specific for vasculitis. 1, 2
• Complement levels: C3 and C4 to assess for hypocomplementemic states. 3
• Cryoglobulins: Tested repeatedly due to fluctuating levels. 2
• Hepatitis B and C serology, HIV testing. 2
• Autoantibodies: ANA, rheumatoid factor. 5, 8
• Inflammatory markers: ESR, CRP. 3
• Renal function: Creatinine, urinalysis for hematuria and proteinuria. 1, 2

Skin Biopsy

• Obtain biopsy extending to subcutis from the most tender, reddish, or purpuric lesional skin, as serial sections are often required for identifying the main vasculitic lesion. 2, 7
• Concomitant biopsy for direct immunofluorescence to distinguish IgA-associated vasculitis from IgG-/IgM-associated vasculitis, which has prognostic significance. 5, 7

Pulmonary Evaluation

• Chest CT scan to characterize the pneumonia pattern (infiltrates, nodules, cavitations) and assess for bilateral/multi-lobe involvement. 1, 2
• Sputum culture and respiratory viral panel including influenza A/B, respiratory syncytial virus, and parainfluenza viruses. 6
• Consider bronchoscopy with bronchoalveolar lavage if diagnosis remains unclear, particularly to exclude infectious etiologies and obtain samples for cytology and culture. 1

Additional Systemic Assessment

• Neurologic examination for mononeuritis multiplex or peripheral neuropathy, particularly common in EGPA and systemic necrotizing vasculitis. 1, 2
• Cardiac evaluation: ECG, troponin, and echocardiography, as cardiomyopathy is common in ANCA-negative EGPA and is an independent risk factor for poor outcome. 1, 2
• Gastrointestinal assessment for abdominal pain or bleeding. 1, 2

Critical Pitfalls to Avoid

• Do not dismiss the pneumonia as simple community-acquired pneumonia without considering vasculitic pulmonary involvement, especially given the concurrent cutaneous vasculitis. 1, 6
• Do not rely on a single negative ANCA test to exclude ANCA-associated vasculitis, as 52-74% of EGPA patients are ANCA-negative, particularly those with predominant respiratory and cardiac involvement. 1
• Do not perform skin biopsy from old or superficial lesions, as this reduces diagnostic yield; always biopsy the most tender, reddish lesional skin extending to subcutis. 2, 7
• Do not assume idiopathic cutaneous leukocytoclastic vasculitis in a 66-year-old with pneumonia without extensive workup for systemic disease, as age >65 years is a poor prognostic factor in systemic vasculitis. 1
• Do not forget to assess the Five-Factor Score (FFS) for EGPA: age >65 years, cardiac symptoms, gastrointestinal involvement, renal insufficiency (creatinine >150 μmol/L), and absence of ENT manifestations, as this predicts mortality. 1

Prognosis and Treatment Implications

• If systemic vasculitis is confirmed, particularly EGPA or GPA, combination therapy with corticosteroids and cyclophosphamide is required, as untreated vasculitis in the vasculitic phase has high mortality. 1, 5, 7
• If drug-induced vasculitis is identified, discontinuation of the culprit drug is usually resolutive with favorable prognosis. 5, 3
• If skin-limited disease without systemic involvement, treatment focuses on symptom management with rest, low-dose corticosteroids, or colchicine. 5, 7
• The prognosis depends on the underlying disease and severity of organ involvement; EGPA with cardiomyopathy or two FFS features has 25.9-46% five-year mortality. 1