Are there any syndromes that encompass peripheral neuropathy, hyperbilirubinemia, and nasal polyps?

Eosinophilic Granulomatosis with Polyangiitis (EGPA/Churg-Strauss Syndrome)

The triad of peripheral neuropathy, hyperbilirubinemia, and nasal polyps strongly suggests Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly Churg-Strauss syndrome), which characteristically presents with asthma, eosinophilia, nasal polyps, and peripheral neuropathy. 1

Clinical Features of EGPA

EGPA is a systemic vasculitis that encompasses all three of your patient's manifestations:

Nasal Polyps and Upper Airway Disease

• Chronic rhinosinusitis with nasal polyps occurs in 60-80% of EGPA patients and is equally distributed between ANCA-positive and ANCA-negative subtypes 1
• Nasal polyps are a baseline manifestation that should be evaluated in all suspected EGPA cases 1
• ENT consultation with nasal endoscopy is recommended as part of the diagnostic workup 1

Peripheral Neuropathy

• Peripheral neuropathy develops in up to 50% of EGPA patients, typically presenting as distal symmetric sensory or sensorimotor polyneuropathy 1
• The neuropathy often appears as asymmetric mononeuritis multiplex in severe cases 1
• Common symptoms include sensory loss, paresthesias, numbness, burning feet, and tingling 1
• Electromyography with peripheral nerve neurophysiological tests should be performed in all patients with suspected peripheral nerve involvement 1

Hepatobiliary Involvement

• While not part of the classic Five-Factor Score, gastrointestinal involvement (which can include hepatic manifestations leading to hyperbilirubinemia) is recognized in EGPA 1
• Gastrointestinal tract involvement is considered when choosing remission-induction strategies 1

Diagnostic Workup

All patients with this clinical triad should undergo comprehensive EGPA evaluation:

Essential Laboratory Tests 1

• Complete blood count with differential - looking for eosinophilia >10% 1
• ANCA testing (p-ANCA/MPO positive in 26-48% of cases, increasing to 75% with renal involvement) 1
• Serum IgE levels - typically elevated 1
• C-reactive protein and ESR 1
• Comprehensive metabolic panel including liver function tests
• Urinalysis with 24-hour proteinuria or protein-to-creatinine ratio 1

Imaging Studies 1

• High-resolution CT chest - to evaluate for pulmonary infiltrates (present in >90% of EGPA patients) 1
• CT sinuses - to document extent of sinonasal disease 1
• Echocardiography - cardiac involvement is a poor prognostic factor 1

Specialized Testing 1

• EMG-electroneurography for peripheral neuropathy documentation 1
• Sural nerve biopsy in selected cases 1
• Tissue biopsy showing eosinophilic infiltrates with or without granulomas and necrotizing vasculitis 1

Differential Diagnosis Considerations

While EGPA is the primary syndrome to consider, other conditions in the differential include:

• Hepatitis C-related extrahepatic manifestations can cause peripheral neuropathy and cryoglobulinemia, but nasal polyps are not characteristic 1
• Sarcoidosis can cause peripheral neuropathy and nasal involvement, but hyperbilirubinemia would be from hypercalcemia-related hepatic dysfunction rather than direct involvement 1

Critical Pitfalls to Avoid

• Do not dismiss nasal polyps as simple chronic rhinosinusitis - the combination with peripheral neuropathy should trigger systemic vasculitis evaluation 1
• Check for asthma history - EGPA almost always includes asthma as part of the syndrome, and its absence should prompt reconsideration of the diagnosis 1
• Assess for cardiac involvement early - cardiomyopathy is a poor prognostic factor in the Five-Factor Score and requires aggressive treatment 1
• Screen for renal involvement - proteinuria >1g/day and renal insufficiency are poor prognostic factors requiring cyclophosphamide or rituximab 1

Treatment Implications

If EGPA is confirmed, treatment intensity depends on disease severity:

• Severe disease (with poor prognostic factors including peripheral neuropathy, cardiomyopathy, GI involvement, or CNS involvement) requires glucocorticoids plus cyclophosphamide or rituximab 1
• Non-severe disease can be managed with glucocorticoids alone 1
• Peripheral neuropathy itself necessitates immunosuppression in most treatment protocols 1