What are the typical symptoms of granulomatosis with polyangiitis (Wegener granulomatosis)?

Symptoms of Granulomatosis with Polyangiitis (Wegener Granulomatosis)

Granulomatosis with polyangiitis (GPA) classically presents with the "ELK" triad: Ear-Nose-Throat (ENT) manifestations, Lung involvement, and Kidney disease, with upper respiratory tract symptoms being the initial presentation in 70-100% of cases. 1, 2

Upper Respiratory Tract Manifestations (Most Common Initial Presentation)

The sinonasal cavity is affected in 85-100% of GPA cases and often represents the first clinical manifestation 2:

Nasal and Sinus Symptoms

• Persistent bloody nasal discharge - a cardinal feature 3
• Nasal crusting - highly characteristic and specific 1, 3
• Chronic sino-nasal congestion and obstruction 1, 3
• Epistaxis (nosebleeds) - recurrent and often severe 1
• Septal perforation leading to saddle nose deformity 1
• Recurrent sinusitis that is refractory to standard treatment 4

Otologic Manifestations

• Conductive or sensorineural hearing loss occurs in approximately 35% (range 19-61%) of cases 2, 3
• Chronic otitis media 2

Other ENT Features

• Cartilaginous involvement of the nose and ears 3
• Sore throat and hoarseness 1

Lower Respiratory Tract Manifestations

The lower respiratory tract is involved in >90% of patients with systemic disease 1:

• Cough - present in >95% of patients with pulmonary involvement 1
• Hemoptysis - occurs in >95% of patients with lung disease 1
• Dyspnea - ranging from mild to rapidly progressive respiratory insufficiency 1
• Pulmonary nodules, masses, or cavitation on chest imaging 1, 3
• Diffuse alveolar hemorrhage - a life-threatening complication 1
• Tracheobronchial stenosis in 15% of patients 1
• Subglottic stenosis in 5-23% of treated patients, presenting with persistent cough, wheezing, and dyspnea that may initially be misdiagnosed as asthma 1

Renal Manifestations

Kidney involvement is a defining feature of systemic GPA 1, 2:

• Rapidly progressive glomerulonephritis - pauci-immune necrotizing type 1, 2, 3
• Hematuria with red blood cell casts 5, 6
• Proteinuria 5
• Reduced glomerular filtration rate progressing to renal failure if untreated 5

Ocular Manifestations

Eye involvement can occur and includes 1:

• Conjunctivitis and conjunctival nodules 1
• Episcleritis and necrotizing scleritis 1
• Proptosis from orbital involvement 1
• Peripheral ulcerative keratitis 1
• Uveitis 1

Constitutional and Systemic Symptoms

General symptoms are common, particularly in systemic disease 1, 7:

• Fever 1
• Fatigue and malaise 7
• Weight loss 7
• Arthralgias and myalgias 8

Clinical Presentation Patterns

Limited vs. Generalized Disease

• Limited forms predominantly affect the upper respiratory tract without renal involvement 1, 4
• Generalized forms include renal manifestations, alveolar hemorrhage, and/or vital organ involvement with systemic symptoms 4

Diagnostic Considerations

The combination of chronic rhinosinusitis with two of the following is highly specific for GPA: nasal crusting, anosmia, and epistaxis 1. However, the prodromal phase where symptoms last for months before diagnosis may suggest infection or malignancy, causing diagnostic delays ranging from one month to three years 8.

On nasal endoscopy, the mucosa may show a characteristic "strawberry skin" appearance with small pale granulomas over erythematous, granular mucosa, though this may be obscured by extensive crusting 1.

Important Clinical Pitfalls

• ANCA may be negative in limited sinonasal disease - c-ANCA/PR3 is positive in 95% of systemic disease but only 50% of limited disease 1
• Nasal biopsies often lack specific diagnostic features - biopsies from other involved organs may be required for definitive diagnosis 1
• Subglottic stenosis symptoms are insidious and may be misdiagnosed as asthma, requiring flow-volume loops for detection 1
• Longer time from symptom onset to diagnosis correlates with more severe disease involvement and increased recurrence risk 8