Diagnosis

Wegener's granulomatosis

Autoimmune systemic vasculitis of the small- to medium-sized vessels causing necrotizing granulomas in different regions such as the respiratory tract and glomerulonephritis.

ANCA-associated vasculitis includes [f7u]

Granulomatosis with polyangiitis (Wegener's granulomatosis)
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Also known as: Granulomatosis with polyangiitis

Etiology

Cause [dgw]

Multi-factorial interactions:
- Genetics (defective alpha-1 antitrypsin, CTLA-4, HLA-DP, FC gamma receptor III b)
- Microbes as an initiating factor for inflammation: S. aureus, HCV, CMV, EBV, parvovirus
- Drugs can induce ANCA-associated vasculitis: Hydralazine, Propylthiouracil, Methimazole, Allopurinol, Sulfasalazine, Minocycline, Penicillamine, Rifampicin, Aminoguanidine, Sofosbuvir, Anti-tumor necrosis factor

Pathophysiology [dgw]

Defective immune-regulatory responses to environmental factors: infection or autoantigens --> ANCA --> activates neutrophils --> adherence to the endothelium --> vasculitis
Neutrophilic microabscesses --> occlusion of blood vessels --> necrotizing granuloma
- Necrotizing sinusitis
- Pulmonary capillaritis
- Glomerulonephritis
Clinical manifestation:
- Generalized disease: fever, malaise, weight loss, polyarthralgia, and myalgia
- Sinus/Nose/Ear involvement: pain, sinus stuffiness, nasal discharge, nasal ulcerations, epistaxis, otitis media, hearing loss
- Lung involvement: cough, hemoptysis, dyspnea, pleuritic chest pain, pleural effusion, tracheal obstruction
- Renal involvement: Glomerulonephritis (RPGN) eventually develops in 80% of patients within 2 years of disease
- Eye involvement: Scleritis, conjunctivitis, keratitis, episcleritis, anterior uveitis, retrobulbar orbital mass, diplopia, proptosis, blindness, nasolacrimal duct obstruction
- Skin: Purpura commonly involving the lower extremities, cutaneous nodules (normally in the olecranon regions). Less commonly, ulcers, papules, vesicles, and subcutaneous nodules (granulomas) may occur.
- Nervous system: Peripheral neuropathy, cranial neuropathies, pachymeningitis, seizures, and cerebritis
- Musculoskeletal: Arthralgia and myalgia
- Cardiac: Valvular lesions, valvular insufficiency, pericarditis, and coronary arteritis

Complications [vlc][dgw]

Hearing loss
Vision loss
Saddle nose deformity or septal perforation
Respiratory failure due to diffuse pulmonary hemorrhage
Chronic kidney failure
Mononeuritis multiplex
Increased risk of heart disease, diabetes, and hypertension due to the vasculitis

Epidemiology

Incidence per 100.000 [kt4][gfy][2q4][eiy][8pa][php][4sp][ena][p3w][19i][sbe]

Symptoms & findings

Symptoms

Anopsia, Anorexia, Arthralgia, Ataxia, Cough, Digital necrosis, Diplopia, Dyspnea, Epistaxis, Exophthalmos, Fasciculations, Fatigue, Fever, Hearing loss, Hematuria, Hemoptysis, Hoarseness, Malaise, Muscle weakness, Myalgia, Nasal congestion, Nasal discharge, Night sweats, Paresis, Paresthesia, Saddle nose deformity, Stridor, Subungual hematoma, Weakness, Weight loss, Wheezing

Clinical findings

ANCA, Anemia, Elevated Creatinine, Elevated CRP, Elevated Sedimentation Rate, Leukocytosis, Necrotizing granuloma, Pericardial effusion

Anamneses

None listed.

Localized findings

Pain

Radiates

MaxillofacialEyesEarsGeneralJointsMuscles

Onset

Gradual (days)

Pattern

Constant

Severity

Mild (1-3)Moderate (4-7)

Rash

Radiates

EyesRegio nasalisCavum oris (inside mouth)Skin

Distribution

GeneralizedLocalizedMultipleSingleSymmetric

Lesion type

BullaErythemaGangrenePetechiaPurpuraPustuleUlcerVesicle

Rash

Radiates

ArmLower body

Distribution

GeneralizedSymmetric

Lesion type

Mottling

Color

BlueRed

Palpation

Cold

Swelling

Radiates

Cavum oris (inside mouth)

Onset

Gradual (days)

Pattern

Constant

Approach

Blood test: ANCA, eosinophil count
Urine analysis
Biopsy of the nasal mucosa, kidney and lung
Chest X-ray
Sinus X-ray
CT caput/thorax

Diagnostic criteria [pd2]

Clinical involvement: Ear, nose, and throat
+3 points: bloody nasal discharge, nasal crusting or sino-nasal congestion
+2 points: cartilaginous involvement
+1 point: conductive or sensorineural hearing loss
Laboratory: ANCA positivity
+5 points: ANCA or anti-proteinase 3 ANCA positivity
-1 point: perinuclear ANCA or anti-MPO ANCA positivity
-4 points: eosinophil count ≥1×109 /L
Radiology: Lungs and sinus
+2 points: pulmonary nodules, mass or cavitation on chest imaging
+1 point: inflammation or consolidation of the nasal/paranasal sinuses on imaging
Biopsy:
+2 points: granuloma or giant cells on biopsy
+1 point: pauci-immune glomerulonephritis on biopsy
Conclusion: After excluding mimics of vasculitis, a score of ≥5 is needed for the diagnosis

Treatment

1st line: Corticosteroids + Cyclophosphamide [vlc][dgw]
- Induction phase: Methylprednisolone 500-1000 mg IV daily for 3 days
- Maintenance phase: Prednisone 1 mg/kg/day for 1 month --> taper to 15 mg/day
- Cyclophosphamide 2 mg/kg/day: 90% response rate
2nd line: Corticosteroids + Rituximab (monoclonal antibody that targets B cells)
Alternative therapy: Intravenous immunoglobulin, Etanercept, Infliximab, azathioprine, methotrexate, and plasmapheresis [dgw]
Surgery: tissue necrosis/stricture/fibrosis in the nose, subglottis, trachea, and bronchi
- Laser treatment
- Mechanical dilation
- Injection of long-acting corticosteroids
- Resection of the stenotic area with reanastomosis

Differential diagnoses

Acute invasive fungal sinusitis, Acute sinusitis, Allergic rhinosinusitis, Allergy, Amyloidosis, Cancer, Carcinomatosis, Chronic sinusitis, Churg-Strauss syndrome, Conjunctivitis, Cryoglobulinemia, Drug side effects, Endocarditis, Episcleritis, Fungal infection, Glomerulonephritis, Goodpasture syndrome, Henoch-Schönlein purpura, Lymphoma, Myocardial infarction, Otitis media, Polyarteritis nodosa, Polyneuropathy, Pyoderma gangrenosum, Rheumatoid arthritis, Sarcoidosis, Sepsis, Systemic lupus erythematosus, Uveitis, Vasculitis

References

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