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Granulomatosis with Polyangitis
(Wegener’s Granulomatosis)
Adam M. Parker, M4
University of Mississippi
School of Medicine
October 2013
To view Speaker Notes – see separate link
Background

Wegener’s Granulomatosis is a systemic disease characterized by
necrotizing granulomatous vasculitis that classically involves the
upper respiratory tract, lower respiratory tract, and kidneys.

1897: Peter McBride (Scotland) first describes the disease

1931: Heinz Klinger adds to McBride’s findings

1936 & 1939: Friedrich Wegener (Germany) clearly defines the
disease and is thus credited with its discovery

1985: c-ANCA is discovered (cytoplasmic antineutrophil
cytoplasmic antibody)

2011: renamed “Granulomatosis with Polyangitis” after Wegener’s
association with the Nazi party is widely publicized
Epidemiology
 Incidence: 1-2 cases per 100,000 population
 Age: most commonly presents between 30-50 y.o. (variable)
 Sex: Male = Female
 Race: Caucasian (90%)
Etiology
 Exact etiology is unknown
o Autoimmune (antineutrophil cytoplasmic antibodies)
o S. aureus colonization
o Drugs
o Environmental toxins
o Genetic factors
Prognosis (Systemic GPA)
 Untreated
o fatal
o ~80% mortality rate within first year
 With Treatment
~90% 5-year survival rate
o Disease remission is possible, but 50% of patients
experience flare-ups or relapse within 2 years.
o
Pathology
 Proteinase-3 is a serine protease enzyme that’s associated
with the primary (azurophilic) granules located in the
cytoplasm of neutrophils.
 c-ANCAs target proteinase-3, and this interaction is believed to
result in neutrophil activation (e.g. endothelial adhesion)
and degranulation.
 Results in localized or systemic small vessel necrotizing vasculitis
with granulomatous inflammation that involves small to
medium sized vessels.
Presentation
 Head and Neck Involvement (70% = initial S/Sx’s)
o Sinonasal (80%)
 Recurrent and Chronic Rhinosinusitis that is unresponsive to
traditional treatment (most common presentation)
 Nasal obstruction, septal perforation, recurrent epistaxis
 Saddle-nose deformity (late complication)
o Otologic

Most commonly serous otitis media +/- CHL
 Acute and Chronic OM (+/- Mastoiditis)

SNHL (involvement of CN VIII or Cochlea)
Presentation
 Larynx and Trachea
o Subglottic ulcerations and stenosis (20% of cases)
 Biphasic stridor, dyspnea, hoarseness
 BV supply
 Pulmonary Disease
o develops in 80% of cases (present in 40% of presenting patients at)
o Cough, stridor, hemoptysis, dyspnea
o Bilateral, cavitating infiltrates or nodules
 Renal Disease
o develops in 75% of cases
o may be subclinical until renal failure develops
o Crescentic Glomerulonephritis (RPGN)
Differential Diagnoses
 Churg-Strauss Syndrome (p-ANCA)
 Microscopic Polyangitis (p-ANCA)
 Sarcoidosis
 Rheumatoid Arthritis
 Fungal Infection
 Mycobacterial Infection
Workup & Diagnosis
 Clinical presentation
 Biopsy (Gold Standard)
o Pulmonary > Renal > Nasal.
o Necrotizing vasculitis with granulomatous inflammation
(multinucleated giant cells and palisading histiocytes)
o Higher false-negative results seen with nasal biopsies.
 c-ANCA
o Specificity: as high as 98%
o Sensitivity: varies with disease activity
 90% (active systemic), 60% (localized), and 30% (remission)
o Titer may be used to follow disease course (controversial)
Workup and Diagnosis cont’d
 Culture
o Rule out infectious etiologies (Fungal, TB)
 CXR
o assess for pulmonary involvement
 Urinalysis
o assess for renal involvement
 Other: Sinus films, BMP, ESR, CRP, Autoimmune
Panel, VDRL or RPR.
Treatment
 Induce Remission
o Cyclophosphamide, Methotrexate, or Azathioprine
o Corticosteroids (e.g. Prednisone)
 Prophylaxis
o Bactrim
 Resistant Disease
o Rituximab
o Infliximab, Etanercept, Lefunomide
 Saline irrigations +/- antibiotics
Treatment
 Subglottic Stenosis
o May resolve with medical treatment alone
o Serial dilation with steroids +/- Mitomycin-C
o Tracheotomy (severe airway compromise)
o Laser therapy, local resection, and laryngotracheal
reconstruction are less efficacious in the treatment of SGS
secondary to Wegener’s Granulomatosis.
References
Vega Braga FL, et al. Otolaryngological Manifestations of Wegener’s Disease. Acta
Otorrinolaringol Esp. 2013;64:45-9.
Taylor SC, Clayburgh DR, Rosenbaum JT, Schindler JS. Clinical Manifestations and Treatment of
Idiopathic and Wegener Granulomatosis-Associated Subglottic Stenosis. JAMA Otolaryngol
Head Neck Surg. 2013;139(1):76-81.
Morales-Angulo C, et al. Ear, Nose and Throat Manifestations of Wegener’s Granulomatosis
(Granulomatosis With Polyangitis). Acta Otorrinolaringol Esp. 2012;63:206-11.
Flint, Paul W., and Charles W. Cummings. Cummings Otolaryngology Head & Neck Surgery.
Philadelphia, PA: Mosby/Elsevier, 2010.
Lee, KJ. Essential Otolaryngology: Head and Neck Surgery : a Board Preparation and Concise
Reference. New York, N.Y: Medical Examination Pub. Co, 1987. Print.
Gubbels SP, Barkhuizen A, Hwang PH. Head and neck manifestations of Wegener’s
granulomatosis. Otolarngol Clin North Am. 2003;36(4):685-705.
Eliachar I, Chan J, Akst L. New approaches to the management of subglottic stenosis in
Wegener’s granulomatosis. Cleveland Clinic Journal of Medicine. 2013;69(2):149-151.
Schokkenbrock AA, Franssen CF, Dikkers FG. Dilation tracheoscopy for laryngeal and tracheal
stenosis in patients with Wegener’s granulomatosis. Eur Arch Otorhinolaryngol. 2008;265:54955.