* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download slides
Creutzfeldt–Jakob disease wikipedia , lookup
Meningococcal disease wikipedia , lookup
Dirofilaria immitis wikipedia , lookup
Middle East respiratory syndrome wikipedia , lookup
Onchocerciasis wikipedia , lookup
Chagas disease wikipedia , lookup
Leptospirosis wikipedia , lookup
Eradication of infectious diseases wikipedia , lookup
Oesophagostomum wikipedia , lookup
Coccidioidomycosis wikipedia , lookup
Leishmaniasis wikipedia , lookup
Schistosomiasis wikipedia , lookup
Visceral leishmaniasis wikipedia , lookup
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.