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Similar to Granulomatosis polyangitis GPA
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Granulomatosis polyangitis GPA
- 1. Granulomatosis with polyangiitis (GPA) MarwaAbo Elmaaty Besar Lecturer Of Internal Medicine (Rheumatology Immunology Unit) (Pediatric Rheumatology)
- 2. Historical view: Firstdescribed by klinger in 1931. Wegener 5 years later; clinico-pathologic entity of GPA. Godman and Churg in 1954; triad features: (a)Necrotizing granulomatous lesions in the upper and/or lower respiratory tract; (b)Generalized necrotizing vasculitis involving both arteries and veins; (c) Glomerulitis. The chapel hill consensus conference in 1994. The revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides of 2012 ; change from “Wegener’s granulomatosis ” to “granulomatosis with polyangiitis (Wegener)”, as a necrotizing granulomatous inflammation of the upper and lower respiratory tract affecting small and medium vessel walls. GPA postulated by the combination of peculiar clinical features with the presence of PR3- CANCA.
- 3. Granulomatosis with polyangiitis(GPA) A systemic, necrotizing vasculitis characterized by Involvement of the upper and lower respiratory tract, Associated with pauci-immune glomerulonephritis. Presence of antineutrophil cytoplasmic antibodies ( ANCA ), Histologically characterized by Granulomas within the medium and small vessel wall. Rare disease; 22–34 cases per million inhabitants ,an incidence rate of 4–9 cases per million/year. Higher incidence in Northern Europe. Age; 50 and 65 years. Male= female. F. Dammacco et al 2016
- 4. Pathogenesis: Curr Rheumatol Rep(2010) 12:399–405
- 5. Clinical features: Constitutionalsigns (fever, asthenia and weight loss) 50% patients. (ENT) ear, nose and throat signs and symptoms all patients. The lower respiratory tract 80% patients. Localized forms of GPA Systemic forms of GPA
- 6. Clinical picture:- ENT sign; Crusting, rhinorrhoea, sinusitis, nasal pain and chronic otitis media. Sinusitis is the most common feature led to nasal obstruction, Stuffiness, and hypo- or anosmia. Erosions of the facial cartilages; perforation of the palate and/or pinna of the ear. The nasal septum is involved, lead to nasal bridge collapse “ saddle-nose” deformity. Localized forms of GPA; ENT involvement only. Hearing loss; • Eustachian tube dysfunction secondary to naso-pharyngeal disease. • Inner ear disease; a sensorineural impairment and/or to a vestibular dysfunction
- 7. Clinical picture: The lowerrespiratory tract; Initial phase; o Hoarseness, cough, wheezing and stridor. o 15-20% patients. o subglottic stenosis, fatal complication, unfortunately asymptomatic. lung involvement, the most common. o Alveolar haemorrhage, (from small to massive quantities, lead to fulminant respiratory failure). o Pulmonary infiltrates. o single or multiple parenchymal nodules.
- 8. Systemic forms Renalinvolvement. o 50–100 % of patients. o Poor prognosis; GFR and the number of normal glomeruli at the renal biopsy. o Glomerulonephritis with segmental necrosis. o Extra-capillary proliferation and pauci-immune crescent formation. Urogenital manifestations (renal pseudotumor, prostatitis, orchitis, epididymitis, ureteral stenosis or penis ulceration). Mucocutaneous manifestations: o 50% patients. o Papules, subcutaneous nodules, o Ulceration , necrotizing lesions or widespread vascular purpura. o Raspberry-red gingivitis, and intraoral and/or genital ulcerations.
- 9. Eur J MedRes (2011) 16: 331-334
- 10. Ocular involvement; 50%patients. scleritis or episcleritis, conjunctivitis, keratitis, uveitis and blindness. Retro-orbital pseudo-tumor or a dacryoadenitis develop, lead to Exophthalmos or ophthalmoplegia
- 11. Clinical picture:- CNS: Peripheral neuropathy o Sensorial and/or motor. o 30% patients. Pachymeningitis. o Rare; 5-10% patients. o Granulomatous deposits, intracerebral vascular lesions or an extension of sinus lesions Cardiovascular o Conduction disorders, pericarditis or myocarditis. o Subclinical to end-stage heart failure Gastrointestinal o Quite unusual. o Ulcerative lesions, intestinal perforation.
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- 13. Work up: Laboratory: oComplete blood count, o Creatinine, BUN, serum electrolytes, o Urine analysis and 24 h-proteinuria. o Serum proteins with electrophoresis. o Erythrocyte sedimentation rate (ESR) o C-reactive protein (CRP) o ANCA (PR3 c-ANCA) 90%, good diagnostic marker for GPA. Endoscopy of nose and larynx: nasal septum erosions and to obtain histological specimen. Radiology: o Conventional chest and nasal-sinus X-ray; nasal sinuses obstruction and single/multiple nodules o CT scan of sinus and chest; extent of inflammation. o Ultrasound on Kidney. o CT scan abdomen and brain. o ECHO. Intervention: Renal biopsy
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- 17. J Rheumatol. Authormanuscript; available in PMC 2017 June 01 Birmingham Vasculitis Activity Score (BVAS): o Is a validated tool for assessment of disease activity for systemic vasculitis. o Assessment of disease activity in giant cell arteritis(GCA). o Later used to assess disease activity for ANCA vasculitis. o Scored items grouped into 9 organ systems, include a broad spectrum of clinical manifestations from vasculitis.
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- 19. Induction of remission: High-dose corticosteroids at 1 mg/kg up to 60 mg/day, weaned down over several weeks to a dose of 10 mg daily after around 3 months or once remission is attained Pulsed intravenous cyclophosphamide : every 2–3 weeks for 3–6 months until disease remission was attained. • Daily oral cyclophosphamide half the dose iv. Methotrexate; was as effective as cyclophosphamide in inducing remission, only localized or early systemic disease without major tissue destruction. Mycophenolate mofetil (MMF) 2–3 g/day. Rituximab is a chimeric monoclonal antibody binding to CD20, an antigen expressed on the surface of B cells, • Reduction in the numbers of circulating B cells for 4–12 months • Induction therapy of AAV. • Reduce relapse • To avoid high cumulative doses of cyclophosphamide. Therapeutics and Clinical Risk Management 2014:10
- 20. Plasma exchange; •AAV with severe renal inflammation causing acute renal dysfunction. • Alveolar haemorrhage. Intravenous immunoglobulin; • patients with active infection or • Patients not tolerated immunosuppression. Tumor necrosis factor (TNF) antagonist. 15-deoxyspergualin (an antiproliferative agent targeting antigen-stimulated B cells). Alemtuzumab (anti-CD52). Therapeutics and Clinical Risk Management 2014:10
- 21. Management of localizedGPA: Course of response; a more delayed response. A multidisciplinary approach (otolaryngologists, ophthalmologists and physicians). Systemic immunosuppression (methotrexate)combined with local therapy. Cotrimoxazole; elimination of nasal carriage of staphylococcus aureus. Rituximab is less effective in treating granulomatous upper airways manifestations of GPA than generalized disease. Obstructive tracheobronchial disease can be poorly responsive to systemic therapy. In addition to systemic therapy need treated with intralesional steroids locally endoluminal surgery with intralesional laser and dilatation Nasal and sinus disease; intranasal corticosteroids, and regular saline douching of nasal crusts. Middle ear obstruction may require insertion of grommets. Reconstructive surgery for nasal bridge collapse. All is only recommended in the absence of active disease.
- 24. Prognosis: Remission 85-90%patientswithin 3-6 months. Relapse risk; 50% at 5 years. Risk factor: o PR3-ANCA-positive patients. o Lung and upper airways involvement o Reduced intensity induction therapy. o Early withdrawal of immunosuppression or glucocorticoids. Close clinical monitoring to detect relapses at an early stage. o Clinical signs of relapse, o Changes in ANCA status, o Monitoring inflammatory markers such as c-reactive protein. Minor relapses; o Increase in oral glucocorticoids or o Optimization of maintenance immunosuppression dose. Major relapses; repeated induction therapy
- 25. Home message:- GPAis a multifocal vasculitis characterized by frequent involvement of the upper and lower respiratory tract and kidneys. The presence of c-ANCA with anti-proteinase 3 specificity is observed in more than 90% of patients with GPA. Two phenotypes of GPA are recognized: systemic forms, with potentially life-threatening manifestations, and the other more limited form. Effective induction therapy with corticosteroids combined with cyclophosphamide or rituximab transformed the survival of patients
- 26. Reference:- 2021 AMERICANCOLLEGE OF RHEUMATOLOGY/VASCULITIS FOUNDATION GUIDELINE FOR ANCA- ASSOCIATED VASCULITIS 2017 ACR/EMA Revised Criteria for too Early Diagnosis of Granulomatosis with Polyangiitis (GPA). Autoimmune Dis Ther Approaches 3:127 Watts RA. ANCA-associated vasculitis. Arthritis Research UK. 2012;1 Panupattanapong S, Stwalley DL, White AJ, Olsen MA, French AR, Hartman ME. Epidemiology and outcomes of granulomatosis with polyangiitis in pediatric and working‐age adult populations in the United States: analysis of a large national claims database. Arthritis Rheumatol 2018;70(12):2067–2076. Ruokonen H, Helve t, arola J, Hietanen J, lindqvist C, Hogstrom J. “Strawberry gingivitis” being the first sign of wegener’s granulomatosis. Eur J Int Med 2009; 20:651-653. Holden NJ, Williams JM, Morgan MD, et al. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process. Ann Rheum Dis. 2011;70:2229–2233. Cambridge University Hospitals NHS Foundation Trust. Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE). NCT01405807&rank=1. NLM identifier: NCT01405807. Accessed July 28, 2011 Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of main tenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44.