Antineutrophil cytoplasmic antibody-associated vasculitis: Experience from Taichung Veterans General Hospital 施凱翔 梁凱莉 顏廷廷

ANCA-associated vasculitis: 3 kinds of small vessel disease Microscopic Polyangiitis Granulomatosis with Polyangiitis (Wegener’s granulomatosis) Eosinophilic Granulomatous with polypangitis (Churg-Strauss syndrome) MPA GPA EGPA

Anti-neutrophil cytoplasmic antibody (ANCA): ANCA activates neutrophils with subsequent activation of the complement pathway, results in vascular damage, non-resolving chronic inflammation Two kinds of staining pattern of ANCA: P-ANCA (staining of MPO) and C-ANCA (staining of PR3) MPO: myeloperoxidase  PR3: proteinase 3

Clinical manifestations: localized or generalized

Patients and Methods Retrospective chart review of patients with ANCA-associated vasculitis based on the classification criteria of American College of Rheumatology and definitions described at the Chapel Hill Consensus Conference 2012

Results From March 2004 to March 2017: 11 patients with ANCA-associated vasculitis were enrolled (9 GPA, 1 MPA, and 1 EGPA) Characteristics Patient (N = 11) N (%) Sex Female Male 8 (73) 3 (27) Age of Dx -yr median (range) distribution -N (%) 18-40 yrs 40-64 yrs ≥65 yrs 44 (20-73) 5 (45) 1 (9)

Results Clinical manifestations Patients (N=11) N (%) Rhinosinusitis Rhinitis or nasal symptoms Sinusitis 11 (100) 10 (91) 7 (64) Fever Hearing impairment 4 (36) Ocular involvement 5 (45) Lung involvement Trachea involvement 6 (55) 2 (18) Renal involvement Central nervous system involvement Mucocutaneous involvement Gastrointestinal involvement 1 (9)

Nose and Sinus: Most common manifestation Usually present with nasal obstruction, rhinorrhea, or bloody nasal discharge

Nose and Sinus: Tissue damage and bone destruction caused by vasculitis Chronic inflammation could result in anosmia, septal perforation, and saddle nose

Ear and peripheral facial palsy Sensorineural hearing loss Otitis media/ effusion/ mastoiditis Facial palsy

Larynx and Trachea, orbit Glotic ulcer or subglottic stenosis Orbital pseudotumor Episcleritis, scleritis

Salivary glands and mucocutaneous findings Parotid or submandibular glands may be swollen and sore

Surrogate markers Serology testing Patients (N = 11) N (%) ANCA positive PR3-ANCA MPO-ANCA 11(100) 6(55) 5(45) GPA n=9 6(67) 3(33) ANA positive ANA equivocal 1(9) 3(27)

Pathological features Nine out of 11 patients had pathological diagnoses. Multiple biopsies in few patients Most positive pathology came from sinonasal regions. Necrotizing granuloma Vasculitis

Treatment modality and outcomes Steroid (11, 100%), cyclophosphamide (7, 63%) Rituximab (6, 45%) Ten out of 11 patients were alive at the end of this study One patient with GPA died from septic shock The disease relapse in 4 out of 9 GPA patients and need additional therapy

Discussions The annual incidence of GPA in Taiwan was 0.37 per million patient-years from 1997 to 2008, according to the NHI database The annual incidence of GPA in Europe was about 4.9 to 10.6 per million years according to different regions Journal of Microbiology, Immunology and Infection, 2015, 48.5: 477-482. Ann Rheum Dis. 2001 Dec; 60(12): 1156–1157.

Discussions Five out of our patients initially seek medical help to ENT doctors. Most patients had multi-system involvement except one. Time between the first show-up to diagnosis range from 1 to 11 months

Discussions GPA MPA EPGA Our study Treatment outcome of our patients was not inferior to literature review GPA MPA EPGA Our study Remission rate 30-93% 75-89% 81-91% 100% 5-year survival 74-91% 45-76% 60-97% 91% Relapse (variably defined) 18-60% 8% 35% 44% Annals of the rheumatic diseases 67.7 (2008): 1004-1010.

Conclusions Otorhinolaryngologist could be the first physician to contact the patients with ANCA-associated vasculitis. This diagnosis must always be taken into consideration in patient with atypical symptoms or unresponsive to standard treatment.

Conclusions Harvest multiple sites, adequate tissue biopsy helps to make diagnosis. Early diagnosis is crucial for therapy implementation and allows avoid irreversible organ damage.

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