title: Diagnostic value of biopsies in identifying cytoplasmic antineutrophil cytoplasmic antibody-negative localized Wegener's granulomatosis presenting primarily with sinonasal disease.
abstract: BACKGROUND
  A substantial proportion of Wegener's disease (WG) patients present with localized disease of the upper airways, i.e., sinonasal and other ear/nose/throat (ENT) symptoms. Because of the oligosymptomatic presentation a timely diagnosis of this potentially  fatal disease is challenging. This study evaluates diagnostic peculiarities between WG in its localized and generalized form of the disease.
  
  
  METHODS
  Retrospective analysis was performed of 82 patients with suspected WG manifesting in the ENT region between 1989 and 2009.  Comparison was performed of the clinical and laboratory results between patients with localized (n = 15) and generalized stage (n = 16) as well as non-WG patients (n = 50).
  
  
  RESULTS
  ENT signs and symptoms were subtle, especially in the population presenting with localized  disease. Therapy refractory rhinosinusitis or serous otitis media were the most frequent presentations of WG. In testing for localized WG, mucosal biopsy had the highest sensitivity (53%) compared with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) with a lower sensitivity (47%)  but highest specificity (96%) and highest positive predictive value (PPV; 78% versus 73%). Patients with generalized WG typically revealed a pathological urine sediment, hemoptysis, or rheumatological symptoms. In the generalized stage, c-ANCA had the highest sensitivity (81%), specificity  (96% versus 95%), and highest PPV (87%).
  
  
  CONCLUSIONS
  Timely diagnosis and treatment of localized WG limited to the ENT region remains problematic. Even with adequate therapy, nearly one-half of patients with sinonasal localization suffer from relapse, at least 1 in 10 will  progress to generalized disease, and up to two-thirds may develop permanent tissue damage. Unfortunately, the diagnostic usefulness of c-ANCA is significantly reduced at this early stage compared with cases with generalized disease (p = 0.04). Hence, the relative diagnostic value of mucosal  biopsy increases especially for the significant proportion of c-ANCA(-) localized WG patients (47%). Sinonasal tissue sampling represents a cornerstone for diagnosis, which unlike c-ANCA testing can be repeated in short intervals and is associated with low morbidity.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, University Hospital, University of Bern, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Borner
authors.forename: Basile Nicolas
authors.initials: BN
authors.lastname: Landis
authors.forename: Yara
authors.initials: Y
authors.lastname: Banz
authors.forename: Peter
authors.initials: P
authors.lastname: Villiger
authors.forename: Piero
authors.initials: P
authors.lastname: Ballinari
authors.forename: Marco
authors.initials: M
authors.lastname: Caversaccio
authors.forename: Patrick
authors.initials: P
authors.lastname: Dubach
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D001706:Biopsy; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009668:Nose Diseases / Q000175:diagnosis*; D010256:Paranasal Sinuses; D012189:Retrospective Studies
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic