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%).

Conclusion: 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.