The Diagnosis of Granulomatosis With Polyangiitis When Serology and Biopsies are Negative

Granulomatosis with polyangiitis (GPA) is a potentially fatal condition which often manifests in the head and neck. Currently, diagnosis relies on antineutrophil cytoplasmic autoantibody (c-ANCA) serology and mucosal or renal biopsy. However, a significant proportion of patients with GPA limited to the head and neck are seronegative and biopsy negative. This study evaluates the role of clinical diagnosis of GPA in the absence of positive laboratory findings.

Case series with chart review.

Academic Tertiary Medical Center.

This was a retrospective review of 143 patients treated in an outpatient otolaryngology clinic at a tertiary care hospital for known or suspected GPA from 1998 to 2021. Presenting symptoms, C-ANCA status at initial presentation, biopsy results, long-term serology results, and time to initiation of treatment were analyzed.

Twenty-six of 143 (18.2%) patients were seronegative; only 3 of these patients (12%) had positive biopsies. Seventeen (73.9%) of these patients presented with nasal and sinus disease and 12 (52.2%) presented with airway involvement. Only 4 (17.4%) patients had renal involvement. Delay in treatment of patients with negative laboratory workup ranged from 0 months to 11 years. All patients who were seronegative and/or biopsy negative at presentation responded clinically to immunosuppressive therapy.

GPA cases are often limited to the upper respiratory tract, making diagnosis difficult, particularly in seronegative patients. These results suggest that, when GPA is suspected, despite negative serology, the diagnosis of GPA should be made on clinical grounds, and empiric therapy encouraged to prevent delay in treatment.