Granulomatosis with polyangiitis

By Marcello Cherchi, MD PhD

For patients

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is an autoimmune disease that can cause symptoms involving the eyes, ears, nose, throat, lungs, kidneys and skin. Diagnosis and treatment is managed by rheumatology. Some patients with GPA get hearing loss. Less commonly they develop tinnitus or disequilibrium.

For clinicians

Overview

Granulomatosis with polyangiitis (GPA) is a member of a broader family of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculidites. It causes granulomas in numerous tissues including the eye, ear, nose throat, lungs, kidneys and skin. Some patients with GPA experience hearing loss that is usually bilateral, can be in any pattern (sensorineural, conductive or mixed), and any tempo (abrupt in onset, or progressive). Fewer patients experience tinnitus and even fewer experience vestibular symptoms. The hearing loss may respond to immunosuppressive treatment, if initiated early. For residual hearing loss, amplification or cochlear implantation can be considered. Management of GPA is typically overseen by a rheumatologist. Practitioners from other subspecialties may be required depending on the specific manifestations (e.g., otolaryngology, nephrology, dermatology).

Introduction

Granulomatosis with polyangiitis (GPA) is a member of a broader family of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculidites (which also includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis).

Historical background

In the 1930s, pathologist Dr. Friedrich Wegener (1907 – 1990) began publishing descriptions (Wegener 1936, 1939) of a disease that came to bear his name for a time, and he provided an overview of this period of his career in an article published in the year of his death (Wegener 1990). In light of subsequent research revealing that Wegener had been a member of the Nazi party (Woywodt and Matteson 2006), in 2010 the eponymous designation was retired and the diagnosis was renamed granulomatosis with polyangiitis (GPA) (Arkuszewski and Cieslak-Arkuszewska 2025).

Dr. Friedrich Wegener (1907 – 1990). From Woywodt and Matteson (Woywodt and Matteson 2006).
Dr. Friedrich Wegener (1907 – 1990). From Woywodt and Matteson (Woywodt and Matteson 2006).

Epidemiology

GPA is rare. Kitching and colleagues state that studies cite a prevalence ranging from 48 to 421 cases per million (Kitching et al. 2020).

Genetics

Some research suggests that there are genetic distinctions between the various antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculidites (Lyons et al. 2012).

Pathophysiological mechanism of disease

GPA damages tissues through its vasculitic effects and the formation of granulomas.

Clinical presentation

GPA is a multi-system disease with variable manifestations. Presentation can include:

  • Constitutional symptoms (fever, weight loss).
  • Ophthalmologic symptoms (visual loss, conjunctivitis, corneal ulceration, scleritis, episcleritis, uveitis, retinal vasculitis, optic neuropathy).
  • Otorhinolaryngological symptoms (hearing loss, disequilibrium, sinusitis, otalgia, rhinorrhea, epistaxis, otorrhea).
  • Tracheo-pulmonary symptoms (cough, stridor, wheezing, dyspnea, hemoptysis, chest pain).
  • Musculoskeletal symptoms (myalgias, arthralgias).
  • Dermatologic symptoms (purpura, ulcers, urticaria, livedo reticularis, skin nodules).
  • Renal symptoms (hematuria).

Patients with GPA can develop hearing loss that is usually bilateral (Sahyouni et al. 2019), and can be in any pattern (Sahyouni et al. 2019): sensorineural (Gomes et al. 2022; Guyot et al. 1990; Illum and Thorling 1982; Kempf 1989; Koenen et al. 2022; Kornblut et al. 1982; McCaffrey et al. 1980; Nakamaru et al. 2016; Ratmeyer et al. 2021; Takagi et al. 2002; Wierzbicka et al. 2011), conductive (Kiessling et al. 2020; McCaffrey et al. 1980; Rahne et al. 2017) or mixed (Bakthavachalam et al. 2004; Busch et al. 2022; Chen et al. 2024; Nakamaru et al. 2016). The conductive hearing loss appears to result from the ability of GPA to cause otitis media (Alkhaldi et al. 2024; Sahyouni et al. 2019; Takagi et al. 2002) with middle ear effusion (Uppal et al. 2014; Wierzbicka et al. 2011) and Eustachian tube dysfunction. GPA can also cause otitis externa (Illum and Thorling 1982). The hearing loss can be gradually progressive (Uppal et al. 2014; Yamazaki et al. 2012) or abrupt in onset (Kim et al. 2016; Ratmeyer et al. 2021).

Some GPA patients develop hypertrophic pachymeningitis (Martinez-Pina et al. 2024; Yildirim et al. 2008), which can cause hearing loss that is mixed (Chen et al. 2024).

Hearing loss is the most common aural symptom in GPA (Rahne et al. 2020; Safavi Naini et al. 2017). Less common aural symptoms include tinnitus (Rahne et al. 2020) and aural fullness (Vainutiene et al. 2024).

Rarely, the aural symptoms may precede other symptoms of GPA (Yamazaki et al. 2012).

A small minority of GPA patients experience vestibular symptoms (Goderis et al. 2015; Kim et al. 2016; Rahne et al. 2020).

Physical examination

Physical examination varies depending on organ system involvement.

Imaging

When GPA has a labyrinthitis-type of presentation, MRI of the internal auditory canals with contrast may show enhancement in the labyrinths, as displayed in the Figure below from Teszler and colleagues (Teszler et al. 2008).

Panel (A): Contrast-enhanced axial T1-weighted MR image at the level of the labyrinthine cavities demonstrates high signal intensity of the basal turn of the cochlea on both sides (white arrowheads). Conversely, there is no enhancement of the vestibular cavities. Panel (B): T2-weighted MR image shows normal high-signal labyrinthine fluid. From Teszler et al. (Teszler et al. 2008).
Panel (A): Contrast-enhanced axial T1-weighted MR image at the level of the labyrinthine cavities demonstrates high signal intensity of the basal turn of the cochlea on both sides (white arrowheads). Conversely, there is no enhancement of the vestibular cavities. Panel (B): T2-weighted MR image shows normal high-signal labyrinthine fluid. From Teszler et al. (Teszler et al. 2008).

Histopathology

Definitive diagnosis of GPA requires biopsy.

Temporal bone histopathology has reported granulation in the tympanic cavity (Ohtani et al. 2000). Yoon and colleagues (Yoon et al. 1989) studied temporal bone specimens from three GPA patients and reported serous middle ear effusion, and abnormalities involving the tympanic membrane, vascular thickening, tensor tympani muscle, Eustachian tube, mesotympanum, epitympanum, mastoid, round window, round window niche and labyrinth .

Differential diagnosis

The differential diagnosis includes:

  • Other members of the family of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculidites (eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis).
  • Polyarteritis nodosa.
  • Anti-glomerular basement membrane antibody disease.

Management

Management of GPA is typically overseen by a rheumatologist. Practitioners from other subspecialties may be required depending on the specific manifestations (e.g., otolaryngology, nephrology, dermatology).

If hearing loss related to GPA is permanent, then consultation with audiology is appropriate to be evaluated for amplification (Dwyer and Janzen 1981). Cochlear implantation is sometimes offered (Bartov et al. 2022; Cacco et al. 2021; Elmas et al. 2017).

Prognosis

When treated with immunosuppressants (such as prednisone and cyclophosphamide), the hearing loss in GPA may improve (Guyot et al. 1990) or resolve (Clements et al. 1989), especially if treatment is initiated early (Sriskandarajah et al. 2012).

References

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Page first published on April 18, 2025. Page last updated on April 18, 2025

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