Limited Otologic Chronic Granulomatosis Polyangiitis: A Delayed Diagnosis

Statement of Significance

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis (WG), is an autoimmune disease characterized by necrotizing granulomas and small-vessel vasculitis. The first sign of disease may be common otolaryngologic symptoms. An initial diagnosis can be frequently missed without pertinent serological testing. The purpose of this report is to highlight the necessity of a high degree of clinical suspicion for commonplace otologic and sinonasal manifestations. Serologic testing allows for early diagnosis and the best chance for remission with appropriate therapies.

Case Presentation

A 67-year-old female was first seen in the clinic with the chief complaint of nasal dyspnea/obstruction. Previously, after multiple visits to her primary care physician, as well as numerous urgent care centers, she was ultimately referred to 2 different otolaryngologists for progressively worsening otolaryngologic symptoms. The 2 general otolaryngologists recommended saline nasal irrigations and prescribed antibiotics without further diagnostic testing. She ultimately sought out a third opinion from our clinic for persistent symptoms of three months. She reported feeling bilateral (AU) aural fullness, sinonasal congestion, nonpulsatile intermittent tinnitus bilaterally worse in her left ear, and facial pressure. These otologic and sinus symptoms had reportedly worsened over the preceding three months leading up to the consultation with our office. After thorough history, the patient also complained of bilateral ear pain with chronic aural fullness bilaterally and “muffled hearing” which had progressively worsened over the preceding three months. Otologic examination revealed bilateral middle ear effusions. Tuning fork testing revealed negative Rinne testing consistent with bilateral conductive hearing loss (CHL) (Weber 512 Hz fork was midline). Audiometric testing revealed mild–moderate conductive hearing loss bilaterally in lower frequencies with a mixed hearing loss with both sensorineural and conductive components in the higher frequencies bilaterally (Figure 1). A high resolution computed tomography (HRCT) scan of the temporal bones revealed non-coalescent chronic mastoid effusion in the right ear (AD) and a mastoid effusion with erosion of septations in the mastoid in the left ear (AS) (Figure 2). The following serologic markers were obtained: ESR, CRP, and C-ANCA profile, which included antiproteinase 3 (PR-3) antibodies. The ESR, PR-3, and C-ANCA were all elevated. Bilateral myringotomies were performed, evacuating serous effusions, and tympanostomy tubes were placed bilaterally. Multi-system assessment excluded renal and respiratory manifestations. The patient was ultimately prescribed a steroid taper, and rheumatologic consultation was recommended; in addition, referral to an otologist at our local academic center. Due to her active limited otologic GPA, the otologist deferred mastoidectomy to allow for disease quiescence with immunosuppressant pharmaco- and biologic therapy, in collaboration with rheumatology recommendations. The patient underwent rituximab biologic pharmacotherapy. Follow-up serologies revealed decreasing PR-3, C-ANCA, ESR, and CRP. Ultimately, her otologic disease responded well to the rheumatologic regimen, and a mastoidectomy was not necessary. Eventually both tympanostomy tubes extruded; however, she developed a left ear chronic non-healing tympanic membrane perforation. She eventually underwent definitive successful tympanoplasty for the non-healing tympanic membrane perforation which was deferred for 6 months, after disease remission was definitive, and her conductive hearing loss resolved in both ears. She remains in remission today with persistent sensorineural hearing loss (SNHL) AU.

Figure 1.

(A) HRCT coronal imaging and (B) HRCT axial imaging demonstrates bilateral mastoid effusions with coalescence of the mastoid septations on the left side consistent with acute coalescent mastoiditis. The right side demonstrates non-coalescent mastoiditis.

Figure 2.

Audiogram at presentation demonstrates a mixed sensorineural and conductive hearing loss bilaterally.

Discussion

GPA was previously known as Wegener’s granulomatosis (WG). GPA is an uncommon immune-mediated systemic small-vessel vasculitis that is pathologically characterized by necrosis, granulomatous inflammation, and vasculitis which occurs in the upper and lower respiratory tracts and the kidneys. Although exact etiology is unknown, it is postulated to be autoimmune in origin and triggered by environmental events with underlying genetic predisposition. ¹ Limited GPA is a restricted form of the disease limited to one organ system. ¹ Isolated ear involvement preceding respiratory and renal manifestations is uncommonly reported. ² Patients typically have recalcitrance, with limited resolution, of their otorhinolaryngologic symptoms when initially treated with antibiotics. The main way to confirm the diagnosis of GPA is through serological testing looking for elevated levels of C-ANCA, as well as elevated PR-3 antibodies, in addition to histopathologic confirmation of necrotizing granulomas, which is often difficult to confirm.^1,3 The patient presented to us with left sided mastoid effusion with erosion of bony septations (Figures 1A, B) and worsening mixed CHL/SNHL AU.

Surgical intervention was deferred due to the active nature of her underlying disease process. ⁴ Academic Center Neuro-otology consultant elected to defer surgical biopsy until disease quiescence, due to limitations of histologic diagnosis and potential morbidity. This case highlights the necessity of both primary care providers and otolaryngologists to have a high index of suspicion and include a broad differential for common otologic and sinonasal symptoms, especially in protracted or recidivistic cases. Furthermore, our case is a relatively uncommon presentation of limited GPA with only otologic involvement. This particular patient saw numerous physicians who failed to consider a rheumatologic etiology in their differential diagnosis and, as a result, delayed diagnosis by not referring for otolaryngologic consultation. More importantly, initial otolaryngologists’ evaluations did not include a broader differential with early serologic and radiographic diagnostic testing, resulting in a delay of diagnosis. Serous otitis media is the most common otologic symptom in GPA. ⁵ Although ultimate immunosuppressive therapy improved her conductive hearing loss, it is well known that a delay in diagnosis and treatment negatively affects prognosis for sensorineural hearing recovery, as demonstrated with our patient’s persistent SNHL AU (Figure 2).^1,6