In the beginning of March 2021, a 78-year-old woman with history of bronchial asthma and diabetes was referred to our hospital with bilateral hearing loss for a week. She was a never smoker. Physical examination findings were as follows: body temperature, 37.0  C; pulse rate, 78/min; respiratory rate, 20/min; and blood pressure, 132/85 mmHg. No skin lesions were observed, but peripheral lymphadenopathy was noted in the bilateral submandibular glands. Respiratory and cardiac sounds were clear. Otolaryngological examination revealed right-sided otorrhea and purulent nasal discharge. However, otorrheal fluid culture yielded no bacterial growth. Audiometric tests showed a severe sensorineural hearing loss: the pure tone averages for the right and left ears were 100.0 dB and 91.3 dB, respectively. Computed tomography (CT) reveled bilateral otitis media, sinusitis, multiple nodular shadows in the lungs, bronchiectatic changes, infiltrates, and centrilobular branching opacities (Fig. 1A). However, there no mass or bone destruction were noted in the ears and paranasal sinuses. The white blood cell count was 8.3 x 109/L with 80.0% neutrophils, 14.2% lymphocytes, 4.0% monocytes, 1.4% eosinophils, and 0.4% basophils. The C-reactive protein level was slightly elevated to 1.31 mg/dL, and the (1   3)-beta-D glucan level was within the normal range. Results of liver and kidney function tests were normal, urinalysis showed no abnormal findings, and QuantiFERON-TB GOLD Plus was negative. Further, serum Proteinase-3 (PR3)-ANCA level was elevated to 19.5 U/mL (normal, < 3.5 U/mL), and myeloperoxidase (MPO)-ANCA was <1.0 U/mL (Table 1). Biopsy of the submandibular gland revealed suppurative sialadenitis without granulation. Antibiotic therapy with intravenous ampicillin/sulbactam (6.0 g/day) was initiated, but the otitis media did not improve. Bronchoscopic examination with endobronchial ultrasonography with a guide sheath was performed on the left B3, and results of polymerase chain reaction tests on the bronchial lavage fluid were negative for Mycobacterium avium-intracellulare and M. tuberculosis. A bronchial lavage fluid smear was positive for acid-fast bacilli (1+; 1-9 acid-fast bacilli per 100 field), but culture revealed no bacterial growth in the mycobacterial growth indicator tube. Furthermore, histological examination of transbronchial biopsy specimens obtained from lung nodules revealed non-specific inflammation without granulomas. The patient was diagnosed with OMAAV based on bilateral severe sensorineural hearing loss, intractable otitis media, and elevated serum PR3-ANCA levels. Moreover, we considered non-tuberculous mycobacteria-associated pulmonary disease (NTM-PD); therefore, oral PSL 40 mg/day was initiated, and we did not administer immunosuppressants to avoid the exacerbation of NTM-PD. After bronchoscopic examination, minocycline 200 mg/day was administered for five months to treat the suppurative sialadenitis of the submandibular gland. The serum PR3-ANCA level decreased to within the normal range in April 2021 with PSL 35 mg/day and remained within the normal range thereafter. As the auditory capacity gradually improved, we tapered the PSL dosage to 20 mg/day. The hearing ability improved to 61.3 dB (right) and 57.5 dB (left) at the end of August 2021.
At the end of September, the patient presented with high fever for three days and visited our emergency center on foot. Chest CT showed multiple cavitary and noncavitary masses with peripheral and upper-lobe predominance in both lungs (Fig. 1B). The CRP and PR3-ANCA levels were significantly elevated to 22.39 mg/dL and 9.8 U/mL, respectively. A second bronchoscopic examination with endobronchial ultrasonography with a guide sheath was performed on the right B2. There was no evidence of bacterial infection, including in the results of polymerase chain reaction tests for Mycobacterium avium-intracellulare complex on the bronchial lavage fluid. Furthermore, histological examination of transbronchial biopsy specimens obtained from masses revealed micro abscesses and necrotizing granulomatous vasculitis, which were consistent with GPA (Fig. 2).
The patient was diagnosed with GPA based on the diagnostic criteria of the Japanese Ministry of Health Labour and Welfare. Therefore, we increased to PSL 50 mg/day (1 mg/kg) with a dose reduction every 2 weeks and administered intravenous cyclophosphamide (CY) 500 mg once every two weeks for 12 weeks as a remission-induction therapy. NTM-PD did not progress, and no anti-mycobacterial therapy was administered. The patient's symptoms and CT findings rapidly improved, and the PR3-ANCA level promptly decreased to within the normal range. However, with regard to the auditory capacity, moderate hearing loss persisted without further improvement in hearing ability at the end of the remission-induction therapy (Fig. 3).