Sudden sensorineural hearing loss (SSNHL) is routinely encountered and is one of the most common emergent diseases in otolaryngology clinics. However, the etiology of SSNHL remains unclear. Due to the inaccessibility of the living human inner ear for biopsy, studies investigating the etiology of SSNHL have been performed by analyzing data obtained from examinations using peripheral blood or imaging. We updated the findings obtained from serological, magnetic resonance imaging, genetic, and viral examinations to reveal the etiology of SSNHL. Regarding viral examination, we focused on sensorineural hearing loss associated with coronavirus disease (COVID-19) because the number of correlated reports has been increasing after the outbreak. The updated findings revealed the following three possible mechanisms underlying the development of SSNHL: thrombosis and resulting vascular obstruction in the cochlea, asymptomatic viral infection and resulting damage to the cochlea, and cochlear inflammation and resulting damage to the cochlea. Thrombosis and viral infection are predominant, and cochlear inflammation can be secondarily induced through viral infection or even thrombosis. The findings about sensorineural hearing loss associated with COVID-19 supported the possibility that asymptomatic viral infection is one of the etiologies of SSNHL, and the virus can infect inner ear tissues and directly damage them.

Inflammasomes are large multimeric protein complexes which regulate the activation of the proinflammatory cytokines interleukins-1β and−18 and inflammatory cell death called pyroptosis. NLRP1, NLRP3, NLRC4, AIM2, and pyrin can induce the formation of inflammasomes. Of these, the NLRP3 inflammasome is the most well-characterized. Recent studies revealed that variants of the NLRP3 gene cause genetic diseases, including systemic inflammatory syndrome called cryopyrin-associated periodic syndrome (CAPS) and non-syndromic sensorineural hearing loss DFNA34. NLRP3 variants cause CAPS and DFNA34 by constitutively activating the NLRP3 inflammasome and increasing IL-1β release. Patients with CAPS show systemic inflammatory symptoms, and hearing loss is a characteristic feature. Patients with CAPS and DFNA34 show progressive bilateral sensorineural hearing loss. Hearing loss has unique characteristics that can be improved or stabilized by anti-interluekin-1 therapy, although it is usually difficult to alleviate genetic hearing loss by drugs. However, it should be noted that there is a window of opportunity to respond to treatment, and younger patients are most likely to respond. It is important to know the characteristics of CAPS and DFNA34 for early diagnosis, and mutation analysis of NLRP3 will lead to a definite diagnosis. In this review, we summarize the current understanding of the mechanisms of the NLRP3 inflammasome and characteristics of patients with CAPS and DFNA34, especially focused on auditory and vestibular findings.

Objective: Habitual sniffing resulting from insufficient Eustachian tube closure is an important etiologic factor in the development and postoperative recurrence of pars flaccida cholesteatoma. In this study, we aimed to investigate the prevalence and clinical characteristics of cholesteatoma associated with habitual sniffing (sniff-related cholesteatoma) among patients with surgically indicated pars flaccida cholesteatoma. Study design: Prospective, multicenter, observational study. Setting: Twenty-six tertiary otologic referral centers. Patients: A total of 128 consecutive patients aged 15 years or above with newly diagnosed pars flaccida cholesteatoma (stage Ib or higher according to the Japan Otological Society staging system) were included. Interventions: None. Main outcome measures: The primary outcome was the prevalence of sniff-related cholesteatoma among patients with surgically indicated pars flaccida cholesteatoma. Patients were classified into 3 groups based on the presence of habitual sniffing episodes and the results of the sniffing test: sniff-related cholesteatoma (both positive), non–sniff-related cholesteatoma (both negative), and others. Demographic and clinical characteristics, including age and sex, were compared among the 3 groups. Results: Among the 128 patients, 53 (41.4%) were classified as having sniff-related cholesteatoma. Furthermore, patients in the sniff-related cholesteatoma group were significantly younger than those in the non–sniff-related group. Conclusions: Approximately 40% of patients with surgically indicated pars flaccida cholesteatoma had sniff-related cholesteatoma, suggesting an association with insufficient Eustachian tube closure. The careful assessment of habitual sniffing may be essential for elucidating disease pathophysiology and optimizing treatment strategies, including postoperative management.

Editorial: Autoinflammation of the inner ear