Page 24 - Read Online

Page 6 of 18 Padoan et al. Vessel Plus 2021;5:41 https://dx.doi.org/10.20517/2574-1209.2021.41

Less commonly, localized AAV may presents only with otologic symptoms, without evidence of other
AAV-related organ lesions. In these patients, not fulfilling the classification criteria for systemic vasculitis,
the term OMAVV (otitis media with AAV) has been proposed [40,41] . Clinical criteria for OMAVV are
reported in Table 1. Hearing loss represents the most common initial symptom, often associated with
otorrhea, tinnitus, and vertigo or dizziness. Pachymeningitis or facial palsy may complicate the clinical
course of OMAVV. An irreversible complete deafness despite treatment may develop in 3.5%-7.2% of
patients .
[40]

TRACHEOBRONCHIAL MANIFESTATIONS
Large airways involvement, in the form of tracheobronchial disease, is a less common GPA
[42]
manifestation . Subglottic stenosis (SGS) is the most frequent tracheobronchial stenosis type, with an
estimated frequency of 16%-23% in adult patients with GPA, while it can be considered uncommon or even
exceptional in EGPA [42-44] [Figure 2]. It is one of the most common manifestations of ENT involvement in
pediatric subjects . SGS is defined as narrowing of the subglottic area within the cricoid cartilage that
[45]
[46]
can lead to upper airway obstruction and potentially life-threatening consequences . Involvement of the
[47]
[48]
glottic and supraglottic larynx may less frequently occur, resulting in multilevel airway stenosis . Stenosis
may also extend into the distal trachea and bronchi including ulcerating tracheobronchitis with or
[48]
without inflammatory pseudotumors .
[49]
SGS patients are commonly female and younger (26-40 years) than patients with tracheobronchial
stenosis [45,47] .

The pathogenesis of subglottic stenosis in GPA remains unclear [50,51] , but the association of a vasculitic
process in the setting of active inflammation due to laryngopharyngeal reflux [44,52] and mechanical forces
[53]
related to turbulent subglottic airflow may synergistically produce a hyperactive healing response that
[50]
leads to cartilaginous fibrotic scarring and stenosis .

Subglottic stenosis likely increases gradually, allowing the patient to adjust his breathing pattern until a
critical stenosis is reached. Typically, patients remain mild symptomatic or asymptomatic until about 75%
of airway stenosis (60% in children) is reached . Some patients report “asthmatic-like” symptoms for many
[50]
years before diagnosis . Patients with SGS may develop symptoms gradually, from non-specific cough,
[43]
hoarseness, shortness of breath, pharyngodynia, hemoptysis, or vocal changes, finally to stridor or dyspnea
on exertion when a critical point of stenosis is reached [18,54,55] . As the airway caliber narrows, obstruction may
result from crusts, mucous plug, and thick secretions caused by inflammation of the mucosa or infections,
as well as the subglottic lesion itself [50,56] . Unilateral or bilateral vocal cord fixation can be a consequence of
cricoarytenoid joint involvement . Occasionally, patients presenting with acute obstruction require
[57]
[18]
emergency tracheostomy . Recognition of active tracheobronchial or SGS in GPA can be challenging
because SGS seems to progress irrespective of systemic GPA disease activity [43,53] . It may present as the first
[48]
symptom or as a late manifestation of the disease . Patients with subglottic inflammation are more likely to
be ANCA negative and to have endobronchial disease, ENT manifestations (destructive sinonasal disease
[47]
[47]
as well), pulmonary manifestations, and constitutional symptoms , and they less frequently have nervous
system and renal involvement . The presence of SGS must be urgently investigated in patients with GPA
[49]
who develop respiratory symptoms, even in the absence of another disease flare [47,50] .
Even though SGS in GPA is a serious and potentially life-threatening complication, no standardized
diagnostic and therapeutic approach exists. It is still debated which diagnostic methods should be
recommended (serial bronchoscopies, lung function tests, and virtual endoscopy) for diagnosis and follow-