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Page 2 of 18 Padoan et al. Vessel Plus 2021;5:41 https://dx.doi.org/10.20517/2574-1209.2021.41

INTRODUCTION
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a group of multi-
system autoimmune disorders, characterized by inflammation of small - to medium-sized vessels,
endothelial injury, and tissue damage. According to the 2012 revised Chapel Hill Consensus Conference
[1,2]
nomenclature of vasculitides and the American College of Rheumatology (1990) classification criteria ,
AAV are classified into three distinct disease phenotypes: granulomatosis with polyangiitis (GPA, formerly
known as Wegener’s granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis
with polyangiitis (EGPA, Churg-Strauss syndrome).

Autoimmunity is documented by serum antibodies targeting cytoplasmic component of neutrophils,
specifically proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA), due to loss of tolerance to
neutrophil primary granule proteins . ANCAs appear more closely associated with a vasculitic
[3]
[4,5]
inflammation , while granulomatous phenotype is predominantly linked to ANCA-negative serology and
localized disease .
[6,7]
Any organ or tissue may be involved in AAV, with clinical presentation ranging from severe organ-
[8]
threatening or life-threatening disease to less severe presentation or organ-limited manifestations . GPA
and MPA commonly affect the upper respiratory tract, lungs, and kidneys, often at the same time, while
EGPA is characterized by asthma, hyper-eosinophilia, and heart and peripheral nervous system
involvement . However, EGPA is characterized by two different subsets, reflecting distinct underlying
[9]
pathogeneses: a predominant “vasculitic phenotype” closely associated to ANCA and an “eosinophilic
phenotype”, which is interleukin-5 (IL-5) driven .
[10]

Ear, nose, and throat (ENT) represent some of the most common sites of AAV manifestations, more often
in GPA and EGPA, which generally precedes pulmonary or renal involvement. Although patients with ENT
symptoms have better survival [7,11] and less renal involvement [7,12] , they typically present a relapsing
[13]
disease .
Typical ENT symptoms may include sinonasal, otologic, pharyngeal, and laryngeal manifestations
[Figure 1]. Up to 95% of GPA patients show evidence of head and neck features and 85% have evidence of
nasal or sinus problems [7,14] . In EGPA, head and neck manifestations could occur in 48%-96% of the cases at
diagnosis [15,16] . Finally, involvement of head and neck organs in MPA is less common, being reported in
20%-30% of the patients .
[17]

The otolaryngologic symptoms of GPA sometimes might be misdiagnosed in etiology as infectious or
allergic. Thus, rapid recognition and early diagnosis of AAV as the cause of the symptoms prevent the risk
of irreversible organ damage. Appropriate interdisciplinary management for early recognition of AAV and
initiation of treatment may reduce morbidity in these patients.

The purpose of this comprehensive review is to describe the clinical, histological, and radiological features
of ENT involvement in AAV and to update their surgical and therapeutic management, with a focus also on
the role of a multidisciplinary team, involving the otorhinolaryngologist.

SINONASAL MANIFESTATIONS
The most frequently observed ENT manifestation of GPA is sinonasal involvement, being present in 60%-
85% of patients [7,18] . One of the first manifestations is nasal blockage, in association with hyposmia or
anosmia when mucosal swelling occurs . Purulent nasal drainage associated with the growth of
[19]