Ear, nose and throat (ENT) manifestations are an important hallmark of inflammatory
rheumatic diseases, varying from mild to life-threatening manifestations. They can
be the first symptoms or occur during the course of the disease. The correct identification
of the underlying physiopathology (inflammation, thrombosis or infection) and proper
treatment of ENT symptoms are therefore of importance in diagnosis and followup of
patients with inflammatory rheumatic disease. Many classification criteria include
ENT manifestations, such as granulomatosis with polyangiitis (GPA), Behçet disease
(BD), relapsing polychondritis (RP), eosinophilic granulomatosis with polyangiitis
(EGPA) and Cogan syndrome (GS). Other autoimmune/autoinflammatory diseases are characterized
by widespread inflammation and may present with ENT symptoms, such as sarcoidosis,
rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE)
and systemic sclerosis (SSc).1, 2, 3, 4, 5
In this editorial, we will review on the main ENT manifestations that have been described
in inflammatory rheumatic diseases.
Auricular chondritis is present in 20% at the onset of RP and 90% during the course
of the disease. The entire ear is swollen, red and painful at contact. The continuous
inflammation can result in pinna cauliflower deformity or ossification of the connective
tissue. RP is characterized by a rare multisystem disease accepted as a complex autoimmune
disorder affecting proteoglycan-rich structures and cartilaginous tissues, especially
the auricular pinna, cartilage of the nose, tracheobronchial tree and various organ’s
connective components. Auricular chondritis can also be observed in GPA. It is a rare
autoimmune disorder characterized by granulomatous inflammation and small-vessel vasculitis
associated with antineutrophil cytoplasmic antibodies (ANCA). GPA has a broad clinical
spectrum that ranges from predominantly granulomatous manifestations restricted to
the respiratory tract to severe, life-threatening necrotizing vasculitis.1, 2, 3
Otalgia, secretory otitis media and otorrhea can be observed in GPA and imunoglobulin
G4 related disease (IgG4-RD). IgG4-RD is a chronic inflammatory disease that involves
many tissues such as pancreas, lacrimal and salivary glands. Ear manifestations are
more common in the middle ear, and the inner ear is rarely affected. Recurrent mastoiditis
and facial numbness can also be observed.
Sensorineural hearing loss (SNHL) can be observed in a variety of systemic autoimmune/autoinflammatory
diseases, having a prevalence of 21-69% for RA, 8-28% for SLE, 21-46% for SS and 20-77%
for systemic sclerosis. Possible mechanisms include disease related (vasculitis, thrombosis
or antibody-mediated) and medication related (ototoxic effect). The presence of vestibuloauditory
symptoms, as sudden onset tinnitus and vertigo that can present with nausea, vomiting,
ataxia and nystagmus in association especially with non-infectious interstitial keratitis,
but also other symptoms (conjunctivitis, uveitis, episcleritis, scleritis, optic neuritis)
should raise the suspicion of Cogan Syndrome (CS).1, 2
SNHL in association with increased inflammatory markers and the presence of recurrent
fever in the absence of infection should alert otolaryngologists to the possibility
of autoinflammatory diseases. Systemic autoinflammatory diseases (SIAD) are a group
of disorders caused by a dysregulation of the innate immune system. One of most common
monogenic SIAD associated with hearing loss is mutation of NOD- like receptor gene
(NLRP3), a condition known as NLRP3-associated autoinflammatory disease (NLRP3-AID),
formerly known as Cryopyrin-associated periodic syndrome (CAPS). Muckle Wells syndrome
(MWS) is the intermediate form of CAPS and can develop to progressive SNHL, secondary
to chronic inflammation of the internal ear. SNHL in MWS often rapidly progresses
from mild high tone deficits to complete deafness. Early hearing loss primarily affects
high frequencies of > 6 kHz reflecting the characteristic high sensitivity pattern
of hair cells to injury as described in other systemic conditions. Cochlear enhancement
on fluid attenuation inversion recovery MRI (FLAIR- MRI) is more frequent in patients
with a higher prevalence of hearing loss, providing some insight into the mechanisms
of SNHL in MWS.
Nose and sinus involvement
Nasal involvement in GPA is present in approximately 42% of patients. Other associated
symptoms related to GPA activity are nasal inflammation, chronic sinusitis, and nasal
crusting with or without bloody rhinorrhea.
Nasal chondritis can affect up to 15% of patients of RP. The inflammation involves
the bridge of the nose, causing nasal pain, redness and swelling, being less marked
than the ears. Nasal obstruction is rare. Both RP and GPA can progress to permanent
damage, such as characteristic ‘saddle-nose’ deformity or septal perforation.
EGPA is a rare necrotizing ANCA-associated vasculitis. EGPA is characterized by the
presence of asthma, peak blood eosinophilia and small-size vessel vasculitis. There
are many nasal manifestations associated with the disease, such as chronic sinusitis,
nasal crusting, allergic rhinitis and bilateral diffuse polyposis. The presence of
these manifestations associated with vasculitis in biopsy or ANCA positivity should
rise the suspicion of EGPA.
Sicca syndrome is by far the most frequent oral manifestation in autoimmune diseases,
being present in more than 95% of patients with SS. Xerostomia may lead to secondary
problems like oral candidiasis, dental caries and periodontal disease. In addition
to that, sicca symptoms can lead to hoarseness and non-productive cough. Recurrent
parotitis is present in 30-50% of patients and is characterized by a firm, diffuse,
non-tender swelling. It is important in differentiate it from recurrent juvenile parotitis,
where ANA antibodies are generally absent.
BD is a systemic vasculitis, affecting vessels of variable sizes. It is characterized
by a myriad of systemic manifestations, including mucocutaneous, arthritis, vascular,
neurological and gastrointestinal. Recurrent oral ulceration is the most frequent
presenting ENT symptom (95% of patients), typically being multiple and variable size
(2-20 mm) and occur extensively on the buccal membrane, tongue, palate and in the
oropharynx. The ulcers are classically painful, surrounded by erythema and the larger
ones heal with scarring. Six or more painful, recurrent ulcers, of variable size with
surrounding erythema occurring on the soft palate or oropharynx should heighten suspicion
of BD.1, 2
SLE mucous membrane involvement is characterized by oral ulcers. Classical lesions
are asymptomatic, occur at the hard palate and are characterized by whitish plaques
with erythema in the center and keratotic striae in the periphery with areas of telangiectasia.1,
Laryngeal chondritis is an important symptom of RP and it manifests as pain above
the thyroid gland and dysphonia, causing laryngomalacia or stenosis in more severe
cases. Hypoglottic stenosis, due to granulomatous inflammation of GPA occurs in 2-20%
and is a potential life-threatening complication and is associated with systemic involvement.
Dyspnea, voice changes and cough are the most common symptoms, and audible stridor
is present in most severe cases.
RA is a chronic inflammatory disease characterized by symmetrical inflammatory joint
disease that may evolve to joint damage and bone destruction. Laryngeal manifestations
of RA involve cricoarytenoid joint (CJ) arthritis and rheumatoid nodules. The symptoms
of CJ arthritis in the acute stage are often fullness in the throat or a feeling of
tension, in addition to hoarseness, odynophagia or dysphagia, as well as pain worsening
by speaking. Chronic disease can be manifest by a husky voice and stridor.1, 2
In summary, inflammatory rheumatic are rare diseases that present with a wide spectrum
of ENT manifestations. A high index of suspicion is necessary for timely diagnosis.
ENT specialists have a crucial role in referring patients with possible inflammatory
diseases to rheumatologists.
National Council for Scientific and Technological Development (CNPQ): 306723/2019-0.
Coordination of Superior Level Staff Improvement (CAPES): 001.
Conflicts of interest
The authors declare no conflicts of interest.