granulomatosis with polyangiitisis ( gpa ) is an idiopathic systemic form of vasculitis characterized by involvement of the upper and lower airways and the kidneys .
the exact cause of gpa is unknown , but it seems to have characteristics of an autoimmune disease .
ent manifestations are present in the vast majority of patients ( 73 - 99% ) , and are usually among the first symptoms . occasionally , ear conditions are the first and only manifestations . therefore , ent physicians have a determining role in recognizing the early onset of this disease and starting the proper therapy . current first line induction therapy for gpa consists of cyclophosphamide with glucocorticoids , which is successful in most ( 70 - 90% ) patients .
although a few patients presenting with otologic symptoms and treated with conventional therapy , such as cytotoxic drugs and steroids , have been described , this case was a rare and meaningful report in otology to date of a patient presenting with unilateral facial nerve palsy and bilateral profound sudden sensorineural hearing loss with vertigo .
we describe here a patient with a resistant fulminant generalized form of gpa initially presenting as bilateral sudden sensorineural hearing loss and facial palsy .
a 47-year - old man visited our hospital due to symptoms of facial paralysis on the left side and abrupt hearing disturbance with dizziness in both ears three days earlier . in physical examination ,
1 ) . at the time of visit to our hospital , impedance audiometry ( grason - stadler gsi 33 middle - ear analyzer ; viasys , conshohocken , pa , usa ) was b - type on both sides ; and pure tone audiometry ( grason - stadler gsi 61 clinical ; nicolet biomedical , madison , wi , usa ) was 95 db on the right side and off scale on the left side ( fig .
tests of auditory brainstem response found that the right side formed a v - wave at 80 nhl , whereas the left side did not form a v - wave at 90 nhl .
computed tomography scans ( general electric medical systems , milwaukee , wi , usa ) showed dense fluid in both external ears and middle ears but no facial canal dehiscence ( fig .
simple chest x - rays showed multiple nodules in both lung fields , while ct of the chest showed that chest cavity was filled with multiple nodules ( fig .
immunological tests showed significantly higher than normal proteinase-3 anti - neutrophil cytoplosmic antibodies ( anca ) representing c - anca . a definitive diagnosis required a lung biopsy sample .
following discharge from the hospital , the patient began coughing severely and developed a continuous fever of about 38. in addition , hearing ability again deteriorated .
chest ct showed increased size and number of nodules in the fine structure of the lungs ( fig .
a lung biopsy sample was obtained , and he was started on high - dose intravenous steroids 500 mg / day for three days .
after six days , c - reactive protein ( crp ) tended to decrease from 18.04 to 4.36 , but he showed no improvement in other symptoms including fever . a lung biopsy taken on day six showed necrotizing granulomatous inflammation with intra alveolar hemorrhagic exudates and capillaritis ( fig .
the patient was started on 1000 mg / day cyclophosphamide , along with steroids , two - week interval . however , erythrocyte sedimentation rate , crp and fever all remained high .
he was therefore administered four infusions of rituximab ( mabthera ; roche pharma , basel , switzerland , 500 mg each ) , an anti - cd20 monoclonal antibody , at two week intervals , along with concurrent iv cyclophosphamide ( endoxan ; bukwang pharm , seoul , korea , 500 mg twice a month for 3 months ) .
after rituximab administration , symptoms including cough , fever , and otologic symptoms , improved significantly . to improve hearing , he received seven intratympanic injections of steroids through the ventilation tubes in each ear .
after four months , pure tone audiometry improved on the right side to 32 db ( fig .
2b ) but did not improve on the left side , and left side facial paralysis improved from hb grade 5 to hb grade 2 . written informed consent was obtained from the patient who participated in this case .
gpa is a relatively rare disease , so treatment focusing on local symptoms in the absence of an accurate diagnosis may have no effect , or even worsen the disease , with the possibility of a secondary infection .
thus , an accurate initial diagnosis and subsequent treatment with steroids and , if necessary , immunosuppressive drugs , are important . the american college of rheumatology ( acr ) criteria for confirming the diagnosis of gpa was found to have a sensitivity of 88.2% and a specificity of 92% .
a diagnosis of gpa requires at least two of the following four criteria : 1 ) hematuria ( more than 5 red blood cells per visual field or the presence of erythrocyte casts ) , 2 ) changes in chest radiographs , 3 ) ulceration of the mouth and/or nose , and 4 ) positive histopathological examination . in addition
about 80 - 90% of these patients are positive for anca , which damage vascular endothelium and cause its necrosis . in evaluating our patient , we initially focused on the areas usually involved in gpa , including the upper and lower airways and the kidneys .
a lung biopsy sample taken from our patient showed necrotizing granulomatous inflammation with intraalveolar hemorrhagic exudates and capillaritis .
he also had intranasal inflammation and nodules and cavities in the chest , thereby satisfying more than two of the four acr criteria .
otologic involvement may include otitis media with effusion , chronic otitis media , sensorineural hearing loss , vertigo , and/or facial palsy .
proposed mechanisms include cochlear nerve compression by an adjacent granuloma , cochlear immune - complex deposition , and local vasculitis involving cochlear vessels .
progression is generally rapid ; however , the condition is occasionally reversible with glucocorticoids or cytotoxic agents .
our patient presented with the otologic symptoms of unilateral facial palsy and bilateral sudden sensorineural hearing loss with vertigo .
hearing loss was likely due to recurrent serous and/or suppurative otitis media and/or sensorineural hearing loss .
sensorineural and conductive hearing loss occurred with similar frequencies , 47% and 33% , respectively , but the latter showed a better response to treatment , indicating a poorer prognosis in patients with sensorineural hearing loss .
the right side hearing threshold in our patient improved to 32 db , but left side showed no improvement .
facial nerve palsy in association with gpa is rare , being present in about 5% of patients , either alone or in combination with hearing loss ; rarely , facial nerve palsy may be the presenting feature .
facial nerve palsy is secondary to compression of the nerve in the middle ear , especially in the presence of a dehiscent facial nerve canal or due to vasculitis .
differential diagnosis is important in patients with facial nerve palsy ; other diseases should be considered , such as chronic otitis media and systemic vascular diseases , including sarcoidosis , polyarteritis nodosa and tuberculosis .
the standard treatment for systemic gpa is an immunosuppressive drug such as cyclophosphamide to alleviate the disease , along with a glucocorticoid .
if these regimens are ineffective , the patient should be treated with rituximab , a chimeric monoclonal antibody directed against cd20 that induces b cell apoptosis and depletion in peripheral blood .
the importance of anca in the pathogenesis of gpa suggests that rituximab reduces anca by depleting b cell concentrations .
this study describes a patient with a rare type of multi - organ involved , treatment resistant , fulminant form of gpa initially presenting as bilateral profound sudden sensorineural hearing loss with vertigo and unilateral facial palsy and illustrates the dramatic effects of rituximab .
 granulomatosis with polyangiitisis [ ( gpa ) or wegener granulomatosis ] is a multi - system disease characterized by granuloma formation and necrotizing vasculitis . 
 gpa classically shows involvement of the respiratory tracts and the renal system 
 . however , locoregional disease is common and may include otologic manifestations . 
 although otologic involvement can occur during the course of gpa , no report has described facial palsy with sudden sensorineural total deafness with vertigo as the presenting feature of gpa . 
 this case describes a patient with multiorgan involving resistant form of gpa initially presenting with bilateral profound sudden sensorineural hearing loss and left facial paralysis with vertigo . 
 the condition responded well to treatment with rituximab . 