immune mediated inner ear disease is occasionally associated with other systemic autoimmune diseases , such as rheumatoid arthritis and wegener 's granulomatosis ( 1 ) . ( igg4)-related systemic disease is proposed to describe systemic manifestation of autoimmune disease characterized by increased serum level of igg4 and infiltration of igg4 positive plasma cells in the involved organs , presenting pancreatitis , sclerosing cholangitis , retroperitoneal fibrosis , lymphadenitis , nephritis , interstitial pneumonia , sialadenitis and prostatitis ( 2 - 4 ) . we report on a patient who showed fluctuating mixed hearing loss as one of the initial manifestations of igg4-related systemic disease , which has not been reported before . a 66-year - old woman was referred from the neurology department for bilateral tinnitus , hearing loss , and ear fullness that had progressed over the last two months . she also had headache , non - whirling type dizziness , left eyeball pain , arthralgia , and chronic cough . four tone average of pure tone thresholds of the right ear were 43 db ( bone conduction ) and 77 db ( air conduction ) , and those of the left ear 17 db and 32 db , respectively ( fig . 1 , october 2008 ) . since follow - up audiometry after 2 weeks of treatment of antibiotics showed the disease to have worsened ( fig . 1 , november 2008 ) , myringotomy and a ventilation tube was inserted in the right ear . the ear drum and middle ear mucosa was markedly edematous . spontaneous nystagmus under frenzel glasses was absent , but an alternating bithermal binaural caloric test showed complete canal paresis of the right side . the direction of nystagmus was not changed with ice water irrigation from supine to prone position . temporal bone computed tomography ( ct ) showed partial haziness in the middle ear and mastoid space and thickening of the tympanic membrane and middle ear mucosa . it looks like mild pituitary gland enlargement or inflammatory haziness around pituitary fossa . because of unilateral orbital pain and near the orbital apex lesion on mri , neurologist suspected tolosa - hunt syndrome , and tried steroid therapy ( prednisolone 60 mg per day for 25 days and then 30 mg per day for 15 days ) . during the steroid treatement , , hearing loss was aggravated again ( fig . 1 , february 2009 ) and left eyeball pain and cough relapsed about two months after steroid therapy . a chest ct was checked to evaluate cough , and it revealed multiple nodules in both lower lung fields and renal mass . light microscopic examination showed dense lymphoplasma cell infiltration in the lacrimal gland , kidney and bronchial mucosa . immunostaining for igg4 showed strong immunoreactivity for igg4 in infiltrating lymphocytes and plasma cells ( fig . g / l ) . based on multiple organ involvement , elevated serum level of igg4 , and infiltration of igg4 positive cells in the pathologic findings , we could diagnose igg4 related systemic disease . we started immunosuppressive treatments consist of methylprednisolone at 60 mg per day and methotrexate at 12.5 mg per week , and her general condition and hearing markedly improved ( fig . immunosuppressive therapy ( prednisolone at 25 mg per day and methotrexate at 15 mg per week ) , there was further improvement of air - bone gap as well as bone conduction threshold ( fig . the dose of prednisolone was gradually tapered and she has been treated with 5 mg daily without further symptoms . this disease is known that it involves various organ and can be diagnosed by elevated serum igg4 level and infiltration of igg4 positive cells in the involved organs . since hamano reported high serum igg4 concentrations in patients with autoimmune pancreatitis ( 5 ) , many authors reported multiple organ disease with hypergammaglobulinemia ( 3 , 4 ) . an autoimmune mechanism is assumed in patients with bilateral progressive or fluctuating mixed hearing loss , especially when they respond to immunosuppressive treatment . similar clinical characteristics were also found in the described patient with igg4-related systemic disease , which suggests the inner ear can be the target of this systemic autoimmune disease . in addition , the severity of air - bone gap parallels the severity of sensorineural hearing loss , and fluctuates according to the course of immunosuppressive therapy . therefore , otitis media was a part of this systemic disease and reflecting that respiratory epithelium including middle ear mucosa can be the target in igg4-related systemic disease . vestibular dysfunction may progress slowly , hence the patient 's dizziness was non - whirling nature without definite history of vertigo or imbalance . oral prednisolone is usually started at 30 - 60 mg / day , and then it is tapered by 5 mg every 1 - 2 week . serological and imaging tests are followed periodically after commencement of steroid therapy . continued maintenance therapy with prednisolone 5 mg / day is sometimes required to prevent relapse without complete discontinuation of steroids ( 3 , 4 ) . in cases of autoimmune inner ear disease , maintenance dose is continued for a variable time but the patients with treatment duration of fewer than 6 months are at increased risk of relapse compared with those treated for 6 months or longer . igg4-related systemic disease is an emerging clinical entity , involving diverse organs and systems including the middle ear and the inner ear .
igg4-related systemic disease , including autoimmune pancreatitis , is a multi - organ disorder characterized by elevated serum immunoglobulin g4 ( igg4 ) concentration and igg4-positive plasma cell infiltration . 
 we report a case of a 66-year - old woman with igg4-related hearing disorder , presenting with fluctuating mixed hearing loss with middle ear effusion . 
 the serum igg4 level was elevated and pathological examination revealed dense infiltration of igg4-positive lymphocyte in the renal parenchyma , lung tissue and lacrimal gland . with intravenous methylprednisolone at a dose of 60 mg daily , improvement of hearing loss were observed . 
 no recurrence was observed for 6 months with mainternance of prednisolone and methotrexate .