Abstract
IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity effecting the head and neck region. Although most commonly seen with salivary gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone and skull base. We report a rare care of a 61-year-old female with IgG4-RD presenting as synchronous lesions of the middle ear and middle cranial fossa with polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological evaluation of her resected ear mass suggested a benign inflammatory process but no specific diagnosis. Her symptoms progressed over 10 months prompting re-evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key pathologic features included prominent lymphoplasmacytic population, storiform fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was treated with high-dose intravenous and oral steroids but was transitioned to azathioprine secondary to steroid-induced myopathy. Radiographic studies before and after treatment reveal marked improvement of the intracranial and extracranial disease. Correspondingly, her cranial neuropathies resolved. A high degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can be supported by elevated serum IgG, elevated IgG index, and pathognomonic histopathological findings. Primary treatment is with corticosteroids. However, immunotherapy using azathioprine or rituximab can be utilized in recurrent disease or patients with steroid intolerance.
1
Introduction
Increasing awareness of IgG4-related disease (IgG4-RD) is helping to characterize this once nebulous disorder. Originally described in the context of autoimmune pancreatitis, IgG4-RD has now been found in nearly all regions of the body The disease has become an important differential diagnosis when considering autoimmune, vasculitic, or inflammatory diseases . Still, there remains much to learn about the diagnosis, biological behavior, and treatment of IgG4-RD.
IgG4-RD has been described in many head and neck locations but most commonly involves the salivary glands . Other frequently involved organs include the lacrimal glands, orbital adnexa, nasal cavity, paranasal sinuses, thyroid, and lymph nodes . The frequency of these subsites being effected is largely unknown as epidemiologic data remains rudimentary. It is understood that many previously named diseases like Mikulicz’s syndrome, Kuttner’s tumor, and Riedel’s thyroiditis fall within the IgG4-RD spectrum . A recent series of 51 patients with IgG4-related sialadenitis found that 78.4% of patients also have lacrimal gland involvement, 74.5% have lymphadenopathy, 58.8% have rhinosinusitis, and others may have otologic, skin, or cranial nerve involvement . Skull base involvement of IgG4-RD has also been described with most accounts being extension from paranasal disease . Orbital disease tends to afflict the periorbital adnexa and very rarely causes compressive optic neuropathy .
Otologic and skull base manifestations of IgG4-RD are less common than the previously listed subsites but the true spectrum of the skull base disease burden and cranial neuropathies remains unknown. Here, we report a rare case of IgG4-RD presenting as synchronous middle ear and middle cranial fossa masses with ipsilateral cranial polyneuropathy that responded clinically and radiographically to corticosteroids and immunotherapy. To our knowledge this is the first reported case with simultaneous facial and optic nerve involvement. We also provide a literature review of IgG4-RD as it pertains to the ear and skull base.
2
Case report
A 61-year-old woman with a history of hypothyroidism and allergic rhinitis presented to the Neurotology Clinic of University Hospitals Case Medical Center with progressive right otalgia and conductive hearing loss. She was found to have a right middle ear mass and radiologic studies showed extension to the petrous apex and encasement of the carotid artery, but no intracranial involvement ( Fig. 1 ). A mastoidectomy was performed demonstrating a large, unencapsulated, avascular mass filling the middle ear and causing local destruction of the stapes. The mass was biopsied and pathology demonstrated lymphoblastic inflammation without evidence of malignancy. A diagnosis of inflammatory pseudotumor was made and she received a three-month prednisone taper with good clinical response.
Ten months later she represented with new right-sided visual impairment. Examination revealed a right pupillary afferent defect, 20/100 right-sided visual acuity, and right cranial nerve VI and VII palsies. Her right facial weakness was a House-Brackmann 5 out of 6. Brain magnetic resonance imaging (MRI) demonstrated a dural-based homogenous enhancing mass extending from the cavernous sinus into the middle and posterior cranial fossae with enhancement of the internal auditory canal (IAC) and geniculate ganglion. Computed tomography (CT) showed recurrence of the right middle ear mass ( Fig. 2 ). Histologic review of the previous mastoid biopsy showed plasmacytic infiltration, storiform fibrosis, and phlebitis. IgG4 staining was positive for >50 cells/HPF ( Fig. 3 ). Serum IgG4 level was normal. Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis (81 cells), elevated IgG index (2.2, normal <0.66), and unremarkable cytology/flow cytometry. A diagnosis of IgG4-RD was made on the basis of the histologic features and staining. She was treated with high dose intravenous dexamethasone and discharged home on prednisone 40 mg daily. Three months after initiating treatment her visual acuity improved to 20/50 OD, she had a normal pupillary response, and no facial weakness. Nine months into treatment, despite tapering the prednisone to 15 mg daily she developed steroid-induced myopathy and had to be transitioned to azathioprine 150 mg daily. Repeat MRI at 3 months, 12 months, and 21 months showed dramatic improvement in pachymeningeal disease ( Fig. 4 ). She continues to have a conductive hearing loss for which she uses a hearing aid. The patient has been followed for 33 months without evidence of recurrence. She remains on azathioprine 150 mg daily.
2
Case report
A 61-year-old woman with a history of hypothyroidism and allergic rhinitis presented to the Neurotology Clinic of University Hospitals Case Medical Center with progressive right otalgia and conductive hearing loss. She was found to have a right middle ear mass and radiologic studies showed extension to the petrous apex and encasement of the carotid artery, but no intracranial involvement ( Fig. 1 ). A mastoidectomy was performed demonstrating a large, unencapsulated, avascular mass filling the middle ear and causing local destruction of the stapes. The mass was biopsied and pathology demonstrated lymphoblastic inflammation without evidence of malignancy. A diagnosis of inflammatory pseudotumor was made and she received a three-month prednisone taper with good clinical response.
Ten months later she represented with new right-sided visual impairment. Examination revealed a right pupillary afferent defect, 20/100 right-sided visual acuity, and right cranial nerve VI and VII palsies. Her right facial weakness was a House-Brackmann 5 out of 6. Brain magnetic resonance imaging (MRI) demonstrated a dural-based homogenous enhancing mass extending from the cavernous sinus into the middle and posterior cranial fossae with enhancement of the internal auditory canal (IAC) and geniculate ganglion. Computed tomography (CT) showed recurrence of the right middle ear mass ( Fig. 2 ). Histologic review of the previous mastoid biopsy showed plasmacytic infiltration, storiform fibrosis, and phlebitis. IgG4 staining was positive for >50 cells/HPF ( Fig. 3 ). Serum IgG4 level was normal. Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis (81 cells), elevated IgG index (2.2, normal <0.66), and unremarkable cytology/flow cytometry. A diagnosis of IgG4-RD was made on the basis of the histologic features and staining. She was treated with high dose intravenous dexamethasone and discharged home on prednisone 40 mg daily. Three months after initiating treatment her visual acuity improved to 20/50 OD, she had a normal pupillary response, and no facial weakness. Nine months into treatment, despite tapering the prednisone to 15 mg daily she developed steroid-induced myopathy and had to be transitioned to azathioprine 150 mg daily. Repeat MRI at 3 months, 12 months, and 21 months showed dramatic improvement in pachymeningeal disease ( Fig. 4 ). She continues to have a conductive hearing loss for which she uses a hearing aid. The patient has been followed for 33 months without evidence of recurrence. She remains on azathioprine 150 mg daily.
