9 Autoimmune Otologic Disorders

Lehnhardt1 suspected as early as 1958 that bilateral hearing loss was secondary to anticochlear antibodies. In 1974 Schiff and Brown² speculated that improvement of sudden hearing loss following administration of adrenocorticotropic hormone (ACTH) and heparin was evidence of an autoimmune etiology. It was in 1979, however, that McCabe³ first reported on a series of 18 patients with sensorineural hearing loss (SNHL) who responded to steroids and cyclophosphamide. He named this distinct clinical entity “autoimmune sensorineural hearing loss.” Available tissue in one of his patients revealed vasculitis.

Since then, several reports have described this entity mainly as “autoimmune inner ear disease.” Because it has been recognized by now that immune-mediated processes affect not only the inner ear but also the auricle (relapsing polychondritis), the middle ear (rheumatoid arthritis), and retrocochlear structures (multiple sclerosis), the term autoimmune otologic disorders (AODs) is perhaps more appropriate.

Immunity of the Inner Ear

The immunity of the inner ear is similar to that of the brain.⁴ It lacks lymphatic drainage and is separated from the serum by the blood–labyrinthine barrier, which helps to maintain the ionic balance of the inner ear fluids.⁵ Immunoglobulins are present in the perilymph at approximately the same concentration as that of the cerebrospinal fluid (CSF), which is about one one-hundredth of the serum titer.⁶ White blood cells enter the cochlea through the spiral modiolar vein and are responsible for the local production of immunoglobulins.⁷

Lymphocytes are present in the endolymphatic sac; however, they are absent in the cochlea.⁵ The endolymphatic sac is considered to be the most immunoactive component of the inner ear and responsible for antigen processing in a fashion similar to that of the intestine as far as absorptive and immunologic functions are concerned. Antibodies from the endolymphatic sac can reach the perilymphatic space via the route of the endolymphatic duct.^8,9 Surgical destruction of the endolymphatic sac or obliteration of the endolymphatic duct has been found to reduce antigen and inflammatory responses as well as cochlear damage.⁵ This structure has been implicated in the pathogenesis of immune-mediated Meniere’s disease.¹⁰

Immune-mediated injury of inner ear tissues may result from a combination of different mechanisms. The most likely is antibody-dependent cytotoxicity (type II hypersensitivity) mediated by antibodies binding to cell antigen (s) with subsequent injury due to complement-dependent reactions, phagocytosis, or activation of nonsensitized Fc cells.¹¹

Antigenic molecules considered to be involved in autoimmune SNHL and Meniere’s diseases include type II collagens, type IX collagens, inner ear 30- and 68-kd proteins, laminin, PO protein, Raf I protein, and β-tubulin.¹² It needs to be mentioned, however, that antigenic targets within the inner ear are diverse, and therefore conclusive evidence for specific autoimmune damage to the inner ear is elusive.¹³ Recently, inner ear specific interferon-γ(IFN-γ)-producing proinflammatory T cells have been implicated in the pathogenesis of autoimmune SNHL.¹⁴

Autoimmune Otologic Disorders

Otologic autoimmune disorders can be either primary processes, which are also called organ-specific and are more common,5 or secondary to a systemic autoimmune disorder. The following are systemic autoimmune disorders with known otologic involvement.

Relapsing Polychondritis

Relapsing polychondritis (RP) is a rare episodic, multi-systemic, and progressive disease of presumed auto-immune etiology. It affects cartilaginous structures such as those of the auricle, nose, larynx, trachea, bronchi, and joints. Because this disease destroys supporting cartilage, saddle-nose deformities and tracheal collapse with severe airway obstruction are common. Additionally, it can affect the eyes, aorta, heart, and skin.¹⁵ The disease may also present with the audiovestibular symptoms, usually bilateral.¹⁶

Diagnosis of this entity is mainly clinical. Elevated erythrocyte sedimentation rate (ESR) may be present. Antibodies against cartilage and to type II and IX collagen can be present, which supports an autoimmune etiology of this entity.¹⁷

A standardized therapeutic protocol has not been established for this entity; however, steroids and nonsteroidal antiinflammatory drugs such as dapsone and colchicine may be effective.¹⁵ Relapsing polychondritis can be a potentially lethal disease. Respiratory infection, systemic vasculitis, airway obstruction, and renal failure are the most common causes of death.¹⁵

Cogan’s Syndrome

Cogan’s syndrome (CS) is a disorder affecting mainly young adults and consists of ocular, cochleovestibular symptoms and nonreactive serologic tests for syphilis.⁵ The etiology of this syndrome has been considered to be an autoimmune response to one or more infectious agents.¹⁸

The typical form of CS is characterized by interstitial keratitis and has excellent prognosis. Life-threatening aortic insufficiency and serious systemic necrotizing vasculitis are rare. Arthritis, inflammatory bowel disease, glomerulonephritis, and splenomegaly have been reported in association with this syndrome.¹⁹

Ocular involvement in the atypical form of CS may consist of uveitis, keratitis, episcleritis, or scleritis. This form is often associated with vasculitis and has a less favorable prognosis than the typical CS.²⁰

Cochleovestibular symptoms include episodic vertigo, tinnitus, and rapidly progressive hearting loss. These symptoms may develop 1 month to 2 years prior to or after the ocular manifestation of the syndrome.⁵ Symptomatology may resemble that of Meniere’s disease, and bilateral involvement is common. In a study of 18 patients with CS, 17 had vertigo and 13 bilateral fluctuating SNHL.²¹

Temporal bone findings in one case of CS were compatible with those seen in an autoimmune process and consisted of acute labyrinthitis with atrophy of inner ear tissues, endolymphatic hydrops, focal and diffuse proliferation of fibrous tissue and bone, and retrograde neuronal degeneration.²²

Systemic steroids and cytotoxic agents including methotrexate may be helpful in treating cochleovestibular symptoms.^23,24 Early diagnosis and aggressive treatment are imperative.

Vogt-Koyanagi-Harada Syndrome

Vogt-Koyanagi-Harada syndrome is a disorder with similarities to CS and is characterized by SNHL, dizziness, granulomatous uveitis, loss of eyelashes, depigmentation of the hair and skin around the orbits, and aseptic meningitis.⁵ The etiology is thought to be an autoimmune reaction to melanocytes and tissues containing these cells such as the skin, uvea, and inner ear.²⁵ In a study of 20 patients with Vogt-Koyanagi-Harada syndrome, all had bilateral eye involvement and 11 had SNHL.²⁶

Systemic steroids have been recommended for this disorder.²⁶ Although in most of the cases visual prognosis is fair following such treatment,²⁶ information regarding cochleovestibular symptoms is not available in the literature.

Wegener’s Granulomatosis

Wegener’s Granulomatosis is a disorder characterized by systemic vasculitis, focal glomerulonephritis, and necrotizing granulomas of the upper and lower respiratory tracts.²⁷ Diagnosis is made with biopsy of any suspicious middle ear or upper respiratory tract tissue and serologic testing for antineutrophil cytoplasmic antibody (ANCA).^28,29 Histopathologic study of a temporal bone from a patient with Wegener’s granulomatosis revealed involvement of the vessels of the endolymphatic sac without involvement of the vasculature of the rest of the inner ear.³⁰

Otologic involvement consists mainly of otitis media with effusion associated with obstruction of the nasopharynx.³¹ In a review of 112 patients with Wegener’s granulomatosis, 21 had ear involvement. Conductive hearing loss, present in all of them, was secondary to otitis media with effusion, suppurative otitis media, perforation of the tympanic membrane, and middle ear granulations. Nine patients also had SNHL, which improved after treatment with prednisone and cyclophosphamide in five of them.³² The combination of these two medications is considered the treatment of choice for this entity. Bilateral facial nerve paralysis has also been reported in association with this disorder.^33,34

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multisystemic disease that can affect the kidneys, heart, joints, central nervous system, eyes, and intestine. In a recent study, discoid lupus, proteinuria, and anti-Sm and anti-RNP autoantibodies were found more commonly in African American patients. Proteinuria, leukopenia, lymphopenia, and thrombocytopenia were approximately three times more common in men compared with women. The prevalence of oral or nasal ulcers and anti-DNA auto-antibodies declined with age.35

Several studies have shown that hearing loss and other otologic symptoms are more prevalent among patients with SLE.^36–38 However, in one study there was no increased incidence of hearing loss in such patients.³⁹ Circulating immune complexes and antiphospholipid antibodies have been implicated in the pathogenesis of hearing loss in SLE patients.⁴⁰

In a histopathology study of 14 temporal bones of seven patients with SLE, the following findings were identified: blue-staining concretions in the stria vascularis of six ears, loss of spiral ganglion cells with various degrees of hair cell loss, and atrophy of the stria vascularis was present in most of the ears. One ear demonstrated formation of fibrous tissue and bone throughout the cochlea with complete loss of the membranous labyrinth; cochlear hydrops was found in one ear.⁴¹

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder that primarily involves joints and affects women two to three times as often as men. The disease usually progresses from peripheral to more proximal joints, and in the majority of patients results in significant disability. Diagnosis, as in many other autoimmune diseases, is based on clinical manifestations and serologic testing. High rheumatoid factor RF titers (1:640) have diagnostic value.⁵ RF is of limited significance in patients older than 65.

In a series of 37 patients with RA, 35% were found to have SNHL, 24% conductive hearing loss, and 11% mixed hearing loss.⁴² In another prospective and age-matched study of 35 RA patients, statistically significant (p <.05) bilateral SNHL was found in 60% of the RA group and in 34% of the control group. A statistically significant conductive hearing loss (p <.05) was found in 17% of the RA patients (6% in the control group). Speech discrimination failed to show a statistically significant difference between the two groups.⁴³ At present there is no available well-documented temporal bone study of an RA patient.

Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic disorder that affects small and medium-size arteries. Rapidly progressive SNHL has been reported in small series of patients with this disorder.^44–46

Proposed diagnostic criteria include the following: (1) biopsy-verified narcotizing vasculitis in small vessels, or glomerulonephritis with few or no immune deposits; (2) involvement of more than one organ system, as indicated by biopsy-verified vasculitis in small to medium-size vessels, or surrogate parameter for glomerulonephritis; and (3) lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system.⁴⁷

Temporal bone study of a PAN case revealed bilateral involvement with thickening of the mucosa of the middle ear, loss of the organ of Corti in the hook portion of the basal coil, absence of the tectorial membrane, and atrophy of the stria vascularis. The scala tympani was obliterated by fibrosis and new bone formation. The scala media was hydropic, and a marked decrease in the spiral ganglion cells and nerve fibers supplying this portion of the cochlea was present. The vestibular structures showed no detectable pathologic changes. Small vessel arteritis was found in the dural and subarcuate vessels in both temporal bones.⁴⁶ In another temporal bone study, fibrosis of the left internal auditory artery was demonstrated as well as fibrosis and bone formation of the cochlea and vestibular apparatus. Endolymphatic hydrops of the basal turn of the cochlea was present as well.⁴⁸

Adamantiades-Behçet’s Disease

Adamantiades-Behçet’s disease is a chronic recurrent inflammatory disorder involving the small and large vessels. Manifestations include oral cavity and genital mucosal ulcerations. Involvement of the skin, eyes, joints, and central nervous system may be present as well.⁴⁹ Sudden and progressive hearing loss and tinnitus have been reported in this disorder.^49–52

Cyclosporine has been reported to be effective in improving hearing in patients with AdamantiadesBehçet’s disease.⁵³

Sjögren’s Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands, particularly the salivary and lacrimal glands. The sicca complex of xerophthalmia and xerostomia is the hallmark feature of this syndrome.⁵⁴ In a prospective and age-matched study of 40 SS female patients, SNHL was found in nine (23%).⁵⁵

Ulcerative Colitis

Sporadic cases of ulcerative colitis associated with hearing loss have been reported in the literature.56–58

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