Comprehensive list of characteristic autoimmune/autoinflammatory diseases targeting various organs, including the inner ear
| Disease (histological/molecular basis) | Primary affected organ | Ear involvement | Molecules/antibodies/histological features |
|---|---|---|---|
| Systemic sclerosis (R) | Abnormal connective tissue thickening and protein accumulation in organs/tissues | Hearing impairment prevalence: 20–77% | Endothelin-1/ATA, ACA, anti-RNAP antibodies/excessive deposition of extracellular matrix, fibrosis |
| Multiple sclerosis (N) | Primarily affects the myelin in the CNS | Vertigo/dizziness occurs in around 33% of patients while hearing loss is rare but can happen due to brainstem involvement | IgG, complement, and Fc gamma receptors in the active lesions |
| Rheumatoid arthritis (R) | Prominent symptoms related to joints and surrounding tissues, impacting various organs including the heart, lungs, skin, and eyes | SNHL is the prevalent form of hearing impairment, with a prevalence ranging from 25–72% | RF, ACPA, anti-CarP antibodies/synovial inflammation, pannus formation, neutrophil infiltration |
| Hashimoto’s thyroiditis (E) | Thyroid gland | Anti-thyroid antibodies significantly impact hearing loss, particularly at lower frequencies, impairing cochlear activity | Anti-TPO and anti-TG antibodies/lymphocytic infiltration, thyroid follicular damage |
| Sjogren’s syndrome (I) | Primarily affects the salivary and lacrimal glands, resulting in dry eyes and mouth | Notable connection between SNHL and primary Sjogren’s syndrome, particularly in the higher frequency ranges | IL-6, TNF-α/anti-Ro (SSA) and anti-La (SSB) antibodies/parenchymal and ductal changes, lymphocyte infiltration, proliferation of the lining cells, formation of epimyoepithelial cell islands, acinar atrophy |
| SLE (I) | Multiple tissues/organs including joints, skin, kidneys, blood cells, brain, heart, and lungs | Development of SNHL | C3, C4/ANA, anti-DNA, anti-Smith and anti-phospholipid antibodies/immune complex deposition |
| Mixed cryoglobulinemia (V) | Cryoglobulins in the bloodstream damage or inflame affected blood vessels and surrounding tissues | 22% of patients experience bilateral SNHL | Circulating cryoprecipitable immune complexes in the serum, C4/association with infectious agents like hepatitis C/leukocytoclastic vasculitis |
| Antiphospholipid antibody syndrome (V) | Recurrent clotting episodes in arteries/veins due to antiphospholipid antibodies | Limited incidence and prevalence of sudden SNHL, with only a few case reports available, including both unilateral and bilateral occurrences | Lupus anticoagulant, ACA, anti-beta-2 glycoprotein I antibodies/thrombotic microangiopathy |
| Behcet’s syndrome (V) | Vasculitic disorder characterized by recurrent oral aphthous ulcers, genital ulcers and uveitis, various systemic manifestations (neurologic, articular, and gastrointestinal) | Sudden deafness and vertigo episodes, with SNHL prevalence ranging from 30–63% | No specific/pathognomonic biomarker, histopathology feature, or laboratory test, pathergy test positivity is suggestive, diagnosis is primarily clinical |
| Giant cell arteritis (V) | Large blood vessel inflammation with multinucleated giant cell formation from fused macrophages particularly affecting the temporal arteries in the head | SNHL is an uncommon complication, with hearing impairment present in 25% of patients. Vertigo and other indications of eighth cranial nerve involvement, such as dizziness and nystagmus | Erythrocyte sedimentation rate, CRP, thrombocytosis/transmural inflammatory infiltrate comprised of lymphocytes, macrophages, and giant cells |
| Wegener’s granulomatosis (or granulomatosis with polyangiitis) (V) | Formation of granulomas and inflammation of blood vessels, primarily affecting the upper and lower respiratory tracts in early stages | Middle ear disease commonly leads to conductive hearing loss, with around 10% of patients experiencing SNHL, primarily affecting low frequencies due to basilar membrane stiffness | Proteinase 3/ANCA/formation of granulomas featuring giant cells, encompassed by plasma cells, lymphocytes, and dendritic cells |
| Cogan’s syndrome (V) | Involvement of the inner ear and ocular structures, corneal/stromal interstitial keratitis, inflammation of the blood vessels | Hearing loss, tinnitus, and spontaneous sudden vertigo | No particular marker/ANA, SMA, lupus anticoagulant, cryoglobulins, ANCA, RF/infiltration by lymphocytes and plasma cells |
| Polyarteritis nodosa (V) | Systemic vasculitis primarily affects small and medium-sized arteries, leading to localized necrosis and inflammatory changes in the arterial wall | Hearing loss can be conductive, mixed, or sensorineural. SNHL usually appears bilaterally and symmetrically, with sudden onset or rapid progression | No definitive laboratory marker/localized necrotizing arteritis along with a mixed inflammatory infiltrate |
| Relapsing polychondritis (R) | Cartilage of the upper airway (ear, nose, trachea) | Conductive or SNHL | Matrilin-1, cartilage oligomeric matrix protein/antibodies against collagens II, IX, and XI/fragmented cartilaginous tissue surrounded by fibrous connective tissue with mononuclear inflammatory infiltrates |
| Takayasu’s arteritis (V) | Vasculitis that affects large and medium vessels | Hearing loss is a rare occurrence | Matrix metalloproteinases/transmural fibrous thickening of the arterial walls, degeneration of elastic fibers, reactive fibrosis |
| Vogt-Koyanagi-Harada’s disease (I) | Immune-mediated destruction of melanocytes by T cells, inflammation in pigmented organs | Auditory and vestibular manifestations in two-thirds of patients, including bilateral, rapidly progressive SNHL, tinnitus, and vertigo | Tyrosinase peptide/non-necrotizing granulomatous inflammation |
| Pyoderma gangrenosum (I) | Neutrophilic dermatosis characterized by chronic ulcers | Few cases of SNHL, several cases of sensorineural deafness in association with ulcerative colitis | Inflammasomes, Janus kinase 2, IL-23/proliferation of clonal T cells, ulceration of the epidermis and dermis associated with intense neutrophilic infiltrate, neutrophilic pustules, and abscess formation |
| Inflammatory bowel disease (I) | Chronic inflammation of the gastrointestinal tract | SNHL is commonly seen in patients with IBD, especially ulcerative colitis | Significant infiltration of the lamina propria by neutrophils, macrophages, dendritic, and NK cells |
| Celiac disease (I) | Chronic immune-mediated enteropathy of the small intestine, triggered by ingestion of gluten in genetically predisposed individuals | SNHL, vertigo with nystagmus | Tissue transglutaminase IgA and IgG, endomysial IgA, deamidated gliadin peptide IgA and IgG/epithelium infiltration with lymphocytes, crypt hyperplasia, villous atrophy |
| Ankylosing spondylitis (R) | Chronic inflammation that leads to progressive new bone formation in the spine, particularly in the sacroiliac joints | SNHL primarily results from cochlear damage, vestibular pathologies from the dysfunction of various neural pathways | Presence of HLA B27 |
| CAPS [familial cold autoinflammatory syndrome, Muckle Wells syndrome and neonatal onset multi-system inflammatory disease (N, R, I)] | Cutaneous, neurological, ophthalmologic, and rheumatologic manifestations | Progressive SNHL | NLRP3 gene mutations, IL-1β-mediated systemic inflammation |
| Susac syndrome (retinocochleocerebral vasculopathy) or SICRET (V) | Endotheliopathy causes dysfunction in the vestibule, cochlea, retinal damage, and multifocal encephalopathy | SNHL occurs in 43% of cases, primarily affecting the lower and mid-frequency ranges. Bilateral involvement is observed in 50% of cases. Additional common symptoms include tinnitus, vertigo, and potential gait impairments | AECA/ischemic infarcts, lack of viable endothelial cells in the blood vessels, thickening of the arterial walls due to amorphous material |
| Autoimmune chronic hypertrophic pachymeningitis (N) | Significant thickening of the cranial dura mater | Cranial nerve palsies, particularly involving the acoustic nerve, progressive SNHL, episodes of dizziness, recurrent bouts of vertigo | Inflammatory infiltrate of B and T lymphocytes, fibroblast activation, collagen deposition, tissue hypertrophy |
| Autoimmune encephalitis (N) | Brain inflammation by immune response against self-antigens expressed in the CNS | Rarely bilateral hearing loss of sudden onset | IgG antibodies against the NR1 subunit of the anti-N-methyl-d-aspartate (NMDA) receptor |
| Autoimmune hepatitis (I) | Chronic inflammatory liver disease | Rapidly progressive, bilateral, asymmetrical, and asynchronous SNHL (case report [32]) | Liver enzymes, IgG/lymphocytic inflammatory infiltration of the liver |
R: rheumatic; N: neurologic; E: endocrine; I: immunologic; V: vascular; ATA: anti-topoisomerase antibodies; ACA: anticentromere antibodies; RNAP: RNA polymerase; CNS: central nervous system; ACPA: anti-citrullinated protein antibodies; CarP: carbamylated protein; TPO: thyroid peroxidase; TG: thyroglobulin; La: lupus antibodies; SSA: Sjogren’s syndrome-related antigen A; C3: complement component 3; ANCA: anti-neutrophilic cytoplasmic antibodies; IBD: inflammatory bowel disease; NK: natural killer; NLRP3: nucleotide-binding and oligomerization domain-like receptor protein 3; SICRET: small infarctions of cochlear, retinal and encephalic tissue; AECA: anti-endothelial cell antibodies (The abbreviations “R”, “N”, “E”, “I”, “V” for “rheumatic”, “neurologic”, “endocrine”, “immunologic” and “vascular”, respectively, are only applicable in the table)
