G.F. Macri

Cogan's syndrome: An autoimmune inner ear disease

OBJECTIVES The objective of our study was to review our current knowledge of the aetiopathogenesis of Cogans syndrome, including viral infection and autoimmunity, and to discuss disease pathogenesis with relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications on the aetiopathogenesis and pharmacotherapy of Cogans syndrome from 1945 to 2012 were analysed. RESULTS AND CONCLUSIONS Cogans syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Menieres syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA). Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogans syndrome.

Sudden sensorineural hearing loss: An autoimmune disease?

OBJECTIVES To review our current knowledge of the pathogenesis of sudden sensorineural hearing loss, including viral infection, vascular occlusion and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications on the pathogenesis of sudden sensorineural hearing loss from 1944 to 2010 were analysed. RESULTS AND CONCLUSIONS Sudden sensorineural hearing loss is defined as hearing loss of 30 dB in three sequential frequencies over 3 days or less. It can be an isolated symptom or the presenting symptom of a systemic disease. The aetiology and pathogenesis remain unknown. Detailed investigation typically reveals a specific cause in about 10% of patients. Proposed theories of causation include viral infections, vascular occlusion and immune system-mediated mechanisms. A variety of therapies have been proposed based on the various proposed aetiologies.

Meniere's disease might be an autoimmune condition?

OBJECTIVES To review our current knowledge of the pathogenesis of Menieres disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Menieres disease from 1861 to 2011 were analysed. RESULTS AND CONCLUSIONS Menieres disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Menieres disease is focused on inner ear antigens. Approximately one-third of Menieres disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear.

Bell's palsy and autoimmunity

OBJECTIVES To review our current knowledge of the etiopathogenesis of Bells palsy, including viral infection or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications on the etiopathogenesis, clinical presentation, diagnosis and histopathology of Bells palsy from 1975 to 2012 were analysed. RESULTS AND CONCLUSIONS Bells palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bells palsy is 15 to 30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45 years). The aetiology of Bells palsy is unknown but viral infection or autoimmune disease has been postulated as possible pathomechanisms. Bells palsy may be caused when latent herpes viruses (herpes simplex, herpes zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin basic protein has been suggested for the pathogenesis of Bells palsy. Bells palsy may be an autoimmune demyelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain-Barré syndrome, a neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In Bells palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reaction against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially the facial nerve. Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present within three days of the onset of symptoms should be offered combination therapy. However it seems logical that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might provide more specific treatment guidelines in the management of Bells palsy.

Clinic manifestations in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis (WG), is an uncommon immunologically mediated systemic small-vessel vasculitis that is pathologically characterised by an inflammatory reaction pattern (necrosis, granulomatous inflammation and vasculitis) that occurs in the upper and lower respiratory tracts and kidneys. Although the aetiology of GPA remains largely unknown, it is believed to be autoimmune in origin and triggered by environmental events on a background of genetic susceptibility. In Europe, the prevalence of GPA is five cases per 100,000 population, with greater incidence in Northern Europe. GPA can occur in all racial groups but predominantly affects Caucasians. Both sexes are affected equally. GPA affects a wide age range (age range, 8–99 years). Granulomatosis with polyangiitis is characterised by necrotising granulomatous lesions of the respiratory tract, vasculitis and glomerulonephritis. Classically, the acronym ELK is used to describe the clinical involvement of the ear, nose and throat (ENT); lungs; and kidneys. Because the upper respiratory tract is involved in 70–100% of cases of GPA, classic otorhinolaryngologic symptoms may be the first clinical manifestation of disease. The nasal cavity and the paranasal sinuses are the most common sites of involvement in the head and neck area (85–100%), whereas otological disease is found in approximately 35% (range, 19–61%) of cases. Diagnosis of GPA is achieved through clinical assessment, serological tests for anti-neutrophil cytoplasmic antibodies (ANCA) and histological analysis. The 10-year survival rate is estimated to be 40% when the kidneys are involved and 60–70% when there is no kidney involvement. The standard therapy for GPA is a combination of glucocorticoids and cyclophosphamide. In young patients, cyclophosphamide should be switched to azathioprine in the maintenance phase. A multidisciplinary approach, involving otorhinolaryngologists, oral and maxillofacial surgeons, oral physicians, rheumatologists, renal and respiratory physicians, and ophthalmologists, is necessary for the diagnosis and therapeutic treatment of GPA. ENT physicians have a determining role in recognising the early onset of the disease and starting an appropriate therapy.

Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo

Objectives. To review the current knowledge of the aetiology of vestibular neuritis including viral infections, vascular occlusion, and immunomediated mechanisms and to discuss the pathogenesis with relevance to pharmacotherapy. Systematic Review Methodology. Relevant publications on the aetiology and treatment of vestibular neuritis from 1909 to 2013 were analysed. Results and Conclusions. Vestibular neuritis is the second most common cause of peripheral vestibular vertigo and is due to a sudden unilateral loss of vestibular function. Vestibular neuronitis is a disorder thought to represent the vestibular-nerve equivalent of sudden sensorineural hearing loss. Histopathological studies of patients who died from unrelated clinical problems have demonstrated degeneration of the superior vestibular nerve. The characteristic signs and symptoms include sudden and prolonged vertigo, the absence of auditory symptoms, and the absence of other neurological symptoms. The aetiology and pathogenesis of the condition remain unknown. Proposed theories of causation include viral infections, vascular occlusion, and immunomediated mechanisms. The management of vestibular neuritis involves symptomatic treatment with antivertiginous drugs, causal treatment with corticosteroids, and physical therapy. Antiviral agents did not improve the outcomes.

Autologous serum skin test reactivity and basophil histamine release test in patients with nasal polyposis: preliminary results.

An eosinophilic inflammatory process is generally observed in patients suffering from nasal polyposis (NP), however its onset has not yet been defined. It has been suggested that immune activation of inflammatory cells may be the cause. The aim of this study is to verify whether autoantibodies and/or histamine-releasing factors are present in the serum of patients suffering from NP. In fact, we assume that autoantibodies and/or histamine-releasing factors, as already demonstrated in chronic idiopathic urticaria and asthma, may be involved in the pathogenesis of NP. In this case-control analytical study 40 patients with NP and 27 control subjects underwent the in vivo autologous serum skin test (ASST). The sera from 6 patients suffering from NP and 9 control group subjects, who had all been previously studied and randomly selected, underwent basophil histamine release assay from normal donor as a pilot study. The ASST showed positive results in 55% of patients suffering from NP versus 8% of the control group (p= .00006), the basophil histamine release test (BHRT) turned out positive in all patients tested and in 11% of the control group. We found a weak positive correlation between the percentage of histamine release and the wheal diameter. ASST reactivity is very frequent in patients suffering from NP, thus suggesting the presence of histamine-releasing factors in the blood stream. The BHRT was positive in the serum of all patients, thus suggesting the presence of anti-FcεRI, anti-IgE autoantibodies and/or other histamine-releasing factors, the presence of which can play a role in triggering and maintaining the eosinophilic inflammatory process in NP.

Evidence and role of autoantibodies in chronic rhinosinusitis with nasal polyps.

In this study, we review our current knowledge of the autoimmune etiopathogenesis of chronic rhinosinusitis with nasal polyps including bacterial infections, viral infections and immunomediated mechanisms and to discuss pathogenesis with relevance for pharmacotherapy. Relevant publications on the etiopathogenesis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) from 1977 to 2013 were analyzed. The characteristic signs and symptoms include appearance of relapsing nasal polyps, with typical symptoms such as nasal obstruction, nasal discharge and, usually, loss of the sense of smell. The etiology and pathogenesis remain unknown. Proposed theories of causation include bacterial or viral infections and immunomediated mechanisms. The autoimmune aetiology of of unknown origin or failure to respond to classic pharmacological treatments with nasal and oral steroids is now suspected. At present, the nature of the antigen trigger, the exact role played by B/T cells and anti-dsDNA autoantibodies in the pathogenesis of nasal polyposis remains unclear. Corticosteroids and surgery are the first line of treatment in CRSwNP. In the case of corticosteroid treatment failure, other drugs can be used such as rituximab, belimumab or omalizumab which have demonstrated clinical efficacy in the treatment of nasal polyposis with comorbid asthma. Immunosuppressive drugs such as methotrexate, and cyclophosphamide have also been used with varying degrees of success.

Immunological Model and Otological Manifestations of Behçet's Disease

Behcets disease (BD) is an autoimmune vasculitis of unknown aetiology that is characterised by relapsing episodes of oral aphthous ulcers, genital ulcers, ocular lesions, skin lesions, and other manifestations, including vascular, gastrointestinal and neurological involvement. Behcets disease exists worldwide, although there are significant regional differences, with the highest number of incidences in the Mediterranean, Middle East, and Far East. Behcets disease occurs mainly between 18 and 40 years of age, and the male-to-female ratio is 7:1. The cause of Behcets disease is unknown. It is believed to be due to an autoimmune process triggered by an infectious or environmental agent (possibly local to a geographic region) in a genetically predisposed individual. T cell homeostasis perturbation, especially Th1 and Th17 expansions and decrease regulation by Tregs are now supposed to be the cornerstone of BD pathogenesis. Inflammatory cytokine such as IL21 plays a critical role in pathogenesis of BD. Inner ear involvement in Behcets disease was first reported by Alajouanine in 1961. Thereafter, many cases of inner ear involvement were described by other authors. The otological features of Behcets disease can be divided into hearing loss and disequilibrium. The incidence of hearing loss in Behcets disease has been reported to be 12 to 80% in several studies in the literature. Recently, some authors observed a significant percentage (59.2%) of hearing loss associated with Behcets disease. According to other studies, hearing loss can be the fourth or even the third most common manifestation of the disease. The treatment of inner ear lesions remains unsatisfactory and is based on immunosuppressive agents and will not be reviewed here. This review focuses on the etiophatogenesis and otological manifestations of Behcets disease and specifies the role of the otorhinolaryngologist as an integral member of the multidisciplinary team for clinical management of these patients.