Rosaria Turchetta

Vogt–Koyanagi–Harada syndrome

OBJECTIVES The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed. RESULTS AND CONCLUSION Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.

Goodpasture's syndrome: A clinical update

Goodpastures syndrome (GS) is a rare and organ-specific autoimmune disease that is mediated by anti-glomerular basement membrane (anti-GBM) antibodies and has pathology characterized by crescentic glomerulonephritis with linear immunofluorescent staining for IgG on the GBM. It typically presents as acute renal failure caused by a rapidly progressive glomerulonephritis, accompanied by pulmonary hemorrhage that may be life-threatening. It was first described as a distinctive syndrome by Pasture in 1919. Autoimmune Inner Ear Disease (AIED) may be associated. The etiology of GS is unknown. Researchers hypothesized a genetic predisposition HLA-associated. Complex immunological mechanisms are in the pathogenesis. The disease is caused by autoantibodies against the NC1 domain of the alpha 3 chain of type IV collagen. The limited presence of this molecule in the body explains the interest confined to specific target organs, such as the lung and kidney. It occurs when the immune system attacks the walls of the lungs and the tiny filtering units in the kidneys. Without prompt diagnosis and treatment, the disease can lead to bleeding in the lungs, kidney failure, and even death.

Sudden sensorineural hearing loss: A vascular cause? Analysis of prothrombotic risk factors in head and neck

Abstract Objective: This aim of this study was to determine the prevalence of thrombophilic risk factors in sudden sensorineural hearing loss, central retinal vein occlusion, and stroke associated with small vessel disease, with the purpose of investigating and reinforcing the vascular hypothesis in the pathogenesis of sudden sensorineural hearing loss. Design: Case-control study. Genetic and acquired risk factors of these three groups were compared with healthy controls. Study sample: Forty-nine, 60, and 101 patients affected respectively by sudden sensorineural hearing loss, central retinal vein occlusion, or stroke associated with small vessel disease, enrolled during a three-year period were compared with 210 healthy controls. Results: The frequency of hyperhomocysteinemia (homocysteine ≥ 15 μmol/L) was higher in each disease group than in controls. A statically significant, albeit weak, correlation between the MTHFR C677T mutation and hyperhomocysteinemia was found in all three diseases. Conclusions: Hyperhomocysteinemia proved to be a risk factor for sudden sensorineural hearing loss. Based on these results, we propose to analyse homocysteine in sudden sensorineural hearing loss patients and, if its values are high, to evaluate the presence of MTHFR C677T mutation.

Microscopic polyangiitis: Advances in diagnostic and therapeutic approaches.

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies.

Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

Oncologic results of the surgical salvage of recurrent laryngeal squamous cell carcinoma in a multicentric retrospective series: Emerging role of supracricoid partial laryngectomy

Several studies in the last decade evaluated conservative surgical procedures and, in particular, supracricoid operations as an alternative to total laryngectomy for the salvage of recurrences of laryngeal squamous cell carcinoma (SCC) after a first attempt of organ preservation.

Oncological results of the surgical salvage of recurrent laryngeal SCC in a multicentric retrospective series. The emerging role of supracricoid partial laryngectomy

Several studies in the last decade evaluated conservative surgical procedures and, in particular, supracricoid operations as an alternative to total laryngectomy for the salvage of recurrences of laryngeal squamous cell carcinoma (SCC) after a first attempt of organ preservation.

Tinnitus Holistic Simplified Classification (THoSC): A New Assessment for Subjective Tinnitus, With Diagnostic and Therapeutic Implications.

Objective: One of the most debated topics in tinnitus is its standard and practical classification. The most popular classification distinguishes subjective from objective tinnitus. Other classifications are based on different features. On the whole, they seem incomplete, and the diagnostic and therapeutic algorithms are often difficult for practical purposes. The aim of this work is to develop a new diagnostic and therapeutic algorithm. Methods: Our model is based on 10 years of experience. In particular, the starting point is the data retrieved from 212 consecutive patients in our Tinnitus Unit between May and December 2013: We found a clear auditory disorder in 74.5% of the population, muscolo-skeletal disorders and/or trigeminal disease in 57.1%, and psychiatric comorbidities in 43.8%. Different features coexisted in 59.9% of the population. Results: Following such data we propose the Tinnitus Holistic Simplified Classification, which takes into account the different tinnitogenic mechanisms and the interactions between them. It differentiates tinnitus that arises from: (1) auditory alterations (Auditory Tinnitus), (2) complex auditory-somatosensory interactions (Somatosensory Tinnitus), (3) psychopathological-auditory interactions (Psychopathology-related Tinnitus), and (4) 2 or all of the previous mechanisms (Combined Tinnitus). Conclusions: In our opinion this classification provides an accurate and easy tailored path to manage tinnitus patients.

Temperature-Dependent Auditory Neuropathy: Is it an Acoustic Uhthoff-like Phenomenon?; A Case Report

Objectives: We describe the case of a young girl in whom transient deafness occurred when her core body temperature rose. Methods: The patient was referred for a series of audiological and neurologic evaluations performed over time in both afebrile and febrile states, as well as after a stress test (with a treadmill) in which the body temperature rise simulated the febrile state. Results: The patient was found to have a temporary bilateral hearing loss, but had normal distortion product otoacoustic emissions. Moreover, auditory brain stem responses revealed the absence of neural synchrony when her core body temperature increased. Conclusions: These results are consistent with a temperature-dependent auditory neuropathy, a rare condition in which patients show normal outer hair cell function and abnormal neural function of the eighth cranial nerve. The symptom is reminiscent of Uhthoffs phenomenon, which is described as transient visual loss and is usually observed in multiple sclerosis. This case of temperature-dependent auditory neuropathy is noteworthy because it sheds light on a disorder of which there have been few reports in the literature. We discuss its similarity to Uhthoffs phenomenon.

Idiopathic bilateral vestibulopathy: an autoimmune disease?

Bilateral vestibulopathy (BV) is the loss of function of both peripheral labyrinths or of the eighth nerves. Its etiology remains obscure in approximately 20% to 50% of cases (so-called idiopathic bilateral vestibulopathy, IBV). Alternatively, the cause could be viral or vascular; to date, causative gene mutations have not been identified. Other potential disease mechanisms include autoimmune disorders. Antibodies have been detected against inner ear tissue (primarily against vestibular membranous labyrinth). The data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, but a small subgroup of organ-specific autoantibodies may synergize with a cellular response to develop vestibular lesions. The two key symptoms of BV are the following: 1. unsteadiness of gait, particularly in the dark or on uneven ground, and 2. oscillopsia associated with head movements. Episodes of vertigo are reported by patients with IBV, particularly early in the development of vestibular loss. Associated hearing loss seldom occurs in the idiopathic type of this condition. Post-mortem examinations revealed a remarkably selective loss of vestibular hair cells in the vestibular end organs but normal hair cells in the cochlea. The diagnosis is made with a simple bedside test for defective vestibular function. The diagnosis can be confirmed by bithermal caloric testing and pendular body rotation. The therapy is based on steroid treatment, and the early initiation of immunosuppression appears to be essential for therapeutic success.