Single-cell immune profiling of Meniere Disease patients.

BACKGROUND: Meniere Disease (MD) is an inner ear syndrome, characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. The pathological mechanism leading to sporadic MD is still poorly understood, however an allergic inflammatory response seems to be involved in some patients with MD. OBJECTIVE: Decipher an immune signature associated with the syndrome. METHODS: We performed mass cytometry immune profiling on peripheral blood from MD patients and controls. We analyzed differences in state and differences in abundance of the different cellular subsets. IgE levels were quantified through ELISA on supernatant of cultured whole blood. RESULTS: We have identified two clusters of individuals according to the single cell cytokine profile. These clusters presented differences in IgE levels, immune cell population abundance, including a reduction of CD56dim NK-cells, and changes in cytokine expression with a different response to bacterial and fungal antigens. CONCLUSION: Our results support a systemic inflammatory response in some MD patients that show a type 2 response with allergic phenotype, which could benefit from personalized IL-4 blockers.

Investigations into audiovestibular manifestations in patients with psoriatic arthritis.

OBJECTIVE: Although psoriatic arthritis (PsA) is a common chronic inflammatory rheumatic disease, little is known about audiovestibular impairment in this condition. We aimed to establish whether audiovestibular manifestations were present in patients with PsA. METHODS: A set of 60 consecutive patients who fulfilled the Moll and Wright criteria for PsA and 60 matched controls were studied. During the period of recruitment, individuals were excluded who had a history of cardiovascular disease, cerebrovascular complications, peripheral artery disease, renal insufficiency, syphilis, Meniere disease and other vestibular syndromes, infections involving the inner ear, barotrauma, or were in treatment with ototoxic drugs. RESULTS: Most patients with PsA were men (63%). The mean age at the time of our study was 52.9 years and the mean age at the onset of symptoms was 33 years. Thirty-six (60%) of the 60 patients showed abnormal hearing loss in the audiogram compared to only 5 (8.3%) of the 60 controls (p < 0.001). Values of audiometric tests (pure-tone average and speech reception threshold) yielded significant differences between patients and controls (p < 0.001). The audiogram disclosed a bilateral and symmetrical sensorineural hearing loss (SNHL) in PsA with predominant pattern of high frequency SNHL in patients with PsA (46.7%) compared to controls (8.3%, p < 0.001). Patients with PsA exhibited abnormal vestibular tests more commonly than controls. A significantly increased frequency of abnormal computerized dynamic posturography with a predominant vestibular loss pattern was also observed in patients (23.3%) compared to controls (0%, p < 0.001). CONCLUSION: Our current study demonstrates strong evidence for inner ear damage in patients with PsA.

Audiovestibular manifestations in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin affecting up to 1% of the population. Little is known about audiovestibular impairment in patients with AS, especially the presence of cochleovestibular dysfunction in these patients. To investigate audiovestibular manifestations in AS, we studied a series of 50 consecutive patients who fulfilled the modified New York diagnostic criteria for AS and 44 matched controls. Individuals with history of cardiovascular disease, cerebrovascular complications, peripheral artery disease, renal insufficiency, syphilis, Meniere and other vestibular syndromes, infections involving the inner ear, barotrauma, or in treatment with ototoxic drugs were excluded. Most patients with AS were men (80%). The mean age at the time of study was 52.5 years, and mean age at the onset of symptoms was 34.4 years. Twenty-nine (58%) patients showed abnormal hearing loss in the audiogram compared to only 8 (18%) controls (p < 0.001). Values of audiometric tests (pure-tone average and speech reception threshold) yielded significant differences between patients and controls (p < 0.001). It is noteworthy that the audiogram shape disclosed a predominant pattern of high-frequency sensorineural hearing loss in AS patients (50%) compared to controls (18%) (p = 0.002). Also, AS patients exhibited abnormal vestibular tests more commonly than controls. AS patients had an increased frequency of head-shaking nystagmus (20%) compared to controls (0%) (p < 0.001). Moreover, patients (26%) showed a significantly increased frequency of abnormal caloric test compared to controls (0%) (p < 0.001). Finally, a significantly increased frequency of abnormal clinical test of sensory integration and balance with a predominant vestibular loss pattern was observed in patients (36%) compared to controls (5%) (p < 0.001). In conclusion, the current study demonstrates strong evidence for inner ear compromise in patients with AS.

Benign paroxysmal positional vertigo and clinical test of sensory interaction and balance in ankylosing spondylitis.

OBJECTIVE: To assess the frequency and characteristics of benign paroxysmal positional vertigo (BPPV) and clinical test of sensory interaction and balance (CTSIB) abnormalities in patients with ankylosing spondylitis (AS). STUDY DESIGN: A series of consecutive patients that fulfilled the modified New York diagnostic criteria for AS and matched controls were studied. SETTING: The study was performed at the Otolaryngology Division of a tertiary reference center. PATIENTS: Fifty-nine patients with AS (47 men [79.6%]) attending hospital outpatient rheumatology clinics between March and October 2008, and 46 controls (34 men [73.9%]) were studied. INTERVENTION: Dix-Hallpike and cephalic rotational tests and CTSIB were performed in AS patients and age-, sex-, and ethnically frequency-matched controls. MAIN OUTCOME MEASURE: Type and frequency of BPPV and CTSIB conditions were assessed. RESULTS: BPPV was diagnosed in 6 patients (10.1%) with AS and in 2 (4.3%) of the controls (p = 0.24). Abnormal caloric test was more commonly observed in patients with AS (n = 15 [25.4%]) than the controls (n = 0) (p < 0.001). Increased frequency of abnormal CTSIB also was observed in patients (19/59 [32%]) compared with the controls (3 [6.5%]) (odds ratio, 6.81 [95% confidence interval, 1.77-38.0]; p = 0.001). Among the abnormal CTSIB patterns, the vestibular loss was the most commonly observed in patients with AS (15/59 [25.4%]). CONCLUSION: The present study shows an increased frequency of abnormal postural control in CTSIB test of vestibular origin in patients with AS.

Benign paroxysmal positional vertigo and clinical test of sensory interaction and balance in systemic sclerosis.

OBJECTIVE: To assess the frequency and characteristics of benign paroxysmal positional vertigo (BPPV) and clinical test of sensory interaction and balance (CTSIB) abnormalities in patients with systemic sclerosis (SSc). STUDY DESIGN: A series of consecutive patients diagnosed with SSc according to well-established classification criteria and matched controls were studied. SETTING: The study was performed at the otolaryngology division of a tertiary reference center. PATIENTS: Forty-two patients (35 with limited SSc [lSSc] and 7 with diffuse SSc [dSSc]) and 74 controls were studied between January and May 2007. INTERVENTION: Dix-Hallpike and cephalic rotational tests and CTSIB were performed in SSc patients and age-, sex-, and ethnically frequency-matched controls. MAIN OUTCOME MEASURE: Type and frequency of BPPV and CTSIB conditions were assessed. RESULTS: Seven patients (17%) fulfilled the diagnostic criteria for BPPV compared with none of the controls (p < 0.001). It was related to the involvement of the posterior semicircular canal in two lSSc patients and the horizontal semicircular canal in another three patients with lSSc and two with dSSc. A significantly increased frequency of abnormal CTSIB was also observed in SSc patients (20 [48%]) compared to controls (7 [10%]; p < 0.0001; odds ratio, 8.70; 95% confidence interval, 2.97-27.2). It was caused by a vestibular pattern in most patients (p < 0.0001). CONCLUSION: The present study shows an increased frequency of BPPV and a vestibular pattern in CTSIB in SSc patients.

Audiovestibular manifestations in patients with limited systemic sclerosis and centromere protein-B (CENP-B) antibodies.

Audiovestibular dysfunction has been reported in patients with connective tissue disease. Systemic sclerosis (SSc; scleroderma) is a rare connective tissue disease of unknown etiology. In the current study we assess whether audiovestibular involvement is present in patients with limited scleroderma (lSSc). To answer this question we studied a series of 35 consecutive patients who fulfilled well-established classification criteria for lSSc and had antibodies against the major centromere protein-B (CENP-B), and 59 matched controls. Individuals with a history of cerebrovascular complications, syphilis, Ménière and other vestibular syndromes, infections involving the inner ear, barotrauma, or in treatment with ototoxic drugs were excluded. The majority of patients with lSSc were women (94%). The mean age at time of study was 64.5 years, and the mean age at time of disease diagnosis was 56.9 years. Besides Raynaud phenomenon, most patients with lSSc had other typical features of CREST (calcinosis, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia) syndrome. Twenty-seven (77%) patients showed abnormal hearing loss in the audiogram compared with only 15 (26%) of the controls (p < 0.001). Values of audiometric tests (pure-tone average and speech reception threshold) yielded significant differences between patients and controls (p < 0.001). The typical pattern of hearing impairment in our series of lSSc patients was a bilateral and symmetrical sensorineural hearing loss with a flat pattern in the audiogram. Abnormal tympanogram and abnormal stapedial reflex were more commonly observed in patients than controls (p < or = 0.001). Similarly, a significantly increased frequency of abnormal oculocephalic response (10 patients, 29%) and head-shaking nystagmus (9 patients, 26%) was observed in patients compared with controls (p < 0.001 for both comparisons). Finally, a significantly increased frequency of abnormal caloric test and clinical test of sensory integration and balance was observed in lSSc patients (31% and 46% of patients, respectively) compared with controls (0% and 12%, respectively) (p < 0.001 for both comparisons). The current study demonstrates strong evidence for inner ear compromise in patients with lSSc.

Human leukocyte antigen-DQB1 and -DRB1 associations in patients with idiopathic sudden sensorineural hearing loss from a defined population of Northwest Spain.

CONCLUSION: The results of this study support the assertion that Southern European individuals have a genetically mediated predisposition to develop idiopathic sudden sensorineural hearing loss (SNHL). OBJECTIVE: To assess the influence of human leukocyte antigen (HLA)-DQB1 and -DRB1 alleles on the susceptibility to and the severity of idiopathic sudden SNHL. MATERIAL AND METHODS: A prospective study of patients diagnosed with idiopathic sudden SNHL between October 2000 and September 2002 was conducted. Patients were included in the study if they were diagnosed with idiopathic sudden SNHL within 1 week after the onset of deafness symptoms and had been followed for at least 12 months. HLA-DQB1 and -DRB1 typing was performed from DNA using molecular-based methods on patients and ethnically matched healthy controls. RESULTS: Thirty-three patients fulfilled the inclusion criteria. No significant differences in HLA-DQB1 phenotype frequencies were found between patients and controls (n = 145). Carriage of HLA-DRB1*0403 was significantly increased in the whole group of patients compared with controls (OR = 11.97; 95% CI 1.99-91.60; p = 0.002; p(corr) = 0.04). In patients without auditory improvement the frequency of the HLA-DRB1*04 phenotype was significantly increased compared with healthy controls (OR = 6.57; 95% CI 1.62-26.70; p = 0.003; p(corr) = 0.04).

Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population.

OBJECTIVE: To assess the frequency and clinical features of biopsy-proven giant cell arteritis (GCA) patients who had fever at the time of diagnosis of the disease, and the relationship between fever, ischemic complications, and the systemic inflammatory response in GCA. METHODS: A retrospective study of biopsy-proven GCA patients diagnosed between 1981 and 2001 was performed at the single referral hospital for a well-defined population in the Lugo region of northwest Spain. Patients were considered as having fever if the axillary temperature at the time of admission or during the followup prior to the onset of corticosteroid therapy was > or =38 degrees C. RESULTS: During the period of study, 21 (10%) of the 210 biopsy-proven GCA patients had fever. Two of them fulfilled criteria for fever of unknown origin. Patients with fever had a lower frequency of severe ischemic manifestations than the rest of biopsy-proven GCA patients. They also exhibited a more severe inflammatory disease, with significant abnormality in most laboratory variables, including higher elevation of erythrocyte sedimentation rate, lower values of hemoglobin, and higher proportion of patients with increased alkaline phosphatase. By logistic regression analysis, we observed that patients with fever had an increased risk of developing anemia (odds ratio [OR] 12.24). In contrast, a negative association between severe ischemic manifestations and fever was found (OR 0.41). CONCLUSION: Biopsy-proven GCA patients with fever constitute a subgroup of patients with more severe inflammatory response and less ischemic disease.

Giant cell arteritis: a new association with benign paroxysmal positional vertigo.

OBJECTIVE: To assess the incidence and characteristics of both benign paroxysmal positional vertigo (BPPV) and positional nystagmus in a series of patients with giant cell arteritis (GCA). STUDY DESIGN: Patients diagnosed with GCA between June 1999 and May 2001 at the single hospital for a defined population were examined prospectively. METHOD: Patients included in this study fulfilled the 1990 American College of Rheumatology classification criteria for GCA. Otologic and oculographic studies were performed. Type, frequency, and outcome of positional oculographic findings was assessed. Patients were required to have been examined within 1 week after the onset of corticosteroid therapy. Data found in GCA patients were compared with those observed in an age, sex, and ethnically matched control population. Further studies in patients and controls were performed 3 and 6 months later. RESULTS: Forty-four patients and 44 matched controls were included in this study. Nine (20.5%) GCA patients fulfilled diagnostic criteria of BPPV compared with only 1 (2.3%) of the controls (P =.007). In seven of these nine GCA patients, BPPV was related to the posterior and two to the horizontal semicircular canals, respectively. Horizontal nystagmus was found in seven GCA patients who developed nystagmus in the head hanging position test compared with none in the controls (P =.006). CONCLUSIONS: The present study shows a higher frequency of BPPV in GCA than in matched controls. Because most clinical manifestations in GCA are caused by ischemic complications, our results suggest an ischemic etiology as responsible for BPPV in these elderly patients. According to these results, GCA may constitute a new association with BPPV.

Giant cell arteritis without clinically evident vascular involvement in a defined population.

OBJECTIVES: To examine the frequency and clinical presentation of biopsy-proven giant cell arteritis (GCA) patients who do not exhibit overt clinical vascular manifestations. To assess whether differences exist between this group of patients and the rest of biopsy-proven GCA patients. METHODS: Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for a well-defined population of almost 250,000 people. Patients were considered as having no evident vascular involvement if cranial ischemic manifestations or other vascular complications of GCA were not present at the time of diagnosis or during at least 12 months' followup. RESULTS: Between 1981 and 2001, 210 patients from the Lugo region of northwest Spain were diagnosed with biopsy-proven GCA. Eleven patients did not show overt vascular manifestations of GCA. Nine of them presented with polymyalgia rheumatica (PMR) and another 2 fulfilled criteria for fever of unknown origin. Patients without clinically evident vascular involvement had a significantly longer delay to diagnosis than those with vascular manifestations. Also, PMR manifestations were more frequently observed in this group of patients. CONCLUSIONS: Biopsy-proven GCA without clinically evident vascular involvement is not exceptional. Despite having a longer delay to diagnosis, these patients constitute a more benign subgroup of GCA.

Geographical and genetic factors do not account for significant differences in the clinical spectrum of giant cell arteritis in southern europe.

OBJECTIVE: To investigate whether genetic and geographical differences may influence the clinical spectrum of giant cell arteritis (GCA), we compared the demographic and clinical features of patients with biopsy-proven GCA from Reggio Emilia (Northern Italy) and Lugo (Northwest Spain) during a 15-year period. METHODS: We performed a retrospective review of the case records of all patients diagnosed with biopsy-proven GCA at Hospital Xeral-Calde (Lugo, Spain) and Hospital Santa Maria Nuova (Reggio Emilia, Italy) between 1 January 1986 and 31 December 2001. Both hospitals are the only referral centers for populations living in central Galicia and central Emilia Romagna, respectively. RESULTS: During the period of study, 194 Lugo residents and 126 Reggio Emilia residents were diagnosed with biopsy proven GCA. Reggio Emilia patients were more likely to be female (74% vs 54%; p = 0.0001). Although Lugo patients complained of headache (86%) more commonly than did those from Reggio Emilia (77%), the difference was only marginally significant (p = 0.05). The proportion of patients with visual manifestations or visual loss was remarkably similar (22% for visual manifestations and 17% for visual loss in Lugo and 29% and 21% for Reggio Emilia residents). The mean erythrocyte sedimentation rate prior to the onset of therapy was also similar. CONCLUSION: Apart from differences in sex, the clinical spectrum of GCA in these 2 Southern European regions was similar.

Influence of age, sex, and place of residence on clinical expression of giant cell arteritis in northwest Spain.

OBJECTIVE: To investigate the epidemiology of giant cell arteritis (GCA), we examined whether differences in clinical and laboratory features exist in patients with biopsy-proven GCA from Northwest Spain according to sex, place of residence, and age at disease onset. METHODS: Retrospective study of biopsy-proven GCA diagnosed from January 1, 1981, to December 31, 2001, at the single hospital for a well defined population of 250,000. A comparative analysis was conducted of clinical and laboratory features according to sex, place of residence (rural or urban), and age at the onset of symptoms (< 70 yrs; >or= 70 yrs). RESULTS: Between 1981 and 2001, 210 patients from the Lugo region were diagnosed with biopsy-proven GCA. In urban areas GCA was significantly more common in women (rate ratio 1.58, 95% CI 1.00-2.53, p = 0.05). Women presented manifestations of polymyalgia rheumatica (PMR) more commonly than men. However, no statistically significant difference in the frequency of visual manifestations or permanent visual loss were observed between the sexes. GCA was slightly more common in rural than in urban areas (annual adjusted incidence rate in rural areas 10.4/100,000 in people age >or= 50 years vs 9.1/100,000 in urban areas; p = 0.34). GCA was more common among men in rural areas (rate ratio 1.73, 95% CI 1.10-2.70, p = 0.02). Patients younger than 70 years at the time of diagnosis (20%) had a trend to a longer delay to diagnosis and a marginal increase in the frequency of PMR compared with those with disease onset at age >or= 70 years. A higher inflammatory response was observed in the patients younger than 70 years. CONCLUSION: In patients with biopsy-proven GCA from Northwest Spain PMR manifestations are more commonly observed in women. The higher inflammatory response and the longer delay to diagnosis in younger patients call for a higher physician awareness of this vasculitis among individuals younger than 70 years.

Audiovestibular manifestations in giant cell arteritis: a prospective study.

Giant cell arteritis (GCA) is a multisystemic vasculitis of elderly people that involves large and medium-sized blood vessels with predisposition to the cranial arteries. Some cranial ischemic manifestations, in particular permanent visual loss, have been widely described. Audiovestibular manifestations have been less commonly reported. In the present study we assessed the frequency and outcome of audiovestibular manifestations in a series of GCA and isolated polymyalgia rheumatica (PMR) patients examined prospectively between June 1999 and May 2001 at the single hospital for a defined population. Patients were included in the study if a temporal artery biopsy had been performed and they were examined within a week after beginning corticosteroid treatment. Patients with abnormal otoscopy or tympanogram, history of cerebrovascular complications, syphilis, Ménière and other vestibular syndromes, infections involving the inner ear, barotrauma, or being treated with ototoxic drugs were excluded. During the study period 44 patients with GCA and 10 patients with biopsy-negative isolated PMR were examined. Patients with isolated PMR were younger. Audiovestibular dysfunction was significantly more frequent in GCA patients than in those with isolated PMR and matched controls. Almost 90% of the GCA patients had vestibular dysfunction, which was generally reversible after several days of steroid treatment; after 3 months of treatment, vestibular dysfunction was observed in only 13 (29.6%) of the 44 GCA patients. These patients with persistent vestibular dysfunction were more likely to have persistent head-shaking nystagmus. Twelve (27.3%) of the 44 GCA patients had hearing improvement after 3 months of therapy. After 6 months of therapy, only 1 of the 44 GCA patients had abnormal vestibular tests. However, no additional improvement in hearing function was observed. The present study confirms a high frequency of audiovestibular manifestations in GCA. It also suggests that audiovestibular damage may be reversible in some patients with GCA.