Eur Arch Otorhinolaryngol DOI 10.1007/s00405-014-3079-2

Otology

Sensorineural hearing loss in pediatric patients with celiac disease Nafiye Urganci · Derya Kalyoncu · Asli Batur Calis 

Received: 8 February 2014 / Accepted: 26 April 2014 © Springer-Verlag Berlin Heidelberg 2014

Abstract  Sensorineural hearing loss (SNHL) as an extraintestinal manifestation of celiac disease (CD) has been reported in several studies. The aim of this study was to determine presence of subclinical sensorineural hearing loss associated with CD in pediatric patients. Otoscopy, tympanometry and pure tone audiometry were performed in 44 patients with CD and 20 healthy age and sex-matched controls. Pure tone audiometry did not show significant sensorineural hearing loss over all frequencies in patients with CD compared with controls (P > 0.05). SNHL was detected in only three (6.8 %) patients with CD. In conclusion, subclinical sensorineural hearing loss was demonstrated in adult patients with CD; therefore, we recommend to perform audiometric examinations in pediatric patients for recognizing hearing loss early during the course of the disease.

Introduction Celiac disease (CD) is an immune-mediated disease triggered by an environmental agent, gluten, in genetically predisposed individuals. Gluten induces the production of specific autoantibodies directed against tissue transglutaminase not only in the small intestine but also in extraintestinal tissues. A relationship between autoimmune diseases and hearing loss is well established, and sensorineural hearing loss (SNHL) has been reported in autoimmune disorders such as Sjögren’s syndrome, systemic lupus erythematosus and inflammatory bowel diseases [1–6]. Subclinical SNHL associated with CD has been investigated in several studies [7–12] where incidence of SNHL has varied from 8.5 [7] to 47.1 % [8]. We aimed to identify whether pediatric patients with CD have a higher incidence of subclinical SNHL than healthy children in this prospective controlled study.

Keywords  Sensorineural hearing loss · Celiac disease · Children Materials and methods

N. Urganci  Division of Pediatric Gastroenterology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey D. Kalyoncu  Department of Pediatrics, Sisli Etfal Training and Research Hospital, Istanbul, Turkey D. Kalyoncu (*)  Istinye State Hospital, Istinye Street No:98, 34465 Sariyer, Istanbul, Turkey e-mail: [email protected] A. B. Calis  Department of Otorhinolaryngology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey

Forty-four children with CD diagnosed and followed up between 2000 and 2012 at Division of Pediatric Gastroenterology of Sisli Etfal Training and Research Hospital (Istanbul, Turkey) and 20 healthy age and sex-matched controls were referred and evaluated for audiological assessment. A questionnaire assessing risk factors for hearing loss was administered for all patients and controls. Disease parameters including type and duration of disease, disease activity, history of medication including duration and doses, coexisting other associated extraintestinal manifestations were determined. Demographic and clinical characteristics of study patients and control group are shown in Table 1. None of the patients had a history of head trauma or noise exposure, exposure to ototoxic drugs, family history of hearing loss or CD.

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Table 1  Demographic and clinical features of CD patients and controls

Age (years) Gender (male/female) BMI (kg/m2) Duration of disease (mean ± SD, years) Clinical presentation  Typical  Atypical Compliance to GFD  Compliant  Non-compliant

Patient group (n = 44)

Control group (n = 20)

8.8 ± 4.54 0.62:1 (17/27) 18.5 ± 3.97 3.1 ± 2.57

9.35 ± 2.4 0.8:1 (9/11) 23.3 ± 3.5

23 (52.2 %) 21 (47.7 %) 27 (61.3 %) 17 (38.6 %)

The diagnosis of CD was based on ESPGHAN criteria [13]. The histopathological changes of small intestinal biopsies were graded according to a modified Marsh classification [14]. Informed consents were obtained from all of the parents before the procedures. During follow-up, dietary compliance to GFD was evaluated on every visit by the same physician and celiac disease activity was monitored by measurement of antibodies against transglutaminase and endomysium. Control subjects were also tested for the presence of anti-gliadin antibody, anti-endomysial antibody, and anti-tissue transglutamine antibody. A family history of autoimmune diseases was determined among first-degree relatives of all patients and controls. Audiological evaluation included otoscopy, tympanometry and pure tone audiometry thresholds at frequencies from 250 to 8,000 Hz (Kamplex AC4 Audiometer, P.C.Worths, London, UK). Air and bone conduction thresholds were measured separately for both right and left ear in all patients and controls and the highest one of these four values was accepted as representative hearing level for each cases. Patients who had values higher than 20 decibel were accepted having SNHL. Statistical analyses Statistical analysis was performed using SPSS 11.0 software (SPSS Inc, Chicago, IL, USA). Results were expressed as mean ± SD for quantitative variables and proportions and as percentage. A value of P < 0.05 was considered statistically significant.

Results The age of patients ranged from 1 to 16 years (mean 8.8  ± 4.54), and male:female ratio was 0.62. The control

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Table 2  Comparison of average hearing levels between study and control groups Patient group (n = 44)

Control group(n = 20)

P

Average hearing levels at 2 kHz Average hearing levels at 4 kHz

16.3 ± 8.6

12.8 ± 1.5

0.07

14.5 ± 6.4

13.6 ± 3.2

0.55

Average hearing levels at 8 kHz

15.8 ± 5.7

13.6 ± 2.5

0.10

P < 0.05 is statistically significant

group consisted of 20 healthy children (11 girls and 9 boys, mean age 9.35 ± 2.4 years, range 1−16 years) with negative serological tests for CD. None of the patients or controls had symptoms such as hearing loss, tinnitus or balance disturbance. No risk factors for hearing loss were identified by questionnaire. All members of each group had normal otoscopy and tympanometry excluding middle ear disease and conductive hearing loss. Pure tone audiometry showed no abnormality. Analysis of each frequency showed that the average hearing thresholds were not significantly different between study group and control group. Comparisons of average hearing levels at each frequency in patients and controls are shown in Table 2. 6.8 % of the patients (3/44) had SNHL diagnosed 1−3 years after the diagnosis of CD. SNHL detected patients did not differ significantly in gender, weight, height, clinical presentation, histological type according to the modified Marsh criteria and compliance to GFD (P > 0.05). There was no statistically significant correlation between average hearing levels and type, activity and duration of disease, and coexisting other extraintestinal manifestations.

Discussion Sensorineural hearing loss has been described in a small number of patients with CD. It is not known exactly whether this is a rare and sporadic association, or whether these reports represent an under-recognized extraintestinal manifestation of CD. Sensorineural hearing loss is thought to be immune mediated. The pathogenetic mechanisms such as immune complex deposition, T-lymphocyte mediated cytotoxicity and vasculitis affecting inner ear have been reported [15, 16]. The study conducted by Hizli et al. [9] showed a higher prevalence of SNHL in pediatric celiac patients than in healthy controls (40.6 vs 3.1 %, respectively) and suggested that hearing impairment should be searched in

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newly diagnosed pediatric CD patients. Similarly, Solmaz et al. [10] have reported statistically significant difference in the audiometric results between the group with CD and the control group. In our study, average hearing thresholds in each frequency showed significantly no difference between the study group and the control group. Our results were compatible with the study reported by Bükülmez et al. [12]. And we also found no difference between type and activity of disease, compliance to GFD according to average hearing levels. 38.6 % (17/44) of our patients were non-compliant with GFD and only one of them developed SNHL. The correlation between the degree of histological changes and the appearance of autoantibodies could not be compared, because according to the modified Marsh criteria, the disease was severe (IIIb/IIIc) in all of the patients enrolled in this study. Our results showed that hearing functions of children with CD were not significantly different than healthy controls when compared with adults. This may be influenced by some factors such as small number of our cases, younger age and shorter duration of their illness. In conclusion, delay in treatment may lead to irreversible hearing loss and early identification of subclinical SNHL improves prognosis. There is thus the need for periodic evaluation of the auditory function of pediatric patients with CD similar to adult patients. In addition, it should be established if poor control of CD correlated with worsening of hearing in patients with CD who had SNHL. Conflict of interest The authors have no conflict of interest.

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