Cochlear involvement in Familial Mediterranean Fever: A new feature of an old disease

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Abstract

Objectives

In this study we first aimed to assess the cochlear functions in children with Familial Mediterranean Fever. The second aim was to investigate the correlation between the hearing levels and some clinical features of Familial Mediterranean Fever including the duration of the disease, age at onset, genetic analysis and colchicine use.

Methods

Thirty-four children with Familial Mediterranean Fever and 27 age matched children were included in the study. Following otologic examination, all children underwent audiometric evaluation, including Pure Tone Average measurements and Distortion Product Otoaoustic Emission testing. Audiological results of the two groups were compared and correlation between the audiologic status and clinical parameters of the disease like the duration of disease, age at onset, mutations and colchicine treatment were studied.

Results

Pure tone audiometry hearing levels were within normal levels in both groups. Hearing thresholds of Familial Mediterranean Fever patients were found to be increased at frequencies 8000, 10,000, 12,500 and 16,000 (p < 0.05). In otoacoustic emission evaluation, distortion products and signal–noise ratio of FMF children were lower in the tested frequencies, from 1400 Hz to 4000 Hz (p < 0.05). Interaction of the disease duration and age of disease onset was found to predict hearing levels, distortion products and signal–noise ratios of children with Familial Mediterranean Fever (F value = 2.034; p = 0.033).

Conclusions

To our knowledge this is the first study demonstrating cochlear involvement in children with Familial Mediterranean Fever which showed increased hearing thresholds at higher frequencies in audiometry together with decreased distortion products and signal–noise ratios demonstrated by distortion product otoacoustic emission testing. Similar studies must be carried out on adult patients to see if a clinical hearing impairment develops. The possible mechanisms that cause cochlear involvement and the effect of colchicine treatment on cochlear functions must be enlightened.

Introduction

Familial Mediterranean Fever (FMF) is an auto-inflamatory disease of serous membranes characterized by recurrent attacks of fever, abdominal, articular and thoracic pain. The disease is an autosomal recessively inherited genetic disease that affects Turks, Arabs, Sephardic Jews and Armenians [1], [2]. The symptoms are seen by the age of ten in 60% of the cases and by 20 in 90% [3]. Amyloidosis is one of the most frequent comlications and the disease involves many organs as kidneys, central nervous system, heart, respiratory and gastrointestinal tracts [4]. In recent years it was seen that FMF patients have increased risk of acquiring vasculitic diseases such as polyarteritisnodosa, Behcet's disease, diverse glomerulopathies and HenochSchonlein Purpura [5]. A rate of 8% of such vasculitic diseases was reported in a series of 207 FMF patients [6].

The diagnosis of the disease remains to be clinical since there are not specific laboratory tests for definitive diagnosis yet. One of the commonly used criterias for diagnosis is Tel Hashomer criteria. Livneh [7] proposed a new diagnostic criteria in 1997 including vasculitis, and then Yalcinkaya et al. [8] also proposed another one including elevated CRP and ESR levels. Because of the absence of exceedingly specific diagnostic tests for FMF and low index of suspicion, the diagnosis usually comes quite later than the first symptom. Therefore, it is mandatory to enlighten all of the characteristics of the disease that may add to the present diagnostic criteria and to provide an opportunity for better understanding of its nature.

Since vasculitic diseases and amyloidosis are seen frequently during the course of FMF and the disease involves many organs as kidneys, central nervous system, heart, respiratory and gastrointestinal tracts by amyloidosis or vasculitis, cochleovestibular involvement related to the course of the disease is probable [4], [5]. To our knowledge, otological involvement in FMF has not been studied until now. In this study we aimed to investigate the cochlear functions in children with FMF using audiometry and otoaoustic emissions (OAE). Additionally, the correlation between the hearing levels and some clinical features of FMF including duration of the disease, age at onset, genetic analysis and colchicine use were planned to be studied.

Section snippets

Patients

This study was conducted after getting IRB approval. The patients with definitive diagnosis of FMF (n = 34) according to Tel Hashomer criteria and healthy controls that admitted to the clinic for nonspecific symptoms (n = 27). Informed consents were obtained from parents and the children if feasible. All patients had genetic analysis performed for the most common mutations (M694V, M680I, M694I, V726A, E148Q, R202Q, F479L, A744S) in our country.

Clinical and laboratory evaluation

Both the patients and the controls were evaluated in

Demographic data

The study group comprised of 34 children (17 males and 17 females) with a mean age of 12.1 years (range 5.2–18.5). The control group composed of 27 children (8 males and 19 females) with a mean age of 11.4 years (range 4.2–17.4). The age (p = 0.552) and sex distribution (p = 0.125) was not significantly different between the two groups. Table 1 summarizes clinical presentations of the children with FMF. The detected mutations were read from the charts and shown in Table 2.

Audiologic data

Two children from the

Discussion

Our results clearly show a cochlear involvement in FMF demonstrated by both audiometry and DPOAE. Audiological findings revealed lower DP and SNR values on DPOAE testing together with higher hearing levels at high frequencies in children with FMF. PTA levels were not in the level of hearing loss and were not different in both groups. Additionally, we showed that the age of disease onset has a significant impact on the cochlear involvement.

FMF is a childhood disease and cochlear functions are

Conclusion

To our knowledge, our study demonstrating cochlear involvement in FMF patients in pediatric age group is the first in medical literature. Similar studies must be carried out in adult patients to see if a clinical hearing loss develops or not. The possible mechanisms that cause cochlear involvement and the effect of colchicine treatment on the cochlea must be enlightened.

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