Evaluation of the Laryngeal Involvement and Voice Quality in Crohn Disease

ORIGINAL ARTICLE LARYNGOLOGY & PHONIATRY DOI: 10.5152/B-ENT.2021.20029

Evaluation of the laryngeal involvement and voice quality in crohn disease

Hüseyin Sarı1 , Ziya Saltürk1 , Tolgar Lütfi Kumral1 , Yasemin Gökden2 , Ayşe Enise Göker1 , Ayça Başkadem Yılmazer1 , Esmail Abdulahi Ahmed1 , Güler Berkiten1 , Yavuz Uyar1

1Department of Otorhinolaryngology-Head and Neck Surgery, Okmeydanı Training and Research Hospital, Istanbul, Turkey 2Department of Gastroenterology, Okmeydanı Training and Research Hospital, Istanbul, Turkey

Cite this article as: Sarı H, Saltürk Z, Kumral TL, et al. Evaluation of the laryngeal involvement and voice quality in crohn disease. B-ENT 2020; 16(4): 217-21.

ABSTRACT Objective: A few cases of laryngeal involvement have been reported for Crohn disease. However, laryngeal involvement may be greater than expected. This study aimed to evaluate the laryngeal involvement and voice quality in patients with Crohn disease. Methods: A total of 100 participants were included in the study: 50 patients with Crohn disease and 50 healthy people in a control group. Maximum phonation time, fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio were measured during acoustic voice analysis. All patients underwent laryngostroboscopic evaluation. A subjective evaluation was performed using the Turkish version of Voice Hand- icap Index-10. Results: There were not any significant differences between the groups in relation to sex and age (p=0.407). In the acoustic analyses, fundamental frequency and voice handicap index measurements did not differ between the groups (p>0.05). In contrast, jitter, shimmer, and noise-to-harmonics ratio measurements were significantly higher in patients with Crohn disease. Maximum phonation time, Voice Handicap Index-10 scores, and stroboscopic evaluation did not differ between the groups. Conclusion: To the best of our knowledge, this is the first study to objectively evaluate the larynx and the vocal folds in particular in patients with Crohn disease. Acoustic analysis revealed significant differences, especially in the perturbation parameters. The stroboscopic evaluation and Voice Handicap Index-10 scores did not differ between patients and control groups. Keywords: Acoustic analysis, Larynx, Crohn’s disease, Stroboscopy, Voice handicap index.

Introduction ever, laryngeal involvement is more frequent in CD than in ulcerative colitis. Only 12 cases of CD and 1 case of ulcerative Crohn disease (CD) is a chronic inflammatory disease associ- colitis involving laryngeal manifestations have been reported ated with noncaseating granulomas in the bowel. CD is largely previously (7). Laryngeal manifestations include edema of the known as a disease of the distal ileum and the colon; however, epiglottis and arytenoid area, multiple ulcerative lesions of the any segment of the gastrointestinal tract may be involved, in- epiglottis, and inflammation of the vocal folds (1). Patients cluding the oropharyngeal and laryngeal regions (1). Although present with dysphonia, chronic cough, odynophagia, or dif- gastrointestinal findings and complaints are more prominent in CD, extraintestinal involvement has been increasingly re- ficulty breathing, which are common findings for all laryngeal ported (2, 3). The most common lesions are oral aphthous ul- diseases. cers of the tongue and buccal mucosa, angular cheilitis, thick- A few cases of laryngeal involvement have been reported for ening and edema of the lips, and gingivitis (4, 5). Sinonasal involvements include inflammation of the nasal mucosa with CD. However, laryngeal involvement may be more in number erosion, ulceration, necrosis, and bleeding when it comes in than expected. Most of the publications in the literature are contact with an object. Patients may complain of nasal ob- case reports. Subclinical cases that are not diagnosed can be struction, epistaxis, impairment of smell, purulent rhinorrhea, revealed, and voice professionals can benefit from these find- crusting, acute or chronic sinusitis, and deformity of the nasal ings. This study aimed to evaluate the laryngeal involvement pyramid (1, 6). Laryngeal manifestations are fairly rare; how- and voice quality in CD.

Corresponding Author: Hüseyin Sarı, [email protected] Received: November 25, 2020 Accepted: March 11, 2021 Available online at www.b-ent.be CC BY 4.0: Copyright@Author(s), “Content of this journal is licensed under a Creative Commons Attribution 4.0 International License.”

217 Sarı et al. Voice quality in Crohn‘s disease B-ENT 2020; 16(4): 217-21

Methods ing to the Reflux Symptom Index (RSI). RSI >13 was accepted as the score for laryngopharyngeal reflux, as recommended by This prospective study enrolled 30 females and 20 males di- Belafsky et al. (10, 11). An overall RSI >13 shows a high correla- agnosed with CD. The study was conducted between Decem- tion with reflux that has been documented by pH monitoring ber 2018 and November 2019, and institutional review board and could be accepted as pathologic. approval was obtained from the local hospital ethical committee (approval number: 1031). Power analysis for a Wilcox- Statistical analyses on signed-rank test was conducted in the G*power 3.1 (Heine Statistical analyses of the data were conducted using The University, Dusseldorf, Germany) program to determine a suf- Statistical Package for Social Sciences version 22.0 software ficient sample size using an alpha of 0.05 and a power of 0.80. (IBM Corp.; Armonk, NY, USA). Data were analyzed using de- The calculated size was 50 in each group. scriptive statistical methods (mean and standard deviation). Shapiro-Wilk test was used to assess the normal distribution Written informed consent was obtained from patients who of the parameters. Mann-Whitney U test was used for the participated in this study. Patients in the gastroenterology comparison of nonparametric data. The results were evaluat- outpatient clinic who had been diagnosed with CD for at least ed using the 95% confidence intervals, and the level of signif- 2 years were included in the study. Exclusion criteria were icance was set at p<0.05. being diagnosed with laryngopharyngeal reflux disease and upper respiratory tract infections, having previous laryngeal Results surgery or pathology, undergoing voice training before this study, having pulmonary problems, undergoing head and neck A total of 100 participants were included in the study: 50 radiotherapy, smoking, and being diagnosed with systemic patients in the study group and 50 in the control group. The disorders and endocrine diseases. mean age of the patients was 40.30±10.70 (range: 18-61) years. There were 38 (36.1%) males and 62 (63.9%) females. All subjects underwent complete head and neck examinations There were no differences between the groups regarding age in addition to laryngostroboscopy and acoustic and aerody- and sex (p>0.05) (Table 1). namic voice analysis. A 70° rigid telescope system (Telecam DX II camera system, Karl Storz, Tuttlingen, Germany) was On stroboscopic examination, we detected erythema and vo- used for the endoscopic examination. Laryngostrobosco- cal fold edema in 1 patient. MPT, F0, jitter, shimmer, NHR, and py was performed using a Pulsar II stroboscope system (Karl Storz) by the same physician. Praat software (version 4.4.13; Table 1. Descriptive statistics of age and sex between the Boersma and Weenink, University of Amsterdam, Amsterdam, groups The Netherlands) was used for the acoustic analysis. All analy- Crohn ses were performed by the same senior laryngologist. The fun- disease Control damental frequency (F0), jitter, shimmer, and noise-to-har- (n=50) (n=50) monics ratio (NHR) were measured during the acoustic voice analysis. Vocal data were recorded using a D5 dynamic mi- Variable Mean±SD Mean±SD P value crophone (AKG, Vienna, Austria) held 15 cm from the lips in Age, years 41.20±12.39 39.40±8.73 .403a a room with acoustic insulation. After a deep inspiration, the Sex, n (%) subject tried to say the vowel sound “a” for as long as possible. This was repeated 3 times, and the longest recording Male 20 (40.00%) 18 (36.00%) .837b time was accepted as the maximum phonation time (MPT). Female 30 (60.00%) 32 (64.00%) Acoustic analysis was also performed with this recording. The aAssesed with Student t-test, bAssessed with a continuity (yates) correction. Stroboscopy Evaluation Rating Form (SERF) was used for the SD: Standard deviation laryngostroboscopic evaluation (8).

The Voice Handicap Index (VHI)-10 was performed for a sub- Table 2. Comparison of voice analysis results between the jective analysis of the voice. The Turkish version of the VHI- groups 10, validated by Kılıç et al. (9) comprises 10 questions and is Crohn disease scored from 0 (never) to 4 (always). (n=50) Control (n=50)

Patients with laryngopharyngeal reflux were excluded accord- Variable Mean±SD Mean±SD P value MPT 21.46±1.61 22.93±1.65 .237 Main Points: F0 193.90±13.99 204.30±48.68 .548 Jitter local (%) 0.49±0.17 0.17±0.11 .001* • Laryngeal involvement can be seen in Crohn disease (CD). Shimmer local (%) 10.59±0.24 8.21±0.25 .002* • The acoustic voice analysis parameters show that the vocal cords are affected in patients with CD compared with those NHR 0.08±0.04 0.05±0.05 .005* of the control group. VHI 3.26±1.51 2.90±1.67 .282 • Voice Handicap Index was not affected in patients with CD. • Laryngeal involvement should be evaluated in patients with Analysis was performed with Mann-Whitney U test. CD who have voice pathology. F0: Fundamental frequency, MPT: Maximum phonation time, NHR: Noise-to- harmonic ratio, SD: Standard deviation, VHI: Voice Handicap Index

218 B-ENT 2020; 16(4): 217-21 Sarı et al. Voice quality in Crohn‘s disease

Table 3. Comparison of the stroboscopic findings between abduction of both vocal folds (13). However, there is no de- the group with Crohn disease and the control group tailed clinical evaluation of vocal fold involvement in patients with CD. Crohn disease (n=50) Control (n=50) Laryngeal involvement is not common in autoimmune dis- Variable Mean±SD Mean±SD P eases. Rheumatoid arthritis, systemic lupus, Wegener disease, Sjogren disease, and dermatologic diseases such as pemphi- Amplitude, R 81.00±18.86 82.32±28.34 0.711 gus may affect the larynx.5,12 Rheumatoid arthritis may cause Amplitude, L 82.00±15.78 81.44±24.622 0.672 cricoarytenoid joint involvement, myositis, epiglottitis, rheu- Mucosal wave, R 88.00±10.33 90.00±15.96 0.982 matoid nodules, and bamboo nodules (14). Systemic lupus causes laryngeal edema and vocal fold paralysis, which can be Mucosal wave, L 86.00±10.33 83.66±24.55 0.759 reversed by steroid therapy (15). Pemphigus is characterized Smoothness, R 0.10±0.79 0.00±0.00 0.821 by defects in the epithelium and can be seen in the larynx. Er- ythema with ulcers and typical bullous lesions can occur in any Smoothness, L 0.20±1.03 0.00±0.00 0.542 part of the larynx (16). Regarding the nonspecific nature of Straightness, R 0.20±0.79 0.00±0.00 0.671 the lesions, these diseases should be ruled out (12, 17). Straightness, L 0.40±1.27 0.00±0.00 0.148 Laryngostroboscopy, laryngoscopy, and acoustic voice anal- Phase closure 2.40±0.79 2.66±0.39 0.148 ysis are commonly used to evaluate vocal fold involvement. Phase asymmetry 79.00±28.60 88.00±15.66 0.156 Laryngostroboscopy is used for detailed visualization of the vocal fold vibration. Voice-vibratory assessment with larynge- Regularity 94.00±13.33 98.00±0.00 0.368 al imaging (VALI) and SERF are the 2 main forms for strobo- Glottal closure 2.90±1.08 3.48±0.90 0.215 scopic evaluation (18, 19). VALI is a new evaluation tool for Analysis was performed with Mann-Whitney U test. stroboscopic examination and has higher interrater reliability L: Left, R: Right, SD: Standard deviation (18, 19) but we preferred SERF because we had more expe- rience in it, and to prevent interrater reliability challenges, all VHI measurements were compared between the 2 groups. the stroboscopic evaluations were performed by the same MPT, F0, and VHI measurements did not differ between person. the groups (p>0.05). In contrast, jitter, shimmer, and NHR measurements were significantly higher in the study group Stroboscopy has been performed in many inflammatory la- (p<0.05) (Table 2). ryngeal diseases. Saltürk et al. (20) revealed the vocal fold involvement in stroboscopy, although acoustic analysis showed In the laryngostroboscopic evaluation and VHI-10 results, no changes in Sjogren disease. Stroboscopy alone should not none of the parameters differed statistically between the be relied on to determine the presence or absence of the la- groups (Table 3). ryngeal pathology. Furthermore, because of the subjective nature of stroboscopic parameter rating systems, strobosco- Discussion pists must be well trained to reduce variation and bias. In our study, there was no amplitude, mucosal wave, phase asym- CD is a chronic inflammatory disease associated with non- metry, or glottal closure abnormality evident in the laryngos- caseating granulomas occurring mainly in the bowel, but it troboscopic evaluation. Furthermore, we detected erythema may affect virtually all organs. Although CD is largely known on the epiglottis and vocal folds of 1 patient who also had as a disease of the distal ileum and the colon, any segment edema on the vocal folds. of the gastrointestinal tract may be involved, including the oropharyngeal and laryngeal regions. Patients usually present MPT is a reflection of the aerodynamic parameter for pho- with complaints of bloody diarrhea, abdominal cramps, weight nation and is a simple and useful method for evaluating the loss, mild anemia, and perianal fistulas.1 The involvement of laryngeal function. The average value is 22 to 34 seconds in the upper aerodigestive system is an uncommon finding. males and 16 to 25 seconds in females. We found that it did not differ in patients with CD. Acoustic parameters obtained A few cases of laryngeal involvement in CD have been report- from voice evaluation provide objective measures for vocal ed. The differential diagnosis of the laryngeal lesions can be fold function. F0, jitter, shimmer, and NHR define the basic challenging if no previous diagnosis has been established for elements of voice quality. The mean F0 value is the main pa- inflammatory bowel disease. Hasegawa et al. (12) suggested rameter of the listener’s perception of a speaker’s pitch. Most that inflammatory lesions of the vocal fold in CD may cause laryngeal disorders do not have a significant influence on the recurrent hoarseness. In their study, the lesion was an ulcer- mean F0. In our study, there was no significant change in the ation of the left vocal fold extending to the false vocal fold. F0 value of patients with CD. Jitter is accepted as one of the Jang et al1 reported on a patient with a large submucosal mass most important physical correlates of perceived hoarseness primarily involving the left arytenoid, approximately 2 to 3 cm or harshness (21). Inflammation of the larynx or very small in diameter, prolapsed over the laryngeal inlet making visual- growths on the vocal folds may influence frequency pertur- ization of the true vocal folds difficult. Laryngeal biopsy es- bation, and larger pathologies may result in increased jitter tablished a diagnosis of laryngeal CD. There has been only 1 values (17, 21). Similarly, our results revealed that CD caused reported case of a patient requiring a tracheostomy for airway a significant increase in jitter values. Shimmer shows the am- control owing to extensive edema of the larynx and limited plitude changes of the sound waves at short intervals. These

219 Sarı et al. Voice quality in Crohn‘s disease B-ENT 2020; 16(4): 217-21 parameters are often used to detect the degree of pathology Conflict of Interest: The authors have no conflict of interest to de- exhibited by a speaker (22). In our study, we also found that clare. shimmer values increased significantly in CD. Increased jitter Financial Disclosure: The authors declared that this study has re- and shimmer values may reflect inflammatory changes on the ceived no financial support. vocal folds (23). NHR correlates with the overall perception of noisiness or roughness. The noise ratio increases in abnormal References sounds (24). We found that CD caused an increase in NHR. Irregular components of the voice can be perceived in higher 1. Yang J, Maronian N, Reyes V, Waugh P, Brentnall T, Hillel A. La- notes, so vocal performers such as professional singers should ryngeal and other otolaryngologic manifestations of Crohn’s dis- be followed carefully in CD. ease. 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