10.14639/0392-100X-N2091
Laryngeal tuberculosis (LTB) is a rare manifestation of tuberculosis (TB), accounting for 1% of all TB cases. Despite its rarity it is the most frequent laryngeal granulomatous disease. We performed a systematic literature review of the last 20 years on LTB and also present a case from our hospital with special focus on voice assessment. The literature review includes a total of 308 cases, involving studies from seven countries. In all, 64.3% of patients were males. At the time of diagnosis, the mean age range was 44.6-56.5 years. Odynophagia, hoarseness and dysphonia were the most frequent presenting symptoms. In 64 cases, the initial suspicion was laryngeal cancer. Most cases involved the true vocal folds. In about a third of cases a primary LTB with normal chest radiographic was found. Although it can be treated successfully, LTB may cause significant changes in voice quality. Nowadays, LTB is rarely diagnosed and may be confused with laryngeal cancer, it should also be included in the differential diagnosis with all other chronic benign inflammatory and non-inflammatory diseases of the larynx.
text/xml
1827-675X
2091
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Marco Stacchini
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ACTA Otorhinolaryngologica Italica
voice assessment
Laryngeal tubercolosis: a case report with focus on voice assessment and review of the literature
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2022-11-23
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1
Marco Stacchini
2022/11/23
10.14639/0392-100X-N2091
407
ENT Department, M. Bufalini Hospital, Cesena, Italy
1827-675X
voice assessment
en
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Laryngeal tubercolosis: a case report with focus on voice assessment and review of the literature
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:407-414; doi: 10.14639/0392-100X-N2091




Review


Laryngeal tubercolosis: a case report with focus
on voice assessment and review of the literature
Tubercolosi laringea: case report con focus sulla valutazione della voce e revisione
della letteratura
Andrea Migliorelli1, Tommaso Mazzocco1, Anna Bonsembiante1, Daniele Bugada1, Marco Fantini2,
Fabrizia Elli3, Marco Stacchini4
1
  ENT & Audiology Department, University Hospital of Ferrara, Ferrara, Italy; 2 Otorhinolaryngology Service. Koelliker Hospital, Turin,
Italy; 3 Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; 4 ENT
Department, M. Bufalini Hospital, Cesena, Italy


SUMMARY
Laryngeal tuberculosis (LTB) is a rare manifestation of tuberculosis (TB), accounting for
1% of all TB cases. Despite its rarity it is the most frequent laryngeal granulomatous dis-
ease. We performed a systematic literature review of the last 20 years on LTB and also
present a case from our hospital with special focus on voice assessment. The literature
review includes a total of 308 cases, involving studies from seven countries. In all, 64.3%
of patients were males. At the time of diagnosis, the mean age range was 44.6-56.5 years.
Odynophagia, hoarseness and dysphonia were the most frequent presenting symptoms. In
64 cases, the initial suspicion was laryngeal cancer. Most cases involved the true vocal
folds. In about a third of cases a primary LTB with normal chest radiographic was found.
Although it can be treated successfully, LTB may cause significant changes in voice quality.
Nowadays, LTB is rarely diagnosed and may be confused with laryngeal cancer, it should
also be included in the differential diagnosis with all other chronic benign inflammatory and
non-inflammatory diseases of the larynx.
KEY WORDS: dysphonia, laryngeal tuberculosis, larynx, voice quality, voice assessment
                                                                                                Received: March 29, 2022
RIASSUNTO                                                                                       Accepted: June 18, 2022
La tubercolosi laringea (LTB) è una rara manifestazione della tubercolosi (TB), e rappre-
senta l’1% di tutti i casi di TB. Nonostante sia una patologia di raro riscontro, rappresenta   Correspondence
la malattia granulomatosa laringea più frequente. In questo studio riportiamo una revisio-      Andrea Migliorelli
ne sistematica della letteratura degli ultimi 20 anni sulla LTB e descriviamo un caso clinico   Department of ENT & Audiology, University
proveniente dal nostro ospedale, con particolare attenzione alla valutazione della voce. La     Hospital of Ferrara, via A. Moro 8 (Cona), 44100
                                                                                                Ferrara, Italy
revisione della letteratura comprende complessivamente 308 pazienti provenienti da sette
                                                                                                E-mail: mglndr1@unife.it
diverse nazioni. Il 64,3% erano maschi. Al momento della diagnosi il range di età media
era di 44,6-56,5 anni. Odinofagia, raucedine e disfonia sono i sintomi di presentazione più
frequenti. In 64 casi il sospetto iniziale era di tumore laringeo. La maggior parte dei casi      How to cite this article: Migliorelli A, Maz-
ha coinvolto le corde vocali vere. In circa un terzo dei casi è stata riscontrata una LTB         zocco T, Bonsembiante A, et al. Laryngeal tu-
primaria con una radiografia toracica non patologica. Anche se trattata con successo, la          bercolosis: a case report with focus on voice
LTB può causare importanti cambiamenti nella qualità della voce.                                  assessment and review of the literature. Acta
                                                                                                  Otorhinolaryngol Ital 2022;42:407-414. https://
Al giorno d’oggi la LTB è raramente diagnosticata e può essere spesso confusa con il
                                                                                                  doi.org/10.14639/0392-100X-N2091
cancro della laringe, inoltre dovrebbe essere considerata nella diagnosi differenziale delle
malattie benigne croniche infiammatorie e non infiammatorie della laringe.
                                                                                                © Società Italiana di Otorinolaringoiatria
PAROLE CHIAVE: disfonia, tubercolosi laringea, laringe, qualità vocale, valutazione             e Chirurgia Cervico-Facciale
della voce
                                                                                                               OPEN ACCESS

                                                                                                This is an open access article distributed in accordance with
Introduction                                                                                    the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                                Commercial-NoDerivatives 4.0 International) license. The
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium                       article can be used by giving appropriate credit and mentio-
                                                                                                ning the license, but only for non-commercial purposes and
tuberculosis. It typically involves the lungs, but may also affect other organs                 only in the original version. For further information: https://
such as the larynx. Occasionally laryngeal tuberculosis (LTB) can also be                       creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                        407
A. Migliorelli et al.




the first clinical manifestation of an asymptomatic active        boscope L video Stroboscopy Otolaryngology) and NBI by
pulmonary TB. The pathogenesis of LTB and clinical syn-           Olympus (Visera Pro CLV-S40Pro).
drome was first described by Dworetzky 1 in 1941 and later        A detailed search in PubMed and Medline on LTB from
by Auerbach 2 in 1946. Nowadays LTB is a rare presenta-           January 2000 to December 2021 was performed. The
tion of TB, overall accounting for 1% of cases, while in the      search yielded a total of 357 relevant articles. We included
first decades of the 20th century it accounted for 25% 3,4.       only papers in English language containing a series of 15
Despite its low percentage of incidence, LTB is the most          or more patients. The number of cases, sex, age, country,
frequent granulomatous disease affecting the larynx 5.            clinical presentation, larynx localisation, fibre-endoscopic
Over the last 20 years there has been a worldwide recru-          findings, pulmonary active or inactive TBC, voice analysis,
descence of tuberculosis, mostly connected to the spread          therapy and follow-up were collected and compared in the
of AIDS and other immunodeficiency conditions. Other              present review.
risk factors are poor quality of life, malnutrition, alcohol      Articles in which these data were missing have been ex-
abuse and smoking 4,6,7. The male to female ratio for LTB         cluded from the study. Ten case series were included in the
is around 2.5:1 with a mean age of 49.5 years. The most           analysis, for a total of 308 cases.
frequent symptoms are hoarseness, dysphonia, weight loss,
cough, dysphagia and odynophagia 3,7,8.                           Results
LTB infection determines an exudation in the subepithe-
lial space with subsequent infiltration of round cells which      Case report
results in fibrosis. This scarring leads in most cases to ir-     A 67-year-old Italian woman referred to the Otolaryngol-
reversible changes in vocal fold structure, with consequent       ogy Department of the M. Bufalini Hospital, Cesena, Emil-
alteration of glottic vibration and dysphonia 9.                  ia-Romagna, Italy. Her main complaint was one-year his-
Misdiagnosis is not rare because endoscopic examination           tory of dysphonia that had worsened in the last two months.
is often characterised by a exophytic and/or ulcerous lesion      Her medical history included smoking (about 40 cigarettes
surrounded by erythema, mimicking malignant laryngeal             a day for the past 15 years). She denied alcohol consump-
disease.                                                          tion and congenital or acquired immunodeficiency. She
Case series have found that both diseases can affect the lar-     was unaware of TB contacts and had not travelled to en-
ynx simultaneously 6,10. Clinicians should be aware of this       demic areas, while a possible exposition could have been
unusual localisation of TB in differential diagnosis.             related to her occupation, being a physician. The patient
Herein, we performed a systematic literature review of the        had no respiratory symptoms, weight loss, fever or other
last 20 years on LTB. In addition, we describe a case di-         systemic manifestations. A laryngoscopy examination
agnosed and treated in our hospital with special focus on         (Fig. 1) revealed a moderate Reinke’s edema of the right
voice assessment.                                                 vocal fold and a diffuse hyperplasic tumour-like aspect of
                                                                  the true left vocal fold, which extended posteriorly to the
                                                                  vocal process of the ipsilateral arytenoid. No granulomato-
Materials and methods                                             sis or ulcerative lesions were detected. The laryngostrobos-
In accordance with the European Laryngological Society            copy revealed a stiff left vocal fold with reduced mucosal
(ELS) guidelines, the phoniatric protocol in our centre in-       wave, while motility and glottic closure were preserved 15.
cludes the use of modified GRBAS scale (Grade, Rough-             Narrow Band Imaging (NBI) examination did not reveal
ness, Breathiness, Asthenia and Strain) for auditory percep-      any specific vascular patterns.
tual voice assessment. The evaluation is performed by two         At the first visit the patient presented G2R2B1A0S2, VHI-
experienced phoniatricians. We adopted the Voice Handi-           10: 27, MPT 6 sec, Jitter 8.6% and Shimmer 18.59%.
cap Index-10 (VHI-10) administration for subjective voice         Chest X-Ray did not show any pathological findings. A
evaluation and Maximum Phonatory Time (MPT) calcula-              neck CT scan with Contrast Enhancement (CE) (Fig. 2)
tion as aerodynamic index 11-14. In addition, jitter and shim-    was also performed and confirmed thickening and CE at
mer were collected from acoustic analysis of the voice.           the level of the posterior superior third of the left hemilar-
Moreover, we provided a morphological and dynamic                 ynx involving the false cord and the left true vocal fold,
evaluation of the vocal folds, with flexible digital fiberoptic   with obliteration of the ipsilateral laryngeal ventricle and
endoscopy and stroboscopy. The vascular pattern of the le-        paraglottic space invasion. Despite a large and deep exten-
sion was evaluated with Narrow Band Imaging (NBI). The            sion of the lesion, the CE was modest and superficial. No
equipment used consisted of: Video Rhinolaryngoscope              erosion of the hyoid bone and laryngeal cartilages was no-
Olympus ENF-VQ, stroboscopy by ATMOS (Endo Stro-                  ticed. The anterior commissure was preserved.



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                                                                                                        Laryngeal tubercolosis: a case report and literature review




A direct microlaryngoscopy was performed. During the                                 After the specific therapy for TB, the patient had complete
procedure, careful laryngeal exploration revealed a lesion                           resolution of the lung and laryngeal pathology confirmed by
of the left hemilarynx that extended from the posterior third                        negative CT scan. A laryngoscopy examination at 12 months
of the true vocal fold to the floor of the ventricle and to the                      from the biopsy and three months from the end of systemic
arytenoid.                                                                           treatment was performed (Fig. 1). The left vocal fold ap-
Due to the deep extension of the disease revealed by CT                              peared diffusely scarred and slightly swollen. Laryngostro-
and the lack of superficial lesions, in order to avoid taking                        boscopy showed a slightly reduced mucosal wave, while vo-
a non-diagnostic biopsy sample, four deep biopsies were                              cal folds motility and glottic closure were preserved. NBI
collected with a CO2 laser.                                                          examination was analogous to pre-treatment evaluation.
The histopathological report described chronic focally ne-                           Voice evaluation after treatment revealed a substantial im-
crotising granulomatous inflammation. Additional histo-                              provement of all parameters, suggesting significant voice
pathological investigations included Ziehl-Neelsen stain-                            improvement: G1R1B0A0S0, VHI-10: 2, MPT greater
ing for alcohol-acid fast bacilli, Congo red staining and                            than 10 sec, Jitter 5.12% and Shimmer 13.86%.
cytokeratin immunohistochemistry for squamous cell car-
cinoma: all were negative.                                                           Literature review
Considering the biopsy findings and the most probable                                Ten articles regarding LTB were identified in the English
inflammatory granulomatous laryngeal diseases 16 (TB,                                literature that matched our inclusion criteria, with a total of
sarcoidosis, fungal laryngitis and Wegener granuloma-                                308 cases (Tab. I).
tosis), the patient was evaluated by a pneumologist who                              The sample was very heterogeneous in terms of country of
prescribed a sputum test even if alcohol-acid fast bacilli re-                       origin: 3 studies were from China, 2 from Japan and 1 from
search and X-Ray of the lungs were negative. The sputum                              Taiwan, South Korea, India, Poland and Brazil each.
test and the culture examination revealed the presence of                            Of the 308 patients, 198 (64.3%) were males and 110
acid-fast bacilli. The patient was then referred to an infec-                        (35.7%) were females. At the time of diagnosis, the mean
tious disease specialist, who clinically suspected an active                         age range was 44.6-56.5 years.
pulmonary TB, confirmed by pulmonary High-Resolution                                 Odynophagia or pharyngodynia (174/308), hoarseness
CT (HRCT) scan.                                                                      (130/308), dysphonia (125/308) and cough (119/308) were
The treatment was completed in 9 months and consisted                                the most frequent presenting symptoms.
of: ethambutol, pyrazinamide, rifampicin and isoniazid for                           Occasionally, the first reported symptoms were dysphagia
2 months, and then rifampicin and isoniazid. Following the                           (35/308), shortness of breath/dyspnoea (35/308) or sys-
latter treatment which caused hepatoxicity, isoniazid was                            temic symptoms (19/308), one patient presented to clinical
discontinued and restarted at a lower dose 17.                                       observation with stridor.




Figure 1. Laryngoscopy: (A) pre-treatment laryngoscopy showed a moderate Reinke’s oedema of the right vocal fold and a diffuse hyperplasic tumour-like aspect
of the true left vocal fold, extended posteriorly to the vocal process of the ipsilateral arytenoid; (B) laryngoscopy after three months from the end of the systemic
treatment revealed a scarred and tumefied left vocal fold.



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A. Migliorelli et al.




Table I. Literature review.
 Author             Country      No.    Sex    Mean age            Symptoms              Fibroscopic findings        Single/      Larynx localization
                                       (M/F)   (yrs ± DS)                                                            Multiple
                                                                                                                      (S/M)
 Nishiike,              Japan    15    M: 11   51.1 ± 3.7       Hoarseness: 11           Ulcerative lesions: 7        S: 6            Epiglottis: 8
 2002 8                                 F: 4                       Cough: 10           Granulomatous lesions: 5       M: 9         True vocal fold: 10
                                                                Odynophagia or         Nonspecific inflammatory                    False Vocal fold or
                                                               pharyngodynia: 9               lesions: 3                               Ventricle: 8
                                                             Systemic symptoms: 7                                                     Arytenoid: 7
                                                                  Dysphagia: 4
 Lim,                   South    60    M: 39      49.7          Hoarseness: 58            Granulomatous: 22           S: 37        True vocal fold: 46
 2006 23                Korea          F: 21                       Cough: 31                Ulcerative: 11            M: 23        False vocal fold: 18
                                                               Odynophagia: 24               Polypoid: 16                             Epiglottis: 12
                                                                                           Nonspecific: 11                            Arytenoids: 7
                                                                                                                                Posterior commissure: 10
 Wang CC                Taiwan   26    M: 19    47.11 ±         Hoarseness: 22         Mucosa white lesion: 10        M: 8         True vocal fold: 21
 2007 20                                F: 7     18.23            Cough: 12                 Ulceration: 13            S: 18     Posterior commissure: 10
                                                                Odynophagia: 8        Granulomatous tumours: 13                    False vocal fold: 10
                                                             Shortness of breath: 5   Nonspecific inflammation: 7                      Epiglottis: 7
                                                             Sistemic symptoms: 3                                                      Subglottis: 1
                                                                   Cervical
                                                             lymphoadenopathy: 2
                                                                   Stridor: 1
 Ling L                 China    19    M: 15      44.6          Hoarseness: 12             Polypoid lesion: 4         S: 11         One vocal fold with
 2010 30                                F: 4                     Sore throat: 3          Diffuse congestion: 3        M: 8       irregular closure gap: 4
                                                                Odynophagia: 6        Rough tumour-like lesion: 4                      Epiglottis: 3
                                                             Systemic symptoms: 3      Diffuse papillary lesion: 8                One true vocal fold: 4
                                                                                                                                    Multiple lesions in
                                                                                                                                bilateral false vocal folds
                                                                                                                                  and true vocal folds: 8
 Bruzgielewicz,         Poland   20    M: 14   56.5 ± 8.5      Hoarseness: 18           Ulcerative tumour: 8          S: 15           Vocal folds: 12
 2014 21                                F: 6                       Cough: 9           Papillomatous tumour: 7         M: 5      Posterior commissure: 8
                                                                 Dysphagia: 4           Chronic hypertrophic                        Vestibular folds: 5
                                                                 Dyspnoea: 2                 laryngitis: 5
                                                            Systemic symptoms: 6
 Kurokawa,              Japan    17    M: 9    51.4 ± 14.0     Hoarseness: 15             Perichondritic: 3            S: 1        True vocal fold: 16
 2015 24                               F: 8                    Odynophagia: 7                Ulcerative: 6            M: 16           Arytenoids: 6
                                                             Abnormal sensation          Granulomatous: 6                          False vocal fold: 4
                                                           syndrome of the throat: 4          Polypoid: 1                              Epiglottis: 4
                                                                  Cough: 13          Nonspecific inflammatory: 1
 Reis,                  Brazil   36    M: 28     47.08 ±        Dysphonia: 32         Granulomatous lesion: 24         S: 8            Epiglottis: 21
 2016 31                                F: 8      14.75           Cough: 32           Nonspecific inflammatory        M: 28       Aryepiglottic fold: 22
                                                               Odynophagia: 27                lesion: 19                           Arytenoid region: 18
                                                           Dyspnoea on exertion: 19     Ulcerated lesion: 14                    Interarytenoid region: 12
                                                                Dysphagia: 11             Erosive lesion: 8                        False vocal fold: 24
                                                             Dyspnoea at rest: 5                                                    True vocal fold: 32
                                                               Reflex otalgia: 2
 Zhao,                  China    61    M: 23      47.7       Voice problems and           Pale edema: 24                -          Vestibular folds: 4
 2017 18                               F: 38                     aphonia: 57              Hyperplasia: 34                            Vocal folds: 20
                                                            Sore throat and painful      Ulcerative lesion: 3                     Aryepiglottic folds: 8
                                                                swallowing: 49                                                        Epiglottis: 4
                                                              Both hoarse voice
                                                            problems/aphonia and
                                                              sore throat/painful
                                                                swallowing: 42
                                                              Cough and sputum
                                                                production: 20
                                                                 Dysphagia: 9
                                                                                                                                                  continues u




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                                                                                                 Laryngeal tubercolosis: a case report and literature review




Table I. Literature review (follows).
 Author             Country No.          Sex    Mean age          Symptoms               Fibroscopic findings          Single/      Larynx localization
                                        (M/F)   (yrs ± DS)                                                             Multiple
                                                                                                                        (S/M)
 Agarwal,             India      15     M: 12       49           Hoarseness: 6        Ulceroproliferative lesion: 10    S: 15             Epiglottis: 8
 2019 32                                 F: 3                   Odynophagia: 6            Exophytic growth: 5           M: 0          True vocal fold: 4
                                                              ‘Change in voice’: 3                                                    false vocal fold: 1
                                                                                                                                   Anterior commissure: 1
                                                                                                                                      Pyriform sinus: 1
 Zang,                China      39     M: 28   47.5 ± 15.8   Dysphonia including      Nonspecific inflammatory         S: 8            Vocal folds: 33
 2020 33                                F: 11                   hoarseness and                lesion: 22                M: 31       False vocal folds: 22
                                                                  aphonia: 33            Ulcerative lesion: 47                       Arytenoid region: 23
                                                              Sore throat including      Exophytic lesion: 55                       Aryepiglottic fold: 17
                                                                odynophagia: 26                                                   Interarytenoid region: 11
                                                                  Dyspnea: 4                                                             Epiglottis: 25
                                                                 Dysphagia: 7                                                            Subglottis: 2



Granulomatous lesion was found at laryngeal fibroendoscopy                    Two aetiopathogenetic mechanisms of LTB have been de-
in 104 cases, ulcerative lesion in 119 findings and non-spe-                  scribed to explain the cause of laryngeal localisation: the
cific inflammatory pattern in 92 cases. Less frequently, laryn-               first is the bronchogenic one. The larynx is directly con-
geal lesions had a polypoid (n = 21), papillomatous tumour                    taminated by bacilli-rich pulmonary secretions, and there-
(n = 12), or mucosal white lesion appearance (n = 10). A sin-                 fore laryngeal involvement occurs secondary to pulmonary
gle lesion was found in 119 patients, whereas multiple lesions                involvement. The posterior larynx is the most affected area
were identified in 128 cases. In 64 cases, the initial suspicion              in secondary LTB because it is where infected secretions
was for laryngeal cancer, and a biopsy was performed.                         most frequently accumulate. The second is the haemato-
The true vocal folds were involved in 163 cases, the false                    genic route. Blood or lymphatics carry bacillus to the lar-
vocal folds and ventricle in 104 patients and the epiglottis in               ynx prevalently affecting the anterior region 19.
92 cases. The remaining cases involved arytenoid (n = 61),                    Known risk factors are HIV, poor quality of life, malnutri-
aryepiglottic fold (n = 47), interarytenoid region (n = 23),                  tion, alcohol abuse and smoking habit 4,6,7.
posterior commissure (n = 28) and subglottis (n = 3).                         Odynophagia or pharyngodynia, hoarseness and dysphonia
Chest X-ray or high resolution computed tomography                            were present in the majority of cases at diagnosis. Respira-
(HRTC) was performed in all patients and evidence of active                   tory failure due to vocal fold immobility is a rare presenting
lung TBC was confirmed in 164 cases. In 45 patients, an inac-                 symptom that can sometimes lead to emergency tracheot-
tive TBC or signs of previous disease was detected. Primary                   omy 20. It is important to underline that the risk factors and
LTB with normal chest radiography was found in 101 cases.                     main presenting symptoms of LTB are the same as those
Where specified, the diagnosis was made by Purified Pro-                      of laryngeal cancer. Furthermore, it should be kept in mind
tein Derivative (PDD), sputum testing, or laryngeal tissue                    that the two diseases can also coexist 21.
histopathology, and confirmed by isolation of Mycobacte-                      In the suspicion of a LTB and even more in the suspicion of
rium tuberculosis in laryngeal tissue culture.                                malignant laryngeal disease, fibrolaryngoscopy is manda-
                                                                              tory. NBI can help in the diagnostic process. The physician
                                                                              should consider pathologies other than laryngeal cancer
Discussion
                                                                              (such as LTB) if NBI is negative for a typical tumour pat-
LTB is an uncommon finding in otolaryngology practice,                        tern 22.
although it is the most frequently reported granulomatous                     The lack of a universally-accepted fibroendoscopic classi-
disease in the larynx 5. LTB is a rare pathology, resulting in                fication makes evaluation and comparison of the present-
a limited number of cases in the literature. To the best of                   ing laryngeal lesions reported in the literature particularly
our knowledge, this is one of the most complete reviews in                    difficult. According to Suetaka et al. 10, almost all studies
the literature on LTB, involving studies from seven coun-                     refer to granulomatous, ulcerative and non-specific inflam-
tries and three continents.                                                   matory lesions as the most frequently presenting laryngeal
In the literature, a predominance of males was described                      lesions. Other authors have added other lesional patterns
(M:F = 2:1), and only one article reported a higher percent-                  to this classification such as polypoid or mucosal white le-
age of females 18.                                                            sions 20,23.



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A. Migliorelli et al.




Figure 2. Neck CT scan with contrast enhancement.


In our opinion, endoscopic classification should go beyond       relevant are TB, sarcoidosis, fungal laryngitis, Wegener
the three most frequent lesions mentioned above, consider-       granulomatosis, leprosy, syphilis and rhinoscleroma 16.
ing that in countries where the incidence of LTB is lower,       As a consequence, biopsies represent an essential tool to
the disease may occur with less common presentations, as         make a proper differential diagnosis between a suspected
in the case we described.                                        cancer, laryngeal tuberculosis, or other granulomatous dis-
Considering the site of presentation, in 163 cases the LTB       eases. The next step for correct diagnosis is bacteriologi-
affected the true vocal fold, while the other most common        cal and histological examination on laryngeal biopsies 25,26.
sites were false vocal fold (n = 104), epiglottis (n = 92) and   The first examination can detect the bacterium (Mycobac-
arytenoid (n = 61). LTB can also compromise motility and         terium tuberculosis) with Ziehl-Neelsen staining. In some
mucosal vibration of the vocal cords. The literature sug-        cases, it is also possible to achieve slow-growing colonies
gests that laryngeal lesions can be multiple or single with-     with an ivory-white cauliflower aspect if the specimen is
out substantial differences in terms of incidence. Jae-Yol       placed on a special culture medium known as Lowenstein-
Lim et al. 23, in a review of 60 patients, reported that mul-    Jensen. On the other hand, histological examination should
tiple lesions are mostly associated with the ulcerative type.    detect the tuberculous follicle characterised by a peripheral
Granulomatous, polypoid and non-specific inflammatory            zone made up of Langhans cells, epithelioid cells and lym-
types are usually associated with single lesion presenta-        phocytes, and a central caseous zone 6,25,26. Furthermore, we
tions.                                                           believe that even when the alcohol-acid fast bacilli research
In addition, other authors believe that protracted disease       and X-Ray of the lungs are negative, if histologic findings
may involve multiple areas of the larynx with the expres-        are suggestive of chronic inflammatory pathology, further
sion of more than one lesion 24.                                 investigation and research including a sputum test should
If LTB is suspected, all diagnostic and therapeutic proce-       be performed, as in the case we described.
dures should be performed while wearing an FFP3 face             Finally, we want to emphasise that although LTB is rare
mask to reduce the risk of infection to operators 3.             and insidious, correct and rapid diagnosis can be achieved
According to the literature, once suspicion of LTB is estab-     thanks to the collaboration of several healthcare profes-
lished by fibre endoscopic examination, a chest radiograph       sional including an ENT, pulmonologist, infectious disease
or preferably HRTC should be performed to detect pulmo-          specialist, pathologist and microbiologist.
nary TB. In most cases, active TB is diagnosed, whereas          As reported in our case and in agreement with the litera-
the finding of a primary LTB is less frequent.                   ture, treatment involves the use of the 4 antituberculosis
As previously mentioned, laryngeal tuberculosis and laryn-       drugs (isoniazid, rifampicin, pyrazinamide and ethambu-
geal cancer may have similar clinical and endoscopic find-       tol) with posology and dosage reported in the guidelines of
ings and clinicians should always consider LTB, even in          each individual centre.
non-endemic areas. Furthermore, it should be emphasised          Dysphonia is one of the main symptoms and most invali-
that LTB has to be included in differential diagnosis with       dating for the patient’s quality of life. Despite this, little
all other inflammatory and noninflammatory benign chron-         focus has been placed on evaluation of post-treatment voice
ic diseases of the larynx. Among the granulomatous dis-          outcomes to date.
eases affecting the larynx, those which are more clinically      We believe that it is very important to perform accurate



412
                                                                                     Laryngeal tubercolosis: a case report and literature review




and multidimensional voice analysis both before and af-          Conflict of interest statement
ter phonosurgical procedures for all laryngeal disorders. In     The authors declare no conflict of interest.
our hospital, according to ELS recommendations, subjec-
tive (VHI-10 and GRBAS) and objective (MPT, Jimmer               Funding
and Shimmer) measures were collected before and after            This research did not receive any specific grant from fund-
surgery 11-14.                                                   ing agencies in the public, commercial, or not-for-profit
Moreover, it is important to perform laryngostroboscopy          sectors.
to investigate vocal fold motility, mucosal wave and glottic
closure 15.                                                      Author contributions
Areas of ambiguity and controversy still exist regarding the     AM and MS: original idea, wrote the paper, conceived and
efficacy of antituberculous therapy in the recovery of dys-      performed the analysis; TM, AB and DB: collected data
phonia. Yelken et al. 27 postulated that TB treatment results    and performed literature search; MF and FE: contributed to
in significant improvement in voice quality in all patients.     data analysis. All authors read and approved the final ver-
Conversely, Ozudogru et al. 28 stated that an irreversible fi-   sion of the manuscript.
brotic change in the vocal fold caused by LTB results in
persistence of dysphonia even after treatment. Currently,        Ethical consideration
specific literature data on post-treatment voice quality are     No Ethical Committee approval was required for this study.
scarce; further studies on this topic should be conducted in     The research was conducted ethically, with all study proce-
the future. In our patient, there was improvement in voice       dures being performed in accordance with the requirements
quality after antituberculous treatment, but a mild degree of    of the World Medical Association’s Declaration of Helsin-
dysphonia persisted.                                             ki. Written informed consent was obtained from each par-
Some authors describe speech therapy as a useful approach        ticipant/patient for study participation and data publication.
to improve voice quality after LTB, and we concur 29. We
proposed speech therapy for vocal rehabilitation to our pa-      References
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