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Year : 2018  |  Volume : 8  |  Issue : 1  |  Page : 1-5

Primary laryngeal tuberculosis: A frequently misdiagnosed disease

1 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Web Publication8-May-2019

Correspondence Address:
Prof Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jlv.JLV_5_18

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Primary laryngeal tuberculosis (PLT) is a granulomatous infection of the larynx caused by Mycobacterium tuberculosis without affecting the lungs. It is a rare type of extrapulmonary tuberculosis seen in clinical practice. After the introduction of antitubercular therapy (ATT), the incidence of LT is reduced and remains stable. However, the incidence of PLT is increasing due to acquired immune deficiency syndrome epidemic. The important clinical presentations of PLT are dysphonia and odynophagia. The diagnosis is confirmed by histopathological examination as it often mimics laryngeal malignancy. The treatment is ATT, whereas surgery is only reserved in certain situations where is compromising the laryngeal airway by its granulomatous growth. Delayed or misdiagnosis or untreatable LT will lead to high morbidity and mortality of a patient. Although primary tubercular lesion has nonspecific clinical presentations, it is very important to have a high index of suspicions to rule out tubercular lesion in the larynx as this disease is a curable one.

Keywords: Antitubercular therapy, extrapulmonary, histopathology, larynx, primary laryngeal tuberculosis

How to cite this article:
Swain SK, Sahu MC, Kar SS. Primary laryngeal tuberculosis: A frequently misdiagnosed disease. J Laryngol Voice 2018;8:1-5

How to cite this URL:
Swain SK, Sahu MC, Kar SS. Primary laryngeal tuberculosis: A frequently misdiagnosed disease. J Laryngol Voice [serial online] 2018 [cited 2023 Mar 20];8:1-5. Available from: https://www.laryngologyandvoice.org/text.asp?2018/8/1/1/257808

   Introduction Top

Tuberculosis is a granulomatous infectious disease caused by Mycobacterium tuberculosis. This disease mainly affects lungs called as pulmonary tuberculosis but can also affect extrapulmonary site such as larynx. Tuberculosis is a major public health problem in developing and underdeveloped countries. It often affects the lungs causing pulmonary tuberculosis, which accounts for 80% of the cases.[1] However, it can involve any other organ of the human body. Laryngeal tuberculosis (LT) is a rare type of extrapulmonary tuberculosis, which constitutes <1% of all types of tuberculosis cases.[2] Due to higher number of immunocompromised persons and rising multidrug-resistant tuberculosis cases, there more number of primary LT (PLT) nowadays. Approximately 530,000 children are suffering with tuberculosis in the developing countries around the world.[3] The extrapulmonary involvement of tuberculosis ranges from 30% to 40%.[4] Larynx is an uncommon site for tuberculosis in the community. PLT may cause mild hoarseness of voice to severe odynophagia and dyspnea due to laryngeal edema and granulations. A clinician or an otorhinolaryngologist should be familiar with unusual site like larynx for tuberculosis. Currently, the worldwide recrudescence of tuberculosis caused due to spread of human immunodeficiency virus (HIV) infection infection. The presentation is often misleading confused with laryngeal cancer. Due to nonspecific clinical presentations and relative lack of familiarity of this lesion amoung clinician, this may lead to the misdiagnosis of PLT. This review article discusses the etiopathology, clinical presentation, investigations, and treatment of PLT. This must be considered in the interest for avoiding misdiagnosis, inappropriate treatment, and untoward outcomes for not only the patient but also the public as well.

   Etiopathology Top

PLT is a rare clinical entity and often caused by direct invasion of the inhaled M. tuberculosis bacilli.[5] Secondary involvement of the larynx occurs by cough and expectoration from tracheobronchial tree or through bloodstream from other than lungs.[6] Lymphatic spread to the larynx is rare. Laryngeal sites affected by tuberculosis in the decreasing order is as follows: true vocal folds (50%–70%), false cords (40%–50%), epiglottis, aryepiglottic folds, arytenoids, posterior commissure, and/or subglottis (10%–15%).[6] The tubercular lesions in the different parts of the larynx may appear as ulcerative [Figure 1], ulcero-fungative, granulomatous lesions [Figure 2], polypoidal [Figure 3], or nonspecific inflammatory.[7] Congestion of unilateral vocal cord should alert one for the possibility of tubercular lesion. The lesions of PLT may mimic leukoplakia, chronic laryngitis, or laryngeal candidiasis.[8] It can affect any part of the larynx.[9] The vocal cords of the larynx are commonly affected in LT. LT is characterized by edema, hyperemia, or ulcerative lesions in the larynx. Arytenoids, posterior commissure, and epiglottis are affected in LT if it coexists with pulmonary tuberculosis. LT is a highly contagious disease of the human being. LT is often associated with pulmonary tuberculosis,[10] but a patient also has LT without a history of pulmonary tuberculosis in case PLT.[11] PLT mostly occurs in adult males aged between 40 and 50 years.[11] It is often seen in persons without BCG vaccination, with malnutrition or in patients of acquired immunodeficiency syndrome, low immunity, and chronic smoking.[10] Of the different predisposing factors, alcohol abuse and smoking are the two known risk factors for PLT.[12] The link between the HIV infection and tuberculosis is documented in the literature.[13] Congestion of unilateral vocal cord should alert the physician for a possible of tubercular lesion. Smoking habit of a person aggravates LT. Smoking affects the mucosa of the larynx by chronic stimulation and causes decrease defensive capability of the larynx.[14] This consideration suggests that mucosal membrane of the larynx is inflamed by smoking and may be more likely affected by the transairway infection from the tuberculosis and so lead to more progressive LT. PLT has no gender or age predilection.
Figure 1: Ulcerative lesions on the vocal folds in primary tubercular laryngitis

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Figure 2: Granulomatous lesion on the arytenoids in primary tubercular laryngitis (arrow mark)

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Figure 3: Polypoidal lesion on the vocal fold in primary tubercular laryngitis (arrow mark)

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   Epidemiology Top

“Captain of all these men of death” is referred to tuberculosis by John Bunyan in the 18th century, which is still the biggest health challenge to the world.[15] The prevalence of tuberculosis is more in underdeveloped and some developing countries of the world. Tuberculosis is the most common cause for death all over the world which includes a quarter of all avoidable death globally.[15] The World Health Organization (WHO) documented that India has the highest incidence of tuberculosis, accounting 168 cases per one lakh population (approximately 42 times the incidence of North America which is 4 per 1 lakh).[16] Extrapulmonary tuberculosis constitutes approximately 25%, of which 10%–35% of the cases at the head and neck area.[17] About 14% of the pulmonary tuberculosis patients are associated with extrapulmonary involvement.[18] Tubercular cervical lymphadenopathy is the most common manifestation in head and neck tubercular lesions followed by tubercular otitis media and LT.[19] LT is a rare type of extrapulmonary tuberculosis which constitutes <1% of all types of tuberculosis cases.[2] Due to higher number of immunocompromised persons and rising of multidrug-resistant tuberculosis cases, there is more number of LT nowadays. The prevalence of HIV infection associated with tuberculosis is 8.8%, which increases the mortality of the patient by 33%.[20]

   Clinical Presentations Top

The tuberculosis of the larynx often presents with hoarseness of voice (80%–100%) and odynophagia (50%–67%), which often mimic other laryngeal diseases also.[21] It may lead to severe dyspnea and stridor due to laryngeal edema and granulations. Hoarseness of voice is the most common clinical presentation, but odynophagia and dyspnea can also be present in case of PLT patients. The constitutional clinical symptoms such as fatigue, weight loss, fever, night sweats, and hemoptysis are often seen in these patients. The clinical signs are often minor in primary tubercular lesions of the larynx and the features such as fever, weight loss, and asthenia are essentially seen in the advanced form of isolated laryngeal tuberculosis with severe odynophagia. The gross laryngoscopic lesions vary from ulcerative lesions to hypertrophic exophytic and polypoid lesions.[22] The macroscopic appearance of PLT is classified into four types: granulomatous, polypoid, ulcerative, and nonspecific. The lesions are either single or multiple. Granulomatous lesions in LT are more common in patients among pulmonary tuberculosis coexisting with laryngeal lesion.[23] The family should be screened as members suffering from tuberculosis may spread bacilli directly to the larynx through inhalation. The differential diagnoses of PLT are syphilis, neoplasm, sarcoidosis, Wegener's disease, leprosy, actinomycosis, lupus, recurrent polychondritis, rheumatoid arthritis, and amyloidosis.[24]

   Investigations Top

PLT is a very uncommon clinical entity and often mimics malignancy in imaging or during laryngoscopy examination.[10] The diagnosis of LT is based on pathological and microbiological findings of the biopsy specimen collected from the larynx [Figure 4]. Diagnosis of PLT is confirmed by histopathological examinations with chronic granulomatous inflammatory exudates with or without caseating necrosis. In some cases of histopathology, picture shows the absence of caseations where the diagnosis is confirmed by recovery of the patients under antitubercular therapy (ATT). Routine blood investigations such as total white cell counts, differential count, and erythrocyte sedimentation rate (ESR) are done in all cases. Blood investigations are often normal, except a slight increase of activated protein C and erythrocyte sedimentation rate. Anti-streptolysin O titers may be elevated. Mantoux test and QuantiFERON assay are often positive.[25] Tuberculin test is also advised in all cases. The tuberculin test is also known as Mantoux test which is a standard procedure during the diagnosis of tuberculosis. It includes intradermal inoculation of purified protein which is derived from M. tuberculosis for assessing the cellular immune response to the antigens. The inflammatory reaction occurs in M. tuberculosis-sensitized patients. The observation of reaction is done after 48–72 h and is valid for 7 days. The evaluation of tuberculin test is based on the diameter of the inflammatory area calculated transversally against the longitudinal direction of the challenged forearm. The inflammation area >10 mm in immunocompetent persons is considered a positive result. The inflammatory area >5 mm in immunocompromised patient indicates positive for tuberculosis. The Mantoux test although used for diagnosis of tuberculosis, it has certain limitations such as the low sensitivity in immunocompromised patients, difficult in children, subjective character of interpretation.[26] ESR and Mantoux tests should not be used for diagnosis but are much helpful in pursuing the patients and subjecting for further investigation on strong clinical suspicion. Sputum microscopy for acid-fast bacilli (AFB) is positive in around 20% of the cases of LT and most of the chest X-ray findings are consistent with pulmonary tuberculosis.[27] Ziehl–Neelsen staining may directly show AFB. The microbiological culture and drug sensitivities of the infective strain are not usually done in practice, whereas the multiple repeated biopsies are often used for confirming the diagnosis and starting the treatment.[28] The polymerase chain reaction (PCR) test is used for the confirmation of tuberculosis. The detection of M. tuberculosis is increased from 2% to 17% on culture to 89%–100% in PCR.[29] In cases of strong clinician suspicion of tuberculosis with negative cultures, samples can be sent for PCR test.[17] QuantiFERON-TB Gold In-Tube (QFT-GIT) is an interferon gamma release assay (IGRA) which is often used to detect tuberculosis. It is an in vitro diagnostic test which needs blood drawn. As per the updated guidelines for IGRAs to find out M. tuberculosis, the QFT-GIT holds promise.[30]
Figure 4: (a) Histopathological examination showing granuloma formation with caseous necrosis. (b) Ziehl–Neelsen staining from biopsy specimens showing acid-fast bacilli

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   Treatment Top

LT responds well to ATT. The treatment of LT is similar to pulmonary tuberculosis with surgical intervention to ensure patent and safe airway if laryngeal airway is threatened by tubercular granuloma. As per the WHO guidelines, LT or extrapulmonary tuberculosis should be treated with four-drug regimen for 2 months followed by two drugs for next 4 months.[31] ATT is the cornerstone of treatment for this disease, and the role of surgery is only done for early diagnosis and maintaining airway if compromised.[32] The drug combination used includes isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by isoniazid and rifampicin for 4 months.[33] However, in case of drug-resistant M. tuberculosis, these guidelines are not appropriate where more drugs are used or treatment is prolonged.[34] Many otolaryngologists may not familiar with clinical presentations and treatment of LT due to paucity of this type of cases. To avoid untoward outcomes amoung patients suffering from this lesion, healthcare workers and public at large should be targeted to improve awareness. It is also vital for the physicians to be familiar with this contagious disease like LT.

   Conclusion Top

PLT is a rare clinical entity in comparison to pulmonary tuberculosis, but nowadays, its incidence is rising in endemic area. It should be considered as a differential diagnosis in case of ulcerative or any inflammatory swelling of the vocal fold. Abnormal chest X-ray showing the features of tuberculosis along with laryngeal lesion suggests the diagnosis, whereas normal chest X-ray cannot exclude the diagnosis. Hence, the clinician should keep in mind the existence of PLT thus avoiding delayed treatment. Delayed diagnosis or untreated LT will lead to high morbidity and mortality of the patient. Although it has nonspecific clinical presentations, it is very important to have a high index of suspicion to rule out tubercular lesion in the larynx as this disease is curable.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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