Primary Tuberculosis of Upper Respiratory Tract – A Comprehensive Review Article

Amal Johnson et al.: Primary Tuberculosis of Upper Respiratory Tract – A Comprehensive Review Article

¹Post graduate, Department of Respiratory Medicine, Apollo Hospitals, Chennai
²Post graduate, Department of E.N.T., Stanley Medical College, Chennai
³Professor and Chief, Department of E.N.T., Stanley Medical College, Chennai

Corresponding Author: Dr. Amal Johnson, Post graduate Department of Respiratory Medicine. Email: amal.johnson2210@gmail.

How to cite this article: Amal Johnson, Anto Sherly Sophia, V. Rajarajan, Primary Tuberculosis of Upper Respiratory Tract – A Comprehensive Review Article, JAPT 2019;2(3):105-116

Introduction

Tuberculosis of the upper airway is usually seen in conjunction with primary pulmonary tuberculosis.1 The continuous airflow and the smooth mucosal lining do not allow the mycobacteria to settle down in the respiratory tract, except the larynx5. Upper respiratory tract TB (URT-TB) is one of the rare forms of extra pulmonary TB (EPTB)15. Before treatment, patients with active pulmonary TB progressively deteriorated and often developed laryngeal, otological, nasal, paranasal, and pharyngeal involvement5.

Epidemiology:

The frequency of involvement may vary from all parts of the upper respiratory tract from the nose to the vocal cords and the larynx5. The most common site of TB in the head and neck involved the cervical lymph nodes and the nasopharynx11.Majority of cases of URT-TB have cervical lymphadenopathy2-9. Tubercular laryngitis is the most infectious form of disease16.

Tuberculous laryngitis manifest in isolation or in combination with tuberculosis of the epiglottis, pharynx, tonsils, or soft palate.13 while other patients had tuberculous otitis media, tuberculous tonsillitis, and tuberculous ulcerations of the tongue andpharynx14.

Common Symptoms and Signs of URT-TB

1. Nose – Nasal discharge, epistaxis, pain, nodule,
ulcer, septal perforation
2. Oral cavity – ulcer, localised swelling, tonsillar
infiltration, sore throat, dysphagia
3. Larynx – hoarseness, odynophagia, dysphagia.

Risk Factors Associated with URT-TB

• HIV
• Diabetes
• Malignancies
• Tobacco smoking
• Drug abuse, alcoholism
• Connective tissue disorders
• Use of immunosuppressive drugs
• Malnutrition
• Poor living condition

Nasal Tuberculosis

Isolated cases of nasal tuberculosis have been reported in developing countries ^{4, 5, 10, 18–21}

Clinical Features:

Patients with nasal TB commonly present with nasal obstruction and purulent rhinorrhea, Bloodstained discharge or frank epistaxis^5,23,25. Lupus vulgaris, a slowly growing, indolent ulcerative lesion caused by Mycobacterium tuberculosis, may affect the nasal vestibule, the septum, and the alae. In few cases, lupus vulgaris with papulonecrotic TB is reported5,25,26. External deformity may result in about one-third of patients.⁵

Examination

• • Pallor of the nasal mucosa with multiple inute apple jelly nodules on diascopy.
  • Nasal septal ulceration and perforation of septal cartilage can occur^2,21.
  • TB of nasal cavity can also present as polypoidal lesion²⁷.
  • Sinonasal TB can invade the surrounding bones, causing osteomyelitis and abscess formation²⁸.
  • Maxillary sinuses are commonly involved in nasal TB⁵.
  • Intracranial extension manifest as epilepsy and optic neuritis^23,29
  • Intrasellar tuberculomas, also had involvement of sphenoid sinus ^5,30

Confirmation of diagnosis is made on mycobacterial culture, histopathological examination, since the acid-fast bacilli (AFB) on smear examination may mimic Mycobacterium leprae. Standard anti-TB therapy is the treatment for Nasal TB⁵

Oral Cavity Tuberculosis:

TB is rarely involved in the oral cavity. Poor dental hygiene and mucosal injury contributed to the infection in the oral cavity. Oral lesions are the
result from the infected sputum being coughed out from concomitant pulmonary TB5, ³⁸ . Due to hematogenous spread, The tongue is the most common site to be involved, almost any part of the tongue, such as the tip, the borders, dorsum, and base, may be involved. ^5,39 .

Clinical Features

• • • Single or multiple ulcers or Nodular lesions in outh manifest in oral cavity
    • Well circumscribed and painful irregular lesions mimicking malignancy.
    • Cervical lymphadenopathy also seen in oral cavity TB.^2,40
    • A painful, deep, irregular ulcer on the dorsum of the tongue is classical oral mucosal lesion including the palate, lips, buccal mucosa and gingiva.^19,39

A recent investigation reported positive oral cultures of M.tuberculosis from samples of saliva, caries lesions, and denture plaque collected from
TB patients, demonstrating the possibility of oral infectivity of these patients41,43. The detection rates from these oral sites using Polymerase chain reaction were higher (between 89% and 100% detection rates) than traditional culture methods (0% to 17%)^42,43.

Tuberculosis of Pharynx:

TB of pharynx may present as ulcerative of lupus vulgaris type or secondary to pulmonary involvement (so-called miliary TB of the pharynx).⁵

Nasopharyngeal TB:

• • The nasopharynx is the most common site of pharyngeal involvement⁵⁰.
  • Cervical lymphadenopathy was the most common presentation (58%) nasal obstruction (10%) tinnitus, Hearing loss, otalgia, rhinorrhea, and nasal twang of the voice,⁵¹snoring².

Direct examination of the nasopharynx revealed a combination of mass and irregularity, granulation

• • • On MRI, Two types of pattern of involvement in nasopharynxare seen: discrete polypoidal mass in the adenoids
    • Pattern of more diffuse soft tissue thickening of one or two walls of the nasopharynx⁵².
    • Extension outside the confines of the nasopharynx was not seen⁵².
    • Post radiation granulomatous inflammation in patients undergoing treatment for nasopharyngeal carcinoma should be suspected as occult tubercular infection and investigated thoroughly³⁵.

Differential Diagnosis for Nasopharyngeal TB

• • • Fungal infections
    • Malignancies
    • Following radiation therapy
    • Prolonged use of nasal spray
    • Wegeners granulomatosis
    • Midline granulomatous disease
    • Leprosy
    • Syphilis

Oropharyngeal Tuberculosis:

Oropharyngeal TB present with symptoms of sore throat, dysphagia, odynophagia^53,54. TB retropharyngeal abscess may also present with dysphagia⁵⁵.

Clinical Features of Oropharyngeal TB

• • Cervical lymphadenopathy
  • Cutaneous lupus vulgaris
  • Scrofuloderma
  • Local hyperemia and irregularity of mucosa
  • Erythematous papules
  • Swelling of the cheek are associated with oropharyngeal tuberculosis⁴⁴.

Tonsillar Tuberculosis:

• Tonsils is other site of involvement in Oropharyngeal TB which may occur in isolation or concomitant with pulmonary or laryngeal TB⁵.
• Tonsillar TB was common in the ingestion unpasteurized milk contaminated with Mycobacterium bovis.

Clinical Features

• • Sore throat
  • cervical lymphadenopathy
  • dysphagia
  • ulceration
  • masses, and white patches are the features of Tonsillar TB^56–58.
  • Pharyngeal TB can also spread to the middle ear through the eustachian tube⁵⁹.
  • Multiple perforation of tympanic membrane, pale, painless profuse otorrhoea, Granulation and profound hearing loss, Preauricular lymph node enlargement and postauricular fistula are pathognomonic of tubercular otitis media.⁶⁰
  • Physical examination includes unilateral tonsillar enlargement, ulcerations, and fibrosis of the tonsils. Incisional biopsy confirms the diagnosis based on histopathological findings and the identification of AFB ⁵.
  • Anti TB Chemotherapy is treatment for Tonsillar Tuberculosis.

Pale nodule in the oropharynx noticed incidentally during fiber optic bronchoscopy for mediastinal lymphadenopathy. Needle aspiration from the nodule revealed necrotizing granulomatous inflammation and multiple, pink stained AFB.⁵

Tuberculosis of Salivary Glands

• • TB of the salivary glands occurs as a result of infection of the oral cavity or secondary to pulmonary TB5,⁶⁶.
  • Parotid involvement is the most common to be involved followed by submandibular glands⁶⁷.
  • It could be acute or chronic parotidomegaly and diagnosis is obtained on histopathological evidence ⁶¹

Mode of transmission:

• • Tuberculous salivary gland infection is most common in older children and adults.
  • The disease is spread by close person to-person contact.
  • Primary salivary gland infection evolved from a focus in the tonsil or gingivobuccal sulcus before ascending to the glands by way of their ducts69.
  • Primary TB infections occur within the parotid gland then spread to the cervical nodes through the lymphatic drainage66
  • Other mechanisms include ascending lymphogenous spread from an infected cervical lymph node and hematogenous spread from a distant focus67.

• • Clinically, tuberculous salivary gland infection presents in two different forms.
  • The first is an acute inflammatory lesion with diffuse glandular edema.
  • A second is chronic, tumorous lesion is seen as a discrete slow-growing mass that mimics a neoplasm69.
  • The chest radiograph show evidence of healed granulomatous disease.

CT Features of TB Salivary Glands:

• CT images of TB infection in the head and neck are described as having three patterns:
• In early course of disease involvement of cervical lymphnodes with nonspecific homogenous enhancement.
• In the second pattern, a nodal mass is apparent with central lucency and thick rims of enhancement and minimally effaced fascial planes.
• The third pattern appears as fibrocalcified nodes, usually seen in patients previouslytreated for TB.⁷²

Diagnosis:

• Preoperative contrast-enhanced computed tomography (CT) show the presence of thickwalled rim-enhancing lesions with a central lucency suggests the diagnosis.
• Tumors and other inflammatory processes show filling defects with or without thin walls.
• Thick-walled round rim enhancing lesions with a central lucency are characteristic of TB.
• Confirmation of the Diagnosis of most forms of extra laryngeal URT-TB requires biopsy5. On suspicion, diagnosis can also be made by fineneedle aspiration cytology⁶¹.
• FNA biopsy is better than incisional biopsy due to lower risk of draining fistula in the former. The FNA sample reveal the characteristic cytologic features: granulomatous inflammation with caseous necrosis and epithelioid histiocytes.
• Polymerase chain reaction (PCR) testing can help identify mycobacteria5,⁷³ In addition, material may be sent for culture and acidfast smears; ^5,74
• When the diagnosis is uncertain or the lesion is resistant to medical therapy, complete surgical excision is both diagnostic and curative. ⁶⁹

Treatment:

Treatment or all patients with pharyngeal and oral-cavity TB consists of anti-TB chemotherapy. The treatment response is generally favorable, and the prognosis is good62. Surgical intervention should be avoided⁶³.

Laryngeal Tuberculosis

TB is the most common cause of granulomatous disease of the larynx. Tubercular laryngitis seems to be increasing recently^{6,7, 64–71}. United States, Japan, and Spain, continue to point to the importance of the laryngeal TB^{5, 67, 72}. Presently, laryngeal TB is reported in 1 to 2% of cases ^{1, 73}.

Two cases of laryngeal TB were reported in renal transplant patients; both responded promptly to anti-TB therapy⁷⁶

Rarely, patients on glucocorticoids can develop laryngeal TB. For example, a patient with Addison’s disease on glucocorticoids and another on inhaled steroid therapy are reported to have developed tubercular infection ^{77, 78}. Laryngeal TB mimics a laryngeal carcinoma ^79–81.

Clinical Features

• • Most patients seen today are without pulmonary symptoms or a history of pulmonary TB, and it is theorized that laryngeal disease is the result of
    hematogenous or lymphatic spread^82,83.
  • The most common presenting symptom is hoarseness.^82-84
  • The primary infection can involve any part of the larynx, predominantly involved the posterior larynx.
  • Other symptoms are dysphagia, odynophagia, cough, and weight loss.^82,84
  • Despite the lack of pulmonary involvement, the purified protein derivative test result is usually positive^85,86.

• The lesions may be nodular, exophytic, or ulcerative,81,84-86 and because of their appearance, laryngeal TB is sometimes mistaken for squamous cell carcinoma (SCC).⁸⁴.
• Diagnosis of laryngeal TB is usually made by the combination of sputum culture,biopsy specimens that test positive for acidfast bacilli, and chest radiographs.⁸⁴
• Anti TB chemo therapy can alleviate symptoms and expedite the improvement in hoarseness⁸⁹.
• The true and false vocal folds were the most commonly affected sites.
• Of these 60 patients, 28 (47%) had active pulmonary disease; 20 of the 60 (33%) had inactive pulmonary TB, and 9 (15%) had isolated laryngeal TB. Lim and colleagues made special note of the focal, atypical, and unilateral laryngeal findings in patients without active pulmonary disease.

Endoscopic features

• • Laryngeal edema and granulomatous involvement of the laryngeal mucosa present in laryngeal TB.
  • Granulation tissue at the level of the glottis, subglottic stenosis,
  • vocal cord paralysis secondary to mediastinal lymphadenopathy present with Upper airway obstruction.⁸⁵.

• Mucosal inflammation, hyperemia, mucosal edema,
• Granulomatousmucosa, Mucosal ulcers ,
• Localized swelling, abscess
• Restricted movements of vocal cords, swelling/mass,
• Polypoidal growth are seen in endoscopic appearance seen in Laryngeal Isolated involvement of the epiglottic, supraglottic, or subglottic region also involved ^85–87.
• A lateral X- ray of the neck and CT can help in differentiating TB from malignancy 90.
• CT scan may show bilateral involvement, thickening of the free margin of the epiglottis, and preservation of the pre-epiglottic and paralaryngeal spaces even in the presence of extensive mucosal involvement in Laryngeal TB (90). Cartilage destruction is more common in malignancies and also seen in TB larynx 92.
• Sputum microscopy is positive for 20% of patients with laryngeal TB.
• Histopathological examination is required for a definite diagnosis.

The differential diagnosis of TB Larynx are

• • Bacterial and fungal infections,
  • granulomatosis with polyangiitis (Wegener’sgranulomatosis),
  • sarcoidosis, and
  • malignancies

Direct laryngoscopic examination with biopsy along with histopathological examination and culture provide the most conclusive evidence for diagnosis of Laryngeal TB. PCR-based analysis help to differentiate from other species of mycobacteria ^{36, 88}.

Treatment and outcome:

The laryngeal lesions of TB respond well to standard anti-TB regimens, within weeks. The larynx is reported to return to its normal appearance in 18 weeks on average 73. Voice outcomes improve after anti-TB treatment in most patients 94. Vocal cord immobility due to fibrosis and adhesion may produce permanent hoarseness in few patients ⁹⁵.

The standard treatment consists of four primary drugs (rifampin, isoniazid, pyrazinamide, and ethambutol) given together during an intensive phase of 2 months, followed by a maintenance phase of 2 or 3 drugs for 4 months. Surgical intervention such as tracheostomy, partial or complete laryngectomy, or laryngotracheoplasty may be required for some patients with abscess formation and progressive disease unresponsive to medical therapy.

In conclusion, TB should be kept in the differential diagnosis of upper airway diseases and/or cervical lymphadenopathy whenever a patient presents with hoarseness of voice/ obstructive symptoms ulcerative or granulomatous lesions, and failure of response to therapy for more common lesions.

It must be differentiated from malignancy from histopathological examination. Classic clinical features may not always be present. Early diagnosis and treatment are essential to prevent long-term complications of Tuberculosis.

References

1. Chakravarti A, Pal S, Sahni JK (2008) Primary tuberculosis oftonsil and posterior oropharyngeal wall. Indian J Tuberc 55(1):48–50
2. Menon K, Bem C, Gouldesbrough D, Strachan DR. 2007. A clinical review of 128 cases of head and neck tuberculosis presenting over a 10-year period in Bradford, UK. J Laryngol Otol 121:362–368.
3. Prasad KC, Sreedharan S, Chakravarthy Y, Prasad SC. 2007. Tuberculosis in the head and neck: experience in India. J Laryngol Otol 121: 979–985.
4. Akkara SA, Singhania A, Akkara AG, Shah A, Adalja M, Chauhan N.2014. A study of manifestations of extrapulmonary tuberculosis in the ENT region. Indian J Otolaryngol Head Neck Surg 66:46–50.
5. Jindal SK, Jindal A, Agarwal R. 2016. Upper respiratory tract tuberculosis. Microbiol Spectrum 4(6):TNMI7-0009- 2016
6. Das S, Das D, Bhuyan UT, Saikia N. 2016. Head and neck tuberculosis: scenario in a tertiary care hospital of northea stern India. J Clin Diagn Res 10:MC04–MC07.
7. Bruzgielewicz A, Rzepakowska A, Osuch-Wójcikewicz E, Niemczyk K,Chmielewski R. 2014. Tuberculosis of the head and neck—epidemiological and clinical presentation. Arch Med Sci 10:1160–1166.
8. Khuzwayo ZB, Naidu TK. 2014. Head and neck tuberculosis in KwaZulu-Natal, South Africa. J LaryngolOt ol 128:86–90.
9. Al-Serhani AM. 2001. Mycobacterial infection of the head and neck: presentation and diagnosis. Laryngoscope 111:2012–2016.
10. Tse GM, Ma TK, Chan AB, Ho FN, King AD, Fung KS, Ahuja AT.2003. Tuberculosis of the nasopharynx: a rare entity revisited. Laryngoscope 113:737–740.
11. Srirompotong S, Yimtae K, Srirompotong S. 2003.Tuberculosis in the upper aerodigestive tract and human immunodeficiency virus coinfections. J Otolaryngol 32:230–233.
12. Chiesa Estomba CM, Betances Reinoso FA, Rivera Schmitz T, OssaEcheverri CC, González Cortés MJ, Santidrian Hidalgo C. 2016. Head and neck tuberculosis: 6-year retrospective study. Acta Otorrinolaringol Esp 67:9–14.
13. CASTLEMAN B, MCNEELY BU (editors): Case records of the Massachusetts General Hospital. N Engl J Med 279:423- 430,1968
14. BULL TR: Tuberculosis of the larynx. Br Med J 2:991-992,1966
15. Rohwedder JJ. 1974. Upper respiratory tract tuberculosis. Sixteen cases in a general hospital. Ann Intern Med 80:708–713.
16. MR. 2004. Primary sinonasal tuberculosis in northwest Pakistan. J Coll Physicians Surg Pak 14:221–224. 17. Butt AA. 1997. Nasal tuberculosis in the 20th century. Am J Med Sci 313:332–335.
17. Butt AA. 1997. Nasal tuberculosis in the 20th century. Am J Med Sci 313:332–335.
18. Nawaz G, Khan Butt AA. 1997. Nasal tuberculosis in the 20th century. Am J Med Sci 313:332–335.
19. MR. 2004. Primary sinonasal tuberculosis in northwest Pakistan. J Coll Physicians Surg Pak 14:221621.
20. Butt AA. 1997. Nasal tuberculosis in the 20th century. Am J Med Sci 313:332–335.
21. Nawaz G, Khan Butt –224
22. Nalini B, Vinayak S. 2006. Tuberculosis in ear, nose, and throat practice: its presentation and diagnosis.
23. Am J Otolaryngol 27:39–45.Masterson L, Srouji I,
24. Kent R, Bath laboratory investigation. J Laryngol Otol 125:210–213.
25. Sardana K, Goel K. 2014. Nasal septal ulceration. Clin Dermatol 32:817–826.
26. Senol M, Ozcan A, Aydin A, Karincaoglu Y, Sasmaz S, Sener S. 2000. Disseminated lupus vulgaris and papulonecrotic tuberculid: case report. Pediatr Dermatol 17:133–135.
27. Nayar RC, Al Kaabi J, Ghorpade K. 2004. Primary nasal tuberculosis: a case report. Ear Nose Throat J 83:188–191.
28. Jha D, Deka RC, Sharma MC. 2002. Tuberculosis of the maxillary sinus manifesting as a facial abscess. Ear Nose Throat J 81:102–104.
29. Das JC, Singh K, Sharma P, Singla R. 2003. Tuberculous osteomyelitis and optic neuritis. Ophthalmic Surg Lasers Imaging 34:409–412.
30. Sharma MC, Arora R, Mahapatra AK, Sarat-Chandra P, Gaikwad SB,Sarkar C. 2000. Intrasellar tuberculoma—an enigmatic pituitary infection: a series of 18 cases. Clin Neurol Neurosurg 102:72–77.
31. Thakur JS, Verma N, Mohindroo S, Azad RK, Mohindroo NK. 1 June 2016. Isolated tubercular hypoglossal nerve paralysis. Trop Doct
32. Deepak D, Panjabi C, Gudwani S, Chaudhary N, Shah A.2001. Nasal septal perforation in a patient with allergic bronchopulmonary aspergillosis and rhinitis on long term corticosteroids. Asian Pac J Allergy Immunol 19:287–290.
33. Lee CR, Yoo CI, Lee J, Kang SK. 2002. Nasal septum perforation of welders. Ind Health 40:286–289.
34. Hughes RG, Drake-Lee A. 2001. Nasal manifestations of granulomatous disease. Hosp Med 62:417–421.
35. Chan AB, Ma TK, Yu BK, King AD, Thakur JS, Verma N, Mohindroo S, Azad RK, Mohindroo NK. 1 June 2016.Isolated tubercular hypoglossal nerve paralysis. Trop Doct
36. Deepak D, Panjabi C, Gudwani S, Chaudhary N, Shah A. 2001. Nasal septal perforation in a patient with allergic bronchopulmonary aspergillosis and rhinitis on long term corticosteroids. Asian Pac J Allergy Immunol 19:287–290.
37. Lee CR, Yoo CI, Lee J, Kang SK. 2002. Nasal septum perforation of welders. Ind Health 40:286–289.
38. Hughes RG, Drake-Lee A. 2001. Nasal manifestations of granulomatous disease. Hosp Med 62:417–421. Chan AB,Ma TK, Yu BK, King AD, Ho FN, Tse GM. 2004.
    Nasopharyngeal granulomatous inflammation and tuberculosis
39. Nasopharyngeal granulomatous inflammation and tuberculosis complicating undifferentiated carcinoma. Otolaryngol Head Neck Surg 130:125– 130.
40. Warndorff DK, Glynn JR, Fine PE, Jamil S, de Wit MY, MunthaliMM, Stoker NG, Klatser PR. 1996. Polymerase chain reaction of nasal swabs from tuberculosis patients and their contacts. Int J Lepr Other Mycobact Dis 64:404–408.
41. Mycobacterium tuberculosis in oral cavity samples.Oral Microbiol Immunol 18:156–159,Kakisi OK,Kechagia AS, Kakisis IK, et al: Tuberculosis
    of the oral cavity: a systematic review. Eur J Oral Sci 118(2):103–109, 2010.
42. Brook I: The bacteriology of salivary gland infections. Oral Maxillofac Surg Clin North Am 21(3):269–274, 2009.
43. Eguchi J, Ishihara K, Watanabe A, et al:PCR method is essential for detecting Tuberculosis
44. Morad NA. Tuberculous cervical lymphadenopathy; should antituberculous therapy be proceeded by histological proof? Tropical Doctor 2000; 30: 18–20.
45. Aktoğu S, Eriş FN, Dinç ZA, Tibet G. 2000. Tuberculosis of the tongue secondary to pulmonary tuberculosis. Monaldi Arch Chest Dis 55:287–288.
46. Iype EM, Ramdas K, Pandey M, Jayasree K, Thomas G, Sebastian P,Nair MK. 2001. Primary tuberculosis of the tongue: report of three cases. Br J Oral Maxillofac Surg 39:402–403.
47. 47.Memon GA, Khushk IA. 2003. Primary tuberculosis of tongue. J Coll Physicians Surg Pak 13:604–605.
48. 48.Dixit R, Sharma S, Nuwal P. 2008. Tuberculosis of oral cavity. Indian J Tuberc 55:51–53.
49. Ilyas SE, Chen FF, Hodgson TA, Speight PM, Lacey CJ, Porter SR.2002. Labial tuberculosis: a unique cause of lip swelling complicating HIV infection. HIV Med 3:283–286.
50. Kiliç A, Gül U, Gönül M, Soylu S, Cakmak SK, Demiriz M.2009. Orificial tuberculosis of the lip: a case report and review of the literature. Int J Dermatol 48:178–180.
51. Ceballos-Salobreña A, Aguirre-Urizar JM, Bagan-Sebastian JV. 1996. Oral manifestations associated with human immunodeficiency virus infection in a Spanish population. J Oral Pathol Med 25:523–526
52. Hale RG, Tucker DI. 2008. Head and neck manifestations of tuberculosis. Oral Maxillofac Surg Clin North Am 20:635–642.
53. Miziara ID. 2005. Tuberculosis affecting the oral cavity in Brazilian HIV-infected patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:179–182.
54. Köktener A. 2001. Nasopharyngeal tuberculosis. Eur J Radiol 39:186–187.
55. Aktan B, Selimoglu E, Uçüncü H, Sütbeyaz Y. 2002.Primary nasopharyngeal tuberculosis in a patient with the complaint of snoring. J Laryngol Otol 116:301–303.56.
56. King AD, Ahuja AT, Tse GM, van Hasselt AC, Chan AB.2003. MR imaging features of nasopharyngeal tuberculosis:report of three cases and literature review. Am JNeuroradiol 24:279–282.
57. Al-Serhani AM, Al-Mazrou K. 2001. Pharyngeal tuberculosis. Am J Otolaryngol 22:236-240
58. Caylan R, Aydin K, Caylan R. 2002. Oropharyngeal tuberculosis causing severe odynophagia and dysphagia.Eur Arch Otorhinolaryngol 259:229–230.
59. Christoforidou A, MetallidisS,Kollaras P,Agathangelidis A, NikolaidisP, Vital V, Markou K. 2012. Tuberculous retropharyngeal abscess as a cause of oropharyngeal dysphagia. Am J Otolaryngol 33:272–274
60. Greenfield BJ, Selesnick SH, Fisher L, et al:Aural tuberculosis. Am J Otol 16:175, 1995.
61. Chen S, Paul B, Myssiorek D: An algorithm approach to diagnosing bilateral parotid enlargement. Otolaryngol Head Neck Surg 148(5):732–739, 2013.
62. Kim YH, Jeong WJ, Jung KY, Sung MW, Kim KH, Kim CS. 2005. Diagnosis of major salivary gland tuberculosis: experience of eight cases and review of the literature. Acta Otolaryngol 125:1318–1322.
63. el-Hakim IE, Langdon JD. 1989. Unusual presentation of tuberculosis of the head and neck region. Report of three cases. Int J Oral Maxillofac Surg 18:194–196.
64. Sierra C, Fortún J, Barros C, Melcon E, Condes E, Cobo J, PérezMartínez C, Ruiz-Galiana J, Martínez-Vidal A, Alvarez F. 2000. Extralaryngeal head and neck tuberculosis.Clin Microbiol Infect 6:644–648.
65. Munck K, Mandpe AH. 2003. Mycobacterial infections of the head and neck. Otolaryngol Clin North Am 36:569–576.
66. Tomblin J, Roberts F: Tuberculous cervical lymphadenitis. Can Med Assoc J 121:324, 1979
67. Lee I, Liu J: Tuberculous parotitis: case report and literature review. Ann Otol Rhinol Laryngol 114(7):547–551, 2005.
68. P. M. Som and H. D. Curtin, Head and Neck Imaging, MosbyYear Book, St Louis, Mo, USA, 3rd edition, 1996
69. Zhang JW, Zhang QH. Tuberculosis of the parotid gland: a report of 12 cases. J Oral Maxillofac Surg 1995; 53: 84951.
70. Rice DH: Chronic inflammatory disorders of the salivary glands. Otolaryngol Clin North Am 32(5):813,1999
71. Stanley R, Fernandez J, Peppard S: Cervicofacial mycobacterial infections presenting as major salivary gland disease. Laryngoscope 93:1271, 1983.
72. Dobie R: Toxoplasmosis lymphadenitis occurring in a parotid gland. Otolaryngol Head Neck Surg 94:237,1986.
73. Marais BJ, Pai M: Recent advances in the diagnosis of childhood tuberculosis. Arch Dis Child 92(5):446–452,2007.
74. Tunkel D, Baroody F, Sherman M: Fine-needle aspiration biopsy of cervicofacial masses in children. Arch Otolaryngol Head Neck Surg 121:533, 1995.
75. Gandhi S, Kulkarni S, Mishra P, Thekedar P. 2012. Tuberculosis of larynx revisited: a report on clinical characteristics in 10 cases. Indian J Otolaryngol Head Neck Surg 64:244–247.
76. Benwill JL, Sarria JC. 2014. Laryngeal tuberculosis in the United States of America: a forgotten disease. Scand J Infect Dis 46:241–249.
77. Topak M, Oysu C, Yelken K, Sahin-Yilmaz A, Kulekci M. 2008. Laryngeal involvement in patients with active pulmonary tuberculosis. Eur Arch Otorhinolaryngol 265:327–330.
78. Schmid D, Fretz R, Kuo HW, Rumetshofer R, Meusburger S, MagnetE, Hürbe G, Indra A, Ruppitsch W, Pietzka AT, Allerberger F. 2008. An outbreak of multidrug-resistant tuberculosis among refugees in Austria, 2005-2006. Int J Tuberc Lung Dis 12:1190–1195.
79. Yun JE, Lee SW, Kim TH, Jun JB, Jung S, Bae SC, Kim TY, Yoo DH.2002. The incidence and clinical characteristics of Mycobacterium tuberculosis infection among systemic lupus erythematosus and rheumatoid arthritis patients in Korea. Clin Exp Rheumatol 20:127–132
80. Tato AM, Pascual J, Orofino L, Fernández-Juárez G, MartínezSan-Millán J, Fogué L, Liaño F, Ortuño J. 1998. Laryngeal tuberculosis in renal allograft patients. Am J Kidney Dis 31:701–705.
81. Egeli E, Oghan F, Alper M, Harputluoglu U, Bulut I. 2003. Epiglottic tuberculosis in a patient treated with steroids for Addison’s disease. Tohoku J Exp Med 201:119–125.
82. Rizzo PB, Da Mosto MC, Clari M, et al: Laryngeal tuberculosis: an often forgotten diagnosis. Int J Infect Dis 7:129–131, 2003.
83. Shin JE, Nam SY, Yoo SJ, et al: Changing trends in clinical manifestations of laryngeal tuberculosis. Laryngoscope 110:1950–1953, 2000.
84. Wang CC, Lin CC, Wang CP, et al: Laryngeal tuberculosis: a review of 26 cases. Otolaryngol Head Neck Surg 137:582–588, 2007.
85. Nishiike S, Irifune M, Doi K, et al: Laryngeal tuberculosis: a report of 15 cases. Ann Otol Rhinol Laryngol 111:916–918, 2002.
86. Kandiloros DC, Nikolopoulos TP, Ferekidis EA, et al:Laryngeal tuberculosis at the end of the 20th century. J Laryngol Otol 111:619621, 1997.
87. Vrabec DP: Fungal infections of the larynx. Otolaryngol Clin North Am 26:1091–1114, 1993.
88. Topak M, Oysu C, Yelken K, et al: Laryngeal involvement in patients with active pulmonary tuberculosis. Eur Arch Otorhinolaryngol 265:327–330,
    2008.
89. Yelken K, Guven M, Topak M, et al: Effects of antituberculosis treatment on self assessment, perceptual analysis and acoustic analysis of voice quality in laryngeal tuberculosis patients. J Laryngol Otol 122:378–382, 2008.
90. Galli J, Nardi C, Contucci AM, Cadoni G, Lauriola L, Fantoni M.2002. Atypical isolated epiglottic tuberculosis: a case report and a review of the literature. Am J Otolaryngol 23:237–240
91. Lim JY, Kim KM, Choi EC, et al: Current clinical propensity of laryngeal tuberculosis: review of 60 cases. Eur Arch Otorhinolaryngol 263:838–842, 2006
92. Richter B, Fradis M, Kohler G, Ridder GJ. Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature. Ann Otol Rhinol Laryngol 2001;110:197-201.