Portuguese Version

Year:  2000  Vol. 66   Ed. 6 - (14º)

Artigo de Revisão

Pages: 666 to 671

Otolaryngological Manifestations of Tuberculosis

Author(s): Andréa G. Martins*,
Marise P. C. Marques**,
Noísio G. M. Ferreira***,
Cláudia M. Valete****,
Shiro Tomita*****,
Arthur O. A. Kós******.

Keywords: tuberculosis, otolaryngology, clinical manifestations

Abstract:
Tuberculosis is a chronic infectious disease mainly caused by Mvcobacterium tuberculosis. It was the leading cause of death, specially in young people, all over the world during eighteenth and nineteenth centuries. Owing to the effective chemotherapy and improved public health, the disease had been decreased. However, during the last years, the number of new cases reported in developed and developing countries has increasing. It has been thought to be related to the association of this disease with immunocompromised hosts and immunosupression treatments. As the microorganism may involve any organ system and some infections could be subclinical, this disease must be suspected. This study discuss the pathogenesis, epidemiology, clinical manifestations, diagnosis and treatment of the tuberculosis, mainly in otolaryngology which usually is secondary to pulmonar disease, and sometimes may be subclinical. Clinical supposition is important to early diagnosis and treatment.

INTRODUCTION

Tuberculosis is a chronic granulomatous infectious-contagious disease caused by Mycobacterium tuberculosis. Pulmonary form is the most frequent presentation of the disease. Among the extrapulmonary forms we may point out otorhinolaryngologic impairments.

Historically, the incidence of tuberculosis reduced progressively since the beginning of the century, thanks to improvement in hygiene and nutrition conditions, appropriate treatment and easier access to health system and prevention programs. However, as from the last decade, there has been an increase in the number of new cases around the world, including the developed countries. Acquired immunodeficiency syndrome, immunosuppressor treatments and the larger number of cases resistant to drugs used in the treatment have contributed to this reappearance5.

This study reinforces the importance of tuberculosis in the differential diagnosis of various granulomatous diseases, especially in clinical Otorhinolaryngology, in which the affection is normally secondary. Complementary exams become relevant for diagnostic confirmation. Early diagnosis and treatment reduce the risk of sequalae in the organs affected by the microorganism.

REVIEW OF LITERATURE

The infection

Tuberculosis is an infectious-contagious disease caused by Mycobacterium tuberculosis. Occasionally, we may also find the disease caused by Mycobacterium bovis or Mycobacterium avis. Mycobacterium tuberculosis is a bacillus that does not form spurs, does not have flagellum, nor produces toxin; however, it needs oxygen to proliferate. It is an intracellular parasite capable of living and reproducing inside phagocytic cells. It is sensitive to the action of physical agents such as heat and ultraviolet radiation, but it resists to chemical agents because of its lipid-rich cell wall. Owing to its characteristics of alcohol and acid resistance, it may be seen in secretions by direct microscopy (bacilloscopy), by means of staining with Ziehl-Neelsen method, and it may also be identified by culture17.

Transmission occurs by the air, through contaminated particles of various sizes launched in the air by speech, cough and/or sneeze of a patients with bacilli. Heavier droplets will deposit; whereas middle ones will be retained in the mucosa of the upper respiratory epithelium later eliminated by mucociliary clearance, swallowed and inactivated by the gastric juice, and finally eliminated in feces. Lighter droplets are maintained suspended in the air and they may get in contact with a susceptible agent, reaching the alveoli and causing a local inflammatory reaction5.

This first contact with the bacillus is called primary infection. After these phase, the multiplication of the bacillus starts, if there is no acquired immunity. Lympho-hematogenic proliferation starts from a pulmonary focus to lymph nodes and other organs. This dissemination is of few bacilli that normally are latent or destroyed by the immunity of the host. The association of the primary pulmonary focus with satellite ganglia of the region is called primary complex of Ranke. If the organism manages to block the advance of the process based on this complex, the subject will remain only infected. The likelihood of becoming sick after primary infection depends on virulence of bacillus, source of infection and immunological characteristics of the subject. Immunological competence of the subject is genetically controlled, although factors such as malnutrition may reduce it. Immunity in tuberculosis is mainly mediated by cell immunological system, with lymphocyte helper T interacting with macrophages. Humoral immunological response does not have effect on the defense of this microorganism, because antibodies are ineffective to destroy its.

Clinical presentations of tuberculosis

We may classify the disease as primary or post-primary. Primary tuberculosis occurs during primary infection, evolving from pulmonary or ganglionar focus or by hematogenic dissemination. From the primary infection, approximately 5% of the infected cases can develop the primary form. Primary form may be lymphonodulopulmonary, pneumonic, cavitary, meningeal and disseminated (miliary). Disseminated or miliary is the most frequent and severe type, resulting in significant systemic compromise and great potential for development of meningitis. The bacteriological diagnosis of pulmonary lesions may be difficult, because the bacilli remain in the pulmonary interstitium. Patients with primary tuberculosis represent a small percentage of the population who has epidemiological importance restricted to transmission of the disease5.

In subjects with previous immunity to bacillus (either due to natural infection or vaccination) there is post-primary tuberculosis owing to an aggravation of an existing focus in the organism (endogenous reactivation) or the reception of a new load of bacilli from the environment (exogenous re-infection). Epidemiological implication of these patients is significant, because 90% of them represent pulmonary forms that may produce bacilli5.

The bacillus may affect any organ, although pulmonary manifestation is the most common one and the main source of infection. Extrapulmonary affection is normally secondary to pulmonary one and it diagnosis may be difficult5.

Based on the bacteriological status of patients with pulmonary affection it is possible to classify them as:

o Bacillipherous: with positive bacilloscopy of sputum (eliminates at least 5,000 bacilli per milliliter of sputum).

o Non-bacillipherous: with negative bacilloscopy, with positive or negative culture.

This classification is important because it identifies a potential for transmission and sickening of communicants. It is noted that bacillipherous patients infect more people than those who only have a positive culture. In countries with high prevalence of the disease, it is observed that those who have positive culture infect communicants at the same proportion of the general population. The more the contact with bacillipherous, the higher the likelihood of having the infection. This is the reason why lower-income people who live in humid, poor ventilated and small houses have higher rates of infection5.

It is interesting to point out that tuberculosis in the elderly is normally of chronic evolution. There is more fibrosis and less potential of transmitting the infection5.

Otorhinolaryngologic manifestations

Laryngeal tuberculosis

Laryngeal tuberculosis is normally secondary to pulmonary disease. It may be diffuse or exsudative or with localized lesions (tuberculoma or polypoid lesion)10. Posterior laryngeal commissure and interarytenoid area are frequently the first sites to be affected15. Tuberculosis is rarely extended into the hypopharynx or the subglottic region, differently from laryngeal cancer10.

Clinically, it is manifested by dysphonia, cough, hemoptysis, dysphagia and/or odynophagia10. Intense odynophagia determines significant difficulty to swallow and worsening of the patient's general status15.

Fibrous tuberculoma and monochorditis are frequently mistaken by carcinoma. Other diseases such as syphilis, Hansen disease, blastomycosis, actinomycosis and hystoplasmosis may be manifested with laryngeal compromise similar to that of tuberculosis. There are reported cases of concomitance of cancer and tuberculosis10.

Appropriate treatment normally results in cure of the tuberculous mucosal lesions and does not leave sequelae. However, fibrotic processes may originate severe stenosis. Ulceration of epiglottis may happen with loss of substance15.

Tuberculous otitis media

Middle ear affection is rare nowadays, differently from what happened before the advent of antibiotics.

The main route of dissemination is hematogenic, although some authors believe that the infection may occur through the auditory tube in bacillipherous cases, through cough and/or regurgitation3. Other routes of dissemination mentioned are direct extension of intracranial lesions or through the external ear canal, in the presence of tympanic perforation. Concomitant pulmonary lesions are found in 50% of the patients6.

There are two clinical forms: acute, which is rare, and chronic. In the acute form, otoscopy shows an increase in vascularization of the anterior process of malleus. The patient tends to progress with multiple perforations in the tympanic membrane that can not be seen, since they quick form one single perforation. The occurrence of polyp in the external ear canal, edema and granulation of the middle ear mucosa is frequent, in addition to destruction of ossicle chain and inner ear compromise. The chronic form is insidious and presents otorrhea with no otalgia and early conductive hearing loss disproportional to otoscopy finding3. Some authors6, 14, 21 pointed out that otorrhea could be accompanied by otalgia. The pressure of the granulomatous tissue inside the mastoid could explain this fact14.

The diagnostic criteria of tuberculous otitis media are: chronic otitis media refractory to antibiotics; significant conductive hearing loss; large quantity of granulation tissue in the middle ear; facial paralysis; history of pulmonary tuberculosis; positive tuberculin test (PPD); regional lymphadenitis, especially in children. The existence of 3 of these signs leads the hypothesis to the diagnosis. Five or more are conclusive of the diagnosis3.

Retroauricular fistula, peripheral facial paralysis, labyrinthitis, osteomyelitis, and acute mastoiditis are possible complications'. Peripheral facial paralysis by tuberculosis was documented in about 21% of the cases with chronic tuberculous otitis media6. Tuberculosis should be suspected in cases of noncholesteatomatous chronic otitis media with facial paralysis14. Recovery of facial paralysis depends on early treatment16. Other authors emphasized that the clinical treatment had a key role; however, the resolution of granulation tissue could be slow enough to keep on affecting the facial nerve, justifying surgical intervention in some cases20.

The most important diagnostic method is the histopathological exam of the granulation tissue. That is why all tissues removed from any otological surgery should be submitted to microbiological and histopathological analyses. The finding of caseous granuloma is practically pathognomonic of the disease, confirmed by Ziehl-Nielsen staining6.

Bacteriological exam of otorrhea is not very sensitive, since the presence of other microorganisms may interfere in the growth of tuberculosis bacilli21. Another justification for this fact is the reduced anti-tuberculosis effect of neomycin in otological drops13.

As to sequelae, they will be treated after cure, as with chronic otitis media. The best results are seen in cases of early diagnosis and tretament13.

Nasal tuberculosis

Nasal tuberculosis is rare, normally secondary to pulmonary tuberculosis. The main route of infection is hematogenic, and the most common area of affection is the anterior-posterior portion of the nasal septum, region of Kisselbach zone, where there is vascular confluence8.

The clinical forms are ulcerative, tuberculoma and lupus, with congested and nodular mucosa8.

The clinical presentation includes purulent rhinorrhea; at anterior rhinoscopy, there is pale and torpid mucosa, sometimes with perforation of quadrangular cartilage. As to diagnostic methods, we may also include bacilloscopy of nasal exsudate and biopsy of the lesion8.

Tuberculosis of oral and pharyngeal cavities

Nasopharynx:

The incidence of tuberculosis in nasopharynx is rare. There may be primary affection of nasopharynx and that is why differential diagnosis with neoplasia, Wegener's granulomatosis, sarcoidosis, Hansen disease, syphilis, lymphoma, nodous polyarthritis and fungal infection is so important1.

The clinical presentation is described as posterior rhinorrhea, epistaxis, nasal obstruction, ear fullness or, more rarely, cervical lymph node1.

Endoscopically, it may present ulcerated or tumor lesions, or even practically normal aspect1.

Oral cavity and oropharynx:

Affection of oral cavity and oropharynx is also rare. It may be primary, a very rare condition, because there would be the need for breaking with the integrity of oral mucosa so that Mycobacterium tuberculosis could come .in. Another form is secondary to pulmonary tuberculosis by hematogenic dissemination or self-inoculation of bronchial secretion12.

There are two clinical presentations: lupus, in which there are non-painful groups of round nodules on the mucosa, and when pressed with a slide, they become yellowish spots; and ulcerative mucosa, in which there are painful ulcerations with irregular borders, superficial or profound, tending to grow progressively, and regional and confluent lymph nodes2.

The tongue is the most frequently involved site of the oral cavity and it may present as an ulcer, fistula, tuberculoma or diffuse glossitis9.

Primary focus may be on the tonsillar region, with lymph node compromise15.

Following the appropriate treatment, painful lesions evolve quickly, with significant improvement of pain, although they are only solved some weeks later9.

Hypopharynx:

Tuberculosis affecting hypopharynx is normally associated with miliary form. Clinical picture consists of constant pain, irradiated to the ears, and on the cervical region, especially during swallowing7.

Affection of pyriform sinus is described, what reinforces the importance of the disease in differential diagnosis, although the location is rare7.

There is a report in the literature describing an 80% incidence of laryngeal tuberculosis in the presence of pharyngeal or oral compromise. Progression of laryngeal tuberculosis may involve oropharynx; however, differently from malignant lesions or other inflammatory non-tuberculous conditions, it seldom extends into the hypopharynx7.

Salivary gland tuberculosis

The most common affection is through hematogenic dissemination to lymph nodes of salivary glands. It may also be secondary to oral cavity infections or self-inoculation with infected sputum, reaching the parenchyma or the lymphatics of the gland19.

There are two clinical presentations: focal presentation by intra-glandular lymph node infection, simulating neoplasia, and diffuse presentation, with involvement of parenchyma. The latter is rare4.

The diagnosis should be based in the anamnesis, physical exam, tuberculin test (PPD) and histopathological exam18.

Fine needle aspiration biopsy as diagnostic method is recommended before surgical intervention4.

Inadequate surgical exploration and delay in diagnosis may result in glandular destruction and formation of fistula4, 18.

Ganglionar tuberculosis

The presence of cervical lymphadenopathy is sometimes an isolated finding. It may be a result of the introduction of bacilli through the tonsils, dental focuses or pharynx, although the most common route is the lympho-hematogenic route from a primary pulmonary focus15.

Normally, there is gradual and insidious increase of lymph nodes, sometimes acute. In children, it is common to find micropolyadenopathies. There is evolution to caseation, and there may be fistulation with output of bacilli-poor caseous material, called scrofulous15.

Diagnosis

The most commonly used diagnostic tests are:

1) Bacteriological exam. May be done by direct method (bacilloscopy) or by culture. Bacilloscopy is a simple, fast and cheap exam. It requires at least 5,000 bacilli per milliliter of sputum sample, induced sputum, gastric lavage (used in children because it is difficult to collect sputum) or bronchial lavage. It identifies the microorganism as alcohol-acid resistant bacilli. The culture enables identification of Mycobacterium tuberculosis. It may be positive in a sample with few bacilli, determining early diagnosis of initial and paucibacillary lesions, but it takes at least 2 to 4 weeks for-the culture to grow. It also evaluates the sensitivity of mycobacterium to chemotherapic agents if the therapeutic response is not as expected5.

2) Radiological exam. Indicated especially in cases of difficult collection of sample or negative bacteriological exam in patients with hypothesis of tuberculosis. We may find pulmonary infiltrate, mediastinal lymphonodemegalia, cavernous5.

3) Histopathological exam. It is useful especially for extrapulmonary presentations. At microscopy, we normally observe granuloma with caseous necrosis, a finding that may also be detected in other diseases. However, the finding of alcohol-acid resistant bacilli in this situation enables confirmation of tuberculous etiology 5.

4) Tuberculin test (PPD - purified protein derivative). It is a test that evaluates cellular immunity. It indicates previous contact with tuberculosis. However, it does not differentiate the infected state of patients.

5) Polymerase chain reaction (PCR). It is an exam that may amplify tiny quantities of specific segments of genome (deoxyribonucleic acid-DNA) of microorganism, such Mycobacterium tuberculosis, present in a sample. In paucibacillary patients, PC R may be positive even with negative bacterioscopy and sputum culture. PCR may be used for diagnosis of extrapulmonary disease, such as tuberculous meningitis11.

Treatment

In Brazil, notification of tuberculosis is mandatory and medication is provided only by the Ministry of Health.

Drugs are used according to stage of disease. In the first stage, bacilli are located inside the macrophages, in an acid medium, multiplying slowly and in a number lower than 100 thousand. In the second stage, bacilli are released from macrophages and are found in caseous focuses, with slow multiplication, poor oxygenation and fewer than 100 thousand. In the third stage, bacilli are under excellent conditions for proliferation and the number is higher than 100 thousand. Drugs play different roles in each stage. Pyrazinamide acts in the intracellular phase, and that is why it is used initially. Extracellular bacilli are affected by Rifampin, whereas Isoniazid acts in middle proliferation bacilli5.

Therefore, treatment is divided into 2 phases: load dose phase (prevents resistance of bacilli with use of Rifampin associated with Isoniazid and Pyrazinamide in the first 2 months) and maintenance dose phase (prevents bacilli persistence with the use of Rifampin associated with Isoniazid for more 4 months, comprising a total period of treatment of 6 months). This regimen is valid for both pulmonary and extrapulmonary forms, although some authors prefer, in extrapulmonary forms, to add 6 more months of treatment with isolate Isoniazid, comprising a total treatment period of twelve month5.

In case of treatment failure, other drugs should be used, such as Streptomycin, Ethambutol, Etyonamide, within a total period of treatment of 12 months5.

All these drugs are not free of side effects. Gastrointestinal symptoms have been reported (nausea, vomiting, diarrhea), skin rash, hemolytic anemia, arthralgia, neurological manifestations and hepatotoxicity. It is important to point out the ototoxic effect of Streptomycin, with vertigo, nystagmus and deafness5.

Treatment control

Treatment control is done by means of monthly bacilloscopy for the specific pulmonary form. Normally, negative results of sputum are obtained between the lst and 2nd months of treatment. This control has not been defined for patients who have only otorhinolaryngologic affection, but clinical improvement as a result of the therapeutic regimen is an important marker5.

Cure control

After 6 months of treatment, with good clinical evolution, radiological improvement and negative bacilloscopy, patients are discharged: In case of aggravation of the disease, they should be treated all over again17.

Communicants control

People that live close to bacillipherous patients should be submitted to medical control util discharge of the patient with whom they were in contact. Children under 5 years of age, even if asymptomatic with normal pulmonary x-ray, reaction to tuberculin test, no history of previous vaccination with bacilli of Calmette and Guerin (BCG) or vaccinated more than two years before, should be submitted to chemoprophylaxis.17

Prophylaxis

Prophylaxis is done by means of intradermal vaccination with BCG, mandatory in children under 1 year of age in Brazil. It protects against the most severe forms of the disease: meningitis and miliary. Chemoprophylaxis is used in subjects normally affected by the bacilli and with great potential to become sick. Therefore, there is control of the small bacterial population in the moment, preventing its proliferation. Isoniazid is used for 6 months. It may be a primary patient (newborn of a bacillilpherous mother) or a secondary patient (patients already infected and with risk of getting sick)17.

DISCUSSION AND FINAL COMMENTS

Taking into consideration the growing number of cases of tuberculosis, and its innumerous clinical manifestations, we should highlight the importance of including this disease in differential diasanosis, especially in the area of Otorhinolaryngology. By doing so, we will be able to diagnose and treat cases earlier, preventing possible sequalae.

REFERENCES

1. AL-SERHANI, A. M.; AL-RIBABI, A. C.; ASSIRY, M. A. -Primary nasopharyngeal tuberculosis: case report and review of the literature. ENT Journal., 76: 41-42, 1997.
2. BECKER, W.; NAUMANN, H. H.; PFALTZ, C. R.-Mouth and Pharynx In: BECKER, W.; NAUMANN, H. H.; PFALTZ, C. R. - Ear, Nose and Throat Diseases. 2° edição New York, Thieme, 1994. pp. 331-332.
3- BENTO, R. F.; MINITI, A.; MARONE, S. A. M. - Doenças do Ouvido Médio In: BENTO, R. F.; MINITI, A.; MARONE, S. A. M. - Tratado de Otologia. São Paulo, Editora da Universidade de São Paulo, 1998. pp. 207-209.
4. BHAT, N. A.; STANSBIE, J. M. - Tuberculous parotitis: a case report. J. Laryngol. Otol., 110: 976-977, 1996.
5. Controle da tuberculose: uma proposta de integração ensino - serviço / CNCT / NUTES. 3ª edição revisada. Rio de Janeiro, 1992. 155 pp.
6. FARRUGIA, E. J., RAZA, S. A., PHILLIPPS, J. J. - Tuberculous otitis media - a case report. J. Laryngol. Otol., 111:58-59, 1997.
7. GOYAL, A. et al..-Tuberculosis of the pyriform fossa - a rare entity. J. Laryngol. Otol., 112: 782-783, 1998.
8. HUNGRIA, H. - Rinites Especificas. Granulomatoses Nasais. In: HUNGRIA, H. -Otorrinolaringologia. 7ª ed. Rio de Janeiro, Guanabara Koogan, 1995. pp 25.
9. JAWAD, J., EL-ZUEBI, F. - Primary lingual tuberculosis: a case report. J. Laryngol. Otol., 110: 177-178, 1996.
10. LINDELL, M., JING, B., WALLACE, S. -Laryngeal tuberculosis. Am J Roentgenol, 129: 677-680, 1977.
11. MARKS, G. L. - Genetics of tuberculosis. Clinics North America, 77(6): 1219-1234, 1993.
12. MINITI, A., BENTO, R. F., BUTUGAN, O. - Doenças da Cavidade Oral In: MINITI, A., BENTO, R. F., BUTUGAN, O. Otorrinolaringologia Clinica a Cirúrgica. São Paulo, Atheneu, 1993. pp. 203.
13. ODETOYINBO, O. - Early diagnosis of tuberculous otitis media. J. Laryngol. Otol., 102: 133-135, 1988.
14. PLESTER, D., PUSALKAR, A., STEINBACH, E. - Middle ear tuberculosis. J. Laryngol. Otol., 94: 1415-1421, 1980.
15. RIBEIRO, F. A. Q.; LOPES FILHO - Doenças Ulcerogranulomatosas em Otorrinolaringologia In: LOPES Filho, O.; CAMPOS, C. A. H. - Tratado de Otorrinolaringologia, São Paulo, Roca, 1994. pp. 83-84.
16. SINGH, B. - Role of surgery in tuberculous mastoiditis. J Laryngol. Otol., 105:907-915, 1991.
17. SOUZA, G. R. M - Tuberculose In: SCHECHTER, M.; MARANGONI, D. V. -Doenças Infecciosas: Conduta Diagnostica e Terapeutica, Rio de Janeiro, Guanabara Koogan, 1994. pp. 197-209.
18. STANLEY, R., FERNANDEZ, J. A., PEPPARD, S. B. Cervicofacial mycobacterial infections presenting as major salivary gland disease. Laryngoscope, 93:1271-1275, 1983.
19. SLTOGLU, Y. et al. - Tuberculosis of the parotid gland. J. Laryngol. Otol., 112: 588-591, 1998.
20. WEINER, G. M., O'CONNELL. J. E., PAHOR, A. L. -The role of surgery in tuberculous mastoiditis: appropriate chemotherapy is not always enough. J. Laryngol. Otol., 111: 752-753, 1997.
21. WINDLE-TAYLOR, P., BAILEY, C. M. -Tuberculous otitis media: a series of 22 patients. Laryngoscope, 90: 1039-1044, 1980.

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* Master studies under course at Service of Otorhinolaryngology of Hospital Universitario Clementino Fraga Filho (HUCFF), Universidade.Federal do Rio de Janeiro (UFRJ).
** Physician and Preceptor of Residents of the Service of Otorhinolaryngology of HUCFF, UFRJ.
*** Joint Professor and Coordinator of the Master Course in the Area of Otorhinolaryngology, Faculdade de Medicina, UFRJ.
**** Assistant Professor of Faculdade de Medicina, UFRJ.
***** Joint Professor and Head of the Service of Otorhinolaryngology of HUCFF, UFRJ.
****** Faculty Professor of Otorhinolaryngology at Faculdade de Medicina, UFRJ.

Service of Otorhinolaryngology of HUCFF, UFRJ.
Study presented at the conclusion of Medical Residence in Otorhinolaryngology at HUCFF/ UFRJ.
Address for correspondence: Andrea Gomes Martins - Rua Conde de Baependi, 133 / 901 - Laranjeiras - 22231-140 Rio de Janeiro/ RJ.
Tel: (55 21) 205-5694-E-mail: andreamaninsbr@hotmail.com
Article submitted can tune 8. 2000. Article accented on September 28. 2000.

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