Manifestations of Mycobacteria Tuberculosis Infection in Otolaryngology
Michael Groves, M.D.
September 6, 2007

I am going to be talking about manifestations of mycobacterium tuberculosis infections in otolaryngology this morning.  I will give a brief case presentation, followed by some basics of mycobacterium tuberculosis biology and review of some of the otolaryngologic manifestations.  In turn, the case presentation will be revisited, and I will discuss some of the diagnostic challenges as well as the role of polymerase chain reaction in meeting those challenges. 

Briefly, BS is a 43-year-old African-American male with a history of chronic infections of his right hip, requiring repeated surgical incision and drainage after he was hit by a car in 2003.  He came into the Ben Taub Emergency Center with the complaint of purulent drainage from that right hip.   When the workup was in process in the emergency center, they meant to get a right hip film when they accidentally ordered a left shoulder film.  That left shoulder film showed that he had a cavitary lesion in the left upper lobe of his left lung.  Chest x-ray confirmed this and also confirmed the presence of multiple granulomas throughout the lung fields.  On further questioning, the patient admitted that he had persistent cough for the past several months, occasional black sputum, as well as a 30-40-pound weight loss and night sweats.  Here is his chest x ray.  It demonstrates here the cavitary lesion in the left upper lobe.  On admission, his examination was significant only for decreased breath sounds in the right lung base as well as crackles in the left upper lobe. Importantly, he had no neurological deficits, which will come into play in a few minutes.  His laboratory data was significant for a white blood cell count that was mildly elevated at 12.9, a significantly elevated erythrocyte sedimentation rate at 117, and a smear of his sputum was positive for acid-fast bacilli. Sputum culture was positive for mycobacterium tuberculosis in a matter of three days.  His hip abscess culture was growing MSSA and his HIV ELISA was negative.  The primary team obtained a CT of his chest which demonstrated T12 vertebral body osteomyelitis, and a subsequent MRI was ordered to evaluate the extent of spinal involvement. This showed enhancement of the anterior and inferior aspects of the vertebral bodies at multiple levels, a lumbosacral phlegmon as well as a large right retropharyngeal fluid collection.  We were consulted at that point, now four days after admission and three days into his antituberculosis chemotherapy treatment.  At that point, the patient denied any significant head and neck complaints specifically odynophagia, dysphagia, or change in his voice, otalgia or pain with movement of his neck.  He had a very low-grade pyrexia in the low 100s and high 99s, and all his other vital signs were stable.  Importantly, on his head and neck physical exam, he had a prominent bulge in the right posterior pharyngeal wall that did not cross the midline, was nontender to palpation, and was obviously fluctuant on palpation. It extended from the mid nasopharynx to the level just below the arytenoid cartilages and displaced those cartilages slightly anteriorly and medially.  Importantly, he was in no respiratory distress and his airway was widely patent.  His neck was supple without tenderness or decreased range of motion. 

Here is an example with some of the films that were obtained.  This is the original MRI where the fluid collection was discovered and, prior to taking this patient to the operating room, we got a CT scan of his neck which demonstrated the large right sided fluid collection as well as some bony erosions of the anterior and inferior surface of the C5 vertebral body which was in direct connection with this fluid collection.  The key point in this case is the fact that the patient was basically asymptomatic.  He was nontoxic in appearance and he had a concurrent active pulmonary tuberculosis as well as adjacent cervical spine osteomyelitis.   With this constellation of features, the patient was given a preoperative diagnosis of a “cold” tuberculous retropharyngeal abscess. 

Mycobacteria are non-motile, non-spore forming aerobic bacilli, which have extremely thick cell walls, rich in lipids that make them hydrophobic and resistant to disinfectants.  Once they are colorized with a red dye, they cannot be decolorized with acid solutions, giving them the name acid-fast bacilli or red snappers, colloquially.  They are ubiquitous in soil, water, unpasteurized milk in both domestic and wild animals.   Here you can see the little red snappers throughout this high-powered microscope field. 

Mycobacterium tuberculosis infection can occur in all tissues of the body, although some are more resistant than others. Pulmonary tuberculosis infection is overwhelmingly most common type of infection representing approximately 80% of all TB cases.  Most damage to the host is by its own immune response to the tubercle bacilli.  It is a cellular-mediated response, a type IV hypersensitivity reaction.  On histopathology you can see caseating granulomas, with abundant necrotic tissue in the center of a granuloma lined with lymphocytes, multinucleated giant cells, and epithelioid cells. 

There is a lot said about the rise in tuberculosis rates at the end of the last century, in the late 80s and early 90s.  This was attributed to an increase in the rate of HIV infection, immigration to this country from endemic areas, the emergence of resistant organisms, and an increase in immunosuppressed patients wuch as transplant recipients, although I suspect that was a very small contribution there.  The most recent WHO data, from 2004, stated that there were nine million new cases of tuberculosis and two millions deaths.  Fortunately, the trend had turned around by that time and, in the early part of this century, rates were stable or falling everywhere, but Africa.  More than 80% of all TB patients live in sub-Saharan Africa and Asia where rates of HIV are much higher than in this country.  In the United States in 2005, the CDC reported 14,000 new cases of tuberculosis, which is actually a decrease of 3.8% from the previous year.  Of course, the rates are higher in foreign-born residents of this country, and the highest rate is seen in Asians whereas the lowest rate is seen in whites.  Unfortunately, there are no statistics available specifically for otolaryngologic manifestations.  The closest they come is categorizing lymphadenopathy as its own category.  All of the others are just grouped under “other,” so it is impossible to give accurate statistics based on CDC data about how common these manifestations are. 

As I said, one particular manifestation that we do know a little bit more about the rate of infection is lymphadenopathy.  It is the most common extrapulmonary manifestation, representing about 8.8.% of United States cases.  Of the lymph node basins, the cervical lymph node basin is the most commonly involved.  Of these, the lymph nodes in the posterior triangle and supraclavicular area are the most common sites of infection.  These nodes can be a single large node or multiple matted smaller nodes and, if left untreated for long enough, will often develop into a draining sinus tract.  Diagnosis is made first with a fine needle aspiration cytology specimen with a fairly high sensitivity and a very good specificity.  On cytology, you would look for necrotic tissue with presence of the epithelioid cells and multi-nucleated giant cells, as well as the presence of acid-fast bacilli on Ziehl Neelsen stain. If the fine needle aspiration is non-diagnostic, which occasionally it will be, excisional biopsy is performed with that specimen being sent for histopathology as well as smear and culture. 

The treatment of cervical lymphadenopathy is fairly straightforward and consists mainly of multi-drug antituberculosis chemotherapy. There are about eleven drugs that are used to treat tuberculosis at this point, but a fairly typical regimen would be isoniazid, rifampin, ethambutol, and pyrazinamide.  An I.D. consult or a medicine consult is always advised to properly choose your medicine.

Indications for surgery include the need of excisional biopsy for diagnosis, as previously mentioned. continued nodal enlargement despite an appropriate course of antituberculosis chemotherapy, and some even believe that all patients undergo surgical excision of the involved nodes.  That technique is not widely accepted in the literature from this country, as it is felt that excision of these nodes prior to proper treatment with the antituberculosis chemotherapy can also lead to a chronic draining sinus tract in the wound bed due to lymphatic engorgement in the area. 

The second most common otolaryngologic manifestation is laryngeal tuberculosis infection.  At the turn of the century, this was the most common affliction of the larynx seen by head and neck physicians.  At that time, the estimated rate of laryngeal involvement was about 25-33% of patients who had pulmonary tuberculosis. Dr. Von Rokitansky gives a classic description of this as being almost always following lung tuberculosis, after this has made some progress. The site of the tubercule is almost constantly and exclusively the mucous membrane and submucous connective tissue over the arytenoid and the contiguous cartilages.  Yet, it is exceptionally in other places also and on the front of the epiglottis.  His point being that the posterior structures of the larynx were most often involved, at this time, and that was thought to be because of the supine position of the patients who were on the TB wards or failure to clear mucus secretions that have active live tubercle bacilli in them.  It was most commonly found in young people ages 20-40. 

At that point, treatment included voice rest and application of silver nitrate to the lesion, but as Morrell McKenzie, who is famous for being one of the founders of the Journal of Laryngology and Otology states in his book, “Diseases of the Throat and Nose,” the prognosis of laryngeal phthisis, which is an archaic term for tuberculosis infection, is “always extremely unfavorable, and it is not certain that any cases ever recover.” 

Fortunately, rates did begin to fall in the first decades of the last century, even prior to introduction of antimicrobial therapy with streptomycin, probably due to earlier detection and treatment of the pulmonary tuberculosis infection, which included lots of fresh air, sunshine, and high altitudes.  Laryngeal tuberculosis now accounts for less than 1% of all tuberculosis infections.  Primary laryngeal infection, meaning without concomitant pulmonary infection, is more common than in the classical descriptions.  The presenting symptom is typically hoarseness, but we can also find patients with odynophagia, dysphagia, otalgia, and cough or stridor.  Note the similarity to the presenting symptoms of laryngeal carcinoma. 

On gross examination, we can see the lesions are characterized in a common way. There is diffuse ulceration of the laryngeal structure, granulomatous changes which can be seen here, polypoid changes of the true vocal cords, and nondescript erythema, which can be seen here on this right true cord.  In contrast to the classical description, the true cords are the most commonly affected area; and the anterior portion of these is more commonly affected than the posterior.  It is also more common to find this in the fifth and sixth decades of life rather than in the young people that were previously infected.   Treatment consists of multidrug antituberculosis treatment therapy, but rarely the patient can necessitate a tracheostomy for acute airway compromise due to extensive involvement of the larynx. 

Like laryngeal TB, nasopharyngeal TB and nasal cavity tuberculosis used to be much more common.  In 1946, Hollander did a series of autopsies on 24 patients who died of tuberculosis infection of the lungs and found 18 of them had nasopharyngeal or nasal cavity lesions.  Admittedly, this is a very small study, but this is the best data that is available for the incidence of these lesions.  Currently, in a larger study that was done in the 80s, 843 patients underwent autopsy, and 1% of these patients with primary pulmonary tuberculosis were found to have the nasopharynx involved.  Conversely, primary pulmonary TB can be seen in 25-44% of patients that have biopsy-proven or culture-proven nasopharyngeal tuberculosis. 

Presenting symptoms include cervical lymph node enlargement, nasal obstruction, hearing loss, tinnitus, and a postnasal drip.  On gross examination, one would note anything from a mucosal fullness to a nondescript mass or ulceration, also very similar to carcinoma.  Posterior triangular or supraclavicular nodes are most frequently involved and, in the nasal cavity itself, septal mucosa is most frequently involved.  Again, as with laryngeal tuberculosis, the mainstay of treatment of multidrug antituberculosis chemotherapy. 

The infection of the structures of the oropharynx, the tonsil, and the salivary gland was once much more common prior to the widespread pasteurization of milk.  Concomitant pulmonary infections are the rule in this case, and it is believed that oral mucosa is relatively resistant to invasion by the mycobacterium tuberculosis bacilli.  It is often stated that the invasion requires disruption of the mucosa to be successful. 

Salivary gland involvement is usually secondary to spread from the oral lesion, making it even less common than oral mucosal involvement.  Painless ulcer and nodular irregularities are what you would find on physical exam.  Once again, the mainstay of treatment is multidrug antituberculosis chemotherapy.  . 

Aural tuberculosis represented about 0.4% of cases of chronic otitis media in one study from 1983.  The presenting symptoms are typically otorrhea which is persistent despite multiple courses of antibiotics, otalgia, hearing loss and, in extreme cases, facial palsy.  Physical examination findings include, classically, multiple perforations of the tympanic membrane and abundant polypoid or avascular white granulation tissue.  Initially, treatment consists of multidrug antituberculosis chemotherapy.  However, surgery is indicated in the case of facial palsy requiring facial nerve decompression, to aid in the effectiveness of the antituberculosis medications by removal of necrotic debris which can harbor tubercle bacilli, to drain any subperiosteal abscess which may develop, for other intracranial complications, as well as a tympanic membrane reconstruction once the infection is effectively resolved with medication.  In 1995, Coker and Stewart pointed out that it is important to distinguish between mycobacterium tuberculosis infection and non-tuberculous mycobacterium infection, as the latter is less sensitive to the typical medications and more often requires surgery to help resolve the infection. 

We will now discuss the type of pathology found in our case presentation, the retropharyngeal abscesses.  There are some conflicting theories as to its pathophysiology.  One is that the retropharyngeal lymph nodes become involved via direct extension from some head and neck or pulmonary lesion, and that it is typically found on the side of the pulmonary involvement.  The other theory is direct extension through the anterior longitudinal ligament of the vertebral column from involved vertebral bodies.  This seems like the more likely event in our case given the direct connection with the bony erosion from the C5 vertebral body.  Presenting symptoms include dysphagia, odynophagia, nuchal tenderness and decreased range of motion, low grade pyrexia, and occasionally respiratory distress.  Although, these are very similar to the presentation for other acute bacterial retropharyngeal abscesses, they are usually much less severe in degree, giving tuberculous retropharyngeal infections the name of a cold abscess.  Diagnosis is often aided by computed tomography, but in resource poor areas, a lateral plain film of the neck will usually suffice.

Treatment can consist of two different modalities.  One is multidrug antituberculosis chemotherapy and, in 2004, Unal et al, did describe one patient who had multiple retropharyngeal as well as some psoas abscesses that were completely resolved with medication alone, as proved with repeat MRIs. More typically, patients require either needle aspiration or incision and drainage in the operating room for resolution of this infection. 

Special considerations in this case are the need for possible neurosurgical consult. This is for patients who have any neurologic deficits, which might be related to direct extension of the abscess into the spinal canal, or for assessment of severity of the cervical instability in patients with pain at the neck with motion.  It is also very important that you communicate carefully with the anesthesia team.  That is most important for airway control.  There are many options for intubating these patients, and the intubation process can actually put them at risk for rupture of the abscess and rapid loss of the airway.  So, making a careful plan with them and communicating effectively is very important. 

In our case, we opted for an awake fiberoptic oral intubation, which proceeded without complication.  After placement of a Crowe-Davis mouth gag, we proceeded with incision and drainage of the abscess via intraoral approach and suctioned approximately 30 cc of pus from the patient’s posterior pharynx.  A culture swab was obtained and sent for analysis and, after few days, the results came back as having no acid-fast bacilli on the smear.  To this date, about four weeks after this patient’s surgery, there have been no microbacteria isolated on culture.  Yet this is not surprising considering the fact that the patient was on the antituberculosis therapy for several days prior to his surgery. At six weeks, cultures from the patient’s retropharyngeal abscess did indeed grow mycobacterium tuberculosis.

Here is a list of some things to consider when thinking about head and neck tuberculosis.  As I mentioned previously, it is quite similar in symptomology and presentation as well as in gross examination, to head and neck malignancies, and it is basically impossible to distinguish between the two based solely on appearance.  There is a large differential diagnosis for these lesions including carcinoma but also ranging to the various vasculitides, lymphoma (especially Hodgkin’s), fungal infections, and numerous other entities that need to be ruled out. 

Specimens that are obtained via excisional biopsy often show low levels of acid-fast bacilli-positive smears.  Therefore, diagnosis typically relies on a positive culture.  The problem with this is that cultures, as mentioned previously, can take several weeks before they become positive. If you are waiting on those results before initiating treatment with the antituberculosis medications, which are not benign, then you often have a delay in treatment with progression of the disease in that time span. 

One possible solution is the polymerase chain reaction, which detects DNA material from a specific organism in a specimen by amplificying that DNA many thousands of times.  These are much faster results than culture and can often be obtained in 24-48 hours.  The benefit is that it can detect as little as one femtpgram of DNA and each TB bacillus itself contains five femtograms, so you really need less than one tubercle bacillus in the specimen.  Also, it does not have to be a living bacillus.  In our patient, there may have been killed bacilli in that specimen that just did not grow on culture but could have been detected by PCR.  They are also developing specific gene probes that can detect antibiotic resistance genes and help guide your antimicrobial medication choice without waiting for sensitivities.  The disadvantage is that these are extremely expensive tests and not widely available, such as at Ben Taub.  There is a very high potential for contamination leading to false positives.  As I have said, a very little amount of DNA needs to be present for a positive test.  So, unless there is a high level of laboratory expertise and very careful maintenance of the equipment, false positive can become a problem.  Yet despite this, it has been stated that that with a pretest probability of 50% based on your clinical symptoms, positive predictive value of the PCR test is as high as 96%, meaning that a positive test is a true positive 96% of the time. 

In conclusion, although these head and neck manifestations of tuberculosis are less common than in the past, they should be considered in the differential diagnosis of many different head and neck lesions; and a high index of suspicion is necessary given their similarity in clinical presentation and appearance to other entities such as head and neck malignancy.  All manifestations are treated with antituberculosis medications, but surgery is occasionally indicated as well.  Finally, polymerase chain reaction may eventually be a standard part of the rapid and accurate diagnosis of mycobacterium tuberculosis infections.

Case Presentation:

BF is a 43-year-old African-American male who presented to the Ben Taub Emergency Center for a draining wound of his right hip.  Patient had a history of repeated wound infections and surgeries in this area since he was hit by a car in 2003.  During EC evaluation, patient was found to have active pulmonary tuberculosis and computed tomography of his chest revealed he also had spinal osteomyelitis at multiple levels.  MRI spine survey demonstrated a large retropharyngeal fluid collection that had not been previously noted on exam.

An otolaryngology consult was requested.  The patient was found to be asymptomatic specifically denying dysphagia, odynophagia, voice changes, otalgia, difficulty breathing, neck tenderness or decreased range of motion. 

Other than multiple surgeries on his hip, patient had no significant past medical, surgical, or social history.  He had low-grade pyrexia, but his other vital signs were stable.  Physical exam was significant for a large bulge of the right posterior pharyngeal wall extending from nasopharynx to just below the level of the arytenoid cartilage.  The area was fluctuant and nontender to palpation.  Patient had no neurological deficits.  Computed tomography showed erosion of the anterior surface of C6 and direct connection with the fluid collection.  Based on lack of acute symptoms, non-toxic appearance, and presence of adjacent cervical osteomyelitis, a preoperative diagnosis of “cold” tuberculous retropharyngeal abscess was made.

The patient was taken to the operating room, where an awake fiberoptic oral intubation was performed.  Thirty milliliters of pus was drained from lesion through an intraoral approach and a sample was sent for smear and culture.  Patient recovered from the operation with no complications and required no further surgical drainage.

Smear and culture results of were negative for acid-fast bacilli to date, however patient had already been on antituberculous medications for several days at the time of drainage.  Polymerase chain reaction may have able to detect the presence of killed tubercle bacilli in the pus, but this was not available at treating hospital.  Patient has responded well to antituberculous medications and continues to recover at home.

Bibliography

Al-Sherhani AM. Mycobacterial infection of the head and neck: presentation and diagnosis. Laryngoscope 2001;111:2012-16.

Auerbach O. Laryngeal tuberculosis. Arch Otolaryngol 1946;44:191-201.

Bailey CM, Windle-Taylor PC. Tuberculous laryngitis: a series of 37 patients. Laryngoscope 1981;91:93-9.

Bhargava SK, Gupta S. Large retropharyngeal cold abscess in an adult with respiratory distress.  J Laryngol Otol 1990;104:157-8.

Bull TR. Tuberculosis of the larynx.  Brit Med J 1966; 2:991-2.

CDC. Reported Tuberculosis in the United States, 2005. Atlanta, GA: U.S. Department of Health and Human Services, CDC, September 2006.

Fageeh NA, Lamothe A. Tuberculosis of the retropharyngeal space. J Otolaryngol 1998;27:43-5.

Hollander R. The nasopharynx: a study in 140 autopsy specimens. Laryngoscope1964;56:282–304.

Kanlikama M, Mumbuc S, Bayazit Y, Sirikci A. Management strategy of mycobacterial cervical lymphadenitis. J Laryngol Otol 2000;114:274-8.

Klatt EC, Garff J, Dennis SE. WebPath: The Internet Pathology Laboratory for Medical Education. Available at: http://www.md.huji.ac.il/mirror/webpath/webpath.html.

Kulkarni NS, Gopal GS, Ghaisas SG, Gupte NA.  Epidemiological considerations and clinical features of ENT tuberculosis.  J Laryngol Otol 2001;115:555-8.

Lau SK, Wei WI, Hsu C, Engzell UC. Efficacy of fine needle aspiration cytology in the diagnosis of tuberculous cervical lymphadenopathy. J Laryngol Otol 1990;104:24-7.

Lim JY, Kim KM, Choi EC, Kim YH, Kim HS, Choi HS. Current clinical propensity of laryngeal tuberculosis: review of 60 cases. Eur Arch Otorhinolaryngol 2006;263:838-42.

Manolidis S. Mycobacterial infection of head and neck. Otolaryngol Head Neck Surg 1993;109:427-33.

Munck K, Mandpe A. Mycobacterial infections of head and neck. Otolaryngol Clin North Am 2003;36:569-76.

Nalini B, Vinayak S. Tuberculosis in ear, nose, and throat practice: its presentation and diagnosis. Am J Otolaryngol 2006;27:39-45.

Nishiike S, Irifune M, Doi K, Sawada T, Kubo T. Laryngeal tuberculosis: a report of 15 cases. Ann Otol Rhinol Laryngol 2002;111:916-18.

Oktem F, Guvenc MG, Yilmaz S, Edizer DT, Kara B. Asymptomatic retropharyngeal abscess related to cervical Pott’s disease.  Amer J Otolaryngol 2006;27:278-80.

Ormerod FC. A review of tuberculosis of the upper air passages during the past thirty years and its treatment by streptomycin.  J Laryngol Otol 1951:461-71.

Piersimoni C, Scarparo C.  Relevance of commercial amplification methods for direct detection of Mycobacterium tuberculosis complex in clinical samples. J Clin Microbial 2003;41:5355-65.

Pulec JL, Deguinne C. Tuberculous chronic otitis media. Ear Nose Throat J 1999;78:820.

Richter B, Fradis M, Kohler G, Ridder GJ. Epiglottic tuberculosis: differential diagnosis and treatment. Ann Otol Rhinol Laryngol 2001;110:197-201.

Robbins SL, Cotran RS. Pathologic Basis of Disease. 6th ed. WB Saunders Co., Philadelphia, PA: WB Saunders; 1999.

Sarmiento OL, Weigle KA, Alexander J, Weber DJ, Miller WC. Assessment by meta-analysis of PCR for diagnosis of smear-negative pulmonary tuberculosis.  J Clin Microbiol 2003;41:3233-40.

Shin JE, Nam SY, Yoo SJ, Kim SY. Changing trends in clinical manifestations of laryngeal tuberculosis. Laryngoscope 2000;110:1950-53.

Sierra C, Fortun J, Barros C, Melcon E, Condes E, Cobo J, Perez-Martinez C, Ruiz-Galiana J, Martinez-Vidal A, Alvarez F. Extra-laryngeal head and neck tuberculosis.  Clin Microbiol Infect 2000;6:644-8.

Soda A, Rubio H, Salazar M, Ganem J, Berlanga D, Sanchez A. Tuberculosis of the larynx: clinical aspects in 19 patients. Laryngoscope 1989;99:1147-49.

Srirompotong S, Yimtae K, Jintakanon D. Nasopharyngeal tuberculosis: manifestations between 1991 and 2000. Otolaryngol Head Neck Surg 2004;131:762-64.

Stewart MG, Troendle-Atkins J, Starke JR, Coker NJ. Nontuberculous mycobacterial mastoiditis. Arch Otolaryngol Head Neck Surg 1995;121:225-8.

Tas E, Sahin E, Vural S, Turkoz HK, Gursel AO. Upper respiratory tract tuberculosis: our experience of three cases and review of article. The Internet Journal of Otorhinolaryngology. 2007;6.

Tse GMK, Ma TKF, Chan ABW, Ho FNY, King AD, Fung KSC, Ahuja A. Tuberculosis of the nasopharynx: a rare entity revisited. Laryngoscope 2003;113:737-40

Unal O, Kayan M, Akpinar F, Cankaya H, Akdeniz N. MRI demonstration of cervical spondylodiscitis and distal full-length bilateral paraspinal cold abscesses successfully treated by drug regimen only.  Skeletal Radiol 2004;33:741-3.

WHO. Global Tuberculosis Control: Surveillance, Planning, Financing. WHO report 2006. Geneva, World Health Organization (WHO/HTM/TB/2006.362).

Weir N. Otolaryngology: An Illustrated History. Boston, MA: Butterworth-Heinemann; 1990.

Williams RG, Douglas-Jones T. Mycobacterium marches back. J Laryngol Otol 1995;109:5-13.

Windle-Taylor PC, Bailey CM. Tuberculous otitis media: a series of 22 patients.  Laryngoscope 1980;90:1039-45.

Grand Rounds Archive | Department Home page