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Case Report

Primary oral tuberculosis in a patient withlepromatous leprosy: Diagnostic dilemma

http://dx.doi.org/10.1016/j.ijmyco.2015.10.0062212-5531/� 2015 Asian African Society for Mycobacteriology. Production and hosting by Elsevier Ltd. All rights reserved.

* Corresponding author at: Number 4/437, Babu Nagar Main Road, Sourashtra Teachers Colony, Anuppanadi, Madurai, TaIndia.

E-mail address: vidhya.md@gmail.com (V. Ganesan).

Peer review under responsibility of Asian African Society for Mycobacteriology.

Vithiya Ganesan a,b,*, Jharna Mandal a

aDepartment of Microbiology, Jawaharlal Institute of Postgraduate Medicine and Research, Puducherry, IndiabDepartment of Microbiology, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India

A R T I C L E I N F O

Article history:

Received 24 September 2015

Received in revised form

29 October 2015

Accepted 31 October 2015

Available online 19 November 2015

Keywords:

Co-infection

Leprosy

Oral tuberculosis

A B S T R A C T

Pulmonary tuberculosis (TB) is the most common form of TB. Primary infection can also

affect the pharynx, cervical lymph node, intestine, or oral mucosa. Historically, the

observed incidence of concomitant infection with leprosy and TB is high. However, reports

of concomitant infection in modern literature remain scarce. Most cases reported in the lit-

erature had borderline/lepromatous leprosy and pulmonary tuberculosis. Extrapulmonary

tuberculosis is reported in only 3.2% of leprosy cases. To the best of our knowledge, this is

the first case report of primary oral tuberculosis of the tongue in a patient with

lepromatous leprosy with Type 2 lepra reaction. The patient was referred to Directly

Observed Treatment, Short-Course clinic and started on Category I treatment. She received

oral prednisolone for lepra reaction, which was subsequently tapered and stopped, how-

ever, she continued to receive other antileprotic drugs (thalidomide and clofazimine).

The patient’s general condition improved and she is on regular follow up.

� 2015 Asian African Society for Mycobacteriology. Production and hosting by Elsevier Ltd.

All rights reserved.

ple tissue from the tip of the tongue was collected and sent

Case report

A 45-year-old female came to the outpatient department with

complaints of low-grade fever for 2 weeks, erythema and

edema of the whole body, and painless ulcers in the tip of

the tongue. She had a history of leprosy, which was treated

and cured 15 years ago. In the dermatology outpatient depart-

ment, she was evaluated for leprosy. Slit-skin smear was

taken from different sites such as the nose, eyebrows,

earlobes, and the results indicated 4+ grading for all the

aforementioned samples. Based on this result, the patient

was diagnosed as a case of lepromatous leprosy with Type 2

reaction and we decided to treat her with multidrug therapy.

To examine the pathology of the ulcer of the tongue, sam-

for various examinations such as KOH mount and fungal

culture, Giemsa stain for histoplasmosis, bacterial culture

and acid-fast staining, and histopathological examination.

Surprisingly, Ziehl–Neelsen staining showed acid-fast bacilli,

which were beaded and not uniformly stained, a finding char-

acteristic of tubercle bacilli. Histopathological examination of

the sample showed a granulomatous reaction with central

caseous necrosis and epithelioid and giant cells suggestive

of tuberculosis (Fig. 1).

Nested polymerase chain reaction was performed after

extracting the DNA from the sample tissue. The extracted

mil Nadu,

Fig. 1 – Histopathological examination showing central caseous necrosis and epithelioid and giant cells suggestive of

tuberculosis.

I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y 5 ( 2 0 1 6 ) 1 0 2 –1 0 5 103

DNA was amplified using two sets of primers coding for

IS6110 (insertion sequence), which is specific for

Mycobacterium tuberculosis. After amplification, gel elec-

trophoresis was carried out, which showed a band corre-

sponding to IS6110 (219 bp; Fig. 2). Based on this result, oral

tuberculosis of the tongue was diagnosed. To identify the pri-

mary focus of infection, we carried out further examinations.

Chest X-ray showed clear lung fields without features of

tuberculosis. Computed tomography of the thorax and abdo-

men did not reveal any primary focus. Venereal Disease

Research Laboratory and human immunodeficiency virus

(HIV) tests were not reactive. A provisional diagnosis of pri-

mary oral tuberculosis of the tongue in lepromatous leprosy

was made and we initiated treatment for both leprosy and

tuberculosis. The patient was advised to stop taking dapsone

and instead received oral prednisolone, thalidomide, and clo-

fazimine. The patient was referred to the Directly Observed

Treatment, Short-Course clinic and started on Category I

treatment. The oral prednisolone dose was subsequently

tapered and stopped, however, she continued to receive the

other antileprotic drugs. The patient’s general condition

improved and she was on regular follow up. We obtained

Institutional Ethical Committee approval and informed con-

sent from the patient for reporting this case.

Discussion

Historically, the observed incidence of concomitant infection

with leprosy and tuberculosis (TB) is high. However, reports

of concomitant infection in modern literature remain scarce.

Estimation of the annual new case detection rate (ANCDR) in

India, where both TB (ANCDR 181/100,000 in 2011) [1] and

leprosy (ANCDR 10–35/100,000 in 2011) [2] remain endemic,

suggests that only 0.019 cases of concomitant infec-

tion/100,000 population would be detected.

It is hypothesized that reduced cell-mediated immunity

plays a role in reactivation of latent TB or superinfection with

TB inmultibacillary patients. Trindade et al. [3] recently inves-

tigated the cell-mediated responses of two patients who were

diagnosed with borderline leprosy and TB [3]. However, they

were unable to find any aberrant response of the interferon-

gamma/interleukin-12/23 axis on immunological evaluation.

Therefore, further studies are needed to support this

hypothesis.

Although there are many well-known risk factors for TB,

including HIV infection, diabetes mellitus, transplant patients

on immunosuppression, and birth and travel in the develop-

ing world, the use of steroids and development of TB are con-

troversial. One weakness in the argument for steroids

increasing the risk of developing TB is that a large number

of leprosy patients, especially those with multibacillary

leprosy, go on to develop lepra reactions, which require ster-

oid treatment. This means that there is a high rate of steroid

prescriptions in leprosy cases. With an estimated ANCDR for

co-infection of 0.019/100,000 patients (in India), the incidence

of patients started on steroids is approximately 66 times

greater than the estimated incidence of co-infection with

both diseases [4]. Therefore, longitudinal work with active

screening of patients before commencing treatment is neces-

sary to identify any temporal relationship between steroids

and TB development.

Fig. 2 – Gel electrophoresis of nested PCR amplicons showing bands corresponding to IS6110 (219 bp). Note: IS = insertion

sequence; M =molecular ladder; PC = positive control; PCR = polymerase chain reaction; T = test.

104 I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y 5 ( 2 0 1 6 ) 1 0 2 –1 0 5

Most co-infection cases reported had borderline/leproma-

tous leprosy and pulmonary tuberculosis. Extrapulmonary

tuberculosis was reported in only 3.2% of leprosy cases. This

includes cutaneous, lymph node, and central nervous system

tuberculosis [4]. To date, only one case of co-infection of

leprosy and oral tuberculosis (larynx) [5] was reported in the

literature.

Oral manifestation of tuberculosis is a rare occurrence,

observedonly in 0.05–5%of theTBpopulation [6]. Saliva, sapro-

phytes, and the very high integrity of oral epitheliumwith stri-

ated muscles resist the bacterial invasion. Usually, oral

tuberculosis is secondary to pulmonary involvement and pre-

sents as a single indurated painful ulcer especially in middle

aged and elderly individuals. Primary oral tuberculosis pre-

senting as a single painless ulcer in younger individuals is

uncommon. The most common site is the lateral margins of

the tongue, which rest against rough, sharp, and broken teeth.

Any area of chronic irritation or inflammationmay favor local-

ization of Mycobacterium associated with the disease [7].

Infectious etiologies to be evaluated include primary syphi-

lis and deep fungal diseases such as histoplasmosis. Noninfec-

tious etiology includes traumatic ulcer and squamous cell

carcinoma.Whenoral lesions of tuberculosis are the soleman-

ifestations of the disease, the clinician may face a diagnostic

challenge. Another concern is whether there is an increased

risk of rifampicin resistance in undiagnosed tuberculosis

co-infection due to multidrug therapy. Although this may be

an unlikely consequence of monthly rifampicin treatment in

India, it may be a greater concern in regions where leprosy

patients take daily rifampicin, such as in the United States.

Conclusion

The relationship between the two mycobacterial diseases

continues to be enigmatic despite decades of research.

Nowadays, oral manifestations of TB are reappearing along-

side many forgotten extrapulmonary infections. Recognition

of oral tuberculosis is important to prevent emergence of

rifampicin-resistant tuberculosis during treatment of leprosy.

These patients require interdisciplinary management and

social support.

Conflicts of interest

None.

R E F E R E N C E S

[1] World Health Organization, Global Tuberculosis Report 2012,World Health Organization, Geneva, Switzerland. Availablefrom: <http://www.who.int/tb/publications/global_report/en/>,(last accessed: 9.11.2015).

[2] National Leprosy Eradication Programme, NLEP – Progressreport for the year 2011–2012, Central Leprosy Division, NewDelhi, India.

[3] M.A. Trindade, D. Miyamoto, G. Benard, et al, Leprosy andtuberculosis coinfection: clinical and immunological report oftwo cases and review of the literature, Am. J. Trop. Med. Hyg.88 (2013) 236–240.

I n t e r n a t i o n a l J o u r n a l o f M y c o b a c t e r i o l o g y 5 ( 2 0 1 6 ) 1 0 2 –1 0 5 105

[4] M.R. Timothy, A. Vaseem, H. Jasmin, et al, Leprosy andtuberculosis concomitant infection: a poorly understood, age-old relationship, Lepr. Rev. 85 (2014) 288–295.

[5] P.M. Flanagan, J.C. McIlwain, Tuberculosis of the larynx in alepromatous patient, J. Laryngol. Otol. 107 (1993) 845–847.

[6] F.A. Ito, C.R. de Andrade, P.A. Vargas, et al, Primarytuberculosis of the oral cavity, Oral Dis. 11 (2005) 50–53.

[7] S. Kapoor, S. Gandhi, N. Gandhi, et al, Oral manifestations oftuberculosis, CHRISMED J. Health Res. 1 (2014) 11–14.