CLINICAL CASE

A 73-year-old male ex-smoker of 20 cigarettes/day, with a history of pancreatitis and tuberculosis over 30 years before, presented to the Service of Stomatology (Valencia University General hospital. Valencia, Spain) with a lower gingival lesion that had been present for the past 6 months. The lesion was painful and produced paresthesias in the territory of the right mental nerve.

Exploration revealed a non-indurated, 2.5-cm ulceration on the edentulous right lower alveolar margin. No adenopathies were noted. A panoramic X-ray study was requested that revealed no bone involvement.

A biopsy was obtained, showing an ulcerated mucosa with fibronecrotic tissue within the ulcer bed, and centrally necrotic epitheloid granulomas at submucosal level, with Langhans-type giant cells and abundant plasma cells distributed around the blood vessels.
The histopathological diagnosis was tuberculosis.

The biochemistry and hematological test results proved normal, with negative syphilis serology (negative antireaginic antibodies and negative anti-Treponema pallidum microhemagglutination (MHA)) and negative HIV. A Mantoux test was requested but could not be performed because the patient failed to present for the visit.

The patient was referred to the Service of Pneumology to evaluate possible reactivation of the past pulmonary tuberculosis documented in the patient case history.
Chest X-rays reported a loss of left hemithorax volume with fibrous tracts and images suggestive of bronchiectasis. Bronchial endoscopy showed atrophic chronic bronchitis, while direct sputum bacilloscopy proved negative (Ziehl-Neelsen staining).

A new fresh tissue biopsy was obtained of the oral ulceration for culture in mycobacteria growth indicator tube (MGIT) medium (Bactec MGIT 960 system); after 15 days, the growth of Mycobacterium tuberculosis was detected.

Oral tuberculosis oral was diagnosed, and treatment was prescribed in the form of isoniazid, rifampicin, pyrazinamide and ethambutol during two months, and rifampicin with isoniazid during four additional months – followed by total resolution of the oral lesion.

                                                                                                                            

Diagnosis: extrapulmonary tuberculosis.

 

DISCUSSION                                                                                                                         

Tuberculosis is chronic infections disease of worldwide distribution, generally caused by Mycobacterium tuberculosis and, less frequently, by Mycobacterium bovis and Mycobacterium africanum. Transmission is fundamentally via the aerial route and, to a lesser degree, through the ingestion of contaminated dairy products.

The incidence of tuberculosis had decreased gradually over the last century, until the 1980s, when it began to increase again (1). This phenomenon has been associated to the appearance of the human immunodeficiency virus (HIV) pandemic, the growing number of immunocompromised patients, increased immigration from endemic zones, and reinforced resistance of the bacterium to chemotherapy. In 1993 the World Health Organization (WHO) declared tuberculosis a worldwide emergency situation, and promoted directly observed treatment of short course (DOTS)(6 months), with a healing objective of 85% of bacteria-carrying patients and the detection of 70% of such individuals by the year 2000. These goals were not achieved, however, and where therefore postponed to 2005. The situation of tuberculosis in Europe is very heterogeneous, with three clearly differentiated zones: western, central and eastern Europe, with respective incidences in 1999 of 13, 44, and 86 cases / 100,000 inhabitants (2). In the year 2002 the global incidence of tuberculosis declared by the WHO for Spain was 18 cases / 100,000 inhabitants (3).

The oral manifestations of tuberculosis are infrequent, and are estimated to occur in only 0.05-0.5% of all patients with the disease. At oral level the disease may present as primary tuberculosis or, more frequently, as lesions secondary to pulmonary tuberculosis – expressing spread of the infection through saliva or via the hematogenous or lymphatic routes (4). The studies of tuberculosis located in the head and neck show no differences in distribution in terms of patient sex, the mean age being between 25 and 44 years (5) – though classically secondary oral tuberculosis has been considered to be more common in elderly patients, while the primary presentation has been associated with younger individuals.

The most commonly affected zone within the oral cavity is the tongue, gums and palate, though any location can be affected (6).

The oral lesions generally manifest as irregular, non-indurated stellate chronic ulcerations with poorly defined margins and a granulomatous bed. Nodular or granular masses have also been observed, and there have even been reports of cases with bone lesions in the form of tuberculous osteomyelitis (1,6-8). The skin, lymph nodes and salivary glands can also be affected.

The clinical differential diagnosis covers a broad range of conditions and requires the exclusion of malignant tumors such as oral squamous cell carcinoma, infectious lesions such as syphilis, histoplasmosis or paracoccidioidomycosis, or systemic disorders such as lymphoma, sarcoidosis or Wegener’s granulomatosis (4).

The clinical picture, with mental nerve paresthesia, was initially suggestive of malignancy, though the chronic nature of the lesion and the absence of infiltration at palpation could be considered indicative of a specific infectious process. It should be mentioned that the patient had not traveled to South America – thus discarding the possibility of deep mycosis endemic to hot climates. The patient moreover presented no immune deficiency or general symptoms that tend to accompany systemic mycoses.

In the face of the clinical findings, the histological and bacteriological results yield the final diagnosis. The histological study revealed the presence of epitheloid granulomas with central necrosis and Langhans type giant cells. This was suggestive of tuberculosis, in concordance with the fact that the patient had suffered pulmonary tuberculosis in the past. Nevertheless, a differential diagnosis must be established with other granulomatous inflammatory reactions such as histoplasmosis, which likewise develops from a primary pulmonary focus and spreads towards other locations such as the oral mucosa. General symptoms are usually seen in the form of sporadic fever, asthenia, rapid weight loss and adenopathies. The oral lesions can vary in appearance, with ulcerations, erythematous nodules or vegetations. The diagnosis is confirmed by the histological study, revealing a chronic, specific granulomatous inflammatory reaction, with identification of the fungus. Hematoxylin-eosin, PAS, Giemsa and Grocott silver staining in turn reveal the fungal morphology (9).

In the event of suspected tuberculosis, tuberculin skin testing indicates prior contact with M. tuberculosis. The identification of the bacillus within the tissues, based on specific staining techniques (Ziehl-Neelsen), yields the diagnosis. However, due to the scarce presence of the microorganism within the host tissues, it may be identified in only 27-60% of cases (4) – confirmation being required by growing the pathogen in culture (Ogawa, Lowenstein-Jensen media) and / or by applying other alternative techniques such as polymerase chain reaction (PCR)(4,10). In our patient culture yielded the final diagnosis.

The patient was subjected to directly observed treatment of short course (DOTS), as advocated by the WHO, with brief supervised chemotherapy cycles of isoniazid and rifampicin during 6 months together with pyrazinamide and ethambutol the first two months (with direct confirmation of ingestion of the drug at least during the first two months)(2,3).

 

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