Oral TB & HIV

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INTRODUCTION
Tuberculosis is still one of the most life threatening infectious diseases, resulting in high mortality in adults.

The World Health Organization (WHO) estimates that worldwide there are 4/30/12

It is very common in India and South-East Asia, where the prevalence rate is about four in every 1,000 people.

India alone accounts for nearly one fifth of the global burden of tuberculosis .

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Every year, approximately 2.2 million individuals develop tuberculosis in India, of which around 0.87 million are infectious cases and it is estimated that annually there are around 330,000 deaths due to TB.

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The incidence of TB in the underdeveloped countries is increasing, and this is thought to be because of associated poor hygienic conditions and a greater prevalence of acquired immunodeficiency syndrome (AIDS).

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Oral tuberculosis
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Chronic granulomatous disease

Caused by:
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Mycobacterium tuberculosis Mycobacterium bovis atypical Mycobacteria.

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Extrapulmonary tuberculosis is rare, occurring in 10% to 15% of all cases. Oral manifestations occur in approximately 3% of cases involving long standing pulmonary and/ or systemic infection.

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Oral Clinical May be as presentation :

Ulcers Erythematous patches Indurated lesions with granular surface Nodules Fissures Plaques Granulomas Vemicous proliferations
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Sites involved:
Most commonly affected site:

Tongue(the lateral border, tip, anterior dorsum and the ventral surface) Lip Cheek Soft palate Uvula Gingiva
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Other sites include:

Types of oral tuberculosis:

Two main types of tubercular infections of oral tissues are recognized

Primary Secondary.

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Primary oral tuberculosis:

Primary lesions develop when tuberculosis bacilli are directly inoculated into the oral tissues of a person who has not acquired immunity to the disease and in fact, any area that is vulnerable to direct inoculation of bacilli from exogenous source can be a potential site.

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These frequently involve

Gingiva Tooth extraction sockets Buccal folds.

Primary oral tuberculous lesions are extremely rare and generally occur in young adults with associated caseation of the dependent lymph nodes; the lesion itself remains painless in most cases. Primary lesions of tuberculosis manifest in the oral cavity as non healing chronic ulcers.
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Barriers to infection:
1. An

intact oral mucosa 2. Cleansing action of saliva 3. Salivary enzymes 4. Tissue antibodies 5. Oral saprophytes
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Secondary oral tuberculosis

Secondary infection of oral tissues can result from either haematogenous or lymphatic spread or from autoinoculation by infected sputum and direct extensions from neighbouring structures. Intraoral sites frequently involved include:

Tongue Palate
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Secondary oral tuberculosis is seen in about 0.05% to 1.5% of cases and usually in older adults.

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Local predisposing factors:

Poor oral hygiene Local trauma Dental extraction Leukoplakia Periapical granuloma Jaw fracture Periodontitis Dental Cyst Dental abscess
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Systemic predisposing factors:

Lowered host resistance Increased virulence of the organisms

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Pathogenesis:
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The mechanisms that prevent activation of latent M.tb and those that bring active TB infection under control are poorly characterized. CD4+ T cells play an essential role in controlling active M.tb infection, but only a minor role in preventing re-activation of latent M.tb infection. CD8+ T cells provide immunity against re4/30/12

Primary M.tb infection Mycobacteria phagocytosed by macrophages Activate CD4+ T cells Cytokines are secreted Activate lymphocytes and mononuclear phagocytes Fuse into multi-nucleated giant cells Forms immunoinflammatory granuloma 4/30/12 (tubercle)

Reactive nitric oxide metabolites produced by activated macrophages play an important role in the intracellular neutralization of the bacteria. CD8+ cytotoxic T effector cells recognize M.tb antigens on infected macrophages in the context of MHC class1 molecules and induce either killing of the intracellular pathogens or lysis of the infected cells by means of granzymes, granulysin or perforin. Furthermore a Th-1cytokine profile is important 4/30/12 for building up a protective

Symptoms:

Persistent productive or unproductive cough Evening rise of temperature Gradual weight loss Malaise

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Clinical features:

An ulcerative lesion of the mucosa is seen. The lesion may be preceded by an opalescent vesicle or nodule which may break down as a result of caseation necrosis to form an ulcer.
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Ulcer of the right buccal mucosa

Intra orally photograph shows an ulcer with well defined margins on the left buccal mucosa covered by a yellow pseudomembrane

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Extraoral photograph shows enlarged cervical lymph node

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Differential diagnosis:

Primary squamous cell carcinoma Traumatic ulcer Syphilitic ulcer Lymphoma Autoimmune disorder Other orofacial granulomatous conditions:

Sarcoidosis

Deep mycotic infection 4/30/12

Invesigations:

Sputum

examination(smea r microscopy) { Ziehl-Neelsen, PAS staining}

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Histopathology:

Multiple confluent and discrete granulomas composed of epithelioid histiocytes and Langhans giant cells with central caseous necrosis, surrounded by lymphocytes and few plasma cells.

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Low magnification micrograph showing numerous noncaseating granulomas.

Higher-magnification micrograph of granulomatous process with Langhans giant cells and epithelioid cells.

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Histopathological slide shows granulomatous inflammation with Langhans giant cells and focal caseous necrosis (hematoxylin and eosin stain)

Langhans cells containing nuclei arranged in a horseshoe shaped pattern at cell periphery

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Several acid-fast bacilli in the sputum (Ziehl-Neelsen stain)

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Chest radiograph without abnormal findings.

Postero-anterior chest
radiograph showing bilateral upper lobe consolidation and cavitation, consistent with pulmonary tuberculosis

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Treatment:
Standard antitubercular therapy with isoniazid, rifampicin ,pyrazinamide and ethambutol.

WHO recommended category 1 antitubercular therapy DOTS (Directly Observed Treatment, Short Course) :
Rifampicin (450 mg), Isoniazid (600 mg), Ethambutol (1200 mg) and Pyrazinamide (1500 mg) for two months, with three times doses per week, followed with a continuation phase with 4/30/12 Isoniazid (300 mg) and Thioacetazone (150 mg)

CASE REPORT
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A 30-year-old female came with a painful sore on the upper left labial mucosa of about 2 weeks duration.

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Age: 30yrs Sex: Female Chief complaint: Patient complains of a painful

sore on the upper left lip region of about 2 weeks duration.

Habits: No habit of smoking or drinking

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Built: Moderate Past medical history: Claimed to be HIV-

seronegative as tested for HIV infection 2 months back.

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Oral examination:
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Two ulcers:

1.On the upper left labial mucosa(painful) 2.On the ventral surface of the tip of the tongue.

The dorsal surface of the anterior margin 4/30/12 of the tongue was hyperaemic with a

Both ulcers were surrounded by a wide area of erythema. The margins of both ulcers were slightly elevated & indurated.

Ulcer on the ventrum of the tip of the tongue,with slightly elevated margins and a wide zone of surrounding erythema.

Dorsum of anterior one-third of the tongue with erythematous, lobulated appearance.

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Histopathology:

Histological examination showed necrotic tissue and chronically inflamed granulation tissue.

Scattered epithelioid cells were present, and Ziehl-Neelsen staining revealed the presence of acid fast bacilli leading to the final diagnosis of oral tuberculosis.
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The chronic granulomatous lesion in the sub mucosa of the lip (H&E stain, 300).

Ziehl-Neelsen stain showing two acid-fast bacilli(1000).

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General examination:
Patient proved to be HIV-seropositive with CD4+T cell count of 429 cells/mm3.

General physical examination:

Unremarkable

Chest radiograph: Didnt show any

evidence of tuberculosis
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Diagnosis:

The diagnosis of primary oral TB was made by biopsy since the clinical features of the oral lesions were nonspecific. On microscopical examination, typical tuberculous granulomas were not evident. The presence of epithelioid cells prompted the Ziehl-Neelsen stain which revealed the acidfast bacilli.
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Treatment:
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A nine-month anti-TB drug regimen of isoniazid,rifampicin, pyrazinamide, and ethambutol was prescribed. The patient did not receive antiretroviral treatment because in government hospitals this is allowed only to patients whose CD4+ T cell counts are lower than 200cells/mm3. Unfortunately our patient could not afford the 4/30/12 medication privately.

Follow-up:

The same site, four weeks after starting antitubercular treatment.

The same region, four weeks after starting antitubercular treatment.

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HIV-M.tb coinfection
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Infection with HIV is the greatest single

risk factor either for the progression of latent infection to active TB or for acquisition of new M.tb infection.

Subjects with HIV-M.tb co-infection more frequently have extrapulmonary TB than do HIV-seronegative subjects, lymph nodes and central-nervous system being the sites most commonly affected.
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Pathogenesis of HIVM.tb co-infection v Complex

v

Multifactorial. The profound HIV-associated cellular immune suppression has several identifiable characteristics: A progressive decrease of CD4+ T cells 4/30/12

M.tb-specific chronic activation of the

cellular arm of the immune response adds to the existing HIV-associated CD4+ T-cell and CD8+ T-cell exhaustion.

M.tb promotes HIV replication by upregulating CXCR4 surface receptors on alveolar macrophages thus permitting the more virulent X4 strains of HIV to enter and replicate in these cells.
4/30/12 This leads to further immune exhaustion and

Diagnosis of HIV-M.tb co-infection

The diagnosis of TB in HIV-seropositive subjects is not always straightforward as the clinical signs and symptoms of TB in these subjects are not as well defined as in HIV-seronegative subjects. HIV-M.tb co-infected subjects are frequently negative to tuberculin skin testing.
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Treatment of HIV-M.Tb co-infection

If highly active antiretroviral therapy (HAART) is introduced early in the course of HIV disease and if concurrent TB is treated expeditiously, then this pernicious cycle will be arrested. The outcome of treatment of TB in either HIVseropositive subjects or HIV-seronegative subjects is similar, but recurrence of, and mortality rates from TB are greater in HIVseropositive subjects .
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TB may also sometimes present as an

immune reconstitution inflammatory syndrome shortly after HAART has brought about a decrease in the HIV load with consequential significant elevation of the CD4+ T cell count.

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