The document describes tuberculosis (TB), a chronic infectious disease caused by mycobacteria. It notes that TB remains a major global health problem, with millions of active cases and deaths annually, especially in developing countries like India. It discusses the pathogenesis of TB infection and highlights that oral TB lesions can occur secondary to pulmonary or systemic infection, presenting as ulcers, nodules, or granulomas most commonly on the tongue. The document also includes a case report of a female patient diagnosed with oral TB based on histological findings of granulomatous inflammation and identification of acid-fast bacilli on staining.

2. 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 approximately 20 million
active cases, of them approximately 3 million people
die each year from tuberculosis, of which 80% are in
developing countries.

3.  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 .

4. 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.

5. 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).

7.  Chronic granulomatous disease
Caused by:
 Mycobacterium tuberculosis
 Mycobacterium bovis
 atypical Mycobacteria.

8.  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.

9. May be as
 Ulcers
 Erythematous patches
 Indurated lesions with granular surface
 Nodules
 Fissures
 Plaques
 Granulomas
 Vemicous proliferations
 Jaw lesions in the form of tuberculous osteomyelitis.

10. Most commonly affected site:
 Tongue(the lateral border, tip, anterior dorsum and
the ventral surface)
Other sites include:
 Lip
 Cheek
 Soft palate
 Uvula
 Gingiva
 Alveolar mucosa
 Tooth socket
 Jaw involvement may present as osteomyelitis

11. Two main types of tubercular infections of oral tissues
are recognized –
 Primary
 Secondary.

12. 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.

13. 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.

14. 1. An intact oral mucosa
2. Cleansing action of saliva
3. Salivary enzymes
4. Tissue antibodies
5. Oral saprophytes
Any breach in these defense mechanisms, such as
abrasions, tears, chronic inflammation,
poor oral hygiene, tooth eruption, extraction sockets,
periodontal disease, and carious teeth with pulp
exposure may lead to infection by tubercle bacilli.

15. 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
 Lips
 Alveolar mucosa
 Buccal mucosa
 Gingiva
 Frenula
 and jaw bones

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

17.  Poor oral hygiene
 Local trauma
 Dental extraction
 Leukoplakia
 Periapical granuloma
 Jaw fracture
 Periodontitis
 Dental Cyst
 Dental abscess
 Poor socio-economic condition with inadequate
nutrition

18.  Lowered host resistance
 Increased virulence of the organisms

19.  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 re-activation of
latent infection, but make only a limited contribution to
the containment of active M.tb infection.

20. 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 (tubercle)

21.  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 for
building up a protective immunoinflammatory response
to M.tb infection.

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

23.  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.
 The typical tuberculous ulcer is an irregular lesion
with ragged undermined edges, minimal induration
and often with a yellowish granular base.
 Tiny single or multiple nodules called 'sentinel
tubercles' may also be seen surrounding the ulcer.

24. 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

25. Extraoral photograph shows enlarged cervical
lymph node

26.  Primary squamous cell carcinoma
 Traumatic ulcer
 Syphilitic ulcer
 Lymphoma
 Autoimmune disorder
 Other orofacial granulomatous conditions:
 Sarcoidosis
 Deep mycotic infection
 Cat-scratch disease
 Foreign body reactions
 Wegener’s granulomatosis
 Crohn’s disease
 Melkersson-Rosenthal syndrome

27.  Sputum examination(smear microscopy)
{ Ziehl-Neelsen, PAS staining}
 Chest radiograph (PA view)
 Intraoral radiograph
 Biopsy
 Tuberculin (Montoux) test
 Mycobacterial culture
 Special staining(Grocott-Gomori stains, Auramine-Rhodamine
stain)
 C-reactive protein test
 Evaluation of immunoglobulins
 ESR
 FNAC
 DNA probes
 Polymerase Chain Reaction(PCR) assays
 ELISA test

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

29. Low magnification micrograph Higher-magnification micrograph of
showing numerous noncaseating granulomatous process with
granulomas. Langhan’s giant cells and epithelioid
cells.

30. Histopathological slide shows Langhan’s cells containing nuclei
granulomatous inflammation with arranged in a horseshoe shaped
Langhan’s giant cells and focal caseous pattern at cell periphery
necrosis (hematoxylin and eosin stain)

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

32. Chest radiograph without Postero-anterior chest radiograph
abnormal findings. showing bilateral upper lobe
consolidation and cavitation,
consistent with pulmonary tuberculosis

33. Standard antitubercular therapy with isoniazid,
rifampicin ,pyrazinamide and ethambutol.
WHO recommended category 1 anti-
tubercular 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 Isoniazid (300 mg) and
Thioacetazone (150 mg) for six months.

34. CASE REPORT

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

36. 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

37. Built: Moderate
Past medical history: Claimed to be HIV-
seronegative as tested for HIV infection 2 months
back.

38.  Twoulcers:
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 of
the tongue was hyperaemic with a lobulated
appearance.

39.  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
Dorsum of anterior one-third of the
tongue,with slightly elevated margins
tongue with erythematous, lobulated
and a wide zone of surrounding
appearance.
erythema.

40.  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.

41. The chronic granulomatous lesion in
Ziehl-Neelsen stain showing two
the sub mucosa of the lip (H&E stain,
acid-fast bacilli(×1000).
×300).

42. Patient proved to be HIV-seropositive with CD4+T
cell count of 429 cells/mm3.
General physical examination: Unremarkable
Chest radiograph: Didn’t show any evidence of
tuberculosis
Other laboratory investigations: All within the
range of normality

43.  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 acid-fast bacilli.
 Failure to express well-defined granulomas with giant
cells is the result of immune suppression due to HIV co-
infection.

44.  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
medication privately.

45. The same site, four weeks after The same region, four weeks after
starting antitubercular treatment. starting antitubercular treatment.

46. HIV-M.tb co-infection

47.  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.
 There is a synergistic relationship between
tuberculosis and HIV infection: each accelerates the
progression of the other; and HIV-seropositive
subjects with TB have a shorter life than TB-free HIV-
seropositive with comparableCD4+ T cell counts.

48.  Complex
 Multifactorial.
 The profound HIV-associated cellular immune
suppression has several identifiable
characteristics:
 A progressive decrease of CD4+ T cells
 Functional impairment of surviving CD4+ T cells
 Functional impairment of macrophages and
polymorphonuclear neutrophils
 Dysregulation of the cytokine network
 CD8+ T cell exhaustion.

49.  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.
 This leads to further immune exhaustion and
impairment, resulting in the perpetuation of
a pernicious cycle of HIV-M.tb co-infection.

50.  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.
 Acid fast bacilli are very scant in their sputum
although sputum culture invariably confirms
pulmonary TB,and pulmonary TB granulomas are
not always present.

51.  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 HIV-
seropositive subjects or HIV-seronegative subjects is
similar, but recurrence of, and mortality rates from TB
are greater in HIV-seropositive subjects .

52.  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.