granulomatous diseases seminar 1-1.pptx

first part

1. GRANULOMATOUS DISEASE OF ORAL CAVITY 1 Presented by, Dr. Nitha Willy Second Year PG Department Of Oral Medicine And Radiology

2. CONTENTS Introduction Classification of granulomatous disorders Granulomatous diseases that may affect the oral tissues 2

3. GRANULOMA ‘Granule’ = circumscribed granule like lesion ‘Oma’ = Tumors /inflammatory mass or collection of macrophages 3

4. Adams defined the granuloma as “a compact (organized) collection of mature mononuclear phagocytes (macrophages and/or epithelioid cells) which may or may not be accompanied by accessory features such as necrosis or the infiltration of other inflammatory leukocytes” Costabel U, du Bois RM, Egan J(eds): Diffuse Parenchymal Lung Disease. Prog Respir Res. Basel, Karger, 2007, vol 36, pp 87-100 4

5. Granuloma is defined as a circumscribed, tiny lesion; about 1mm in diameter, composed predominantly of collection of modified macrophages called epitheloid cells and rimed at the periphery by lymphoid cells. - Harshmohan Granulomatous inflammation is a distinctive form of mononuclear inflammation usually evoked by infectious agents that resist eradication and are capable of stimulating strong T cell–mediated immunity. - Robbin’s – Pathologic basis of disease 5

6. Granulomatous inflammation is characterized by accumulation of activated macrophages called “epithelioid” cells , which may fuse to form giant cells. 6

7. Granulomatous diseases are a heterogeneous group of disorders that are characterized by a specific pattern of chronic inflammation called granulomatous inflammation, in which granulomas are formed. GRANULOMATOUS DISEASES 7

8. Components of the granulomatous tissue Macrophages Epitheloid cells Giant cells Lymphocytes Fibroblasts 8

9. PATHOGENESIS OF THE GRANULOMAS Two factors contribute to the pathogenesis of the granulomatous process. When the inducer agent is a pathogen/invader or foreign body the intrinsic toxicity of the agents can damage the tissues. 2) The vigorous immune-inflammatory T cell-mediated response evoked by the pathogen recruits macrophages and other cells that during the activated stage and phagocytosis secrete tissue-damaging substances. 9

10. The process of granuloma formation Triggering of T cells by antigen presenting cells Release of cytokines and chemokines with multiple and overlapping functions Accumulation and in situ proliferation of immunocompetent cells at sites of ongoing inflammation Organized structure of granuloma 10

11. After exposure to antigen, resident cells initiate cellular recruitment Pre- stored TNF released by mast cells recruits neutrophils, which activate tissues and circulating monocytes 1. INITIATION OF IMMUNE RESPONSE IFN- γ produced by NK and T-cells further activates resident tissue histiocytes and macrophages 11

12. 2. PRODUCTION OF Ag- SPECIFIC T CELLS: Macrophages produce IL-12 and present antigen to CD4+T cells Under the influence of IL-12,CD4+ cells and TH1 cells CD4+TH1 secrete IL-2 T- cell survival and proliferation Expansion of the population of Ag- specific TH1 cells 12

13. 3. FORMATION OF MATURE GRANULOMA Perivascular T-cell infiltrate is progressively replaced by macrophages Epitheloid cells Fuse in the presence of IFN- γ Giant Cells Granuloma 13

14. PATHOLOGICAL FEATURES OF MATURE GRANULOMAS Pagán AJ, Ramakrishnan L. The Formation and Function of Granulomas. Annu Rev Immunol. 2018 Apr 26;36(1):639-65. 14

15. FATE OF GRANULOMAS 1.Cold abscess 2.Sinus tracts 3.Size increase 4.Calcification and ossification 15

16. Granulomas can be classified 1) T cell-mediated immune granulomas formed to infectious agents. 2) Granulomas with unknown etiology but with a T lymphocyte-mediated profile. 3) Foreign body granulomas induced by inanimate substances. 4) Granulomas associated with malignant tumors 16

17. TYPES OF GRANULOMAS Aróstegui Aguilar J, Diago A, Carrillo Gijón R, Fernández Figueras M, Fraga J, García Herrera A, et al. Granulomas in Dermatopathology: Principal Diagnoses - Part 1. Actas Dermo- Sifiliográficas (English Edition). 2021 Sep;112(8):682-704. 17

18. TUBERCULOID GRANULOMAS epithelioid granulomas This forms when cell-mediated immunity is operative . The most common type of granuloma in tuberculosis . It usually display central caseous necrosis 18

19. SARCOID GRANULOMAS Common in sarcoidosis Sarcoid granulomas do not normally have a prominent peripheral inflammatory infiltrate, and are therefore described as naked . They represent a “proliferative” rather than “necrotizing” pattern. 19

20. Necrobiotic granuloma suggests the presence of “dead” tissue in the center of the granuloma. It include granuloma annulare, necrobiotic xanthogranuloma , rheumatoid nodules, and necrobiosis lipoidica . Also known as palisaded granulomas , as the histiocytes surrounding the central area of degenerated tissue may follow a palisading pattern NECROBIOTIC GRANULOMA 20

21. They form in response to a wide range of foreign bodies. Giant cells often encapsulate and adapt their shape to the foreign particles they are attempting to engulf. It is composed of histiocytes and lymphocytes and do not have a consistent or predefined shape FOREIGN BODY GRANULOMAS 21

22. SUPPURATIVE GRANULOMAS Suppurative granulomas show abundant polymorphonuclear neutrophils in their center. They are most often seen in infections caused by fungi or atypical mycobacteria. 22

23. MESSY GRANULOMAS Messy granulomas are formed by loose, randomly arranged epithelioid histiocytes. The loose appearance is due to the abundant cytoplasm and glassy appearance of the histiocytes. Messy granulomas are a characteristic finding in leishmania. 23

24. XANTHOGRANULOMAS Xanthogranulomas are mainly composed of histiocytes and giant cells with xanthomatous (foamy cytoplasmic)changes due to the accumulation of lipid content. 24

25. MIESCHER GRANULOMA Miescher granuloma is characterized by a collection of small histiocytes with pale cytoplasm surrounding a central cleft. Miescher granuloma is quite specific to erythema nodosum 25

26. Most granulomas fall into one of two categories: CASEATING : with a necrotic center NON-CASEATING : without any necrosis Caseating granulomas - caused by infections Non-caseating granulomas - caused by an inflammatory condition 26

27. CLASSIFICATION OF GRANULOMATOUS DISORDERS 27

28. GRANULOMATOUS DISORDERS 5. Chemicals 6.Neoplasia 7.Hypersensitivity Pneumonitis 8.Miscellaneous infections James DG. A clinicopathological classification of granulomatous disorders. Postgraduate Medical Journal. 2000 Aug 1;76(898):457-65. 28

29. 1.INFECTIONS Bacterial Tuberculosis Leprosy Syphilis Cat Scratch disease Tularemia Granuloma inguinale Brucellosis Glander’s disease Actinomycosis Listerosis Nocardiosis Salmonellosis 2. Chlamydial Lymphomagranuloma venerum 3. Fungal Blastomycosis Coccidioidomycosis Cryptococosis Histoplasmosis 4. Parasitic Aniskiasis Capillariasis Echinococcosis Schistosomiasis 5.Protozoal Leishmaniasis Toxoplasmosis 29

30. 2.VASCULITIS Wegener’s Granulomatosis Necrotising Sarcoidal Granulomatosis Churg- strauss Syndrome Lymphomatoid Granulomatosis Polyarteritis Nodosa Bronchocentric Granulomatosis Giant Cell Arteritis Systemic Lupus Erythematosus 30

31. Sarcoidosis Crohn’s disease Primary biliary cirrhosis Hepatic granulomatous disease Langerhan’s granulomatosis Orofacial granulomatosis ( Melkersson -Rosenthal syndrome) Peyronie’s disease Blau’s syndrome Hypogammaglobulinaemia Histiocytosis X Immune complex disease 3.IMMUNOLOGICAL ABERRATIONS 31

32. 4. LEUCOCYTE OXIDASE DEFECTS Chronic granulomatous disease of childhood and adults 5. CHEMICALS Berylllium Zirconium Silica Starch Talc 32

33. 33

34. 7. NEOPLASIA Carcinoma Reticulosis Pinealoma Dysgerminoma seminoma Reticulum cell sarcoma Malignant nasal granuloma 8.MISCELLANEOUS INFECTIONS Whipple’s disease Cat scratch disease Lymphogranuloma Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis Buruli ulcer 34

35. BASED ON TYPE OF NECROSIS CASEATING/SUPPURATIVE GRANULOMAS Tuberculosis Syphilis Cat scratch disease Actinomycosis Blastomycosis Cryptococcosis Coccidiodomycosis 35

36. NON-CASEATING/NON- SUPPURATIVE GRANULOMAS Leprosy Sarcoidosis Crohn’s disease Silicosis Foreign body granulomas 36

37. GRANULOMATOUS DISEASES THAT MAY AFFECT THE ORAL TISSUES Foreign bodies Oral foreign body reactions Bacterial Tuberculosis Leprosy Syphilis Cat Scratch disease Fungal Blastomycosis Paracoccidioidomycosis Aspergillosis Histoplasmosis Protozoal Leishmaniasis Toxoplasmosis Vasculitis Wegener’s Granulomatosis Churg- strauss Syndrome Systemic Lupus Erythematosus Immunological Sarcoidosis Crohn’s disease Orofacial granulomatosis Reactive lesions Pyogenic granuloma Peripheral giant cell granuloma Periapical granuloma 37

38. BACTERIAL 38

39. TUBERCULOSIS 39

40. INTRODUCTION Also known as “ WHITE DEATH” One of the deadliest diseases in the world Tuberculosis flourishes wherever there is poverty, crowding, and chronic debilitating illness. 40

41. DEFINITION Tuberculosis (TB) is a chronic infectious granulomatous disease caused by Mycobacterium tuberculosis characterized by formation of granulomas in infected tissue by cell mediated hypersensitivity 41

42. CAUSED BY Members of the species Mycobacterium Tuberculosis complex (MTBC): Mycobacterium tuberculosis Mycobacterium bovis Mycobacterium africanum 42

43. SITE SPECIFIC MYCOBACTERIAL DISEASE Major Less common Pulmonary M.Tuberculosis M.Bovis M.Xenopi M.Kansasii M.Malmoense MAC Lymph node M.Tuberculosis MAC M.Malmoense M.Fortuitum M.Bovis M.chelonei Soft tissue/skin M.Leprae M.Ulcerans M.Tuberculosis M.Marinum M.Fortuitum M.Chelonei Disseminated MAC M.Haemophilum M.Genavensae M.Fortuitum M.Chelonei 43

44. REASONS FOR THE INCREASING INCIDENCE OF PULMONARY TUBERCULOSIS Developed countries : HIV, Immigration from high prevalence areas, Increasing life expectancy of the elderly, social deprivation, drug resistance, Reduced priority for TB control Developing countries: HIV, Population increase, Lack of access to health care, Poverty, civil unrest, ineffective control programmes, drug resistance 44

45. FACTORS INCREASING THE RISK OF TUBERCULOSIS PATIENT RELATED ASSOCIATED DISEASES Age (children>young adults) First generation immigrants from high prevalence countries Close contact of patients with smear-positive pulmonary tuberculosis Chest radiography evidence of self-healed tuberculosis Primary infection<1 year previously HIV Silicosis Immunocompromise Malignancy Type 1 Diabetes Mellitus Chronic Renal Failure Gastrointestinal Disease Associated With Malnutrition 45

46. TRANSMISSION OF M. TUBERCULOSIS 46

47. Four factors determine the likelihood of transmission of M. tuberculosis: the number of organisms being expelled into the air the concentration of organisms in the air, determined by the volume of the space and its ventilation the length of time an exposed person breathes the contaminated air presumably the immune status of the exposed individual. 47

48. MODES OF TRANSMISSION OF TB Inhalation Ingestion Inoculation Transplacental 48

49. Modes of transmission of TB with their percentages 49

50. SPREAD OF TUBERCULOSIS 1.Local spread 2.Lymphatic spread 3.Haematogenous spread 4.By the natural passages: lung lesions into pleura Transbronchial spread into adjacent lung segments TB salpingitis into peritoneal cavity Infected sputum into larynx Swallowing of infected sputum Renal lesions into ureter and down to bladder 50

51. Pathogenesis of TB Inhalation of the MTb . Inflammatory Cell Recruitment Control of Mycobacteria Proliferation Post-Primary Tuberculosis. Zuñiga J, Torres-García D, Santos-Mendoza T, Rodriguez-Reyna TS, Granados J, Yunis EJ. Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis. Clinical and Developmental Immunology. 2012;2012:1-18. 51

52. Luies L, du Preez I. The Echo of Pulmonary Tuberculosis: Mechanisms of Clinical Symptoms and Other Disease-Induced Systemic Complications. Clin Microbiol Rev. 2020 Sep 16;33(4): 52

53. EVOLUTION OF TUBERCLE HARD TUBERCLE : Around the mass of epitheloid cells and giant cells is a zone of lymphocytes, plasma cells and fibroblasts. SOFT TUBERCLE: within 10-14 days center of cellular mass begins to undergo caseation necrosis characterised by cheesy appearance and high lipid control. Hallmark of tuberculous lesion 53

54. STAGES OF INFECTION OF TB 54

55. There Are Several Stages: • Primary Infection • Latent Infection • Active Disease 55

56. LATENT INFECTION 56

57. ACTIVE DISEASE 57

58. TIMETABLE OF TUBERCULOSIS Time from infection Manifestations 3-8 weeks Primary complex, positive tuberculin skin test 3-6 months Meningeal, miliary and pleural disease Up to 3 years Gastrointestinal , bone and joint and lymphnode disease Around 8 years Renal tract disease From 3 years onwards Post-primary disease due to reactivation or reinfection 58

59. The current classification system, referred to as “the American Thoracic Society (ATS)” classification system, is based on the pathogenesis of TB CLASSIFICATION OF TUBERCULOSIS 59

60. 60

61. CLINICAL PATHOLOGIC PATTERNS OF TUBERCULOSIS 61

62. 62

63. PRIMARY TUBERCULOSIS Develops in a previously unexposed , and therefore unsensitized, person. The source of the organism is exogenous . The inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe , usually close to the pleura. 63

64. As sensitization develops , a 1-1.5-cm area of gray-white inflammation with consolidation emerges, known as the GHON FOCUS . The center of this focus undergoes caseous necrosis . Tubercle bacilli, either free or within phagocytes, drain to the regional nodes, which also often caseate. This combination of parenchymal lung lesion and nodal involvement is referred to as the GHON COMPLEX 64

65. GHON’S COMPLEX in lungs consists of 3 components: Pulmonary component : Ghon’s focus is 1-2 cm solitary area of tuberculosis pneumonia located under the pleura just above or just below the inter lobes fissure between upper and lower lobes of the lung. Lymph node component : this consists of enlarged hilar and tracheo-bronchial lymph nodes in the area drained. The affected lymph nodes are matted and show caseation necrosis. 65

66. 3.Lymphatic vessel component: Lymphatics draining the lung lesion contain phagocytes containing bacilli. 66

67. FATE OF PRIMARY TUBERCULOSIS Primary complex may follow one of the following sequelae: 1.Fibrosis,calcification,ossification 2.Progressive primary tuberculosis 3.Primary miliary tuberculosis 4.Progressive secondary tuberculosis 67

68. SECONDARY TUBERCULOSIS The pattern of disease that arises in a previously sensitized host . Most commonly stems from reactivation of a latent infection Also result from exogenous reinfection in the face of waning host immunity or when a large inoculum of virulent bacilli overwhelms the host immune system. 68

69. Classically involves the apex of the upper lobes of one or both lungs. The initial lesion is usually a small focus of consolidation, less than 2 cm in diameter, within 1 to 2 cm of the apical pleura Foci are sharply circumscribed, firm, gray-white to yellow areas that have a variable amount of central caseation and peripheral fibrosis 69

70. The regional lymph nodes are less prominently involved. Cavitation occurs readily. Erosion of the cavities into an airway is an important source of infection because the person now coughs sputum that contains bacteria. 70

71. FATE OF SECONDARY TUBERCULOSIS 1.The lesions may heal with fibrosis and calcification 2.Lesions may coalesce together to form larger area of tuberculosis pneumonia and produce progressive secondary pulmonary tuberculosis with the following pulmonary and extra pulmonary involvements: Fibrocaseous tuberculosis Tuberculous caseous pneumonia Miliary tuberculosis 71

72. CLINICAL MANIFESTATIONS OF TUBERCULOSIS 72

73. CLINICAL PRESENTATIONS OF TUBERCULOSIS Pulmonary Tuberculosis: Primary and Secondary Extrapulmonary Tuberculosis Lymph node tuberculosis Tuberculous meningitis Tuberculosis of bones and joints Urogenital tuberculosis Abdominal tuberculosis Tuberculous pleural effusion Tuberculous pericardial effusion Cutaneous tuberculosis 73

74. CLINICAL FEATURES: PULMONARY DISEASE PRIMARY PULMONARY TUBERCULOSIS Occurs soon after the initial infection with tubercle bacilli. This form of disease is often seen in children. Middle and lower lung zones are most commonly involved 74

75. The lesion forming after infection is usually peripheral and accompanied by hilar or paratracheal lymphadenopathy. The lesion heals spontaneously and may later be evident as a small calcified nodule. Primary tuberculosis is usually self-limiting 75

76. MILIARY TB Blood-borne dissemination gives rise to miliary TB Characterized by 2–3 weeks of fever, night sweats, anorexia, weight loss and a dry cough. Hepatosplenomegaly may develop The presence of a headache may indicate coexistent tuberculous meningitis. 76

77. The classical appearances on chest X-ray are of fine 1–2 mm lesions (‘millet seed’) Anemia and leucopenia reflect bone marrow involvement. Cryptic miliary TB is an unusual presentation sometimes seen in old age 77

78. CRYPTIC TB Age over 60 years Intermittent low-grade pyrexia of unknown origin Unexplained weight loss, general debility Normal chest X-ray Blood dyscrasias, leukemoid reaction, pancytopenia Negative tuberculin skin test Confirmation by biopsy of liver or bone marrow 78

79. SECONDARY PULMONARY TUBERCULOSIS Adult – type, reactivation or post primary disease Post primary tuberculosis remains primarily a disease of adolescence and adulthood. It occurs in patients previously sensitized to M tuberculosis. The term post primary tuberculosis is generally used to refer to both reinfection with and reactivation of tuberculosis. 79

80. Post primary tuberculosis is progressive with cavitation as its hallmark, resulting in hematogenous dissemination of the disease as well as disease spread throughout the lungs. Localized to the apical and posterior segments of the upper lobes, where the substantially higher mean oxygen tension favours mycobacterial growth 80

81. The extent of lung parenchymal involvement varies greatly from small infiltrates to extensive cavitary disease. With cavity formation, liquefied necrotic contents are ultimately discharged into the airways, resulting in satellite lesions within the lungs that may in turn undergo cavitation. 81

82. Tuberculosis involving any site may produce symptoms and findings that are not specifically related to the organ or tissue involved but, rather, are systemic in nature . 82

83. Luies L, du Preez I. The Echo of Pulmonary Tuberculosis: Mechanisms of Clinical Symptoms and Other Disease-Induced Systemic Complications. Clin Microbiol Rev. 2020 Sep 16;33(4) 83

84. EXTRAPULMONARY TB In descending order of frequency, the extrapulmonary sites most commonly involved in TB are the lymph nodes, pleura, genitourinary tract, bones and joints, meninges, peritoneum, and pericardium. 84

85. LYMPH NODE TB (TUBERCULOUS LYMPHADENITIS) The most common presentation of extrapulmonary TB in HIV-seronegative individuals HIV-infected patients. Lymph node disease is particularly frequent among HIV-infected patients and among children. 85

86. Cervical and mediastinal glands are affected most frequently, followed by axillary and inguinal, and more than one region may be involved. Disease may represent primary infection, spread from contiguous sites or reactivation. 86

87. 87 STAGES OF TUBERCULOUS LYMPHADENITIS

88. 88 CLINICAL FEATURES Swelling in the neck which is firm, matted . Cold abscess is soft, smooth, nontender, fluctuant , without involvement of the skin. It is not warm. Cold abscess ruptures out of the deep fascia to form collar stud abscess Discharging sinus is formed It can be multiple, wide open mouth, often undermined, nonmobile with bluish color around the edge and usually not indurated.

89. 89 Tonsils may be studded with tubercles and so clinically should always be examined. Bluish hyperpigmented involved overlying skin is called as scrofuloderma. Tuberculous pus with caseating cheesy creamy material is infective as it contains multiplying organisms. Sinus may persist due to—fibrosis, calcification, secondary infection, inadequate reach of drug to maintain optimum concentration in caseation.

90. 90 DIFFERENTIAL DIAGNOSIS Nonspecific lymphadenitis. Lymphomas, and chronic lymphatic leukaemia. Secondaries in the neck. Branchial cyst mimics cold abscess. Lymph cyst mimics cold abscess. HIV with lymph node involvement. When there is discharging sinus—actinomycosis.

91. TUBERCULOUS MENINGITIS TB of the central nervous system (CNS) accounts for ∼5% of extrapulmonary cases It is seen most often in young children but also develops in adults, especially those infected with HIV. Results from the hematogenous spread of primary or postprimary pulmonary TB or from the rupture of a subependymal tubercle into the subarachnoid space. 91

92. Presents as headache and slight mental changes after a prodrome of weeks of low-grade fever, malaise, anorexia, and irritability. Because meningeal involvement is pronounced at the base of the brain , paresis of cranial nerves (ocular nerves in particular) is a frequent finding, and the involvement of cerebral arteries may produce focal ischemia . The ultimate evolution is toward coma, with hydrocephalus and intracranial hypertension 92

93. TUBERCULOMA An uncommon manifestation of TB of the CNS Presents as one or more space-occupying lesions Causes seizures and focal signs. 93

94. ∼10% of extrapulmonary cases. In bone and joint disease, pathogenesis is related to reactivation of hematogenous foci or to spread from adjacent paravertebral lymph nodes. Weightbearing joints (the spine in 40% of cases, the hips in 13%, and the knees in 10%) are most commonly affected. TUBERCULOSIS OF BONES AND JOINTS 94

95. SPINAL TB (POTT’S DISEASE OR TUBERCULOUS SPONDYLITIS ) Often involves two or more adjacent vertebral bodies . The most common site of spinal tb in children : upper thoracic spine in adults : the lower thoracic and upper lumbar vertebrae 95

96. From the anterior superior or inferior angle of the vertebral body, the lesion slowly reaches the adjacent body, later affecting the intervertebral disk . With advanced disease : collapse of vertebral bodies results in Kyphosis (gibbus). 96

97. A paravertebral “cold” abscess may also form. In the upper spine : this abscess may track to and penetrate the chest wall, presenting as a soft tissue mass In the lower spine : it may reach the inguinal ligaments or present as a psoas abscess a catastrophic complication of Pott’s disease is paraplegia, which is usually due to an abscess or a lesion compressing the spinal cord. 97

98. TB of the hip joints , usually involving the head of the femur, causes pain TB of the knee produces pain and swelling . If the disease goes unrecognized, the joints may be destroyed. 98

99. TUBERCULOUS PLEURAL EFFUSION ∼20% of extrapulmonary cases. Isolated pleural effusion usually reflects recent primary infection, and the collection of fluid in the pleural space represents a hypersensitivity response to mycobacterial antigens. Result from contiguous parenchymal spread , as in many cases of pleurisy accompanying post primary disease. 99

100. TUBERCULOUS EMPYEMA Less common complication of pulmonary TB. It is usually the result of the rupture of a cavity, with spillage of a large number of organisms into the pleural space. This process may create a bronchopleural fistula with evident air in the pleural space. 100

101. TUBERCULOUS PERICARDIAL EFFUSION Due either to direct extension from adjacent mediastinal or hilar lymph nodes or to hematogenous spread Disease of the elderly in countries with low TB prevalence Develops frequently in HIV-infected patients. 101

102. The onset may be subacute, although an acute presentation, with dyspnea, fever, dull retrosternal pain, and a pericardial friction rub , is possible. An effusion eventually develops Cardiovascular symptoms and signs of cardiac tamponade may ultimately appear. 102

103. UROGENITAL TUBERCULOSIS ∼10–15% of all extrapulmonary cases Clinical manifestations are cryptic and protean. Patients may be asymptomatic and their disease discovered only after destructive lesions of the kidneys have developed. Symptoms are often nonspecific, and include those of urinary tract infection with frequency, dysuria, nocturia and hematuria, and abdominal or flank pain. 103

104. Genital TB is diagnosed more commonly in female than in male patients. In female patients , it affects the fallopian tubes and the endometrium and may cause infertility, pelvic pain, and menstrual abnormalities. In male patients , genital TB preferentially affects the epididymis, producing a slightly tender mass that may drain externally through a fistulous tract; orchitis and prostatitis may also develop. 104

105. GASTROINTESTINAL TUBERCULOSIS 3.5% of extrapulmonary cases Various pathogenetic mechanisms are involved: swallowing of sputum with direct seeding hematogenous spread ingestion of milk from cows affected by bovine TB. The terminal ileum and the cecum are the sites most commonly involved. 105

106. Common findings at presentation: Abdominal pain (at times similar to that associated with appendicitis) Swelling, obstruction, hematochezia A palpable mass in the abdomen Fever, weight loss, anorexia, and night sweats With intestinal wall involvement , ulcerations and fistulae may simulate Crohn's disease Anal fistulae should prompt an evaluation for rectal TB. 106

107. Either the direct spread of tubercle bacilli from ruptured lymph nodes and intraabdominal organs (e.g., Genital TB in women) or hematogenous seeding. Nonspecific abdominal pain, fever, and ascites Paracentesis reveals an exudative fluid with a high protein content and leukocytosis that is usually lymphocytic (although neutrophils occasionally predominate). TUBERCULOUS PERITONITIS 107

108. LESS COMMON EXTRAPULMONARY FORMS TB TUBERCULOUS OTITIS : is rare and presents as hearing loss, otorrhea, and tympanic membrane perforation. NASOPHARYNX TB : may simulate granulomatosis with polyangiitis. CUTANEOUS MANIFESTATIONS OF TB : include primary infection due to direct inoculation, abscesses and chronic ulcers, scrofuloderma , lupus vulgaris (a smoldering disease with nodules, plaques, and fissures), miliary lesions, and erythema nodosum. 108

109. TUBERCULOUS MASTITIS : results from retrograde lymphatic spread, often from the axillary lymph nodes ADRENAL TB : manifestation of disseminated disease presenting rarely as adrenal insufficiency. CONGENITAL TB : results from transplacental spread of tubercle bacilli to the foetus or from ingestion of contaminated amniotic fluid. 109

110. 110 DRUG-RESISTANT TB Drug-resistant TB is defined by the presence of resistance to any first-line agent. Multidrug-resistant tuberculosis (MDR-TB) is defined by resistance to at least rifampicin and isoniazid, with or without other drug resistance. Extensively drug-resistant tuberculosis (XDR-TB) is defined as resistance to at least rifampicin and isoniazid, in addition to any quinolone and at least one injectable second-line agent.

111. 111 Factors contributing to the emergence of drug-resistant tuberculosis Drug shortages Poor-quality drugs Poor concordance with drugs Lack of appropriate supervision Transmission of drug-resistant strains Prior antituberculosis treatment Treatment failure (culture-positive at 5 months)

112. 112 COMPLICATIONS OF PULMONARY TUBERCULOSIS Bronchiectasis Massive haemoptysis Cor pulmonale Fibrosis/emphysema Atypical mycobacterial infection Aspergilloma/chronic pulmonary aspergillosis Obstructive airways disease Bronchopleural fistula Lung/pleural calcification and pleural thickening

113. 113 NON-PULMONARY COMPLICATIONS Empyema necessitans Laryngitis Enteritis Anorectal disease Amyloidosis Poncet’s polyarthritis

114. ORAL MANIFESTATIONS The majority of oral lesions seen are secondary to infection in some other part of the body, particularly lungs. Rarely primary tuberculosis involves the oral structure 114

115. INCIDENCE OF ORAL MANIFESTATIONS: Relatively rare In tropics, oral involvement can be expected to occur in a significant number of patients. Mainly seen in middle aged and older persons Males more affected than females with ratio of 5:1 115

116. PATHOGENESIS OF ORAL INVOLVEMENT Intact epithelium does not permit tubercle bacilli to gain entry into the underlying connective tissue. The cleansing action of saliva and its antibacterial properties also provide against tubercle bacilli. 116

117. The onset of oral tuberculosis infection appears to depend on certain systemic and local factors Systemic factors Local factors Lowered host resistance , increased virulence of the organisms Poor oral hygiene, local trauma, preexisting leukoplakia , periapical granulomas, dental cysts, jaw fractures, periodontitis. 117

118. Two main types of tuberculous infections of oral tissue: 1.PRIMARY 2.SECONDARY 118

119. PRIMARY LESIONS Primary lesions are uncommon, seen in younger patients often associated with enlarged cervical lymph nodes. Develop when bacilli are directly inoculated into the oral tissues of a person who has not had tuberculosis in the past and who has not acquired immunity to the disease. Primary infections although rare frequently involves gingiva, tooth extraction socket, buccal folds. 119

120. SECONDARY INFECTION Secondary oral TB usually coexists with pulmonary disease, may occur in all age groups; middle‑aged and older people are more likely involved. Can result by either hematogenous or lymphatic spread or from inoculation by infected spectrum. Hematogenous or lymphatic spread of the infection to oral tissues appears to be more frequently in cases of extrapulmonary tuberculosis. 120

121. Direct extension into the oral cavity by tuberculous bacilli in neighboring structures such as pharynx is a possible source of secondary oral tuberculosis. Frequently involved sites include tongue, palate, lips, alveolar mucosa and the jaw bones. 121

122. SITES OF ORAL INVOLVEMENT When the mucosa is involved : lesions present themselves as ulcerations, or less commonly as nodules, vesicles, fissures, plaques, granulomas, and verrucous proliferation. When the jawbones are involved : it presents features of chronic steomyelitis cervical lymph nodes and salivary gland involvement is usually seen as swellings with or without a fistulous tract. 122

123. MUCOSA The most common form of oral tuberculosis is an ulcerative lesion of the mucosa . Preceded by an opalescent vesicle or nodule that as a result of caseation necrosis breaks down into an ulcer. The ulcer is usually single. The topical tuberculosis ulcer is an irregular lesions with ragged, undermined edges, minimal indurations and with yellowish granular base . 123

124. The mucosa surround the ulcer is inflamed and edematous . The single or multiple nodules called 'sentinel tubercles' may also be seen surrounding the ulcer. At the mucocutaneous junction, tuberculous ulcers are usually extremely shallow with a granulating base. Crusting and oozing may be seen when the lesion is involving the adjacent cutaneous surface. Tuberculous ulcers are usually painful. 124

125. de Souza BC, de Lemos VMA, Munerato MC. Oral manifestation of tuberculosis: a case-report. The Brazilian Journal of Infectious Diseases. 2016 Mar;20(2):210-3. 125

126. TONGUE: The most common sites: lateral trauma from sharp cusp border, tip, anterior dorsum, and base of tongue Primary lingual tuberculosis is rare lesion of tongue is usually in the form of ulcer. Tuberculous ulcer on the tongue may show deep fissures; closely resemble malignancy Tongue lesions are usually painful, grayish-yellow, firm and well demarcated. 126

127. The clinical aspect and microscopic features confirmed the appearance of tubercular ulcers as irregular, pale, and indolent with inverted margins and granulations on the floor with sloughing tissue. The usual presentation of secondary TB is an irregular, superficial, or deep, painful ulcer that tends to increase slowly in size Kant S, Sharma S, Bajpai J, Pathak P, Pradhan A, Singh P. Oral tuberculosis - Current concepts. J Family Med Prim Care. 2019;8(4):1308. 127

128. PALATE: Hard palate is more commonly involved then soft palate. Palatal involvement is secondary to pulmonary tuberculosis palatal lesions may be seen as granules of ulcerations. Palatal lesions are usually small. Jhingta P, Machhan P, Sharma D, Vaid S, Bhardwaj V, Gupta N. Primary isolated gingival tuberculosis: A rare case report. Int J Health Allied Sci. 2015;4(1):45. 128

129. GINGIVA: Half of gingival involvement is examples of primary infection lesions may be seen simultaneously with marginal periodontitis. Primary oral TB usually involves gingival and presents as a diffuse, hyperemic, nodular, or papillary proliferation of the gingival tissues. 129

130. LIPS : Any part of the lips including the commissures may be involved. The lower lip appears to be most frequently involved when the lesion involves the mucocutaneous function it is usually in form of a shallow granulating ulcer 130

131. TOOTH APEX AND SOCKET INVOLVEMENT: Non-specific apical granulomas in tuberculous patients may become secondary infected by tuberculosis. One common mode of entry for the microorganism is into an area of periapical inflammation by way of the bloodstream. 131

132. It is also possible that these microorganisms may enter the periapical tissues by direct immigration through the pulp chamber and root canal of a tooth with an open cavity. The lesion produced is essentially a tuberculous periapical granuloma or tuberculoma Kant S, Sharma S, Bajpai J, Pathak P, Pradhan A, Singh P. Oral tuberculosis - Current concepts. J Family Med Prim Care. 2019;8(4):1308. 132

133. JAWBONE INVOLVEMENT: Tuberculous involvement of the maxilla and mandible usually results in tuberculous osteomyelitis. Infection of jaw bones is usually secondary to tuberculosis of the lungs Jaw bone involvement occurs as a result of either deep extension of a gingival lesion from are infected, post extraction socket, from an extension of a tuberculous granuloma at the apex of the tooth or by means of hematogenous spread of infection . 133

134. Jaw involvement occur mostly in children under the age of 16 years. Characterized by a slow course often appearing a calcifying osteitis. A slow process of necrosis results in sequestration of bone which may ultimately lead to intraoral and extraoral sinuses. The mandible shows a greater predisposition to infection than maxilla 134

135. Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle. 1991 Mar;72(1):1-6. Tuberculosis of mandible causes swelling The symptoms : difficultly in eating, trismus, paresthesia of lower lip, and enlargement of regional lymph nodes involved bone undergoes caseous necrosis and suppuration sets in fistula drain either intraorally or extraorally often with a blue margin. 135

136. In maxilla the infraorbital region, particularly in the young is a used site of involvement. A cold abscess develops in this area, which eventually may drain through fistulae. Shamanna K, Gopi R, Deshpande GA. A Rare Case of Tubercular Osteomyelitis of Maxilla: A Case Report. Indian J Otolaryngol Head Neck Surg. 2023 Sep;75(3):2477-81. 136

137. 137 Four clinical forms of TB of the mandible: Superficial or alveolar form that involves the alveolar process Deep or central form in which the angle of the mandible is involved Diffuse form characterized by progressive extensive necrosis of mandible that might involve the TMJ Acute osteomyelitis form.

138. Maxillary sinus and paranasal air sinuses Very few cases of maxillary sinus TB have been reported till date. TB of paranasal sinuses is usually a disease of adults. Most commonly, it presents as nasal discharge, stuffiness of nose, crust formation and sometimes with epistaxis. It is usually associated with pulmonary TB . 138

139. Three types of sinonasal TB have been described: mucosal involvement leading to formation of polyps with minimal pus discharge bony involvement and fistula formation with abundant discharge of acid-fast bacilli (AFB) hyperplastic changes with formation of tuberculoma Out of three types of paranasal sinus TB, hyperplastic type has granuloma formation and mimicks a malignancy. 139

140. Occasionally it may be associated with a malignancy. It can also present as fluctuant swelling, i.e., Potts puffy tumour and may resemble a malignant lesion. If not treated early, it can lead to complications like brain abscess and deterioration of vision. 140

141. INVOLVEMENT OF MAJOR SALIVARY GLANDS The major salivary glands may be the sites of primary or secondary tuberculosis involvement. When the involvement is primary, the salivary gland lesions most likely arise from a focus in the tonsils or from gingiva . Infection of the glands is usually via the duct system . 141 Süoğlu Y, Erdamar B, Cölhan I, Katircioğlu OS, Cevikbas U. Tuberculosis of the parotid gland. J Laryngol Otol. 1998 Jun;112(6):588-91.

142. The parotid glands are more frequently involved followed by submandibular and sublingual glands. Bilateral involvement of the gland is uncommon. Tuberculosis of a salivary gland develops either as a periglandular or interglandular lymph node mass or by direct involvement of the glandular parenchyma Nodal involvement is characterized by an acute inflammatory reaction with diffuse generalized glandular swelling mimicking sialadenitis or glandular abscess 142

143. 143 DIAGNOSIS OF TUBERCULOSIS

144. 144 RADIOGRAPHIC PROCEDURES CXR is a rapid imaging technique that has historically been used as a primary tool to detect pulmonary TB. CXR has high sensitivity but poor specificity. The “classic” picture is that of upper-lobe disease with infiltrates and cavities ,virtually any radiographic pattern—from a normal film or a solitary pulmonary nodule to diffuse alveolar infiltrates in a patient with adult respiratory distress syndrome—may be seen.

145. 145 Specimens required Pulmonary Sputum (induced with nebulised hypertonic saline if patient not expectorating) Bronchoscopy with washings or BAL Gastric washing (mainly used for children)

146. 146 EXTRAPULMONARY Fluid examination (cerebrospinal, ascitic, pleural, pericardial, joint): yield classically very low Tissue biopsy (from affected site or enlarged lymph node): bone marrow/liver may be diagnostic in disseminated disease

147. 147 DIAGNOSTIC TESTS STAIN Auramine fluorescence Ziehl– Neelsen NUCLEIC ACID AMPLIFICATION

148. 148 Culture Solid media ( Löwenstein –Jensen, Middlebrook) Liquid media (e.g. MGIT) Pleural fluid : adenosine deaminase Response to empirical antituberculous drugs Baseline blood tests Full blood count, C-reactive protein, urea and electrolytes, liver function tests

149. 149 The choice of a diagnostic tool for TB depends on the purpose of testing: Detecting LTBI Active TB disease Drug resistance

150. 150 For the diagnosis of latent tuberculosis infection, two main immune-based approaches are currently used and included in WHO guidelines: The tuberculin skin test: TST The interferon- γ release assay: IGRA TESTS FOR LATENT TUBERCULOSIS INFECTION

151. 151 The TST, performed using the Mantoux technique, consists of an intradermal injection of 5 tuberculin units (5‑TU) of purified protein derivative (PPD) S or 2 TU of PPD RT23. In a person who has cell-mediated immunity to these antigens, a delayed-type hypersensitivity reaction will occur within 48–72 hours. Interpretation of the TST takes into account the size of induration. The diameter of indurated area should be measured across the forearm and is positive when ≥ 5 mm

152. 152 IGRAs detect the release of interferon-gamma (IFN-γ) from sensitized T cells in response to antigens, such as early secretory antigenic target (ESAT)-6 or culture filtrate protein (CFP)-10, which are encoded by genes specific to M. tuberculosis and are not shared with BCG or opportunistic mycobacteria . IGRAs are more specific than skin testing and logistically more convenient, as they require a single blood test. The IGRA can also distinguish between BCG-induced and M. tuberculosis infection- induced positive TST responses.

153. 153 TESTS FOR ACTIVE TB DISEASE Four main technologies are used: Imaging techniques : chest x‑rays and PET-CT Microscopy : sputum smears Culture-based methods Molecular tests Whereas imaging tests are used for screening, active TB disease requires a microbiological diagnosis.

154. 154 Microscopic examination of specially stained smears to detect acid-fast organisms such as Mycobacterium tuberculosis and nontuberculous mycobacteria. Smear-positivity and grade indicates relative bacterial burden and correlates with disease presentation. AFB SMEAR MICROSCOPY

155. 155 FLUORESCENCE: : AURAMINE STAINING Also known as Fluorochrome staining Contrast light & dark BRIGHTFIELD: CARBOL FUCHSIN STAINING Contrast red AFB on blue or green background

156. 156 TESTS FOR DETECTION OF DRUG RESISTANCE Culture-based (that is, testing the ability of bacteria to grow in the presence of anti‑tb drugs) Molecular-based (based on the detection of genetic mutations in M. Tuberculosis that confer drug resistance) methods

157. 157 NEW DIAGNOSTICS The goal is to expand the range of molecular technologies that could replace sputum smear microscopy. New molecular tools can identify drug resistance mutations

158. 158 Progressively replacing smear microscopy, as they ensure rapid confirmation of all types of TB. Rapid diagnosis of TB with high specificity and sensitivity: fully automated, real-time nucleic acid amplification technology known as the XPERT MTB/RIF assay. XPERT MTB/RIF can simultaneously detect tb and rifampin resistance in <2 h and has minimal biosafety and training requirements. NUCLEIC ACID AMPLIFICATION TECHNOLOGY

159. 159 The most widely used tests to detect patients at increased risk of drug resistant TB. LPAS are a family of DNA strip based tests capable of detecting bacterial DNA and identifying drug resistance-associated mutations. This assay reveals the presence of M. Tuberculosis as well as mutations in target resistance-gene regions. MOLECULAR LINE PROBE ASSAYS (LPAS)

160. 160 WHO recommends that they may be used to detect resistance to isoniazid and rifampin when patients have sputum smear–positive specimens or a cultured isolate of M. tuberculosis Initial test for rapid detection of resistance to the fluoroquinolones or the second-line injectable drugs

161. 161 The two main aims of TB treatment are: To prevent morbidity and death by curing TB while preventing recurrences and emergence of drug resistance, and To interrupt transmission by rendering patients noninfectious to others. Chemotherapy for TB became possible with the discovery of streptomycin in 1943. TREATMENT

162. 162 RECOMMENDED DOSAGE FOR INITIAL TREATMENT OF TUBERCULOSIS IN ADULTS AND CHILDREN DRUG DAILY DOSE Adult Pediatric Isoniazid 5 mg/kg, max 300 mg 10(7-15) mg/kg, max 300 mg Rifampin 10 mg/kg, max 600 mg 15(10-20) mg/kg, max 600 mg Pyrazinamide 25 mg/kg, max 2 g 35(30-40)mg/kg Ethambutol 15 mg/kg 20(15-25) mg/kg

163. 163 Well absorbed after oral administration With peak serum levels at 2–4 h Nearly complete elimination within 24 h. Isoniazid and rifampin, two key ANTI-TB drugs, are recommended on the basis of their bactericidal activity All four agents are recommended in light of their sterilizing activity and the lowered risk that drug-resistant mutant bacilli will be selected when the drugs are used in combination.

164. 164 REGIMENS Standard regimens are divided into an intensive (bactericidal) phase a continuation (sterilizing) phase. During the intensive phase , the majority of tubercle bacilli are killed, symptoms resolve, and usually the patient becomes noninfectious. The continuation phase is required to eliminate persisting mycobacteria and prevent relapse.

165. 165 The treatment regimen of choice for virtually all forms of drug susceptible TB in adults consists of a 2-month initial (intensive) phase of isoniazid, rifampin, pyrazinamide, and ethambutol followed by a 4-month continuation phase of isoniazid and rifampin. This regimen can cure TB in >90% of patients.

166. 166 RECOMMENDED ANTITUBERCULOSIS TREATMENT REGIMENS INDICATION INTENSIVE PHASE CONTINUATION PHASE Duration, months Drugs Duration, months Drugs New smear or culture positive cases 2 HRZE 4 HR New culture negative cases 2 HRZE 4 HR Pregnancy 2 HRE 7 HR Resistance to H 6 RZEQ Intolerance to Z 2 HRE 7 HR

167. 167 REGIMENS FOR THE TREATMENT OF LATENT TUBERCULOSIS INFECTION IN ADULTS REGIMEN SCHEDULE DURATION Isoniazid plus rifapentine 900mg(15 mg/kg) weekly plus 900 mg (for weight >50 kg ) weekly 3 months Rifampin 600 mg/d(10 mg/kg) 4 months Isoniazid plus rifampin 300 mg/d (5mg/kg) plus 600 mg/d (10mg/kg) 3 months isoniazid 300 mg/d (5mg/kg) Alternative : 900 mg twice weekly(15 mg/kg) 6-9 months

168. 168 SIMPLIFIED APPROACH TO TREATMENT OF ACTIVE TUBERCULOSIS (TB) IN ADULTS Culture results Intensive phase Continuation phase Extension of total treatment Culture – positive, drug susceptible HRZE for 2 months, daily or 3 times per week HR for 4 months, daily or 5 days per week or HR for 4 months, 3 times per week Continuation phase extended to 7 months if 2 months of Z is not completed, if the patient is infected with HIV and is not receiving antiretroviral therapy , or if culture conversion is prolonged and /or cavitation is evident on chest radiography. Culture-negative HRZE for 2 months HR for 2 months, daily or 2 or 3 times per week Continuation phase extended to 4 months if the patient is infected with HIV Extrapulmonary, Drug - susceptible HRZE for 2 months HR for 4-7 months, daily or 5 days per week Continuation phase extended to 10 months in TB meningitis;7 months recommended by some authorities for bone/joint TB

169. 169 GROUPS OF DRUGS RECOMMENDED FOR USE IN LONGER MDR-TB REGIMENS AND APPROACH TO THE DESIGN OF A LONGER REGIMEN FOR ADULTS AND CHILDREN GROUP DRUG Group A: Drugs to be prioritized and included in all regimens, unless they cannot be used Levofloxacin or moxifloxacin Bedaquiline Linezolid Group B: Drugs to be added in all regimens, unless they cannot be used Clofazimine Cycloserine or terizidone Group C: Drugs to be used to complete the regimen and when drugs from groups A and B cannot be used Ethambutol Delamanid Pyrazinamide Imipenem- cilastatin or meropenem Amikacin or streptomycin Ethionamide or prothionamide p- Aminosalicylic acid

170. 170 SIMPLIFIED APPROACH TO TREATMENT OF DRUG- RESISTANT TUBERCULOSIS (TB) IN ADULTS Culture results Intensive phase Continuation phase Extension of total treatment Resistant to H Levofloxacin or moxifloxacin for 6 months Prolonged culture conversion and evidence of cavitation on CXR Resistant to HR(MDR) WHO short course regimen Bedaquiline, Levofloxacin/ moxifloxacin, ethionamide, ethambutol, pyrazinamide, high dose isoniazid, clofazimine for 4-6 months Levofloxacin/ moxifloxacin, clofazimine, ethionamide, pyrazinamide for 5 months Prolonged culture conversion , delayed response and evidence of cavitation on CXR WHO extended regimen At least five effective second line agents, including all group A and at least one Group B, add group C if intolerant to A or B drugs for 5-7 months 4 drugs for a total of 18-20 months or for 15-17 months after culture conversion Prolonged culture conversion , delayed response and evidence of cavitation on CXR

171. 171

172. 172 PREVENTION The primary way to prevent TB is : to diagnose and isolate infectious cases rapidly to administer appropriate treatment until patients are rendered noninfectious (usually 2–4 weeks after the start of proper treatment) and the disease is cured. Additional strategies include BCG vaccination and preventive treatment of persons with TB infection who are at high risk of developing active disease.

173. 173 BCG VACCINATION One of the most used vaccines in the history of medicine BCG was derived from an attenuated strain of M. Bovis First administered to humans in 1921 BCG vaccine is safe and rarely causes serious complications. The local tissue response begins 2–3 weeks after vaccination, with scar formation and healing within 3 months. Side effects: most commonly, ulceration at the vaccination site and regional lymphadenitis

174. 174 TB PREVENTIVE TREATMENT (TPT) Also called chemoprophylaxis or preventive chemotherapy Previously referred to as “treatment of latent TB infection” is a fundamental intervention in TB control and elimination strategies.

175. 175 RECOMMENDED REGIMENS AND DRUG DOSAGES FOR TUBERCULOSIS PREVENTIVE TREATMENT REGIMEN DOSE Isoniazid alone for 6 or 9 months Adults: 5mg/kg(max 300mg) per day Children<10 years of age: 10 mg/kg per day (range 7-15 mg) Rifampin alone for 4 months Adults: 10 mg/kg per day Children <10 years of age:15 mg/kg(range 10-20 mg) per day Isoniazid plus rifampin for 3 months As above Rifapentine plus isoniazid for 3 months Adults and children: Isoniazid:15 mg/kg (900 mg) weekly Rifapentine:15-30 mg/kg (900 mg) weekly Rifapentine plus isoniazid for 1 month Age>13 years only: Isoniazid 300 mg and rifapentine 600 mg daily (28 doses)

176. 176 “DOTS STRATEGY” Early detection of cases and bacteriologic confirmation of the diagnosis, administration of standardized short-course chemotherapy, with direct supervision to ensure adherence to treatment and the provision of social support to patients; availability of drugs of proven quality, with an effective supply and management system; and a monitoring and evaluation system, including assessment of treatment outcomes

177. 177 The new “END TB” STRATEGY promoted by the WHO since 2016 builds on three pillars and relies on increased investments and efforts by all governments, their national programs, and a multitude of partners within and beyond the health sector: (1) integrated, patient-centered care and prevention (2) bold policies and supportive systems (3) Intensified research and innovation.

178. 178 DENTAL CONSIDERATIONS FOR TB PATIENTS: PRE TREATMENT: Establish previous history of TB exposure, medical treatment and follow-up, and any prophylactic therapy. May need physician consult if poor history or unclear treatment. Patient with history of positive tuberculin test and without signs and symptoms of active tuberculosis. Suggest previous exposure to the tubercle bacilli. In these cases detailed questions about the event, treatment if any and medical follow-up may be asked.

179. 179 DURING TREATMENT Patients with active TB: ➤Dental emergencies only ➤ Controlled environment (protective gear/respirator, presurgical air flow) Patients with signs and symptoms suggestive of TB: ➤Dental emergencies only ➤ Consider referred for medical evaluation and working to rule out TB. ➤ Protective gear (respirator mask)

180. 180 Patients with a history of TB: ➤ Routine dental treatment (after establishing that the patient has been adequately treated and followed and there are no signs and symptoms of active disease. Patients with a positive tuberculin test with no history of tb and no signs or symptoms of active disease. ➤ Routine dental treatment consults with physician if there is any question of presence of active disease. AFTER TREATMENT : No specific precaution

181. 181