1. CASE CONFERENCE Ang, Kevin Aningalan, Arvin Antonio, Aby Aramburo, Jan Cruel, Anna

2. General Data J.R. 1 yr and 11 mos, Female Santa Cruz, Manila Filipino, Roman Catholic Informant: Mother Reliability: good

3. History of Present Illness Mother palpated multiple movable, firm, non-tender masses over lateral aspects of neck No other symptoms noted No consult was done 6 weeks PTC

4. History of Present Illness Patient experienced intermittent low- grade fever (37.8°C), occurring at night time, not relieved by intake of Paracetamol No accompanying symptoms – no anorexia – no weight loss – no cough – no colds – no medications given no consult done 2 weeks PTC

5. History of Present Illness Patient experienced cough and colds with clear discharge (-) anorexia (-) weight loss (-) difficulty of breathing 8 days PTC

6. History of Present Illness Patient sought consult at OPD – (+) boggy turbinates – (+) multiple cervical lymphadenopathy, movable, firm, non-tender over lateral aspects of neck Assessment: to r/o PTB Plans: PPD, CXR, to follow-up with results 5 days PTC

7. History of Present Illness PPD test: 10mm Chest X-Ray PA and Lateral: suggestive of Primary Koch’s Consult

8. Review of Systems (-) weight loss, (-)anorexia (-) itchiness, pigmentation, rash, active dermatoses (-) blurring of vision, redness, itchiness, Iacrimation (-) deafness, tinnitus, aural discharge (-) anosmia, epistaxis, sinusitis, nasal discharge (-) bleeding gums, oral sores, tonsillitis (-) neck mass, neck stiffness, limitation of motion (-) chest pain, nocturnal dyspnea, palpitation, syncope, edema (-) phlebitis, varicosities, claudication (-) dysphagia, nausea, vomiting, retching, hematemesis, melena, hematochezia, belching, indigestion, diarrhea, constipation (-) urinary frequency, urgency, hesitancy, dysuria, hematuria, nocturia (-) joint stiffness, joint pain, muscle pain, cramps (-) heat-cold intolerance, polydipsia, polyphagia, polyuria (-) headache, depression, seizures

9. Past Medical History No Previous Surgeries Past Medical Illnesses – Acute pyelonephritis (January 2009) – Acute rhinitis (February 2009) – Acute nasopharyngitis, probably viral (September 2009) Immunizations: complete Hepa B1,2,3 Hib 1,2,3 MMR DPT 1,2,3 booster BCG OPV 1,2,3 booster Measles Allergies: none

10. Family History (+) Hypertension – mother (+) DM – grandfather (+) PTB – uncle who stays at home with patient (-) Cardiovascular diseases, stroke

11. Family Profile FamilyAgeOccupationHealth Status Father: V.R.34SeamanHealthy Mother: M.R.31HousewifeHealthy Sister: L.R.4N/AHealthy

12. Gestational and Birth History Patient born to a 31 y/o G2P1 unemployed housewife married to a 34 y/o seaman With regular prenatal check-up since 7 weeks AOG. Denied illnesses during the entire pregnancy Outcome was live term singleton female delivered via NSD AS 8,9 MT 38-39 wks AGA BW 3.01 BL 47 HC 33.5 CC 31.5 AC 30. No complications

13. Socioeconomic and Environmental History

14. Physical Examination General Survey: Awake, alert, not in cardiorespiratory distress, well- nourished, well-hydrated Vital Signs: HR 90bpm RR 20cpm T 36.7 o C Anthropometric Data: 82.5cm (Z score above 0) Weight: 15kg (Z score above 0) HC: 48 cm WFL: above zero Skin: Warm moist skin, no rashes, no jaundice, no active dermatosis Head: Normocephalic, pink palpebral conjunctiva, anicteric sclera, isochoric pupils, midline septum, no alar flaring, (+) nasoaural discharge, turbinates congested, no oral ulcers, moist buccal mucosa, non- hyperemic pharyngeal wall, tonsils not enlarged, no aural pits or tags, no tragal tenderness, nonhyperemic EAC, intact TM, AU

15. Physical Examination Adynamic precordium, apex beat at 4 th LICS, MCL, no lifts, no heaves, no thrills, S1>S2 at the apex, S2>S1 at the base, (-) S3, (-) murmurs Supple neck, (+) multiple cervical lymphadenopathies, trachea at midline Symmetrical chest expansion, no barrel chest, no supraclavicular retractions, clear breath sounds, (-) wheezes, (-) crackles Abdomen flabby, no scars, normoactive bowel sounds, tympanitic all over, no direct or rebound tenderness, no masses

16. Salient Features SUBJECTIVEOBJECTIVE 1 year and 11 mos, Female Exposure to PTB disease at home (+) 2 week duration of intermittent low-grade fever (37.8°C), occurring at night time (+) 8 day duration of cough, colds, clear discharge (+) multiple cervical lymphadenopathies in lateral aspects of neck PPD: 10mm CXR suggestive of Primary Koch’s infection

17. Approach to Diagnosis

18. Presenting Manifestation 2 week history of intermittent low grade fever (37.8 C), occurring at night time 8 day history of cough and colds (+) multiple cervical lymphadenopathies Exposure to PTB PPD test: 10mm Chest X-Ray PA and Lateral: suggestive of Koch’s infection

19. Approach to Diagnosis A presenting manifestation pointing to the least number of diseases Fever + Cervical Lymphadenopathy – PTB – Group A Strep Pharyngitis – Lymphoma – Kawasaki disease

20. Fever + Cervical Lymphadenopathy InfectiousNoninfectious Viral Infection Bacterial Infection Mycobacterial Infection Lymphoma Kawasaki disease Cough Positive PPD Chest xray findings of TB

21. PatientLymphomaGroup A Sreptococcal infections Kawasaki Disease Mycobacteria l 2 weeks Fever Colds Fever, night sweats, weight loss Fever, sorethroat At least 5 days of fever Changes in extremities Changes in lips and oral cavity Fever/ cough > 2 weeks Poor weight gain movable, firm, non-tender R lateral aspect of neck Congested nasal turbinates Tonsils not enlarged Very firm, rubbery nodes Cervical nodes warm, erythematous, and tender Pharyngeal exudates Unilateral cervical lympadeonop athy Painless, firm/matted cervical nodes

22. Primary Tuberculosis Infection Epidemiology: TB is endemic in the Philippines The majority of children with tuberculosis infection develop no signs or symptoms at any time. Non-specific signs & symptoms

23. Signs and Symptoms Cough of more than 2 weeks duration Fever of more than 2 weeks duration Painless cervical and/or other lymphadenopathies Poor weight gain Failure to make a quick return to normal health after infection Failure to respond to appropriate antibiotics

24. Tuberculin Skin test Screening test of high risk individuals Used to determine – Latent TB infection – Infected persons Measure of a person’s cellular immune responsiveness

25. Interpretation ≥ 5mm – Non BCG vaccinated – < 5 years old ≥ 10mm – BCG vaccinated – < 5 years old with positive exposure ≥ 15mm – > 5 years old with or without BCG

26. Tuberculosis Disease At least 3 of the following: (+) exposure to PTB (+) TST Clinical signs and symptoms of PTB Radiographic Findings of PTB

27. Assessment Pulmonary Tuberculosis Disease

28. Diagnosis Skin test AFB Staining Culture and sensitivity Chest x-ray Chest CT scan and MRI

29. Tuberculin Skin Test The recommended TST is the Mantoux test. The dosage of 0.1 mL or 5 TU purified protein derivative (PPD) should be injected intradermally into the volar aspect of the forearm using a 27-gauge needle. 48-72 hours after administration measure the amount of induration and not erythema

30. Tuberculin Skin Test Induration of 5 mm or more is considered a positive TST result in the following children: Children having close contact with known or suspected contagious cases of the disease, including those with household contacts with active tuberculosis whose treatment cannot be verified before exposure Children with immunosuppressive conditions (eg, HIV) or children who are on immunosuppressive medications Children who have an abnormal chest radiography finding consistent with active tuberculosis, previously active tuberculosis, or clinical evidence of the disease

31. Tuberculin Skin Test Induration of 10 mm or more is considered a positive TST result in the following children: Children who are at a higher risk of dissemination of tuberculous disease, including those younger than 5 years or those who are immunosuppressed because of conditions such as lymphoma, Hodgkin disease, diabetes mellitus, and malnutrition Children with increased exposure to the disease, including those who are exposed to adults in high-risk categories (eg, homeless, HIV infected, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons); those who were born in or whose parents were born in high- prevalence areas of the world; and those with travel histories to high-prevalence areas of the world

32. Tuberculin Skin Test Induration of 15 mm or more is considered a positive TST result in children aged 5 years or older without any risk factors for the disease

33. Tuberculin Skin Test – False-positive reactions often are attributed to asymptomatic infection by environmental nontuberculous mycobacteria (due to cross- reactivity). – False-negative results may be due to vaccination with live-attenuated virus, anergy, immunosuppression, immune deficiency, or malnutrition.

34. AFB Staining staining of AFB provides preliminary confirmation of the diagnosis Staining can also give a quantitative assessment of the number of bacilli being excreted (eg, 1+, 2+, 3+).

35. Culture and Sensitivity Definitive diagnosis of tuberculosis depends on isolation of the organism from secretions or biopsy specimens. Culture of mycobacterium is the definitive method to detect bacilli Gastric aspirates are used in lieu of sputum in very young children (<6 y) who usually do not have a cough deep enough to produce sputum for analysis

36. Chest X-ray classic diagnostic tool when evaluating patients for pulmonary tuberculosis. Radiologic findings: Parenchymal involvement (acinar consolidation, atelectasis) Lymph node involvement ( hilar or paratracheal LN enlargement) Airway involvement ( hyperaeration, segmental atelectasis, collapse) Pleural involvement

37. CT scan and MRI not routinely indicated when chest radiography findings are unremarkable can help demonstrate hilar lymphadenopathy, endobronchial tuberculosis, pericardial invasion, and early cavitations or bronchiectasis.

38. Treatment Plans Curative: – Isoniazid 200mg/5ml, 1.5 ml (5mg/kg/d) OD – Rifampicin 200mg/5ml, 3 ml (10mg/kg/d) OD – Pyrazinamide 250mg/5ml, 3.5 ml (15mg/kg/d) OD – Streptomycin 1g/2ml, 0.5 ml IM (22mg/kg/d) OD – Refer to DOTS – Refer to ENT

39. Treatment Plans Supportive – Multivitamins – Dietary advice given

40. Preventive – Advise the patient to strictly comply and complete the regimen – Anticipatory guidelines – Follow-up on vaccination – Avoid overcrowded and unsanitary areas

41. Follow up after 2 weeks

42. First Line Anti-TB drugs Isoniazid(H) Rifampicin(R) Pyrazinamide(Z) Streptomycin(S) Ethambutol(E)

43. Treatment a 6-month course of isoniazid (INH) and rifampin, supplemented during the first 2 months with pyrazinamide. Because poor adherence to these regimens is a common cause of treatment failure, directly observed therapy (DOT) is recommended for treatment of tuberculosis.

44. Treatment

46. BRIEF DISCUSSION OF THE DIAGNOSIS

47. Tuberculosis Mycobacterium tuberculosis is the most important cause of tuberculosis disease in humans. Other causes include: M. bovis, M. africanum, M. microti, M. Canetti.

48. Latent Tuberculosis infection Occurs after inhalation of infective droplet nuclei containing Mycobacterium tuberculosis. Reactive tuberculin skin test (TST) and absence of clinical and radiographic manifestation are the hallmark of this stage Disease occurs when signs and symptoms and radiographic changes become apparent Untreated LTB have up to 40% likelihood of developing TB in children.

49. Transmission Person to person By airborne mucus droplet 4-5um in diameter Increased when patient has positive AFB smear, extensive upper lobe infection/cavity, copious production of thin sputum and severe and forceful cough Young children rarely infect others because tubercle bacilli are sparse in the endobronchial secretions of children with PTB and cough is often absent or lack tussive force required to suspend infectious particles for transmission.

50. Pathogenesis Primary complex includes local infection at the portal of entry and the regional lymph nodes that drain the area Tubercle bacilli multiply initially within the alveoli and alveolar ducts, most of the bacilli are killed, but some survive within nonactivated macrophages, which carry them through lymphatic vessels to the regional lymph nodes.

51. Tissue reaction in the lung parenchyma and lymph nodes intensifies over the next 2-12 weeks. The parenchymal portion of the primary complex often heals completely by fibrosis or calcification after undergoing caseous necrosis and encapsulation.

52. Tuberculin Skin Testing (TST) The development of delayed type hypersensitivity reaction in most individuals infected with tubercle bacillus makes the TST a useful diagnostic tool. The Mantoux Tuberculin Skin Test is the intradermal injection of 0.1mL containing 5 tuberculin units of purified protein derivative (PPD. T cells sensitized by prior infection are recruited to the skin where they release lymphokines that induce induration through local vasodilatation, edema, fibrin depositon and recruitment of other inflammatory cells to the area.

53. TST should be read by a trained person 48-72 hours after administration. Occasional patients will have the induration >72 hours after placement, this is also a positive result. Immediate hypersensitivity reaction are shortlived (<24 hours) and are not considered a positive result.

54. Tuberculin sensitivity develops 3 weeks to 3 months after inhalation of organism Factors that can depress skin test reaction: – Very young age – Malnutrition – Immunosuppresion – Viral infection – Vaccines with live virus – Overwhelming tuberculosis

55. False positive reaction to TST can be caused by cross sensitization to antigens on non tuberculous mycobacteria Previous BCG (Especially if 2 doses of BCG are already given) In general, a > or equal to 10mm in a BCG vaccinated child indicates infection

56. Tuberculin Skin Test Induration of 5 mm or more is considered a positive TST result in the following children: Children having close contact with known or suspected contagious cases of the disease, including those with household contacts with active tuberculosis whose treatment cannot be verified before exposure Children with immunosuppressive conditions (eg, HIV) or children who are on immunosuppressive medications Children who have an abnormal chest radiography finding consistent with active tuberculosis, previously active tuberculosis, or clinical evidence of the disease

57. Tuberculin Skin Test Induration of 10 mm or more is considered a positive TST result in the following children: Children who are at a higher risk of dissemination of tuberculous disease, including those younger than 5 years or those who are immunosuppressed because of conditions such as lymphoma, Hodgkin disease, diabetes mellitus, and malnutrition Children with increased exposure to the disease, including those who are exposed to adults in high-risk categories (eg, homeless, HIV infected, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons); those who were born in or whose parents were born in high- prevalence areas of the world; and those with travel histories to high-prevalence areas of the world

58. Tuberculin Skin Test Induration of 15 mm or more is considered a positive TST result in children aged 5 years or older without any risk factors for the disease

59. Clinical Manifestations Majority develop no signs or symptoms Occasionaly, with low grade fever and mild cough Rarely with high fever, cough, malaise and flu like symptoms.

60. Primary Pulmonary Disease Primary complex includes parenchymal pulmonary focus and regional lymph nodes Initial parenchymal inflammation is usually not visible on chest radiograph Hallmark of primary tuberculosis in the lungs is the relatively large size of regional lymphadenitis compared with the relatively small size of the intial lung focus

61. Usual sequence is hilar lymphadenopathy, focal hyperinflation, and then atelectasis – The resulting radiographic shadows has been called collapse-consolidation The symptoms and physical signs of primary pulmonary tuberculosis in children are meager considering the degree of radiographic changes seen

62. Non-productive cough and mild dyspnea are the most common symptoms Systemic complaints such as fever, and night sweats are seen less often Pulmonary signs are even less common.

63. Diagnosis Most specific confirmation of pulmonary TB is isolation of Mycobacterium tuberculosis For infants who can’t expectorate sputum, a jet nebulizer, chest percussion followed by nasopharngeal suctioning can be done. The traditional culture specimen is the early morning gastric acid obtained just before the child has arisen

64. However, 3 consecutive morning gastric aspirate yield organism in only less than 50% of cases Negative culture should never exclude the diagnosis in children Diagnosis can be made if: – Positive TST – Abnormal chest radiograph findings suggestive of TB – History of exposure

65. Treatment Insert table from NElsons