Pediatric TB Intensive Houston, Texas October 14, 2013 Extrapulmonary TB in Children Kim Connelly Smith, MD, MPH October 14, 2013
Kim Connelly Smith, MD, MPH has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity
Extrapulmonary TB the Great Imitator Nonspecific symptoms Location: anywhere in body Mimics other more common diseases Broad differential diagnosis TB diagnostic tests not very sensitive Lab tests often negative due to paucibacilary disease Obtaining specimens may require: Hospitalization Invasive procedures When laboratory tests negative, diagnosis is made on clinical grounds
Extrapulmonary TB Disease Sites Lymphadenitis Central nervous system Miliary Pleural Bone and joint Abdominal TB in lymph nodes or solid organs Genitourinary Otitis media and mastoiditis Pericardial Ocular Cutaneous
Common Symptoms Fever Enlarged peripheral lymph nodes Neurologic or central nervous system symptoms Cough Weight loss Palpable mass Night sweats
TB Disease Adult TB Disease Pediatric TB Disease 15% 85% 25% 75% Pulmonary Extrapulm Pulmonary Extrapulmonary
Adult Extrapulmonary TB Disease (15%) Bone/Joint 10% Meningeal 4% Miliary 9% Other 13% GU 16% Lymphatic 25% Pleural 23% Lymphatic Pleural GU Meningeal Bone/Joint Miliary Other
Other 5% Miliary 5% Bone/Joint 5% Extrapulmonary TB Disease in Children (25%) Pleural 6% Meningeal 14% Lymphatic 65% Lymphatic Meningeal Pleural Miliary Other Bone/Joint
Diagnosis of TB Disease Culture is the gold standard for TB diagnosis Collect tissue or fluid for culture 2-8 weeks for results Low sensitivity in children and extrapulmonary TB Combination of findings important Risk factors Contact testing/exposure history Skin testing and/or IGRA blood test may help Radiographic findings suggestive of TB Pathology from tissue biopsies may suggest TB Rule out other diseases
TB Cultures and AFB Smears Sensitivity poor due to low number of bacteria Lymph nodes Biopsy or FNA for path and culture AFB smears: usually negative Culture sensitivity: 30-70% TB meningitis High volume sample (>6 ml CSF) improves culture yield AFB smears negative 98% Culture sensitivity: 12-50% (Ave 20%) Nucleic acid amplification tests (NAAT) - Future new tool for extrapulmonary TB Negative test does not rule out TB
TB Meningitis
Case 15 month old Fever, irritability and cough for 7 days Treated for otitis media Developed ataxia 2 days prior to admission Admitted with acute seizure History Past medical history, healthy Traveled to India to visit GM at 8 months Grandmother with cough, later found to have TB Labs CSF WBC 223, 70% Lymphs CSF Protein 178 MRI Hydrocephalus, leptomeningeal enhancement
Initial MRI at Diagnosis Follow up MRI in 2 months
Diagnosis of TB Meningitis Clinical criteria including exposure history CSF findings CNS imaging Evidence of TB elsewhere Exclusion of other causes
Principi. Tuberculosis 92 (2012) 377-383 Clinical Criteria
TB Meningitis Youssef FG, et al. Diagn Microbiol Infect Dis 2006;55(4):275-8
TBM Clinical and CSF findings British Infectious Disease Society. Jr of Infection (2009) 59, 167-187
Diagnostic Evidence of TB Meningitis Brain MRI or CT Suggestive of TBM Basal meningeal enhancement Hydrocephalus Tuberculoma Infarcts Evidence of TB Disease Elsewhere Radiographic evidence of TB outside CNS CXR/CT suggestive of TB Miliary Hilar LAN TB Cx + from another site Sputum, GA, Bx, urine, blood Positive NAAT
[ Brain CT Findings in TB Meningitis Comparison of CT findings in children with TB meningitis Study Total Patients Children # Hydrocephalus (%) Basal enhancement (%) Infarcts (%) Tuberculoma (%) Artopoulos 9 9 100 11 44 56 Bhargava 60 36 83 82 28 10 Farinha 33 33 94 93 33 15 Kingsley 25 12 72 67 Kumar 94 94 81 83 19 24 Leiguarda 65 65 89 69 38 27 Patwari 136 136 32 13 27 Waeker 30 30 100 37 37 Andronikou 37 37 68 89 62 13.5 Altunbasak 52 52 98 52 25 De 21 21 76 67 50 10 Kemaloglu 156 156 46 22 4 Ozates 289 214 80 15 14 4 Tung 7 7 100 14 29 Upadhyaya 59 59 100 6 8 Schoeman 198 198 83 75 38 11 Adapted from Andronikou S. Pediatr Radiol. 2004 34(11):876-85
TB Meningitis Treatment and Clinical Course 9-12 months RIPE therapy Better CNS penetration with ethionamide Steroids for 1-2 month with 2-3 week taper Decreases CNS inflammation Repeat brain imaging recommended 1-2 months after treatment started Possible complications Prolonged fever and/or worsening symptoms common initially Seizures Hydrocephalus CNS tuberculoma, stroke, mental disabilities, CP Mortality high (>90%) if not diagnosed and treated
TB Meningitis Outcome Doerr, Starke, Ong. J Pediatr. 1995 Jul;127(1):27-33. Clinical and public health aspects of tuberculous meningitis in children.
Extrapulmonary Cases
o Mother Congenital TB Case o Pneumonia diagnosed at 34 wks of pregnancy o TST Omm, no known exposure o Treated with azithromycin & pneumonia resolved o Baby o Became ill 4 weeks after birth o Developed extensive pneumonia and hilar LAN o Progressed to respiratory failure o Required ECMO o AFB smear positive from tracheal aspirate grew MTB, pan susceptible
Outcome Mother Repeat TST after baby diagnosed, 15mm CXR normal, no other source identified Uterine biopsy showed granulomas consistent with TB endometritis Treated for uterine TB disease Baby Treated 12 months for miliary and TB meningitis Required home oxygen and NG tube feedings for 8 months Healed with complete recovery and no sequella
Tuberculosis, In Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and
Congenital Tuberculosis Congenital TB disease very rare Only 200-300 cases reported Higher risk if mother has primary or disseminated TB during pregnancy Postnatal transmission via exposure to pulmonary TB disease more common
17 year old Hispanic female Teen Case Abdominal pain and fever for 10 days Past Medical Hx: Healthy US born, no history of BCG vaccination Social: High school student No drugs or alcohol, is sexually active Lives with her 15 mo baby, her boyfriend and his parents No known TB exposure, parents from Mexico Physical exam: Lungs normal Nodes: no lymphadenopathy Abdomen: tender with guarding Pelvic exam: + cervical motion tenderness
Differential Diagnosis Pelvic inflammatory disease Appendicitis or ruptured appendix Ovarian abscess or torsion Ectopic pregnancy Lower lobe pneumonia causing acute abdomen symptoms Mesenteric lymphadenitis
Teen Case Labs and Radiographs STD testing HIV, GC, Chlamydia, RPR all negative Pregnancy test negative Abdominal CT nonspecific inflammation large peritoneal effusion normal appendix no lymphadenopathy or masses
Abdominal CT and MRI Enhancement of the peritoneal surface indicates peritonitis (arrow). T2-weighted MRI shows the high signal intensity peritoneal fluid (F).
Teen Case, cont Exploratory laparotomy by GYN Caseous material from fallopian tubes Culture from laparotomy specimen AFB smear negative M. tuberculosis identified on culture Contact investigation of household Patient TST negative, O mm Household Members: 5/7 with LTBI, TST positive & CXRs normal 2/7 TB Disease: Father-in-law, TST negative, chronic cough, CXR with cavitary disease, AFB smear and culture positive
Diagnosis based on Teen Case Clinical picture Pneumonia Caseous surgical material Other diagnoses ruled out Contagious adult source case identified MTB on Culture (2-8 weeks later)
TB Lymphadenitis
Cervical Lymphadenitis 4 year old girl with acute 4 cm anterior cervical LAN PMH Strep throat treated 1 week prior Severe head lice and scalp dermatitis Otherwise healthy TST 11 mm CXR normal Social US born, no BCG Grandparents from Mexico Uncle with cough
Cervical Lymphadenitis, cont Differential diagnosis Reactive LAN from strep throat and/or head lice Tuberculosis or nontuberculous cervical LAN Other causes Management options Treat common/acute diseases first Gather more information, contact investigation +/- RIPE, now or later +/- Biopsy
Outcome Cervical LAN LAN treated with clindamycin Head lice and scalp dermatitis treated TB treatment held until follow up LAN resolved in 2 weeks Patient treated for LTBI Contact investigation Uncle diagnosed with pulmonary disease Multiple family members with LTBI
Teen Case 15 year old AA boy with 5 week history Abdominal pain Cough, fever, 20 lb weight loss Denies high risk behavior No foreign travel or known TB exposure Physical 220 lb, football player Cervical LAN Abdomen normal, no HSM Lungs clear TST: negative, O mm CXR normal
Teen Case, cont Laboratory: CBC H/H 9.6/29, WBC 16, PLT normal Peripheral smear negative for cancer ESR 83 (normal < 20) HIV negative, x 2 CT of neck and abdomen Lymphadenopathy
Abdominal CT shows multiple lymph nodes with low attenuation centers and prominent rim enhancement (arrow).
Neck CT
Teen Case of Lymphadenopathy Case, cont Differential diagnosis Lymphoma, leukemia HIV, EBV, other disseminated infections Tuberculosis Laboratory IGRA - positive Node biopsy: AFB smear negative TB culture positive at 5 weeks for MTB Susceptible to all drugs Treatment RIPE, 9 months total for disseminated disease
Bone Disease 3 year old Hispanic boy 2 months of knee pain and limping Physical exam: knee with swelling and tenderness Knee x-ray with mass in femur Seen at MD Anderson Hospital for suspected cancer
Bone Disease X-ray Mass vs chronic osteomyelitis ESR 67 Biopsy Path: + granuloma No evidence of cancer AFB negative
Bone Disease Patient s PPD 20 mm Contact Investigation: Mother, father and father s girl friend PPD positive Source case identified Father s girl friend with pulmonary disease Bone biopsy grew MTB on culture Treatment: RIPE for 12 months
15 year old female Bone Disease Headache, back pain, fever and paresthesias
Potts Disease or TB Spondylitis
9 year old boy-tb Exposed Child with 5 mm TST Father with pulmonary TB disease
9 year old exposed to dad with TB TST 5 mm Initial CXR No treatment started
6 weeks later Fever and respiratory difficulty
TB Pleural Effusions Uncommon in children 1-2% cases in US More common in boys and adolescents Usually unilateral 70% associated with parenchymal disease Cultures Pleural fluid often culture negative Pleural biopsy and/or sputum best specimens for culture
Treatment of Extrapulmonary TB Medications RIPE therapy standard Isoniazid, rifampin, PZA and ethambutol Duration 6 months for lymph node disease 9 months recommended for multisite disease 9-12 months for bone and joint and TB meningitis Steroids standard for 1-2 months for TB meningitis followed by 2-3 week taper
Expected Clinical Course for Extrapulmonary TB Disease Hilar Lymphadenopathy Months, sometimes years for regression on x-ray Lymphadenitis Swelling may obstruct airways or GI tract Often gets worse before improves May rupture and drain Months, rarely years for regression Meningitis Inflammation increases initially with treatment Fever common for 2-3 weeks but may persist for months Tuberculoma, infarcts and/or hydrocephalus may develop weeks after diagnosis and treatment started
Summary Extrapulmonary TB Children at higher risk for extrapulmonary TB especially TB meningitis Diagnostic dilemma common Consider and rule out other diseases Tissue diagnosis and/or culture important FNA or surgical biopsy if indicated Low sensitivity due to paucibacilary disease Full resolution is a long process Paradoxical reactions may occur Symptoms may worsen initially before gradual improvement