Post on 24-Apr-2018
EXCELLENCE EXPERTISE INNOVATION
Pediatric TB Intensive Houston, Texas
October 14, 2013
Extrapulmonary TB in Children Kim Connelly Smith, MD, MPH
October 14, 2013
EXCELLENCE EXPERTISE INNOVATION
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
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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
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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
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Common Symptoms
• Fever
• Enlarged peripheral lymph nodes
• Neurologic or central nervous system symptoms
• Cough
• Weight loss
• Palpable mass
• Night sweats
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TB Disease
Pulmonary
Extrapulm
15% 85%
Pulmonary
Extrapulmonary
25% 75%
• Adult TB Disease • Pediatric TB Disease
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Lymphatic 25%
Pleural 23%
GU 16%
Meningeal 4%
Bone/Joint 10%
Miliary 9%
Other 13%
Adult Extrapulmonary TB Disease (15%)
Lymphatic
Pleural
GU
Meningeal
Bone/Joint
Miliary
Other
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Lymphatic 65%
Meningeal 14%
Pleural 6%
Miliary 5%
Other 5%
Bone/Joint 5%
Extrapulmonary TB Disease in Children (25%)
Lymphatic
Meningeal
Pleural
Miliary
Other
Bone/Joint
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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
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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
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TB Meningitis
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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
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Diagnosis of TB Meningitis
• Clinical criteria including exposure history
• CSF findings
• CNS imaging
• Evidence of TB elsewhere
• Exclusion of other causes
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Clinical Criteria
Principi. Tuberculosis 92 (2012) 377-383
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TB Meningitis
Youssef FG, et al. Diagn Microbiol Infect Dis 2006;55(4):275-8
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TBM Clinical and CSF findings
British Infectious Disease Society. Jr of Infection (2009) 59, 167-187
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Diagnostic Evidence of TB Meningitis
• Basal meningeal enhancement
• Hydrocephalus
• Tuberculoma
• Infarcts
• 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 MRI or CT Suggestive of TBM
• Evidence of TB Disease Elsewhere
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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
Brain CT Findings in TB Meningitis
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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.
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Extrapulmonary Cases
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Congenital TB Case o Mother
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
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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
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Tuberculosis, In Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and
Newborn Infant. Philadelphia, WB Saunders, 1983, p576.)
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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
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Teen Case • 17 year old Hispanic female
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
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Differential Diagnosis
• Pelvic inflammatory disease
• Appendicitis or ruptured appendix
• Ovarian abscess or torsion
• Ectopic pregnancy
• Lower lobe pneumonia causing acute abdomen symptoms
• Mesenteric lymphadenitis
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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
T2-weighted MRI shows the high signal intensity peritoneal fluid (F).
Enhancement of the peritoneal surface indicates peritonitis (arrow).
Abdominal CT and MRI
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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
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Teen Case
• Diagnosis based on Clinical picture
Pneumonia
Caseous surgical material
Other diagnoses ruled out
Contagious adult source case identified
MTB on Culture (2-8 weeks later)
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TB Lymphadenitis
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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
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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
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Cervical LAN • Outcome
– 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
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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
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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
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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
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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
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Bone Disease
• X-ray
– Mass vs chronic osteomyelitis
• ESR 67
• Biopsy
– Path: + granuloma
– No evidence of cancer
– AFB negative
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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
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Bone Disease
• 15 year old female
• Headache, back pain, fever and paresthesias
Potts Disease or TB Spondylitis
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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
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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
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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
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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
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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
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