1 Dr MPS Chawla MD, FIACM, FICP •An astute clinician, a keen academician and a popular teacher. Several Publications in Indexed journals •Associate Editor of API Medicine Update 2009 •Associate Editor of Clinical Medicine Update 2013 •Associate Editor, journal of Indian Association of Clinical Medicine •Hon Gen Secretary, API Delhi State Chapter •Member. Governing Body, API Senior Internist PGIMER, Dr RML Hospital New Delhi Photogr
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MD, FIACM, FICP - APIDSC · pericardial calcification ... Male genital tract TB ² acute epidydymitis or epidydmoorchitis -may cause caseation and fistula, chronic prostatitis and
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1
Dr MPS Chawla
MD, FIACM, FICP
•An astute clinician, a keen academician and a popular teacher.
Several Publications in Indexed journals
•Associate Editor of API Medicine Update 2009
•Associate Editor of Clinical Medicine Update 2013
•Associate Editor, journal of Indian Association of Clinical
Medicine
•Hon Gen Secretary, API Delhi State Chapter
•Member. Governing Body, API
Senior Internist PGIMER, Dr RML Hospital
New Delhi
Photogr
2
Challenges and Perspectives in The
Diagnosis of Extrapulmonary TB
Dr MPS Chawla
MD, FIACM, FICP
Senior Internist
PGIMER, Dr RML Hospital, New Delhi
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Tuberculosis
One of the world’s deadliest communicable disease, 2nd
biggest killer among infectious agents
In 2014, an estimated 9.6 million people developed
TB(5.4 m men,3.2 m women and 1 m children ) and 1.5
million died from the disease, 360 000 of whom were
HIV-positive, 37% of new cases remained undiagnosed
or not reported. 4,80,000 cases of MDR TB
1/3 rd of world’s population infected with MTB
India—highest burden country
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Case Definitions
Pulmonary tuberculosis (PTB) refers to a case of TB involving the lung
parenchyma.
Extrapulmonary tuberculosis (EPTB) refers to a case of TB involving
organs other than the lungs
Diagnosis should be based on at least one specimen with confirmed
M. tuberculosis or histological or strong clinical evidence consistent
with active EPTB, followed by decision by clinician to treat with full
course of TB chemotherapy
Can/should still treat presumptively if strong clinical evidence
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Case Definitions
If several sites affected, case definition of an EPTB case depends on
the site representing the most severe form of disease.
Miliary tuberculosis is classified as pulmonary TB because there are
Coronal T1-weighted gadolinium-enhanced magnetic resonance image demonstrates characteristic abnormal leptomeningeal enhancement (short, thick, white arrow), with intensely enhancing walls of both lateral ventricles (black arrows). High signal within the left frontal lobe represents an enhancing tuberculoma (thin white arrow). Entrapment of the left temporal horn (long, thick, white arrow) and midline shift to the right are due to the ventricular mass lesion.
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Pericardial Tuberculosis May result in acute pericarditis, chronic pericardial effusion, cardiac
temponade or pericardial constriction
Accounts for 2/3 rd of cases of constrictive pericarditis in India
Results from direct extension from mediastinal lymph nodes or
lymphohematogenous route from a focus elsewhere
Stages– dry, effusive, absortive and constrictive
May present with fever with no localisation
Cardiomegaly on CXR PA view may be the only clue
Low voltage and shifting axis on ECG
Echocardiography
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Characteristic Findings in Body Fluids in various forms
of EPTB Variable Pleural Fluid Pericardial Fluid CSF
Appearance Straw colored Straw colored or
serosanguinous
Clear early, turbid with
chronicity
pH 7.3-7.4, never more than 7.4 Not well described Not well described
Cell count
Total Count
Differential
1000-5000
50-90% lymphocytes, few
mesothelial cells
Not well described
Leucocyte count increased,
PMN preponderance early,
later mononuclear cells
predominate
100-500
PMN preponderance
early,Laterupto 95%
mononuclear
Protein Usually high
More than 2.5 g/dL
Usually high Ususally high(100-500
mg/dL), can be very high
with blockage or chronicity
Glucose Less than serum conc Low 50% of bld glucose
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Miliary TB
Miliary TB occurs when tubercle bacilli enter the bloodstream and are
carried to all parts of the body
Wide range of presentations
May include on one extreme ARDS and on the other extreme failure
to thrive without fever
Symptoms may be dominated by whatever organ system is primarily
involved
Typical patient has a febrile wasting syndrome of 2-4 months
duration
Fulminant disease esp in primary form—septic shock, ARDS and MOF
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Miliary Tuberculosis
Sputum smear is positive in about 25% of cases in both
HIV and non-HIV patients
In sputum smear negative miliary TB, bronchoscopy led to
an immediate diagnosis in 65% and this increased to 79%
with culture
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Bone TB
Pott’s spine-commonest site- thoracic spine and thoracolumbar junction
Occurs as a result of hematogenous transmission
Local pain, swelling and limitation of joint movement may precede
radiological changes by 4-8 wks
Structural damage to the skeleton may produce deformities and
compression of nerve roots and spinal cord
Affected bone may fracture and may produce spinal cord compression
Untreated TB may involve adjacent soft tissues and epidural space
Vertebral abscess may travel along psoas muscle- Psoas abscess
Extraspinal tuberculous osteomyelitis, Poncet’s
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Genitourinary Tuberculosis MTB reach kidneys, epidydimis or female genital organs via
hematogenous spread
Peak incidence in females of age 20-40 yrs
Risk factors– male gender, HIV infection, hemodialysis and ESRD,
recipients of renal transplant
Kidneys- most common site of GU TB
Renal TB—Symptoms—urinary frequency, urgency, dysuria and nocturia
Urine– classical triad of hematuria, proteinuria and sterile pyuria
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Urogenital Tuberculosis
Male genital tract TB—acute epidydymitis or
epidydmoorchitis-may cause caseation and fistula,
chronic prostatitis and extensive scarring of
epidydmus, ejaculatory ducts and seminal vesicles
leading to male infertility
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Female GU TB
May present with infertility, menstrual irregularities and chronic pelvic or
lower abdominal pain
Fallopian tubes—most commonly affected, followed by endometrium,
ovaries and cervix
Tubo-ovarian abscesses and adnexal masses mimicking ovarian cancer
mostly in presence of peritoneal involvement and when serum levels of
CA-25 marker are raised
Requires a high index of suspicion
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A 75-year-old woman with ureteric tuberculosis. (A) Retrograde pyelogram image demonstrates irregularity of the ureter and absence of contrast in the strictured distal portion (arrow). (B, C) Contrast-enhanced computed tomography image in the portal venous phase of the same patient demonstrates rightsided hydronephrosis (arrow, B) caused by stricturing and thickening of the distal ureter (arrow, C).
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A 30-year-old woman who presented with fever of unknown origin,later found to have tuberculous peritonitis and salpingitis. Contrast-enhanced computed tomography image in the portal venous phase demonstrates massive ascites (23 HU), diffuse peritoneal enhancement (black arrow), omental caking (thin white arrow), and nodular soft-tissue thickening (thick white arrow).
tenderness,ascitis,mass in right iliac fossa, intestinal
obstruction
Classic doughy abdomen– 5-10 %
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Peritoneal TB
Results often from the re-activation of latent peritoneal TB foci
Classical risk factors --HIV infection, cirrhosis and CAPD; diabetes
mellitus, underlying malignancy and therapy with anti-TNF agents
Ascitic fluid is exudative, with a SAAG ≤ 1.1 g/dl and leukocyte count
variable from 150 to 4000/mm3 with a lymphocytic predominance,
although neutrophyllic pleocytosis can be seen in cases undergoing
peritoneal dialysis
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investigations
Abdominal lymphadenopathy-retroperitoneal, peripancreatic, porta
hepatic and mesentric-on CT
Caseous lymph nodes appear as low attenuating necrotic centres with
thick enhancing inflammatory rim
Preferential thickening of medial caecal wall with exophytic mass
engulfing terminal ileum associated with massive lymphadenopathy—typical of TB
Short segments of mural thickening with normal intervening bowel
associated with ileo-caecal involvement
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Investigations
Colonoscopy- edematous, deformed ileocaecal valve
with both sides diseased, ulceration, girdle strictures
FNAC, Biopsy
Laproscopy—multiple yellowish white miliary nodules
over peritoneum, erythematous, thickened, hypremic
peritoneum
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TB of Adrenal Glands
5th most common site of EP TB, after the liver, spleen, kidneys, and bones
In 6% of patients with active TB and is nearly always b/L, The gland
becomes enlarged and demonstrates rim enhancement and central low
attenuation consistent with caseous necrosis.
Patients may present with an Addisonian-type clinical picture.
A 60-year-old woman with adrenal tuberculosis. Contrast enhanced computed tomography image in the portal venous phase demonstrates right adrenal enlargement, rim enhancement and central low attenuation
consistent with caseous necrosis (arrow).
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Cutaneous Tuberculosis
Lupus vulgaris
Scrofuloderma
Tuberculous verrucosa cutis
Tuberculids- erythema nodosum,
erythema induratum
Prosector’s warts
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Ocular Tuberculosis
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TNF alpha Inhibitor Associated Tuberculosis
Seen in patients with RA or Crohn’s disease after t/t
with TNF alpha inhibitors, especially infliximab
EPTB in 52-57 %
Patients should be screened for latent tuberculosis
infection or active disease before initiation of therapy with
a TNF-alpha inhibitor.
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Microscopy
Direct visualization of AFB-- the first microbiological test to be performed
ZN staining/ Kinyoun staining, low sensitivity
Light emitting diode (LED) technology --cheaper and viable alternative to
Ziehl–Neelsen microscopy and to fluorescence microscopy based on
mercury vapor or halogen lamps, 10%more sensitive, 1/4th time
In some cases, concentration of large volumes of sampled fluid(CSF,
ascites, etc.) and repeated analyses can increase the diagnostic yield
Microscopy, as well as culture, may be affected by the rapid mycobacterial
killing operated by some antibiotic agents like fluoroquinolones, resulting
in false-negative results
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IGRAs
based on the assessment of the IFN-g released after stimulation of
sensitized T-cells by highly MTB-specific antigens, including ESAT 6 and
CFP10,
two commercially available IGRAs: QuantiFERON-TBGold In Tube assay
(QIAGEN corp., Hilden, Germany), which utilizes an ELISA technique to
measure the amount of IFN-g secreted, and the T.SPOT-TB (Oxford
Immunotec, Abingdon,UK), which uses an ELI Spot assay to quantify the
number of IFN-g-producing cells
cannot distinguish between latent infection and active TB; therefore, they
are not suited to diagnose active TB.
Next generation tests--Dual cytokines-Interferon gamma and IL 2
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Culture
Most sensitive diagnostic test, with a lower limit of detection of 10 bacilli/mL of
sputum
Liquid culture --mainstay for the diagnosis of EPTB., BACTEC MGIT 960 based
on modified Middlebrook 7H9 Broth with an oxygen-sensitive fluorescent