Overview of lymph node TB, extra-PTB, INDEX TB GUIDELINE FOR TUBERCULAR LYMPHADENITIS OR LYMPH NODE TUBERCULOSIS

1. Dr. Suresh Kumar Yogi
MBBS & MD
RESPIRATORY MEDICINE

2.  The burden of EPTB is high, ranging from 15–20% of
all TB cases in HIV-negative patients.
 While in HIV-positive people it accounts for 40–50%
of new TB cases.
 Tuberculous lymphadenitis is among the most frequent
presentations of extrapulmonary tuberculosis (TB).
Text book of tuberculosis-3rd edition S K SHARMA

3.  Lymph node TB ( TB lymphadenitis) may occur as the sole
manifestation of TB infection, or alongside pulmonary or
miliary TB.
 LNTB is the most common form of EPTB in India, accounting
for around 35% of EPTB cases .
 Total estimated incidence of LNTB was 30.8 per 100 000
population in India in 2013 (RNTCP, 2014).
 In rural India, the prevalence of tuberculous lymphadenitis in
children up to 14 years of age is approximately 4.4 cases per
1000 .(1)
1.Narang P, , Mendiratta DK, Sharma SM, et al. Prevalence of tuberculous lymphadenitis in children in Wardha
district, Maharashtra State, India. Int J Tuberc Lung Dis 2005;9:188-94.

4.  Tuberculous lymphadenitis is considered a local manifestation
of the systemic disease, whereas lymphadenitis due to
nontuberculous Mycobacteria is truly a localized disease.
 TB lymphadenitis may occur due to:
 Reactivation of healed focus involved during primary
infection
 Progressive primary tuberculosis i.e. spread from lung into
mediastinal lymph node
 Spread from tonsil and
 Hematogenous spread due to miliary TB
Text book of tuberculosis-3rd edition S K SHARMA

5.  Tuberculous lymphadenitis most frequently involves
the cervical lymph nodes followed in frequency by
mediastinal, axillary, mesenteric, hepatic portal,
perihepatic, and inguinal lymph nodes.

6.  Tb cervical lymphadenitis tends to occur more often in
female and presents in young adults.
 Slowly enlarging lymph nodes and may otherwise be
asymptomatic.
 Some patients my present with fever ,weight loss,
fatigue and night sweats.
 Cough is prominent symptom in mediastinal
lymphadenopathy.

7. Stages of TB lymphadenitis.
Stage 1 -Enlarged, firm, mobile, discrete nodes.
Stage 2- Large rubbery nodes fixed to surrounding
tissue
Stage 3- Central softening abscess.
Stage 4-Collar stud formation.
Stage 5-Sinus tract formation. Typical TB sinus has
thin, bluish, undermined edges with scanty
watery discharge
Jones PG, Campbell PE. Tuberculous lymphadenitis in childhood: The significance of
anonymous mycobacteria. Br J Surg 1962;50:302-14

8. Text book of tuberculosis-3rd edition S K SHARMA

9.  Reactive lymphadenitis, (secondary to viral, bacterial
infections)
 Tuberculosis
 Lymphomas
 lymphadenopathy of NTM
 Generalised lymphadenopathy of HIV
 Sarcoidosis
 Secondary carcinomas
 Uncommon causes like fungal diseases, toxoplasmosis

10.  Multiplicity, matting and caseation are the three
features which helps in the diagnosis of TB
lymphadenitis.

11. Presumptive peripheral LNTB
 Patients with enlarged lymph nodes (over 1 cm across)
in the neck, armpit or groin.
 And / or with symptoms of
 fever,
 weight loss,
 night sweats and
 cough

12. Presumptive mediastinal LNTB
 Patients presented with cough, fever, shortness of
breath, weight loss or night sweats.
 And hilar widening on chest X-ray and/or mediastinal
lymphadenopathy on chest CT in the absence of
evidence of active pulmonary TB.
Presumptive abdominal LNTB
 Patients with dull or colicky abdominal pain,
abdominal distension, weight loss, night sweats or
fever, and
 Evidence of abdominal lymphadenopathy on
abdominal ultrasound scan, CT or MR

13.  chest X-ray and HIV test should be done in all patients
presenting with symptoms consistent with LNTB, to
seek for active or previous pulmonary TB.
 EPTB is associated with HIV infection. All patients
should be offered integrated counseling and testing.

14. Fine needle aspiration cytology (FNAC)
 should be done in all patients.
 Send specimen for:
 Microscopy and culture for Mtb with drug susceptibility testing;
 Cytology
 Xpert MTB/RIF test;
Excision biopsy
 In selected- If FNAC has been inconclusive, or where malignancy is
suspected.
 Send specimen for:
1.In normal saline
 Xpert MTB/RIF test;
 Microscopy and culture for Mtb with drug susceptibility testing;
2. In formalin
 histopathology

15. Ultrasound or CT scans of chest and abdomen
 Selected
 Indicated when diagnosis is not clear, and
 In HIV positive people Finding abdominal lymphadenopathy should
prompt biopsy to rule out lymphoma as a differential diagnosis.
 Lymphadenopathy in abdominal tuberculosis usually occurs in mesenteric,
peri-pancreatic, periportal, and para-aortic groups of lymph nodes. The
distribution reflects the lymphatic drainage of sites in the small bowel and
liver that have been seeded haematogenously.
 The nodes may be seen as conglomerate masses and/or as scattered
enlarged nodes with hypoechoic or anechoic centres because of necrosis.
 The involvement of retroperitoneal nodes and lesions not confined to one
anatomic area of drainage are more suggestive of lymphoma.
@-Jain R, Sawhney S, Bhargava DK, Berry M. Diagnosis of abdominal tuberculosis: sonographic findings
in patients with early disease. AJR 1995; 165: 1391-5.

16.  A thickening of the small bowel mesentery of 15 mm or
more and an increase in mesenteric echogenicity
combined with mesenteric lymphadenopathy has been
reported as the characteristic sonographic feature of
early abdominal tuberculosis.(@)
@-Jain R, Sawhney S, Bhargava DK, Berry M. Diagnosis of abdominal tuberculosis: sonographic findings
in patients with early disease. AJR 1995; 165: 1391-5.

17.  Multiple enlarged (≥12 mm) abdominal lymph nodes were
significant predictors of tuberculosis with a positive likelihood
ratio of 11.4, but the 95% CIs were wide (4.3–30.3) due to the
small numbers of patients with tuberculosis .
Sculier D, Vannarith C, Pe R, et al. Performance of abdominal ultrasound for diagnosis of tuberculosis in HIV-
infected persons living in Cambodia. J Acquir Immune Defic Syndr 2010; 55:500–2.
Sonographic image of (a) enlarged lymph nodes in the periportal area; (b) focal lesions in
the spleen of approximately 3 mm in diameter; (c) focal lesions in the spleen of
approximately 10 mm in diameter

18. Lymph node TB
 Xpert MTB/RIF should be used as an additional test to
conventional smear microscopy, culture and cytology
in fine-needle aspiration cytology (FNAC) specimens.
(Strong recommendation, low quality evidence for sensitivity
estimate, high quality evidence for specificity estimate.)
 Pooled sensitivity and specificity against culture are 83.1%
and 93.6% respectively.

19. Bacteriologically confirmed LNTB case
A patient with symptoms and signs of LNTB and has
at least one of the following:
 Positive microscopy for AFB on examination of lymph
node fluid or tissue
 Positive culture of Mtb from lymph node fluid or tissue
 Positive validated PCR-based test (such as Xpert
MTB/RIF)

20. Clinically diagnosed LNTB case
A presumptive LNTB patient who undergoes
diagnostic testing and has all of:
 Negative microscopy, negative culture and
negative PCR based tests.
 No other diagnosis made to explain signs and
symptoms.
 Strongly suggestive evidence on other tests, such
as radiological findings, histopathological
findings, clinical course.

21. First line treatment for adults and children with LNTB-
 2RHZE/4RHE
 Duration - Six months, standard first-line regimen is
recommended for peripheral lymph node TB

22.  In patients with drug-resistant TB, the treatment must
rely upon the recent PMDT (WHO )guidelines which
are primarily based on drug sensitivity pattern.

23. Assess response to treatment at 4 months.
 Consider possible treatment failure in patients who
have worsened or deteriorated after initial improvement
– this requires diagnostic investigation and possibly a
change of treatment.
 Deterioration in the first 3 months may be due to
paradoxical reaction – this does not require repeat
diagnostic tests or change of treatment.

24.  IRIS –”immune reconstitution inflammatory syndrome”, in
PLHA patients on ART
 Paradoxical reaction is generally used to describe a clinical
worsening of TB disease in HIV – seropositive and negative
patients after initiation of ATT.
 Symptomatic management is sufficient in vast majority of
cases.
 In case of ARDS, TUBERCULOMA, and pericardial effusion,
glucocorticoid therapy is needed for few weeks.
 DST should be done in all case of paradoxical reactions.
Text book of tuberculosis-3rd edition S K SHARMA

25. Some patients with LNTB have residual
lymphadenopathy at the end of treatment.
The largest node is-
 < 1 cm in size - usually do not have continued active
TB infection. Reassured the patient.
 > 1 cm in size- classified as partial responders.
The expert group suggested, these patients should
receive an additional 3 months of RHE, followed by a
biopsy sent for histology and TB culture in patients
who fail to respond to that.

26. For mediastinal TB,
 Progress on ATT can be monitored with chest X-ray, but
CT scan may be indicated if lymph nodes do not reduce
in size after 4 months.
 In patients who fail to improve on ATT, the alternative
diagnoses of lung cancer, lymphoma, sarcoidosis and
fungal infection should be considered.
 Current expert opinion on when to stop ATT in patients
with persistently enlarged mediastinal lymph nodes is to
stop when there is documentation of absence of interval
change in CT/MRI of mediastinal lymph nodes for more
than 4 months, with resolution of all other signs and
symptoms.

27. The indications for surgical management of TB
lymphadenitis are:
 Treatment failure: Surgical treatment is beneficial to establish
the diagnosis and management of drug-resistant organisms
 Adjuvant treatment for drug sensitive cases: For patients who
have discomfort from tense, fluctuant lymph nodes surgical
treatment is beneficial
 Paradoxical reaction: In a retrospective review, aspiration,
incision, and drainage or excision were associated with a trend
toward a shorter duration of paradoxical reactions
 Nontuberculous mycobacteria: In children with NTM lymph
node removal has been associated with better outcomes
Fontanilla JM, Barnes A, von Reyn CF. Current diagnosis and management of peripheral
tuberculous lymphadenitis. Clin Infect Dis 2011;53:555-62.

28.  Appearance of freshly involved nodes
 Enlargement of the existing nodes
 Development of fluctuation
 Appearance of sinus tracts
 Residual lymphadenopathy after completion of
treatment
 Relapses.
Gupta PR. Difficulties in managing lymph node tuberculosis. Lung India 2004;21:50-3.

29. 1.Record all the possible sites of involvement, nature, and size
of the involved lymph nodes at the starting of treatment.
2. Identify any coexisting disease and treat it simultaneously.
3. Performe TB Gene X-pert or line probe assay on initial lymph
node sample, so that if lymph nodes enlarge during therapy, it
becomes clear whether this is due to a paradoxical reaction or
drug resistance.
Gupta PR. Difficulties in managing lymph node tuberculosis. Lung India 2004;21:50-3.

30. 4. Most nodes that enlarge during therapy or appear afresh ultimately
respond to treatment. Only a close follow up is required for these
patients.
5. Appearance of fluctuation in one or more lymph nodes calls for
aspiration under all aseptic precautions.
6. Any secondary bacterial infection should be dealt with appropriately
that may include incision and drainage.
7. Any worsening after 8 weeks of therapy calls for en-bloc resection
of the involved lymph node chain to avoid appearance of ugly sinus
tracts.
8. Nonhealing sinus tracts need resective surgery.
Gupta PR. Difficulties in managing lymph node tuberculosis. Lung India 2004;21:50-3.

31. 9. On completion of treatment, if any residual lymph nodes
exist, they should be observed closely. Any increase in the size
or appearance of symptoms calls for excisional biopsy for
histopathology, culture, and TB Gene Xpert. Most patients
respond to retreatment with the same regimen.
10. Relapse: Relapse rates of up to 3.5% have been reported in
patients treated for TB lymphadenitis. This should be treated
with the same drugs but culture or molecular diagnostic test
must be performed to rule out resistance or NTM disease.[$]
$-Breen RA, Smith CJ, Bettinson H, Dart S, et al. Paradoxical reactions during tuberculosis
treatment in patients with and without HIV co-infection. Thorax 2004;59:704-7

32. 11. Drug resistance: [#]
 Though it is at times difficult to confirm drug-resistance in LNTB, it
is essential to demonstrate drug resistance prior to starting multidrug-
resistant regime.
 Similarly, single agent (fluoroquinolones or others) should never be
introduced even if response to treatment is not appropriate.
 Each case should be reasonably investigated with culture or molecular
diagnostic tools.
 Further, appropriate measures should be taken to prevent the use of
second-line drugs in unproven cases.
#-Deveci HS, Kule M, Kule ZA, Habesoglu TE. Diagnostic Challenges in Cervical Tuberculous
Lymphadenitis: A review. North Clin Istanbul 2016;3:150-5.

33. 12. Systemic steroids have been shown to reduce inflammation
during the early phase of therapy for lymph node tuberculosis
and may be considered if a node is compressing a vital structure,
i.e. bronchus or in diseases involving cosmetically sensitive
areas.
 Prednisolone 40 mg per day followed by gradual tapering over
the next 6 weeks, along with appropriate chemotherapy is
adequate.
 However, the safety and utility of this approach remains largely
unproven except in intrathoracic disease where it was found to
relieve the pressure on the compressed bronchus.
Gupta PR. Difficulties in managing lymph node tuberculosis. Lung India 2004;21:50-3.

34. Thank you