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Tuberculous Lymphadenitis
감염내과 R3 김동현
INTRODUCTION
 Tuberculous lymphadenitis

In Korea, 11~17% of patients with TB have extrapulmonary disease,
TB pleursy, TB lymphadenitis, abdominal TBc, bone and joint TB was
the order.
Korea tuberculosis information management system June 2010

Epidemiology

Male < Female ( about 2 folds )

Common in the 20 to 40 age group
INTRODUCTION

In developed countries
Most cases occur adult immigrants from TB endemic countries
 Peak age of onset in developed countries has shifted from
childhood to ages 20 to 40 years

Curr Infect Dis Rep. 2001;3(3):233.

In developing countries

Extrapulmonary TB occurs in up to 60 % of HIV-infected patients with TB
and is frequently accompanied by signs of pulmonary involvement
(CD4 counts <300 / uL, usually < 100 / uL)
Clin Infect Dis. 1992;15(4):601.
Pathogenesis

Usually, reactivation of disease at a site seeded hematogenously
during primary TB, perhaps years earlier
Medicine (Baltimore). 1984;63(1):25


Cervical TB lymphadenitis
 Due to TB infection involving the tonsils, adenoids and Waldeyer 's ring

Abdominal TB lymphadenopathy
 Ingestion of sputum or milk infected with M. tuberculosis / M. bovis
Miliary dissemination of primary infection can also occur
Am Rev Respir Dis. 1991;144(5):1164
Clinical manifestations

Depend on 1) the site of the lymphadenopathy and 2) the
immune status of the patient

Cervical lymphadenopathy

The most common manifestation (63~77%)
Most frequently a unilateral mass appears in the ant, or posterior
cervical triangles, Bilateral disease is uncommon (up to 26 %)

Schlossberg D. Tuberculosis & nontuberculous mycobacterial infections. 5th ed.
.
Cervical Lymphadenopathy
Clinical manifestations

Other involved nodes

Axillary, inguinal, mesenteric, mediastinal, and intramammary LNs

Mediastinal LAP
 Dysphagia, esophageal perforation, vocal cord paralysis, pulmonary
artery occlusion

Intra-abdominal LAP
 Peritoneal LAP
• most commonly LNs in the periportal region, followed by
peripancreatic and mesenteric LNs.
 Hepatic lymph node involvement can lead to jaundice, portal vein
thrombosis, and portal hypertension.
Axillary lymphadenopathy
Mediastinal lymphadenopathy
Mediastinal lymphadenopathy
Intra-abdominal LAP
Clinical manifestations

HIV (+) patients
Significant mycobacterial load with concomitant systemic findings
(eg. fever, sweats, & weight loss)

More likely to have disseminated TB with lymphadenitis at more
than one site

Differential Diagnosis

Isolated peripheral lymphadenopathy
Malignancy (eg, HL & NHL)
 Other infections (eg, NTM, cat scratch disease, fungal infection,
sarcoidosis, and bacterial adenitis).
 Kikuchi's disease


.
Difficult to differentiate TB from other causes of lymphadenitis on
clinical grounds.
Diagnosis
 Established by

Histopathology examination

Along with AFB smear and culture of lymph node material.

Chest imaging should be obtained
Diagnosis - Histopathology

Fine needle aspirate (FNA)

Initial evaluation of cervical lymphadenopathy

The yield appears to be highest in the setting of HIV infection and
in regions where the prevalence of TB is high.

Specimens should be submitted for 1) Microscopy, 2) Culture,
3) Cytology, and 4) PCR testing
Diagnosis - Histopathology
Infection and Chemotherapy: Vol.40, No.2, 2008
Diagnosis - Histopathology

Lymph node biopsy

In cases when FNA is not diagnostic
 47 patients evaluated for TB lymphadenitis in San Francisco,
the diagnosis of TB was established by excisional biopsy in all cases;
FNA was definitive in only 62 percent
Laryngoscope. 1992;102(1):60.

Caseating granulomas on histopathology is highly suggestive of TB
Diagnosis
Diagnosis - Imaging


Chest imaging

Many patients (90~100 %) with TB lymphadenitis have no evidence of
active pulmonary TB on chest x-ray

Chest imaging suggestive of active pulmonary TB should prompt
further evaluation
Neck imaging

Ultrasonography

Computed tomography
 Useful tool to distinguish between TB lymphadenitis and lymphoma.
Ularasonography
Diagnosis - Others

Sputum smear and culture


Positive sputum cultures are uncommon (0 ~ 14 %)
Blood culture

Rarely positive, but may be positive in disseminated TB especially in
patients with HIV and other forms of immunosuppression
Diagnosis - Others

Tuberculin skin test (PPD test)


Sensitivity and specificity of 65 & 81%,
Interferon-Gamma Release Assays (IGRA)

Sensitivity and specificity of 86-94% & 81-87%
Diagn Microbiol Infect Dis. 2009;63(2):182.

HIV testing

Patients with suspected or proven TB should undergo HIV testing
Interferon-Gamma Release Assays

Diagnostic tools for latent tuberculosis infection
 Measure T cell release of IFN-r following stimulation by antigens
specific to M. tuberculosis (Specificity >95 % for diagnosis of LTBI)

Type of assay
 Quantiferon-TB Gold In-Tube® (Cellestis)
 T-SPOT.TB® (oxford immunotec)

Superial to TST
 Not affected by BCG vaccination status

Limitation
 IGRAs cannot distinguish between latent infection and active
TB disease
Interferon-Gamma Release Assays
Treatment

In general all patients should receive antimycobacterial therapy.

Choice of therapy

Recommended duration for HIV (-) adults is 6 mo.

2 mo.
 Rifampicin, isoniazid, ethambutol, & pyrazinamide

Followed by 4 mo.
 Rifampicin, isoniazid, ethambutol
Infect and Chemother 36 (Suppl2):S124-31, 2004.
Treatment

Longer duration of therapy also may be appropriate

HIV infection with evidence of suboptimal response

Intolerable first line medications

Infection due to resistant organisms
Am J Respir Crit Care Med. 2003;167(4):603.
Treatment

Response to therapy


TB lymphadenitis tends to respond slowly to effective treatment.
Paradoxical reaction

Increase in LN size and/or enlargement of additional LNs during or after
cessation of treatment

Due to an immune response to dying M. tuberculosis organisms
Treatment

Paradoxical reaction - continued

Clinical manifestation


LN enlargement (12 %), fluctuance (11 %), erythema and/or
spontaneous discharge (7 %). Constitutional symptoms are rare
The differential diagnosis


Treatment failure
• Resistance
• Non-comliance
Another infection
Treatment

Paradoxical reaction - continued

FNA for AFB and culture may be pursued to distinguish between a
paradoxical reaction and treatment failure.

Management - no consensus guidelines
 Aspiration, surgical excision, or a trial of NSAIDs, corticosteroids,
Infliximab

Course
 In one study of 235 HIV (-) patients. spontaneous resolution
of paradoxical lymph node enlargement occurred in 56 % of cases
J Infect 2009;59:56-61.
Treatment

Relapse rates

Relapse rates of up to 3.5 percent

7 to 11 % of patients have residual lymph nodes present at the end of
the treatment course
Leukocytoclastic vasculitis
 Infections (including TBc, HIV)
 Medications
 Connective tissue diseases
 Malignancy