Mycobacterium tuberculosis Lymphadenitis



Mycobacterium tuberculosis Lymphadenitis


Tariq Muzzafar, MBBS










Scanning electron micrograph of M. tuberculosis. The bacterium ranges from 2-4 µm long and 0.2-0.5 µm wide. (Courtesy J. Carr, CDC Public Health Image Library, #9997.)






Thin section transmission electron micrograph demonstrates M. tuberculosis bacilli. (CDC Public Health Image Library, #8433.)


TERMINOLOGY


Abbreviations



  • Acid-fast bacilli (AFB)


  • Tuberculosis (TB)


Definitions



  • Lymphadenitis caused by infection with Mycobacterium tuberculosis


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Mycobacterium tuberculosis


Immunocompetent Patients



  • Reactivation of disease at site seeded during primary infection by hematogenous route


  • Infection of tonsils, adenoids, and Waldeyer ring


  • Abdominal involvement may occur via ingestion of milk or sputum infected with M. tuberculosis


Immunocompromised Patients



  • Human immunodeficiency virus (HIV) infection most common


  • Reactivation of latent infection


  • Part of generalized infection, miliary dissemination



    • Greater mycobacterial load than immunocompetent patients


CLINICAL ISSUES


Epidemiology



  • Incidence



    • ˜ 40% of peripheral lymphadenopathy in developing world


    • Prevalence of TB lymphadenitis in children ≤ 14 years in rural India: 4.4/1,000


    • Lymphadenitis is most common form of extrapulmonary tuberculosis (5-10% of cases)


    • In developed countries, most cases occur in immigrants and travelers to endemic areas



      • Immigrant populations mostly originate from Southeast Asia and Africa


    • In USA, 20% of TB cases are extrapulmonary



      • ˜ 30% of these cases present with lymphadenitis


    • M. tuberculosis is common in HIV-positive individuals



      • Part of pulmonary or disseminated disease


      • Most extrapulmonary TB cases occur with CD4 counts ≤ 100 cells/µL


  • Age



    • Historically, common in children


    • At present, children affected predominantly in developing countries


    • Peak age in developed countries: 20-40 years


  • Gender



    • M:F ratio = 1:2


  • Ethnicity



    • Asian Pacific Islanders more susceptible


Presentation



  • Characteristically, multiple lymph nodes (LNs) involved


  • 90% involve superficial LNs in head and neck region



    • Anterior and posterior cervical (most common)


    • Supraclavicular, submandibular, preauricular, submental also involved


  • Other LNs: Axillary, inguinal, mesenteric, mediastinal, and intramammary


  • Isolated intraabdominal LNs can be involved



    • Periportal, peripancreatic, and mesenteric


  • Generalized lymphadenopathy and hepatosplenomegaly in 5%


  • Painless progressive swelling in neck


  • Parabronchial and paratracheal involvement can lead to airway compromise



  • 5% of children develop lymphadenopathy within 6 months of infection


  • In adults, TB represents reactivation of previous infection


  • Up to 1/3 of patients report previous or family history of TB


  • LN on physical examination



    • Firm, rubbery, discrete, and nontender


    • May be swollen and tender due to secondary bacterial infection


  • Ulcer &/or sinus tract formation in 10%


Laboratory Tests



  • Tuberculin skin test (TST)



    • Positive in 90% of cases with TB lymphadenopathy


    • May be negative in HIV-positive patients with TB


  • Interferon-γ release assays



    • Measure in vitro T-cell interferon-γ release in response to 2 unique antigens



      • Sensitivity in active TB: 75-90%


      • Highly specific for M. tuberculosis


      • Negative in prior BCG vaccination and in sensitization to nontuberculous mycobacteria


      • Cannot distinguish between latent and active tuberculosis


    • 2 widely studied tests



      • Enzyme-linked immunospot (ELISpot) (T-SPOT.TB; Oxford Immunotec; Oxford, UK)


      • Enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold; Cellestis; Chadstone, VIC; Australia)


    • For diagnosis of latent infection



      • Sensitivity of ELISA similar to TST


      • ELISpot more sensitive


  • Direct staining



    • Carbolfuchsin stains (Ziehl-Neelsen stain; Kinyoun stain) highlight AFB



      • AFB are bright red against blue or green background, depending on counterstain


      • Must be scanned under oil-immersion


      • Time consuming due to limited size of field viewed at 1 time


    • Fluorochrome stain (auramine O, with or without rhodamine)



      • Scanning quicker since slides can be scanned at 25x objective


      • Confirmation may require 40x objective


      • Bacteria bright yellow (auramine) or orange-red (rhodamine) against dark background


  • Microbiological culture



    • Loewenstein-Jensen (L) medium



      • Less sensitive


      • Recommended only for chromogenic studies and biochemical tests


    • Middlebrook 7H10 and 7H11 agar medium used for isolation and susceptibility testing


    • Automated Radiometric Detection Systems: BACTEC 460 (BD Diagnostic Systems; Sparks, MD; USA)


    • Automated Nonradiometric Detection Systems



      • MGIT 960 (BD Diagnostic Systems)


      • MB/BacT System (BioMerieux; Durham, NC; USA)


      • BACTEC MYCO/F lytic blood culture bottle (BD Diagnostic Systems)


      • ESP Culture System II (TREK Diagnostic Systems, Inc.; Cleveland, OH; USA)


  • Gas-liquid and high-performance liquid chromatography



    • Useful in culture confirmation


  • Molecular diagnosis



    • Uses



      • Culture confirmation of isolates


      • Identification of isolates


      • Direct detection


      • DNA fingerprinting


      • Strain-typing


    • Quicker identification than by traditional methods


    • 2 amplification-based methods FDA approved in USA



      • Amplicor M. tuberculosis PCR assay (Roche Diagnostics; Indianapolis, IN; USA)



      • Amplified M. tuberculosis Direct Test (Gen-Probe Incorporated; San Diego, CA; USA)


    • Home-brew PCR, including real-time PCR assays, have been developed but need validation by individual laboratories


    • DNA sequencing can make rapid and accurate identification


    • Strain-typing has been used in detection of drug resistance


Treatment



  • Surgical approaches



    • Needed in minority of patients


    • Indications: Failure of antimicrobial chemotherapy, pressure effect


    • Excisional biopsy preferred since incisional biopsy may result in sinus tract formation


  • Drugs



    • All patients treated with antituberculous agents


    • Treatment may be started prior to culture confirmation



      • Particularly when pathologic features suspicious or in high-risk subject


    • Adults: 6 months of isoniazid, rifampin, pyrazinamide, and ethambutol


    • Children: 2 months of isoniazid, rifampin, and pyrazinamide, plus 2 months of isoniazid and rifampin


    • Mediastinal lymph node involvement treated with same regimen as lung involvement


Prognosis



  • Antimicrobial therapy curative; relapse rates of up to 3.5%


  • In 30% of patients after beginning therapy



    • Paradoxical increase in LN size


    • New enlarged LNs may develop


    • Mechanism is immune response to mycobacterial killing


    • Must be differentiated from relapse


  • HIV-positive patients who begin HAART may develop immune reconstitution inflammatory syndrome with worsening lymphadenopathy


  • Residual palpable LNs after completion of therapy may be present in 5-30% of patients


  • Retreatment generally considered to be unnecessary if



    • Cultures are negative


    • Compliance with treatment is documented


IMAGE FINDINGS


General Features



  • Not definitively diagnostic of TB lymphadenitis


Radiographic Findings



  • 80% of children and 20% of adults show evidence of recent or active tuberculosis in lungs

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mycobacterium tuberculosis Lymphadenitis
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