Our step-wise approach to the evaluation and initial management of cervical lymphadenopathy in children that does not appear to be caused by an infection

1. History and examination to look for obvious causes or worrisome features*

2. Refer children with worrisome features for early biopsy^¶

3. Evaluate and treat causes that appear obvious based on initial evaluation

4. When the cause remains uncertain after the initial evaluation:

Lymph node <2 cm (0.8 inches) in longest diameter:
- Observe for 10 to 14 days:
  - Regression in size – No additional evaluation or therapy
  - No regression in size:
    - Obtain CBC/differential; ESR/CRP; serology for EBV, CMV, and HIV; evaluate for Kawasaki disease and other uncommon causes of cervical lymphadenopathy as indicated by the history and examination^Δ
    - Provide referral or treatment as indicated based upon results
Lymph node ≥2 cm (0.8 inches) in longest diameter
- Obtain CBC, ESR/CRP, and chest radiograph
  - Worrisome features* – Refer for biopsy
  - No worrisome features and cause remains uncertain (including possible occult infection) – Perform TST and provide 10- to 14-day trial of antibiotics^◊
    - TST positive – Additional testing may be necessary to establish diagnosis of tuberculosis or nontuberculous mycobacteria
    - TST negative and lymph node regresses in size – No additional evaluation or therapy
    - TST negative and lymph node does not regress:
      - Obtain serology for EBV, CMV, and HIV; evaluate for Kawasaki disease and other uncommon causes of cervical lymphadenopathy as indicated by the history and examination^Δ
      - Provide referral or treatment as indicated based upon results

5. Obtain biopsy^¶ after 4 weeks if the diagnosis remains uncertain and the lymph node has not regressed in size or there is no response to antimicrobial therapy/broadened antimicrobial therapy^§

CBC: complete blood count; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; EBV: Epstein-Barr virus; CMV: cytomegalovirus; TST: tuberculin skin test; CA-MRSA: community-associated methicillin-resistant Staphylococcus aureus.
* Worrisome features include: systemic symptoms (fever >1 week, night sweats, weight loss [>10% of body weight]), fixed nontender nodes in the absence of other symptoms; abnormal chest radiograph (eg, mediastinal mass or hilar adenopathy), abnormal CBC/differential, lack of upper respiratory tract symptoms, lymph nodes >2 cm in diameter that have increased in size from baseline or have not responded to 2 weeks of antibiotic therapy, and persistently elevated ESR/CRP or rising ESR/CRP despite antibiotic therapy.
¶ Excisional biopsy is preferred; fine-needle aspirate biopsies usually are inadequate for evaluation of pediatric malignancies or infiltrative diseases.
Δ Refer to UpToDate topic on evaluation of peripheral lymphadenopathy in children for details.
◊ Empiric antibiotic therapy should include coverage for common pathogens such as group A Streptococcus and Staphylococcus aureus (eg, clindamycin in areas with a high prevalence of CA-MRSA or a first-generation cephalosporin [eg, cephalexin] or amoxicillin-clavulanate in areas with a low prevalence of CA-MRSA). If the patient's systemic symptoms (eg, fever) do not improve within 72 hours or the lymph node increases in size (at any point during treatment), we broaden the antimicrobial coverage to include coverage for common pathogens that were not included initially (eg, CA-MRSA, Bartonella henselae [for children with exposure to cats or kittens]). Refer to UpToDate topic on evaluation of peripheral lymphadenopathy in children for details.
§ For lymph nodes <2 cm (0.8 inches) in diameter, continued observation may be reasonable if there are no worrisome features.

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Our step-wise approach to the evaluation and initial management of cervical lymphadenopathy in children that does not appear to be caused by an infection