Our step-wise approach to the evaluation and initial management of generalized lymphadenopathy in children

1. History and examination to look for obvious causes

2. Early biopsy* of most abnormal node for children with:

Supraclavicular nodes
Massively enlarged nodes (ie, >4 cm [1.6 inches])
Group of nodes with a total diameter >3 cm (1.2 inches)

3. Initial testing typically includes:

CBC with differential, ESR/CRP
LDH
Serology for CMV and EBV
Serology for other viral illnesses as warranted by the history and examination^¶
TST
Chest radiograph

4. Provide treatment or additional evaluation as indicated for conditions that are identified through initial history, examination, and testing

5. When the cause remains uncertain after the initial evaluation, obtain the following second-tier tests if there are indications based on the initial evaluation^¶:

Serology for Bartonella henselae, toxoplasmosis, histoplasmosis, coccidiomycosis, brucellosis, syphilis, HIV, and other viruses
ANA

5. Obtain biopsy* of the most abnormal node within 4 weeks of initial evaluation if:

Any lymph nodes increase in size
There is a lymph node ≥2 cm (0.8 inches) in diameter and either of the following:
- The diagnosis remains uncertain after 4 weeks
- There is no response to therapy as indicated by the findings of initial or second-tier tests

CBC: complete blood count; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; LDH: lactate dehydrogenase; CMV: cytomegalovirus; EBV: Epstein-Barr virus; TST: tuberculin skin test; ANA: antinuclear antibody.
* Excisional biopsy is preferred; fine needle aspirate biopsies usually are inadequate for evaluation of pediatric malignancies or infiltrative diseases.
¶ Refer to UpToDate topic on evaluation of peripheral lymphadenopathy in children for details.

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Our step-wise approach to the evaluation and initial management of generalized lymphadenopathy in children