Lymphadenopathy: Causes, Diagnosis, and Differential Approach
Lymphadenopathy is a condition characterized by hyperplasia (enlargement) of lymph nodes. This term serves as a preliminary diagnosis that requires further clarification through clinical and laboratory evaluation, as well as dynamic observation. The main causes of lymph node hyperplasia in children can be categorized as follows:
- Infectious causes, which may be viral, bacterial, fungal, or parasitic in nature.
- Malignancy-associated causes, including leukemia, lymphoma, and metastases from solid tumors.
- Immunological disorders, such as hemophagocytic lymphohistiocytosis, Langerhans cell histiocytosis, Kawasaki syndrome, and autoimmune diseases like autoimmune lymphoproliferative syndrome, systemic lupus erythematosus, juvenile idiopathic arthritis, sarcoidosis, and hereditary immunodeficiencies.
- Inherited metabolic disorders (storage diseases), e.g., Niemann-Pick disease, Gaucher disease.
- Drug-induced lymphadenopathy, associated with phenytoin, hydralazine, procainamide, isoniazid, allopurinol, and dapsone.
Key Diagnostic Considerations
A crucial part of differential diagnosis involves answering several key questions:
- Are the lymph nodes truly enlarged?
- Is the condition localized or generalized?
- Is the process progressive over time?
- Are there indications of an infectious etiology?
- Is there suspicion of a malignant process?
For example, supraclavicular lymphadenopathy is always considered suspicious for malignancy.
In pediatric practice, the most common challenge is distinguishing infectious from malignant causes of lymph node hyperplasia. A stepwise approach is essential, as post-infectious lymph node enlargement can sometimes be mistaken for pathology.
Normal Pediatric Lymph Nodes (Age <10 years):
- Palpable in the cervical, submandibular, and inguinal regions
- Size: <1 cm (submandibular <2 cm)
- Soft-elastic consistency, mobile, non-tender
Infectious Lymphadenopathy
In most cases, lymphadenopathy in children has an infectious origin. Both local and systemic infections can lead to lymph node enlargement.
Signs Suggesting an Infectious Cause:
- Visible entry site for infection (dental issues, tonsillitis, oral ulcers, skin lesions, excoriations from allergic dermatitis).
- Localized pain/redness (hyperemia).
- History of systemic childhood infections (e.g., rubella, scarlet fever).
Common Patterns in Children:
- Bilateral cervical lymphadenopathy is typically viral (adenovirus, cytomegalovirus, Epstein-Barr virus, HHV-6, HIV) or may result from streptococcal pharyngitis.
- Acute unilateral cervical lymphadenopathy is more common with staphylococcal infections, with tonsils as the primary infection site.
- Subacute (chronic) lymphadenopathy may indicate cat scratch disease, atypical mycobacteria, or tularemia (often overlooked but still reported in Europe).
Diagnostic Workup
Initial evaluation includes:
- Complete blood count (CBC) + ESR
- C-reactive protein (CRP)
- Ultrasound (US) of lymph nodes
Both blood tests and ultrasound findings help differentiate inflammatory from other causes.
Antibiotic Therapy as a Diagnostic Tool
One step in the differential diagnosis algorithm is empirical antibiotic therapy, particularly for cervical lymph node hyperplasia of suspected infectious origin. If bacterial, a clear improvement is expected within 10–14 days, classifying the condition as lymphadenitis.
Observational Period
The average follow-up period is two weeks to assess for:
- Regression
- Persistence
- Progression
When to Expand Diagnostic Investigations
If lymph node enlargement does not resolve after antibiotics or has no clear infectious cause, further workup is warranted:
- Lactate dehydrogenase (LDH), ferritin, uric acid (elevations suggest neoplasia).
- Serology/PCR for Epstein-Barr virus, cytomegalovirus, HHV-6, and bacterial causes of chronic lymphadenopathy (Bartonella henselae, Brucella).
- HIV testing if lymphadenopathy persists for >1 month.
- Mantoux test (for tuberculosis screening).
- Ultrasound with Doppler of affected lymph nodes.
- Abdominal ultrasound to assess abdominal lymph nodes.
- Chest X-ray to evaluate intrathoracic lymph nodes.
Red Flags: When to Suspect Malignancy
Special attention is required for:
- Lymph nodes >1.5 cm in diameter, firm, and non-mobile.
- B symptoms (suggestive of lymphoma or systemic disease):
- Profuse night sweats
- Fever >38°C
- Unintentional weight loss >10% over 6 months
These symptoms can indicate tuberculosis, HIV/AIDS, invasive intestinal infections (e.g., amebiasis), or Hodgkin’s lymphoma.
Lymph Node Biopsy
If malignancy is suspected, immediate excisional biopsy is recommended.
Bone Marrow Examination
If lymphadenopathy is accompanied by anemia or thrombocytopenia and autoimmune or inherited immune disorders are excluded, bone marrow aspiration is indicated.
This review highlights common and significant causes of lymphadenopathy, but each case requires individualized diagnostic decisions. Clinical expertise is often more valuable than rigid adherence to algorithms, making experience and clinical judgment essential.
Based on materials from the German Society of Pediatric Oncology and Hematology:
Minisymposium on Pediatric Infectious Diseases (University Hospital Bern, Switzerland, 2012)
Source: Management der Lymphadenitis Minisymposium Infektiologie 25. Oktober 2012
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