What are the causes of lymphadenopathy?

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Causes of Lymphadenopathy

Lymphadenopathy is most commonly caused by infections, but can also result from malignancies, autoimmune disorders, immunodeficiency syndromes, and medication reactions.

Infectious Causes

Localized Lymphadenopathy

  • Bacterial infections:
    • Streptococcal/staphylococcal infections (cervical nodes)
    • Cat scratch disease (regional lymphadenopathy)
    • Tuberculosis (cervical, supraclavicular nodes)
    • Sexually transmitted infections:
      • Syphilis (inguinal, generalized in secondary stage) 1
      • Lymphogranuloma venereum (inguinal/femoral lymphadenopathy) 1
      • Granuloma inguinale (inguinal nodes) 1

Viral Infections

  • HIV infection (generalized lymphadenopathy) 1
  • Epstein-Barr virus (cervical lymphadenopathy)
  • Cytomegalovirus
  • Viral hepatitis

Other Infectious Causes

  • Fungal infections
  • Parasitic infections (e.g., toxoplasmosis)

Malignant Causes

  • Lymphoma (Hodgkin's and non-Hodgkin's)
  • Leukemia
  • Metastatic cancer:
    • Testicular cancer (retroperitoneal nodes) 2
    • Breast cancer (axillary nodes)
    • Head and neck cancers (cervical nodes)
    • Lung cancer (hilar, mediastinal nodes)

Supraclavicular, popliteal, and iliac lymphadenopathy should always raise suspicion for malignancy 3

Autoimmune/Inflammatory Disorders

  • Sarcoidosis (hilar and mediastinal lymphadenopathy) 1
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Autoimmune lymphoproliferative syndrome (ALPS) (chronic non-malignant lymphadenopathy) 1

Immunodeficiency Disorders

  • Primary immunodeficiency disorders 1:

    • Common variable immunodeficiency (15-20% have lymphadenopathy) 4
    • Activated phosphoinositide 3-kinase delta syndrome 4
    • Combined immunodeficiency disorders 4

  • Secondary immunodeficiency:

    • HIV/AIDS (persistent generalized lymphadenopathy) 1
    • Iatrogenic immunosuppression

Medication-Related Causes

  • Phenytoin
  • Allopurinol
  • Antibiotics (particularly sulfonamides)
  • Hydralazine

Risk Factors for Malignant Lymphadenopathy

  • Age >40 years 3, 5
  • Male sex 3
  • White race 3
  • Supraclavicular location 3, 5
  • Firm, fixed nodes 5
  • Duration >2 weeks 5
  • Systemic symptoms (fever, night sweats, weight loss) 3

Special Considerations in HIV Patients

  • Non-malignant causes of lymphadenopathy are more common in patients with higher viral loads and lower CD4+ T-cell counts 1, 2
  • Both infectious (opportunistic) and malignant causes should be considered 1, 2
  • Lymphadenopathy may be due to HIV infection itself, opportunistic infections, or malignancies 1

Diagnostic Approach

When evaluating lymphadenopathy, consider:

  1. Distribution: Localized (75% of cases) vs. generalized (25% of cases) 6
  2. Duration: Acute (<2 weeks) vs. persistent (>2 weeks)
  3. Associated symptoms: Fever, weight loss, night sweats
  4. Physical characteristics: Size, consistency, tenderness, mobility
  5. Location: Supraclavicular nodes are highly concerning for malignancy

For unexplained lymphadenopathy without concerning features, observation for one month is reasonable before proceeding to specific testing or biopsy 5.

Remember that while lymphadenopathy can be concerning, most cases in primary care settings are benign, with malignancy rates as low as 1.1% 5.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Retroperitoneal Lymphadenopathy Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Lymphadenopathy and malignancy.

American family physician, 2002

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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