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Lymph Node Enlargement

Causes of generalized lymphadenopathy

Editors Note:
Generalized lymphadenopathy is always a puzzling entity. The presence of fever may suggest an infectious cause or lymphoma. The presence of rash may suggest an infectious or autoimmune process. Request a full blood count to exclude hematological causes. A lymph node biopsy is needed if the picture is suggestive of lymphoma.

Essentially 5 broad etiologic categories lead to lymph node enlargement (Ghirardelli, 1999).

  • An immune response to infective agents (eg, bacteria, virus, fungus)
  • Inflammatory cells in infections involving the lymph node
  • Infiltration of neoplastic cells carried to the node by lymphatic or blood circulation (metastasis)
  • Localized neoplastic proliferation of lymphocytes or macrophages (eg, leukemia, lymphoma)
  • Infiltration of macrophages filled with metabolite deposits (eg, storage disorders)


  • Infectious mononucleosis.
  • Cytomegalovirus may cause a syndrome similar to infectious mononucleosis.
  • TB: In a child with tuberculosis, generalized lymphadenopathy may indicate hematogenous spread of tubercle bacilli.
  • Brucellosis may accompany chronic or intermittent lymphadenopathy.
  • Salmonella infection can correspond to generalized adenopathy.
  • Tularemia may be accompanied by regional or generalized adenopathy, most commonly cervical, with local tenderness, pain, and fever.
  • Bubonic plague is caused by Y pestis.

Immunologic or connective tissue disorders

  • Juvenile rheumatoid arthritis should be considered in unexplained fever and persistent lymphadenopathy in a child.
  • Serum sickness can correspond with generalized tender lymphadenopathy.
  • Chronic graft versus host disease.

Primary disease of lymphoid or reticuloendothelial tissue

  • Acute leukemia
  • Hodgkin disease
  • Non-Hodgkin lymphoma
  • Lymphosarcoma
  • Nonendemic Burkitt tumor
  • Nasopharyngeal rhabdomyosarcoma
  • Neuroblastoma
  • Reticulum cell sarcoma
  • Malignant histocytosis or histocytic lymphoma
  • Thyroid carcinoma, chronic lymphocytic thyroiditis
  • Histiocytosis X
  • Benign sinus histiocytosis
  • Angioimmunoblastic or immunoblastic lymphadenopathy
  • Chronic pseudolymphomatous lymphadenopathy (chronic benign lymphadenopathy)

Immunodeficiency syndromes

  • Acquired immunodeficiency syndrome
  • Chronic granulomatous disease of childhood
  • Hyperimmunoglobulin E (Job) syndrome

Metabolic and storage diseases

  • Gaucher disease
  • Histiocytosis X
  • Cystinosis
  • Niemann-Pick disease

Hematopoietic diseases

  • Thalassemia
  • Congenital hemolytic anemia
  • Autoimmune hemolytic anemia
  • Sickle cell anemia

Other disorders

  • Sarcoidosis demonstrate either generalized or hilar lymphadenopathy.
  • Drug: mesantoin, hydantoin use may produce lymphadenopathy as an adverse effect.
  • Castleman disease or benign giant lymph node hyperplasia may cause lymphadenopathy in the mediastinum, abdomen, neck, or axilla.
  • Kawasaki disease


1. Ghirardelli ML, Jemos V, Gobbi PG: Diagnostic approach to lymph node enlargement. Haematologica 1999 Mar; 84(3): 242-7.

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