Lymphadenopathy

Differential Diagnosis

• Neoplasm
  • Hematologic: lymphoma, leukemia
  • Solid tumour: squamous cell cancer of the head and neck
  • Metastasis
• Infection
  • Viral: HIV, EBV, HSV, CMV, mumps, measles, rubella, hepatitis B, dengue
  • Bacterial
    • Regional: streptococcal pharyngitis, skin and soft tissue infection, tularemia, plague, cat scratch disease, diphtheria, chancroid, rat bite fever, Lyme disease
    • Generalized: brucellosis, leptospirosis, lymphogranuloma venereum, typhoid fever, secondary syphilis
  • Mycobacterial: tuberculosis, non-tuberculous mycobacteria
  • Fungal: histoplasmosis, coccidiomycosis, cryptococcosis
  • Parasitic: toxoplasmosis, leishmaniasis
• Non-neoplastic lymphoproliferative disorders
  • Angioimmunoblastic lymphadenopathy with dysproteinemia
  • Autoimmune lymphoproliferative disease
  • Rosai-Dorfman disease
  • Hemophagocytic lymphohistiocytosis
• Immune-mediated
  • Serum sickness
  • Drug reactions: allopurinol, atenolol, captopril, carbamazepine, cephalosporins, ethosuximide, gold, hydralazine, imatinib, lamotrigine, penicillin, phenytoin, primidone, pyrimethamine, quinidine, sulfonamides, sulindac
  • IgG4-related disease
• Endocrine and metabolism
  • Addison disease
  • Lipid storage disease
• Other
  • Sarcoidosis
  • Multicentric Castleman disease
  • Amyloidosis
  • Histiocytosis
  • Chronic granulomatous disease
  • Kikuchi disease
  • Kawasaki disease
  • Inflammatory pseudotumor
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Still disease
  • Dermatomyositis
  • Eosinophilic granulomatosis with polyangiitis

Differential by Location

• Cervical: EBV, CMV, toxoplasmosis, tuberculosis or non-tuberculous mycobacteria (if more chronic with less tenderness), cat scratch disease, metastatic head-and-neck cancer
• Preauricular: conjunctivitis, Parinaud oculoglandular syndrome (cat scratch disease)
• Postauricular: parietotemporal scalp infection, rubella
• Suboccipital: posterior scalp infection
• Supraclavicular: malignancy (especially intraabdominal malignancy)
• Axillary: infections of the arm (including cat scratch disease), malignancy (including breast and metastasis), foreign body reaction to silicone breast implants
• Epitrochlear: infections of the forearm or hand, lymphoma, sarcoidosis, tularemia, and secondary syphilis
• Inguinal: trauma, lower limb infections, STIs (chancroid, LGV, herpes, syphilis), malignancy (including skin on legs, cervix, vulva, skin on trunk, rectum/anus, ovary, penis)
• Generalized:
  • More common: HIV, tuberculosis, mononucleosis, lupus, medications, sarcoidosis, lymphoma
  • Less common: Castleman disease, Kikuchi disease, Kawasaki disease, angioimmunoblastic T-cell lymphoma, inflammatory pseudotumour, amyloidosis, Kimura disease, progressive transformation of germinal centres, Fosai-Dorfman disease, IgG4-related disease

Causes by risk factor

• Animal exposure
  • Cat: cat-scratch disease, toxoplasmosis
• Undercooked meat: toxoplasmosis
• Tick bite: Lyme disease, tularemia
• Tuberculosis: tuberculous adenitis
• Transfusion or transplant: CMV, HIV
• High-risk sexual behaviour: HIV, syphilis, HSV, CMV, hepatitis B
• Intravenous drug use: HIV, endocarditis, hepatitis B
• Occupational
  • Hunters and trappers: tularemia
  • Fishermen and butchers: erysipeloid
• Travel-related
  • Arizona, southern California, New Mexico, and western Texas: coccidiomycosis
  • Southwestern US: plague
  • Southeastern or central US: histoplasmosis
  • Southeast Asia, India, or northern Australia: scrub typhus
  • Central or west Africa: African trypanosomiasis
  • Central or South America: American trypanosomiasis
  • East Africa, Mediterranean, China, or South/Central America: leishmaniasis
  • Mexico, Peru, Chile, India, Pakistan, Egypt, or Indonesia: typhoid fever