55. Lymphadenopathy

• Tuberculosis

• Syphilis

• Lymphogranuloma venereum

• Staphylococcal/streptococcal skin infections

• Lyme disease

• Typhoid fever

• Cat-scratch disease

• Brucellosis

• Tularemia

• Rickettsial scrub typhus

• HIV

• Epstein-Barr Virus (EBV)

• Cytomegalovirus (CMV)

• Adenovirus

• Herpes zoster

• Rubella

• Fungal: aspergillosis, candidiasis, cryptococcus

• Parasitic

  • Helminthic: schistosomiasis, lymphatic filariasis

  • Protozoal: toxoplasmosis, malaria, visceral leishmaniosis

• Leukemias (e.g., acute lymphoblastic leukemia)

• Lymphomas (e.g., Hodgkin lymphoma)

• Kaposi sarcoma

• Metastases

• Systemic lupus erythematosus

• Rheumatoid arthritis, Still disease

• Sjogren syndrome

• Dermatomyositis

• Medication

  • Allopurinol

  • Antibiotics (e.g., penicillins, trimethoprim/sulfamethoxazole)

  • Antihypertensives (e.g., hydralazine, captopril)

• Other: Kawasaki disease, histiocytosis X, sarcoidosis, Castleman disease

• Lymph node structure and function: See “Lymph nodes” in “Lymphatic system.”

• Pathophysiology of lymph node enlargement

  • Lymphadenitis: proliferation and formation of immune cell clusters as a result of localized/systemic inflammation (most common cause of lymphadenopathy)

  • Malignant proliferation of cells that have settled in the affected lymph node (e.g., lymphoma cells or metastases of solid tumors)

  • Storage diseases: accumulation of metabolites (e.g., ceramide trihexoside in the case of Fabry disease)

  • Drug-induced: Certain drugs such as phenytoin, allopurinol, atenolol, hydralazine, and antibiotics such as penicillin or cephalosporins can induce generalized lymphadenopathy.

• Duration of lymph node swelling

• Symptoms:

  • Pain or tenderness: suggests benign inflammatory process

  • Acute fever, skin changes (common in viral infections)

  • Signs of inflammation in the lymph node drainage area

  • B symptoms

• Underlying diseases

• Medications

• Travel history

• Social and sexual history

• Animal contacts

• General: assess for both local inflammatory processes (e.g., enlarged neck lymph nodes due to tonsillitis) and signs of systemic disease (e.g., hepatomegaly and splenomegaly)

• Peripheral lymph node examination:

  • Inspection

    • Visible enlargement: Lymph nodes should not be visible in healthy individuals, as they are only a few millimeters in diameter.

    • Local erythema, swelling, or lesion

  • Palpation

    • Gentle palpation using fingertips

    • The area to be examined should be relaxed to facilitate differentiation of the lymph node from the surrounding tissue (e.g., muscles, tendons).

    • Evaluation of size and level of pain consistency, and fixation.

• Acute, painful (localized or systemic) lymph node enlargement potentially associated with localized inflammation or infection (e.g., herpes labialis, pharyngitis).

  • In general, no further diagnostic testing is necessary.

  • If diagnosis and treatment decision is unclear, test for:

    • Inflammatory markers (e.g., CRP, ESR) in the case of severe inflammatory processes

    • If systemic infection is suspected: detection of pathogen (e.g., Monospot test in EBV, RPR/VDRL in syphilis, ELISA in HIV)

In general, no further diagnostic testing is necessary

This type of lymph node enlargement is a remnant of previous infections and may frequently be observed in the cervical region of healthy individuals.

• Painless, slowly progressing lymph node enlargement (generalized or localized) or in any other case of unexplained lymph node enlargement suggestive of malignant disease

  • Laboratory tests:

    • CBC, liver function tests and BUN/creatinine

    • Blood smear, LDH, uric acid

    • If suspected, diagnostic tests for tuberculosis

  • Imaging

    • Sonography: can help to characterize lymphadenopathy

      • Physiological lymph nodes or lymph node changes due to inflammation: sharply delimited, oval shape, presence of fatty hilum

      • Malignant lymph nodes: round , irregular, blurred margins, loss of fatty hilum

      • Allows for differentiation from other pathologic conditions (e.g., abscesses, cysts)

    • Chest x-ray: unexplained generalized lymphadenopathy requires evaluation of the hilar and mediastinal lymph nodes, especially if tuberculosis is suspected

    • If necessary, CT/MRI may be performed to better visualize lymph nodes.

  • Lymph node biopsy and histological analysis: if cancer is suspected or localized or generalized lymphadenopathy does not resolve in 3–4 weeks and imaging has been inconclusive