Lymphadenopathy is very common among HIV-infected individuals and may occur at any stage of HIV infection. It may be the first indication of a serious local or systemic condition, and it should be evaluated carefully. Rapid enlargement of a previously stable lymph node or a group of nodes requires evaluation to identify the cause and to determine whether treatment is needed. Similarly, nodes that are abnormal in consistency, tender to palpation, fluctuant, asymmetrical, adherent to surrounding tissues, or accompanied by other symptoms should be evaluated promptly.

Lymphadenopathy may be generalized or localized and usually is characterized by lymph nodes that are >1 cm in diameter. A multitude of conditions can cause lymphadenopathy, including HIV itself, opportunistic or other infections, and malignancies. The likely causes of lymphadenopathy, and thus the diagnostic workup, will depend in part on the patient's degree of immunosuppression. The risk of opportunistic and certain malignant conditions increases at lower CD4 cell counts (see chapter Risk of HIV Progression/Indications for ART).

Many individuals with primary HIV infection (see chapter Early HIV Infection) have generalized lymphadenopathy that may resolve or may persist for months to years. If lymphadenopathy of >2 cm in size occurs in two or more noncontiguous sites and persists for more than 3 months, and if appropriate evaluation reveals no other cause, the patient is diagnosed with persistent generalized lymphadenopathy (PGL). PGL usually is caused by follicular hyperplasia from chronic HIV infection. Antiretroviral therapy (ART) should be initiated or optimized, but as long as enlarged nodes are stable in number, location, and size, persons with PGL require no specific management other than monitoring of nodes at each physical examination. Changes in the character of the lymph nodes should prompt further evaluation. Rapid involution of PGL may occur with advanced HIV disease and is a poor prognostic sign.

S: Subjective

The patient complains of new, worsening, or persistent glandular swellings in the neck, axilla, groin, or elsewhere.

Ascertain the following during the history:

  • Symptoms that accompany the lymphadenopathy, particularly constitutional symptoms such as fever, sweats, fatigue, and unintentional weight loss
  • Localized symptoms or conditions that involve areas of the body with lymphatic drainage into the area of abnormal lymph nodes (e.g., in the case of axillary lymphadenopathy, ask about breast masses and skin conditions or trauma involving the arm)
  • A full review of systems
  • HIV-related or other malignancies, opportunistic illnesses
  • Recent travel, country or region of origin, disease exposures (e.g., tuberculosis [TB], sexually transmitted diseases [STDs]), and risk behaviors (e.g., injection drug use)
  • Recent initiation of ART (may indicate immune reconstitution inflammatory syndrome [IRIS])
  • Trauma or injury (including cat scratches)
  • Exposure to household pets
  • Current medications

O: Objective

  • Review recent CD4 cell counts and HIV viral load measurements.
  • Check vital signs.
  • Perform a complete examination of lymph nodes, including the cervical, submandibular, supraclavicular, axillary, epitrochlear, and inguinal sites. Document the location, size, consistency, mobility, and presence or absence of tenderness of all abnormal nodes. In cases of localized lymphadenopathy, examine the area drained by the node.
  • Check for hepatosplenomegaly.
  • Perform a focused examination (e.g., lung, breast, skin, genitals) to identify signs of local or systemic illness.

A: Assessment

The differential diagnosis of lymphadenopathy in HIV-infected patients depends in part on the degree of immunosuppression. For further information, see chapter Risk of HIV Progression/Indications for ART.

Infectious Causes

Generalized lymphadenopathy

  • HIV infection, including PGL
  • Mononucleosis; Epstein-Barr virus
  • Mycobacterium avium complex
  • TB
  • Cytomegalovirus
  • Secondary syphilis
  • Toxoplasmosis
  • Histoplasmosis, other fungal diseases
  • Bartonella infection
  • Hepatitis B
  • Lyme disease
  • Widespread skin infections
  • IRIS involving various infections
  • Follicular hyperplasia
  • Castleman disease

Localized lymphadenopathy

  • Any of the above
  • Oropharyngeal and dental infections
  • Cellulitis or abscesses
  • TB (scrofula)
  • Chancroid
  • Chlamydia (lymphogranuloma venereum [LGV])
  • Other STDs

Neoplastic Causes

  • Lymphoma
  • Acute and chronic lymphocytic leukemias
  • Other malignancy; metastatic cancer
  • Kaposi sarcoma

Other Causes

  • Reactive process (benign)
  • Sarcoidosis
  • Hypersensitivity reaction to medications
  • Serum sickness
  • Rheumatoid arthritis

P: Plan

Diagnostic Evaluation

After the history and physical examination, the cause of lymphadenopathy may be clear and further diagnostic testing may not be necessary. If the cause of the lymphadenopathy is still uncertain, perform diagnostic testing as indicated by the patient's presentation. This may include the following tests:

  • CD4 count (with or without HIV viral load), to determine the risk of opportunistic illnesses
  • Complete blood count with differential; liver function tests; urinalysis
  • Chest X-ray
  • TB screening (tuberculin skin test [TST] or interferon-gamma release assay [IGRA])
  • Syphilis screening (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL] test)
  • Blood cultures, if patient is febrile (bacterial, mycobacterial, and fungal, as indicated)
  • Testing for specific infections if suspected (e.g., Bartonella, LGV)

If a node is large, fixed, nontender, or otherwise worrisome, or if the diagnosis is unclear after initial evaluation, fine-needle aspiration (FNA) biopsy may provide a diagnosis. If FNA is nondiagnostic (false-negative results are relatively common), obtain an excisional biopsy for definitive evaluation. Biopsy specimens should be sent for bacterial, mycobacterial, and fungal cultures; acid-fast staining for mycobacteria; and cytologic examination.

If a node is large, inflamed, tender, or fluctuant, and a bacterial infection is suspected, consider initiating empiric antibiotic treatment and monitoring the patient over the course of 1-2 weeks. If the node does not respond to antibiotic treatment or the patient becomes more symptomatic, arrange for FNA or open biopsy to establish the diagnosis.


Treatment will depend on the cause of lymphadenopathy. Refer to section Comorbidities, Coinfections, and Complications or to OI management guidelines as appropriate. In the case of HIV-related lymphadenopathy, ART may be effective.

Patient Education

  • Lymphadenopathy may come and go throughout the course of HIV infection, but it may be a sign of a serious condition.
  • Advise patients to notify their care provider if lymph nodes increase in size or change in character.


  • Boswell SL. Approach to the Patient with HIV Infection. In: Goroll AH, Mulley AG, eds. Principles of Primary Care, 5th ed. Philadelphia: JB Lippincott, 2005;78-91.
  • Kocurek K, Hollander H. Primary and Preventive Care of the HIV-Infected Adult. In: Sande MA, Volberding PA, eds. Medical Management of AIDS, 6th ed. Philadelphia: WB Saunders, 1999;125-126.
  • Simon HB. Evaluation of Lymphadenopathy. In: Goroll AH, Mulley AG, eds. Principles of Primary Care, 5th ed. Philadelphia: JB Lippincott, 2005;73-77.