Approach to peripheral lymphadenopathy: Clinical sciences

Peripheral lymphadenopathy refers to enlarged peripheral lymph nodes that may have an abnormal consistency. Enlarged lymph nodes are generally defined as 1 cm or larger; however, some lymph nodes are considered abnormal if they’re larger than 5 mm, like those in the supraclavicular, epitrochlear, or popliteal regions. The timing of symptom onset and the characteristics of the lymphadenopathy are helpful in distinguishing peripheral lymphadenopathy due to infection or malignancy, as well as immunologic or inflammatory conditions.

If your patient presents with peripheral lymphadenopathy, first perform an ABCDE assessment to determine if they are unstable or stable.

If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and begin continuous vital sign monitoring including blood pressure, heart rate, and pulse oximetry. Provide supplemental oxygen, if needed.

Okay, let’s go back to the ABCDE assessment. If your patient is stable, first obtain a focused history and physical exam. Patients may report feeling a mass or a lump, and they might have a fever. Physical exam typically reveals enlarged, palpable lymph nodes, usually in the region of the neck, axilla, or groin. These lymph nodes might also be painless or tender to palpation; mobile or fixed to surrounding tissue; or soft or hard in consistency. Lymph nodes may also become matted, meaning that they’re joined together so they feel connected when palpated. If you encounter enlarged lymph nodes with an abnormal consistency, diagnose peripheral lymphadenopathy!

Here’s a clinical pearl! Localized or regional lymphadenopathy is limited to one area of the body, whereas generalized lymphadenopathy occurs in two or more non-contiguous lymph node groups. Look for other areas of enlarged lymph nodes if you encounter localized lymphadenopathy; and if otherwise asymptomatic, reexamine in 3 to 4 weeks. On the other hand, generalized lymphadenopathy should always prompt immediate work-up for an underlying cause.

And here’s a high yield fact! Enlarged supraclavicular lymph nodes are always abnormal regardless of their palpable features and should be evaluated further!

Okay, your next step is to assess the timing of symptom onset!

Let's begin with rapid onset, typically over a few days to two weeks or less.

First up is localized infection!

These patients develop symptoms consistent with a localized infection, like a sore throat, ear pain, skin wound, or a genital lesion. They might also have constitutional symptoms like fever or fatigue. Physical exam reveals localized signs of infection, such as enlarged tonsils, a red or bulging tympanic membrane, skin abscess, or genitourinary discharge, along with tender lymphadenopathy localized at the site of infection or along its drainage path. In these patients, diagnose lymphadenopathy due to localized infection!

Here’s a clinical pearl! Lymphadenopathy due to localized infection is commonly seen with Streptococcal pharyngitis, herpes simplex, and gonorrhea; as well as in conditions like mononucleosis, otitis externa or media, and skin abscess.

In addition, localized lymphadenopathy in the cervical and axillary lymph node groups is a recognized adverse reaction to the COVID-19 vaccination that can persist for one to two weeks after administration!

Okay, now let’s discuss disseminated or persistent infections.

These patients develop constitutional symptoms such as fever, malaise, and fatigue, which might be accompanied by headache, diarrhea, or a diffuse rash. Physical exam will reveal localized or generalized tender lymphadenopathy, as well as signs of systemic infection, such as erythematous skin. In this case, consider lymphadenopathy due to disseminated or persistent infection!

Your next step is to order specific testing based on your patient’s history and symptoms, which may include polymerase chain reaction, or PCR; serologies; or cultures for specific viral, bacterial, fungal, or parasitic infections. In addition, you may consider obtaining imaging studies, like a chest X-ray. If the results of the PCR, serology, or culture are positive; or if the imaging is positive; then diagnose lymphadenopathy due to disseminated or persistent infection!

Here’s a clinical pearl! Disseminated or persistent infections that cause lymphadenopathy can be due to viruses, like EBV, CMV, and HIV; parasitic infections such as Toxoplasma gondii, which causes toxoplasmosis; and bacterial pathogens such as Bartonella henselae, responsible for cat scratch disease; and Borrelia burgdorferi, the cause of Lyme disease. Other infections associated with lymphadenopathy include tuberculosis and syphilis, so if you suspect these conditions, be sure and order the appropriate work-up, including PPD or RPR.

And another clinical pearl! Certain medications like phenytoin and allopurinol can also cause lymphadenopathy, so be sure to take a careful history to exclude these potential causes before undertaking an extensive workup.

Now let’s switch gears and discuss situations where the onset has been gradual, over two weeks to a few months. First up is malignancy!