Approach to peripheral lymphadenopathy: Clinical sciences

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Introduction 0:00–0:41

Peripheral lymphadenopathy refers to enlarged peripheral lymph nodes that may have an abnormal consistency, enlarged lymph nodes are generally defined as one centimeter or larger.
However, some lymph nodes are considered abnormal if they're larger than five millimeters, 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.

Unstable0:41–1:06

Next, obtain IV access and begin continuous vital sign monitoring including BP, heart rate and pulse oximetry, provide supplemental oxygen if needed.
Ok. Let's go back to the ABCD E assessment.

Stable 1:06–2:31

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 noncontiguous 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 workup 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.

Assess Timing of Symptom Onset 2:31–2:42

Ok. 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.

Localized Infection 2:42–3:52

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 diagnosed 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 1 to 2 weeks after administration.
Ok. Now, let's discuss disseminated or persistent infections.

Disseminated or Persistent Infection 3:52–5:47

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 Hensley responsible for cat scratch disease and Borrelia Burgdorferi.
The cause of a lyme disease. Other infections associated with lymphadenopathy include tuberculosis and syphilis.
So, if you suspect these conditions be sure and order the appropriate workup 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 lets switch gears and discuss situations where the onset has been gradual over two weeks to a few months. First up is malignancy.

Gradual (> 2 Weeks to Months) 5:47–5:54

Malignancy 5:54–8:26

Your patient will typically report constitutional symptoms which could include fever, malaise night sweats or weight loss.
They might also report symptoms concerning for malignancy such as a mass cough or bone pain. Physical exam reveals signs suspicious for malignancy, which may include a palpable mass, bony tenderness to palpation, hepatomegaly or splenomegaly.
Lymphadenopathy is either localized or generalized and the lymph nodes are typically nontender firm and immobile. With this constellation of findings consider lymphadenopathy due to malignancy.
Here's a high yield fact, the consistency of lymph nodes seen in lymphoma are commonly non tender, firm, rubbery and immobile.
On the flip side, lymph nodes invaded by metastatic solid organ. Malignancies are usually hard and matted.
And now a clinical pearl, a Virchow node is an enlarged and palpable, left supraclavicular lymph node associated with underlying malignancy.
Most commonly gastrointestinal in origin such as colon or gastric cancer. This lymph node is at the end of the thoracic duct sits deep in the supraclavicular region and can't be felt in a healthy person.
However, as the node becomes enlarged and hard when invaded by metastatic cells. This makes it easy to feel.
Ok. The next step is to identify the underlying cause of lymphadenopathy order labs including tumor markers such as carcino embryonic antigen alpha fetoprotein and ca 19 9.
Whenever possible, obtain a biopsy of the affected lymph node, which may require imaging studies and procedures specific to the location of the suspected primary cancer or sites of metastasis.
These may include an ultrasound CT MRI or pet scans, a mammogram as well as a colonoscopy, bronchoscopy or even a bone marrow biopsy.
If the tumor markers, biopsy, imaging or procedures show evidence of malignancy, diagnose lymphadenopathy due to a malignancy.
Here's a high yield fact. While most patients with underlying malignancy develop lymphadenopathy.
Gradually, patients with acute leukemia such as acute lymphoblastic leukemia usually have a more rapid onset of 1 to 2 weeks compared to other types of cancers such as lymphoma or solid tumor cancers.
Ok. Now, let's move on to immunologic or inflammatory diseases.

Immunologic or Inflammatory Disease 8:26–10:39

These patients typically report constitutional symptoms which may include fever, malaise or weight loss and inflammatory symptoms like joint pain or a rash.
Physical examination may show inflammatory signs which could include joint effusion or skin changes along with generalized lymphadenopathy.
With these findings consider lymphadenopathy due to an immunologic or inflammatory condition. Your next step is to order labs including antibodies like antinuclear antibodies or ana and rheumatoid factor or RF biomarkers such as angiotensin converting enzyme or ace C three and C four as well as a serum calcium also obtain imaging such as a chest X ray and a biopsy of the affected lymph node or skin lesion.
Your patients antibodies might be positive with abnormal biomarkers like a low serum C three or C four or elevated ace level and the serum calcium might be elevated.
A chest X ray may show hilar adenopathy and the lymph node or skin biopsy might show evidence of immunologic or inflammatory disease.
With these findings diagnose lymphadenopathy due to an immunologic or inflammatory condition. Here's a high yield fact, sarcoidosis is a systemic inflammatory condition which can present with bilateral hilar and peripheral lymphadenopathy, interstitial lung disease, uveitis and erythema nodosum serum ace and calcium levels are commonly elevated but a lymph node biopsy showing non caseating granulomas is diagnostic and one last clinical Pearl Kawasaki disease also called mucocutaneous lymph node syndrome is a medium vessel vasculitis.
Most commonly seen in Children under five years of age. Hallmarks of the disease include erythema of the mouth and pharynx known as strawberry tongue, systemic macular erythematous rash, and cervical lymphadenopathy.
If you see lymphadenopathy in a child with these findings, be sure to work your patient up for Kawasaki disease. All right.
As a quick recap, peripheral lymphadenopathy is the presence of enlarged lymph nodes that have an abnormal consistency and is typically caused by infection, malignancy or immunologic and inflammatory conditions.

Review10:39–11:42

First, assess symptom onset to determine the underlying cause rapid onset of symptoms point you toward either localized or disseminated infection.
Obtain disease specific labs to diagnose the infectious cause to confirm your diagnosis. On the other hand, if your patient has a more gradual onset of symptoms and non tender firm and immobile lymph nodes consider an underlying malignancy as the cause order disease specific tumor markers, imaging studies procedures and biopsy to confirm your diagnosis.
Finally, if lymphadenopathy is associated with immunologic or inflammatory symptoms and signs. Order disease specific labs, imaging studies and biopsy to confirm an immunologic or inflammatory condition as the underlying cause of peripheral lymphadenopathy.