Approach to peripheral lymphadenopathy (pediatrics): Clinical sciences

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Introduction0:00–0:46

Peripheral lymphadenopathy refers to subcutaneous lymph nodes that have an abnormal size or consistency. Lymph node size varies by age and normally increases from infancy to childhood, with a subsequent decrease in size during late childhood and adolescence.
In general, enlarged lymph nodes are 1 centimeter or larger, but any degree of lymph node enlargement in atypical areas, such as the supraclavicular region, is considered abnormal.
The most important underlying causes of peripheral lymphadenopathy include malignancy, autoimmune conditions, and infections.Now, if your patient presents with peripheral lymphadenopathy, obtain a focused history and physical examination.

H&P0:46–1:21

Patients or their caregivers typically describe a lump or mass, occasionally with symptoms like fever, fatigue, or poor appetite.
Additionally, the physical exam findings will reveal one or more enlarged subcutaneous lymph nodes that could be tender to palpation.
These findings confirm the presence of peripheral lymphadenopathy.Now, the next step is to assess for malignancy. Physical exam findings include nontender nodes that are firm and immobile and fixed to the surrounding tissue as well as nodes that are matted, meaning that nodes are joined together so they feel connected when palpated.

Malignancy1:21–1:50

Palpable supraclavicular nodes are also concerning for malignancy, as well as persistently enlarged nodes. If your patient has any of these findings, consider the possibility of malignancy.Next, assess for signs and symptoms of leukemia or lymphoma.

Leukemia1:50–2:25

Let’s start with leukemia. These patients often report abnormal bleeding or bone pain, while their physical exam typically reveals pallor, bruising, or petechiae.
With these findings, consider leukemia and obtain a CBC with a peripheral smear and consider performing a bone marrow biopsy.
If the CBC reveals leukocytosis and anemia; and if immature blasts are seen on the peripheral blood smear or bone marrow biopsy, diagnose leukemia.Now, let’s move on to lymphoma.

Lymphoma2:25–2:55

These patients typically report night sweats, and possibly dyspnea or cough. Their physical exam usually reveals hepatosplenomegaly.
With these findings, consider the possibility of lymphoma, and obtain a lymph node biopsy and possibly a chest X-ray. A biopsy revealing malignant cells and chest X-ray findings indicating a mediastinal mass confirm the diagnosis of lymphoma.Now let’s discuss patients with no signs or symptoms suggestive of malignancy.

Autoimmune condition2:55–3:23

In this case, your next step is to assess for signs and symptoms suggesting an autoimmune condition. The history may reveal symptoms like joint pain or fever, and a physical exam may detect a rash, along with non-tender, mobile lymph nodes.
With these findings, consider the possibility of an autoimmune condition.First, let’s discuss Kawasaki disease! These patients typically have a fever for at least 5 days.

Kawasaki disease3:23–3:50

Physical exam reveals bilateral nonexudative conjunctivitis, cracked lips, a strawberry tongue, and a polymorphic rash, in combination with erythema or edema of the hands or feet and a single enlarged cervical lymph node.
With these findings, diagnose Kawasaki disease.Next up is systemic lupus erythematosus, or SLE! If your patient reports skin photosensitivity, and the physical exam reveals a malar rash, oral ulcers, and joint swelling, consider SLE.

SLE3:50–4:35

In this case, order labs, including a CBC, urinalysis, antinuclear antibody test, or ANA, anti-double stranded DNA, or anti-ds DNA, and anti-Smith antibody.
The CBC may demonstrate leukopenia, anemia, or thrombocytopenia; and urinalysis may reveal blood. If the ANA, anti-ds DNA, or anti-Smith antibody are positive; diagnose SLE.
Finally, let’s discuss systemic juvenile idiopathic arthritis, or systemic JIA for short. Affected patients are less than 16 years old that report pain and stiffness in one or more joints for six weeks or more, along with fever which is often accompanied by a salmon-pink macular rash in patients with light skin.

Systemic JIA4:35–5:22

The exam shows joint swelling and hepatomegaly. With these findings, consider systemic JIA and obtain labs, including CBC, ANA, and rheumatoid factor, or RF.
If the CBC reveals leukocytosis and thrombocytosis in combination with negative ANA and RF, diagnose systemic JIA.On the other hand, if your patient has no signs or symptoms of an autoimmune condition, your next step is to assess for signs and symptoms of infection.

Infection5:22–5:45

If symptoms have been present for less than 4 weeks and the exam reveals tender, mobile lymph nodes, consider the possibility of an infection, and assess the distribution of the lymphadenopathy.If only a single lymph node is enlarged, consider a primary lymph node infection.

Bacterial lymphadenitis5:45–7:01

Let’s start with bacterial lymphadenitis. In these patients, history reveals an abrupt onset of fever, occasionally with other symptoms like sore throat.
The physical exam reveals erythema of the skin overlying an enlarged, warm, and tender lymph node, typically in the cervical chain.
Some patients may also have pharyngeal erythema with enlarged tonsils. In this case, you can make a clinical diagnosis of bacterial lymphadenitis.Now, here’s a clinical pearl to keep in mind!
In neonates, acute bacterial lymphadenitis is most commonly caused by group B streptococcus, while in older children, group A Streptococcus and Staphylococcus aureus are common causes.And here’s another clinical pearl!
Nontuberculous mycobacterial lymphadenitis is a subacute infection that develops over several weeks or months and typically presents without fever or systemic symptoms.
These patients have firm, non-tender adenopathy with violaceous skin overlying the affected node.Now let’s move on to cat-scratch disease!

Cat-scratch disease7:01–7:36

If your patient reports exposure to a cat, and you detect erythema overlying a tender cervical or axillary lymph node, consider the possibility of cat-scratch disease.
Next, perform serologic testing for Bartonella henselae with enzyme immunoassay. Positive serologic testing confirms the diagnosis of cat-scratch disease.
Now, let’s switch gears and discuss patients with regional lymphadenopathy, which means there are multiple enlarged lymph nodes in a single region of lymph node drainage.

Regional lymphadenopathy7:36–7:55

Regional lymphadenopathy suggests that a local infection has caused an inflammatory reaction in nearby lymph nodes.Regional lymphadenopathy is often seen in conditions like cellulitis or otitis media.

Cellulitis & otitis media7:55–8:28

If your patient has had a break in the skin like skin-penetrating injury, cut, or abrasion; and the skin exam reveals a well-demarcated area of warmth, tenderness, and erythema; diagnose cellulitis.
On the other hand, if your patient reports fever and ear pain, and the physical exam shows a bulging, red tympanic membrane; then your patient has otitis media.
Finally, regional lymphadenopathy could also be due to group A streptococcal pharyngitis. If your patient reports a sore throat and fever, and the exam demonstrates pharyngeal erythema and enlarged tonsils with exudate, consider group A streptococcal pharyngitis.

Group A Streptococcal pharyngitis8:28–9:34

Next, obtain a rapid antigen detection test or a throat culture, and if either test is positive, diagnose group A strep pharyngitis.
Now, here’s a clinical pearl! Many other localized infections are associated with regional lymphadenopathy.
For example, upper respiratory infections and sinusitis commonly cause cervical lymphadenopathy, while pelvic and urinary tract infections can cause inguinal lymphadenopathy.
Regional lymphadenopathy typically does not require additional evaluation as long as it resolves after treatment of the underlying condition.
Finally, let’s discuss patients with generalized lymphadenopathy, meaning the lymph nodes are enlarged in 2 or more non-contiguous regions of lymph node drainage.

Generalized lymphadenopathy9:34–9:52

In this case, consider the possibility of a systemic infection.Let’s start with acute human immunodeficiency virus, or HIV infection.

Acute HIV9:52–10:45

These patients usually report non-specific symptoms, such as headaches, sore throat, vomiting, or diarrhea. Additionally, there might be a known HIV exposure.
The physical exam typically reveals a diffuse non-pruritic erythematous maculopapular rash, possibly in combination with thrush or oral ulcers.
With these findings, consider acute HIV infection, and obtain HIV ELISA antibody, p24 antigen, and HIV RNA PCR testing. If the ELISA is negative, the p24 antigen is positive, and the RNA PCR reveals more than 50,000 copies per milliliter, diagnose acute HIV infection.Now let’s move on to Epstein-Barr virus, or EBV infection.

EBV10:45–11:22

These patients typically report a sore throat, fatigue, and occasionally, a rash. Meanwhile, the exam shows enlarged tonsils and splenomegaly.
With these findings, consider EBV infection. Next, obtain EBV VCA IgM titers.
If titers are high, diagnose acute EBV infection, which is also called infectious mononucleosis.Next, let’s discuss Cytomegalovirus, or CMV infection.

CMV11:22–12:02

Although most patients with acute CMV infection are asymptomatic, some patients develop a mononucleosis-like syndrome with malaise and fatigue.
With these findings, consider CMV. For immunocompetent patients, you can usually make a clinical diagnosis, but if your patient is immunocompromised or pregnant, you should order confirmatory testing with CMV cultures of the urine, blood, or saliva; or PCR.
If the cultures or PCR are positive, diagnose CMV infection.Next up is toxoplasmosis. In this case, history will reveal exposure to cats or undercooked meat.

Toxoplasmosis12:02–12:32

While immunocompetent patients are often asymptomatic, some may develop fever and flu-like symptoms, including headache, fatigue, and myalgia.
These findings should make you consider toxoplasmosis, so order a Toxoplasma IgM and IgG. If the Toxoplasma serology is positive, diagnose toxoplasmosis.Let’s finish with adenovirus infection!

Adenovirus12:32–13:53

The history in these patients commonly includes fever and symptoms of upper respiratory tract infection, such as sore throat, runny nose, and cough; and in some cases, diarrhea.
Physical exam typically demonstrates pharyngeal erythema and conjunctival injection, with preauricular lymphadenopathy. In this case, consider adenovirus infection, which is typically a clinical diagnosis.
However, sometimes adenoviral infections can mimic other conditions, like Kawasaki disease, so, if needed, order an adenovirus PCR test.
A positive PCR confirms adenovirus infection.One last clinical pearl! Some less common conditions associated with generalized lymphadenopathy include sarcoidosis and chronic granulomatous disease, as well as infections like tuberculosis, measles, and zoonoses like brucellosis and tularemia.
Generalized lymphadenopathy is also a feature of some metabolic disorders, like Gaucher and Niemann-Pick disease. Finally, generalized lymphadenopathy could be seen in serum sickness or exposure to medications such as cephalosporins, phenytoin, and carbamazepine.Alright, as a quick recap… Peripheral lymphadenopathy refers to subcutaneous lymph nodes that have an abnormal size or consistency.

Review13:53–14:36

Non-tender, firm, non-mobile, matted, or supraclavicular lymph nodes suggest malignancy; while joint pain or a rash with non-tender, mobile lymph nodes suggests an autoimmune condition.
Next, tender lymphadenopathy suggests an underlying infection. A single, warm, and enlarged node indicates primary lymph node infection; regional lymphadenopathy suggests a local infection; and generalized lymphadenopathy can be seen in various systemic infections.