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Peripheral lymphadenopathy in children: Evaluation and diagnostic approach

Peripheral lymphadenopathy in children: Evaluation and diagnostic approach
Literature review current through: Jan 2024.
This topic last updated: Nov 28, 2022.

INTRODUCTION — Lymphadenopathy is common and usually not clinically important in and of itself. However, it can be a manifestation of serious underlying disease. The challenge for clinicians is to avoid aggressive evaluation and biopsy of most children, while making timely, specific diagnoses in children with serious underlying disease.

This topic will provide guidelines for our approach to the evaluation of peripheral lymphadenopathy in children. The guidelines are intended to supplement clinical judgment in the absence of research that directly addresses how children with unexplained lymphadenopathy should be evaluated. The causes of peripheral lymphadenopathy in children (table 1A-B and table 2), cervical lymphadenitis in children, and peripheral lymphadenitis in adults are discussed separately. (See "Peripheral lymphadenopathy in children: Etiology" and "Cervical lymphadenitis in children: Etiology and clinical manifestations" and "Evaluation of peripheral lymphadenopathy in adults".)

ANATOMY AND DEFINITIONS — The location of peripheral lymph node groups is shown schematically in the figures (figure 1 and figure 2).

"Lymphadenopathy" refers to enlargement of the lymph nodes. The threshold for enlargement varies with location. (See 'Lymph nodes' below.)

Strictly speaking, "lymphadenitis" refers to enlarged lymph nodes that are inflamed, but it is often used interchangeably with "lymphadenopathy."

GENERAL PRINCIPLES

Urgency and extent of evaluation — Peripheral lymphadenopathy in children generally is benign and self-limited. It is not necessary to identify the underlying etiology in every patient, particularly at the time of initial presentation in the primary care setting. The urgency and extent of the evaluation is determined by how ill the patient appears and whether there are clinical features suggestive of malignancy (table 3). The pace of the evaluation is rapid if the child is ill appearing. It can be more deliberate if the child looks well. Sometimes the lymphadenopathy resolves without explanation before invasive diagnostic testing is undertaken.

Step-wise approach — Our approach to the evaluation of peripheral lymphadenopathy in children occurs in stages over approximately four weeks:

"Early" excisional biopsy refers to biopsy when the child is initially seen at a referral center. Early excisional biopsy is indicated for children with worrisome features (table 3); it also may be indicated for suspected nontuberculous mycobacterial (NTM) infection (eg, young child with unilateral, nontender, cervicofacial lymphadenitis with violaceous, thin overlying skin). (See "Nontuberculous mycobacterial lymphadenitis in children", section on 'Clinical suspicion' and "Nontuberculous mycobacterial lymphadenitis in children", section on 'Management'.)

For those without worrisome features:

The first stage is to evaluate and treat conditions that appear obvious based upon the history and examination (eg, throat culture for group A streptococcal pharyngitis, heterophile antibodies or specific titers for Epstein-Barr virus or cytomegalovirus mononucleosis, serology for Bartonella henselae for cat scratch disease, medical or surgical therapy for NTM).

If the cause remains uncertain after the initial evaluation, the second stage is to evaluate and/or treat common causes of generalized or localized lymphadenopathy (according to site) or to provide a two-week trial of antibiotic therapy or a two- to three-week period of observation.

If the cause remains uncertain after the second stage evaluation and treatment and the adenopathy has not decreased in size, less common causes and causes that require specific treatment (eg, tuberculosis) are evaluated.

If after four weeks of observation and/or empiric therapy, the diagnosis remains uncertain and the lymph node has not regressed in size, biopsy may be warranted.

The evaluation may include blood tests (complete blood count [CBC], erythrocyte sedimentation rate/C-reactive protein [ESR/CRP], lactate dehydrogenase [LDH], serology), cultures, imaging, a trial of antimicrobial therapy, and/or lymph node biopsy. The sequence varies depending upon associated symptoms, whether the lymphadenopathy is generalized or localized, and the site of localized lymphadenopathy. (See 'Diagnostic tests' below.)

This stepwise approach may avoid unnecessary biopsies. In many patients, the adenopathy will resolve or the cause will become obvious during the evaluation period, with or without therapy [1]. Even with "can't miss" diagnoses, such as leukemia, lymphoma, or tuberculosis, the four-week period of evaluation is unlikely to affect treatment success.

Worrisome features — In children with peripheral lymphadenopathy, worrisome clinical features include [1-6]:

Systemic symptoms (fever >1 week, night sweats, weight loss [>10 percent of body weight])

Supraclavicular (lower cervical) nodes (see 'Supraclavicular lymphadenopathy' below)

Generalized lymphadenopathy (see 'Generalized lymphadenopathy' below)

Fixed, nontender nodes in the absence of other symptoms (see 'Lymph nodes' below)

Lymph nodes of >1 cm (0.4 inches) with onset in the neonatal period (<1 month of age)

Lymph nodes >2 cm (0.8 inches) in diameter that have increased in size from baseline or have not responded to two weeks of antibiotic therapy

Abnormal chest radiograph, particularly mediastinal mass or hilar adenopathy (see 'Chest radiograph' below)

Abnormal CBC and differential (eg, lymphoblasts, cytopenias in more than one cell line) (see 'CBC and ESR/CRP' below)

Elevated LDH

Lack of infectious symptoms in the ear, nose, and throat regions

Persistently elevated ESR/CRP or rising ESR/CRP despite antibiotic therapy

Several studies have correlated clinical features and biopsy results to predict the risk of malignancy or other treatable etiology in children with peripheral lymphadenopathy [2-4]. In a prospective study of biopsy results in 45 children <18 years (mean age 7.8 years) with nonfluctuant peripheral lymphadenopathy, the risk of malignancy increased with increasing age, size of node, number of sites of adenopathy, supraclavicular nodes, fixed nodes, and abnormal radiographs [2]. Factors that were not helpful for discriminating between benign and malignant causes were fever; cough; splenomegaly; skin erythema, discoloration, or induration; tender nodes; or leukocytosis. In a similar study in 123 patients (9 to 25 years of age), the risk of malignancy or granulomatous disease was increased in patients with lymph node size >2 cm (0.8 inches); abnormal chest radiograph; lack of ear, nose, and throat symptoms; and presence of systemic symptoms (eg, night sweats, weight loss, hemoglobin ≤10 g/dL) [3].

Avoidance of glucocorticoids — Treatment with glucocorticoids must be avoided before a definitive diagnosis is established. Glucocorticoid treatment could mask or delay the histologic diagnosis of leukemia, lymphoma, or histiocytic disease. Glucocorticoids typically are used during the induction phase of chemotherapy for these disorders, and patients who received glucocorticoids before initiation of induction therapy assigned to a higher risk category or may be ineligible for a clinical trial. Treatment with glucocorticoids also may exacerbate an infectious disease. (See "Treatment of acute lymphoblastic leukemia/lymphoma in children and adolescents" and "Overview of Hodgkin lymphoma in children and adolescents".)

INITIAL EVALUATION

History — Important aspects of the history in a child with peripheral lymphadenopathy include details about the lymph node enlargement, associated symptoms (local and systemic), potential exposures, and past medical history (table 4) [7-11].

Physical examination

General examination — The physical examination is focused on signs of local or systemic disease or infection [7-10]:

Weight – Weight loss of >10 percent of body weight may be indicative of malignancy.

Head, eyes, ears, nose, throat

Scalp infection – Tinea capitis

Conjunctival erythema – Kawasaki disease, leptospirosis

Oculoglandular syndrome (conjunctivitis and preauricular adenopathy) – Cat scratch disease, tularemia, herpes simplex virus [HSV], adenovirus, or pyogenic bacterial infection (ie, Staphylococcus aureus, group A Streptococcus [GAS])

Nasal obstruction or depression of the soft palate – Rhabdomyosarcoma, nasopharyngeal carcinoma

Oropharynx – Dental problems, pharyngitis, herpangina (picture 1), HSV gingivostomatitis (picture 2A-B)

Chest – Adventitious sounds may indicate a systemic process (eg, histoplasmosis; asthma, which may be associated with eosinophilic granulomatosis with polyangiitis [Churg-Strauss]; diffuse pulmonary Langerhans histiocytosis) (see "Diagnosis and treatment of pulmonary histoplasmosis" and "Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)" and "Pulmonary Langerhans cell histiocytosis")

Abdomen – Hepatosplenomegaly (systemic process such as Epstein-Barr virus [EBV], cytomegalovirus [CMV], brucellosis, human immunodeficiency virus [HIV], syphilis, neoplastic disease, rheumatologic disease); abdominal mass (eg, neuroblastoma)

Skin – Localized lesions (cat scratch disease (picture 3), tularemia (picture 4), S. aureus or GAS, HSV, etc); generalized rash (viral illness)

Lymph nodes

Location – Localized lymphadenopathy (present in only one region) generally suggests local causes and should prompt a search for pathology in the area of node drainage (table 2). (See 'General examination' above.)

However, some systemic diseases can present with local adenopathy. These include plague (Yersinia pestis (picture 5)), tularemia, and aggressive lymphomas. Unilateral localized lymphadenopathy occurs in Hodgkin lymphoma or Rosai-Dorfman disease, whereas bilateral localized lymphadenopathy occurs in non-Hodgkin lymphoma and autoimmune lymphoproliferative disease. (See "Peripheral lymphadenopathy in children: Etiology", section on 'Uncommon but important causes'.)

Small occipital and postauricular nodes are common in infants but not in older children [9,12]. However, multiple pea-sized occipital nodes are often found in children with acute lymphoblastic leukemia. Cervical and inguinal nodes are more common in children ≥2 years than in those <6 months of age [9,12]. Epitrochlear and supraclavicular adenopathy are uncommon at any age, unless there are skin infections or injuries distal to the node.

Generalized adenopathy (present in two or more noncontiguous regions) usually is a manifestation of systemic disease (table 1A-B). Palpation of inguinal, cervical, and axillary nodes, in addition to the liver and spleen, can determine whether lymphadenopathy is localized or generalized.

Size – The size of a lymph node that is considered to be normal varies depending upon the lymph node region and age of the child. In neonates (<1 month of age), normal lymph nodes are <1 cm (0.4 inches) in diameter. In children ≥1 month, normal lymph nodes in most regions generally are less than 1 cm (0.4 inches) in their longest diameter; normal lymph nodes in the epitrochlear region usually are less than 0.5 cm (0.2 inches) in diameter, and normal lymph nodes in the inguinal region usually are less than 1.5 cm (0.6 inches) in diameter. Normal lymph nodes tend to be larger in childhood (ages 2 to 10 years) than later in life.

The risk of malignancy is increased in lymph nodes >2 cm (0.8 inches) in diameter, although malignancy may occur in smaller nodes [2,13]. In a series of 75 biopsies performed in children 8 months to 17 years, 15 patients had nodes >3 cm (1.2 inches) in diameter [5]. Among these, six patients had reactive hyperplasia, seven had granulomatous disease, and two had lymphomas.

Consistency – The consistency of the node may suggest an etiologic category:

Fluctuance usually indicates infection within the node; rapidly developing fluctuance and drainage suggests a bacterial infection, usually S. aureus or GAS; spontaneous drainage and/or formation of a fistulous tract that develops over weeks to months suggests mycobacterial infection.

Hard (fibrotic) nodes generally are due to cancer or previous inflammation.

Firm, rubbery nodes may indicate lymphoma or chronic leukemia; nodes in acute leukemia tend to be softer. (See "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children".)

Fixation – Normal lymph nodes are freely movable in the subcutaneous space. Abnormal nodes can become fixed to adjacent tissues (eg, deep fascia) by invading cancers or inflammation in tissue surrounding the nodes. They also can become fixed to each other ("matted") by the same processes.

Tenderness – Tenderness suggests that recent, rapid enlargement has caused tension in the pain receptors in the capsule. Tenderness typically occurs with inflammatory processes, but it also can occur because of hemorrhage into a node, immunologic stimulation, and malignancy [2]. Thus, tenderness is not particularly helpful in discriminating between infectious and noninfectious causes of lymphadenopathy.

Initial laboratory evaluation — The initial laboratory evaluation focuses on the evaluation of conditions that are suspected based upon the history and examination (eg, throat culture for GAS pharyngitis, heterophile antibodies or specific titers for EBV or CMV mononucleosis, serology for B. henselae for cat scratch disease) (table 1A-B and table 2). (See 'Diagnostic tests' below.)

DIAGNOSTIC APPROACH

Generalized lymphadenopathy — Generalized adenopathy (present in two or more noncontiguous regions) usually is a manifestation of systemic disease (table 1A-B). When due to an infection, generalized lymphadenopathy is more commonly caused by viruses (eg, cytomegalovirus [CMV], Epstein-Barr virus [EBV]) or Mycobacterium tuberculosis than by S. aureus or group A Streptococcus (GAS) [14].

Indications for early biopsy – Children with generalized lymphadenopathy and any of the following should undergo early biopsy (ie, when initially seen at a referral center) of the most abnormal node (see 'Lymph node biopsy' below):

Supraclavicular nodes

Massively enlarged lymph nodes (ie, >4 cm [1.6 inches])

A group of nodes with a total diameter >3 cm (1.2 inches)

Initial tests – The laboratory evaluation for the child with generalized adenopathy varies depending upon the findings in the history and physical examination. Our initial evaluation for children with generalized lymphadenopathy typically includes (table 5):

Complete blood count (CBC) and differential count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (see 'CBC and ESR/CRP' below)

Lactate dehydrogenase (LDH)

Serology for CMV and EBV (see 'Cultures and serology' below)

Serology for other viral illnesses as warranted by the history and examination (table 1A) (see 'Cultures and serology' below)

Tuberculin skin testing (TST) (see 'Tuberculin skin test' below)

Chest radiograph (CXR) (see 'Chest radiograph' below)

We provide treatment or additional evaluation as indicated for conditions that are identified through initial testing (eg, treatment for M. tuberculosis, early biopsy of the most abnormal lymph node for children with mediastinal mass).

Second-tier tests – Second tier tests, which may be indicated in children with generalized lymphadenopathy in whom the diagnosis remains uncertain after the initial evaluation, are usually of low yield in the absence of a specific indication. We perform the following second tier tests as indicated by the initial evaluation:

Serologic testing for B. henselae, toxoplasmosis, histoplasmosis, coccidiomycosis, brucellosis, syphilis, HIV, and other viruses as indicated by clinical features (table 1A). Children with positive serology should be treated as indicated. (See 'Cultures and serology' below.)

Antinuclear antibody as a screen for vasculitis syndromes (eg, systemic lupus erythematosus, rheumatoid arthritis) (table 1B). (See "Measurement and clinical significance of antinuclear antibodies".)

Indications for biopsy within four weeks – We obtain a biopsy of the most abnormal node within four weeks if (see 'Lymph node biopsy' below):

Any lymph nodes increase in size

There is a lymph node ≥2 cm (0.8 inches) in diameter and either of the following:

-The diagnosis remains uncertain after four weeks

-There is no response to therapy as indicated by the findings of initial or second tier tests

Localized adenopathy — The causes of localized adenopathy vary with the lymph node region (table 2).

Supraclavicular lymphadenopathy — Supraclavicular (or lower cervical) lymphadenopathy is associated with malignancy in children, including leukemia, lymphoma, histiocytosis, neuroblastoma, and germ cell tumors [2,9].

We evaluate children who have supraclavicular adenopathy with CBC and differential count, ESR, LDH, CXR, and lymph node biopsy unless there is an obvious skin abscess or cellulitis draining to that lymph node, in which case we provide a trial of antimicrobial therapy. We provide treatment or additional evaluation as indicated for conditions that are identified through initial testing. (See "Overview of common presenting signs and symptoms of childhood cancer", section on 'Lymphadenopathy' and 'Diagnostic tests' below.)

Axillary lymphadenopathy — Common causes of axillary adenopathy include cat scratch disease and pyogenic infections (ie, S. aureus, GAS) of the upper arm (table 2).

For children and adolescents with axillary lymphadenopathy and an obvious cause (eg, cat exposure and typical papular lesion (picture 3)), we provide initial treatment as indicated. (See "Treatment of cat scratch disease".)

Our approach to children and adolescents with axillary lymphadenopathy and no obvious cause depends upon the size of the lymph nodes (table 6):

≥2 cm in diameter – For children with axillary adenopathy ≥2 cm (0.8 inches) in diameter, we obtain a CBC and differential count, ESR/CRP, LDH, and CXR and proceed directly to biopsy if the child has any worrisome features (table 3). (See 'Lymph node biopsy' below.)

For children without worrisome features, we either observe for two to three weeks or provide a trial of antimicrobial therapy if the history or examination suggests an infection within or distal to the node. In children with signs of infection, we obtain cultures and other microbiologic studies as indicated before initiation of antibiotics. (See 'Cultures and serology' below and 'Trial of antibiotic therapy' below.)

If the adenopathy regresses in size with observation or antimicrobial therapy, no additional evaluation is necessary.

Biopsy usually is required if the adenopathy does not respond to antibiotic therapy or two to three weeks of observation. (See 'Lymph node biopsy' below.)

<2 cm in diameter – The initial evaluation and management of axillary lymphadenopathy <2 cm (0.8 inches) in diameter depends upon associated signs of infection:

In children with axillary adenopathy <2 cm (0.8 inches) in diameter and symptoms or signs of infection within or distal to the node, we initiate empiric antimicrobial therapy as indicated by the history and examination. Cat scratch disease is a particular concern in children with exposure to cats. We obtain cultures and other microbiologic studies as indicated if there is an obvious site of infection or the history suggests a specific cause. (See "Treatment of cat scratch disease".)

For children without symptoms or signs of infection, we observe for two to three weeks.

Subsequent evaluation and management depends upon the response to observation or antimicrobial therapy:

If the adenopathy regresses in size with observation or antimicrobial therapy, no additional evaluation is necessary.

If the adenopathy does not regress in size with observation or antimicrobial therapy, we obtain a CBC with differential, perform TST, and initiate or broaden antimicrobial therapy (eg, to include coverage for community-associated methicillin-resistant S. aureus [CA-MRSA] or cat scratch disease if not previously covered and the child has cat exposure). (See 'Trial of antibiotic therapy' below and "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease", section on 'Differential diagnosis'.)

-If the CBC and differential have any findings concerning for malignancy (eg, lymphoblasts, cytopenias in more than one cell line), we obtain an early biopsy. (See 'CBC and ESR/CRP' below and 'Lymph node biopsy' below.)

-If the TST is positive, additional testing may be necessary to establish the diagnosis of tuberculosis or nontuberculous mycobacterial lymphadenitis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Nontuberculous mycobacterial lymphadenitis in children", section on 'Diagnosis'.)

-If the TST is negative and the adenopathy regresses in size in response to antibiotic therapy/broadened antimicrobial therapy, no additional evaluation is necessary.

-If the TST is negative and the adenopathy does not regress in size, we obtain ESR, CRP, and serology for EBV, CMV, HIV, and B. henselae; we evaluate other conditions as indicated by the history and examination (table 2). (See 'Diagnostic tests' below.)

-We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node has not regressed in size or there is no response to antimicrobial therapy/broadened antimicrobial therapy.

Inguinal lymphadenopathy — Common causes of inguinal lymphadenopathy in children and adolescents include sexually transmitted infections (eg, herpes simplex virus, syphilis, gonorrhea) and lymphoma (table 2). For children and adolescents with inguinal lymphadenopathy and an obvious cause (eg, distal skin or soft tissue infection, sexually transmitted infection), we provide initial treatment as indicated. (See "Skin and soft tissue infections in children >28 days: Evaluation and management", section on 'Management approach'.)

For children and adolescents with inguinal lymphadenopathy, no obvious cause, and no worrisome features (table 3), our approach varies depending upon the size of the lymph nodes, whether they are tender, and whether there are symptoms or signs of infection (table 7):

≥2 cm in diameter, tender – For children with tender inguinal lymphadenopathy ≥2 cm (0.8 inches) in diameter, we provide a 10 to 14 day trial of antibiotics, broadening coverage to include CA-MRSA and/or B. henselae (in children with cat exposure) if the lymph node does not regress in size or enlarges during therapy. (See 'Trial of antibiotic therapy' below.)

If the lymph node regresses during therapy, no additional evaluation is necessary.

If the lymph node does not improve with antibiotic therapy, we obtain CBC, ESR/CRP, CXR, TST, and B. henselae serology (in children with cat exposure). We provide referral or treatment as indicated based on the results of these tests.

We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node not regressed in size or there is no response to antimicrobial therapy/broadened antimicrobial therapy.

≥2 cm in diameter, nontender, with symptoms or signs of infection – For children with nontender inguinal lymphadenopathy ≥2 cm (0.8 inches) in diameter and symptoms or signs of infection within or distal to the node, we obtain bacterial and fungal cultures or other fungal studies as indicated by the history, examination, and B. henselae serology (in children with cat exposure) and provide a 10 to 14 day trial of antibiotics, broadening coverage to include CA-MRSA and/or B. henselae (in children with cat exposure) if the lymph node does not regress in size or enlarges during therapy. (See 'Trial of antibiotic therapy' below.)

If the lymph node regresses during antimicrobial therapy/broadened antimicrobial therapy, no additional evaluation is necessary.

If the lymph node does not regress during therapy, we obtain CBC, ESR, CRP, and CXR to evaluate worrisome features (table 3).

We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node has not regressed in size or there is no response to antimicrobial therapy/broadened antimicrobial therapy.

≥2 cm in diameter, nontender, no symptoms or signs of infection – For children with nontender inguinal lymphadenopathy ≥2 cm (0.8 inches) in diameter and no signs or symptoms of infection within or distal to the node, we obtain CBC, ESR, CRP, LDH, CXR, and abdominal ultrasonography looking for abdominal masses and/or abdominal lymphadenopathy. Subsequent evaluation and management depend upon the results of these tests.

If the initial evaluation reveals worrisome features (table 3), abdominal mass, or abdominal lymphadenopathy, early biopsy is indicated. (See 'Lymph node biopsy' below.)

If the findings of the initial evaluation are not worrisome, there is no abdominal mass or lymphadenopathy, and the cause remains uncertain (including the possibility of occult bacterial infection, we perform TST and provide a 10- to 14-day trial of antibiotics.

-If the TST is positive, additional testing may be necessary to establish the diagnosis of tuberculosis or nontuberculous mycobacterial lymphadenitis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Nontuberculous mycobacterial lymphadenitis in children".)

-If the TST is negative and the lymph node regresses during antimicrobial therapy, no additional evaluation is necessary.

-If the TST is negative and the lymph node does not regress during antimicrobial therapy, we obtain additional microbiologic studies as indicated by the history and examination (table 2). We provide referral or treatment based upon the results.

We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node has not regressed in size or there is no response to antimicrobial therapy/broadened antimicrobial therapy.

<2 cm in diameter – We generally proceed directly to biopsy for children with inguinal lymphadenopathy <2 cm (0.8 inches) in diameter if they have worrisome features (table 3). (See 'Lymph node biopsy' below.)

We generally observe children with inguinal lymphadenopathy <2 cm (0.8 inches) in diameter if they do not have worrisome features, even if the lymph node does not regress in size after four weeks.

Cervical lymphadenopathy — For children and adolescents with cervical lymphadenopathy and an obvious cause (eg, GAS pharyngitis), we provide initial treatment as indicated.

Symptoms or signs of infection – The diagnostic approach to cervical adenopathy in children with signs or symptoms of infection is discussed separately. (See "Cervical lymphadenitis in children: Diagnostic approach and initial management".)

No symptoms or signs of infection, <2 cm in diameter – For children with cervical lymphadenopathy <2 cm (0.8 inches), no findings of infection within or distal to the node, no worrisome features, and no obvious cause based on the history and examination, we observe for 10 to 14 days (table 8).

If the lymph node regresses during observation, no additional evaluation is necessary.

If the lymph node does not regress or enlarges, then a course of antibiotic therapy may be indicated. We also obtain CBC, ESR/CRP, and serology for EBV, CMV, and HIV; and evaluate for Kawasaki disease and other uncommon causes of cervical lymphadenopathy as indicated by the history and examination. (See 'Trial of antibiotic therapy' below and "Peripheral lymphadenopathy in children: Etiology", section on 'Uncommon but important causes'.)

We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node has not regressed in size. However, continued observation may be reasonable if there are no worrisome features.

No symptoms or signs of infection, ≥2 cm in diameter – For children with cervical lymphadenopathy ≥2 cm (0.8 inches), no findings of infection, and no worrisome features, our initial evaluation includes a CBC, ESR/CRP, and CXR. (See 'CBC and ESR/CRP' below and 'Chest radiograph' below.)

If the initial evaluation reveals features suggestive of malignancy (table 3), we refer for early biopsy. (See 'Lymph node biopsy' below.)

If the initial evaluation does not suggest malignancy and the cause remains uncertain (including possible occult infection), we perform TST and provide a 10- to 14-day trial of antibiotics.

-If the TST is positive, additional testing may be necessary to establish the diagnosis of tuberculosis or nontuberculous mycobacterial lymphadenitis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Nontuberculous mycobacterial lymphadenitis in children".)

-If the TST is negative and the lymph node regresses during antimicrobial therapy, no additional evaluation is necessary.

-If the TST is negative and the lymph node does not regress during antimicrobial therapy, we obtain serology for EBV, CMV, and HIV, and evaluate for Kawasaki disease and other uncommon causes of cervical lymphadenopathy as indicated by the history and examination. (See "Peripheral lymphadenopathy in children: Etiology", section on 'Uncommon but important causes'.)

We obtain a biopsy after four weeks if the diagnosis remains uncertain and the lymph node has not regressed in size.

Epitrochlear lymphadenopathy — Epitrochlear lymphadenopathy may be associated with leukemia.

For children with epitrochlear lymphadenopathy, we obtain CBC and differential count, ESR/CRP, lactate dehydrogenase, and B. henselae serology. We proceed to biopsy in children with worrisome features (table 3). For children without worrisome features, we provide treatment or additional evaluation as indicated for conditions that are identified through initial testing. If the lymph node does not regress in size within four weeks, we obtain lymph node biopsy, even if the node is <2 cm (0.8 inches) in diameter. However, continued observation may be reasonable if there are no worrisome features. (See "Overview of common presenting signs and symptoms of childhood cancer", section on 'Lymphadenopathy' and 'Diagnostic tests' below.)

Other localized lymphadenopathy

Worrisome features – In children with localized lymphadenopathy of the head or popliteal region and worrisome features (table 3), we proceed directly to biopsy. (See 'Lymph node biopsy' below.)

No worrisome features – Localized lymphadenopathy of the head (occipital, posterior auricular, preauricular, submental, submandibular) generally is related to local infections of the head, conjunctivae, or oropharynx, and the cause is often obvious after the initial evaluation (eg, tinea capitis, dental infection) (table 2). Localized lymphadenopathy of the popliteal region generally is related to local infections of the posterior leg and knee, and the cause is often obvious after the initial evaluation.

If, after four weeks of observation or treatment for an obvious cause, lymph nodes of the head or popliteal region have not regressed in size and are >2 cm (0.8 inches) in diameter, we generally obtain lymph node biopsy. (See 'Lymph node biopsy' below.)

DIAGNOSTIC TESTS — Diagnostic tests in the evaluation of peripheral lymphadenopathy in children may include complete blood count (CBC), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP), lactate dehydrogenase (LDH), microbiologic tests, tuberculin skin testing (TST), chest radiograph (CXR), ultrasonography, a trial of antimicrobial therapy, and lymph node biopsy. The timing and sequence of the tests and/or trial of antibiotic therapy varies depending upon the site(s) and size of the enlarged nodes, and associated clinical features. (See 'Generalized lymphadenopathy' above and 'Supraclavicular lymphadenopathy' above and 'Localized adenopathy' above.)

CBC and ESR/CRP — The results of the CBC and differential may lend more or less support to particular diagnostic considerations [6]. (See "Overview of common presenting signs and symptoms of childhood cancer", section on 'Blood count abnormalities'.)

As examples [14]:

Cytopenias in more than one cell line – Leukemia, lymphoma, bone marrow metastatic disease (eg, neuroblastoma), systemic lupus erythematosus (SLE), autoimmune lymphoproliferative syndrome

Isolated leukopenia or neutropenia – Viral infection, leukemia

Leukocytosis with left shift – Bacterial infection

Atypical lymphocytes – Epstein-Barr virus, cytomegalovirus, human herpesvirus 6

Eosinophilia – Parasitic infection

Anemia – SLE, M. tuberculosis

Thrombocytosis – Kawasaki disease

ESR and CRP are acute phase reactants. Elevation of ESR and/or CRP is a nonspecific marker of inflammation: It does not distinguish infection from other causes of inflammation (eg, malignancy, rheumatologic disease). In the evaluation of children with peripheral lymphadenopathy of uncertain etiology, elevation of ESR and/or CRP raises the level of concern. Persistent or increasing elevation despite a trial of antimicrobial therapy may warrant biopsy.

Lactate dehydrogenase — LDH is present in white and red blood cells as well as liver and muscle cells. In children with peripheral lymphadenopathy, elevated LDH may be due to:

Infection (eg, acute hepatitis, M. tuberculosis, histoplasmosis, toxoplasmosis)

Hemolysis

Malignancy (eg, leukemia, lymphoma, testicular germ cell tumor, tumor lysis syndrome) (see "Overview of common presenting signs and symptoms of childhood cancer", section on 'Lymphadenopathy')

Rheumatologic conditions (eg, SLE, rheumatoid arthritis)

Cultures and serology — Our indications for cultures and serology depend upon the clinical circumstances:

Throat culture for group A Streptococcus (GAS) – Children with cervical lymphadenopathy and acute exudative tonsillopharyngitis without associated viral features (eg, rhinorrhea).

Blood cultures – Children who appear systemically ill and in whom bacterial infection is suspected.

Bacterial cultures of the drainage from skin lesions – Children with draining skin lesions.

Fungal cultures of skin lesions or fungal serology (eg, coccidiomycosis, histoplasmosis, blastomycosis) – Children with a history suggestive of fungal infection or evidence of infection and no response to antibacterial therapy.

Lymph node cultures – Ill-appearing children with localized lymphadenopathy that is fluctuant; material for culture may be obtained via excisional biopsy (if tuberculous or nontuberculous mycobacterial infection is strongly suspected), needle aspiration, or incision and drainage; abscess fluid should be sent for Gram stain and bacterial culture (aerobic and anaerobic), mycobacterial stain and culture, and fungal stain and culture. (See 'Lymph node biopsy' below and "Cervical lymphadenitis in children: Diagnostic approach and initial management", section on 'Acute unilateral'.)

Serologic testing – To confirm diagnoses suspected after the initial evaluation or as part of the subsequent evaluation in children in whom the diagnosis remains uncertain after the initial evaluation; the choice of serologic test(s) varies with the site of adenopathy and associated clinical features (table 1A and table 2). (See 'Generalized lymphadenopathy' above and 'Axillary lymphadenopathy' above and 'Inguinal lymphadenopathy' above and 'Cervical lymphadenopathy' above.)

Tuberculin skin test — TST is indicated to screen for M. tuberculosis infection. TST also may result in reactive induration in children with nontuberculous mycobacterial (NTM) infection. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis" and "Nontuberculous mycobacterial lymphadenitis in children", section on 'Preliminary differentiation from M. tuberculosis'.)

Chest radiograph — Decisions regarding CXRs in children with peripheral lymphadenopathy are made on a case-by-case basis. We generally obtain chest radiographs in children with:

Generalized lymphadenopathy at the time of presentation (see 'Generalized lymphadenopathy' above)

Supraclavicular lymphadenopathy at the time of presentation (see 'Supraclavicular lymphadenopathy' above)

Cervical or inguinal adenopathy ≥2 cm in diameter who do not have signs or symptoms of infection or who have signs of infection but did not respond to a trial of antimicrobial therapy

In children with lymphadenopathy, CXRs are obtained primarily to look for mediastinal masses or hilar adenopathy.

Mediastinal mass may indicate lymphoma or other malignancy, depending upon its location (see "Overview of common presenting signs and symptoms of childhood cancer", section on 'Mediastinal masses')

Hilar adenopathy may indicate sarcoidosis, tuberculosis, or Hodgkin lymphoma (see "Clinical manifestations and diagnosis of sarcoidosis" and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Overview of Hodgkin lymphoma in children and adolescents", section on 'Clinical presentation')

Other CXR findings also may be helpful in determining the cause of lymphadenopathy (eg, pulmonary infiltrates in children with coccidiomycosis or histoplasmosis).

Ultrasonography — Ultrasonography of the lymph node may be helpful in defining the presence and extent of an abscess if lymph node fluctuance is not obvious by manual examination. Ultrasonography of the lymph node also may help to differentiate metastatic from infectious cervical lymph nodes based upon the more circular shape, eccentric nodal borders, and hilar distribution of perfusion in metastatic lymph nodes [4,15-18]. However, these features do not provide definitive information, so biopsy is often necessary regardless of the results of the ultrasound.

Abdominal ultrasonography may be warranted in children with unexplained inguinal adenopathy who do not have symptoms of infection, looking for abdominal masses and/or abdominal lymphadenopathy, which may be associated with malignancy (eg, neuroblastoma, lymphoma).

Trial of antibiotic therapy — A trial of antibiotic therapy is both a diagnostic and therapeutic intervention in children with localized adenopathy, uncertain diagnosis, and no worrisome features. The trial of antibiotics may be undertaken even in the absence of symptoms and signs of infection because localized (nonsupraclavicular) adenopathy is so frequently caused by S. aureus, GAS, atypical mycobacteria, or B. henselae [14]. (See 'Localized adenopathy' above.)

Initial regimen – We generally provide initial empiric coverage for GAS and S. aureus. The antibiotic choice is influenced by the prevalence of community-associated methicillin-resistant S. aureus (CA-MRSA):

High CA-MRSA prevalence – Clindamycin (see "Skin and soft tissue infections in children >28 days: Evaluation and management", section on 'Management approach')

Low CA-MRSA prevalence – First-generation cephalosporin (eg, cephalexin) or amoxicillin-clavulanate

For patients with exposure to cats or kittens, we also include coverage for B. henselae (eg, azithromycin) in the initial regimen. (See "Treatment of cat scratch disease", section on 'Lymphadenitis'.)

Broadened coverage – If the patient's systemic symptoms (eg, fever) do not improve within 72 hours or the lymph node increases in size (at any point during treatment), our first step generally is to broaden the antimicrobial coverage to include coverage for common pathogens that were not included initially. As examples:

For patients initially treated with a first-generation cephalosporin or amoxicillin-clavulanate, we switch to clindamycin to provide coverage for CA-MRSA

For patients with exposure to cats or kittens, we add coverage for B. henselae (eg, azithromycin) if it was not included in the initial regimen (see "Treatment of cat scratch disease", section on 'Lymphadenitis')

For patients initially treated with clindamycin, we may add coverage for NTM if there are clinical features suggestive of NTM infection and contraindications to surgical excision (if the suspicion for NTM is high, excisional biopsy is more appropriate) (see "Nontuberculous mycobacterial lymphadenitis in children", section on 'Antimycobacterial therapy')

Lymph node biopsy — Early excisional lymph node biopsy (ie, when initially seen at a referral center) may be indicated in patients with worrisome features (table 3) [2,3,5,9]. Excisional biopsy is also recommended for patients in whom tuberculous or NTM infection is suspected because simple aspiration may result in the development of a fistulous tract [19-22]. (See 'Worrisome features' above and "Nontuberculous mycobacterial lymphadenitis in children", section on 'Surgical excision (preferred)'.)

The biopsy should be performed at a medical center specializing in the care of children, and the pathologist should know in advance that there will be a lymph node biopsy. This will ensure that the proper smears, stains, and cultures will be performed. Parts of the sample (unfixed) should be reserved to permit marker studies (eg, immunophenotyping, cytogenetics, and molecular studies). Isolation of unusual organisms (eg, Candida spp, Serratia marcescens, Chromobacterium violaceum) from biopsy specimens should prompt consideration of chronic granulomatous disease. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infections'.)

Approximately 20 percent of lymph node biopsies demonstrate a treatable disease (eg, leukemia, lymphoma, tuberculosis) [2,5,9]. Supraclavicular location is probably the most important factor in predicting malignancy, but the character or size of the nodes also may be helpful in deciding when a biopsy is necessary. (See 'Worrisome features' above.)

The most abnormal node is selected if multiple node groups are involved. If no single node predominates, the choice in descending order of preference is supraclavicular, cervical, axillary, and inguinal because the chances of a nonspecific result are greatest with axillary and inguinal nodes. In addition, the likelihood of complications (eg, infection, damage to the neurovascular structures) is higher in the inguinal and axillary regions.

We prefer open biopsy to fine needle aspiration (FNA) for evaluation of concerning peripheral lymphadenopathy in children. Histologic examination of intact tissue provides information about abnormal cells (carcinoma, microorganisms) and abnormal node architecture, which is necessary for the diagnosis of lymphomas. False-negative results occur if the wrong node is taken, which is not uncommon. Open biopsy usually is performed on an outpatient basis under local anesthesia. FNA has a high false-negative rate because of sampling error and difficulty in recognizing well-differentiated lymphomas [23]; false-positive results are uncommon. FNA for cytology has traditionally been most useful when evaluating cancer recurrence.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Swollen neck nodes in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

General principles – Peripheral lymphadenopathy in children generally is benign and self-limited. It is not necessary to identify the underlying etiology in every patient. The urgency and extent of the evaluation is determined by how ill the patient appears and whether there are clinical features suggestive of malignancy (table 3). (See 'Urgency and extent of evaluation' above.)

We generally evaluate children with peripheral lymphadenopathy in a step-wise fashion over approximately four weeks. (See 'Step-wise approach' above.)

Early excisional biopsy is indicated for children with worrisome features (table 3); it also may be indicated for suspected nontuberculous mycobacterial infection.

Treatment with glucocorticoids must be avoided before a definitive diagnosis is established. (See 'Avoidance of glucocorticoids' above.)

Initial evaluation – The etiology of peripheral lymphadenopathy often is obvious after a complete history and physical examination (table 1A-B and table 2). Additional evaluation may be necessary to confirm the suspected cause or if the diagnosis remains uncertain after the initial clinical evaluation. (See 'Initial evaluation' above.)

History and examination – The history is focussed on symptoms suggestive of infection (eg, exposures, travel, immunization status), malignancy (constitutional symptoms, paraneoplastic syndromes), and medications associated with lymphadenopathy (table 4). The general examination is focussed on signs of systemic disease or infection. (See 'History' above and 'General examination' above and 'Lymph nodes' above.)

Location-based diagnostic approach – The location of the lymph nodes is the most important feature in generating a differential diagnosis (table 1A-B and table 2) and directing the approach to diagnosis (see 'Diagnostic approach' above):

-Generalized lymphadenopathy (table 5)

-Axillary lymphadenopathy (table 6)

-Inguinal lymphadenopathy (table 7)

-Cervical lymphadenopathy (table 8)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robert H Fletcher, MD, MSc, who contributed to an earlier version of this topic review.

  1. Oguz A, Karadeniz C, Temel EA, et al. Evaluation of peripheral lymphadenopathy in children. Pediatr Hematol Oncol 2006; 23:549.
  2. Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg 1999; 34:1447.
  3. Slap GB, Brooks JS, Schwartz JS. When to perform biopsies of enlarged peripheral lymph nodes in young patients. JAMA 1984; 252:1321.
  4. Niedzielska G, Kotowski M, Niedzielski A, et al. Cervical lymphadenopathy in children--incidence and diagnostic management. Int J Pediatr Otorhinolaryngol 2007; 71:51.
  5. Lake AM, Oski FA. Peripheral lymphadenopathy in childhood. Ten-year experience with excisional biopsy. Am J Dis Child 1978; 132:357.
  6. Ling RE, Capsomidis A, Patel SR. Urgent suspected cancer referrals for childhood lymphadenopathy. Arch Dis Child 2015; 100:1098.
  7. Malley R. Lymphadenopathy. In: Textbook of Pediatric Emergency Medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott Williams and Wilkins, Philadelphia 2006. p.421.
  8. Margileth AM. Sorting out the causes of lymphadenopathy. Contemp Pediatr 1995; 12:23.
  9. Knight PJ, Mulne AF, Vassy LE. When is lymph node biopsy indicated in children with enlarged peripheral nodes? Pediatrics 1982; 69:391.
  10. Morland B. Lymphadenopathy. Arch Dis Child 1995; 73:476.
  11. Greenfield S, Jordan MC. The clinical investigation of lymphadenopathy in primary care practice. JAMA 1978; 240:1388.
  12. Herzog LW. Prevalence of lymphadenopathy of the head and neck in infants and children. Clin Pediatr (Phila) 1983; 22:485.
  13. Karadeniz C, Oguz A, Ezer U, et al. The etiology of peripheral lymphadenopathy in children. Pediatr Hematol Oncol 1999; 16:525.
  14. Weinberg GA, Segel GB, Hall CB. Lymphadenopathy. In: Signs & Symptoms in Pediatrics, Adam HF, Foy JM (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.637.
  15. Ying M, Ahuja AT, Evans R, et al. Cervical lymphadenopathy: sonographic differentiation between tuberculous nodes and nodal metastases from non-head and neck carcinomas. J Clin Ultrasound 1998; 26:383.
  16. Steinkamp HJ, Mueffelmann M, Böck JC, et al. Differential diagnosis of lymph node lesions: a semiquantitative approach with colour Doppler ultrasound. Br J Radiol 1998; 71:828.
  17. Wu CH, Chang YL, Hsu WC, et al. Usefulness of Doppler spectral analysis and power Doppler sonography in the differentiation of cervical lymphadenopathies. AJR Am J Roentgenol 1998; 171:503.
  18. Tschammler A, Ott G, Schang T, et al. Lymphadenopathy: differentiation of benign from malignant disease--color Doppler US assessment of intranodal angioarchitecture. Radiology 1998; 208:117.
  19. Panesar J, Higgins K, Daya H, et al. Nontuberculous mycobacterial cervical adenitis: a ten-year retrospective review. Laryngoscope 2003; 113:149.
  20. Kanlikama M, Mumbuç S, Bayazit Y, Sirikçi A. Management strategy of mycobacterial cervical lymphadenitis. J Laryngol Otol 2000; 114:274.
  21. Schaad UB, Votteler TP, McCracken GH Jr, Nelson JD. Management of atypical mycobacterial lymphadenitis in childhood: a review based on 380 cases. J Pediatr 1979; 95:356.
  22. Tunkel DE. Surgery for cervicofacial nontuberculous mycobacterial adenitis in children: an update. Arch Otolaryngol Head Neck Surg 1999; 125:1109.
  23. Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls. Acta Cytol 1995; 39:76.
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