Eduard H. Panosyan, MD; Moran Gotesman, MD; and Joseph L. Lasky III, MD, FAAP


A 12-year-old girl is brought to the office with swelling of the anterior cervical nodes, which has persisted for 2 weeks. Intermittent fever with temperatures as high as 38.3°C (101°F) and decreased appetite have been associated with the condition. On physical examination, her temperature is 38.0°C (100.4°F) and her other vital signs are normal. Three to 4 nontender nodes 1 to 2 cm in diameter are present bilaterally. The remainder of the examination is normal.


1. When is lymphadenopathy of medical concern?

2. What are the clinical features of childhood diseases that present as cervical lymphadenopathy?

3. What are the diagnostic approaches to the evaluation of children with lymphadenopathy?

4. What is an appropriate therapeutic approach to cervical lymphadenopathy in children?

Lymphadenopathy is among the most common clinical problems encountered in pediatrics. Palpable lymph nodes are a source of anxiety for parents, often prompting a visit to the pediatrician for evaluation. Although most cases are caused by a benign, self- limited infectious process, lymphadenopathy may also signal a serious underlying systemic illness. It is important for the pediatrician to make this distinction so that appropriate diagnostic and therapeutic measures can be initiated when necessary.


Lymphadenopathy occurs frequently in childhood, and even healthy children may have palpable lymph nodes in the anterior cervical, inguinal, and axillary regions. Localized lymphadenopathy is mainly caused by an infectious etiology, whereas generalized lymphadenopathy occurs with systemic illnesses, such as systemic infections (ie, viral, bacterial, protozoal, fungal), autoimmune disorders, storage disorders, and malignancies.

Clinical Presentation

Lymphadenopathy may be localized or generalized on presentation. Localized or regional lymphadenopathy refers to enlargement of lymph nodes within contiguous regions, whereas generalized lymphadenopathy involves more than 2 noncontiguous lymph node groups (Box 100.1). Infection is the most frequent cause of localized lymphadenopathy in children. The anterior cervical lymph node region is the most commonly involved area because it is affected by upper respiratory infections (URIs), which occur frequently in childhood. Bilateral cervical lymphadenopathy often occurs in viral and bacterial URIs, and the nodes tend to be soft, mobile, and nontender. Viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can present with prominent posterior cervical lymphadenopathy as well as generalized adenopathy and occasionally hepatosplenomegaly. Direct bacterial invasion of lymph nodes produces lymphadenitis, which typically is unilateral, tender, erythematous, and fluctuant. Subacute or chronic lymphadenopathy may be caused by atypical mycobacterial infections, tuberculosis, cat-scratch disease, EBV, CMV, toxoplasmosis, coccidioidomycosis, or HIV. Generalized lymphadenopathy is concerning for an underlying systemic illness (ie, infection, autoimmune process, storage disease, malignancy). Lymphadenopathy resulting from malignancy typically is characterized by fixed, firm, nontender lymph nodes in the setting of other signs and symptoms, such as fever, pallor, night sweats, and weight loss.


Lymph nodes are an integral part of the immune system in which phagocytic cells filter both microorganisms and particulate matter and antigens are presented, thereby provoking a cellular or humoral mediated lymphocyte response. Lymph nodes are distributed in groups throughout the body and drain specific regions (ie, head, neck, axilla, mediastinum, abdomen, extremities) (Table 100.1). Enlargement of a lymph node may be caused by proliferation of lymphocytes intrinsic to the lymph node (as a physiologic immune response or a malignant transformation) or infiltration by either pathogens or extrinsic inflammatory or metastatic malignant cells.

Box 100.1. Diagnosis of Lymphadenopathy in Children

Enlarged lymph nodes


Tenderness or warmth over the lymph nodes (signs of inflammation [ie, lymphadenitis])

Antecedent infection (eg, pharyngitis, upper respiratory infection, otitis media, skin and soft tissue infections)


Weight loss

Bone pain

Night sweats

Table 100.1. Lymph Node Drainage Patterns
Group Drainage Pattern
Occipital Posterior scalp
Preauricular Superficial orbital and periorbital tissue, temporal scalp
Submental/submandibular Mouth
Cervical Mouth, pharynx, ear, parotid gland, deep structures of neck (ie, thyroid, larynx, trachea, upper esophagus)
Supraclavicular Head, neck, arms, lungs, mediastinum, and abdomen
Mediastinal Lungs, heart, thymus, esophagus
Axillary Chest wall, breast, upper extremity
Abdominal Abdominal organs, pelvis, lower extremities
Iliac and inguinal Lower extremities, genitalia, buttocks, pelvis

Differential Diagnosis

The duration and extent of lymphadenopathy, that is, localized versus generalized; characteristics of the lymph nodes; and presence of associated symptoms help focus the differential diagnosis. A list of common causes of lymphadenopathy in children is provided in Table 100.2.

Localized lymphadenopathy is most often caused by an infectious etiology. Acute bilateral cervical lymphadenopathy is most frequently caused by viral URIs (ie, respiratory syncytial virus, adenovirus, parainfluenza and influenza viruses) or EBV and CMV, which can also cause generalized adenopathy. Bacterial pharyngitis (most commonly Streptococcus species) and oral infections or dental abscesses can present with cervical adenopathy. Unilateral lymphadenitis is most often caused by Staphylococcus aureus, followed by Streptococcus pyogenes, anaerobes, and other species. When the condition appears subacute, the following etiologies should be considered: cat-scratch disease, tuberculosis (ie, scrofula), atypical mycobacteria, toxoplasmosis, tularemia, and, less commonly, histoplasmosis, brucellosis, and syphilis. Cervical lymphadenopathy can also occur with Kawasaki disease, with high fever (5 days’ duration); redness, swelling, and desquamation of extremities; nonpurulent conjunctivitis; rash; and swollen lips and tongue.

Generalized lymphadenopathy may be caused by systemic infections (eg, EBV, CMV, HIV, toxoplasmosis), autoimmune disorders (eg, juvenile idiopathic arthritis, systemic lupus erythematosus), storage disorders (eg, Niemann disease, Gaucher disease), histiocytic disorders (eg, Langerhans cell histiocytosis, hemophagocytic lym-phohistiocytosis), drug reactions (eg, phenytoin), or malignancies. Malignancies include leukemia and lymphoma (Hodgkin and non-Hodgkin) as well as solid tumors that can metastasize to lymph nodes (eg, neuroblastoma, rhabdomyosarcoma). With neoplastic infiltration, enlarged nodes are generally nontender, firm, rubbery, and immobile. In Hodgkin disease, the nodes enlarge sequentially, with involvement spreading from 1 chain to the next. Supraclavicular or epitrochlear adenopathy is strongly suggestive of malignancy.

Several head and neck lesions that occur in the pediatric population are often confused with cervical lymphadenopathy. These lesions include cystic hygromas, branchial cleft cysts, thyroglossal duct cysts, and epidermoid cysts. These are congenital malformations that often present as a neck mass in the young child and can easily be mistaken for a lymph node, particularly if infected (see Chapter 94).



A thorough history and review of symptoms is essential in determining the underlying etiology of lymphadenopathy in children. Inquiries should be made about the duration of the lymphadenopathy, rate of nodal enlargement, and occurrence of associated fever and other constitutional symptoms, such as bone pain, weight loss, fever, and night sweats. Recent illnesses or infections, insect or animal bites, and local trauma should be determined. A history of distant travel, recent emigration from countries with endemic tuberculosis (eg, Mexico, Central America, Southeast Asia), recent travel to areas with endemic histoplasmosis (eg, southeastern United States) or coccidioidomycosis (eg, San Joaquin Valley, CA), a detailed history of pet contact (eg, cats or kittens, which can transmit toxoplasmosis and cat-scratch disease), and exposure to ill contacts, particularly individuals known to have tuberculosis, are also important (Box 100.2). In addition, it is important to obtain a history of chemical exposure and steroid use.

Physical Examination

When evaluating a child with lymphadenopathy, the enlarged nodes should be examined and measured at their widest diameter and evaluated for evidence of erythema, tenderness, and warmth, all of which are suggestive of infection. The characteristics of the enlarged lymph node should be noted (eg, soft, firm, rubbery, mobile, matted, tender, discrete). The surrounding skin and soft tissue region that is drained by the involved lymph node should be examined for signs of inflammation or skin breakdown. The extent of the lymphadenopathy should be determined, and the presence or absence of hepatosplenomegaly should be noted.

Box 100.2. What to Ask


How long have the nodes been enlarged?

Was the child sick before the swelling began?

Does the child currently have any symptoms, such as fever, weight loss, pallor, night sweats, or anorexia?

Does the child come in contact with any animals, particularly cats?

Has the child traveled anywhere?

Is the child taking any medications?

Has the child been in contact with anyone who is ill?

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Aug 28, 2021 | Posted by in PEDIATRICS | Comments Off on Lymphadenopathy
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