Pediatric cervical lymphadenopathy is a challenging medical condition for the patient, family, and physician. There are a wide variety of causes for cervical lymphadenopathy and an understanding of these causes is paramount in determining the most appropriate workup and management. A thorough history and physical examination are important in narrowing the differential diagnosis. Diagnostic studies and imaging studies play an important role as well. This article reviews the common causes of lymphadenopathy, and presents a methodical approach to a patient with cervical lymphadenopathy.
Key points
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Cervical lymphadenopathy is a common and usually benign finding.
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A thorough history and physical examination usually are sufficient to establish a diagnosis.
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Most often, cervical lymphadenopathy is self-limited, and treatment is not required.
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Further diagnostic laboratory and imaging studies may be warranted in the event of persistent or worrisome lymphadenopathy.
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Surgery should be reserved for lymphadenopathy that remains undiagnosed or has failed to resolve with medical treatment.
Introduction
Enlarged cervical lymph nodes are a common finding on physical examination in the pediatric population. Lymph nodes are discrete, ovoid structures that are widely distributed throughout the body. Lymphadenopathy is defined as an abnormality in the size and/or character of the lymph node. In general, lymph nodes larger than 1 cm in diameter are considered enlarged, and defined as cervical lymphadenopathy.
Most commonly, lymphadenopathy represents a transient response of lymphatic tissue hyperplasia to a local benign inflammatory process. Up to 90% of children between the ages of 4 and 8 have palpable cervical lymph nodes.
Lymphadenopathy, however, can also represent other more significant pathology, including a neoplastic process. Specifically, about 15% of biopsied cervical lymph nodes in children represent a malignancy. It is therefore critical to understand the differential diagnosis to direct an appropriate and timely evaluation ( Fig. 1 ).
Introduction
Enlarged cervical lymph nodes are a common finding on physical examination in the pediatric population. Lymph nodes are discrete, ovoid structures that are widely distributed throughout the body. Lymphadenopathy is defined as an abnormality in the size and/or character of the lymph node. In general, lymph nodes larger than 1 cm in diameter are considered enlarged, and defined as cervical lymphadenopathy.
Most commonly, lymphadenopathy represents a transient response of lymphatic tissue hyperplasia to a local benign inflammatory process. Up to 90% of children between the ages of 4 and 8 have palpable cervical lymph nodes.
Lymphadenopathy, however, can also represent other more significant pathology, including a neoplastic process. Specifically, about 15% of biopsied cervical lymph nodes in children represent a malignancy. It is therefore critical to understand the differential diagnosis to direct an appropriate and timely evaluation ( Fig. 1 ).
Pathophysiology
The lymphatic system is the defense system of the human body, and lymph nodes are the “police headquarters” that aid in this immune defense. When the human body is presented with a pathogen, a local inflammatory reaction occurs, that results in the pathogen being carried to the lymph nodes. Once in the lymph nodes, neutrophils are the initial defense cell that acts on the pathogen. If this does not eradicate the pathogen, macrophages are summoned, which trap, phagocytose, degrade and present the organisms as antigens on the MHC molecules. Other defense mechanisms include the complement system that is activated by proteins in the blood that attach to the pathogen. If the pathogen evades these defense mechanisms and invades the human cell, a stress signal can be released that causes the natural killer T cell to cause the human cell to die, eradicating the pathogen with it. Another method that the body employs to defend itself from pathogens is to use antibodies, which are produced by B cells. These antibodies attach to the pathogen surface proteins, which can activate the complement cascade or interfere with the function of the pathogen itself. Other cells utilized include dendritic cells that can induce helper T cells to release chemicals that enhance B cell function, as well as stimulate macrophages and neutrophils to arrive at the lymph node. Lastly, the cytotoxic T cell can be summoned to the lymph node to directly kill the cell. This entire immune response within the lymph node ultimately leads to its size increase.
Etiology
The causes of cervical lymphadenopathy can be classified into 6 major categories :
- 1.
Infections:
The most common cause of cervical lymphadenopathy in children is from a viral upper respiratory tract infection. The other viruses listed in Box 1 have all been associated with cervical lymphadenopathy as well.
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Group A β-hemolytic streptococci and Staphylococcus aureus are the most common causes of bacterial cervical lymphadenitis in children.
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Prevalence of methicillin-resistant S aureus (MRSA) is increasing; one study reports a rate rising from 15% to 40% in a 3-year period, whereas other studies report much higher rates.
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Anaerobic bacteria from dental caries and periodontal disease are other bacterial causes of cervical lymphadenopathy.
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Cat scratch disease caused by Bartonella henselae is estimated to have an annual incidence of 9.3 per 100,000 with most cases reported from September to January.
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Atypical mycobacteria and mycobacteria are other important causes of subacute or chronic cervical lymphadenopathy.
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Fungal infections associated with lymphadenopathy are typically seen in immunocompromised patients.
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Cervical adenopathy caused by parasitic infections other than Toxoplasma gondii is uncommon in the United States.
Box 1
- a.
Upper Respiratory Tract Infection Viruses
- i.
Rhinovirus
- ii.
Adenovirus
- iii.
Influenza virus
- iv.
Parainfluenza virus
- v.
Respiratory synctial virus
- i.
- b.
Epstein Bar Virus
- c.
Cytomegalovirus
- d.
Togavirus
- e.
Varicella-zoster virus
- f.
Herpes Simplex virus
- g.
Paramyxovirus
- h.
Coxackievirus A and B
- i.
Echovirus
- j.
Enterovirus
- k.
Human Herpesvirus-6
- l.
Human Immunodeficiency Virus
Viral infections that cause cervical lymphadenopathy
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- 2.
Immunologic diseases:
- a.
Rheumatoid arthritis
- b.
Mixed connective tissue disease
- c.
Sjogren syndrome
- d.
Graft-versus-host disease
- a.
- 3.
Malignancies:
The most common malignancies that are known to cause cervical lymphadenopathy are listed in Box 2 .
Malignancies
- a.
Hodgkin Lymphoma
- b.
Non-Hodgkin lymphoma
- c.
Neuroblastoma
- d.
Leukemia
- e.
Rhabdomyosarcoma
- f.
Metastatic disease
During the first 6 years of life, neuroblastoma and leukemia are the most common tumors associated with cervical lymphadenopathy, followed by rhabdomyosarcoma and non-Hodgkin lymphoma. After 6 years of life, Hodgkin lymphoma is the most common tumor associated with cervical lymphadenopathy, followed by non-Hodgkin lymphoma and rhabdomyosarcoma ( Fig. 2 ).
Metastatic disease can also present as cervical lymphadenopathy. The common diseases associated with this are thyroid carcinoma and nasopharyngeal carcinoma ( Fig. 3 ).
- 4.
Lipid storage diseases:
- a.
Gaucher disease
- b.
Niemann-Pick disease
- a.
- 5.
Endocrine diseases
- a.
Hyperthyroid
- b.
Adrenal insufficiency
- c.
Thyroiditis
- a.
- 6.
Miscellaneous:
Other miscellaneous causes of cervical lymphadenopathy are listed in Box 3 .
- a.
Kawasaki disease: The presence of nonsuppurative cervical lymphadenopathy greater than 1.5 cm is the 1 of the 5 diagnostic criteria.
- b.
Serum sickness: an allergic reaction, which can also provoke cervical and generalized lymphadenopathy by forming systemic antigen-antibody complexes after exposure to certain medications. A list of these medications is listed in Box 3 .
- c.
Diphtheria, tetanus, and pertussis (DTP)-induced cervical lymphadenopathy: a rare complication from the vaccination from unknown etiology.
- d.
Kikuchi-Fujimoto disease: formerly known as subacute necrotizing histiocytic lymphadenitis, is a rare cause of persistent cervical adenopathy, which is unresponsive to antibiotic therapy. It usually affects young Japanese women with tender lymphadenopathy.
Box 3
Miscellaneous
- a.
Kawasaki disease
- b.
Drugs
- i.
Phenytoin
- ii.
Isoniazid
- iii.
Pyrimethamine
- iv.
Allopurinol
- v.
Phenylbutazone
- i.
- c.
Serum sickness
- d.
Post vaccination
- e.
Rosai-Dorfman disease
- f.
Kikuchi Fujimoto disease
- g.
Sarcoidosis
Other causes of cervical lymphadenopathy
- a.
Clinical evaluation
A thorough history of the present illness is paramount in the diagnosis and management of a neck mass. Important details of the history are listed in the following paragraphs.
Age
The age of the child can sometimes help narrow the list of infectious organisms or disease process
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Staphylococcus aureus is most commonly seen in ages from neonates to 4 years of age.
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Group B streptococcus has a predilection for neonates and infants.
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Streptococcus pyogenes and atypical mycobacteria are more commonly seen in children between the age of 1 and 4.
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Between the ages of 5 and 15, Bartonella Henselae and anaerobic bacteria are the more common infectious causes of cervical lymphadenopathy.
Location and Time Duration of Lymph Nodes
The laterality and chronicity of the lymph nodes vary by the disease processes, as described in Table 1 . Usually lymphadenopathy of a shorter duration (days to weeks) is associated with a reactive disorder, whereas a longer duration is more concerning for malignancy. However, this is not reliable in separating benign from malignant disease.
| Acute Unilateral Cervical Lymphadenopathy | Acute Bilateral Cervical Lymphadenopathy | Subacute/Chronic Cervical Lymphadenopathy |
|---|---|---|
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|
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