Lymphadenopathy 

Lymph nodes, in conjunction with the spleen, tonsils, adenoids, and Peyer patches, are highly organized centers of immune cells that filter antigen from the extracellular fluid. Directly interior to the fibrous capsule is the subcapsular sinus. This allows lymph, an ultrafiltrate of blood, to traverse from the afferent lymph vessels, through the sinuses, and out the efferent vessels. The sinuses are studded with macrophages, which remove 99% of all delivered antigens.

Interior to the subcapsular sinus is the cortex, which contains primary follicles, secondary follicles, and the interfollicular zone. Follicles within the cortex are major sites of B-cell proliferation, whereas the interfollicular zone is the site of antigen-dependent T-cell differentiation and proliferation. The deepest structure within the lymph node is the medulla, consisting of cords of plasma cells and small B lymphocytes that facilitate immunoglobulin secretion into the exiting lymph.

The lymph node, with its high concentration of lymphocytes and antigen-presenting cells, is an ideal organ for receiving antigens that gain access through the skin or gastrointestinal tract. Nodes have considerable capacity for growth and change. Lymph node size depends on the person's age, the location of the lymph node in the body, and antecedent immunological events. In neonates, lymph nodes are barely perceptible, but a progressive increase in total lymph node mass is observed until later childhood. Lymph node atrophy begins during adolescence and continues through later life.

Most lymphadenopathy in children is due to benign self-limited disease such as viral infections, and adenopathy is secondary to an increase in normal lymphocytes and macrophages in response to an antigen. Other less common mechanisms responsible for adenopathy include nodal accumulation of inflammatory cells in response to an infection in the node (lymphadenitis), neoplastic lymphocytes or macrophages (lymphoma), or metabolite-laden macrophages in storage diseases (Gaucher disease).

Frequency

United States

The precise incidence of lymphadenopathy is not known, but estimates of palpable adenopathy in childhood vary from 38-45%,^[1] and lymphadenopathy is one of the most common clinical problems encountered in pediatrics.^[2] Determining whether adenopathy is simply a normal response to frequent viral infections within an age group or if it is significant enough to consider more serious underlying disease is often difficult.

In the United States, common viral and bacterial infections are overwhelmingly the most common cause of adenopathy. Infectious mononucleosis and cytomegalovirus (CMV) are important etiologies, but adenopathy is usually caused by common viral upper respiratory tract infections. Localized lymphadenitis is most often caused by staphylococci and beta-hemolytic streptococci.

Other infections, such as human immunodeficiency virus (HIV), malignancies, and autoimmune diseases, are less common causes of adenopathy.

International

Infections that are rarely observed in the United States, such as tuberculosis, typhoid fever, leishmaniasis, trypanosomiasis, schistosomiasis, filariasis, and fungal infections, are common causes of lymphadenopathy in developing nations.^[3] HIV infections must be strongly considered in areas of high incidence.

Mortality/Morbidity

In the United States, mortality and serious morbidity caused by adenopathy are unusual given the common infectious etiologies.

• Malignancies, such as leukemia, lymphomas, and neuroblastoma, are the primary causes of mortality in the United States.^[4]
• Significant morbidity and mortality are also associated with autoimmune disorders (eg, juvenile rheumatoid arthritis, systemic lupus erythematosus), histiocytoses, and storage diseases.
• HIV is an uncommon cause of adenopathy in the United States, but its associated mortality requires consideration.

Race

Race is not a factor in most lymphadenopathy. Rare causes may be associated with particular ethnic groups (eg, sarcoidosis in Africans, Kikuchi-Fujimori disease in Asians).

Sex

Sex does not influence childhood lymphadenopathy.

Age

Adenopathy is most common in young children whose immune systems are responding to newly encountered infections. Adenopathy may be seen in one third of neonates and infants, usually in nodes that drain areas with mild skin irritation. Generalized adenopathy is rare in the neonate and suggests congenital infections, such as CMV. Adenopathy related to malignancy is rare at all ages. If diagnosed, it is often secondary to leukemia or neuroblastoma in younger children, and to Hodgkin lymphoma in adolescents.^[5]