CHAPTER 47 ■ LYMPHADENOPATHY KIYETTA H ALADE, BETH M D’AMICO INTRODUCTION Lymphadenopathy, defined as an enlargement of lymph nodes, is a frequent presenting sign in children Most illnesses causing lymphadenopathy are common viral or bacterial infections that improve spontaneously or with an appropriate course of antimicrobial therapy However, some serious illnesses, including malignancies, can present first as lymphadenopathy Thus, a focused history, thorough physical examination, and knowledge of various causes of adenopathy are important in formulating an appropriate differential diagnosis MECHANISM OF LYMPHADENOPATHY Enlargement of lymph nodes can be due to physiologic or pathologic causes Most commonly, when lymph nodes perform their normal function, antigenic stimulation causes proliferation of lymphocytes, and nodes increase in size This response is particularly active in children, who are frequently exposed to new antigens, thus accounting for the common observation of lymphadenopathy associated with pediatric infections A second cause of lymph node enlargement occurs when bacteria or other pathogens that are present in lymphatic fluid stimulate an influx of inflammatory cells, local cytokine release, and symptoms of lymphadenitis These include enlargement of the node, erythema, edema, and tenderness of the overlying skin A third cause of adenopathy is neoplastic disease, where malignant cells originate in or migrate to lymph nodes, infiltrating the node and causing enlargement Lastly, in rare cases, genetic storage diseases may lead to deposition of foreign material within the node A number of studies have described the presence of palpable lymph nodes in healthy infants and children A seminal study of well infants and children up to years of age reported more than half of the children had palpable nodes, most commonly in the cervical, occipital, and submandibular regions It is commonly accepted that lymph nodes in the cervical and axillary regions up to cm in diameter, nodes in the inguinal region up to 1.5 cm in diameter, and nodes in the epitrochlear region up to 0.5 cm in diameter are considered normal in children DIFFERENTIAL DIAGNOSIS As the differential diagnosis of lymphadenopathy is extensive, it is helpful to distinguish localized from generalized lymphadenopathy, and an acute from chronic time course Localized adenopathy includes lymphadenopathy in a single region, and generally occurs in response to a focal infectious process Generalized lymphadenopathy is defined as enlargement of more than two noncontiguous lymph node regions The most common causes of generalized adenopathy are systemic infections, autoimmune diseases, and