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 neoplastic processes Lymphadenopathy of greater than weeks’ duration is considered chronic The clinician caring for a child with lymphadenopathy will benefit from knowledge of the anatomic distribution of nodes in the area and their drainage patterns as described in Figures 47.1 and 47.2 , as well as Table 47.1 The location of lymphadenopathy is often suggestive of a possible cause CAUSES OF LYMPHADENOPATHY BY REGION Cervical Enlargement of cervical lymph nodes is a common presenting sign in a variety of pediatric illnesses In order to narrow the differential diagnosis, it is helpful to identify the time course of swelling (acute or chronic); history or presence of localized infections; occurrence of systemic symptoms; and specific location, symmetry, and characteristics of enlarged nodes Cervical anatomy is complex, however nodes in the region can be classified generally as either superficial or deep Superficial cervical nodes, palpated readily along the anterior and posterior borders of the sternocleidomastoid muscle, drain the shallow structures of the head and neck—particularly the oropharynx, external ear, and parotid In contrast, deep cervical nodes, both superior and inferior, receive lymphatic drainage from a wider area of underlying structures of the head and neck, including the nasopharynx, tonsils and adenoids, larynx, and trachea While there are numerous infectious and noninfectious causes of acute and chronic cervical lymphadenopathy, the most common etiologies in children are infectious (see Chapter 94 Infectious Disease Emergencies ) By far, the most common cause of acute cervical adenopathy in children is reactive adenopathy associated with a viral upper respiratory tract infection Superficial nodes are generally symmetrically enlarged, mobile, and minimally tender Reactive adenopathy may persist for to weeks beyond the resolution of a viral illness However, there should be no progression in the size or the extent of the adenopathy after resolution of symptoms of the virus Another common infectious cause of cervical lymph node enlargement, particularly in preschool-aged children, is lymphadenitis Lymphadenitis occurs when an enlarged node becomes inflamed and tender over the course of a few days, as the result of a viral or bacterial infection Viral adenitis is often associated with fever, conjunctivitis, pharyngitis, or other symptoms of an upper respiratory tract infection and causes acute bilateral swelling Common causes are rhinovirus, adenovirus, enterovirus, influenza virus, respiratory syncytial virus, Epstein–Barr virus (EBV), and cytomegalovirus (CMV) Less commonly, herpes simplex, human herpesvirus type (roseola), or measles, mumps, or rubella are causative agents In contrast, bacterial adenitis typically is unilateral and presents with the rapid onset of a firm, tender, lymph node over to days The overlying soft tissue becomes warm, edematous, and erythematous Fever often accompanies the infection If left untreated, the node may become suppurative, which is detectable on examination as fluctuance Acute bacterial adenitis is most often caused by group A β-hemolytic Streptococcus or Staphylococcus aureus (including methicillinresistant S aureus [MRSA]) Prompt initiation of oral antimicrobial therapy that empirically covers MRSA can prevent progression to a suppurative infection However, patients who have failed to improve with oral antimicrobial therapy or those who present with signs of toxicity require parenteral therapy Drainage of the suppurative nodes is sometimes required, even in appropriately treated cases ( Figs 47.3 and 47.4 ) FIGURE 47.1 Lymph nodes of the head and neck A Deep nodes: Level B Superficial nodes (Reprinted with permission from Mancuso AA Head and Neck Radiology Philadelphia, PA: Lippincott Williams & Wilkins; 2010.) ... REGION Cervical Enlargement of cervical lymph nodes is a common presenting sign in a variety of pediatric illnesses In order to narrow the differential diagnosis, it is helpful to identify the