FIGURE 47.5 Child with nontuberculous mycobacterium (NTM) lymphadenitis In addition to infectious causes of cervical lymphadenopathy, there are numerous noninfectious etiologies that cause cervical node enlargement as a manifestation of systemic disease Such noninfectious etiologies that may be encountered in pediatric patients include Kawasaki disease, malignancy, histiocytosis, lymphoproliferative disorders, and periodic fever syndromes An important cause of acute cervical adenopathy in young children is Kawasaki disease, or mucocutaneous lymph node syndrome (see Chapter 86 Cardiac Emergencies ) Kawasaki disease usually affects children younger than years of age and is rare after years of age Typical presentation of the disease is characterized by fever of at least days’ duration, along with bilateral nonexudative conjunctivitis, changes to oral mucosa, peripheral extremity changes, a polymorphous rash, and cervical lymphadenopathy The cervical lymphadenopathy in Kawasaki disease, seen in approximately 50% to 70% of patients, occurs during the early phase of the illness and may be unilateral or bilateral The nodes are firm, mildly tender, and at least 1.5 cm in diameter It is important to diagnose Kawasaki disease early because prompt treatment with intravenous immune globulin (IVIG) and aspirin can prevent coronary artery aneurysms, the most serious complication of this disease Various malignancies, including lymphoma and neuroblastoma may present with chronic cervical adenopathy Lymph nodes in Hodgkin lymphoma are painless, with a rubbery and firm consistency, and located in the cervical, supraclavicular, or axillary regions Palpation of such nodes in children, particularly when a history of nonspecific symptoms such as fatigue, anorexia, and weight loss are elicited, should lead to prompt evaluation with chest radiograph to evaluate for mediastinal masses Neuroblastoma, most common in infants and children less than years of age, is a neuroendocrine tumor arising in the adrenal glands, but can originate in the high thoracic and cervical sympathetic ganglia or metastasize to cervical and supraclavicular lymph nodes Again, prompt imaging with chest radiograph, as well as abdominal imaging with computed tomography (CT) or magnetic resonance imaging (MRI) should be initiated in cases of suspected neuroblastoma Rare noninfectious causes of chronic cervical lymphadenopathy deserve consideration in the appropriate clinical context Sarcoidosis is a multisystem granulomatous disorder that affects young adults, particularly African Americans, causing systemic symptoms such as weight loss, cough, fatigue, and joint pain Patients often have chronic bilateral cervical adenopathy, and chest radiograph in such patients may reveal hilar adenopathy as well Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale–Smith syndrome, is a genetic disorder of lymphocyte apoptosis leading to lymphadenopathy, splenomegaly, and pancytopenia Children with ALPS present in the first year of life with massive cervical adenopathy and splenomegaly Histiocytic disorders, another uncommon group of diseases that cause prominent cervical adenopathy, occur when there is an overproduction of dendritic cells or macrophages which cause organ damage and tumor formation Langerhans cell histiocytosis (LCH) affects children less than years of age, causing lytic bone lesions and unilateral or bilateral soft and matted cervical lymphadenopathy Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) presents in children as massively enlarged, nontender cervical lymphadenopathy, along with involvement of the nasal cavity, lytic bone lesions, pulmonary nodules, or rash Finally, the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is an autoinflammatory disease presenting in young children that cycles every to weeks Children with PFAPA experience tender cervical lymphadenopathy with flares There is no specific diagnostic test, and though corticosteroids and nonsteroidal anti-inflammatory drugs alleviate symptoms, the condition resolves spontaneously by 10 years of age Other Lymphadenopathy of the Head and Neck Beyond cervical lymphadenopathy, acute localized adenopathy of the head and facial regions has a more narrow differential diagnosis, and the location of lymphadenopathy often suggests a cause, based on the location of focal infections and drainage patterns of nodes Submandibular and submental nodes, draining the lips, buccal mucosa, and floor of the oropharynx, enlarge with infection within the oral cavity This includes dental caries and abscesses, as well as gingivostomatitis Herpetic gingivostomatitis generally affects the anterior tongue, buccal mucosa, or lips, while Coxsackievirus gingivostomatitis affects the posterior oropharynx, sparing the gingiva and lips, and causes characteristic lesions on palmar and plantar surfaces Lymphadenopathy in the submandibular or submental regions on physical examination should prompt a careful oral and dental examination Preauricular nodes, located anterior to the ear, drain the conjunctiva and lateral eyelids These nodes enlarge with eye or conjunctival infections, of which viral infections are a prominent cause The combination of conjunctivitis and ipsilateral preauricular adenopathy is called oculoglandular syndrome, or Parinaud syndrome Infections that can present as oculoglandular syndrome include adenovirus or chlamydial conjunctivitis in neonates Rarely, catscratch disease and tularemia manifest as an oculoglandular syndrome Posterior auricular nodes, located behind the ear, and occipital nodes, found at the base of the scalp, commonly enlarge in response to scalp infections or chronic inflammation Pediculosis (lice), tinea capitis, bacterial scalp infections, and inflammation from seborrheic dermatitis are all common causes of such node enlargement in children Axillary and Epitrochlear Axillary adenopathy is commonly present with any infection or inflammation of the upper extremities Most commonly, injuries to the hand, such as occur after falling or with puncture wounds or bites, may present with concomitant axillary adenopathy as a reactive response to disruption in skin integrity Axillary adenopathy is also a common part of B henselae infection (catscratch disease), as outlined previously as a cause of cervical adenopathy Epitrochlear adenopathy is significantly less common than axillary adenopathy in children, and any epitrochlear node greater than 0.5 cm is considered enlarged Epitrochlear nodes may become inflamed after infections of the third, fourth, or fifth finger; medial portion of the hand; or ulnar portion of the forearm Most commonly, these infections are caused by pyogenic bacteria (e.g., Streptococcus pyogenes or S aureus, including MRSA), but depending on the inciting event, other pathogens may be responsible (e.g., Streptobacillus moniliformis and Spirillum minus in rat-bite fever or F tularensis in tularemia) Rare causes of both axillary and epitrochlear adenopathy include rheumatologic disease of the hand or wrist and secondary syphilis Inguinal Inguinal adenopathy most often results from lower extremity skin or soft tissue infection However, inguinal lymph nodes also drain tissues in the perianal region and unexplained adenopathy in this area should prompt examination for perirectal abscesses, fissures, or other inflammation In addition, sexually transmitted diseases such as chlamydia or gonorrhea may cause inguinal adenopathy Acute genital infection with herpes simplex virus-2 (HSV-2) often presents with tender inguinal adenopathy, occasionally as the only sign Chancroid, lymphogranuloma venereum, and syphilis are rare causes of inguinal node swelling and tenderness The presence of genital lesions, which may be either painful (as in herpes simplex virus or chancroid) or painless (as in syphilis), offers clues to these diagnoses Therefore, careful history taking and physical examination are necessary to exclude these possibilities Iliac Enlarged iliac nodes are palpable deeply over the inguinal ligament and become inflamed with lower extremity infection, urinary tract infection, abdominal trauma, and appendicitis Of note, iliac adenitis, which can present with fever, limp, and inability to fully extend the leg, may mimic the signs and symptoms of septic hip arthritis Unlike in hip disease, however, hip motion is not limited on examination Iliac adenitis may also be confused with appendicitis, but the pain initially occurs in the thigh and hip rather than in the periumbilical region or right lower quadrant GENERALIZED LYMPHADENOPATHY Generalized lymphadenopathy, defined as enlargement of lymph nodes in two or more noncontiguous regions, can be a manifestation of both infectious and noninfectious systemic illnesses ( Table 47.2 ) Akin to localized lymphadenopathy, generalized lymphadenopathy in children is most often caused by bacterial or viral infections As an example, the high incidence of vomiting and abdominal pain in streptococcal pharyngitis has been attributed to abdominal lymph node swelling and inflammation, suggesting a more systemic pattern of adenopathy in streptococcal disease More rare bacterial causes of generalized lymphadenopathy include the zoonotic infections brucellosis, leptospirosis, and tularemia Brucellosis is acquired by exposure to cattle, sheep, goats, or unpasteurized milk or cheese and causes systemic symptoms including fever, night sweats, weight loss, arthralgias, and epididymoorchitis, as well as nonspecific examination findings including generalized lymphadenopathy and hepatosplenomegaly Leptospirosis is most common in tropical climates, acquired via exposure to contaminated soil or water (particularly during swimming) Clinical manifestations are nonspecific, including fever, rigors, myalgias, headache, conjunctivitis, rash, hepatosplenomegaly, and lymphadenopathy Brucellosis, leptospirosis, and tularemia (discussed previously) should be considered in the differential diagnosis of a child presenting with systemic symptoms, particularly fever, and physical examination findings of generalized lymphadenopathy if the appropriate exposure history is elicited Common viral causes of generalized adenopathy include EBV or CMV mononucleosis, and rubella and measles infections in parts of the world where these diseases are endemic Though EBV mononucleosis classically causes fever, pharyngitis, and anterior and posterior cervical adenopathy; axillary and inguinal lymphadenopathy may also be presenting signs In children with symptoms of infectious mononucleosis but a negative monospot and/or negative antibody titers to EBV antigens, CMV may be the cause Rubella produces a prodrome of low-grade fever and lymphadenopathy (posterior cervical, postauricular, or generalized) followed by the development and rapid spread of a pink, maculopapular rash from face to the trunk and extremities Measles (rubeola) produces a prodrome of fever, malaise, and anorexia followed by cough, conjunctivitis, coryza, and characteristic Koplik spots on the buccal mucosa The exanthem of measles also has a cranial to caudal progression of a blanching, maculopapular rash, and lesions can become confluent Children with severe measles may exhibit generalized