TABLE 47.3 DRUGS IMPLICATED IN SERUM SICKNESS AND DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) Serum sickness Common causes: Antimicrobials: penicillin, trimethoprim-sulfamethoxazole, cefaclor Uncommon causes: Aspirin, indomethacin Antimicrobials: ciprofloxacin, clarithromycin, itraconazole Antiepileptics: carbamazepine Captopril Bupropion, fluoxetine Heparin Insulin Iron-dextran Barbiturates DRESS Antiepileptics: carbamazepine, lamotrigine, phenytoin Antimicrobials: vancomycin, minocycline, dapsone, sulfamethoxazole Sulfasalazine Allopurinol Neoplastic disease that causes generalized adenopathy may be primary to the lymph node, as in lymphoma or it may be caused by an invasion of the lymph node by extrinsic malignant cells, as in leukemia Hodgkin lymphoma, discussed previously, results most often in cervical or supraclavicular adenopathy In contrast, non-Hodgkin lymphoma presents with relatively rapid development (over weeks) of nontender, diffuse lymphadenopathy accompanied by abdominal pain, vomiting, facial swelling, or wheezing due to compression of surrounding structures in the mediastinum or abdomen Children with acute leukemia often have generalized adenopathy, and nodes are firm or rubbery, nontender, and matted These children usually appear ill, having other systemic signs, including fevers, weight loss, bony pain, bruising, petechiae, and hepatosplenomegaly with anemia and thrombocytopenia Histiocytic disorders, caused by the accumulation and infiltration of macrophages and dendritic cells in affected tissues, are a rare cause of generalized adenopathy LCH and sinus histiocytosis (Rosai–Dorfman disease), discussed previously, cause cervical adenopathy; while hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease in children less than age that manifests with generalized adenopathy in one-third of patients It presents as a febrile illness with adenopathy, cytopenias, coagulopathy, hepatitis, splenomegaly, and neurologic involvement Characteristic laboratory findings include anemia, thrombocytopenia, and elevated liver enzymes, as well as extremely elevated ferritin levels and hypertriglyceridemia Immune and cytokine studies, as well as genetic testing and bone marrow studies showing hemophagocytosis are used to establish the diagnosis Finally, rare causes of systemic adenopathy include lipid storage diseases, such as Gaucher disease and Niemann–Pick disease, which can cause diffuse adenopathy and are almost always associated with hepatosplenomegaly Bone marrow biopsy, showing lipidladen histiocytes, is diagnostic LIFE-THREATENING LYMPHADENOPATHY In rare instances, lymphadenopathy can lead to a life-threatening condition In children and adolescents affected by Hodgkin or non-Hodgkin lymphoma or metastatic neuroblastoma, bulky or rapidly enlarging mediastinal lymph nodes can cause compression of the superior vena cava (SVC) or the tracheobronchial tree In SVC syndrome, lymph nodes that encircle the vena cava enlarge and cause obstruction to central venous blood flow This obstruction leads to clinical manifestations including dilated chest and neck veins, facial swelling and plethora, and dyspnea Progression may lead to headaches, confusion, and altered mental status as well as progressive respiratory distress Children with bulky adenopathy of the mediastinal or paratracheal nodes may present solely with respiratory symptoms, including stridor or wheezing, caused by compression of the trachea or bronchi by enlarged lymph nodes Emergency physicians who take care of children with suspected lymphoma must be aware of the acute risk of airway obstruction that may be exacerbated by changes in position (lying flat) or with sedation or anesthesia In addition, when treating children with SVC syndrome, physicians must be careful to administer all intravenous therapy in the lower extremities, as poor circulation in the upper extremities and torso because of venous obstruction results in poor drug distribution and places the patient at increased risk of thrombus formation EVALUATION AND DECISION The pediatric emergency physician who evaluates a child with lymphadenopathy is faced with an extensive differential diagnosis However, a targeted history and thorough physical examination can help focus evaluation of the patient and will often lead to the correct diagnosis Historical data that need to be obtained include the time of onset, rate of growth, and presence of other symptoms Local symptoms suggestive of infection are particularly relevant, including fever, conjunctivitis, otitis, pharyngitis, gingivostomatitis, or cellulitis, as these may correlate with acute regional lymphadenopathy In well-appearing children, recent illnesses must be considered, particularly because reactive adenopathy may persist for to weeks after the resolution of a viral illness During evaluation, it is important to note the presence of “red flag” constitutional symptoms, including prolonged fevers, weight loss, night sweats, arthralgias, rashes, and bruising or petechiae that may suggest underlying systemic pathology and prompt more aggressive evaluation Social history and ill contacts of children also provide important information in constructing a differential diagnosis Ill contacts of children at school or in the home, particularly affected by viral respiratory infections, infectious mononucleosis, or group A streptococcus infections, should be noted Inquiry about a child’s close contacts with a diagnosis of tuberculosis, symptoms of active disease, travel, or risk factors for acquisition is imperative when considering tuberculous adenitis Asking about pets (cats or fish tanks), residence (exposure to livestock), recent travel or outdoor activity (animal exposure and insect bites), and dietary patterns (consumption of unpasteurized milk or cheese, or undercooked meats) can provide key information in a given clinical context Finally, the clinician must ask about medication use and whether any prior treatment, such as antibiotic therapy, treatment with glucocorticoids, or attempted aspiration with cultures, has been initiated For example, children with NTM adenitis or Kawasaki disease may present to the emergency department after a course of antistaphylococcal antibiotic therapy failed to reduce the size of the node This information can often guide the physician to include or exclude certain diagnoses The importance of avoiding glucocorticoids prior to making a definitive diagnosis of the cause of lymphadenopathy should be emphasized Glucocorticoid treatment can mask or delay the histologic diagnosis of malignancy such as leukemia or lymphoma, and should not be given empirically to decrease node swelling The physical examination should include a careful measurement of the size of the enlarged nodes and documentation of the number of nodes involved to provide an adequate baseline for follow-up Describing a node’s consistency (soft, firm, rubbery, indurated, fluctuant), mobility (mobile or fixed), and degree of tenderness to palpation is essential Skin changes around the node (erythematous and edematous, or violaceous and paper-thin) should be noted Lymphadenopathy in any region should prompt examination of lymph nodes in all regions to assess for generalized involvement Finally, a complete physical examination noting rashes, hepatosplenomegaly, joint swelling, or other abnormalities is critical In well-appearing children without systemic symptoms, further evaluation of acute localized lymphadenopathy is generally unnecessary Children with symptoms of lymphadenitis (a unilateral node with erythema, edema, or tenderness) can be empirically treated with a 10- to 14-day course of antibiotics with MRSA coverage and reevaluated There are several predictors for a suppurative adenitis that may require surgical drainage These can be independently used in the decision-making process for diagnostic imaging and surgical consultation; absence of pharyngitis, age ≤3 years, WBC >15,000/mm3, and anterior cervical chain location Children without symptoms of an acute bacterial lymphadenitis can be observed over the same time course, provided they have no enlargement of the adenopathy and lack worrisome constitutional symptoms Reactive adenopathy that occurs after a viral illness typically resolved within to weeks In children with localized adenopathy that persists past to weeks, ill-appearing children, and children with generalized lymphadenopathy, further evaluation should be performed, guided by the differential diagnosis that was formed based on history and physical examination Any suspicion of malignancy warrants assessment with CBC with differential and peripheral blood smear examination, as well as chest radiograph to assess for mediastinal adenopathy In addition, lactate dehydrogenase and uric acid may be elevated, indicating tissue damage and rapid cell turnover Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are nonspecific, but may be elevated in children with systemic inflammatory diseases and can be helpful in monitoring response to treatment In children with nonspecific infectious symptoms, viral serologies (EBV, CMV, HIV) may be informative As indicated by history and examination, serology for B henselae, or tuberculin skin testing or serum testing for M tuberculosis may be performed Various imaging modalities may aid in the diagnosis of lymphadenopathy, including ultrasound (US), CT, and MRI The type of diagnostic radiology necessary to evaluate lymphadenopathy depends on the location and chronicity of the lymph node(s) In efforts to limit radiation to doses as low as reasonably achievable (ALARA principle), US has proven to be a very effective, noninvasive, inexpensive, highly available, and nonradiating type of imaging to evaluate lymphadenopathy in children US can distinguish between simple node enlargement and a suppurative lesion with higher sensitivity than CT Color Doppler imaging can demonstrate increased blood flow to inflamed lymph nodes as well as a hypoechoic (dark) center in a suppurative node Characteristics of the grouping of the lymph nodes can also aid the radiologist in narrowing the patient’s differential diagnosis It is important to note that children age >1 year with neck swelling ≤3 days are at low risk of having US findings that require surgical drainage CT may be preferred in the evaluation of lymphadenopathy when greater anatomic detail is desired, as in a preoperative radiologic evaluation or in the evaluation of deep cervical space neck infections Contrast-enhanced CT is more sensitive than US for the diagnosis of an abscess but lacks specificity due to the similar radiologic appearance of frank pus and phlegmonous changes MRI may provide these fine details without ionizing radiation, but the cost of imaging and need for sedation make CT a more preferable and easily accessible modality when accessed from the emergency department Finally, in the course of evaluation of lymphadenopathy, the decision to perform a biopsy on an enlarged node remains a clinical one In general, early node biopsy should be considered in children who are ill with systemic symptoms, persistent fever, or weight loss Deep inferior cervical or supraclavicular adenopathy, with or without an abnormal chest film, is pursued aggressively with biopsy, given the concern for malignancy, in particular lymphoma Beyond this, in the face of an otherwise negative diagnostic workup, serial measurement over a period of weeks showing progressive or rapid enlargement of the affected node raises suspicion for malignant disease and biopsy should be strongly considered Biopsy should also be considered if an enlarged node fails to regress in size after approximately weeks of observation ... and places the patient at increased risk of thrombus formation EVALUATION AND DECISION The pediatric emergency physician who evaluates a child with lymphadenopathy is faced with an extensive differential... including stridor or wheezing, caused by compression of the trachea or bronchi by enlarged lymph nodes Emergency physicians who take care of children with suspected lymphoma must be aware of the acute... has been initiated For example, children with NTM adenitis or Kawasaki disease may present to the emergency department after a course of antistaphylococcal antibiotic therapy failed to reduce the