2010 U P D AT E Pediatric, Adolescent Surgical Associates, P.C. w w w. p a s a p c . c o m S P R I N G Approach to Lymphadenopathy in Children What the pediatrician needs to know Overview The cause of lymphadenopathy often is obvious after a complete history and physical examination. Important aspects of the history and examination include symptoms and signs suggestive of infection and/or systemic disease, and the location, size, consistency, fixation, and tenderness of the lymph nodes. Diagnostic Approach The diagnostic approach to children with peripheral lymphadenopathy varies from observation and reassurance to comprehensive diagnostic testing and aggressive medical and surgical therapy, depending upon the findings from the history and physical examination. It is not necessary to identify the underlying etiology in every patient since most cases are benign and self-limited. The pace of the evaluation is dictated by how ill the patient appears. Laboratory testing can be used to confirm a diagnosis that is suspected on the basis of the history and physical examination (eg, throat culture for group A streptococcal pharyngitis, heterophile antibodies for Epstein-Barr virus mononucleosis, serology for Bartonella henselae for cat scratch disease). In more difficult cases, or in cases in which the lymphadenopathy remains unexplained after the initial history, examination, and laboratory tests, additional laboratory tests and lymph node biopsy may be necessary. In ALL cases, treatment with corticosteroids must be avoided before a definitive diagnosis is made. Such treatment could mask or delay the histologic diagnosis of leukemia or lymphoma. History The history in a patient with lymphadenopathy should focus upon the following: • Location, duration, and laterality of adenopathy • Local symptoms suggestive of infection (eg, cough, pharyngitis, dental problems) or malignancy (eg, Horner syndrome, opsoclonus-myoclonus) • Associated constitutional symptoms (fever, weight loss, night sweats, arthralgias, skin rash) may suggest malignancy. Mycobacterium tuberculosis (TB), or rheumatologic disease. Fever typically accompanies lymphadenopathy caused by infections and is not particularly helpful in discriminating between infectious and noninfectious causes of lymphadenopathy. • Contacts (viral respiratory infections, cytomegalovirus [CMV], Epstein-Barr virus [EBV], group A streptococcal infection [GAS, Streptococcus pyogenes], TB) • Dental problems or mouth sores • Skin lesions or trauma (Staphylococcus aureus, GAS, herpes simplex virus, cat scratch disease • Animal exposures (cat scratch disease, toxoplasmosis [cats] PASA Surgical Staff General examination A complete physical examination should be performed to look for signs of systemic disease or infection: (eg, ecchymoses, rash, pharyngitis) • Weight loss of >10 percent of body weight may be indicative of malignancy. • Scalp lesions, conjunctival injection, nasal obstruction • Dental problems, pharyngitis, herpangina, herpes simplex virus gingivostomatitis. • Hepatosplenomegaly (systemic process such as EBV, CMV, HIV, syphilis, neoplastic disease, rheumatologic disease); abdominal mass (eg, neuroblastoma). • Localized lesions; generalized rash (viral illness). The lymph nodes should be examined with the following characteristics in mind: Location Localized lymphadenopathy (present in only one region) suggests local causes and should prompt a search for pathology in the area of node drainage although some systemic diseases, such as lymphomas, can present with local adenopathy. Generalized adenopathy (present in two or more non-contiguous regions) usually is a manifestation of systemic disease. Palpation of inguinal, cervical, and axillary nodes, in addition to the liver and spleen, can determine whether lymphadenopathy is localized or generalized. Size Abnormal nodes generally are greater than 2.5 cm in diameter. Although malignancy can be found in smaller nodes, it is more likely to be found in nodes larger than 2 cm Consistency Hard nodes are found in cancers that induce fibrosis and when previous inflammation has left fibrosis. Firm, rubbery nodes are found in lymphomas and chronic leukemia. Fixation Normal lymph nodes are freely movable in the subcutaneous space. Abnormal nodes can become fixed to adjacent tissues by invading cancers or inflammation in tissue surrounding the nodes. They also can become fixed to each other (“matted”) by the same processes. continued on page 2 continued from page 1 Tenderness Tenderness suggests that recent, rapid enlargement has caused tension in the pain receptors in the capsule. Tenderness typically occurs with inflammatory processes. The ancillary evaluation for patients with peripheral adenopathy may include blood tests, cultures, imaging, a trial of antimicrobial therapy, incision and drainage, and/or lymph node biopsy. The sequence of the evaluation varies depending upon whether the lymphadenopathy is localized or generalized and the presence of associated symptoms. Blood tests that may be necessary in the evaluation of a child with lymphadenopathy include Complete blood count (CBC), Erythrocyte sedimentation rate (ESR), Serology for EBV, Bartonella henselae, among others. Leukopenia and the presence of atypical lymphocytes are important findings as they may suggest an etiology (eg, malignancy, autoimmune lymphoproliferative disease, EBV). Although the ESR does not help to differentiate infection from malignancy, it tends to be higher (eg, ≥50 mm/hr) in patients with Hodgkin’s lymphoma. Cultures of the throat, skin, blood, and/or lymph node may be indicated in selected circumstances: Excisional biopsy (if tuberculous or nontuberculous mycobacterial infection is strongly suspected) or incision and drainage may be indicated in the moderately or severely ill child with acute unilateral lymphadenitis. Tuberculin skin testing (TST) may be indicated to exclude M. tuberculosis infection. TST also may result in reactive induration in children with nontuberculous mycobacterial (NTM) infection, but TST is not sensitive for NTM disease. Chest radiographs (CXR) may be necessary in the evaluation of the child with peripheral lymphadenopathy. CXR are performed to look for mediastinal masses or hilar adenopathy. Although persistent lymph node enlargement prompts clinicians to obtain a biopsy, as few as 20 percent of biopsies demonstrate a treatable disease. In some reported series, the character or size of the nodes is helpful in deciding when a biopsy is indicated, but location is probably the most important factor. Early lymph node biopsy may be indicated in patients with the following clinical features: • Systemic symptoms include fever >1 week, night sweats, weight loss (>10 percent of body weight) • Supraclavicular and lower cervical nodes • Fixed, nontender nodes in the absence of other symptoms • Abnormal CXR or CBC • Lack of infectious symptoms Numerous reviews have suggested approaches to the diagnosis of lymphadenopathy. One model was able to predict the need for biopsy in 97% of young patients (ages 9 to 25 years) based upon three variables: abnormal CXR, lymph node size greater than 2 cm and lack of ear, nose, and throat symptoms. Another surgical review demonstrated significant correlations between adenopathy and malignancy when patients were 10 years or older, had nodes greater than 3 cm, supraclavicular or fixed nodes, or an abnormal CXR. Localized nodes — The evaluation of children with localized adenopathy depends upon the location and size of the nodes Supraclavicular — Children with supraclavicular adenopathy should always be evaluated with CBC, CXR, and biopsy. Axillary — The evaluation of axillary adenopathy depends upon the size of the nodes. In children with small axillary adenopathy (<2.5 cm), bacterial (especially B. henselae) and fungal cultures may be obtained and empiric therapy initiated as indicated by the history and examination. Biopsy is indicated for those who fail to respond to appropriate antimicrobial therapy or whose lymphadenopathy persists for >1 month without improvement. Large axillary adenopathy (≥2.5 cm) usually requires biopsy. Cervical or inguinal — Patients with localized lymphadenopathy at other sites (eg, cervical, inguinal), can be observed for three to four weeks and treated empirically with antibiotics when appropriate, provided that nothing else in the history and physical examination suggests malignancy (eg, weight loss >10 percent of body weight, abnormal CBC or CXR, elevated ESR, fever, and lack of upper respiratory tract infection symptoms). The empiric antibiotic therapy should include coverage for common pathogens such as group A streptococcus and Staphylococcus aureus; the choice is complicated by the increasing prevalence of community-associated methicillin S. aureus (CA-MRSA) and clindamycin or TMP-SMX as initial treatment is reasonable. Antimicrobial therapy is usually continued for 10 to 14 days. This approach is safe and avoids unnecessary biopsies; in many patients, the adenopathy will resolve or the cause will become obvious during the two weeks of observation, with or without therapy. Even with diagnoses such as Hodgkin’s lymphoma, non-Hodgkin lymphoma, or tuberculosis, the window of opportunity for effective treatment is likely to remain open during this brief period of observation. Biopsy is appropriate if an abnormal node has not resolved after four weeks, or immediately in patients with other findings suggestive of malignancy, including weight loss (>10 percent of body weight), abnormal CBC or CXR, fevers, and lack of upper respiratory tract infection symptoms. To learn more details about lymphadenopathy in children or to discuss a specific patient for possible referral, please contact Pediatric, Adolescent Surgical Associates, P.C. at 404.252.3353. To view the evaluation and treatment algorithms for lymphadenopathy, view the clinical articles on our website at www.pasapc.com and click on Newsletters in the right menu bar.