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Evaluation of Unexplained Lymphadenopathy Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis HEIDI L. GADDEY, MD, and ANGELA M. RIEGEL, DO, Ehrling Bergquist Family Medicine Residency Program, Offutt Air Force Base, Nebraska Lymphadenopathy is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoim- mune disorders, as well as medications and iatrogenic causes. The history and physical examination alone usually identify the cause of lymphadenopathy. When the cause is unknown, lymphadenopathy should be classified as local- ized or generalized. Patients with localized lymphadenopathy should be evaluated for etiologies typically associated with the region involved according to lymphatic drainage patterns. Generalized lymphadenopathy, defined as two or more involved regions, often indicates underlying systemic disease. Risk factors for malignancy include age older than 40 years, male sex, white race, supraclavicular location of the nodes, and presence of systemic symptoms such as fever, night sweats, and unexplained weight loss. Palpable supraclavicular, popliteal, and iliac nodes are abnormal, as are epitrochlear nodes greater than 5 mm in diameter. The workup may include blood tests, imaging, and biopsy depend- ing on clinical presentation, location of the lymphadenopathy, and underlying risk factors. Biopsy options include fine-needle aspiration, core needle biopsy, or open excisional biopsy. Antibiotics may be used to treat acute unilateral cervical lymphadenitis, especially in children with systemic symptoms. Corticosteroids have limited usefulness in the management of unexplained lymphadenopathy and should not be used without an appropriate diagnosis. (Am Fam Physician. 2016;94(11):896-903. Copyright © 2016 American Academy of Family Physicians.) CME This clinical content ymphadenopathy refers to lymph associated symptoms, and location (localized conforms to AAFP criteria nodes that are abnormal in size vs. generalized). Table 2 lists common his- for continuing medical 2 education (CME). See (e.g., greater than 1 cm) or con- torical clues and their associated diagnoses. CME Quiz Questions on sistency. Palpable supraclavicular, Other historical questions include asking page 868. Lpopliteal, and iliac nodes, and epitrochlear about time course of enlargement, tender- Author disclosure: No rel- nodes greater than 5 mm, are considered ness to palpation, recent infections, recent evant financial affiliations. abnormal. Hard or matted lymph nodes may immunizations, and medications.4 suggest malignancy or infection. In primary care practice, the annual incidence of unex- AGE AND DURATION plained lymphadenopathy is 0.6%.1 Only About one-half of otherwise healthy chil- 1.1% of these cases are related to malignancy, dren have palpable lymph nodes at any one but this percentage increases with advancing time.4 Most lymphadenopathy in children is age.1 Cancers are identified in 4% of patients benign or infectious in etiology. In adults and 40 years and older who present with unex- children, lymphadenopathy lasting less than plained lymphadenopathy vs. 0.4% of those two weeks or greater than 12 months without younger than 40 years.1 Etiologies of lymph- change in size has a low likelihood of being adenopathy can be remembered with the neoplastic.2,5 Exceptions include low-grade MIAMI mnemonic: malignancies, infections, Hodgkin lymphomas and indolent non- autoimmune disorders, miscellaneous and Hodgkin lymphoma, although both typically unusual conditions, and iatrogenic causes have associated systemic symptoms.6 (Table 1).2,3 In most cases, the history and physical examination alone identify the cause. EXPOSURES Environmental, travel-related, animal, and History insect exposures should be ascertained. Factors that can assist in identifying the etiol- Chronic medication use, infectious expo- ogy of lymphadenopathy include patient age, sures, immunization status, and recent duration of lymphadenopathy, exposures, immunizations should be reviewed as well. 896Downloaded American from the Family American Physician Family Physician website at www.aafp.org/afp.www.aafp.org/afp Copyright © 2016 American AcademyVolume of Family 94, NumberPhysicians. 11 For ◆ theDecember private, noncom 1, 2016- mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Unexplained Lymphadenopathy SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Ultrasonography should be used as the initial imaging modality for children up to 14 years C 15 presenting with a neck mass with or without fever. Computed tomography should be used as the initial imaging modality for children older than C 15 14 years and adults presenting with solitary or multiple neck masses. In children with acute unilateral anterior cervical lymphadenitis and systemic symptoms, empiric C 17 antibiotics that target Staphylococcus aureus and group A streptococci may be given. Corticosteroids should be avoided until a definitive diagnosis of lymphadenopathy is made because C 4 they could potentially mask or delay histologic diagnosis of leukemia or lymphoma. Fine-needle aspiration may be used to differentiate malignant from reactive lymphadenopathy. C 19-22 A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort. Table 3 lists medications commonly associ- drainage patterns, as well as common etiol- ated with lymphadenopathy.2 Tobacco and ogies of lymphadenopathy in these regions.2 alcohol use and ultraviolet radiation expo- A skin examination should be performed to sure increase concerns for neoplasm. An rule out other lesions that would point to occupational history that includes mining, malignancy and to evaluate for erythema- masonry, and metal work may elicit work- tous lines along nodal tracts or any trauma related etiologies of lymphadenopathy, such that could lead to an infectious source of as silicon or beryllium exposure. Asking the lymphadenopathy. Finally, abdomi- about sexual history to assess exposure to nal examination focused on splenomegaly, genital sores or participation in oral inter- although rarely associated with lymph- course is important, especially for ingui- adenopathy, may be useful for detecting nal and cervical lymphadenopathy. Finally, family history may identify familial causes of lymphadenopathy, such as Li-Fraumeni 2 Table 1. MIAMI Mnemonic for Differential Diagnosis syndrome or lipid storage diseases. of Lymphadenopathy ASSOCIATED SYMPTOMS Malignancies A thorough review of systems aids in iden- Kaposi sarcoma, leukemias, lymphomas, metastases, skin neoplasms tifying any red flag symptoms. Arthralgias, Infections muscle weakness, and rash suggest an auto- Bacterial: brucellosis, cat-scratch disease (Bartonella), chancroid, cutaneous immune etiology. Constitutional symptoms infections (staphylococcal or streptococcal), lymphogranuloma venereum, of fever, chills, fatigue, and malaise indicate primary and secondary syphilis, tuberculosis, tularemia, typhoid fever an infectious etiology. In addition to fever, Granulomatous: berylliosis, coccidioidomycosis, cryptococcosis, drenching night sweats and unexplained histoplasmosis, silicosis weight loss of greater than 10% of body Viral: adenovirus, cytomegalovirus, hepatitis, herpes zoster, human immuno- weight may suggest Hodgkin lymphoma or deficiency virus, infectious mononucleosis (Epstein-Barr virus), rubella non-Hodgkin lymphoma.2,3,6 Other: fungal, helminthic, Lyme disease, rickettsial, scrub typhus, toxoplasmosis Physical Examination Autoimmune disorders Overall state of health and height and Dermatomyositis, rheumatoid arthritis, Sjögren syndrome, Still disease, systemic lupus erythematosus weight measurements may help identify Miscellaneous/unusual conditions signs of chronic disease, especially in chil- Angiofollicular lymph node hyperplasia (Castleman disease), histiocytosis, 7 dren. A complete lymphatic examination Kawasaki disease, Kikuchi lymphadenitis, Kimura disease, sarcoidosis should be performed to rule out generalized Iatrogenic causes lymphadenopathy, followed by a focused Medications, serum sickness lymphatic examination with consideration of lymphatic drainage patterns. Figures 1 Information from references 2 and 3. through 3 demonstrate typical lymphatic December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 897 Unexplained Lymphadenopathy infectious mononucleosis, lymphocytic leu- qualitative characteristics are unable to reli- kemias, lymphoma, or sarcoidosis.2,5 ably predict malignancy. Painful or tender lymphadenopathy is nonspecific and may NODAL CHARACTER AND SIZE represent possible inflammation caused The quality and size of lymph nodes should by infection, but it can also be the result of be assessed. Lymph node qualities include hemorrhage into a node or necrosis.3 No spe- warmth, overlying erythema, tenderness, cific nodal size is indicative of malignancy.3 mobility, fluctuance, and consistency. Shotty lymphadenopathy is the presence of multiple Localized Lymphadenopathy small lymph nodes that feel like “buck shots” HEAD AND CERVICAL under the skin.8 This usually implies reac- Head and neck lymphadenopathy can be tive lymphadenopathy from viral infection. classified as submental,
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