Lymphadenopathy, Generalized
Lymphadenopathy, Generalized: Excerpt from The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
Jeffrey D. Harrison
Lymph nodes of abnormal size, consistency, or number define lymphadenopathy. Generalized lymphadenopathy refers to these abnormal nodes when they are found in two or more noncontiguous sites. Generalized lymphadenopathy should prompt further investigation by the physician.
Approach
A. Epidemiology. Few reliable studies exist regarding the incidence of unexplained lymphadenopathy; however, one large Dutch study places the incidence at 0.6% annually (1). Generalized lymphadenopathy comprises approximately 25% of these cases (3). No gender differences occur in regard to incidence (2). Nonspecific lymphadenopathy is found more frequently in those aged less than 40 years.
B. Causes. Infectious, autoimmune, granulomatous, or malignant diseases can cause generalized lymphadenopathy. Studies have shown a 4% cancer risk in those patients older than 40 years and a 0.4% cancer risk in those less than 40 years who present with generalized lymphadenopathy (1). Lymphadenopathy present for more than a year is usually from a nonspecific cause, whereas that present less than 2 weeks usually has an infectious cause.
History
should focus on those common causes of generalized lymphadenopathy.
A. History of present illness should focus on the duration, location, quality, and context of the lymphadenopathy. Note associated signs and symptoms such as rash, fever, sore throat, and cough (4) (Chapters 2.6, 8.1, and 13.6). The goal is to ascertain if the adenopathy is attributable to a specific cause.
B. Past medical history should focus on known illness, medication usage, and allergies. Serum sickness from antibiotic use as well as diphenylhydantoin for seizure prevention can cause generalized lymphadenopathy. Common chronic illnesses (e.g., lupus erythematosus and rheumatoid arthritis) can also cause generalized lymphadenopathy.
C. Social history should focus on the patient’s occupation, sexual history, and alcohol use. Hepatitis B, secondary syphilis, and early human immunodeficiency virus (HIV) can all present with generalized lymphadenopathy. Patients with Hodgkin’s disease can develop painful adenopathy with alcohol use.
D. Family history. Inquire about family illness with a genetic predisposition as well as any exposures to household contacts with infectious diseases (e.g., tuberculosis, infectious mononucleosis, or hepatitis B).
E. Review of systems should focus on constitutional symptoms such as weight loss, fatigue, night sweats, malaise, arthralgias, nausea, and vomiting (1).
Physical examination
A. General. A comprehensive physical examination should be performed on all patients with generalized lymphadenopathy. Focus on those findings consistent with the most frequent causes of generalized lymphadenopathy. Note the patient’s temperature and weight, because fever and weight loss are frequent findings. Examine the skin, mucous membranes, abdominal organs, and joints; specifically, the presence of rash, mucocutaneous ulceration, organomegaly, and arthritis can be a guide to possible causes of the adenopathy. The presence of splenomegaly in a patient with adenopathy implies a systemic illness (e.g., infectious mononucleosis, lymphoma, leukemia, lupus, sarcoidosis, toxoplasmosis, or cat scratch disease) (Chapter 15.4). Additionally, search for other abnormal lymph nodes. Studies have shown that clinicians identified only 17% of those cases of generalized lymphadenopathy when it was present (1).
B. Nodal examination. The abnormal lymph node groups should be specifically examined.
1. Size. Lymph nodes enlarged up to 1 cm in diameter can be considered normal in size. These have a low malignancy risk and can usually be observed. Lymph nodes greater than 1.5 cm × 1.5 cm in area have been shown to have a 38% risk of cancer involvement and merit further workup (2).
2. Location. Anterior cervical, submandibular, and inguinal nodes are normally palpable. The presence of supraclavicular adenopathy is always abnormal and carries a 90% cancer risk in those aged more than 40 years. Postocciptal nodes are associated with infectious mononucleosis, scalp lesions, toxoplasmosis, and non-Hodgkin’s lymphoma. Axillary nodes are associated with upper extremity infections, breast cancer, cat scratch disease, and lymphomas. Epitrochlear nodes are associated with pyogenic infections, sarcoidosis, tularemia, and syphilis. Inguinal nodes are associated with lower extremity infections and sexually transmitted diseases.
3. Pain. The presence or absence of pain is not a reliable indicator of the cause of adenopathy. Capsular swelling from acute infections can cause pain as can necrotic hemorrhage from a malignant lymph node.
4. Consistency. Rock hard nodes are consistent with metastatic disease (2). Firm rubbery nodes are found with lymphomas. Soft nodes tend to occur with infectious causes; however, this should not be considered diagnostic.
Testing
A. Primary laboratory test. Initial laboratory testing should include a complete blood count (CBC) and a slide test for infectious mononucleosis (IM) (1). Atypical lymphocytes are suggestive of IM, cytomegalovirus, or toxoplasmosis. Neutropenia is found with viral illness, lupus, brucellosis, and bone marrow replacement. Severe anemia can be seen with malignancy and autoimmune processes. If the initial mononucleosis spot is negative, the test should be repeated at intervals of 1, 2, and 3 weeks, if atypical lymphocytes are present in the CBC.
B. Secondary testing. If the initial laboratory results are nondiagnostic, order a purified protein derivative (PPD), antinuclear antibody, hepatitis B surface antigen, HIV, rapid plasma reagin, cytomegalovirus serology, and chest X-ray (CXR) study. Although the CXR is seldom positive, it can be helpful in finding tuberculosis (TB), histoplasmosis, lymphoma, or sarcoidosis. Although a PPD will not be diagnostic of TB, it can be helpful in differentiating sarcoid from TB on a node biopsy (2).
C. Lymph node biopsy. If the aforementioned laboratory testing is nondiagnostic, then lymph node biopsy may be indicated. The largest and most pathologic node should be removed. Axillary and inguinal nodes should be avoided as they often reveal only reactive hyperplasia. Biopsy should be avoided in cases of suspected IM and drug reaction because the histologic picture is easily confused with malignant lymphoma (2). Experienced hematologists or hematopathologists should handle all specimens. The value of fine needle aspiration is controversial, with reasonable arguments both for and against (4).
Diagnostic assessment
Generalized lymphadenopathy merits evaluation beyond mere observation, as a specific systemic illness will be the likely cause. The history and examination should focus on infectious, autoimmune, granulomatous, and malignant causes. If a specific entity is suspected based on the history and physical examination, then that entity should be specifically evaluated. In the event the cause is unclear, first order a CBC and mononucleosis spot. If these are negative, then serologic testing and a CXR are warranted. Consider lymph node biopsy in those cases where the node is rock hard or larger than 1.5 cm × 1.5 cm in size (1). Biopsy should be avoided in those cases where viral causes are clinically suggested.
References
1. Ferrer R. Lymphadenopathy: differential diagnosis and evaluation. Am Fam Physician 1998;58:1313–1320.
2. Pangalis GA, Vassilalopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol 1993;20:570–582.
3. Williamson HA. Lymphadenopathy in a family practice. J Fam Pract 1985;20:
449–452.
4. Henry P, Longo D. Enlargement of lymph nodes and spleen. Harrison’s on line 1999;61. www.harrisonsonline.com/
Book Source Details
- Book Title: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
- Author(s): Robert B. Taylor (editor)
- Year of Publication: 2000
- Copyright Details: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, Copyright © 2000 Lippincott Williams & Wilkins.
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