This chapter is intended to serve as a guide to the evaluation of patients who present with enlargement of the lymph nodes (lymphadenopathy) or the spleen (splenomegaly). Lymphadenopathy is a rather common clinical finding in primary care settings, whereas palpable splenomegaly is less so.
Lymphadenopathy may be an incidental finding in patients being examined for various reasons, or it may be a presenting sign or symptom of the patient's illness. The physician must eventually decide whether the lymphadenopathy is a normal finding or one that requires further study, up to and including biopsy. Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy children and young adults; healthy adults may have palpable inguinal nodes of up to 2 cm, which are considered normal. Further evaluation of these normal nodes is not warranted. In contrast, if the physician believes the node(s) to be abnormal, then pursuit of a more precise diagnosis is needed.
Approach to the Patient: Lymphadenopathy
Lymphadenopathy may be a primary or secondary manifestation of numerous disorders, as shown in Table 59–1. Many of these disorders are infrequent causes of lymphadenopathy. In primary care practice, more than two-thirds of patients with lymphadenopathy have nonspecific causes or upper respiratory illnesses (viral or bacterial) and <1% have a malignancy. In one study, 84% of patients referred for evaluation of lymphadenopathy had a "benign" diagnosis. The remaining 16% had a malignancy (lymphoma or metastatic adenocarcinoma). Of the patients with benign lymphadenopathy, 63% had a nonspecific or reactive etiology (no causative agent found), and the remainder had a specific cause demonstrated, most commonly infectious mononucleosis, toxoplasmosis, or tuberculosis. Thus, the vast majority of patients with lymphadenopathy will have a nonspecific etiology requiring few diagnostic tests.
Table 59–1 Diseases Associated with Lymphadenopathy
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Table 59–1 Diseases Associated with Lymphadenopathy
|1. Infectious diseases|
|a. Viral—infectious mononucleosis syndromes (EBV, CMV), infectious hepatitis, herpes simplex, herpesvirus-6, varicella-zoster virus, rubella, measles, adenovirus, HIV, epidemic keratoconjunctivitis, vaccinia, herpesvirus-8|
|b. Bacterial—streptococci, staphylococci, cat-scratch disease, brucellosis, tularemia, plague, chancroid, melioidosis, glanders, tuberculosis, atypical mycobacterial infection, primary and secondary syphilis, diphtheria, leprosy|
|c. Fungal—histoplasmosis, coccidioidomycosis, paracoccidioidomycosis|
|d. Chlamydial—lymphogranuloma venereum, trachoma|
|e. Parasitic—toxoplasmosis, leishmaniasis, trypanosomiasis, filariasis|
|f. Rickettsial—scrub typhus, rickettsialpox, Q fever|
|2. Immunologic diseases|
|a. Rheumatoid arthritis|
|b. Juvenile rheumatoid arthritis|
|c. Mixed connective tissue disease|
|d. Systemic lupus erythematosus|
|f. Sjögren's syndrome|
|g. Serum sickness|
|h. Drug hypersensitivity—diphenylhydantoin, hydralazine, allopurinol, primidone, gold, carbamazepine, etc.|
|i. Angioimmunoblastic lymphadenopathy|
|j. Primary biliary cirrhosis|
|k. Graft-vs.-host disease|
|m. Autoimmune lymphoproliferative syndrome|
|3. Malignant diseases|
|a. Hematologic—Hodgkin's disease, non-Hodgkin's lymphomas, acute or chronic lymphocytic leukemia, hairy cell leukemia, malignant histiocytosis, amyloidosis|
|b. Metastatic—from numerous primary sites|
|4. Lipid storage diseases—Gaucher's, Niemann-Pick, Fabry, Tangier|
|5. Endocrine diseases—hyperthyroidism|
|6. Other disorders|
|a. Castleman's disease (giant lymph node hyperplasia)|
|c. Dermatopathic lymphadenitis|
|d. Lymphomatoid granulomatosis|
|e. Histiocytic necrotizing lymphadenitis (Kikuchi's disease)|
|f. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)|
|g. Mucocutaneous lymph node syndrome (Kawasaki's disease)|
|h. Histiocytosis X|
|i. Familial Mediterranean fever|
|j. Severe hypertriglyceridemia|
|k. Vascular transformation of sinuses|
|l. Inflammatory pseudotumor of lymph node|
|m. Congestive heart failureAbbreviations: CMV, cytomegalovirus; EBV, Epstein-Barr virus.|
The physician will be aided in the pursuit of an explanation for the lymphadenopathy by a careful medical history, physical examination, selected laboratory tests, and perhaps an excisional lymph node biopsy.
The medical history should reveal the setting in which lymphadenopathy is occurring. Symptoms such as sore throat, cough, fever, night sweats, fatigue, weight loss, or pain in the nodes should be sought. The patient's age, sex, occupation, exposure to pets, sexual behavior, and use of drugs such as diphenylhydantoin are other important historic points. For example, children and young adults usually have benign (i.e., nonmalignant) disorders that account for the observed lymphadenopathy such as viral or bacterial upper respiratory infections; infectious mononucleosis; toxoplasmosis; and, in some countries, tuberculosis. In contrast, after age 50, the incidence of malignant disorders increases and that of benign disorders decreases.
The physical examination can provide useful clues such as the extent of lymphadenopathy (localized or generalized), size of nodes, texture, presence or absence of nodal tenderness, signs of inflammation over the node, skin lesions, and splenomegaly. A thorough ear, nose, and throat (ENT) examination is indicated in adult patients with cervical adenopathy and a history of tobacco use. Localized or regional adenopathy implies involvement of a single anatomic area. Generalized adenopathy has been defined as involvement of three or more noncontiguous lymph node areas. Many of the causes of lymphadenopathy (Table 59–1) can produce localized or generalized adenopathy, so this distinction is of limited utility in the differential diagnosis. Nevertheless, generalized lymphadenopathy is frequently associated with nonmalignant disorders such as infectious mononucleosis [Epstein-Barr virus (EBV) or cytomegalovirus (CMV)], toxoplasmosis, AIDS, other viral infections, systemic lupus erythematosus (SLE), and mixed connective tissue disease. Acute and chronic lymphocytic leukemias and malignant lymphomas also produce generalized adenopathy in adults.
The site of localized or regional adenopathy may provide a useful clue about the cause. Occipital adenopathy often reflects an infection of the scalp, and preauricular adenopathy accompanies conjunctival infections and cat-scratch disease. The most frequent site of regional adenopathy is the neck, and most of the causes are benign—upper respiratory infections, oral and dental lesions, infectious mononucleosis, or other viral illnesses. The chief malignant causes include metastatic cancer from head and neck, breast, lung, and thyroid primaries. Enlargement of supraclavicular and scalene nodes is always abnormal. Because these nodes drain regions of the lung and retroperitoneal space, they can reflect lymphomas, other cancers, or infectious processes arising in these areas. Virchow's node is an enlarged left supraclavicular node infiltrated with metastatic cancer from a gastrointestinal primary. Metastases to supraclavicular nodes also occur from lung, breast, testis, or ovarian cancers. Tuberculosis, sarcoidosis, and toxoplasmosis are nonneoplastic causes of supraclavicular adenopathy. Axillary adenopathy is usually due to injuries or localized infections of the ipsilateral upper extremity. Malignant causes include melanoma or lymphoma and, in women, breast cancer. Inguinal lymphadenopathy is usually secondary to infections or trauma of the lower extremities and may accompany sexually transmitted diseases such as lymphogranuloma ...