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Cervical Lymphadenopathy in the Dental Patient: a Review of Clinical Approach Ernesta Parisi, DMD1/Michael Glick, DMD2

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Cervical Lymphadenopathy in the Dental Patient: a Review of Clinical Approach Ernesta Parisi, DMD1/Michael Glick, DMD2 QUINTESSENCE INTERNATIONAL Cervical lymphadenopathy in the dental patient: A review of clinical approach Ernesta Parisi, DMD1/Michael Glick, DMD2 Lymph node enlargement may be an incidental finding on examination, or may be associated with a patient complaint. It is likely that over half of all patients examined each day may have enlarged lymph nodes in the head and neck region. There are no written guidelines specify- ing when further evaluation of lymphadenopathy is necessary. With such a high frequency of occurrence, oral health care providers need to be able to determine when lymphadenopathy should be investigated further. Although most cervical lymphadenopathy is the result of a benign infectious etiology, clinicians should search for a precipitating cause and examine other nodal locations to exclude generalized lymphadenopathy. Lymph nodes larger than 1 cm in diameter are generally considered abnormal. Malignancy should be considered when palpable lymph nodes are identified in the supraclavicular region, or when nodes are rock hard, rubbery, or fixed in consistency. Patients with unexplained localized cervical lympha- denopathy presenting with a benign clinical picture should be observed for a 2- to 4-week period. Generalized lymphadenopathy should prompt further clinical investigation. This article reviews common causes of lymphadenopathy, and presents a methodical clinical approach to a patient with cervical lymphadenopathy. (Quintessence Int 2005;36:423–436) KEY WORDS: cervical lymphadenitis, cervical lymphadenopathy, clinical evaluation, differen- tial diagnosis, head and neck lymphadenopathy, lymphadenitis, lymphaden- opathy, medications and lymphadenopathy, toxoplasmosis BACKGROUND cytes. These cells function to coordinate an antigenic response. Upon detection of for- Lymph node enlargement is part of our eign proteins and microorganisms, the body’s normal immune response. Lymph macrophages and dendritic cells, or antigen- nodes are distributed along the lymphatic presenting cells, are carried through lymphatic system and found throughout the human channels to the nearest lymph node. These body; they are centers for antigen presenta- antigen-presenting cells travel through the tion, antigen processing, and antigen recog- lymph node, presenting antigens to lympho- nition. The cell population within a lymph cytes found within the node. B-cells are found node consists mainly of macrophages, den- within the lymphoid follicles of the cortex, dritic cells, B-lymphocytes, and T-lympho- and T-cells reside in the paracortical regions. When antigen recognition occurs, B-cell surface immunoglobulin binds with the anti- gen and forms a germinal center within the 1Assistant Professor, Division of Oral Medicine, University of lymph node. Next, an immunoglobulin gene Medicine and Dentistry of New Jersey, Newark. with higher affinity for the antigen is pro- 2Professor and Chair, Department of Diagnostic Sciences, duced. Migration of the B-cell to the medul- University of Medicine and Dentistry of New Jersey, Newark. lary region occurs, followed by differentiation Reprint requests: Ernesta Parisi, DMD, Division of Oral of the B-cell to a plasma cell, which then se- Medicine, University of Medicine and Dentistry of New cretes modified immunoglobulin. When T-cells Jersey, 110 Bergen Street, D-860, Newark, NJ 07101. E-mail: [email protected] encounter antigen and recognition occurs, VOLUME 36 • NUMBER 6 • JUNE 2005 423 QUINTESSENCE INTERNATIONAL Parisi/Glick Table 1 Causes of lymphadenopathy I. Infectious Diseases a. Viral—infectious mononucleosis (EBV, CMV), infectious hepatitis, herpes simplex, HHV-6, VZV, rubella, measles, adenovirus, HIV b. Bacterial—streptococcus, staphylococcus, cat-scratch disease, brucellosis, tularemia, chancroid, tuberculo- sis, atypical mycobacterial infection, primary and secondary syphilis, diphtheria, leprosy c. Fungal—histoplasmosis, coccidioidomycosis, paracoccidioidomycosis d. Chlamydial—lyphogranuloma venereum, trachoma e. Parasitic—toxoplasmosis, leismaniasis, trypanosomiasis, filariasis f. Rickettsial—scrub typhus, richettsialpox II. Immunologic diseases a. Rheumatoid arthritis b. Mixed connective tissue disease c. Systemic lupus erythematosus d. Dermatomyositis e. Sjogren’s syndrome f. Serum sickness g. Drug hypersensitivity h. Primary biliary cirrhosis i. Graft-vs-host disease j. Silicone-associated III. Malignant diseases a. Hematologic (Hodgkin’s, non-Hodgkin’s, ALL, CLL, hairy cell leukemia, malignant histocytosis, T-cell lymphoma, multiple myeloma with amyloidosis) b. Metastatic—from primary sites IV. Lipid storage disease—Gaucher’s, Niemann-Pick, Tangier V. Endocrine disease—hyperthyroid, adrenal insufficiency, thyroiditis VI. Other disorders a. Castleman’s disease (giant lymph node hyperplasia) b. Sarcoidosis c. Dermatopathic lymphadenitis d. Lymphomatoid granulomatosis e. Kikuchi’s disease (histiocytic nectrotizing lymphadenitis) f. Kawasaki’s disease (mucocutaneous lymph node syndrome) g. Histocytosis X h. Severe hypertriglyceridemia the T-cell proliferates and produces T-cells swelling of the lymph nodes. Lymphadenitis specific for the inciting antigen. Conse- is the pathologic term for inflammation of the quently, this humoral and cell-mediated lymph nodes. When enlarged lymph nodes response results in expansion of the lymph are detected, a cause can sometimes be node. Antibodies and specified T-cells spill determined by careful medical history, thor- from the node, entering the lymphatic circu- ough physical examination, judicious selec- lation and eventually travel into the blood- tion of laboratory tests and, if necessary, a stream, where they will be able to localize to lymph node biopsy. the site of infection. In general, there are two mechanisms of lymphadenopathy—hyperplasia and infiltra- tion. The former occurs in response to ETIOLOGY OF immunologic or infectious stimuli, and the lat- LYMPHADENOPATHY ter is the result of infiltration by various cell types, including cancer cells, lipid cells, or The differential diagnosis for enlarged lymph glycoprotein-laden macrophages. nodes is extensive. Lymphadenopathy may When this occurs, lymph nodes may be be caused by drug reactions, infections, detected clinically. Lymphadenopathy is the immunologic disorders, malignancies, and term used to describe the clinical sign of several other disorders of uncertain etiology 424 VOLUME 36 • NUMBER 6 • JUNE 2005 QUINTESSENCE INTERNATIONAL Parisi/Glick (Table 1). An investigation of 454 patients Table 2 Medications associated with presenting with enlarged lymph nodes in the lymphadenopathy head and neck region showed that 61 Diphenylhydantoin (13.4%) were diagnosed with cat-scratch dis- Carbamazepine ease, 54 (11.9%) had primary lymphade- Hydralazine nopathy due to other infectious causes, and Allopurinal 41 (9.0%) had cervical lymphadenopathy Primidone Gold associated with primarily systemic infections. Cephalosporins In more than one-third of these patients, the Captopril cause of cervical lymph node enlargement Atenolol was not determined.1 In a survey of a family care practice, 56% of patients examined had palpable cervical lymph nodes.2 Drug reaction eral, acutely swollen and tender, and may Multiple medications have been associated persist for weeks after the resolution of other with systemic signs and symptoms, including symptoms. Nodes may be palpable in the lymphadenopathy (Table 2). Anticonvulsants anterior triangle of the neck. Diagnosis is and sulphonamides are most commonly often based on symptomatology. Viral cul- associated with causing lymphadenopathy.3 tures of the nasopharyngeal region are Although the mechanism is largely unknown, expensive, and seldom affect the therapeutic it may be related to a hypersensitivity re- outcome. Bacterial throat cultures or sero- sponse. This hypersensitivity response can logic antigen detection may be useful in present with mucocutaneous eruptions, fever, cases of persistent infection. hematologic abnormalities, organ involvement Due to the self-limiting nature of upper res- such as hepatitis or interstitial nephritis, and piratory infections, proper management is lymphadenopathy. Although the reaction re- dependent upon the etiology. Diagnostic solves upon drug withdrawal, the mortality tests are useful when the patient has persist- rate may be as high as 10%.4,5 Complications ent symptoms and may aid in selection of the can be avoided by early recognition of the appropriate treatment. Palliative treatment is hypersensitivity reaction and consequent often the only recommended therapy for viral withdrawal of the suspected medication. pharyngitis, however, antibiotics may also be indicated for bacterial infections. Infections Upper respiratory infections. Acute bilateral Local infection cervical lymphadenopathy is commonly Cervical lymphadenopathy is a common fea- caused by viruses and bacteria that infect the ture of localized infection. Local bacterial upper respiratory tract in both adults and infections of the head and neck often cause children.6 Viruses that frequently cause cervical adenopathy when draining nodes upper respiratory infections include aden- respond to local infection, or when the infec- ovirus, influenza virus, and respiratory syncy- tion localizes within the node itself. Bacterial tial virus. Group A beta hemolytic Strepto- infections often result in acutely enlarged coccus is the most common cause of bacte- lymph nodes that are warm, erythematous, rial pharyngitis, which is a type of upper res- and tender. Patients
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