Cervical Lymphadenitis: Etiology, Diagnosis, and Management Alexander K.C. Leung , MBBS, FRCPC, FRCP(UK&Irel), FRCPCH, and H. Dele Davies , MD, MS, MHCM, FRCPC Corresponding author differential diagnosis, clinical and laboratory evaluation, Alexander K.C. Leung, MBBS, FRCPC, FRCP(UK&Irel), FRCPCH and management of children with cervical lymphadenitis. Department of Pediatrics, University of Calgary, Alberta Children’s Hospital, Room 200, 233 16th Avenue NW, Calgary, Alberta, Canada T2M 0H5. E-mail: [email protected] Pathophysiology Current Infectious Disease Reports 2009, 11:183 –189 The superfi cial cervical lymph nodes lie on top of the ster- Current Medicine Group LLC ISSN 1523-3847 nomastoid muscle and include the anterior group, which Copyright © 2009 by Current Medicine Group LLC lies along the anterior jugular vein, and the posterior group, which lies along the external jugular vein [ 4••]. The deep cervical lymph nodes lie deep to the sternomas- Cervical lymphadenopathy is a common problem in toid muscle along the internal jugular vein and are divided children. The condition most commonly represents into superior and inferior groups. The superior deep nodes a transient response to a benign local or general- lie below the angle of the mandible, whereas the inferior ized infection. Acute bilateral cervical lymphadenitis deep nodes lie at the base of the neck. is usually caused by a viral upper respiratory tract The superfi cial cervical lymph nodes receive afferents infection or streptococcal pharyngitis. Acute unilat- from the mastoid, tissues of the neck, and the parotid (preau- eral cervical lymphadenitis is caused by streptococcal ricular) and submaxillary nodes [4•• ]. The efferent drainage or staphylococcal infection in 40% to 80% of cases. terminates in the superior deep cervical lymph nodes [ 4••]. Common causes of subacute or chronic lymphad- The superior deep cervical nodes drain the palatine tonsils enitis include cat-scratch disease and mycobacterial and the submental nodes. The lower deep cervical nodes infection. Generalized lymphadenopathy is often drain the larynx, trachea, thyroid, and esophagus. caused by a viral infection, and less frequently by Offending organisms usually fi rst infect the upper respi- malignancies, collagen vascular diseases, and medi- ratory tract, anterior nares, oral cavity, or skin in the head cations. Laboratory tests are not necessary in most and neck area before spreading to the cervical lymph nodes. children with cervical lymphadenopathy. Most cases The lymphatic system in the cervical area serves as a bar- of cervical lymphadenitis are self-limited and require rier to prevent further invasion and dissemination of these no treatment. The treatment of acute bacterial cervi- organisms. The nodal enlargement occurs as a result of cal lymphadenitis without a known primary source proliferation of cells intrinsic to the node (eg, lymphocytes, should provide adequate coverage for both Staphylo- plasma cells, monocytes, and histiocytes) or by infi ltration of coccus aureus and Streptococcus pyogenes . cells extrinsic to the node (eg, neutrophils). Because infections involving the head and neck areas are common in children, cervical lymphadenitis is common in this age group [ 5 ]. Introduction Enlarged cervical lymph nodes are common in children [ 1 ]. About 38% to 45% of otherwise normal children have pal- Etiology pable cervical lymph nodes [ 2 ]. Cervical lymphadenopathy Causes of cervical lymphadenopathy are listed in Table 1 is usually defi ned as cervical lymph nodal tissue measuring [ 1 ]. The most common cause is reactive hyperplasia result- more than 1 cm in diameter [ 3 ]. Cervical lymphadenopathy ing from an infectious process, typically a viral upper most commonly represents a transient reactive response to respiratory tract infection [ 6 ]. Upper respiratory tract a benign local or generalized infection, but occasionally it infection might be caused by rhinovirus, parainfl uenza might herald the presence of a more serious disorder (eg, virus, infl uenza virus, respiratory syncytial virus, coro- malignancy). Lymphadenitis specifi cally refers to lymph- navirus, adenovirus, or reovirus [ 1 , 4•• ]. Other viruses adenopathies that are caused by infl ammatory processes associated with cervical lymphadenopathy include Epstein- [ 4•• ]. This article reviews the pathophysiology, etiology, Barr virus (EBV), cytomegalovirus (CMV), rubella, rubeola, 184 I Upper Respiratory, Head, and Neck Infections Table 1. Causes of cervical lymphadenopathy henselae (cat-scratch disease), nontuberculosis mycobacteria A. Infection (eg, Mycobacterium avium-intracellulare, Mycobacterium scrofulaceum ), and Mycobacterium tuberculosis (“scrofula”) 1. Viral are important causes of subacute or chronic cervical lymph- a. Viruses causing upper respiratory infection (eg, rhino- adenopathy [8 ]. Chronic posterior cervical lymphadenitis is virus, parainfl uenza virus, infl uenza virus, respiratory syncytial virus, coronavirus, adenovirus, reovirus) the most common form of acquired toxoplasmosis and is the b. Epstein-Barr virus sole presenting symptom in 50% of cases [ 1 ]. c. Cytomegalovirus More than 25% of malignant tumors in children occur d. Rubella in the head and neck, and the cervical lymph nodes are e. Rubeola the most common site [ 1 ]. During the fi rst 6 years of life, f. Varicella-zoster virus neuroblastoma and leukemia are the most common tumors g. Herpes simplex virus h. Coxsackievirus associated with cervical lymphadenopathy, followed by i. HIV rhabdomyosarcoma and non-Hodgkin’s lymphoma [ 1 ]. After 6 years of age, Hodgkin’s lymphoma is the most common 2. Bacterial tumor associated with cervical lymphadenopathy, followed a. Staphylococcus aureus by non-Hodgkin’s lymphoma and rhabdomyosarcoma. b. Streptococcus pyogenes c. Haemophilus infl uenzae The presence of cervical lymphadenopathy is an d. Anaerobes important diagnostic feature for Kawasaki disease. The e. Corynebacterium diphtheriae other features include fever lasting 5 days or more, bilat- f. Bartonella henselae eral bulbar conjunctival injection, infl ammatory changes g. Mycobacterium tuberculosis, Mycobacterium in the mucosa of the oropharynx, erythema or edema of avium-intracellulare, Mycobacterium scrofulaceum the peripheral extremities, and polymorphous rash. i. Nocardia brasiliensis j. Pasteurella multocida Generalized lymphadenopathy might be a feature of k. Treponema pallidum systemic-onset juvenile rheumatoid arthritis, systemic lupus erythematosus, or serum sickness. Certain drugs— 3. Protozoal notably phenytoin, carbamazepine, hydralazine, and a. Toxoplasma gondii isoniazid—might cause generalized lymphadenopathy. Cervi- b. Leishmania species cal lymphadenopathy has been reported after immunization 4. Fungal with diphtheria-pertussis-tetanus, poliomyelitis, or typhoid a. Candida albicans fever vaccine [ 1 ]. Rosai-Dorfman disease is a benign form b. Histoplasma capsulatum of histiocytosis characterized by generalized proliferation of c. Blastomyces dermatitides sinusoidal histiocytes. The disease usually manifests in the d. Coccidioides immitis fi rst decade of life with massive and painless cervical lymph- e. Aspergillus fumigatus adenopathy, often accompanied by fever, malaise, weight loss, B. Malignancies neutrophilic leukocytosis, elevated erythrocyte sedimentation 1. Neuroblastoma rate, and polyclonal hypergammaglobulinemia. Kikuchi-Fuji- 2. Leukemia moto disease (histocytic necrotizing lymphadenitis) is a benign 3. Lymphoma cause of lymph node enlargement, usually in the posterior 4. Rhabdomyosarcoma cervical triangle [ 9 ]. The condition primarily affects young C. Miscellaneous females. Fever, nausea, weight loss, night sweats, arthralgia, 1. Kawasaki disease myalgia, or hepatosplenomegaly might be present. The etiol- 2. Collagen vascular diseases ogy of Kikuchi-Fujimoto disease is unknown, but a viral cause 3. Serum sickness has been implicated [ 9 ]. Classical pathologic fi ndings include 4. Drugs 5. Postvaccination patchy areas of necrosis in the cortical and paracortical areas 6. Rosai-Dorfman disease of the enlarged lymph nodes and a histiocytic infi ltrate [ 9 ]. 7. Kikuchi-Fujimoto disease (Modifi ed from Leung and Robson [5].) Differential Diagnosis The differential diagnosis of neck masses is different in varicella-zoster virus, herpes simplex virus (HSV), coxsacki- children due to a higher incidence of infectious diseases evirus, and HIV. Bacterial cervical lymphadenitis is usually and congenital anomalies and the relative rarity of malig- caused by Streptococcus pyogenes (group A β -hemolytic nancies in the pediatric age group. Cervical masses in streptococci) or Staphylococcus aureus [ 7 ]. Anaerobic bac- children might be mistaken for enlarged cervical lymph teria can cause cervical lymphadenitis, usually in association nodes. In general, congenital lesions are painless and are with dental caries and periodontal disease. Group B strepto- present at birth or identifi ed soon thereafter [ 10 ]. Clinical cocci and Haemophilus infl uenzae type b are less frequent features that may help distinguish the various conditions causal organisms. Diphtheria is a rare cause. Bartonella from cervical lymphadenopathy are as follows. Cervical Lymphadenitis: Etiology, Diagnosis, and Management I Leung and Davies I 185 Mumps History The swelling of mumps parotitis crosses the angle of the Age of the child jaw. On the other hand, cervical lymph nodes are usually Some organisms have a predilection for specifi c age below