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Infectious and noninfectious etiologies of cervical lymph- adenopathy are summarized in Tables 26–2 and 26–3.
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Infectious Causes of Lymphadenitis by Lymph Node Location
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Acute Bilateral Cervical Lymphadenitis
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Acute bilateral lymphadenitis is commonly associated with other constitutional symptoms including fever, cough, rhinorrhea, conjunctivitis, or pharyngitis of upper respiratory or oropharyngeal infections. Viral etiologies include adenovirus, rhinovirus, parainfluenza, influenza, respiratory syncytial virus, and coronavirus. In adenoviral infections, anterior and posterior cervical nodal enlargements are more common than preauricular lymphadenopathy.9
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Both Epstein–Barr Virus (EBV) and cytomegalovirus (CMV) can cause acute bilateral cervical adenitis associated with infectious mononucleosis. EBV is more commonly the cause of cervical adenitis than is CMV.9 In both EBV and CMV infections, posterior cervical nodes are more commonly enlarged than are anterior cervical nodes. Cervical lymphadenitis may present prior to generalized lymphadenopathy in many cases of EBV or CMV infectious mononucleosis.9
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Other infectious etiologies responsible for bilateral cervical lymphadenitis include HIV, rubella, varicella, HSV, measles, coxsackie, and roseola (HHV-6) viruses. Associated symptoms are important factors in arriving at the correct diagnosis. Gingovistomatitis caused by HSV or herpangia from coxsackie virus infection is commonly associated with bilateral enlargement of the anterior cervical, submental, and submandibular nodes.9 In addition, many of these viral agents, which cause generalized infections, will also produce generalized lymphadenopathy.
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Acute Unilateral Cervical Lymphadenitis
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Acute, unilateral, suppurative bacterial cervical lymphadenitis is the classic form of cervical lymphadenitis brought to medical attention. S. aureus and GABHS are responsible for the majority of these infections. Reports of 40–80% of isolated organisms were S. aureus or GABHS in studies where fine needle aspiration or excision was performed.10–13 These infected lymph nodes may result from upper respiratory, throat, dental, or scalp infections. In children aged 1–4 years, S. aureus and GABHS are common etiological agents. In older children, GABHS and anaerobic infections are most frequently seen.9 Streptococcal infections in this age group appear to represent the natural incidence of streptococcal pharyngitis in this group. Anaerobic organisms associated with dental abscesses, gingival infections, and mucositis have been cultured from biopsied lymph nodes. Bacteroides,Peptostreptococcus,Proteus, Escherichia coli, Pseudomonas, mixed infections of both Staphylococcus and Streptococcus, coagulase-negative staphylococcal species, Actinomyces israelii, Streptococcus milleri group, Haemophilus influenzae, Francisella tularensis, Aspergillus spp., Nocardia spp., and NTM have all been isolated from pediatric patients with acute cervical adenitis or abscess.1,9,13–16
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The primary sites of acute cervical lymphadenitis are submandibular (50–75%), cervical (13–39%), submental (5–8%), and occipital (2–3%).1,15 Suppuration occurs most commonly with Staph. aureus infection, with a rate of 25% of all acute bacterial cervical adenitis.15,16
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Subacute or Chronic Unilateral Cervical Lymphadenitis
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The most common causes of subacute or chronic lymphadenitis are mycobacterial infection, CSD, and toxoplasmosis.17
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Cervical lymphadenitis is the most common mycobacterial infection found in children. These infections are typically caused by NTM rather than M. tuberculosis; M. avium-intracellulare complex is isolated most often. Adenitis caused by mycobacteria generally affects healthy children between the ages of 1 and 5 years. The involved cervical lymph nodes are frequently located in the submandibular and preauricular nodal groups. The size of the node can vary between 1 and 7 cm in diameter. Symptoms may have been ongoing for several weeks to months before seeking medical attention.2 In the early phase of the infection, the lymph nodes are firm with minimal tenderness, erythema, or warmth. Later, a necrotic center develops. Without treatment, the infection leads to progressive lymph node necrosis, overlying violaceous skin discoloration with a papyraceous or cigarette paper-like appearance, and, subsequently, draining skin sinus.2,18
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CSD is usually a localized, self-limited disease but may be complicated by encephalitis, neuroretinitis, or Parinaud oculoglandular syndrome, a syndrome of unilateral conjunctivitis associated with regional lymphadenopathy and a characteristic neuroretinitis that occurs after conjunctival inoculation.6–8,19 The primary clinical feature is lymphadenitis, which is single or regional and restricted to the drainage area of the site of the inoculation. The involved nodes tend to be as large as several centimeters in diameter. These may be elastic, mobile, and tender. Spontaneous regression of the nodes usually occurs in 2 weeks to 2 months. A primary lesion or papule may be located at the site of a scratch. This lesion typically precedes the development of lymphadenitis. CSD is generally associated with systemic symptoms such as fever and malaise. There is usually a history of contact with a kitten or a cat.6–8
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Lymphadenopathy without fever is the most frequent clinical manifestation of acute acquired infection with T. gondii in the immunocompetent individual. The majority of acquired T. gondii infections are asymptomatic. The adenopathy may be present for months and tends to be nonsuppurative and only occasionally tender. Toxoplasmic lymphadenitis most frequently involves a solitary lymph node in the head and neck regions, without systemic symptoms.8
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Cervical lymphadenitis caused by TB is uncommon in the United States. However, in endemic areas, TB remains a significant cause of cervical lymphadenitis.4
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Subacute or Chronic Bilateral Cervical Lymphadenitis
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Viral etiologies such as EBV, CMV, and HIV infections can cause bilateral subacute chronic cervical lymphadenitis. Syphilis can also cause lymphadenitis. However, the above infections account for only a small proportion of the clinically diagnosed cervical lymphadenopathies.
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Infectious Causes of Lymphadenitis by Demographic Characteristics and Epidemiologic Exposures
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The most common cause of acute cervical lymphadenitis in infants is S. aureus. However, group B Streptococcus can cause a late-onset cellulitis-adenitis syndrome in neonates. Presenting features of cellulitis-adenitis syndrome include poor feeding, irritability, fever, and unilateral facial, preauricular, or submandibular swelling with overlying erythema. Adenitis presents within 2–3 days after onset of soft-tissue infection. Reported cases have a male predominance (72%). Blood culture and culture of the soft tissue or lymph node are almost always positive. This syndrome had previously been thought not to be associated with meningitis, but, in 1998, two cases of meningitis were reported in association with group B Streptococcus cellulitis-adenitis syndrome in afebrile, well-appearing neonates.20,21
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Staph. aureus and GABHS are the most common etiologies (80%) of acute cervical adenitis in children aged 1–4 years. The majority of cases of acute cervical lymphadenitis occur in this age group. Children aged 5 years and older are more likely to have lymphadenitis caused by NTM, T. gondii, B. henselae, EBV, CMV, and tularemia.9
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Lack of immunizations can predispose patients to preventable causes of cervical adenitis including measles, rubella, varicella, H. influenzae type b, and Corynebacterium diphtheriae. In rare cases, cervical lymphadenopathy has been reported following immunization with some vaccines (diphtheria–pertussis–tetanus, poliomyelitis, typhoid fever, and Bacille Calmette–Guerin).1,7,17
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Zoonoses are a common cause of cervical lymphadenitis in children. History of exposure to animals is very important in the diagnosis of CSD, toxoplasma, tularemia, anthrax, brucellosis, and plague.
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Pasturella multocida can cause acute adenitis following bites or scratches from animals.16 Tularemia results from infection with F. tularensis via insect vectors, direct contact with infected animals or carcasses, or ingestion of contaminated food or water. Approximately 250 animal species can be infected with tularemia including the rabbit. Occurrence is seasonal (June through September and November through February), which corresponds to vector and rabbit-hunting activities. Tularemia is highly infectious, with as few as 10 organisms being needed to cause infection. The ulceroglandular form is most common (75% cases) and causes ulcer at site of inoculation with regional lymphadenopathy. Exposure to F. tularensis through the conjunctiva can result in Parinaud oculoglandular syndrome, which is indistinguishable from that caused by B. henselae.22
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Cutaneous anthrax begins as a focal pustule at the site of skin wound, and within 2–3 days, the lesion rapidly progresses with ulceration and eschar formation. Regional lymphadenitis may develop.22 Brucellosis is contracted via direct contact with animals or ingestion of unpasteurized dairy products. In rare cases, brucellosis causes chronic lymphadenopathy with chronic fatigue-like syndrome. Yersinia pestis is endemic in rodents and several notable outbreaks in the southwest United States have occurred in the recent years. Bubonic plague, the most common form of the disease, is transmitted to humans via flea bites, leading to regional lymphadenitis characteristic of the classic bubo.22
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Contact with Sick Individuals
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GABHS and the respiratory viral pathogens are all highly communicable via respiratory droplet transmission. History of a close contact with symptoms suggestive of TB, travel to endemic parts of the world, or history of incarceration should prompt evaluation for M. tuberculosis infection. Both congenital HIV and acute retroviral syndrome are characterized by lymphadenopathy.
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Underlying Illness or Predisposing Condition
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Patients with underlying undiagnosed immunodeficiency disease may present with lymphadenopathy or lymphadenitis. For example, suppurative lymphadenitis is one of the common initial presentations for patients with either chronic granulomatous disease or Job syndrome (hyperimmunoglobulin E syndrome). HIV infection may also present with generalized lymphadenopathy.
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Noninfectious Causes of Lymphadenitis
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PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) is characterized by the onset of fever, malaise, chills, headaches, aphthous ulcers, pharyngitis, and tender cervical adenopathy. This cluster of symptoms cyclically recurs at 4–6-week intervals, and the episodes resolve spontaneously approximately 4–5 days.7 PFAPA is discussed further in the “Periodic Fever Syndromes” chapter (Chapter 61).
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Kawasaki Syndrome (discussed in Chapter 62) manifests with nonsuppurative cervical lymphadenopathy (usually a single, large node). The other associated symptoms of fever, conjunctival injection, rash, and subsequent desquamation suggest the diagnosis. However, diagnosis may be difficult if unilateral lymphadenitis precedes mucocutaneous manifestations.23
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Kikuchi disease (histocytic necrotizing lymphadenitis) is a self-limited condition characterized by cervical lymphadenopathy and fever. It usually occurs in women of Asian decent.7 Other inflammatory diseases such as juvenile rheumatoid arthritis may present with lymphadenopathy.
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Infected congenital cysts such as bronchial cleft cysts, cystic hygromas, or thyroglossal duct cysts can mimic lymphadenitis. Congenital cysts should be considered, especially in cases when there appears to be recurrent cervical lymphadenitis.
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Malignancy should be considered in the cases of indolent adenopathy, especially with a history of anorexia, weight loss, and other systemic symptoms.