Download Cervical Lymphadenopathy and Adenitis

Cervical Lymphadenitis
Introduction
Appropriate management of children who have enlarged lymph nodes ranges
from observation and reassurance to extensive diagnostic evaluation and aggressive
medical and surgical intervention. Initial evaluation begins with a thorough history and
physical examination. One can then use a thoughtful approach towards any necessary
diagnostic or therapeutic interventions.
Lymphadenopathy, or enlargement of lymph nodes, can be caused by
proliferation of normal lymphatic tissue, by invasion of inflammatory cells
(lymphadenitis), or by invasion of neoplastic cells. The complex array of lymph nodes of
the head and neck defend against infection and often are considered in anatomic
groupings based on lymph drainage patterns. Cervicofacial lymph nodes may reside in
the anterior triangle forward of the sternocleidomastoid muscle, the posterior triangle
behind the sternocleidomastoid, the submandibular region below the jaw line, the
supraclavicular region in the lower neck, and the preauricular and occipital regions.
Progressively enlarging and nontender lymph nodes may suggest malignancy, especially
when located in the posterior triangle. Supraclavicular lymphadenopathy is considered
pathologic and should be biopsied. Generalized lymphadenopathy, hepatosplenomegaly,
and/or radiographic mediastinal lymphadenopathy suggest systemic illness.
The discussion below will focus mainly on the common infectious causes of
cervical lymphadenitis.
Pathogenesis of Infectious Lymphadenitis
Microorganisms reach the infected lymph node via lymphatic flow from an
inoculation site, by lymphatic flow from adjacent lymph nodes, or by hematogenous
spread of systemic infection. Local cytokine release results in neutrophil recruitment,
vascular engorgement, and nodal edema. Involvement of the soft tissues adjacent to the
node can result in cellulitus and abscess formation. Eventually, the node heals with
fibrosis. Microorganisms that cause subacute or chronic inflammatory changes generally
produce less of an inflammatory response.
Generalized infectious lymphadenopathy (most commonly caused by viral illness)
results in nodal hyperplasia without necrosis and resolves spontaneously as the illness
resolves.
A helpful classification in determining the etiology of infectious causes of
cervical lymphadenitis is considering four categories: 1) acute unilateral cervical
lymphadenitis, 2) acute bilateral cervical lymphadenitis, 3) subacute/chronic bilateral
cervical lymphadenitis, and 3) subacute/chronic unilateral cervical lymphadenitis.
Acute Unilateral Cervical Lymphadenitis
Acute unilateral cervical lymphadenitis is usually caused by Staphyloccocus
aureus or Streptococcus pyogenes (group A) in over 80% of cases. Submandibular and
cervical nodes are most frequently involved and occur most commonly in children
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between 1 and 4 years of age. Patients may have a history of recent upper respiratory
tract infection or impetigo. Nodes may be very large (up to 6 cm) and infected children
may suffer overlying cellulitus and high fever. Nodes infected with Staph aureus are
more likely to suppurate.
Acute unilateral cervical lymphadenitis in the newborn is caused by Staph aureus
in most cases. Another important cause of neonatal acute cervical lymphadenitis is lateonset group B streptococcal infection (Streptococcus agalactiae) – the “cellulitusadenitis” syndrome. Onset is between 7 and 90 days of age. Most affected patients are
between 3 and 7 weeks of age, male in 75% of cases, febrile, irritable, and have poor
feeding. Examination reveals tender, erythematous facial or submandibular swelling with
ill-defined margins. Bacteremia is common.
In children with poor dentition or history of periodontal disease, anaerobes should
be strongly considered.
A history of a near-by animal bite should prompt suspicion of Pasturella
multocida as a possible etiologic agent.
Tularemia is a febrile illness caused by infection with Francisella tularensis that
usually occurs following contact with infected animals (eg, rabbits, pet hamsters; more
than 100 species have been implicated), the bite of blood-sucking arthropods, inhalation
of organisms in contaminated environments, or ingestion of contaminated water. The
most common clinical presentation is the ulceroglanular form, characterized by a papular
lesion in the drainage field of the inflamed lymph node within 72 hours of infection, with
painful ulceration following within days. Glandular tularemia is similar in presentation,
but there is no skin lesion. Most cases in the United States occur in the south-central
region.
Acute Bilateral Cervical Lymphadenitis
Acute bilateral cervical lymphadentitis is the most common clinical presentation.
It is usually caused by benign, self-limited viral upper respiratory infection (eg,
adenovirus, influenza virus, enterovirus, RSV). Symptoms of cough, rhinorrhea, and
nasal congestion may suggest these etiologies. The lymph nodes are small, rubbery,
mobile, discrete, minimally tender, and without erythema or warmth. They are often
referred to as “reactive” or “shotty” lymphadenopathy. Although the clinical course is
self-limited, the lymph node enlargement may persist for weeks.
Group A streptococcal pharyngitis is another common cause of acute bilateral
cervical lymphadenitis and generally occurs in children older than 3 years of age.
Patients complain of sore throat, fever, and difficulty swallowing due to pain. Headache
and abdominal pain are not infrequent complaints. Examination reveals pharyngitis (may
or may not be exudative) and tender anterior cervical adenopathy.
Acute bilateral cervical lymphadenitis also is associated with pharyngitis resulting
from Mycoplasma pneumoniae.
EBV and CMV often cause generalized lymphadenopathy, but may present as
acute bilateral cervical lymphadenitis.
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Subacute/Chronic Bilateral Cervical Lymphadenitis
Subacute or chronic bilateral lymphadenitis is most often caused by EBV or CMV
infection. EBV causes infectious mononucleosis that can present with fever, exudative
pharyngitis, lymphadenopathy, and hepatosplenomagaly. CMV also causes a
mononucleosis-like illness. Both infections are more likely in school-aged children and
adolescents.
A less common cause of prolonged bilateral cervical lymphadenitis is acquired
Toxoplasma gondii infection, although it may also be unilateral. When symptomatic, it
may present as cervical lymphadenopathy and fatique, usually without fever, and is more
likely to occur in school-aged children and adolescents. Adenopathy may be localized or
generalized, tender or nontender, and may persist for many months. This disease usually
is benign and self-limited and should be considered in patients in whom infectious
mononucleosis is suspected, but who have negative EBV serology. Oocysts are excreted
from the stool of cats, the definitive host for T. gondii. Human infection occurs by
ingesting poorly cooked meat that contains cysts or by inadvertently ingesting oocysts
from soil, litter boxes, or contaminated food.
Other uncommon causes of chronic bilateral cervical adentitis include HIV
infection, Mycobacterium tuberculosis (although more commonly unilateral), syphilis,
brucellosis, and histoplasmosis. It is important to realize that all of above mentioned
infectious etiologies of subacute and chronic bilateral lymphadenitis often are also
associated with generalized lymphadenopathy.
Subacute/Chronic Unilateral Cervical Lymphadenitis
Subacute or chronic cervical lymphadenitis is usually caused by nontuberculous
mycobacterium (NTM - Mycobacterium avium-intracellulare and Mycobacterium
scrofulaceum most commonly). Most NTM infections occur in immunocompetent
children younger than 5 years of age. The organisms are ubiquitous in the environment.
Infection usually is insidious, with node enlargement occurring over weeks or months,
although onset may be very rapid and the clinical course indistinguishable from acute
unilateral cervical lymphadenitis. Infected lymph nodes progress to fluctuance, and the
overlying skin often becomes violaceous and thin. Fever and marked tenderness are
unusual. Untreated lymphadenitis caused by NTM may resolve, but often it progresses to
spontaneous drainage with sinus tract formation and scarring.
If exposure to kittens or cats is elicited, infection with Bartonella henselae should
be considered. However, such a history is not present in all cases. This is a relatively
common infection caused by inoculation of Bartonella henselae into the skin following a
lick, bite, or scratch from a kitten or cat. Infection usually results in a unilateral, chronic,
and tender lymphadenitis most commonly in the cervical or axillary region.
Constitutional symptoms, when present, are generally mild, with fever occurring in fewer
than 50% of patients. Cat-scratch disease may also manifest as Parinaud oculoglandular
syndrome, with conjunctivitis and preauricular or submandibular lymphadenopathy
following conjunctival inoculation.
Mycobacterium tuberculous (TB) should also be considered in a patient with a
persistent unilateral lymphadenitis that fails to respond to appropriate antimicrobial
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therapy or historically has risk factors for TB exposure or clinical symptoms compatible
with TB. Infection of the cervical nodes is usually caused by extension from the
paratracheal nodes to the tonsillar and submandibular nodes. It also can occur by direct
spread from the apical pleura to the supraclavicular nodes.
Toxoplasmosis can also present as subacute or chronic unilateral lymphadenitis.
Diagnosis
It is not necessary or possible to identify an organism in all children who have
infectious lymphadenitis. Observation with reassurance often is the most appropriate
management course for children in whom self-limited infection is presumed.
Patients who have acute bilateral cervical lymphadenitis are often managed
conservatively because infection with respiratory viruses is so common. Nasopharyngeal
viral testing is expensive and seldom helpful. Bacterial culture of the pharynx is useful as
it may identify group A streptococcal infection treatable with penicillin. For patients in
whom systemic or subacute infections are suspected or are febrile and ill-appearing, a
complete blood count, blood culture, and measurement of liver transaminases may be
indicated. Serologic studies for EBV, CMV, HIV, Treponema pallidum, Toxoplasma
gondii, or Brucella sp can be helpful in selected cases.
Children with acute unilateral cervical lymphadenitis may appear well or may
suffer high fever and toxicity. For well-appearing children in whom Staph aureus or
group A streptococcal infection is suspected and have no evidence of abscess formation,
a therapeutic trial with an oral antibiotic without diagnostic testing is often appropriate.
However, attempts should be made to isolate the causative organism in the ill-appearing
child who has acute suppurative cervical lymphadenitis. Ultrasound exam or CT
scanning can be useful in evaluating for an underlying abscess and extent of infection.
Needle aspiration is a reliable means of obtaining material for further diagnostic testing.
Rarely, an excisional lymph node biopsy may be needed. Material should be sent for
gram stain, bacterial culture (aerobic and anaerobic), as well as mycobacterial and fungal
stains and cultures, although these organisms more typically cause chronic lymphadenitis.
Lymph node tissue should be sent for histopathologic examination. Blood culture is also
indicated in the febrile, ill-appearing child.
Children with subacute or chronic cervical lymphadenopathy often undergo
extensive diagnostic evaluation before an etiology is identified. Special attention should
be given to the possibility of TB and HIV disease, and a PPD and serologic testing for
HIV should likely be done. Any material obtained from the affected lymph nodes should
be sent for all of the studies mentioned above. The hematologic and serologic testing
noted previously is usually indicated. Urine antigen tests for Histoplasma capsulatum
may also be helpful.
The most common causes of subacute or chronic cervical lymphadenopathy in
children are NTM infection and cat-scratch disease, and as mentioned previously, cause
unilateral disease. Blood samples can be sent for an indirect fluorescent antibody test for
detection of antibody to Bartonella species. Patients with NTM lymphadenopathy may
have a normal or minimally indurated PPD skin test and a normal chest radiograph.
NTM infection is diagnosed best using material obtained from a suppurative lymph node,
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which can be stained and cultured for acid-fast organisms. Material can also be sent for
polymerase chain reaction (PCR) examination to detect B hensalae and NTM infection.
See Table 1 below to review many of the infectious causes of cervical
lymphadenitis. Also, see Table 2 for a differential diagnosis of other noninfectious
causes of cervical lymphadenitis and neck swelling.
Table 1. Infectious Causes of Cervical Lymphadenitis
Presentation
Acute Unilateral
Common
-Staphylococcus
aureus
-Group A
streptococcus
-Anaerobic bacteria
Uncommon
-Group B
streptococcus
-Tularemia1
-Pasturella
multocida
-Gram negative
bacteria
-Yersinia pestis2
Acute Bilateral
-Numerous common -Roseola 2
upper respiratory
-Parvovirus B19 2
tract viruses
-Herpes Simplex
Virus
-Epstein-Barr
virus1,2
-Cytomegalovirus1,2
-Group A
streptococcus
-Mycoplasma
pneumoniae
Chronic Bilateral
-Epstein-Barr virus2 -HIV2
-Cytomegalovirus2
-Tuberculosis2
-Toxoplasmosis2
-Syphilis2
Chronic Unilateral
-Nontuberculous
-Tuberculosis2
mycobacterium
-Toxoplasmosis2
-Cat-scratch disease -Actinomycosis
1 – Infection can persist and become more chronic in appearance.
2 – Often associated with generalized lymphadenopathy
Adapted from UpToDate
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Rare
-Anthrax
-Corynebacterium
diphtheriae
-Measles
-Mumps 2
-Rubella 2
-Brucellosis2
-Histoplasmosis2
-Nocardia
brasiliensis
-Aspergillosis
Table 2. Noninfectious Causes of Suspected Cervical Lymphadenitis
Malignancy (lymphoma, leukemia, neuroblastoma, rhabdomyosarcoma, thyroid
cancer nasopharyngeal carcinoma, parotid tumors, metastatic disease)
Collagen vascular disease (juvenile rheumatoid arthritis, sytemic lupus
erythematosus)
Drugs (phenytoin, carbamazepine)
Kawasaki disease
Postvaccination
PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis)
Kikuchi disease (histiocytic necrotizing lymphadenitis)
Histiocytosis
Sarcoidosis
Castleman disease
Congenital neck masses (branchial cleft cysts, cystic hygroma, thyroglossal duct
cyst, bronchogenic cyst, epidermoid cyst, sternocleidomastoid tumor)
Treatment
Treatment of children who have lymphadenitis will depend on the etiology. Once
the etiology is known, therapy should be initiated after review of current literature and/or
consultation with a specialist in infectious diseases if necessary. Table 3 below is a
summary of the management of some of the more common causes of bacterial
lymphadenitis. A total antibiotic course of 10 to 14 days is generally sufficient to treat
uncomplicated lymphadenitis caused by Staph aureus or group A streptococcus. These
patients will usually respond to therapy within 72 hours. Failure to improve should
prompt reconsideration of diagnosis and treatment. Surgery (incision and drainage) may
be necessary if an abscess has formed.
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Table 3. Treatment of Acute Pyogenic Bacterial Lymphadenitis
(Children > 1 month of age)
Symptomatic Therapy
Identify primary focus with drainage, if appropriate
Apply warm, moist dressings to accelerate localization
Prescribe analgesics as needed
Incise and drain nodes that have suppuration
Antimicrobial Therapy
Suspected Staphylococcus aureus or Group A Beta-hemolytic Streptococcus
Infection
For children who do not appear toxic and have no apparent abscess or
cellulites, oral empiric therapy with cephalexin, dicloxacillin, augmentin or
clindamycin
For ill-appearing children who have abscess formation or cellulits, node
aspiration if appropriate and intravenous therapy with cefazolin, nafcillin or
oxacillin, clindamycin, or vancomycin
Suspected Infection With Anaerobic Bacteria
For children who have cervical lymphadenitis associated with periodontal
disease therapy with oral penicillin or clindamycin
IV equivalents in the presence of moderate-to-marked systemic symptoms and
node aspiration if appropriate
Suspected Nontuberulous Mycobacteria Infection
Surgical excision of the infected lymph node without antibiotic therapy
For patients in whom surgery or complete excision is not feasible, a
macrolide-containing multi-drug antimycobacterial regimen
Cat-scratch Disease
Some experts recommend no antimicrobial therapy in immunocompetent
patients who have uncomplicated lymphadenopathy. Agents that may be used
in cat scratch disease include azithromycin, rifampin, trimethoprimsulfamethoxazole, or parenteral gentamicin. Surgical removal of nodes
infected with Bartonella frequently results in persistent drainage and poor
wound healing. Repeated node aspiration for management of suppurative
lymphadenopathy caused by Bartonella infection.
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LPCH Blue Team and PEC Rotations
February 2009