A Clinical guide to pediatric infectious disease

9

Cervical Adenitis

Swelling of cervical lymph nodes is a common pediatric problem.

The differential diagnosis of cervical adenitis is extensive and includes acute and chronic infections, Kawasaki syndrome, and malignancy. The evaluation process should be logical with the history and physical guiding the subsequent workup.

Acute Infections associated with Cervical Adenitis

Etiology (Bacterial)

The most common bacterial cause of acute unilateral cervical adenopathy is infection with Staphylococcus aureus or Streptococcus pyogenes(group A streptococci). These two organisms are the cause of acute unilateral disease in more than 80% of cases.

Presentation

There is often sudden onset of fever, swelling, tenderness, and overlying erythema.

Diagnosis

Diagnosis of acute bacterial adenitis is typically made by the clinical history and examination.

Management

Therapy is with an antibiotic with activity against both S. aureus and group A streptococci. A first generation cephalosporin or clindamycin can be used. Children who appear toxic with high fever and decreased oral intake may need to be managed

P.92


initially as inpatients; for these children, ampicillin-sulbactam (Unasyn) is a good intravenous agent. It is often difficult to predict in a particular patient which nodes will suppurate and thus require surgical drainage. Serial exams and the use of computed tomography of the neck are helpful in determining whether the child will require surgery (Fig. 9.1). Once the child is afebrile and taking fluids well, these serial examinations can be done as an outpatient while on oral antibiotics.

The traditional surgical approach to suppurative cervical adenitis that had failed to respond completely to medical management was open incision and drainage. Drawbacks to this technique included the need for general anesthesia and a large scar. There is increasing experience with needle aspiration in the surgical management of suppurative cervical adenitis. The advantage of needle aspiration over incisional drainage is that general anesthesia may not be required and surgical scarring may be minimized. Many pediatric surgeons are now using this technique as a first-line method for suppurative adenitis unresponsive to antibiotic treatment (Table 9.1).

Etiology (Viral)

Acute bilateral cervical lymphadenitis is frequently caused by viral infections, including Epstein-Barr virus, cytomegalovirus, and adenovirus.

 

FIG. 9.1. Computed tomograph revealing cervical adenitis with abscess formation.

TABLE 9.1. Causes of Acute Bacterial Cervical Adenitis

Acute infection (Staphylococcus aureus, Streptococcus pyogenes)

1. Associated with fever, erythema, tenderness

2. May proceed to suppuration and require incisional drainage

3. Outpatient therapy

4. Cephalexin (Keflex), 25–50 mg/kg/d in 4 divided doses

5. Clindamycin, 20–40 mg/kg/d in 3 divided doses

6. Augmentin (amoxicillin-clavulanate), 25–45 mg/kg/d; for children <40 kg

7. Inpatient therapy
Ampicillin-sulbactam (Unasyn), 100–200 mg/kg/d of ampicillin component divided q6h

P.93

 

Presentation

Patients often have associated cough and rhinorrhea.

Diagnosis

Diagnosis of viral adenopathy is usually made clinically, based on associated symptoms and the absence of fever and erythema, which characterize acute bacterial disease.

Management

Care in these cases is supportive. It is important to realize that after a viral infection, the lymph node enlargement may persist for many weeks, even though the acute symptoms of fever, cough, and coryza have resolved.

Chronic Infections associated with Cervical Adenitis

The two major causes of chronic infectious lymphadenitis in children are nontuberculous mycobacteria and cat-scratch disease. Additional causes of chronic infectious lymphadenopathy include toxoplasmosis and actinomycosis.

Nontuberculous Mycobacteria

Etiology

Nontuberculous mycobacteria (NTM) is a common cause of chronic cervical lymphadenitis in children. The nontuberculous mycobacterium that most often causes pediatric adenopathy is Mycobacterium avium-intracellulare (MAI). These organisms are ubiquitous in nature, often found in soil and contaminated water. The mycobacteria enter the oral cavity and may infect cervical lymph nodes. Although disseminated MAI is a common illness in end-stage acquired immunodeficiency disease (AIDS) patients, adenopathy in pediatrics is not considered a symptom of underlying immunodeficiency.

P.94

 

Presentation

Patients present with chronic lymph node enlargement over several weeks to months, although occasionally acute infection is seen. Affected nodes progress to fluctuation with an accompanying overlying violaceous color (Fig. 9.2). Without treatment, these nodes often rupture and develop sinus tracts.

Diagnosis

NTM infection should be considered in any patient with progressive adenitis not responding to traditional antibiotics. Needle aspiration often shows white blood cells but with negative Gram stain and culture. Tuberculin skin testing for Mycobacterium tuberculosis (MTB) may reveal a small degree of induration because MTB shares certain antigens with MAI. There is currently no skin test approved by the U.S. Food and Drug Administration (FDA) specifically for NTM. Children with MAI adenitis have negative chest x-rays and are not contagious.

Management

NTM are not susceptible to traditional antituberculous medications. For this reason, the treatment of MAI adenitis is complete surgical excision of the affected

P.95


node. Excisional biopsy is both diagnostic and therapeutic. The use of fine-needle aspiration or incision and drainage should be avoided because they can help facilitate formation of chronic fistula. The gold standard for the diagnosis of NTM adenitis is culture of the organism. Because growth of acid-fast bacteria may take several weeks, there has been some investigation regarding whether the histopathology of the excised node can help differentiate infections caused by NTM from MTB. Features associated with NTM infection include lack of significant caseation and less defined granuloma formation. There are instances in which the clinician will need to start antituberculous therapy pending final culture results.

 

FIG. 9.2. Chronic cervical adenitis seen in atypical mycobacterial infection. (see color plate).

In the cases in which complete excision is not possible because of extensive disease, medical therapy can be attempted. For Mycobacterium avium complex, a macrolide antibiotic such as clarithromycin or azithromycin, combined with ethambutol, is recommended.

Mycobacterium tuberculosis

Etiology

MTB is an unusual cause of cervical adenitis in developed countries. Transmission is person to person, with initial infection caused by aerosolized bacteria. After deposition in pulmonary alveoli, mycobacteria can travel through the lymphatic vessels to cervical lymph nodes.

Presentation of MTB adenitis can be similar to adenitis from NTM, with chronic infection progressing to purplish discoloration and fistula formation.

Diagnosis

Major distinguishing points of NTB adenitis include purified protein derivative (PPD), which often has greater than 15 mm of induration. Chest radiographs may reveal hilar adenopathy. Excisional biopsy and culture are often needed for definitive diagnosis.

Management

Unlike NTM adenitis, treatment is medical with at least two antituberculous medications effective against the mycobacteria (see chapter 12).

Cat-Scratch Disease

Etiology

Another common cause of chronic adenopathy in children is cat-scratch disease. This infection is caused by Bartonella henselae. The organisms are introduced through the skin by a cat scratch or bite; the most commonly affected area is the upper extremity, resulting in epitrochlear or axillary node enlargement.

P.96

 

Presentation

Lymphadenopathy is the most common presentation of cat-scratch disease. A scratch to the facial area may cause significant cervical lymphadenopathy. B. henselae can also cause additional clinical syndromes, including aseptic meningitis and encephalitis. Parinaud oculoglandular syndrome is infection with B. henselae following inoculation of the conjunctiva and presents with conjunctivitis and periauricular adenopathy.

Diagnosis

A history of cat exposure should always be elicited in evaluation of chronic cervical adenitis. Diagnosis can be confirmed by serology using indirect immunofluorescence antibody (IFA). Immunoglobulin G (IgG) antibody titers higher than 1:512 have been reported to suggest acute infection. IgM antibodies against B. henselae have been found only infrequently in the early stages of cat-scratch disease. Polymerase chain reaction analysis of a lymph node aspirate or biopsy can be performed, although B. henselae DNA may be present in lymph nodes only in the first weeks of illness.

Management

Most patients with cat-scratch disease have spontaneous resolution. There is no consensus on the use of antibiotics for cat-scratch disease. There have been reports that oral antibiotics, including macrolides, trimethoprim-sulfamethoxazole, and ciprofloxacin, may be effective. A single randomized and double-blind placebo-controlled study found that a 5-day course of oral azithromycin resulted in significant reduction in lymphadenopathy caused by cat-scratch disease when patients were treated within the first month of illness. Needle aspiration can be used for nodes that are suppurative and painful. Unlike chronic adenitis from NTM, surgical excision is generally neither needed nor advised.

Toxoplasma gondii

Etiology

  1. gondiiis an intracellular protozoan that is acquired by contact with cats or consumption of undercooked meats. Toxoplasmosis eventually infects a significant portion of the adult population.

Presentation

Patients who become symptomatic with this infection often have fever, sore throat, and posterior cervical adenopathy. Nodes may be mildly tender but as a rule

P.97


do not progress to fluctuance. Toxoplasmosis adenopathy can persist for several months. The clinical course is usually benign and self-limited in the immunocompetent host.

Diagnosis

Toxoplasmosis adenitis can be diagnosed serologically. Biopsy of affected nodes reveals characteristic features, including epithelioid cells that encroach on the margins of lymphoid germinal centers.

Management

No treatment is usually required in patients with normal immune function.

Actinomycosis

Etiology

Actinomyces species are gram-positive bacilli that are acid-fast negative. They are part of the gastrointestinal tract flora and can cause infection following oral or facial trauma.

Presentation

Actinomyces species causes three major categories of disease, including cervicofacial, thoracic, and abdominal. Cervicofacial disease is the most common manifestation and often occurs after facial trauma or dental procedures. The typical presentation is progressive swelling and development of a “woody,” lumpy jaw not responsive to traditional antibiotics. There is increasing appreciation that cervical facial actinomycosis may often be a polymicrobial process. S. aureus or group A streptococci may be involved as a co-pathogen in the development of cervicofacial disease; when this occurs, an acute painful abscess or cellulitis may be the initial manifestation. Actinomycosis should be considered in the proper setting, particularly with progressive cervical adenopathy present in a patient following significant dental work or facial trauma.

Diagnosis

Biopsy of the affected area reveals beaded and branched acid-fast negative gram-positive bacilli. Sulfur granules are present in about 25% of cases and can be visualized in biopsy specimens. Culture of actinomycosis is difficult, and often the Gram stain and biopsy findings suggest the correct diagnosis.

P.98

 

Management

Therapy of actinomycosis involves high-dose intravenous penicillin G, 100,000 to 250,000 units/kg per day in four divided doses for several months, followed by oral penicillin, clindamycin, or tetracycline. Duration of therapy is 6 to 12 months. Surgical drainage may be needed for cases that do not respond to appropriate antimicrobials.

Major Chronic Infections of Cervical Adenitis

1.   Nontuberculous mycobacteria (MAI)

1.   Associated with purplish discoloration, sinus tract formation

2.   PPD < 10 mm induration

3.   Excisional biopsy

2.   Cat-scratch disease

1.   Caused by Bartonella henselae

2.   Diagnosis

1.   Serology

2.   Biopsy reveals stellate abscesses

3.   Treatment: azithromycin

4.   Needle aspiration

3.   Mycobacterium tuberculosis

1.   Rare in developed countries

2.   PPD > 15 mm induration

3.   Positive chest x-ray

4.   Medical therapy

Noninfectious Causes of Cervical Adenopathy

Kawasaki syndrome

Etiology

Kawasaki syndrome is an acute inflammatory illness of unknown etiology. The original term for Kawasaki syndrome was the mucocutaneous lymph node syndrome, and cervical adenitis can be a feature of this illness. Most children diagnosed with Kawasaki syndrome are younger than 5 years of age.

Presentation

The cause of Kawasaki syndrome is unknown; therefore, the diagnosis is based on clinical criteria. The diagnostic criteria include fever, edema and erythema of the

P.99


palms and soles, nonpurulent conjunctivitis, redness of the lips, strawberry tongue, cervical adenitis, and a skin rash. It is not uncommon for patients with Kawasaki syndrome to present initially with a unilateral cervical adenitis, only to progress to the full manifestation of the syndrome. It is for this reason that children with unilateral cervical adenitis who have continued fever despite appropriate antibiotics should be evaluated with the Kawasaki syndrome criteria in mind.

Diagnosis

Diagnosis of Kawasaki syndrome is made by having five of the six clinical criteria and by exclusion of other syndromes such as viral illnesses or toxin-producing bacterial disease. Additional non-criteria signs of Kawasaki disease, including sterile pyuria, marked elevation of the sedimentation rate, and early growing desquamation, are frequently helpful in the diagnosis. Thrombocytosis and palmar desquamation after the first 2 weeks of illness are also characteristic.

A recent study suggested that the cervical lymph nodes in Kawasaki disease may have specific ultrasonographic features; ultrasound appearance of the inflamed nodes in Kawasaki syndrome is often a mass of multiple hypoechoic nodes resembling a cluster of grapes. This is distinct from the ultrasound features of routine bacterial lymphadenitis and can be helpful in patient evaluation.

The management of Kawasaki syndrome includes the use of intravenous immune globulin (IVIG) at a dose of 2 mg/kg. High-dose aspirin, 80 to 100 mg/kg per day in four divided doses, is used until the patient has resolution of fever. The patient is then maintained on low-dose aspirin, 3 to 5 mg/kg per day for about 6 weeks until platelet count and sedimentation rate become normal.

Malignant Causes of Cervical Adenopathy

Etiology

The possibility of malignancy in a child with enlarged nodes is always present in the minds of caretakers. There has been considerable effort made to define those children whose enlarged lymph nodes may be caused by a malignancy such as Hodgkin's disease, non-Hodgkin's lymphoma, or leukemia.

Presentation

Up to 30% of children whose adenopathy is caused by a malignancy have associated fever, anorexia, and weight loss. Additional factors associated with malignancy include an abnormal chest x-ray and increasing node size. Eosinophilia can also be seen in patients with Hodgkin's disease. Extreme elevation of sedimentation rate, uric acid, and lactate dehydrogenase (LDH) can be seen. A frequently quoted study from the early 1980s found that children with supraclavicular adenopathy, unexplained weight loss, or fixation of the lymph node to overlying

P.100


skin have a high likelihood of malignant disease and should be considered for early biopsy.

TABLE 9.2. Noninfectious Causes of Cervical Adenitis

Cause

Comments

1. Kawasaki disease

1. Criteria include 5/6 of the following:

1. Fever greater than 5 days

2. Nonpurulent conjunctivitis

3. Swollen palms, feet

4. Cervical arthritis

5. Rash

6. Erythematous mucous membranes

2. Malignancy

1. Associated with

1. Unexplained fever

2. Unexplained weight loss

3. Fixation of node to overlying skin

4. Supraclavicular adenopathy

5. Eosinophilia

Diagnosis

The diagnosis of malignancy always requires biopsy.

Management

Therapy is dependent on the particular malignancy diagnosed (Table 9.2).

Evaluation of Pediatric Lymphadenopathy

Testing starts with a complete history and physical examination. Duration of the lymphadenopathy, along with associated symptoms, including fever, anorexia, weight loss, and animal exposure, should always be obtained. Examination of the child should be focused on the enlarged lymph node, whether it is red, tender, or fluctuant and associated organomegaly and lymphadenopathy at other areas.

If a node is consistent with an acute bacterial infection, oral antibiotics can be given. If the clinical picture suggests a more chronic condition, laboratory evaluation can include a complete blood count with differential and a metabolic panel including LDH and uric acid. Chest x-ray looking for hilar adenopathy, along with a tuberculous skin testing, is also helpful. Serology for particular pathogens, including toxoplasmosis and cat-scratch disease, may be obtained as suggested by the history.

Ultimately, nodes that remain enlarged and whose etiology is not defined need to be considered for excisional biopsy. Fine-needle aspiration is frequently used to evaluate adenopathy in the adult population. Pediatric specialists are less enthusiastic about this procedure because a significant number of fine-needle aspirations in children do not obtain tissue for appropriate pathology and diagnostic studies (Table 9.3).

TABLE 9.3. Evaluation of Pediatric Cervical Adenitis

1. History
   Duration of lymph node swelling
   Associated symptoms/ fever, weight loss, pallor, bruising
   Travel history (Endemic areas for tuberculosis)
   Exposure history (cats)

2. Examinations
   Associated nodes (particularly supraclavicular)
   Organomegaly
   Tenderness; erythema of node
   Associated criteria for Kawasaki disease

3. Evaluation   
   Chest x-ray
   Complete blood count, sedimentation rate, metabolic panel
   Purified protein derivative
   Serologies (as suggested by history)
      Epstein-Barr virus
      Cytomegalovirus
      Cat-scratch disease
      Toxoplasmosis

Biopsy

P.101

 

Selected Readings

Knight PJ, Mulne AF, Vaggy LE. When is lymph node biopsy indicated in children with enlarged peripheral nodes? Pediatrics1982;69(4):391–396.

Peters TR, Edward KM. Cervical lymphadenopathy and adenitis. Pediatr Rev 2000;21(12)399–405.

Ridder GJ, Boedeker CC, Technau-Ihling K, et al. Role of cat-scratch disease in lymphadenopathy in the head and neck. Clin Infect Dis2002;35(6):643–649.

Serour F, Gorenstein A, Somekh E. Needle aspiration for suppurative cervical adenitis. Clin Pediatr 2002;41(7):471–4744.

Tashiro N, Matsubara T, Uchida M, et al Ultrasonographic evaluation of cervical lymph nodes in Kawasaki disease. Pediatrics2002;09(5):E77.

Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am 2002;49(5):1009–1025.