Pediatric Otorhinolaryngology: Diagnosis and Treatment, 1st Ed.

18

Neck Infections

Gi Soo Lee

Pediatric neck infections are unique due to their variety of etiologies as well as the potential for severe complications. Aggressive management of the airway is often the most urgent aspect of care, and the diagnosis must be made expeditiously to prevent delay in either antibiotic or surgical management. A careful history and examination, along with judicious use of various diagnostic imaging and laboratory tests can aid the physician in determining the potential etiology. This chapter discusses the more common and uncommon causes of neck infections in the neonate to adolescent age group.

Streptococcal Pharyngotonsillitis

Bacterial pharyngitis and tonsillitis in the pediatric population can be distinguished from its viral counterpart by the absence of coryza symptoms of cough, rhinorrhea, and malaise and the greater-than-expected severity of sore throat, fever, and lymphadenopathy.1 Bacterial pharyngotonsillitis is most commonly caused by Group A beta-hemolytic Streptococcus pyogenes (GABHS). In fact, while Hemophilus influenzae was the most commonly identified organism in the core of tonsils removed for obstructive symptoms, Group A Streptococcus was the predominant organism identified in those excised for chronic tonsillitis.2 S. pyogenes are gram-positive cocci with multiple strains characterized by their antigenic differences in the configuration of cell wall polysaccharides. These differences are classified into groups (A, B, G, etc). GABHS is characterized by the presence of a zone of complete hemolysis when grown on agar plates, sensitivity to bacitracin, and production of specific enzymes.

Streptococcal pharyngotonsillitis presents with marked oropharyngeal erythema and pain, odynophagia, indurated palate and uvula, palatal petechiae, referred otalgia, and tender cervical lymphadenopathy. In all cases of suspected infection, obtaining a throat culture is considered the standard criterion for diagnosis. Rapid antigen detection tests (rapid strep test) have a high specificity but lower sensitivity (96 to 98% vs. 70 to 95%),35 and are often used while culture results are pending to institute antibiotic therapy.

For medical therapy, penicillin is the first-line antibiotic treatment of choice. Till date, no penicillin-resistant S. pyogenes has been isolated in the clinical setting.6,7 Those patients allergic to penicillins are treated with macrolides such as erythromycin or azithromycin.

Tonsillectomy is recommended after seven or more episodes of culture-proven streptococcal pharyngitis in 1 year, five episodes per year for two consecutive years, or three episodes per year for 3 years.8Surgical management of the asymptomatic streptococcal carrier, however, remains controversial. An estimated 15 to 20% of all schoolchildren are carriers of Streptococcus in their saliva or nasal secretions, depending on their location and the season, even after adequate antibiotic therapy.9,10 These carriers may harbor infection that may then be spread to other family or school members. In some children, it may be difficult to determine whether the carrier state or an active infection exists. For this reason, it still may be reasonable to recommend a tonsillectomy even in cases in which the carrier has minimal clinical morbidity.

Streptococcal pharyngotonsillitis can result in localized and disseminated suppurative complications. Peritonsillar cellulitis can progress to peritonsillar abscess (classically referred to as a quinsy tonsillitis in the older literature), characterized by drooling, trismus, a “hot potato” voice, and tender cervical lymphadenopathy. Peritonsillar infection can subsequently spread medially into the retropharyngeal space or laterally into the parapharyngeal space. Either of these deep-space infections may track inferiorly into the mediastinum. Septic thrombi may also produce metastatic spread resulting in osteomyelitis, meningitis, or brain abscess. All these conditions require intravenous antibiotic therapy and deep-space infections require surgical drainage. If a peritonsillar abscess is recurrent or associated with a history of chronic tonsillar infection, tonsillectomy may be indicated.11

Streptococcal infections can also cause other systemic complications. Scarlet fever presents as a generalized, nonpruritic, erythematous, macular skin rash that is worse on the extremities. The associated “strawberry tongue” is bright red and tender due to superficial desquamation of the papillae. Typically, the rash lasts for 4 to 7 days and is accompanied by fever and arthralgias. Rheumatic fever is rare today with only sporadic outbreaks12; however, in the 1940s and 1950s, it was a complication that was seen in 3% of streptococcal pharyngitis infections.13 Bacterial vegetations affect the mitral and tricuspid heart valves leading to murmurs, persisting relapsing fevers, and valvular stenosis or incompetence. Septic arthritis with painful, hot, joint effusions is a known complication of streptococcal pharyngitis. The bacteria can be isolated by needle aspiration of the effusion. Treatment with parenteral antibiotics for at least 6 weeks is necessary to avoid osteitis, arthrodesis, and long-term morbidity from restricted range of movement. Acute post-streptococcal glomerulonephritis can result in 10 to 15% of those streptococcal pharyngeal infections caused by certain nephritogenic strains of the bacteria. Generalized edema, hypertension, bradycardia or tachycardia, and gross hematuria/proteinuria are common signs. Treatment includes various supportive measures in addition to antihypertensives, diuretics, and strict diet and fluid management usually results in full recovery.

Non-Group A Streptococcus Pharyngotonsillitis

Pharyngotonsillitis can be caused by a multitude of organisms, including various anaerobic bacteria that reside in the oral cavity as normal flora. Beta-lactamase producing Bacteroides species, Fusobacteriumspp., and Haemophilus influenzae have been isolated from tonsil cores of 73 to 80% of children with a history of GABHS tonsillitis, and from 40% of tonsils from those with non-GABHS infections.14Additionally, other organisms such as Prevotella, Porphyromonas spp., and Actinomycetes have been isolated from peritonsillar and retropharyngeal abscesses.15 Bacteroides, the most common anaerobic organism isolated from tonsil tissue, has been implicated in the development of tonsillitis that may progress to frank peritonsillar abscess formation following penicillin therapy.1618 In this scenario, surgical incision and drainage is performed with antibiotic coverage either with clindamycin or amoxicillin/clavulanate.

Retropharyngeal Abscess

Retropharyngeal abscesses (RPAs) are uncommon but serious complications of upper respiratory tract infections that extend into the retropharyngeal lymph nodes. Suppuration of these nodes leads to abscess formation. This is nearly exclusively a pediatric diagnosis, with most incidents occurring in children in the age group of 6 months to 6 years (mean age: 3 to 5 years).1921 This is in contrast to parapharyngeal and peritonsillar abscesses that occur more frequently in older children and adolescents. Primary infections include pharyngotonsillitis, adenoiditis, otitis, sinusitis, and dental infections. In some instances, osteomyelitis of the spine can develop from extension of infection from the prevertebral space. Additionally, penetrating trauma can also result in retropharyngeal space infections, including foreign body impalement in the oral cavity, impacted fish bones in the oropharynx/hypopharynx, and instrumentation during surgery.

Group A Streptococcus is the most common bacterial cause, though other Streptococcus species, Staphylococcus, Neisseria, and Haemophilus species have also been cultured.22,23 Bacteroides species are the most common anaerobic organisms.

Children with an RPA present with a constellation of symptoms and signs including fever, chills, decreased appetite, sore throat, odynophagia, trismus, decreased neck range of motion, torticollis, altered voice, and globus sensation. Fever and neck pain are the most common symptoms.24 Cervical lymphadenopathy, neck swelling, oropharyngeal fullness (usually asymmetric), stridor, and drooling are also noted.

When an RPA is suspected, a lateral neck X-ray plain film is often first performed. This is taken during inspiration with normal neck extension. However, there are some limitations to making the diagnosis with this imaging modality, therefore computed tomography (CT) is recommended in any patient with a high index of suspicion.25 A CT scan provides much more information than a plain film, with sensitivity of 90%.24 Positive predictive value has been estimated at 82%, and the negative predictive value has been estimated to be 100%.26

Determining airway stability is critical when managing a patient with retropharyngeal abscess. Patients must remain in a position of comfort, usually supine with the neck extended, as neck flexion or forcing a child to sit up can occlude the airway. Once the diagnosis is made, broad-spectrum antibiotic coverage is initiated. Clindamycin is often a first-line treatment, but due to the increasing frequency of resistant bacteria, treatment may include a combination with cefoxitin or a beta-lactamase–resistant penicillin, such as ticarcillin/clavulanate, piperacillin/tazobactam, or ampicillin/sulbactam. Close cardiopulmonary monitoring is also important. If airway compromise is impending, the examination should be done in the operating room. A needle aspiration can often decompress the lesion, followed by transoral surgical drainage. If there is extension laterally into the parapharyngeal space, the collection may need to be drained via a transcervical approach. Notably, the preferred treatment for RPAs has been controversial. Recently, some have advocated antibiosis as the primary mode of treatment, with surgery reserved for those who do not respond.27,28

Lemierre Syndrome

Lemierre syndrome is an anaerobic, bacteria-mediated, suppurative thrombophlebitis of the internal jugular vein that occurs as a complication of head and neck infections. Oropharyngeal processes including pharyngotonsillitis comprise 85% of the primary sites. There is mucosal invasion and spread of the infection into the lateral pharyngeal space with subsequent infiltration of the internal jugular vein either by direct extension or via lymphatic or hematogenous spread. Other primary sources of infection including parotitis, mastoiditis, otitis, and dental infections have been reported.29,30 Lemierre syndrome usually affects healthy young adults and adolescents. The most common causative organism (in 84% of cases) is Fusobacterium necrophorum, a gram-negative obligate anaerobe,29 but others, including BacteroidesStreptococcus, and Lactobacillus species, have also been identified.

Patients will report a history of fever and acute pharyngitis or other head and neck infection, followed by neck swelling and tenderness. Septic emboli can result in empyema, lung cavitation, and hypoxia. Other complications such as septic arthritis, hepatic abscesses, and osteomyelitis have also been reported. Imaging of the neck by ultrasound or CT will demonstrate internal jugular vein thrombosis and blood cultures will confirm septicemia. Treatment involves surgical drainage of abscesses with possible ligation or excision of the affected portion of the vein, and prolonged antibiotic therapy directed at anaerobes.

Atypical Mycobacterial Infection

Nontuberculous mycobacteria (NTM) are a group of acid-fast bacilli that have been recognized as a cause of cervico-facial lymphadenitis in healthy children since 1956,31 though they were previously identified in human secretions in 1885.32 These organisms, collectively referred to as “atypical mycobacteria,” include, among others, Mycobacterium avium-intracellulare, M. scrofulaceum, M. kansasii, and M. bohemicum. Endemic in the Midwest and southwest United States, they are ubiquitous in soil, water, vegetation, dairy products, and animals. Human-to-human transmission has not been documented. Affected patients are generally immunocompetent and healthy children between ages 1 to 5 years.33,34 Incidence has been reported as 1.21 per 100,000 children per year.35

Infections caused by NTM generally present as chronic, nontender cervical lymphadenitis that develop over weeks to months. A single lymph node, or collection of unilateral nodes, gradually enlarges in the upper cervical or submandibular area—the “beard distribution.” Occasionally it presents in the preauricular, intraparotid, or posterior neck regions. Initially, they are firm and well-circumscribed; as the disease progresses, the nodes become more superficial, and overlying skin becomes thin and violaceous. Eventually, the suppuration breaks through the skin and causes a chronic drainage. The dolor and calor usually associated with other suppurative lymphadenopathy are absent, as are generalized systemic signs of infection.

The diagnosis of NTM infection is primarily clinical, since culturing the organism is difficult and time-consuming. Purified protein derivative (PPD) tuberculin skin testing is only positive in approximately 50% of patients.36

Optimal treatment for cervicofacial NTM has not been established. Left untreated, the frank suppuration results in a chronically draining sinus tract that may persist for months before spontaneously resolving. This leads to significant epidermolysis and scarring. Total surgical excision of the affected lymph nodes is still considered the gold standard and the primary management strategy for infections in children. Cure rates vary from 80 to 95%.35,3739For lesions not amenable to total excision (extensive draining fistulae or involvement of facial nerve), alternatives include needle aspiration, incision and drainage, and curettage. Some authors advocate these methods as primary treatment modalities and have exhibited good results.40,41 While atypical mycobacteria are unresponsive to many common antibiotics, reports have demonstrated reasonable efficacy with the clarithromycin-based therapies.4245Currently, no standardized antibiotic regimens exist, but clarithromycin alone or with a second drug such as ethambutol, rifampin, or rifabutin are most commonly utilized. The treatment is often prolonged (up to months), and may be more beneficial in early infections without suppuration.

Cat Scratch Disease

This worldwide anthropozoonosis is caused by Bartonella henselae, a gram-negative proteobacterium. The bacterium is present in 30 to 60% of healthy domestic and wild cats; while feline-to-feline transmission occurs via fleas, human are inoculated by direct contact (scratches or bites).46 The incidence of this disease in United States is 1.8 to 9.3 per 100,000 persons.47,48

A self-limited, unilateral, and tender cervical lymphadenopathy results after exposure. This may occur up to several weeks after contact, and a 1- to 10-mm nontender papule sometimes presents at the inoculation site. Systemic signs of mild fever and malaise occur in approximately 50% of cases.49 Serologic testing is widely available, and the organisms can be identified with Warthin-Starry stain.

The infection spontaneously resolves over months, and treatment typically is supportive. Suppuration occurs in more than 80% of patients, but only 10% of abscesses are significant enough to requires surgical intervention.50Complications, including Parinaud oculoglandular syndrome (preauricular lymphadenopathy and conjunctivitis), encephalitis, and hepatitis, may form in 5 to 13% of cases, especially if immunocompromised.51 Antibiotic use is controversial, and there is no standardized regimen. Macrolides, fluoroquinolones, and sulfa-based medications can be helpful, but are often used only when complications arise.52

Tularemia

Tularemia is caused by Francisella tularensis, an aerobic gram-negative, facultative intracellular, pleomorphic coccobacillus. It is one of the most infectious bacteria known, causing illness in humans with exposure to as few as 10 to 50 organisms. F. tularensis is considered a category A biowar-fare agent due to its high infectivity, ease of dissemination, and ability to cause substantial illness and death.53 Natural hosts include rabbits and rodents. Biting flies and ticks are the most common vectors in the United States. There is a bimodal age prevalence: one peak at 5 to 9 years and the second at 75 years.54

The ulceroglandular form of tularemia is the most common in both adults and children. A primary skin ulcer forms at the site of inoculation 2 to 5 days after exposure; the painful lesion necroses and forms a black eschar—this is associated with tender lymphadenopathy. Greater than 20% of cases will suppurate if left untreated or if treatment is delayed over 2 weeks.55 Oropharyngeal tularemia, the second most common form in children, presents with an exudative pharyngitis and tonsillitis, mucosal ulcers, stomatitis, ipsilateral adenitis, gastrointestinal symptoms, headaches, and fevers. A less common glandular form presents with lymphadenopathy only without epidermal or mucosa involvement.

The diagnosis is made clinically, with a history of animal exposure and a tick bite. Serologic testing is available, but cross-reactivity with other organisms including YersiniaBrucella, and Pseudomonasmakes it unreliable. Additionally, while F. tularensis can be cultured, its highly contagious nature makes it a danger to laboratory personnel. Streptomycin is the treatment of choice, but within 24 hours of exposure, prophylaxis with ciprofloxacin or doxycycline is recommended.

Actinomycosis

Actinomyces israelii is the cause of this chronic granulomatous infection. It is a gram-positive microaerophilic bacterium commonly found in the oropharynx; one study found a 28% incidence of A. israelii in tonsil tissue specimens.56 Cervicofacial actinomycosis, which comprises 55% of all cases and makes it the most common form,57 is thought to be due to injury to oral mucosa, secondary to maxillofacial trauma, dental infections, or surgery. The infection spreads via lymphatic or hematogenous means into adjacent tissues. Sinus tracts form followed by the emergence of firm, nontender erythematous or violaceous masses. These masses eventually suppurate and drain. True lymphadenopathy is rare. Any tissue in the head and neck region can be affected, including major salivary glands, tongue, palate, sinuses, nasopharynx, larynx, ear, and thyroid.5864

Histological examination of the draining fluid will often reveal “sulfur granules”; yellow-hued flecks representing clumps of bacteria. The organism is difficult to culture and treatment includes antibiotic therapy for months to years. The bacteria are susceptible to penicillin, clindamycin, macrolides, and tetracycline. Draining masses are surgically excised.

Histoplasmosis

Histoplasmosis is an opportunistic infection caused by dimorphic fungus Histoplasma capsulatum. It is the most common fungal infection in humans, and is contracted by inhaling particles from bat guano or poultry droppings containing H. capsulatum spores. Though found worldwide, it is endemic to central and northeast United States. In these locations, 75 to 80% of the population are asymptomatic carriers.65,66 Progressive disseminated histoplasmosis occurs in 4 to 27% of infected children, those immunocompromised, or in the elderly,67 and may present with head and neck findings.

Most patients with acute pulmonary histoplasmosis present with a flu-like infection; symptoms include malaise, fevers, cough, mylagias, and chills. Onset is 3 to 14 days after exposure.68 Those who develop a chronic, progressive disseminated infection often present with wart-like lesions that evolve to painful, ulcerated lesions on the aerodigestive mucosa and mimic neoplasms or granulomatous diseases. These lesions are found on the tongue, palate, buccal mucosa, and larynx.6971

Diagnosis is made with sputum or blood cultures, and antigen/antibody testing. Sputum cultures are positive in 15% of acute pulmonary and 60 to 85% of chronic pulmonary histoplasmosis cases, and blood cultures are positive in 50 to 70% of progressive disseminated histoplasmosis cases.72 No treatment is required for asymptomatic or mildly symptomatic patients. Prolonged or more severe cases are treated with itraconazole or amphotericin B.

Infectious Mononucleosis

Acute infectious mononucleosis is the most common manifestation of primary infection with Epstein-Barr virus (EBV), also known as the human herpesvirus-4. This ubiquitous gammaherpesvirus infects approximately 95% of the world's population. In the United States, 50% of children acquire the virus by the age of 5.73 Infectious mononucleosis primarily affects adolescents and young adults. Infection in infants and younger children are often asymptomatic or mild74; nonetheless, children can present with the acute infection. Oral manifestations include sore throat—the most common symptom, exudative pharyngitis—the most common clinical finding, tonsillar hypertrophy with associated dysphagia or airway obstruction, and petechiae at the hard and soft palate junction (present in 25 to 60% of patients).

The enlarged and erythematous tonsils exhibit a gray, exudative membrane. This can be easily scraped off without bleeding. In younger children, respiratory distress due to obstruction may require treatment with high-dose steroids or, rarely, placement of a nasal airway or endotracheal tube. The tonsils can remain grossly hypertrophied following the resolution of infectious mononucleosis, and necessitate a future tonsillectomy.75 However, this procedure may be associated with an increased risk of post-tonsillectomy hemorrhage.76

The diagnosis of infectious mononucleosis is made by a positive heterophile antibody agglutination test with confirmation by positive blood titers to the virus. Clinically, generalized cervical lymphadenopathy and hepatosplenomegaly often suggests the diagnosis. The blood smear typically displays many atypical lymphocytes. Infection with cytomegalovirus may mimic that caused by EBV but is usually less severe clinically. Low-grade fever, fatigue, and malaise may continue for months. Treatment is supportive, with rest, good oral hygiene, hydration, and use of corticosteroids for severe cases. Secondary bacterial infections or oral ulcerations can occur in the tonsils, and antibiotic therapy may be necessary.77 The use of ampicillin, however, is associated with a greater incidence of a cutaneous papular rash.

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