Denis Pauze
Sore throat is a common chief complaint among pediatric emergency department (ED) patients, and accounts for more than 7 million ED visits annually (1). Many infectious agents cause acute inflammation of the tonsils and pharynx, including Epstein–Barr virus (EBV), adenovirus, parainfluenza virus, rhinoviruses, group A and other β-hemolytic streptococci, and Mycoplasma pneumoniae (2–5). Nonbacterial agents are the cause of pharyngitis in 70% to 85% of patients, especially in adolescents and in children younger than 2 years of age (3).
Group A β-hemolytic Streptococcus (GABHS) remains the most important cause of acute pharyngitis (2–4). Though other pharyngeal infections typically resolve without intervention, GABHS infection if inadequately treated may lead to suppurative complications, including peritonsillar and retropharyngeal abscesses, sinusitis, otitis media, mastoiditis, cervical adenitis, and the nonsuppurative complication of acute rheumatic fever (ARF). Given the breadth of illnesses and potential associated complications, for individual and public health reasons, GABHS infections should be diagnosed and effectively treated.
CLINICAL PRESENTATION
Generally, patients with pharyngitis complain of a sore throat. Additional symptoms may include fever, headache, nausea, vomiting, myalgias, dysphagia, cough, runny nose, and fatigue.
GABHS pharyngitis has an incubation period of 2 to 5 days and affects children between ages of 5 and 15, mostly during the winter and spring months (3). Transmission occurs via respiratory droplets and is associated with close contact (3). Most children with acute pharyngitis present with one or more complaints in addition to sore throat. Those with GABHS infection typically report the sudden onset of throat pain which may be associated with fever, headache, abdominal pain, nausea, or vomiting (2–4). On physical examination, patients with streptococcal pharyngitis usually have tonsillopharyngeal erythema with or without tonsillar exudates, palatal petechiae, and tender anterior cervical adenopathy (2–4). Other findings may include a beefy, red, swollen uvula, excoriated nares (especially in infants), and rarely a fine, diffusely papular erythroderma (“sandpaper” or scarlatiniform rash) in cases of toxin-producing strains of GABHS (4). Bacterial pharyngitis is uncommon in children younger than 3 years; patients in the 3- to 5-year age group are more likely to present atypically with copious purulent rhinorrhea, as opposed to pharyngeal exudates (1,2).
No findings are specific for GABHS pharyngitis, and patients frequently exhibit atypical combinations of signs and symptoms compared to those considered “classic” (4). For example, some children may present with abdominal pain as the chief complaint. A systematic review evaluating the predictive accuracy of signs and symptoms in GABHS identified no single diagnostic sign or symptom. However, five findings were noted to increase diagnostic accuracy by to more than 50%: scarlatiniform rash, palatal petechiae, pharyngeal exudates, vomiting, and tender cervical lymph nodes (6).
DIFFERENTIAL DIAGNOSIS
The differential diagnosis includes a number of life-threatening conditions. Pertinent negatives related to these diseases should be noted as part of the evaluation. These conditions include Kawasaki disease, Stevens–Johnson syndrome, epiglottitis, Lemmiere syndrome, deep space abscesses (both retro- and peripharyngeal abscesses), and Ludwig’s angina. Other less threatening but nonetheless important agents include EBV, herpes simplex virus, adenovirus, parainfluenza viruses, rhinovirus, and human immunodeficiency virus. Important bacterial causes besides GABHS include Fusobacterium necrophorum,Neisseria gonorrhoeae, group C streptococcus, Mycoplasma, and Corynebacterium.
Fortunately, epiglottitis due to Hemophilus influenzae type B (Hib) is now rare in the developed world thanks to widespread use of the Hib vaccine. Presently, viruses, non-B Hemophilus serotypes, and other bacteria are the primary causes of acute epiglottitis. Changing trends in the post-Hib vaccination era note a shift towards older patients, with an increase in the mean age of disease from 5.8 to 14.6 years over the decade 1992 to 2002 (7). Conversely, national trends found an increase in cases of epiglottitis in infants less than 1 year of age from 1998 to 2006 (8). While the overall incidence has decreased, however, cases of pediatric epiglottitis occur and the diagnosis should be suspected in immunosuppressed or unvaccinated or partially vaccinated children.
Lemmiere syndrome is a life-threatening form of pharyngitis caused by normal oropharyngeal bacteria (including anaerobic gram-negative bacteria such F. necrophorum). It is characterized by sore throat or pharyngitis, bacteremia, and thrombosis of the internal jugular vein. Although rare, Lemmiere syndrome is rising in incidence (9). Patients are usually adolescents or young adults with fever and pharyngitis who often have failed outpatient antibiotic treatment for suspected GABHS. Patients are often ill-appearing, with swelling or tenderness over the sternocleidomastoid muscle, and may have respiratory complaints related to an associated pneumonia or septic pulmonary emboli. Demonstration of a jugular vein thrombosis by CT or ultrasound can make the diagnosis early.
Acute pharyngitis may be accompanied by peritonsillar, parapharyngeal, or retropharyngeal abscess. Patients with deep tissue abscess appear ill, are febrile, and have localized pain. A patient with a peritonsillar abscess often presents with trismus, a muffled (“hot potato”) voice, and unilateral swelling of the soft palate with uvular deviation away from the affected side. Parapharyngeal abscess is frequently associated with tender unilateral neck swelling on the affected side. Younger children with acute pharyngitis may develop retropharyngeal lymphadenitis that spreads into the retropharyngeal space. The diagnosis of retropharyngeal abscess should be considered, along with epiglottitis, in a toxic-appearing toddler with dysphagia, drooling, signs of airway obstruction, and pain with neck movement.
ED EVALUATION
The diagnosis of acute pharyngitis can be made from historical and physical examination findings, but differentiating GABHS from other causative organisms is challenging. Patients with GABHS may have more significant pharyngeal inflammation, prominent exudates, and tender anterior cervical lymphadenopathy than patients with viral etiologies, but these findings are not reliable. Numerous studies over the past 60 years document clinicians’ inability to clinically differentiate GABHS from non-GABHS pharyngitis (6). Certain signs or symptoms may be more suggestive of nonstreptococcal causes, however. For example, Mycoplasma often presents with a history of prolonged cough or pneumonia or bronchitis (2,4). EBV may present with extreme fatigue, significant pharyngeal exudates, generalized lymphadenopathy, and/or hepatosplenomegaly. Adenoviral pharyngitis is typically accompanied by nonpurulent conjunctivitis and preauricular adenopathy. Coxsackie pharyngitis is associated with the discrete painful posterior pharyngeal ulcers of herpangina, whereas parainfluenza virus causes croup or laryngitis in older children.
While no sign or symptom is specific or sensitive enough to diagnose GABHS, a number of clinical decision rules (CDRs) have been developed to aid diagnosis. The Centor criteria are perhaps the best known and consist of four signs, with one point each given for fever, exudates, tender nodes, and absence of cough. Patients with a score of 0 or 1 are presumed to have viral pharyngitis and require no further testing, whereas higher scores are progressively more likely to reflect GABHS infection. The performance of CDRs for the diagnosis of GABHS in the pediatric population however, is weak at best (4).
In spite of these diagnostic challenges, patients with pharyngitis must be evaluated for conditions that require acute intervention; these include airway compromise, pain, and dehydration. Edematous tonsils may obstruct the upper airway, resulting in respiratory distress or sleep apnea. Often, children refuse to drink because of pain and can become dehydrated, occasionally requiring admission. Secondly, patients should be evaluated for suppurative complications. A CT scan of the neck with intravenous contrast may be indicated if a deep space abscess is suspected.
Patients should be evaluated for GABHS using a rapid antigen detection test (RADT), if available. RADTs provide quick and highly specific identification of the GABHS antigen and have been shown to increase appropriate care of ED patients with GABHS pharyngitis (10). Recent data suggest that RADTs using newer technologies such as optical immunoassay or DNA probes may be more sensitive than other RADTs and perhaps sensitive enough for use without a confirmatory backup throat culture (3,6,11). However, in contrast to diagnostic recommendations for adults with pharyngitis, numerous advisory groups continue to recommend that confirmatory cultures be performed in children and adolescents with negative RADTs because of the relatively higher pediatric incidence of streptococcal infection and ARF (6,11). These advisory groups recommend that physicians who elect to use any RADT in children and adolescents without confirmation of negative results by blood agar plate (BAP) culture should do so only after adequately demonstrating in their own practice that their RADT is as sensitive as BAP culture, which remains the gold standard for diagnosis of GABHS pharyngitis (3,6,11). False-negative RADTs often result from obtaining inadequate amounts of tonsillar or pharyngeal secretions on the specimen swab. To minimize false-negative results, specimens should be obtained by vigorous swabbing of both tonsils and the posterior pharyngeal wall (1,4,6).
ED MANAGEMENT
For airway obstruction secondary to enlarged tonsils, a nasopharyngeal airway should restore airway patency and intravenous fluid resuscitation and analgesics may be used to treat acute dehydration and pain. Most often, analgesics such as acetaminophen or ibuprofen in association with cold fluids provide adequate pain relief. Steroid treatment for pain relief still remains controversial. The Infectious Disease Society of America does not currently recommend steroid therapy for pain relief, but the topic remains controversial and there is evidence to support their use (5,12).
If GABHS is identified by laboratory testing, antibiotic therapy is currently recommended in the United States. Although antimicrobial therapy for GABHS may shorten the clinical course of illness, the disease is usually self-limited, with resolution within 3 or 4 days, even without treatment (4). This is why some countries do not treat GABHS pharyngitis. Therapy can be postponed up to 9 days from initial to the onset of symptoms and still safely prevent rheumatic fever; empiric therapy is thus not recommended (1,2,4,7). Numerous antibiotics are effective for GABHS pharyngitis (4). However, penicillin—an inexpensive drug with a narrow spectrum of activity and well-proven efficacy and safety—remains the drug of choice (1–4). A 10-day course of oral penicillin V is recommended at 400,000 U (250 mg) two to three times daily for children weighing 27 kg (60 lb) or less, or 800,000 U (500 mg) twice daily for those weighing more than 27 kg (1). In patients who are felt to be unlikely to complete a 10-day course of therapy, benzathine penicillin G, 600,000 U intramuscularly, should be given to children weighing less than 27 kg (60 lb), and 1.2 million U to larger children (1,3). Amoxicillin for 10 days at the doses described is equivalent to penicillin and may improve compliance, given its better palatability in suspension.
From a compliance perspective, 10-day treatment regimens have become controversial. It is estimated that only about 10% of patients complete a full 10-day course of antibiotics, but with no increased incidence of complications (13). Shorter courses have been studied, including the use of azithromycin or cephalosporins (10). A recent Cochrane review included over 13,000 cases of confirmed GABHS pharyngitis and compared short-course antibiotics to standard 10-day treatment with penicillin and found them to be equivalent (14). Preliminary data suggest that a 10-day course of oral amoxicillin given as a single-daily dose is as effective as 10 days of penicillin V given three times daily (1,4). If confirmed by additional studies, once-daily amoxicillin could eventually become an alternative treatment option given its low cost, acceptable taste, and relatively narrow antimicrobial spectrum (4). While once-daily amoxicillin is supported by the AAP, both the AAP and IDSA currently recommend a standard 10-day course of either penicillin or amoxicillin as first-line treatment.
Penicillin allergic patients should be treated with a cephalosporin. For those patients with a Type 1 hypersensitivity to penicillins, the provider should consider clindamycin (20 mg/kg/day in 3 divided dosages, max 1.8 g/day). Macrolides are also acceptable alternatives for treatment, although macrolide resistance has been reported (15). The AAP does not recommend tetracyclines, fluroquinolones or sulfonamides for the treatment of GABHS penicillin-allergic patients who do not have immediate hypersensitivity-type reactions to penicillin is a 10-day course of a first-generation cephalosporin such as cefadroxil or cephalexin (1). Due to the relatively higher cost and wider spectrum of antibacterial activity of cephalosporins when compared to penicillins, however, this class of agents is not recommended for routine use in patients with GABHS pharyngitis who are not penicillin-allergic (1,4). Numerous once-daily and short-course antibiotic regimens have been approved by the Food and Drug Administration for treatment of GABHS pharyngitis in recent years. However, these regimens generally use unnecessarily broad-spectrum antibiotics and are less cost-effective when compared to penicillin; therefore, they are not recommended as first-line therapy (4,11).
It is important to acknowledge antibiotic treatment for GABHS is controversial. Many Western European countries do not treat confirmed GABHS and there is no evidence of increased rates of ARF or other suppurative complications (16,17). Antibiotic prescribing trends in England over a 10-year period support a similar conclusion, where a 50% reduction in antibiotic prescriptions was not associated with an increased incidence of rheumatic fever. The decision to treat or not to treat depends on careful communication with parents about the pros and cons of treatment relative to the needs of the individual patient.
DISPOSITION
Most children with pharyngitis can be evaluated and managed as outpatients. For patients with airway obstruction or deep tissue abscesses, admission to monitored settings is recommended. An otolaryngologist should evaluate patients with confirmed abscesses to assess the need for surgical drainage. Admission should also be considered for those children who continue to refuse oral intake and require intravenous rehydration.
CRITICAL INTERVENTIONS
Acute Pharyngitis
• Assess and manage airway patency, hydration status, and pain.
• Always look closely (even in the uncooperative child) for oropharyngeal abscess.
• Diagnose and treat GABHS pharyngitis with appropriate antibiotics.
Common Pitfalls
Acute Pharyngitis
• Failure to obtain an adequate throat swab for RADT or culture.
• Failure to send a confirmatory throat culture if RADT is negative in children and adolescents.
• Failure to evaluate and document the airway examination.
REFERENCES
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