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Strep throat: Guidelines for diagnosis and treatmentAlthough penicillin remains the treatment of choice for strep throat, other therapeutic considerations include patient adherence to an antibiotic regimen, recurrent disease, and whether tonsillectomy is indicated.Tom Colletti, MPAS, PA-C; Peggy Robinson, MS, MHS, PA-CTom Colletti is Academic Coordinator and Assistant Clinical Professor in the Physician Assistant Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, NC. Peggy Robinson is Assistant Clinical Professor in the Physician Assistant Program at Duke. The authors have indicated no relationships to disclose relating to the content of this article.
Sore throat of viral origin is a common clinical presentation in the primary care setting. Findings in the National Ambulatory Care Survey indicate that acute pharyngitis is one of the top 20 reported diagnoses and represents 1.1% of primary care visits.1 In fact, the Infectious Diseases Society of America (IDSA) has established clinical guidelines to help the clinician manage this common infection.2 Infection with group A beta-hemolytic streptococci (GABHS) is the only common cause of acute pharyngotonsillitis that routinely requires antibiotic treatment,2 accounting for 15% to 30% of sore throats in children and 5% to 10% in adults.3 While the highest rates of infection are in children aged 5 to 11 years, a study by Berkovitch and colleagues found that children as young as 3 months had documented GABHS pharyngitis.4
PathogenesisThe etiologic agent for streptococcal pharyngitis is the gram-positive organism Streptococcus pyogenes. The symptoms of strep throat, which most commonly occurs in the winter and early spring,2 are preceded by a 24- to 72-hour incubation period. Transmission is by hand contact with nasal discharge;5 fomites and pets are not believed to be vectors of transmission. In addition to pharyngitis, GABHS are also responsible for the infectious skin lesions of impetigo and perianal streptococcal cellulitis. Clinical presentationSymptoms of streptococcal infection often start with the sudden onset of sore throat, dysphagia, and fever. Children may also present with headache, nausea, vomiting, and abdominal pain. Findings on clinical presentation include pharyngeal erythema, tonsillar exudates, anterior cervical lymphadenitis, palatine petechiae, erythematous papillae of the tongue, and a sandpaper rash (scarlatiniform rash). Clinical findings are not diagnostic, although they can help to identify those patients in whom the probability of strep throat is high.
Differential diagnosisThe list of organisms included in the differential diagnosis of pharyngitis is extensive. Many viruses—including rhinovirus, adenovirus, influenza, respiratory syncytial virus, coxsackievirus, echovirus, and herpesvirus (such as Epstein-Barr)—are implicated as etiologic agents of acute pharyngitis.2 Up to 20% of pharyngitis may be associated with rhinovirus alone.8 Infectious mononucleosis is one of the more common differential diagnoses in the 15- to 30-year-old age group. Although the infection may be mild or subclinical, some cases can result in significant morbidity.9 The classical presentation of infectious mononucleosis is with fever, pharyngitis, tender cervical lymphadenopathy, and splenomegaly. A prodromal period of malaise, fatigue, headache, arthralgia, fever, chills, dysphagia, and anorexia lasting several days may precede the acute phase.8 A common finding is the development of a classic maculopapular rash in 90% of patients with mononucleosis who are treated with amoxicillin or ampicillin.10 This appears to be a hypersensitivity to the antibiotic that develops with the acute infection. Laboratory evaluationConsider the clinical, historical, and epidemiologic evidence before deciding to perform microbiological tests to evaluate patients with symptoms of acute pharyngitis. Those who have signs and symptoms that are not suggestive of streptococcal infection do not require diagnostic tests. Diagnostic confirmation of strep throat is helpful in those patients whose presentation suggests it, however, because symptoms of bacterial and viral infections often overlap and because bacteriologic confirmation is necessary to resolve any uncertainty as to the etiology. Throat cultureCulture of throat swabs on a blood agar plate remains the gold standard for detecting GABHS. Obtain specimens from both tonsils and the posterior pharyngeal wall to be accurate. Collected and plated properly, the culture has a 90% to 95% sensitivity.2 Although the culture may first be read at 24 hours, the recommendation is to examine the plates and make final decisions after 48 hours of incubation.11 A detailed patient history is essential because if the patient took antibiotics shortly before the samples for culture were taken, false-negative results may occur. Rapid antigen detection testingRapid antigen detection testing is more expensive than obtaining a throat culture; however, results are available within a few minutes as compared to one or two days. This rapid result allows patients to receive treatment sooner, helping to prevent the spread of the infection and allowing the patient to return to work or school more quickly. Many of the rapid antigen detection tests (RADTs) have excellent specificities of 95% or higher; a high specificity means that the test is reliable if it is positive.2 However, many RADTs have a sensitivity of only 80% to 90%, compared to the higher sensitivity of blood agar plate cultures;2 thus, a negative RADT result may actually be false. A confirmed diagnosis of streptococcal pharyngitis can be based on positive findings on throat culture or on a positive RADT result. Because of the low prevalence of rheumatic fever (RF) in adults, a confirmatory throat culture need not be obtained in this population.12 However, since children and adolescents have a higher prevalence of infection with GABHS and subsequent RF, confirm a child’s negative RADT result by culturing throat swabs.2 Follow-up throat cultures are not routinely recommended in the asymptomatic patient who was adequately treated for the initial infection.2 Past streptococcal infectionAntistreptococcal antibody titers are not useful in the diagnosis of acute infection because an elevated titer reflects past infection with GABHS. Confirmation of past infection is helpful in those persons suspected of having acute RF or acute poststreptococcal glomerulonephritis (PSGN). It may also be useful to distinguish between patients with acute streptococcal infection and pharyngeal carriers presenting with an interceding viral pharyngitis. The findings from RADTs and throat cultures do not accurately distinguish between asymptomatic carriers and those acutely infected. TreatmentCorrect diagnosis and treatment of streptococcal pharyngitis are important to decrease complications, including acute RF and acute PSGN. However, there are two caveats. First, the infection is self-limited and symptoms may disappear within 3 days even in the absence of treatment. Second, treatment may be delayed for up to 9 days and still be effective in preventing the development of RF.2 These facts allow some leeway in instituting therapy while evaluating a patient with a sore throat. Penicillin, introduced more than 50 years ago, remains the drug of choice for the treatment of streptococcal infection (see Table 2).13 No documentation suggests that any clinical isolate of GABHS is resistant to penicillin.2 Oral penicillin V and IM benzathine penicillin G are both effective in eradicating the pathogen from the upper respiratory tract and preventing RF. Poor patient adherence to the traditional schedule of taking penicillin 3 to 4 times daily is a valid concern; studies have shown that penicillin twice daily for 10 days is as effective as the traditional regimens.14 Amoxicillin is often used in the place of oral penicillin V because it tastes better, and it appears to be equally effective.2
Erythromycin is an alternative treatment for those allergic to penicillin. Although reports of high levels of streptococcal resistance to macrolide antibiotics have surfaced in several countries, in general less than 5% of isolates in the United States have been shown to be resistant to erythromycin.15 Although macrolide resistance has been reported recently in the United States, no evidence suggests that this is a widespread problem.2 As with any infectious disease, clinicians should be aware of local patterns of resistance. In addition, the macrolides clarithromycin and azithromycin are FDA approved for treatment of infection with GABHS.16 Sulfonamides and tetracycline are not recommended as therapy for streptococcal infection because rates of resistance to these agents are high.17 Although not first-line choices, other agents, such as amoxicillin/clavulanic acid, cephalosporins, and clindamycin, are effective in the treatment of infection caused by GABHS.8 Duration of treatmentThe traditional protocol is a 10-day course of penicillin, although recent studies suggest that shorter courses of treatment may be equally effective. Research shows that a 5-day course of either a cephalosporin or azithromycin is effective in eradicating streptococcal infection;18 the only drugs that are FDA approved for this regimen are cefdinir, cefpodoxime, and azithromycin.2 In addition, only cefdinir, azithromycin, cefadroxil, and cefixime are FDA approved for once-daily therapy for streptococcal infection in children.2 Since most throat cultures become negative within 24 hours of starting medication, the patient is presumed to be no longer contagious at this point and may return to school or work.19 Treatment that targets beta-hemolytic streptococci other than group A streptococci is not indicated, and antibiotic therapy for other streptococcal infection offers no symptomatic benefit.8 Management of contacts, carriers, and recurrencesThe IDSA does not recommend routine throat culture or treatment of asymptomatic household contacts except in specific situations where risk of nonsuppurative complications such as RF is increased.2 As many as 20% of asymptomatic school-age children may be streptococcal carriers and can remain colonized for several months. Asymptomatic carriers do not usually need treatment because spread from carriers to close contacts is unlikely. Carriers are also at very low risk for developing suppurative or nonsuppurative complications.2 In cases where a patient is experiencing recurrent episodes of acute pharyngitis over a period of many months, subsequent positive findings on throat cultures or a positive RADT result are likely to represent a carrier state. These patients are probably experiencing nonstreptococcal infections.2 In the case of “ping-pong” spread of infection in a household, try to obtain specimens simultaneously from all family members and treat those for whom culture results are positive. There is no evidence that family pets are reservoirs for GABHS. Other group A beta-hemolytic streptococcal infectionsScarlet fever The clinical manifestations of scarlet fever (scarlatina) are the result of an erythrogenic toxin produced by GABHS. Although scarlet fever usually follows streptococcal pharyngitis, it may also follow streptococcal infection at other sites on the affected patient. The patient, usually 5 to 15 years old, develops circumoral pallor with petechiae on all mucosal surfaces. The rash first appears 12 to 24 hours after the onset of illness.20 The skin appears diffusely erythematous, sunburned, and roughened; this is the typical sandpaper rash so characteristic of scarlet fever. The rash is more pronounced in the skinfolds of the neck, groin, and axillae, producing confluent lines of petechiae referred to as Pastia’s lines.6 The rash, which is caused by increased capillary fragility, begins to fade in 3 to 4 days and then desquamates, first on the face and then on the palms. Desquamation becomes generalized in about a week. The tongue also has a characteristic appearance in scarlet fever. During the first few days, it has a white coating and has red, edematous papillae, the so-called white strawberry tongue. After about 2 days, the tongue desquamates and appears beefy red with prominent papillae; it is then called a strawberry tongue (see the September 2005 print issue of JAAPA for Figure 1).20 Perianal streptococcal cellulitis This is a unique pediatric infection, occurring mainly in children 6 months to 10 years of age.21 Patients may present with blood-streaked stools or constipation secondary to painful defecation. Other signs and symptoms include perianal dermatitis in 90% of patients and perianal itching in 78% (see the September 2005 print issue of JAAPA for Figure 2).22 Physical examination reveals perianal erythema and tenderness. Diagnosis is confirmed by RADT or culture of a perirectal swab specimen, which usually grows out copious amounts of the organism. Digital self-contamination from an infected oropharynx or skin lesion may be the source of the infection. Streptococcal vaginitis is a variant form of this condition seen in prepubescent females. Signs and symptoms include a clear vaginal discharge, vulvar erythema, and dysuria. Vulvar pain can be so severe that it causes painful ambulation. Differential diagnosis of these conditions includes candidiasis, psoriasis, sexual abuse, and pinworms. Treatment for perianal streptococcal cellulitis, as for streptococcal pharyngitis, is with amoxicillin, penicillin, erythromycin, or a cephalosporin. Treatment is often delayed because of misdiagnosis but generally resolves the disorder rapidly. Impetigo Nonbullous impetigo is a superficial infection of the skin caused by GABHS. Mixed infection with staphylococci is common. Bullous impetigo, however, is a distinct entity caused by Staphylococcus aureus.23 Primary GABHS impetigo infection is usually precipitated by minor trauma or insect bites that cause a break in the skin; secondary impetiginization is common in certain underlying dermatoses, specifically atopic dermatitis, herpetic infections, and scabies. Most cases occur in young children and adolescents. Impetigo occurs most commonly during the summer months in temperate climates and year round in warm, humid regions.23 Erythematous papules turn into vesicles that rupture, forming shallow erosions with the characteristic honey-colored crust (see the September 2005 print issue of JAAPA for Figure 3). Pruritus is variable, and systemic symptoms, though rare, can occur. Erysipelas is a GABHS infection of the deeper dermis and subcutaneous tissues. Look for well-demarcated, shiny, erythematous plaques on the lower extremities, usually along with systemic symptoms. Treatment of localized nonbullous impetigo is with 2% mupirocin ointment; treatment of widespread impetigo or erysipelas is with beta-lactamase-resistant penicillin or a first-generation cephalosporin.23 Complications of infection with GABHSComplications of streptococcal infections are divided into two categories: suppurative and nonsuppurative. Suppurative infections include peritonsillar abscess, retropharyngeal abscess, otitis media, sinusitis, lymphadenitis, and pneumonia.8 These infections result from direct extension of the organism from the nasopharynx. Hematogenous dissemination, however, can cause septic arthritis and meningitis. Toxic shock and necrotizing fasciitis are the most severe of the invasive GABHS infections. Nonsuppurative complications include acute RF and PSGN. Except for occasional resurgences, acute RF is rare in industrialized countries, and in the past few decades, the number of cases has decreased.24 Widespread use of antibiotics for the treatment of streptococcal pharyngitis is partly responsible. PSGN can follow streptococcal infections of the skin or throat, but acute RF is specifically a sequela of pharyngeal infections, although the reasons for this distinction are not clear.25 Both acute RF and PSGN develop 1 to 3 weeks after the streptococcal infection. RF occurs in males and females equally, but PSGN is twice as common in males. Antibiotic treatment for streptococcal pharyngitis prevents RF but not PSGN. Indications for tonsillectomy
ConclusionStreptococcal infections are common in primary care, and recognizing the variety of presentations enables clinicians to treat infections promptly and prevent complications. Recent research confirms the guidelines for basing diagnostic testing and treatment on patient presentation.27 Treatment options can be tailored to specific patient needs. The clinician who is aware of the complications of infection with GABHS and indications for tonsillectomy will be able to an-swer the many questions patients and their parents will have. A streptococcal vaccine is currently under study,28 but in the interim, proper recognition and management of streptococcal disease continues to be a primary care imperative. REFERENCES
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Signs and symptoms that help rule in streptococcal pharyngitis include tonsillar exudates and pharyngeal exudates; exposure to strep throat in the previous 2 weeks is also suspicious (see Table 1).6 Signs and symptoms that are suggestive of viral rather than bacterial etiology for sore throat include conjunctivitis, cough, hoarseness, coryza, anterior stomatitis, discrete ulcerative pharyngeal lesions, and the absence of fever.2 An evidence-based patient encounter form, developed by McIsaac and colleagues for screening patients with symptoms of pharyngitis, utilizes the presence or absence of these signs and symptoms.7 The findings help the clinician to decide whether rapid antigen testing
is indicated.
Understanding the appropriate indications for tonsillectomy has reduced the incidence of the surgical procedure by 50% from the 1960s and 1970s. Although no indications are universally agreed upon, Discolo and colleagues have proposed one useful set of criteria, which uses the number of tonsillar infections in a given time period.26 Tonsillar infections are defined by a fever higher than 101°F (38.3°C), dysphagia, cervical adenopathy, positive GABHS culture, and tonsillar exudates (see Figure 4). Using this definition, the patient who has seven documented tonsil infections in a single year, five documented infections in each of 2 consecutive years, or three documented infections in each of 3 consecutive years appears to benefit from tonsillectomy.26 For patients with recurrent GABHS tonsillitis, the decision to operate must always be individualized.