INFECTIONS OF THE PHARYNX AND ORAL CAVITY Oropharyngeal infections range from mild, self-limited viral illnesses to serious,

life-threatening bacterial infections. The most common presenting symptom is sore throatone of the most frequent reasons for ambulatory care visits among adults and children. Although sore throat is a symptom in many noninfectious illnesses as well, the overwhelming majority of patients with a new sore throat have acute pharyngitis of viral or bacterial etiology. ACUTE PHARYNGITIS Millions of visits to primary care providers each year are for sore throat; the majority of cases of acute pharyngitis are caused by typical respiratory viruses. The most important source of concern is infection with group A _-hemolytic Streptococcus (S. pyogenes), which can progress to acute rheumatic fever and acute glomerulonephritis, the risk for both of which can be reduced by timely penicillin therapy. Etiology A wide variety of organisms cause acute pharyngitis. The relative importance of the different pathogens can only be estimated, since a significant proportion of cases (_30%) have no identified cause. Respiratory viruses are the most common identifiable cause of acute pharyngitis, with rhinoviruses (_20% of cases) and coronaviruses (at least 5%) accounting for a large proportion. Influenza virus, parainfluenza virus, and adenovirus also account for a measurable share of cases, the latter as part of the more clinically severe syndrome of pharyngoconjunctival fever. Other important but less common viral causes include herpes simplex virus (HSV) types 1 and 2, coxsackievirus A, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Acute HIV infection can present as acute pharyngitis and should be considered in high-risk populations.

Acute bacterial pharyngitis is typically caused by S. pyogenes, which accounts for _5to 15% of all cases of acute pharyngitis in adults; rates vary depending on the season and on health care system utilization. Group A streptococcal pharyngitis is primarily a disease of children 5to 15 years of age; it is uncommon among children _3 years old, as is rheumatic fever. Streptococci of groups C and G account for a minority of cases, although these serogroups are nonrheumatogenic. The remaining bacterial causes of the acute pharyngitis are seen infrequently (_1% each) but should be considered in appropriate exposure groups because of the severity of illness if left untreated; these etiologic agents include Neisseria gonorrhoeae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Yersinia enterocolitica, and Treponema pallidum (in secondary syphilis). Anaerobic bacteria can also cause acute pharyngitis (Vincents angina) and can contribute to more serious polymicrobial infections, such as peritonsillar or retropharyngeal abscess (see below). Atypical organisms such as M. pneumoniae and C. pneumoniae have been recovered from patients with acute pharyngitis; whether these agents are commensals or causes of acute infection is debatable. Manifestations Although the signs and symptoms accompanying acute pharyngitis are not reliable predictors of the etiologic agent, the clinical presentation occasionally suggests that one etiology is more likely than another. Acute pharyngitis due to respiratory viruses such as rhinovirus or coronavirus is usually not severe and is typically associated with a constellation of coryzal symptoms better characterized as nonspecific URI. Findings on physical examination are uncommon; fever is rare, and tender cervical adenopathy and pharyngeal exudates are not seen. In contrast, acute pharyngitis from influenza virus can be

severe and is much more likely to be associated with fever as well aswith myalgias, headache, and cough. The presentation of pharyngoconjunctival fever due to adenovirus infection is similar. Since pharyngeal exudate may be present on examination, this condition can be difficult to differentiate from streptococcal pharyngitis. However, adenoviral pharyngitis is distinguished by the presence of conjunctivitis in one-third to one-half of patients. Acute pharyngitis from primary HSV infection can also mimic streptococcal pharyngitis in some cases, with pharyngeal inflammation and exudate, but the presence of vesicles and shallow ulcers on the palate can help differentiate the two diseases. This HSV syndrome is distinct from pharyngitis caused by coxsackievirus (herpangina), which is associated with small vesicles that develop on the soft palate and uvula and then rupture to form shallow white ulcers. Acute exudative pharyngitis coupled with fever, fatigue, generalized lymphadenopathy, and (on occasion) splenomegaly is characteristic of infectious mononucleosis due to EBV or CMV. Acute primary infection with HIV is frequently associated with fever and acute pharyngitis as well as with myalgias, arthralgias, malaise, and occasionally a nonpruritic maculopapular rash, which later may be followed by lymphadenopathy and mucosal ulcerations without exudate. The clinical features of acute pharyngitis caused by streptococci of groups A, C, and G are all similar, ranging from a relatively mild illness without many accompanying symptoms to clinically severe cases with profound pharyngeal pain, fever, chills, and abdominal pain. A hyperemic pharyngeal membrane with tonsillar hypertrophy and exudate is usually seen, along with tender anterior cervical adenopathy. Coryzal manifestations, including cough, are typically absent; when present, they suggest a viral etiology. Strains of S. pyogenes that generate erythrogenic toxin can also produce scarlet fever, characterized

by an erythematous rash and strawberry tongue. The other types of acute bacterial pharyngitis (e.g., gonococcal, diphtherial, and yersinial) often present as exudative pharyngitis with or without other clinical features. Their etiologies are often suggested only by the clinical history. Diagnosis The primary goal of diagnostic testing is to separate acute streptococcal pharyngitis from pharyngitis of other etiologies (particularly viral) so that antibiotics can be prescribed more efficiently for patients to whom they may be beneficial. The most appropriate standard for the diagnosis of streptococcal pharyngitis, however, has not been definitively established. Throat swab culture is generally regarded as such. However, this method cannot distinguish between infection and colonization, and it takes 24 to 48 h to yield results that vary according to technique and culture conditions. Rapid antigendetection tests offer good specificity (_90%) but lower sensitivity that varies across the clinical spectrum of disease (65to 90%). Several clinical prediction systems (see Table 27-1) can increase the sensitivity of rapid antigen-detection tests to _90% in controlled settings. Since the sensitivities achieved in routine clinical practice are often lower, several medical and professional societies continue to recommend that all negative rapid antigen-detection tests in children be confirmed by a throat culture to limit transmission and complications of illness caused by group A streptococci. The CDC, the Infectious Diseases Society of America, the American College of Physicians, and the American Academy of Family Physicians do not recommend backup culture when adults have a negative rapid antigen-detection test, however, given the lower prevalence and smaller benefit in this age group. Cultures and rapid diagnostic tests for other causes of acute pharyngitis, such as influenza virus, adenovirus, HSV, EBV, CMV, and

M. pneumoniae, are available in some locations and can be used when these infections are suspected. In general, the monospot test for EBV is preferable to an assay for EBV antibodies, since the latter does not distinguish antecedent from current infection. Testing is also available for HIV RNA or antigen (p24) when acute primary HIV infection is suspected. If other bacterial causes are suspected (particularly N. gonorrhoeae, C. diphtheriae, or Y. enterocolitica), specific cultures should be requested since these organisms may be missed on routine throat swab culture. TREATMENT Antibiotic treatment of pharyngitis due to S. pyogenes confers numerous benefits, including a decrease in the risk of rheumatic fever. The magnitude of this benefit is fairly small, however, since rheumatic fever is now a rare disease, even in untreated patients. When therapy is started within 48 h of illness onset, however, symptom duration is also decreased. An additional benefit of therapy is the potential to reduce the spread of streptococcal pharyngitis, particularly in areas of overcrowding or close contact. Antibiotic therapy for acute pharyngitis is therefore recommended in cases where S. pyogenes is confirmed as the etiologic agent by rapid antigen-detection test or throat swab culture. Otherwise, antibiotics should be given in routine cases only when another bacterial cause has been identified. Effective therapy for streptococcal pharyngitis consists of either a single dose of intramuscular benzathine penicillin or a full 10-day course of oral penicillin (Table 27-1). Erythromycin can be used in place of penicillin, although erythromycin resistance among S. pyogenes strains in some parts of the world (particularly Europe) can prohibit the use of this drug. Newer (and more expensive) antibiotics are also active against streptococci but offer no greater efficacy than the above agents. Testing for cure is unnecessary and may reveal only chronic colonization. There is no evidence to support antibiotic treatment of group C or G streptococcal

pharyngitis or of pharyngitis in which Mycoplasma or Chlamydia has been recovered. Penicillin prophylaxis (benzathine penicillin G, 1.2 million units intramuscularly every 3 to 4 weeks) is indicated for patients at risk of recurrent rheumatic fever. Treatment of viral pharyngitis is entirely symptom-based except in infection with influenza virus or HSV. For influenza, a number of therapeutic agents exist, including amantadine, rimantadine, and the two newer agents oseltamivir and zanamivir. All of these agents need to be started within 36 to 48 h of symptom onset to reduce illness duration meaningfully. Of these agents, only oseltamivir and zanamivir are active against both influenza A and influenza B and therefore can be used when local infection patterns are unknown. Oropharyngeal HSV infection sometimes responds to treatment with antiviral agents such as acyclovir, although these drugs are often reserved for patients who are immunosuppressed. Complications Although rheumatic fever is the best-known complication of acute streptococcal pharyngitis, its risk following acute infection remains quite low. Other complications include acute glomerulonephritis and numerous suppurative conditions, such as peritonsillar abscess (quinsy), otitis media, mastoiditis, sinusitis, bacteremia, and pneumoniaall of which occur at extremely low rates. Although antibiotic treatment of acute streptococcal pharyngitis can prevent the development of rheumatic fever, there is no evidence that it can prevent acute glomerulonephritis. Some evidence supports antibiotic use to prevent the suppurative complications of streptococcal pharyngitis, particularly peritonsillar abscess, which can also involve oral anaerobes. Abscesses are usually accompanied by severe pharyngeal pain, dysphagia, and fever, often with medial displacement of the tonsil on examination. Oral penicillin remains the recommended therapy

for peritonsillar abscess, with clindamycin as an alternative. Early use of antibiotics in these cases has substantially reduced the need for surgical drainage. ORAL INFECTIONS Aside from periodontal disease such as gingivitis, infections of the oral cavity most commonly involve HSV or Candida species. In addition to causing painful cold sores on the lips, HSV can infect the tongue and buccal mucosa, causing the formation of irritating vesicles. Although topical antiviral agents (such as acyclovir or penciclovir) can be used externally for cold sores, oral or intravenous acyclovir is often needed for primary infections, extensive oral infections, and infections in immunocompromised patients. Oropharyngeal candidiasis (thrush) is caused by a variety of Candida species, most often C. albicans. Thrush occurs predominantly in neonates, immunocompromised patients (especially those with AIDS), and patients who have received prolonged antibiotic or glucocorticoid therapy. In addition to sore throat, patients often complain of a burning tongue, and physical examination reveals friable white or gray plaques on the gingiva, tongue, and oral mucosa. Treatment usually consists of an oral antifungal suspension (nystatin or clotrimazole) or oral fluconazole. In the cases of fluconazole-refractory thrush seen occasionally in patients with AIDS, the limited therapeutic options include oral suspensions of either itraconazole or amphotericin B. Vincents angina, also known as acute necrotizing ulcerative gingivitis or trench mouth, is a unique and dramatic form of gingivitis characterized by painful, inflamed gingiva with ulcerations of the interdental papillae that bleed easily. Since oral anaerobes are the cause, patients typically have halitosis and frequently present with fever, malaise,

and lymphadenopathy. Treatment consists of debridement and oral administration of penicillin plus metronidazole, with clindamycin alone as an alternative. Ludwigs angina is a rapidly progressive, potentially fulminant cellulitis involving the sublingual and submandibular spaces that typically originates from an infected or recently extracted tooth, most commonly the lower second and third molars. Improved dental care has substantially reduced the incidence of this disorder. Infection in these areas leads to dysphagia, odynophagia, and woody edema in the sublingual region, forcing the tongue up and back with the potential for airway obstruction. Fever, dysarthria, and drooling may also be noted, and patients may speak in a hot potato voice. Intubation or tracheostomy may be necessary to secure the airway, as asphyxiation is the most common cause of death. Patients should be monitored closely and treated promptly with intravenous antibiotics directed against streptococci and oral anaerobes. Recommended agents include ampicillin/sulbactam and high-dose penicillin plus metronidazole. Postanginal septicemia (Lemierres disease) is a rare anaerobic oropharyngeal infection caused predominantly by Fusobacterium necrophorum. The illness typically starts as a sore throat (most commonly in adolescents and young adults), which may present as exudative tonsillitis or peritonsillar abscess. Infection of the deep pharyngeal tissue allows organisms to drain into the lateral pharyngeal space, which contains the carotid artery and internal jugular vein. Septic thrombophlebitis of the internal jugular vein can result, with associated pain, dysphagia, and neck swelling and stiffness. Sepsis usually occurs 3 to 10 days after the onset of sore throat and is often coupled with metastatic infection to the lung and other distant sites. Occasionally, the infection can extend along the carotid sheath and into the posterior mediastinum, resulting in mediastinitis, or it can erode into the carotid artery, with the early sign of repeated small bleeds into the mouth. The mortality rate from these invasive infections can be as high as

50%. Treatment consists of intravenous antibiotics (penicillin G or clindamycin) and surgical drainage of any purulent collections. The concomitant use of anticoagulants to prevent embolization remains controversial but is often advised.