key: cord-022281-xn0cf33a authors: Tanz, Robert R.; Shulman, Stanford T. title: Sore Throat date: 2009-05-15 journal: Practical Strategies in Pediatric Diagnosis and Therapy DOI: 10.1016/b978-0-7216-9131-2.50005-1 sha: doc_id: 22281 cord_uid: xn0cf33a nan Sore throat is a common chief complaint. Each year approximately 20 million patients in the United States visit physicians because of throat complaints. The majority of these illnesses are nonbacterial and neither necessitate nor are alleviated by antibiotic therapy (Tables 1-1 to 1-3). Acute streptococcal pharyngitis, however, warrants accurate diagnosis and therapy to prevent serious suppurative and nonsuppurative complications. Furthermore, life-threatening infectious complications of streptococcal and nonstreptococcal oropharyngeal infections may manifest with mouth pain, pharyngitis, parapharyngeal space infectious extension, and airway obstruction (Tables 1-4 and 1-5). Most episodes of pharyngitis are caused by viruses (see Tables 1-2 and 1-3). It is difficult to clinically distinguish between viral and bacterial pharyngitis with a very high degree of precision, but certain clues may help the physician. Accompanying symptoms of conjunctivitis, rhinitis, croup, or laryngitis are common with viral infection but rare in bacterial pharyngitis. Many viral agents can produce pharyngitis (see Tables 1-2 and 1-3). Some cause distinct clinical syndromes that are readily diagnosed without laboratory testing (see Tables 1-1 , 1-4, and 1-6). In pharyngitis caused by parainfluenza and influenza viruses, rhinoviruses, coronaviruses, and respiratory syncytial virus (RSV), the symptoms of coryza and cough often overshadow sore throat, which is generally mild. Influenza virus may cause high fever, cough, headache, malaise, myalgias, and cervical adenopathy in addition to pharyngitis. In young children, croup or bronchiolitis may develop. RSV is associated with bronchiolitis, pneumonia, and croup in young children. RSV infection in older children is usually indistinguishable from a simple upper respiratory tract infection. Pharyngitis is not a prominent finding of RSV infection in either age group. Parainfluenza viruses are associated with croup and bronchiolitis; minor sore throat and signs of pharyngitis are common at the outset but rapidly resolve. Infections caused by parainfluenza, influenza, and RSV are often seen in seasonal (winter) epidemics. Adenoviruses can cause upper and lower respiratory tract disease, ranging from ordinary colds to severe pneumonia. The incubation period of adenovirus infection is 2 to 4 days. Upper respiratory tract infection typically produces fever, erythema of the pharynx, and follicular hyperplasia of the tonsils, together with exudate. Enlargement of the cervical lymph nodes occurs frequently. When conjunctivitis occurs in association with adenoviral pharyngitis, the resulting syndrome is called pharyngoconjunctival fever. Pharyngitis may last as long as 7 days and does not respond to antibiotics. There are many adenovirus serotypes; adenovirus infections may therefore develop in children more than once. Laboratory studies may reveal a leukocytosis and an elevated erythrocyte sedimentation rate. Outbreaks have been associated with swimming pools and contamination in health care workers. The enteroviruses (coxsackievirus and echovirus) can cause sore throat, especially in the summer. High fever is common, and the throat is slightly red; tonsillar exudate and cervical adenopathy are unusual. Symptoms resolve within a few days. Enteroviruses can Primary infection caused by herpes simplex virus (HSV) usually produces high fever with acute gingivostomatitis, involving vesicles (which become ulcers) throughout the anterior portion of the mouth, including the lips. There is sparing of the posterior pharynx in herpes gingivostomatitis; the infection usually occurs in young children. High fever is common, pain is intense, and intake of oral fluids is often impaired, which may lead to dehydration. In addition, HSV may manifest in adolescents with pharyngitis. Approximately 35% of new-onset HSV-positive adolescent patients have herpetic lesions; most patients with HSV pharyngitis cannot be distinguished from patients with other causes of pharyngitis. The classic syndrome of herpetic gingivostomatitis in infants and toddlers lasts up to 2 weeks; data on the course of more benign HSV pharyngitis are lacking. The differential diagnosis of vesicular-ulcerating oral lesions is noted in Table 1-6. A common cause of a local and large lesion of unknown etiology is aphthous stomatitis ( Fig. 1-1) . Some children have a combination of periodic fever (recurrent at predictable fixed times), aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA); this syndrome is idiopathic and may respond to oral prednisone or cimetidine. PFAPA usually begins before the age of 5 years and is characterized by high fever lasting 4 to 6 days, occurring every 2 to 8 weeks, and resolving spontaneously. Infants and toddlers with measles often have prominent oral findings early in the course of the disease. In addition to high fever, cough, coryza, and conjunctivitis, the pharynx may be intensely and diffusely erythematous, without tonsillar enlargement or exudate. The presence of Koplik spots, the pathognomonic white or bluewhite enanthem of measles, on the buccal mucosa near the mandibular molars provides evidence of the correct diagnosis before the rash develops. Acute exudative pharyngitis commonly occurs with infectious mononucleosis caused by primary infection with Epstein-Barr virus (EBV) ( Table 1-7) . Mononucleosis is a febrile, systemic, self-limited lymphoproliferative disorder that is usually associated with hepatosplenomegaly and generalized lymphadenopathy. The pharyngitis may be mild or severe, with significant tonsillar hypertrophy (possibly producing airway obstruction), erythema, and impressive tonsillar exudates. Regional lymph nodes may be particularly enlarged and slightly tender. Infectious mononucleosis usually occurs in adolescents and young adults; EBV infection is generally milder or subclinical in preadolescent children. In United States high school and college students, attack rates are 200 to 800 per 100,000 population per year. EBV is transmitted primarily by saliva. After a 2-to 4-week incubation period, patients with infectious mononucleosis usually experience an abrupt onset of malaise, fatigue, fever, and headache, followed closely by pharyngitis. The tonsils are enlarged with exudates and cervical adenopathy. More generalized adenopathy with hepatosplenomegaly often follows. Fever and pharyngitis typically last 1 to 3 weeks, while lymphadenopathy and hepatosplenomegaly subside over 3 to 6 weeks. Malaise and lethargy can persist for several months, possibly leading to impaired school or work performance. Laboratory studies of diagnostic value include atypical lymphocytosis; these lymphocytes are primarily EBV-specific, cytotoxic T lymphocytes that represent a reactive response to EBV-infected B lymphocytes. A modest elevation of serum transaminase levels, reflecting EBV hepatitis, is common. Tests useful for diagnosis include detection of heterophile antibodies that react with bovine erythrocytes (most often detected by the monospot test) and specific antibody against EBV viral capsid antigen (VCA), early antigen (EA), and nuclear antigen (EBNA). Acute infectious mononucleosis is usually associated with a positive heterophile test result and antibody to VCA and EA ( Fig. 1-2) . The findings of acute exudative pharyngitis together with hepatomegaly, splenomegaly, and generalized lymphadenopathy suggest infectious mononucleosis. Early in the disease and in cases without liver or spleen enlargement, differentiation from other causes of pharyngitis, including streptococcal pharyngitis, is difficult. Indeed, a small number of patients with infectious mononucleosis have a throat culture positive for group A streptococci. Serologic evidence of mononucleosis should be sought when splenomegaly or other features are present or if symptoms persist beyond 7 days. Patients with infectious mononucleosis require supportive treatment. Corticosteroids may be indicated for acute life-threatening conditions, such as airway obstruction caused by enlarged tonsils. In the evaluation of a patient with sore throat, the primary concern is usually accurate diagnosis and treatment of pharyngitis caused by group A streptococci, which accounts for about 15% of all episodes of pharyngitis. The sequelae of group A streptococcal pharyngitis, especially acute rheumatic fever and acute glomerulonephritis, at one time resulted in considerable morbidity and mortality in the United States and continue to do so in other parts of the world. Prevention of acute rheumatic fever in particular depends on timely diagnosis of streptococcal pharyngitis and prompt antibiotic treatment. Group A streptococci are characterized by the presence of group A carbohydrate in the cell wall, and they are further distinguished by several kinds of cell wall protein antigens (M, R, T). These protein antigens are useful for studies of epidemiology and pathogenesis. Group A streptococcal pharyngitis has been endemic in the United States; epidemics occur sporadically. Episodes peak in the late winter and early spring; rates of group A streptococcal pharyngitis are highest among children aged 5 to 11 years old. Spread of group A streptococci in classrooms and among family members, especially in crowded living conditions, is common. Transmission occurs primarily by inhalation of organisms in large droplets or by direct contact with respiratory secretions. Pets do not appear to be a frequent reservoir. Untreated streptococcal pharyngitis is particularly contagious early in the acute illness and for the first 2 weeks after the organism has been acquired. Antibiotic therapy effectively prevents disease transmission. Within 24 hours of institution of therapy with penicillin, it is difficult to isolate group A streptococci from patients with acute streptococcal pharyngitis, and infected children can return to school. Molecular epidemiology studies of streptococcal pharyngitis have shown that numerous distinct strains of group A streptococci circulate simultaneously in the community during the peak season. "DNA-fingerprinting" techniques further demonstrate that children with streptococcal pharyngitis serve as a community reservoir for strains that cause invasive disease (e.g., sepsis, streptococcal toxic shock syndrome, cellulitis, necrotizing fasciitis) in the same geographic area and season. The classic patient with acute streptococcal pharyngitis has a sudden onset of fever and sore throat. Headache, malaise, abdominal pain, nausea, and vomiting occur frequently. Cough, rhinorrhea, conjunctivitis, stridor, diarrhea, and hoarseness are distinctly unusual and suggest a viral etiology. Examination of the patient reveals marked pharyngeal erythema. Petechiae may be noted on the palate, but they can also occur in viral pharyngitis (see Table 1 -7). Tonsils are enlarged, symmetric, and red, with patchy exudates on their surfaces. The papillae of the tongue may be red and swollen; hence the designation "strawberry tongue." Anterior cervical lymph nodes are often tender and enlarged. Combinations of these signs can be used to assist in diagnosis; in particular, tonsillar exudates in association with fever, palatal petechiae, and tender anterior cervical adenitis strongly suggest infection with group A streptococci. However, other diseases can produce this constellation of findings. Some or all of these classic characteristics may be absent in patients with streptococcal pharyngitis. Younger children often have coryza with crusting below the nares, more generalized adenopathy, and a more chronic course, a syndrome called streptococcosis. When rash accompanies the illness, accurate clinical diagnosis is easier. Scarlet fever, so-called because of the characteristic fine, diffuse red rash, is essentially pathognomonic for infection with group A streptococci. Scarlet fever is rarely seen in children younger than 3 years old or in adults. The rash of scarlet fever is caused by infection with a strain of group A streptococci that contains a bacteriophage encoding for production of an erythrogenic (redness-producing) toxin, usually erythrogenic (or pyrogenic) exotoxin A. Scarlet fever is simply group A streptococcal pharyngitis with a rash and should be explained as such to patients and their families. Although patients with the streptococcal 6 Section One Respiratory Disorders Streptococcal toxic shock syndrome is usually associated with a primary cutaneous rather than a pharyngeal focus of infection. The rash of scarlet fever has a texture like sandpaper and blanches with pressure. It usually begins on the face, but after 24 hours it becomes generalized. The face, especially the cheeks, is red, and the area around the mouth often appears pale in comparison (circumoral pallor). Accentuation of erythema occurs in flexor skin creases, especially in the antecubital fossae (Pastia's lines). The erythema begins to fade within a few days. Desquamation begins within a week of onset on the face and progresses downward, often resembling that seen after a mild sunburn. On occasion, sheetlike desquamation occurs around the free margins of the fingernails and is usually more coarse than the desquamation seen with Kawasaki disease. The differential diagnosis of scarlet fever includes Kawasaki disease, measles, and staphylococcal toxic shock syndrome (Table 1-9). Although signs and symptoms may strongly suggest acute streptococcal pharyngitis, laboratory diagnosis is highly recommended, even for patients with scarlet fever (Fig. 1-3) . Scoring systems for diagnosing acute group A streptococcal pharyngitis on clinical grounds have not proved very useful. Using clinical criteria alone, physicians overestimate the likelihood that patients have streptococcal infection. The throat culture has traditionally been used to diagnose streptococcal pharyngitis. Plating a swab of the posterior pharynx and tonsils on sheep blood agar, identifying β−hemolytic colonies, and testing them for the presence of sensitivity to a bacitracinimpregnated disk is the "gold standard" diagnostic test, but it takes 24 to 48 hours to obtain results. There are a number of rapid diagnostic tests that take less than 15 minutes. These "rapid strep" tests detect the presence of the cell wall group A carbohydrate antigen after acid extraction of organisms obtained by throat swab. Rapid strep tests are highly specific (generally >95%), with the throat culture used as the standard. Unfortunately, the sensitivity of most of these rapid tests can be considerably lower. In comparison to hospital or reference laboratory throat culture results, the sensitivities of these tests are generally 80% to 85% and can be lower. However, when both throat cultures and rapid tests performed in physicians' offices are compared with cultures performed in reference laboratories, the sensitivities, specificities, and overall accuracy of the office culture and the office rapid test are quite similar; the latter often performs better than the culture. The low sensitivity of these tests, coupled with their excellent specificity, has led to the recommendation that two swabs be obtained from patients with suspected streptococcal pharyngitis. One swab is used for a rapid test. When the rapid antigen detection test result is positive, it is highly likely that the patient has group A streptococcal infection, and the extra swab can be discarded. When the rapid test result is negative, group A streptococci may nonetheless be present; thus, the extra swab should be processed for culture. Physician offices that have demonstrated that their rapid test and throat culture results are comparable may be able to rely on the rapid test result even when it is negative, without performing a backup culture. In general, patients with a negative result of the rapid test do not require treatment before culture verification unless there is a particularly high suspicion group A streptococcal infection (e.g., scarlet fever, peritonsillar abscess, or tonsillar exudates in addition to tender cervical adenopathy, palatal petechiae, fever, and recent exposure to a person with group A streptococcal pharyngitis). Testing patients for serologic evidence of an antibody response to extracellular products of group A streptococci is not useful for diagnosing acute pharyngitis. Because it generally takes several weeks for antibody levels to rise, streptococcal antibody tests are valid only for determining past infection. Specific antibodies include antistreptolysin O (ASO), anti-DNase B, and antihyaluronidase (AHT). When antibody testing is desired in order to evaluate a possible post-streptococcal illness, more than one of these tests should be performed to improve sensitivity. Treatment begun within 9 days of the onset of group A streptococcal pharyngitis is effective in preventing acute rheumatic fever. Therapy does not appear to affect the risk of the other nonsuppurative sequela, acute post-streptococcal glomerulonephritis. Antibiotic therapy also reduces the incidence of suppurative sequelae of group A streptococcal pharyngitis, such as peritonsillar abscess and cervical adenitis. In addition, treatment produces a more rapid resolution of signs and symptoms and terminates contagiousness within 24 hours. For these reasons, antibiotics should be instituted as soon as the diagnosis is supported by laboratory studies. There are numerous antibiotics available for treating streptococcal pharyngitis (Table 1 -10). The drug of choice is penicillin. Despite the widespread use of penicillin to treat streptococcal and other infections, penicillin resistance among group A streptococci has not developed. Penicillin can be given by mouth for 10 days or intramuscularly as a single injection of benzathine penicillin. Intramuscular benzathine penicillin alleviates concern with patient compliance. A less painful alternative is benzathine penicillin in combination with procaine penicillin. Intramuscular procaine penicillin alone is inadequate for prevention of acute rheumatic fever because adequate levels of penicillin are not present in blood and tissues for a sufficient time. Other β-lactams, including semisynthetic derivatives of penicillin and the cephalosporins, are at least as effective as penicillin for treating group A streptococcal pharyngitis. Their broader spectrum, their higher cost, and the lack of formal data concerning prevention of acute rheumatic fever relegate them to second-line status. The decreased frequency of dose administration of some of these agents may improve patient compliance and makes their use attractive in selected circumstances. Patients who are allergic to penicillin should receive erythromycin or another non-β-lactam antibiotic, such as clarithromycin, azithromycin, or clindamycin. Resistance of group A streptococci to erythromycin has increased dramatically in areas such as Japan, France, Spain, Taiwan, and Finland, where erythromycin has been widely used. This has not yet emerged as a major problem in the United States, where the rate of macrolide resistance is about 5%. Sulfa drugs (including sulfamethoxazole combined with trimethoprim), tetracyclines, and chloramphenicol should not be used for treatment of acute streptococcal pharyngitis because they do not eradicate group A streptococci. Antibiotic therapy has greatly reduced the likelihood of developing suppurative complications caused by spread of group A streptococci from the pharynx or middle ear to adjacent structures. Peritonsillar abscess ("quinsy") manifests with fever, severe throat pain, dysphagia, "hot potato voice," pain referred to the ear, and bulging of the peritonsillar area with asymmetry of the tonsils and sometimes displacement of the uvula (Fig. 1-4 ; see Table 1 -4). On occasion, there is peritonsillar cellulitis without a well-defined abscess cavity. Trismus may be present. When an abscess is found clinically or by an imaging study such as a computed tomographic scan, surgical drainage is indicated. Peritonsillar abscess occurs most commonly in older children and adolescents. Sore Throat Necrotizing fasciitis Diarrhea *Case definition of streptococcal toxic shock syndrome requires (I) isolation of group A streptococci from (a) a normally sterile site (blood, synovial or peritoneal fluid) or (b) a nonsterile site (throat, wound). (II) Severity is defined by (a) hypotension and (b) two or more of renal impairment, coagulopathy, liver involvement, adult respiratory distress syndrome, a generalized erythematous macular rash (with or without later desquamation), and soft tissue necrosis (necrotizing fasciitis, myositis, gangrene). The definitive diagnosis requires criteria IA and IIA plus B. Criteria IB and IIA plus B are considered probable if no other identifiable cause is present. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen. Retropharyngeal abscess represents extension of infection from the pharynx or peritonsillar region into the retropharyngeal (prevertebral) space, which is rich in lymphoid structures (Figs. 1-5 and 1-6; see Table 1 -4). Children younger than 4 years old are most often affected. Fever, dysphagia, drooling, stridor, extension of the neck, and a mass in the posterior pharyngeal wall may be noted. Surgical drainage is often required if frank suppuration has occurred. Spread of group A streptococci via pharyngeal lymphatic vessels to regional nodes can cause cervical lymphadenitis. The markedly swollen and tender anterior cervical nodes that result can suppurate. Otitis media, mastoiditis, and sinusitis also may occur as complications of group A streptococcal pharyngitis. Additional parapharyngeal suppurative infections that may mimic streptococcal disease are noted in Table 1 -4. Furthermore, any pharyngeal infectious process may produce torticollis if there is inflammation that extends to the paraspinal muscles and ligaments, producing pain, spasm, and, on occasion, rotary subluxation of the cervical spine. The differential diagnosis of torticollis is presented in Table 1 -11. Oropharyngeal torticollis lasts less than 2 weeks and is not associated with abnormal neurologic signs or pain over the spinous process. Nonsuppurative complications include acute rheumatic fever (see Chapters 11 and 44), acute post-streptococcal glomerulonephritis (see Chapter 25), and possibly reactive arthritis/synovitis. In addition, an association between streptococcal infection and neuropsychiatric disorders such as obsessive-compulsive disorder and Tourette syndrome has been postulated. This possible association has been called PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococci). Therapy with an appropriate antibiotic within 9 days of onset of symptoms is highly effective in preventing rheumatic fever, but acute glomerulonephritis is not prevented by treatment of the antecedent streptococcal infection. Pharyngitis caused by one of the nephritogenic strains of group A streptococci precedes the glomerulonephritis by about 10 days. Unlike acute rheumatic fever, which occurs only after group A streptococcal pharyngitis, acute glomerulonephritis also can follow group A streptococcal skin infection. Treatment with penicillin cures group A streptococcal pharyngitis but is unable to eradicate group A streptococci from the pharynx in approximately 25% of patients ( Fig. 1-7) . This causes considerable consternation among such patients and their families. Penicillin resistance is not the cause of treatment failure. A small proportion of these patients are symptomatic and are thus characterized as having clinical treatment failure. Reinfection with the same strain or a different strain is possible, as is intercurrent viral pharyngitis. Some of these patients may be chronic pharyngeal carriers of group A streptococci who are suffering from a new superimposed viral infection; others may be noncompliant with regard to therapy. Many patients who do not respond to antimicrobial treatment are asymptomatic and are identified when follow-up culture specimens are obtained, a practice that is usually unnecessary. Patients who are compliant with regard to therapy are at minimal risk for acute rheumatic fever. One explanation for asymptomatic persistence of group A streptococci after treatment is that these patients were chronic carriers of group A streptococci who were initially symptomatic because of a concurrent viral pharyngitis and who did not truly have acute streptococcal pharyngitis. Patients who are chronically colonized with group A streptococci are called chronic carriers. Carriers do not appear to be at risk for acute 10 Section One Respiratory Disorders headache pyuria (sterile); gallbladder hydrops rheumatic fever or for development of suppurative complications, and they are rarely sources of spread of group A streptococci in the community. There is no reason to exclude these carriers from school. There is no easy way to identify chronic carriers prospectively among patients with symptoms of acute pharyngitis. The clinician should consider the possibility of chronic group A streptococcal carriage when a patient or a family member has multiple culturepositive episodes of pharyngitis, especially when symptoms are mild or atypical. A culture specimen is usually positive for group A streptococci when the suspected carrier is symptom-free or is receiving treatment with penicillin (intramuscular benzathine penicillin is recommended in order to eliminate concern about compliance). Carriers often receive multiple unsuccessful courses of antibiotic therapy in attempts to eliminate group A streptococci. Physician and patient anxiety is common and can develop into "streptophobia." Unproven and ineffective therapies include tonsillectomy, prolonged administration of antibiotics, use of β-lactamase-resistant antibiotics, and culture or treatment of pets. Available treatment options for the physician faced with a chronic streptococcal carrier include the following: 1. Obtaining a rapid test, throat culture, or both each time the patient has pharyngitis with features that suggest streptococcal pharyngitis, and treating with penicillin each time a test is positive. 2. Treating with one of the regimens effective for terminating chronic carriage. The first option is simple, as safe as penicillin, and appropriate for many patients. The second option should be reserved for particularly anxious patients; those with a history of acute rheumatic fever or living with someone who had it; or those living or working in nursing homes, chronic care facilities, hospitals, and perhaps schools. The two antibiotic treatment regimens that have been effective for eradication of the carrier state are: • Intramuscular benzathine penicillin plus oral rifampin (10 mg/kg/ dose up to 300 mg, given twice daily for 4 days beginning on the day of the penicillin injection) • Oral clindamycin, given for 10 days (20 mg/kg/day up to 450 mg, divided into three equal doses) Clindamycin may be preferred because it is easier to use than intramuscular penicillin plus oral rifampin and may be somewhat more effective. In controlled, comparative trials, no other antibiotic regimens have been demonstrated to reliably terminate the chronic streptococcal carrier state. Successful eradication of the carrier state makes evaluation of subsequent episodes of pharyngitis much easier, although chronic carriage can recur upon reexposure to group A streptococci. Some patients seem remarkably susceptible to group A streptococci. The reasons for frequent bona fide acute group A streptococcal pharyngitis are obscure, but appropriate antibiotic treatment results in resolution of symptoms and eradication of group A streptococci. The role of tonsillectomy in the management of patients with multiple episodes of streptococcal pharyngitis is controversial. Fewer episodes of sore throat have been reported among patients treated with tonsillectomy (in contrast to patients treated without surgery) during the first 2 years after operation. The patients enrolled in that study had experienced numerous episodes of pharyngitis, but it appears that not all episodes were caused by group A streptococci. Of particular concern is the reported tonsillectomy complication rate of 14% and the improvement over time noted among the nontonsillectomy patients. In addition, the presence of tonsils is not necessary for group A streptococci to infect the throat. Tonsillectomy cannot be recommended except in unusual circumstances. It seems preferable to treat most patients with penicillin whenever symptomatic group A streptococcal pharyngitis occurs. Obtaining follow-up throat specimens for culture helps distinguish recurrent pharyngitis from chronic carriage. Certain β−hemolytic streptococci of serogroups other than group A cause acute pharyngitis. Well-documented epidemics of food-borne group C and group G streptococcal pharyngitis have been reported in young adults. In these situations, a high percentage of individuals who have ingested the contaminated food promptly developed acute pharyngitis, and throat cultures yielded virtually pure growth of the epidemiologically linked organism. There have been outbreaks of group G streptococcal pharyngitis among children. However, the role of these non-group A streptococcal organisms as etiologic agents of acute pharyngitis in endemic circumstances has been difficult to establish. Group C and group G β streptococci may be responsible for acute pharyngitis, particularly in adolescents. However, the exact role of these agents, most of which are carried asymptomatically in the pharynx of some children and young adults, remains to be fully characterized. When they are implicated as agents of acute pharyngitis, groups C and G organisms do not appear to necessitate treatment, inasmuch as they cause self-limited infections. Acute rheumatic fever is not a sequela to these infections, although post-streptococcal acute glomerulonephritis has been documented in rare cases after epidemic group C and group G streptococcal pharyngitis. Arcanobacterium (formerly Corynebacterium) haemolyticum is a gram-positive rod that has been reported to cause a scarlet fever-like illness with acute pharyngitis and scarlatinal rash, particularly in teenagers and young adults. Detecting this agent requires special methods for culture, and it has not routinely been sought in patients with scarlet fever or pharyngitis. The clinical features of A. haemolyticum pharyngitis are indistinguishable from group A streptococcal pharyngitis; pharyngeal erythema is present in almost all patients, patchy white to gray exudates in about 70%, cervical adenitis in about 50%, and moderate fever in 40%. Palatal petechiae and strawberry tongue may also occur. The scarlatiniform rash usually spares the face, palms, or soles. It is erythematous and blanches; it may be pruritic and demonstrate minimal desquamation. Erythromycin appears to be the treatment of choice. Section One Respiratory Disorders (1990 to 1995) , and infection has been documented in several travelers from Western Europe. The pathogenesis of diphtheria involves nasopharyngeal mucosal colonization by C. diphtheriae and toxin elaboration after an incubation period of 1 to 5 days. Toxin leads to local tissue inflammation and necrosis (producing an adherent grayish membrane made up of fibrin, blood, inflammatory cells, and epithelial cells) and it is absorbed into the blood stream. Fragment B of the polypeptide toxin binds particularly well to cardiac, neural, and renal cells, and the smaller fragment A enters cells and interferes with protein synthesis. Toxin fixation by tissues may lead to fatal myocarditis (with arrhythmias) within 10 to 14 days and to peripheral neuritis within 3 to 7 weeks. Acute tonsillar and pharyngeal diphtheria is characterized by anorexia, malaise, low-grade fever, and sore throat. The grayish membrane forms within 1 to 2 days over the tonsils and pharyngeal walls and occasionally extends into the larynx and trachea. Cervical adenopathy varies but may be associated with development of a "bull neck." In mild cases, the membrane sloughs after 7 to 10 days and the patient recovers. In severe cases, an increasingly toxic appearance can lead to prostration, stupor, coma, and death within 6 to 10 days. Distinctive features include palatal paralysis, laryngeal paralysis, ocular palsies, diaphragmatic palsy, and myocarditis. Airway obstruction (from membrane formation) may complicate the toxigenic manifestations. Accurate diagnosis requires isolation of C. diphtheriae on culture of material from beneath the membrane, with confirmation of toxin production by the organism isolated. Laboratories must be forewarned that diphtheria is suspected. Other tests are of little value. Treatment includes equine antitoxin to neutralize circulating toxin, as well as systemic penicillin or erythromycin. In a teenager, the retropharyngeal space normally does not exceed 7 mm when measured from the anterior aspect of the C2 vertebral body to the posterior pharynx. In infants, the retropharyngeal space is usually less than one width of the adjacent vertebral body. However, during crying, this distance may be three widths of the vertebral body. Also, under normal circumstances, the retrotracheal space does not exceed 22 mm in teenagers when measured from the anterior aspect of C-6 to the trachea. Dotted lines depict the "thumbprint" sign, noted on a lateral neck radiograph, made by a swollen epiglottis. (From Reilly BM: Sore throat. In Practical Strategies in Outpatient Medicine, 2nd ed. Philadelphia: WB Saunders, 1991.) Acute symptomatic pharyngitis caused by Neisseria gonorrhoeae occurs occasionally in sexually active individuals as a consequence of oral-genital contact. In cases involving young children, sexual abuse must be suspected. The infection usually manifests as an ulcerative, exudative tonsillopharyngitis but may be asymptomatic and resolve spontaneously. Gonococcal pharyngitis occurs in homosexual men and heterosexual women after fellatio and is less readily acquired after cunnilingus. Gonorrhea rarely is transmitted from the pharynx to a sex partner, but pharyngitis can serve as a source for gonococcemia. Diagnosis requires culture on appropriate selective media (e.g., Thayer-Martin medium). Recommended therapeutic regimens include a single intramuscular dose of 125 mg of ceftriaxone or a single oral 500-mg dose of ciprofloxacin. Spectinomycin is ineffective 14 Performance of a predictive model for streptococcal pharyngitis in children Group A streptococcal infections and acute rheumatic fever Acute pharyngitis Optical immunoassay test for Group A ß-hemolytic streptococcal pharyngitis: An office-based, multicenter investigation Potential mechanisms for failure to eradicate group A streptococci from the pharynx The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome: A retrospective populationbased study Persistence of group A streptococci in eukaryotic cells-A safe place? What is a throat culture Streptococcal pharyngitis: The carrier state, definition and management Streptococcus associated toxic shock Persistence of acute rheumatic fever in the intermountain area of the United States Outbreak of group A streptococcus septicemia in children: Clinical, epidemiologic, and microbiological correlates Working Group on Severe Streptococcal Infections: Defining the group A streptococcal toxic shock syndrome: Rationale and consensus definition Other Pathogens Community-wide outbreak of group G streptococcal pharyngitis Periodic fever, aphthous stomatitis, pharyngitis, adenitis: a clinical review of a new syndrome Arcanobacterium haemolyticum in children with presumed streptococcal pharyngotonsillitis or scarlet fever Chlamydial pharyngitis Mononucleosis caused by Epstein-Barr virus and cytomegalovirus in children: A comparative study of 124 cases Pharyngitis associated with herpes simplex virus in college students Pharyngoconjunctival fever caused by adenovirus type 11 Epstein-Barr virus infections: Biology, pathogenesis, and management Epstein-Barr virus infectious mononucleosis in children: I. Clinical and general laboratory findings Epstein-Barr virus infectious mononucleosis in children: II. Heterophil antibody and viral-specific responses Arcanobacterium haemolyticum: Biology of the organism and diseases in man Life-threatening infections of the head and neck Clinical infections and nonsurgical treatment of parapharyngeal space infections complicating throat infection Pharyngitis followed by hypoxia and sepsis: Lemierre syndrome Peritonsillar abscess: Clinical and microbiologic aspects and treatment regimens Upper respiratory tract infections in young children: Duration of and frequency of complications Deep neck infections and respiratory distress in children New approaches to the treatment of group A streptococcal pharyngitis Treatment of streptococcal pharyngotonsillitis: Reports of penicillin's demise are premature Penicillin and the marked decrease in morbidity and mortality from rheumatic fever in the United States Efficacy of tonsillectomy for recurrent throat infection in severely affected children: Results of parallel randomized and nonrandomized clinical trials Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis Resistance to erythromycin in group A streptococci Streptococcal pharyngitis: The case for penicillin therapy Duration of positive throat cultures for group A streptococci after initiation of antibiotic therapy Clindamycin treatment of chronic pharyngeal carriers of group A streptococci in gonococcal pharyngitis. Examination and testing for other sexually transmitted diseases and pregnancy are recommended. Chlamydia species and Mycoplasma pneumoniae may cause pharyngitis, although the frequency of these infections is disputed. Chlamydia trachomatis has been implicated serologically as a cause of pharyngitis in as many as 20% of adults with pharyngitis, but isolation of the organism from the pharynx has proved more difficult. Chlamydia pneumoniae has also been identified as a cause of pharyngitis. Because antibodies to this organism show some crossreaction with C. trachomatis, it is possible that infections formerly attributed to C. trachomatis were really caused by C. pneumoniae. Diagnosis of chlamydial pharyngitis is difficult, whether by culture or serologically, and neither method is readily available to the clinician.M. pneumoniae most likely causes pharyngitis. Serologic (positive mycoplasma immunoglobulin M [IgM]) or, less often, culture methods can be used to identify this agent, which was found in 33% of college students with pharyngitis in one study. Polymerase chain reaction (PCR) is diagnostic.There is no need to seek evidence of these organisms routinely in pharyngitis patients in the absence of ongoing research studies of nonstreptococcal pharyngitis. The efficacy of antibiotic treatment for M. pneumoniae and chlamydial pharyngitis is not known, but these illnesses appear to be self-limited. Treatment of more complicated M. pneumoniae infections, such as pneumonia (Table 1 -12), is indicated with erythromycin, azithromycin, or clarithromycin; doxycycline may be used if the patient is older than 10 years.