Most causes of sore throat are nonbacterial and neither require nor are alleviated by antibiotic therapy ( Tables 1.1, 1.2, and 1.3 ). Accurate diagnosis is essential: Acute streptococcal pharyngitis warrants diagnosis and therapy to ensure prevention of serious suppurative and nonsuppurative complications. Life-threatening infectious complications of oropharyngeal infections, whether streptococcal or nonstreptococcal, may manifest with mouth pain, pharyngitis, parapharyngeal space infectious extension, and/or airway obstruction ( Tables 1.4 and 1.5 ). In many cases, the history and/or physical exam can help direct diagnosis and treatment, but the enormous number of potential causes is too large to address all of them.
| Infection |
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| Irritation |
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| Other |
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| Definite Causes |
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| Probable or Occasional Causes |
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| Bacteria |
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| Virus |
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| Fungus |
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Viral Pharyngitis
(See Nelson Textbook of Pediatrics , p. 2019)
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, cough, discrete ulcerations, 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 ( Table 1.6 ; see also Tables 1.1 and 1.4 ). 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, myalgia, and cervical adenopathy in addition to pharyngitis. In young children, croup or bronchiolitis may develop. When influenza is suspected on clinical and epidemiologic grounds or confirmed by testing (polymerase chain reaction [PCR] is most accurate), specific antiviral therapy is available for treatment of patients and prophylaxis of family members. 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 any 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. Many agents can be identified using multiplex or targeted PCR testing, but there is rarely reason to test outpatients and infrequent benefit to testing inpatients except to confirm and treat influenza.
| Gingivostomatitis | Herpangina | Hand-Foot-Mouth Disease | Chickenpox | Systemic Lupus Erythematosus (SLE) | Inflammatory Bowel Disease (IBD) | Aphthous Stomatitis | Behçet Disease | Vincent Stomatitis | Recurrent Scarifying Ulcerative Stomatitis (Sutton Disease) | |
|---|---|---|---|---|---|---|---|---|---|---|
| Etiology | Herpes simples virus (HSV I) | Cocksackievirus A, B; echovirus or HSV (rarely) | Cocksackievirus A, cocksackievirus B (rarely) | Varicella-zoster virus | Autoimmune | Autoimmune | Unknown | Unknown; vasculitis | Unknown; or anaerobic bacteria | Unknown |
| Location | Ulcerative vesicles of pharynx, tongue, and palate plus lesions of mucocutaneous (perioral) margin | Anterior fauces (tonsils), soft palate (uvula), less often pharynx | Tongue, buccal mucosa, palate, palms, soles, anterior oral cavity | Tongue, gingiva, buccal mucosa, marked cutaneous lesions; trunk > face | Oral, nasal mucosa; palate, pharynx, buccal mucosa | Lips, tongue, buccal mucosa, oropharynx | As in IBD | Oral (similar to IBD); genital ulcers | Gingiva; ulceration at base of teeth | Tongue; buccal mucosa |
| Age | Less than 5 yr | 3-10 yr | 1 yr-teens | Any age | Any age | Any age | Teens and adulthood | Teens, adulthood, occasionally <10 yr | Teens; if younger, consider immunodeficiency and blood dyscrasia | Teens |
| Manifestations | Fever, mouth pain, toxic, fetid breath, drooling, anorexia, cervical lymphadenopathy; cracked, swollen hemorrhagic gums; secondary inoculation possible (fingers, eye, skin); reactivation with long latency (any age) | Fever, sore throat, odynophagia; summer outbreaks; 6-12 lesions (2-4 mm papule) → vesicle → ulceration; headache, myalgias | Painful bilateral vesicles, fever | Fever, pruritic cutaneous vesicles, painful oral lesions | Renal, central nervous system, arthritis, cutaneous, hematologic, other organ involvement; ulcers minimally to moderately painful; may be painless | Multiple recurrences; painful ulcerations 1-2 mm, but may be 5-15 mm | Similar to IBD | Painful ulcerations (heal without scarring); uveitis, arthralgia, arthritis, lower gastrointestinal ulceration (similar to IBD); recurrences; spontaneous remissions | Fever, bleeding gums; gray membrane | Deep, large, painful ulcerations; relapsing; scarring with distortion of mucosa |
Adenoviruses can cause upper and lower respiratory tract disease, ranging from ordinary colds to severe pneumonia and multisystem disease, including hepatitis, myocarditis, and myositis. The incubation period of adenovirus infection is 2-4 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. Adenovirus 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 erythematous but usually not bright red; tonsillar exudate and cervical adenopathy are unusual. Symptoms resolve within a few days. Enteroviruses can also cause meningitis, myocarditis, rash, and two specific syndromes that involve the oropharynx.
Herpangina is characterized by distinctive discrete, painful, gray-white papulovesicular lesions distributed over the posterior oropharynx (see Table 1.6 ). The vesicles are 1-2 mm in diameter and are initially surrounded by a halo of erythema before they ulcerate. Fever may reach 39.5°C. The illness is due to enteroviruses and generally lasts less than 7 days, but severe pain may impair fluid intake and occasionally necessitates medical support.
Hand-foot-mouth disease is caused by coxsackievirus A16. Painful vesicles that ulcerate can occur throughout the oropharynx. Vesicles also develop on the palms, soles, and, less often, on the trunk or extremities. Fever is present in most cases, but many children do not appear seriously ill. This disease lasts less than 7 days.
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 as pharyngitis in adolescents. Approximately 35% of new-onset HSV-positive adolescent patients have herpetic lesions; most teenage 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 ). PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) is an idiopathic periodic fever syndrome that occurs predictably every 2-8 weeks. The onset of PFAPA is usually before the age of 5 years. In addition to aphthous stomatitis and pharyngitis, PFAPA is characterized by high fever lasting 4-6 days. Individual episodes resolve spontaneously but may respond to oral prednisone or cimetidine. There are reports of improvement after tonsillectomy. In most patients PFAPA completely resolves before puberty without sequelae. The diagnosis is based on clinical criteria after excluding cyclic neutropenia, other periodic fever syndromes, infections, and malignancy.
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 blue-white enanthem of measles, on the buccal mucosa near the mandibular molars provides the evidence of the correct diagnosis before the rash develops. Measles can be complicated by pneumonia and encephalitis. In the United States, widespread use of the measles vaccine has virtually eliminated transmission of natural measles infection except among unvaccinated subpopulations (children <12 months old, families who have refused immunization). Most cases are imported by unimmunized visitors from countries with endemic measles.
Infectious Mononucleosis
(See Nelson Textbook of Pediatrics , p. 1586)
Pathogenesis
Acute exudative pharyngitis commonly occurs with infectious mononucleosis caused by primary infection with the Epstein-Barr virus (EBV). Mononucleosis is a febrile, systemic, self-limited lymphoproliferative disorder that is usually associated with hepatosplenomegaly and generalized lymphadenopathy. Acute 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 U.S. high school and college students, attack rates are 200-800 per 100,000 per year. EBV is transmitted primarily by saliva.
Clinical Features
After a 2-4 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 1-3 weeks, and lymphadenopathy and hepatosplenomegaly resolve over 3-6 weeks. Malaise and lethargy can persist for several months and can affect school or work performance.
Diagnosis
Laboratory studies of diagnostic value include atypical lymphocytosis; these lymphocytes are primarily EBVspecific, 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 a 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. (They are likely streptococcal carriers; see subsequent text.) An indistinguishable syndrome can occur with cytomegalovirus, but differentiation is rarely of clinical importance. Serologic evidence of mononucleosis should be sought when splenomegaly or other features are present or if symptoms persist longer than expected.
Primary infection with human immunodeficiency virus (HIV) may produce a mononucleosis-like illness with sore throat, fever, lymphadenopathy, rash, myalgias, and hepatosplenomegaly. Early infection may be detected by viral RNA or DNA load because immunoglobulin (Ig)M or IgG titers may have not yet developed.
Group A Streptococcal Infection
(See Nelson Textbook of Pediatrics , p. 2018)
In the evaluation of a patient with sore throat, the primary concern in the United States is usually accurate diagnosis and treatment of pharyngitis caused by group A streptococci (GAS) or Streptococcus pyogenes , which accounts for about 15% of all episodes of pharyngitis. The sequelae of GAS pharyngitis, especially acute rheumatic fever (ARF) and acute glomerulonephritis (AGN), 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 ARF 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 cell wall protein antigens (M, R, T). These protein antigens, especially the M protein, a virulence factor, are useful for studies of epidemiology and pathogenesis but are not used in clinical care.
Epidemiology
GAS pharyngitis is endemic in the United States; epidemics occur sporadically. Episodes peak in the late winter and early spring. Rates of GAS pharyngitis are highest among children aged 5-11 years old. Spread of GAS in classrooms and among family members is common, especially in the presence of crowded living conditions. Transmission occurs primarily by the 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, but antibiotic therapy effectively prevents disease transmission. Within 24 hours of institution of therapy with penicillin, it is difficult to isolate GAS from patients with acute streptococcal pharyngitis, and infected children can return to school.
Molecular epidemiology studies of streptococcal pharyngitis have shown that the prevalent M protein types vary among communities and over time. Numerous distinct strains of GAS can circulate simultaneously in a community during the peak season. GAS M proteins can be identified in research studies by using PCR to establish the specific M protein gene ( emm gene); M protein identification is not available for use in clinical care. Children with streptococcal pharyngitis can serve as a local reservoir for strains that cause invasive disease (e.g., sepsis, streptococcal toxic shock syndrome, cellulitis, necrotizing fasciitis) in the same geographic area and season.
Clinical Features
The classic patient presentation of acute streptococcal pharyngitis involves a sudden onset of fever and sore throat. Headache, malaise, abdominal pain, nausea, and vomiting occur frequently. Cough, rhinorrhea , conjunctivitis, stridor, diarrhea, discrete ulcerated lesions, 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, especially mononucleosis. 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 GAS. However, other diseases can produce this constellation of findings, including infectious mononucleosis. Some or all of these classic characteristics may be absent in patients with streptococcal pharyngitis. Symptoms usually resolve within 5 days even in the absence of antibiotic therapy. Younger children can have a syndrome called streptococcosis ―coryza with crusting below the nares, more generalized adenopathy, and a more chronic course. 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.
Scarlet Fever
The rash of scarlet fever is caused by infection with a strain of GAS that contains a bacteriophage encoding for production of an erythrogenic (redness producing) toxin, usually erythrogenic (also called pyrogenic) exotoxin A (designated SPE A). Scarlet fever is simply GAS pharyngitis with a rash and should be explained as such to patients and their families. Although patients with the streptococcal toxic shock syndrome are also infected with GAS that produces SPE A, most GAS pharyngeal infections are not associated with development of severe invasive or systemic disease.
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 is red, especially over the cheeks, and the area around the mouth often appears pale in comparison, giving the appearance of circumoral pallor. Accentuation of erythema occurs in flexor skin creases, especially in the antecubital fossae (Pastia 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 mild sunburn. On occasion, sheet-like desquamation occurs around the free margins of the fingernails; this is usually coarser than the desquamation seen with Kawasaki disease. The differential diagnosis of scarlet fever includes Kawasaki disease, measles, and staphylococcal toxic shock syndrome ( Table 1.7 ).
