Nonstreptococcal Pharyngitis

ETIOLOGY Most cases of acute pharyngitis in children are caused by viral infections. Examples include adenovirus, Epstein-Barr virus (see below), influenza virus, parainfluenza virus, rhinovirus, herpes simplex virus, and enterovirus. Although many of these viruses cause symptoms in addition to sore throat and fever, such as cough, coryza, conjunctivitis, or mucosal ulcerations, some viral infections can be clinically difficult to distinguish from GABHS.

Mycoplasma and Chlamydia have been suggested as uncommon causes of pharyngitis in adults and adolescents, however neither organism appears to be an important cause of pharyngitis in children.2 25 Many organisms—viral, bacterial, fungal, and even protozoal—have been associated with pharyngitis; however, only a relatively few are of practical significance to the emergency evaluation of pharyngitis in the immune competent child. Recent studies have suggested that Arcanobacterium haemoliticum (formerly Corynebacterium haemoliticum) might be a cause of non-GABHS tonsillopharyngitis with or without a scarlatiniform rash. 26 Erythromycin is the treatment of choice; however, no prospective therapeutic studies are available. Among bacterial pathogens, GABHS is clearly the most important, accounting for 15 to 40 percent of all pharyngeal infections in school-age children. GABHS pharyngitis is unusual in children under 3 years of age, and rheumatic fever is rare in this age group.252!

DIAGNOSIS AND TREATMENT The few non-GABHS organisms that occasionally require specific diagnosis are Corynebacterium diphtheriae, Neisseria gonorrhoeae, EBV, and human immunodeficiency virus type 1. Despite the many etiologic possibilities, in school-age children the diagnostic task is most often reduced to distinguishing GABHS, which requires specific antibiotic therapy, from nonstreptococcal pharyngitis.

Diphtheria is a rare but serious cause of pharyngitis in developed countries. Immunization in infancy with an alum-precipitated toxoid combined with pertussis antigen and tetanus antigen (DPT) has been effective in nearly eliminating diphtheria in childhood, but it can occur in crowded conditions where there are socioeconomic barriers to immunization. Morbidity occurs because of both infectious and toxic reactions. Infectious invasion and spread occur with enough tissue necrosis to produce a pseudomembrane that can progress to cause airway obstruction. The C. diphtheriae bacteria also produce an exotoxin that can cause widespread organ damage, including myocarditis and cardiac dysrhythmia, neuritis with both bulbar and peripheral paralysis, nephritis, and hepatitis. Diagnosis must be clinical in order to expedite effective therapy; however, the bacteria can be grown on Loeffler media. Treatment is directed at both killing the bacteria and neutralizing the exotoxin. Therefore, both antibiotic (penicillin or erythromycin) and horse-serum antitoxin must be given.

N. gonorrhoeae is an infrequent but important cause of pharyngitis in sexually active adolescents. Gonococcal pharyngitis in younger children strongly suggests child sexual abuse. Gonococcal pharyngitis may either be asymptomatic or cause very mild symptoms with occasional exudative tonsillitis and/or cervical lymphadenopathy. Pharyngeal throat swabs should be plated on Thayer-Martin medium to recover the organism. Rectal and vaginal or urethral cultures as well as serum to test for syphilis and hepatitis B should be obtained whenever gonorrhea is suspected or documented. Gonococcal pharyngitis in children and adolescents should be treated with ceftriaxons (125 mg intramuscularly once). Children who cannot tolerate ceftriaxone may be treated with a 5-day regimen of trimethoprim-sulfamethoxazole. Children 9 years or older should also receive oral doxycycline (100 mg bid for 7 days) for presumptive Chlamydia infection. Children 8 years or younger should receive erythromycin 40 mg/kg/day in divided doses]. Azithromycin (20 mg/kg, 1 g maximum) orally in a single dose is an alternative treatment for Chlamydia in all age groups.28

EBV is a herpesvirus that is a common cause of infection in childhood and adolescence. While EBV has been associated with a variety of clinical syndromes, most children infected with EBV are asymptomatic or have only mild nonspecific symptoms. EBV can cause isolated tonsillopharyngitis and pharyngitis as a manifestation of infectious mononucleosis (IM). Clinically, the classic IM syndrome begins with malaise, fatigue, and sore throat. Fever and adenopathy are the most common signs. Splenomegaly and hepatomegaly are also present in the majority of infected children, while skin rash, enanthem, eyelid edema, and jaundice occur much less commonly. Pharyngitis occurs in nearly all children with IM. The appearance of the throat can resemble that of bacterial GABHS disease. Dual infection with EBV and

GABHS has also been documented. Classic IM is much less common in children under the age of 2 years, when EBV tends to cause a nonspecific febrile illness. However, recently IM has been reported to occur in toddlers more commonly than was once thought. These younger children most often have a syndrome characterized by fever, tonsillitis, lymphadenopathy, and hepatosplenomegaly. ™3°

The laboratory can be helpful in establishing the diagnosis of IM. There is an increase in both the proportion and the absolute number of atypical lymphocytes in the peripheral blood smear (generally 350 percent lymphocytes and 310 percent atypical lymphocytes). Liver transaminase levels show moderate elevation [generally aspartate aminotransferase (AST) is <600 U/dL]. The heterophil antibody is present (and can be demonstrated by rapid slide test methods) in over 90 percent of children over the age of 5 with IM, but in only 75 percent between the ages of 2 and 4, and in fewer than 30 percent under the age of 2. EBV-specific serologic testing can provide information as to the likelihood of acute, postacute, old quiescent, and reactivation-type infection. These determinations are made on the basis of the presence of specific patterns of IgM and IgG responses to viral capsid antigen and IgG responses to EBV early antigen and the Epstein-Barr nuclear antigen. 31

IM is generally a benign, self-limited, but somewhat prolonged illness. In general, treatment involves nonspecific supportive modalities (fluids, acetaminophen, and rest). Fatal complications are rare. Death can be caused by neurologic complications (e.g., meningoencephalitis or Guillain-Barre syndrome), splenic rupture and hemorrhage, and bacterial and fungal sepsis. Immunocompromised children may have unusual susceptibility to fulminant EBV infection. Airway obstruction secondary to tonsillar hypertrophy can also occur. This complication responds rapidly to glucocorticoid administration (dexamethasone 1 mg/kg to 10 mg maximum; then 0.5 mg/kg every 6 h) and rarely requires intubation. Airway obstruction is the only complication for which the use of steroids is widely accepted.

Human immunodeficiency virus type 1 is a recently recognized cause of acute pharyngitis. Primary retroviral infection can produce a mononucleosis-like illness with fever, sore throat, and lymphadenopathy that can last for a few days or a few weeks. Such findings as gastrointestinal symptoms or mucocutaneous lesions occur more commonly with acute HIV infection and are very unusual with mononucleosis caused by EBV. Primary HIV infections should be considered in high-risk populations.32

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