Epstein-Barr virus (EBV) is the agent responsible for infectious mononucleosis and is the cause of sore throat in 5% to 10% of young adults. Prodromal symptoms include malaise, headache, and fatigue, followed by fever, sore throat, and cervical lymphadenopathy. Sore throat is the most common feature. The pharynx shows enlarged tonsils and erythema. About half of the patients develop tonsillar exudates, and about one third of patients have petechiae at the junction of the hard and soft palate. Both anterior and posterior cervical adenopathy may develop; generalized adenopathy often follows. Splenomegaly is noted in about half of cases, and hepatomegaly and tenderness are present in about 10%. Clinical hepatitis sometimes ensues. A faint maculopapular rash and transient supraorbital edema occasionally appear on presentation, but the rash appears in >90% of patients exposed to amoxicillin. Atypical lymphocytes are often present on complete blood count, and thrombocytopenia is frequently seen.

Herpes simplex virus and coxsackie A virus are other causes of pharyngitis. Herpes infection may mimic streptococcal infection with an exudative pharyngitis; shallow ulcers on the posterior palate are characteristic. Coxsackie A infection (herpangina) is characterized by vesicles and ulcers on the tonsillar pillars and soft palate.

Acute infection with the human immunodeficiency virus (HIV) can lead to a mononucleosis-like syndrome known as the acute retroviral syndrome. Fever, pharyngitis, lymphadenopathy, and rash are present, but the disease onset is more acute than with EBV infection. Any patient with this presentation should be assessed for HIV risk factors and tested if appropriate. Antibodies to HIV will not be present, and a viral load (quantitative HIV RNA assay) confirms the diagnosis.

Chlamydophila pneumoniae and Mycoplasma pneumoniae may account for a surprising percentage of patients presenting with pharyngitis, based on serologic evidence of infection, although the clinical significance of this finding is unclear. The diagnosis of M. pneumoniae is rarely made clinically in the absence of pneumonitis.

Arcanobacterium (formerly known as Corynebacterium) haemolyticum is a gram-positive bacillus that can cause pharyngitis and scarlatiniform rash, particularly in teenagers and young adults. The administration of penicillin or erythromycin produces rapid improvement.

Meningococci are found in the pharynx in 5% to 15% of healthy people. Although sore throat may be a prodromal symptom of meningococcemia, isolated pharyngitis due to meningococcal infection is rare. Most instances of positive pharyngeal cultures for meningococcus represent asymptomatic colonization.

Diphtheria is rare in the United States but can occur in international travelers and cause outbreaks in unimmunized populations. The infection is characterized by the development of an adherent grayish pharyngeal exudate (“pseudomembrane”) that covers the pharynx and causes bleeding if removal is attempted. Bacterial strains that produce diphtheria toxin cause myocarditis and polyneuritis.

Pneumococci and staphylococci commonly reside in the nasopharynx and can cause severe disease in other parts of the respiratory tract. However, they do not cause pharyngitis except
under the most unusual circumstances. When these bacterial species are cultured from the pharynx in both symptomatic and asymptomatic individuals, colonization, not causation, by these organisms should be suspected. However, mixed infections with normal mouth flora do occur in debilitated patients.

Fusobacteria and spirochetes can cause gingivitis (“trench mouth”) or necrotic tonsillar ulcers (“Vincent angina”). Patients present with foul breath, pain, pharyngeal exudate, and a dirty gray membranous inflammation, which bleeds easily. A similar combination of bacteria and spirochetes can produce an extremely serious invasive gangrene of the mouth known as cancrum oris. This process occurs only in malnourished infants or patients with advanced malignancy and immunosuppression and, fortunately, is rare. More recently, Fusobacterium necrophorum has been implicated in uncomplicated pharyngitis in young adults and adolescents, with a concern for the potential to develop into Lemierre syndrome (septic thrombophlebitis of the internal jugular vein). Treponema pallidum can cause pharyngitis as part of primary or secondary syphilis. The diagnosis requires a high index of suspicion and serologic confirmation.

Yersinia enterocolitica infection typically presents as enterocolitis, but occasionally in adults, it presents as pharyngitis in the absence of enteritis. Fatalities have been reported.

Candida albicans, present in the normal mouth flora, can produce pharyngitis if antibiotics, immunosuppressive agents, or debilitating illness upsets microbial interactions or host defenses. Oropharyngeal moniliasis (thrush) can be painful and is characterized by a cheesy white exudate, which can be scraped off to demonstrate yeast forms by smear and culture. Oral moniliasis may be the first symptomatic manifestation of HIV infection (see Chapter 13).