Introduction
Background
Herpangina is an acute febrile illness associated with small vesicular or ulcerative lesions on the posterior oropharyngeal structures (enanthem). Herpangina typically occurs during the summer and usually develops in children, occasionally occurring in newborns, adolescents, and young adults. Herpangina is one of many manifestations of enterovirus infection and can occur in association with enteroviral exanthem, aseptic meningitis, encephalitis, acute flaccid paralysis, and other clinical syndromes.
Pathophysiology
Herpangina is a pharyngeal infection typically caused by various enteroviruses. In recent years, coxsackievirus A16, enterovirus 71, and coxsackievirus B have been implicated most often. Less-common causes include echovirus, parechovirus 1, adenovirus, and herpes simplex virus (HSV).1,2 Enterovirus 71 has emerged as an important public problem, causing severe clinical illness and, potentially, death in young children.3 . Enteroviruses that cause herpangina belong to the Picornaviridae family.
Coxsackievirus B4 virions under electron microscopy. (This image is in the public domain and thus free of any copyright restrictions. Content provider: Centers for Disease Control and Prevention)
A distinct phenotype of enterovirus 71 causes herpangina. This is in contrast to the phenotype of enterovirus 71 that causes encephalitis, aseptic meningitis, myocarditis, poliomyelitislike paralysis, and neonatal sepsis.
Viruses that cause herpangina are typically spread via the fecal-oral route, although they may spread via the respiratory route or through fomites. Freshwater sources (eg, lakes) may act as a reservoir for transmission.
Herpangina typically has an incubation period of 4-14 days. Viremia occurs after inoculation and subsequently results in distant sites of infection. Viral replication at these secondary sites leads to characteristic clinical symptoms and oropharyngeal lesions. Bilateral, anterior, cervical lymphadenopathy may occur, resulting from infection of the posterior oropharynx. Coxsackievirus A may be recovered from the nasopharynx, feces, blood, urine, and cerebrospinal fluid (CSF). After clinical symptoms have resolved, asymptomatic enteroviral infection may persist in the gastrointestinal tract.
Frequency
United States
Enteroviral infections are most common during the summer and fall in temperate climates and occur year-round in tropical climates.
International
Enteroviral infections occur worldwide. Acute fatal epidemics have been reported in at least 5 parts of the world, the most recent being described in Kanagawa Prefecture, Japan, in 2007.4
Mortality/Morbidity
Herpangina is typically a mild and self-limited illness. Although most children who develop herpangina recover, the disease is occasionally complicated by CNS lesions and cardiopulmonary failure. Fatalities associated with herpangina have been reported, primarily in infants aged 6-11 months.
Sex
Herpangina does not have a sexual predilection.
Age
Herpangina most commonly affects infants and young children aged 3-10 years. Herpangina is less common in adolescents and adults.
Clinical
History
Approximately 50% of enteroviral infections are asymptomatic. Clinical manifestations may vary, depending on the strain of the virus.
- All enteroviral infections may cause fever, which may be the first apparent symptom. Patients with enteroviral infection typically develop a temperature of 101-104°F.
- Most symptomatic patients report malaise.
- Sore throat and pain upon swallowing may develop and precedes the development of the enanthem by a few hours to one day.
- Older children frequently report headache and backache.
- Persons with enteroviral infection may experience anorexia, emesis, or abdominal pain, which may mimic appendicitis.
- Infants with enteroviral infection may appear listless.
- Exanthem: Characteristics and occurrence rates vary, depending on the viral subtype. Persons with enteroviral infection may develop a rash that is not pruritic and that does not cause skin desquamation. The following are other rash characteristics:
- Macular
- Maculopapular
- Papulopustular
- Papulovesicular
- Vesicular
- Morbilliform
- Urticarial
- Petechial
- Hemangiomalike
Physical
- Oropharyngeal lesions (herpangina)
- Hyperemia of the pharynx is associated with lesions that characteristically appear as discrete erythematous-based macules. These evolve into papules that vesiculate and then ulcerate centrally, creating an erythematous halo.
- In most cases, these lesions are the first physical finding of herpangina. The lesions are typically smaller than 5 mm in diameter. Most cases of herpangina involve 2-12 lesions.
- Uninvolved portions of the pharynx usually appear normal. The most commonly affected structures include the anterior pillars of the fauces, soft palate, uvula, tonsils, and posterior pharyngeal wall.
- Occasionally, lesions caused by herpangina appear on the tongue and posterior buccal mucosa (see Table for differential diagnoses of oral lesions).
- The ulcers may persist for up to one week, even after the fever has subsided.
- Pharyngitis: Erythema of the pharynx may range from mild to severe. Pharyngitis in enteroviral infections may be associated with pleurodynia, meningitis, and/or exanthem.
- Bilateral, anterior, cervical lymphadenopathy may develop.
- Acute lymphonodular pharyngitis is a variant of herpangina associated with coxsackievirus A10 infection. Tiny nodules of packed lymphocytes develop in the same distribution as herpangina oropharyngeal lesions. However, unlike the lesions of herpangina, these recede without vesiculation or ulceration.5
Causes
- Coxsackieviruses A 1-10, 12, 16, and 22 represent the most common pathogens that cause herpangina.
- Less-common causes of herpangina include the following:
- Coxsackievirus B 1-5
- Echovirus 3, 6, 9, 11, 16, 17, 22, 25, and 30
- Enterovirus 71 (see Pathophysiology)
- Parechovirus 1
- Herpes simplex virus
- Adenovirus
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| References |
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References
Mandell GL, et al. Enteroviruses. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Vol 1. 7th ed. 2010:817-818.
Cherry JD, et al. Herpangina. In: Textbook of Pediatric Infectious Diseases. Vol 1. 6th ed. 2009:Chap 11.
Chen KT, Chang HL, Wang ST, Cheng YT, Yang JY. Epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in Taiwan, 1998-2005. Pediatrics. Aug 2007;120(2):e244-52. [Medline].
Sano T, Saito T, Kondo M, Watanabe S, Onoue Y, Konnai M, et al. Enterovirus detection status of patients with herpangina and hand, foot and mouth disease in epidemic season 2007, Kanagawa Prefecture, Japan. Jpn J Infect Dis. Mar 2008;61(2):162-3. [Medline].
Mandell GL, et al. Herpangina. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Vol 2. 7th ed. 2010:2355-56.
Wang SM, Liu CC. Enterovirus 71: epidemiology, pathogenesis and management. Expert Rev Anti Infect Ther. Aug 2009;7(6):735-42. [Medline].
Li C, Wang H, Shih SR, et al. The efficacy of viral capsid inhibitors in human enterovirus infection and associated diseases. Curr Med Chem. 2007;14(8):847-56. [Medline].
Chen HL, Huang JY, Chu TW, Tsai TC, Hung CM, Lin CC, et al. Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection. Vaccine. Jun 2 2008;26(23):2882-9. [Medline].
Chang LY, King CC, Hsu KH, et al. Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan. Pediatrics. Jun 2002;109(6):e88. [Medline].
Chawareewong S, Kiangsiri S, Lokaphadhana K, et al. Neonatal herpangina caused by Coxsackie A-5 virus. J Pediatr. Sep 1978;93(3):492-4. [Medline].
Cherry JD. Enteroviruses: Coxsackieviruses, Echoviruses, and Polioviruses. In: Textbook of Pediatric Infectious Diseases. Vol. 2. 1998:1787-1839.
Chole RA, Domb GH. Differential diagnosis of superficial ulcerations of the oral mucosa. Otolaryngol Head Neck Surg. Nov-Dec 1979;87(6):734-40. [Medline].
Christie AB. Enteroviral infections (Coxsackieviruses and echoviruses). In: Infectious Diseases: Epidemiology and Clinical Practice. 1987:753-81.
Delaney JE, Keels, MA. Soft tissue lesions of the oral cavity in children. UpToDate. Available at www.uptodate.com. Accessed November 10, 2009.
Foo DG, Alonso S, Phoon MC, Ramachandran NP, Chow VT, Poh CL. Identification of neutralizing linear epitopes from the VP1 capsid protein of Enterovirus 71 using synthetic peptides. Virus Res. Apr 2007;125(1):61-8. [Medline].
Haskell R. Oral vesiculo-bullous lesions. J Laryngol Otol. Jan 1976;90(1):101-4. [Medline].
Ho M, Chen ER, Hsu KH, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med. Sep 23 1999;341(13):929-35. [Medline].
Kung CM, King CC, Lee CN, et al. Differences in replication capacity between enterovirus 71 isolates obtained from patients with encephalitis and those obtained from patients with herpangina in Taiwan. J Med Virol. Jan 2007;79(1):60-8. [Medline].
Lin TY, Chang LY, Hsia SH, et al. The 1998 enterovirus 71 outbreak in Taiwan: pathogenesis and management. Clin Infect Dis. May 1 2002;34 Suppl 2:S52-7. [Medline].
Melnick JL. Enteroviruses: Polioviruses, Coxsackieviruses, Echoviruses, and Newer Enteroviruses. In: Field's Virology. 1990:549-98.
Miyazawa I, Azegami Y, Kasuo S, Yoshida T, Kobayashi M, Shiraishi T. Prevalence of enterovirus from patients with herpangina and hand, foot and mouth disease in Nagano Prefecture, Japan, 2007. Jpn J Infect Dis. May 2008;61(3):247-8. [Medline].
Modlin JF. Clinical manifestation and diagnosis of enterovirus infections. UpToDate. Available at www.uptodate.com. Accessed November 10, 2009.
Rosenblatt RM, Domb GH. Herpangina in an anesthesiologist. Anesth Analg. May 1980;59(5):384-5. [Medline].
Further Reading
Keywords
herpangina, enteroviral herpangina, coxsackievirus herpangina, Picornaviridae, coxsackievirus, coxsackievirus A, coxsackievirus B, echovirus, enterovirus, enteroviruses, enteroviral infection, enterovirus 71, EV71
