Herpangina

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2]

Synonyms: Vesicular stomatitis, Acute lymphonodular pharyngitis

Overview

Herpangina is a self-limited infection of the upper respiratory tract caused by enteroviruses. Serotypes of coxsackie A virus are frequently implicated. Outbreaks of herpangina often occur during the summer period, and the pediatric age group is predominantly affected. Herpangina often begins with a sudden fever, sore throat, dysphagia, and the appearance of the enanthem. The diagnosis is usually clinical and it generally resolves within one week of infection without any sequelae.

Historical Perspective

The name 'herpangina' was coined by Zahorsky, and he was also the first person to give a full description of the clinical entitity in 1920. The first isolation and description of the coxsackie virus was in 1948 by Dalldorf and Sickles.

Causes

Herpangina is caused by enteroviruses. The majority of herpangina cases are caused by coxsackie A viruses (commonly A1, A2, A6, A8, A10, A16, and A22) but it can also be caused by other enteroviruses such as some serotypes of coxsackie B virus, echovirus and enterovirus 71.

Pathophysiology

The mode of transmission of enteroviruses is usually via fecal–oral transmission. However, enteroviruses can also be spread through contact with virus-contaminated oral secretions, vesicular fluid, contaminated surfaces or fomites, and viral respiratory droplets. Following ingestion of the enterovirus, viral replication occurs in the lymphoid tissues of the oropharyngeal cavity and the small bowel (Peyer's patches). Dissemination of enteroviruses to the reticuloendothelial system and other parts of the body such as the skin and mucous membranes can occur, and this coincides with the onset of the clinical features.

Risk Factors

Some of the risk factors that have been found to be associated with herpangina are:

• Attendance at a kindergarten/child care center
• Contact with herpangina cases
• Residence in rural areas
• Overcrowding
• Poor hygiene
• Low socioeconomic status

Differential Diagnosis

The following diseases may mimic herpangina:

• Herpetic gingivostomatitis- This is caused by herpes simplex virus(HSV) infection, and affects the anterior oral cavity. It commonly affects the inner parts of the lips, the buccal mucosa, and the tongue. Gingivitis and cervical lymphadenitis can be seen in HSV infection but these are usually absent in herpangina.
• Bacterial pharyngitis
• Tonsillitis
• Aphthous stomatitis
• Hand-foot-mouth disease

Oral lesions caused by herpangina must be differentiated from other diseases presenting with pain and blistering within the mouth (gingivostomatitis and glossitis). The differentials include:

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh ≤1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles
Herpangina	Sudden fever Sore throat and dysphagia- These can occur several hours(up to 24 hours), before the appearance of the enanthem. Vomiting Abdominal pain Myalgia Headache Pharyngeal lesions	Attendance at a kindergarten/child care center Contact with herpangina cases Residence in rural areas Overcrowding Poor hygiene Low socioeconomic status	Clincial diagnosis Pharyngeal viral and bacterial cultures can be taken to exclude HSV infection and streptococcal pharyngitis.	Skin Oral Cavity	Characteristic enanthem- Punctate macule which evolve over a period of 24 hours to 2-4mm erythematous papules which vesiculate, and then centrally ulcerate. The lesions are usually small in number, and evolve rapidly. The lesions are seen more commonly on the soft palate and uvula. The lesions can also be seen on the tonsils, posterior pharyngeal wall and the buccal mucosa.	Erythema, vesicles and ulcerating lesions in herpangina
Primary herpetic gingivoestomatitis	Pin-head vesicles rupture to form painful irregular ulcerations covered by yellow-grey membrane Severe pain Submandibular lymphadenopathy Halitosis It involves buccal mucosa, tongue, posterior pharynx, and gingival and palatal mucosa	Direct contact HIV infection	Tzanck test demonstrates multinucleated epithelial giant cells Viral culture is the gold standard for diagnosis Direct immunofluorescence	Oral cavity Mucous membranes	Ulcers are common on lips, gums, throat, front of tongue, inside of the cheeks and roof of the mouth Treatment is with antiviral agents such as Valacyclovir and Famciclovir
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue		Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg

Epidemiology

Incidence

The incidence of herpangina has been found to have seasonal variations and there is usually a peak in the incidence during the summer season. The incidence was studied for a period of 8 years in Taiwan and was found to vary between 0.8-19.9 cases per sentinel physician per week.

Age

Herpangina is seen predominantly in children and summer outbreaks are not uncommon. It occurs more frequently in children between the ages of 3-10yrs. Adolescents and young adults are occasionally affected.

Sex

There is no known sex predilection.

Natural History, Complications, Prognosis

Natural History

Herpangina is a self-limited infection of the upper respiratory tract.

Complications

Complications such as meningitis rarely occurs.

Prognosis

The prognosis is excellent and complete resolution generally occurs in a week.

Diagnosis

History and Symptoms

The history and symptoms may include the following:

• Sudden fever
• Sore throat and dysphagia- These can occur several hours(up to 24 hours), before the appearance of the enanthem.
• Vomiting
• Abdominal pain
• Myalgia
• Headache
• Pharyngeal lesions
• Most patients do not appear severely ill

Physical Examination

Erythema, vesicles and ulcerating lesions in herpangina

Examination of the throat can reveal the following:

• Erythema
• Exudate of the tonsils which is usually mild.
• Characteristic enanthem- Punctate macule which evolve over a period of 24 hours to 2-4mm erythematous papules which vesiculate, and then centrally ulcerate.
• The lesions are usually small in number, and evolve rapidly. The lesions are seen more commonly on the soft palate and uvula. The lesions can also be seen on the tonsils, posterior pharyngeal wall and the buccal mucosa.

Laboratory Tests

• The diagnosis of herpangina is clinical.
• When unsure of the diagnosis, pharyngeal viral and bacterial cultures can be taken to exclude HSV infection and streptococcal pharyngitis.
• Approximately 1 week after infection, type-specific antibodies appear in the blood with maximum titer occurring in 3 weeks.

Treatment

Herpangina is a self-limited infection, and the treatment comprises the management of the symptoms. This entails:

• Symptomatic treatment of sore throat with saline gargles, analgesic throat lozenges and liberal oral fluid intake.
• Analgesic medications for pain
• Antipyretic medications when indicated
• Avoidance of antiviral and antibacterial medications as symptoms generally resolve within 1 week.

Prevention

The prevention of herpangina is best achieved by adoption of infection control practices such as:

• Good personal hygiene like hand-washing.
• Cleaning and disinfection of premises and objects/articles.
• Ensuring infected children are quarantined.

References