Hand, foot, and mouth disease and herpangina

INTRODUCTION — Hand, foot, and mouth disease (HFMD) is a clinical syndrome characterized by an oral enanthem and a macular, maculopapular, or vesicular rash of the hands and feet (and possibly other locations) [1]. HFMD is one of the most recognizable viral exanthems in children and adults [2]. HFMD was first described in a summer outbreak that occurred in Toronto, Canada in 1957 and was caused by coxsackievirus A16 [3]. Since then, at least 15 other enterovirus serotypes have been shown to cause HFMD, most commonly Coxsackievirus A serotypes.

Herpangina is a benign clinical syndrome characterized by fever and a painful papulo-vesiculo-ulcerative oral enanthem [4]. It can be clinically differentiated from HFMD and primary herpetic gingivostomatitis [5]. Herpangina was first described in the 1920s, but the viral etiology was not established until 1951 [4,6,7]. Herpangina is caused by 22 enterovirus serotypes, most commonly Coxsackievirus A serotypes.

An overview of HFMD and herpangina will be presented here. Other enterovirus infections are discussed separately. (See "Enterovirus and parechovirus infections: Epidemiology and pathogenesis" and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention".)

VIROLOGY — Multiple enterovirus serotypes cause HFMD and herpangina (table 1). The majority of these serotypes belong to the Enterovirus A species of the genus Enterovirus. (See "Enterovirus and parechovirus infections: Epidemiology and pathogenesis", section on 'Classification'.)

Coxsackievirus A16 and enterovirus A71 are the serotypes most frequently associated with HFMD and are responsible for the majority of large outbreaks [8,9]. Enterovirus A71 has been associated with outbreaks involving thousands of persons in the Asia-Pacific region [10,11]. Beginning in 2008, coxsackievirus A6 has been increasingly reported as a cause of outbreaks of HFMD around the world [9,12-19]. (See 'Enterovirus A71 HFMD' below and 'Coxsackievirus A6 HFMD' below.)

The principal enterovirus serotypes associated with herpangina are coxsackievirus A1 to 6, 8, 10, and 22 [20-22]. In the Asia-Pacific region, where large outbreaks of enterovirus 71 and coxsackievirus A16 have occurred, these serotypes are a common cause of herpangina [23,24].

PATHOGENESIS — Human enterovirus infection occurs after oral ingestion of virus that is shed from the gastrointestinal or upper respiratory tract of infected individuals (ie, via the ingestion of fecal material, oral secretions, or, for some serotypes, respiratory secretions) [25]. Human enterovirus infection also may occur following contact with vesicle fluid or oral and respiratory secretions [3,13,25].

Virus may be detected in the stool for six weeks and sometimes for several months after infection. The duration of shedding from the oropharynx is generally less than four weeks. Prolonged shedding in the stool and the innate environmental stability of the enteroviruses favors their transmission.

Once ingested, the enteroviruses replicate in the submucosal lymphoid tissues of the lower intestine and, to a lesser extent, the pharynx. Following replication, the enteroviruses spread to the regional lymph nodes. Replication at these sites results in a "minor viremia" that disseminates virus throughout the body, resulting in infection of reticuloendothelial tissues and multiple organs (eg, central nervous system, heart, liver, skin). Replication at these sites is responsible for the clinical manifestations of enteroviral infections. Further replication at the disseminated sites leads to a "major viremia," which continues until the host produces type-specific antibodies. Enterovirus replication in organ tissues results in the death of infected cells, with accompanying inflammation and necrosis. (See "Enterovirus and parechovirus infections: Epidemiology and pathogenesis", section on 'Pathogenesis'.)

Biopsies of HFMD vesicular lesions show loose strands of fibrin, lymphocytes, monocytes, and neutrophils within the vesicular fluid [2]. Extensive acantholysis with reticular degeneration is seen in the overlying epidermis with perivascular foci of lymphocytic, monocytic, and neutrophilic leukocytes in the upper dermis. In adults with HFMD due to coxsackievirus A6, skin biopsies demonstrated spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, and basal cell vacuolization [26]. The upper epidermis showed shadow cells, and the follicles and sweat glands contained necrotic cells. There was a dense superficial dermal infiltrate of CD31 lymphocytes and strong granulysin expression. Light microscopy of biopsies of skin lesions or scrapings of the base of vesicles does not demonstrate nuclear inclusion bodies and multinucleated giant cells, which helps to distinguish HFMD from varicella-zoster virus and herpes simplex virus [2,26-29]. Intracytoplasmic inclusion bodies have been observed in only one report [28].

EPIDEMIOLOGY — HFMD and herpangina occur worldwide. Outbreaks involving daycare centers, schools, summer camps, hospital wards, military installations, communities, large geographic areas, and entire countries have been reported [30-32]. Intrafamily spread occurs in both HFMD and herpangina.

Most cases of HFMD and herpangina occur in infants and children, particularly those younger than five to seven years [15,22,30,33-39]. However, sporadic cases and epidemics principally affecting older children, adolescents, and adults have been reported [26,34,40-42].

HFMD and herpangina usually occur during the summer and early autumn, similar to other clinical syndromes caused by enteroviruses. However, outbreaks and sporadic cases of HFMD can occur during the winter months [37,43-46]. In tropical areas, cases of HFMD occur during the rainy season [15]. Temperature and humidity affect the incidence of HFMD [47,48], raising the possibility that the increasing global incidence of HFMD may be related to climate change [47]. (See "Enterovirus and parechovirus infections: Epidemiology and pathogenesis", section on 'Epidemiology'.)

TRANSMISSION — The viruses that cause HFMD and herpangina usually are transmitted from person to person by the fecal-oral route. However, they also can be transmitted by contact with oral and respiratory secretions and, in the case of HFMD, vesicle fluid [3,13,25].

Nucleic acid amplification testing demonstrates fecal shedding of enterovirus for up to 10 weeks and respiratory tract shedding for up to 30 days after the onset of infection, depending upon enterovirus type and severity of illness [49,50]. Traditional methods of viral detection demonstrated fecal shedding for four to six weeks and respiratory tract shedding for ≤3 weeks [51]. An outbreak investigation of HFMD due to coxsackievirus A16 in a daycare center suggests that children are infectious for <7 days [52]. Both infection and viral shedding can occur without clinical signs of illness [51].

INCUBATION PERIOD — The incubation period for HFMD typically is three to five days, but has been reported to be as short as two days and as long as seven days [1,3,29,43,53,54].

The average incubation period for herpangina is three to five days [7], with a range of 1 to 10 days [6,7,30,31].

CLINICAL FEATURES

Hand, foot, and mouth disease

Presentation — HFMD typically presents with complaints of mouth or throat pain (in verbal children) or refusal to eat (in nonverbal children) [1,3,28,55,56]. Fever, if present, generally is below 38.3°C (101°F) [1,3,28,55,57].

Prodromal symptoms usually are absent [1,55]. When reported, they include fever, fussiness, abdominal pain, emesis, and diarrhea [43,57].

Examination findings — The cardinal findings of HFMD are the oral enanthem (picture 1A-B) and the exanthem (picture 2). However, the enanthem may occur without the exanthem and the exanthem may occur without the enanthem [28,56,58,59].

Oral enanthem — The oral lesions of HFMD are anterior to the faucial pillars, most commonly on the tongue and buccal mucosa (picture 1A-B); less commonly in the gingivolabial groove and on the soft and hard palates; and occasionally on the uvula, lips, and tonsils.

The enanthem begins as erythematous macules, which progress to vesicles surrounded by a thin halo of erythema (picture 1B) [1-3,27,28,55,57,59]. Vesicle diameter usually ranges from 1 to 5 mm (0.04 to 0.2 inches) but may be greater. The vesicles quickly rupture and form superficial ulcers with a greyish-yellow base and an erythematous rim (picture 1A). Ulcer diameter typically ranges from 1 to 10 mm (0.04 to 0.4 inches), but diameters of 20 mm (0.8 inches) have been reported [3,27].

Exanthem — The exanthem associated with HFMD may be macular, maculopapular, or vesicular (picture 2) [1,3,28,55,57,59-61]. All three lesions may occur in a single patient [59]. The vesicles arise from macules or macule-papules [3,35]. Vesicle diameter ranges from 1 to 10 mm (0.04 to 0.4 inches). The vesicles are thin walled, contain a clear or turbid fluid, and are surrounded by a thin (1 mm [0.04 inch]) halo of erythema.

The skin lesions of HFMD are nonpruritic [1,3]. They usually are not painful, but may be painful when HFMD is caused by certain serotypes (eg, coxsackievirus A6). The lesions typically resolve in three to four days [1,3].

The exanthem typically involves the hands (dorsum of the fingers, interdigital area, palms), feet (dorsum of the toes, lateral border of the feet, soles, heels), buttocks, legs (upper thighs), and arms (picture 3A) [1,3,27,28,35,55,57]. Less commonly, vesicles may be seen on the torso and face. Lesions on the buttocks are more commonly maculopapular than vesicular [57,59]. They also occur more frequently in infants and young children than in older children and adults [1,57,59,60].

Enterovirus A71 HFMD — HFMD caused by enterovirus A71 has been associated with severe illness, complicated by central nervous system disease (rhombencephalitis, acute flaccid paralysis, aseptic meningitis), pulmonary edema and hemorrhage, and heart failure [23,36,37,62-68]. (See 'Complications' below and 'Clinical course' below.)

Coxsackievirus A6 HFMD — Since 2008, a novel coxsackievirus A6 genotype has been associated with more severe disease in both children and adults than generally occurs with "typical" HFMD, including (picture 3A and picture 3B) [13,16,26,41,69-73]:

●Higher fever

●Wider distribution – Involvement of the extremities, face, lips and perioral area, buttocks, groin, and perineum; the lesions are concentrated in areas of active or dormant eczema ("eczema coxsackium") (picture 4)

●More extensive skin involvement – Vesiculobullous lesions, bullae, erosions, ulcerations, and eschar formation (picture 3C)

●Longer duration (mean duration 12 days)

●Palmar and plantar desquamation one to three weeks after HFMD

●Nail dystrophy (eg, transverse ridges of the nail plate [Beau lines], shedding of the nail [onychomadesis]) one to two months after HFMD

Atypical HFMD associated with coxsackievirus A6 is discussed in greater detail separately. (See "Atypical exanthems in children", section on 'Atypical hand, foot, and mouth disease'.)

Herpangina

Presentation — The onset of herpangina is typically abrupt with high fever (38.9 to 40°C [102 to 104°F]) [4-7,31,38,39]. Fever up to 40.6°C (105°F) occasionally occurs. Seizures may accompany the onset of fever [6]. In the infants and young children unable to express themselves verbally, anorexia, emesis, and fussiness/irritability are commonly seen, individually or in combination. Older children may also complain of malaise, headache, sore throat, dysphagia, and abdominal pain.

In the sole report of a herpangina outbreak among young adults requiring hospitalization, fever (96 percent) and sore throat (96 percent) were the most frequent symptoms, followed by headache (72 percent), pain and stiffness of the neck (72 percent), pain and stiffness of the back (65 percent), nausea (50 percent), anorexia (46 percent), and abdominal colic (46 percent) [74].

Examination findings — Examination of the throat reveals hyperemia and yellow/greyish-white papulovesicular lesions. The areas most frequently involved are the anterior pillars of the fauces, soft palate, tonsils, and uvula. Very occasionally, a lesion may be seen on the hard palate, tongue, or buccal mucosa. The number of lesions varies but is usually less than 10 [6,7,30,38,39,74].

The lesions begin as papules that undergo the vesiculation in 24 hours [6]. The vesicles usually measure 1 to 2 mm in diameter and are surrounded by an areola of erythema. After approximately 24 hours, the vesicles rupture, leaving 3 to 4 mm in diameter, shallow, yellow/grayish ulcerations with a rim of intense erythema (picture 5) [30,31,38].

In children, there are usually no other physical findings. However, additional findings in adults may be significant [74]. Among young adults requiring hospitalization for herpangina, 57 percent had neck stiffness, 80 percent had a positive Kernig sign (ie, inability or reluctance to allow full extension of the knee when the hip is flexed 90 degrees), and 49 percent had cervical adenitis.

COMPLICATIONS — Serious complications of HFMD rarely occur, except with HFMD caused by enterovirus 71. Complications of HFMD may include [23,34,63-65,75-78]:

●Decreased oral intake, which may result in dehydration and may necessitate hospitalization for parenteral fluid therapy (see "Clinical assessment of hypovolemia (dehydration) in children" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings")

●Rhombencephalitis (brainstem encephalitis) (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Encephalitis')

●Acute flaccid paralysis (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Acute paralysis and brainstem encephalitis')

●Aseptic meningitis (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Viral (aseptic) meningitis')

●Myocarditis (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Myopericarditis')

●Pancreatitis (rare)

●Fetal loss (rare) (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Pregnant females')

●Conjunctival ulceration (rare) (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Ocular infections')

●Onychomadesis (shedding of the nail) is a late complication (occurring three to eight weeks after illness onset), particularly in patients with atypical HFMD (eg, caused by coxsackievirus A6) [79,80] (see "Atypical exanthems in children", section on 'Atypical hand, foot, and mouth disease')

Complications are more common with HFMD caused by enterovirus A71 than other enteroviruses [23,36,37,62-66].

Herpangina is an extremely benign disease. Complications are rare and almost exclusively occur when herpangina is caused by enterovirus A71 [23]. Complications may include:

●Rhombencephalitis (brainstem encephalitis) (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Encephalitis')

●Acute flaccid paralysis (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Acute paralysis and brainstem encephalitis')

●Aseptic meningitis (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Viral (aseptic) meningitis')

DIAGNOSIS — The diagnosis of HFMD usually is made clinically, based upon the typical appearance and location of the oral enanthem (picture 1A-B) and exanthem (picture 2). The diagnosis of HFMD may be more difficult when only the enanthem or only the exanthem is present [28,59]. In most case series, approximately 75 percent of patients have both the exanthem and the enanthem, and 10 to 15 percent have only the enanthem or exanthem [1,28,56,59,77]. (See 'Hand, foot, and mouth disease' above.)

The diagnosis of herpangina is also made clinically, based upon the typical appearance and location of the oral enanthem (fewer than 10 hyperemic yellow/greyish-white papulovesicles on the anterior pillars of the fauces, soft palate, tonsils, and uvula) and associated high fever. (See 'Herpangina' above.)

Confirmation of a specific viral etiology is seldom necessary in children with uncomplicated HFMD or herpangina, but may be warranted if the diagnosis is uncertain (eg, isolated exanthem) and would affect management (eg, atypical HFMD versus eczema herpeticum) and in children with complications. (See 'Coxsackievirus A6 HFMD' above and 'Complications' above and 'Differential diagnosis' below.)

When etiologic confirmation is necessary, throat, stool, and vesicular fluid samples should be obtained for cell culture or nucleic acid amplification (eg, polymerase chain reaction) [81]. For samples from all sites, nucleic acid amplification is preferred to cell culture because of increased sensitivity and the speed with which a result can be obtained (hours versus days) [82]. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Laboratory diagnosis'.)

Identification or isolation of an enterovirus from vesicular fluid (or cerebrospinal fluid if HFMD is complicated by meningitis) confirms the viral etiology of HFMD. Identification or isolation of an enterovirus from the stool or throat does not definitively establish causality. Following acute infection, enteroviruses are shed from the stool and throat for prolonged periods (six weeks to several months and up to four weeks, respectively) and the isolated virus may or may not be responsible for the current symptoms [82]. (See 'Pathogenesis' above.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of herpangina and HFMD includes other conditions associated with oral lesions, including (see "Soft tissue lesions of the oral cavity in children"):

●Aphthous ulcers – Aphthous ulcers are painful, shallow oral ulcerations with a greyish base (picture 6A-B). Patients with aphthous ulcers usually do not have skin lesions. (See "Oral lesions", section on 'Erosive, ulcerative, and bullous lesions'.)

●Primary herpes simplex gingivostomatitis – Primary herpes simplex gingivostomatitis is the result of primary infection with herpes simplex virus (HSV) type 1. A prodrome of fever, anorexia, irritability, malaise, and headache precedes the appearance of oral changes. Oral changes initially consist of erythema and edema of the gingiva with clusters of vesicles. The gums are friable and bleed easily (picture 7A). Large painful ulcers are formed when the vesicles rupture and coalesce. The areas of ulceration may become covered by an eschar. The buccal mucosa, tongue, gingiva, hard palate, pharynx, lips, and perioral skin are commonly involved (picture 7B). Although patients with HSV stomatitis may have associated skin lesions (eg, herpetic whitlow), the skin lesions usually are unilateral, in contrast to the lesions of HFMD, which usually are bilateral. (See "Herpetic gingivostomatitis in young children", section on 'Clinical features'.)

The differential diagnosis of HFMD also encompasses conditions with maculopapular or vesicular rashes, including:

●Pruritic lesions:

•Insect bites (papular urticaria) – Papular, pruritic lesions may arise at the site of an insect bite (picture 8A-B). They may be seen following bites from mosquitos, fleas, or bedbugs. The buttocks, perineum, genitals, perianal, and axillary areas are spared. The absence of oral lesions and pruritus distinguish papular urticaria from HFMD. (See "Insect and other arthropod bites", section on 'Papular urticaria'.)

•Varicella – Varicella (chickenpox) is caused by a deoxyribonucleic acid (DNA) virus of the herpes family of viruses. The exanthem of varicella appears in crops over several days and is usually pruritic. The rash begins as macules that rapidly progress to papules followed by vesicles and, ultimately, crusts (picture 9). The clinical course and pruritus distinguish varicella from HFMD. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Clinical manifestations'.)

•Id reaction – Id reaction is an autoeczematization reaction that consists of a pruritic, papulovesicular eruption and occurs secondary to dermatophyte infections such as tinea pedis, tinea manuum, tinea cruris, tinea corporis, or tinea capitis (picture 10). It is believed to be secondary to delayed-type hypersensitivity response to fungal antigens. Pruritus distinguishes id reactions from HFMD. (See "Dermatophyte (tinea) infections", section on 'Id reactions'.)

•Contact dermatitis – Contact dermatitis is an allergic or irritant dermatitis that results from direct exposure of the skin to the agent causing the reaction. The rash is papular, erythematous, and pruritic. The margins of the lesion are indistinct. The lesions are in the area(s) of exposure to the inciting agent (picture 11). Pruritus distinguishes contact dermatitis from HFMD. (See "Allergic contact dermatitis in children".)

●Erythema multiforme major – The immune-mediated skin lesions of erythema multiforme have a characteristic target- or bull's eye-like appearance (picture 12C). The enanthem which may involve the mucosa of the mouth (picture 12A-B), genitals, or eyes consists of erosions or bullae. In contrast to HFMD, erythema multiforme major usually occurs in young adults. However, increasing numbers of cases of atypical HFMD in adults, presenting with similarities to erythema multiforme, have been reported [83]. In these cases, histologic features of HFMD include large numbers of neutrophils in parakeratosis and in the viable epidermis, neutrophils forming intraepidermal collections, and necrotic keratinocytes in the upper one-third of the epidermis (compared with the lower-one third in erythema multiforme). (See "Erythema multiforme: Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations'.)

●Eczema herpeticum – Eczema herpeticum (cutaneous HSV infection in patients with eczema) is characterized by multiple herpetic vesicles at the site of preexisting eczema (picture 13). The vesicles may become hemorrhagic and coalesce to form large ulcerated, bleeding areas. The involved areas are painful. Most patients have fever. Eczema herpeticum requires prompt treatment with antiviral therapy. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Eczema herpeticum' and 'Indications for hospitalization' below.)

Laboratory tests may be necessary to differentiate eczema herpeticum from atypical HFMD associated with coxsackievirus A6, in which the skin lesions may be concentrated in areas of active or dormant eczema ("eczema coxsackium" (picture 4)). These may include nucleic acid amplification tests (eg, polymerase chain reaction for enterovirus and HSV) and/or light microscopy of vesicle scraping (HSV is associated with multinucleated giant cells; enterovirus is not).

CLINICAL COURSE — HFMD generally is a mild clinical syndrome. Complete resolution of symptoms and signs typically occurs within 7 to, at most, 10 days [1,29,33,43,55-57]. However, complications may occur. (See 'Complications' above.)

In a meta-analysis of 19 studies from the Asia-Pacific region (thus focused on HFMD caused by enterovirus 71 rather than classic HFMD), severe HFMD (neurologic, respiratory, or circulatory complications or death) was associated with [84]:

●Temperature ≥37.5°C (99.5°F)

●Fever (≥37.5°C [99.5°F]) ≥3 days

●Lethargy

●Vomiting

●Enterovirus A71 infection

●Young age

Laboratory studies usually are not necessary in children with HFMD. However, in this meta-analysis, severe HFMD was also associated with hyperglycemia (odds ratio 2.8, 95% CI 2.1-3.7) and increased neutrophil count (weight mean difference 0.6, 95% CI 0.5-0.7) [84].

Herpangina typically is benign and short lived, with complete recovery. Resolution of the fever occurs, on average, in two days (range two to four days) [6,38,39,85]. The throat lesions resolve in five to six days (range 3 to 10 days) [30,39].

MANAGEMENT — Management is mainly supportive. Children with complications may require hospitalization. No specific antiviral therapy is available for the treatment of the enteroviruses. The genome of the enteroviruses does not encode for thymidine kinase, the enzyme necessary for acyclovir activity. In addition, controlled trials demonstrating evidence of benefit of acyclovir in patients with HFMD are lacking.

Indications for hospitalization — Indications for hospitalization in children with HFMD and herpangina may include:

●Inability to maintain adequate hydration (see "Clinical assessment of hypovolemia (dehydration) in children" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings")

●Development of neurologic or cardiovascular complications, such as:

•Encephalitis (see "Acute viral encephalitis in children: Treatment and prevention")

•Meningitis (see "Viral meningitis in children: Management, prognosis, and prevention")

•Flaccid paralysis (see "Poliomyelitis and post-polio syndrome", section on 'Poliomyelitis')

•Myocarditis (see "Treatment and prognosis of myocarditis in children")

●The inability to differentiate eczema coxsackium (picture 4) from eczema herpeticum (picture 13) (for HFMD only)

Supportive care — For both HFMD and herpangina, the pain and fever generally are short lived. Pain and discomfort due to fever can be managed with ibuprofen or acetaminophen, although these agents should be avoided in children with dehydration until volume correction has been achieved. In severe cases oral opioids may be required.

We do not routinely suggest topical therapies containing lidocaine or other topical therapies (eg, diphenhydramine, Kaolin pectin) to coat oral lesions and/or soothe pain in children with HFMD given the lack of evidence of benefit from clinical trials [86], the potential for harm (eg, toxicity from systemic absorption, allergic reaction) [87,88], and difficulty of application in young children.

Children who are unable to drink sufficiently to maintain hydration should be hospitalized for parenteral fluid therapy. The assessment and treatment of dehydration are discussed separately. (See "Clinical assessment of hypovolemia (dehydration) in children" and "Maintenance intravenous fluid therapy in children" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)

PREVENTION

●Hygiene – Hand hygiene is important in the prevention of community-acquired HFMD and herpangina [89,90]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Hand hygiene'.)

Surfaces that come in contact with oral secretions or feces should be cleaned and disinfected. Fomites that may spread the virus should also be cleaned and disinfected. (See "Infection prevention: General principles", section on 'Cleaning, disinfection, and sterilization'.)

●Child care settings – Strict adherence to hand hygiene protocols is important when changing diapers because enteroviruses are shed in the stool for weeks following infection.

Exclusion of infants and children from child care does not prevent the spread of HFMD [91]. The viruses that cause HFMD can be spread by children without symptoms and children whose symptoms have resolved. Exclusion from child care is appropriate if the child is febrile or not feeling up to participating in class, and may be necessary if the child has many open blisters (to prevent secondary skin infection) or has extensive drooling from mouth lesions (which may require care from the child care provider that may compromise care for other children).

●Isolation – For hospitalized patients with HFMD and herpangina, contact precautions, in addition to standard precautions, should be used for the duration of the illness [92]. Cohorting of infected infants was effective in controlling an enterovirus outbreak in a neonatal intensive care unit [93].

●Vaccine – Vaccination for prevention of enterovirus and parechovirus infection is discussed separately. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Vaccines'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Hand, foot, and mouth disease and herpangina (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Hand, foot, and mouth disease (HFMD) and herpangina typically occur during the summer and early autumn. HFMD and herpangina usually affect children younger than seven years but may occur in all age groups. (See 'Epidemiology' above.)

●Transmission – The viruses that cause HFMD and herpangina (table 1) usually are transmitted from person to person by the fecal-oral route; they also can be transmitted by oral and respiratory secretions and, in cases of HFMD, vesicle fluid. The incubation period usually is three to five days. (See 'Transmission' above and 'Incubation period' above.)

●Clinical features

•Typical HFMD – Clinical features of typical HFMD include (see 'Hand, foot, and mouth disease' above):

-Painful oral lesions on the tongue and buccal mucosa that may interfere with oral intake (picture 1A-B); oral lesions may occur in isolation

-Macular, maculopapular, or vesicular nonpruritic, nontender skin lesions on the hands, feet, buttocks, and extremities (picture 2); skin lesions may occur in isolation

-When present, fever is below 38.3°C (101°F)

•Coxsackievirus A6 HFMD – HFMD caused by coxsackievirus A6 is more severe than "typical" HFMD (picture 3A-C). Clinical features include (see 'Coxsackievirus A6 HFMD' above):

-Higher fever

-Wider distribution of lesions

-Vesicobullous lesions, bullae, erosions, ulcerations, and eschar

-Longer duration

-Plamar/plantar desquamation

-Nail dystrophy

•Herpangina – Clinical features of herpangina include (see 'Herpangina' above):

-Abrupt onset with high fever

-Oral lesions on the anterior fauces, tonsils, and soft palate (picture 5) that may interfere with oral intake

-May be associated with vomiting, anorexia, irritability, or fussiness

●Complications – Complications of HFMD and herpangina are rare. They occur more commonly with enterovirus A71 than other types of enteroviruses. Complications of HFMD caused by enterovirus A71 include central nervous system disease, pulmonary edema and hemorrhage, and heart failure. Children with complications may require hospitalization. (See 'Complications' above and 'Enterovirus A71 HFMD' above.)

●Diagnosis – The diagnosis of HFMD usually is made clinically, based upon the typical appearance and location of the oral enanthem (picture 1A-B) and exanthem (picture 2). (See 'Diagnosis' above.)

The diagnosis of herpangina also is made clinically, based upon the typical appearance and location of the oral enanthem (fewer than 10 hyperemic yellow/greyish-white papulovesicles on the anterior pillars of the fauces, soft palate, tonsils, and uvula) and associated high fever. (See 'Diagnosis' above.)

It is seldom necessary to confirm a specific viral etiology for HFMD or herpangina.

●Differential diagnosis – The differential diagnosis of HFMD and herpangina includes:

•Other conditions associated with oral lesions (eg, aphthous ulcers (picture 6A-B), herpes simplex gingivostomatitis (picture 7A-B)).

•Other conditions associated with maculopapular or vesicular rashes (eg, papular urticaria (picture 8A-B), id reaction (picture 10), contact dermatitis (picture 11), erythema multiforme major (picture 12A-C), and eczema herpeticum (picture 13)).

Associated clinical features usually distinguish HFMD and herpangina from these conditions. (See 'Differential diagnosis' above.)

●Management – Most cases of uncomplicated HFMD and herpangina resolve spontaneously within seven days. Management is supportive. Pain and discomfort can be managed with ibuprofen or acetaminophen. We suggest not routinely using topical therapies for oral lesions of children with HFMD (Grade 2C). (See 'Clinical course' above and 'Management' above.)