Changes

May 2025 — reviewed.  A literature search was conducted in April 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. There have been minor structural changes to the topic, and changes to the recommendations have been updated in line with updated literature. A recommendation to consider the use of topical oromucosal antiseptics or anaesthetics has been added to the management advice section.

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of hand, foot, and mouth disease.
• Provide information on self-care advice and preventing transmission.
• Refer people for further assessment or admission, if appropriate.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

What is it?

• Hand, foot, and mouth disease (HFMD, also known as enteroviral vesicular stomatitis) is an acute viral illness characterized by vesicular eruptions in the mouth and papulovesicular lesions of the distal limbs. It should not be confused with foot-and-mouth disease in animals (cattle and other cloven-hoofed animals), which is caused by a different virus.
• HFMD is usually mild and self-limiting. The incubation period is 3–5 days. The mucocutaneous lesions appear 1–2 days after a prodromal period of fever, malaise, and myalgia, and last approximately 7–10 days with spontaneous resolution.
• HFMD is caused by enteroviruses from the picornavirus family (small, non-enveloped, single-stranded RNA viruses which are resistant to a variety of changes in environmental conditions, high concentration ethanol and gastric acid). The main enterovirus serotypes responsible for HFMD are the Coxsackie viruses. 
• In Europe and the US, HFMD is most commonly associated with group A Coxsackie viruses:
  • Coxsackie A16 and A6 are the most common causes of HFMD, although a considerable number of outbreaks have also been associated with the A10 strain.
  • The Coxsackie virus A6 strain causes an atypical HFMD, with a more widespread and extensive skin disease (including larger vesicles which frequently coalesce into bullae — vesiculobullous eruptions), more severe pyrexia, nail shedding, and higher risk for adult infection. Younger children can develop a significant erosive napkin dermatitis (nappy rash).
  • Group B Coxsackie viruses and echoviruses may also be causative.
  • Less commonly, but more seriously, HFMD can be caused by enterovirus 71 (EV71), which has caused epidemics in East and Southeast Asian countries. To date, no major outbreaks of EV71 have occurred in Europe.

[Ventarola et al, 2015; Esposito, 2018; Li et al, 2018; Leung, 2022; Yan, 2022; Griffin, 2023; Zhu, 2023; Kalam, 2024; Machado, 2024]

How is it transmitted?

• Hand, foot, and mouth disease (HFMD) is spread by:
  • Direct contact with the nasal and throat secretions of an infected person, for example, via coughing and sneezing.
  • Direct contact with fluid from the blisters.
  • Faeco-oral transmission. This can also occur from infected people who are asymptomatic, but who may still excrete the virus in their faeces.
  • Following exposure, the virus replicates in the lymphoid tissue of the lower intestine and the pharynx. From here, it spreads to regional lymph nodes and then to multiple organs, including the skin and oral mucosa, producing the vesicular eruptions characteristic of HFMD.
• It is transmissible immediately before and during the acute stage of illness, and for longer in some people, due to its prolonged presence in faeces and saliva.
  • People with HFMD are most contagious in the first 7 days of illness.
  • Faecal shedding can persist for up to 10 weeks, and respiratory shedding can persist for up to 30 days after the onset of illness.
  • The period of faecal and respiratory shedding is likely dependent on the severity of the disease and the specific causative pathogen.
• Factors associated with transmission include:
  • Lack of access to clean water.
  • Poor personal hygiene.
  • Overcrowding.
  • Large family size.
  • Attendance at childcare or educational settings.
• Vertical spread from mother to fetus can occur.
  • Vertical transmission is estimated to occur in 30–50% of cases.
• HFMD is not transmitted to or from animals. It is not related to foot and mouth disease of animals.

[Ventarola et al, 2015; Esposito, 2018; Giachè, 2021; DermNet NZ, 2022; Leung, 2022; Yan, 2022; CDC, 2024; Kalam, 2024; UKHSA, 2025a]

How common is it?

• Hand, foot, and mouth disease (HFMD) occurs worldwide and is most common in late summer or early autumn in temperate climates.
  • High temperatures and high levels of humidity have been associated with increased susceptibility.
• The average annual incidence is estimated to be 90–2400 cases per 100,000 people.
• It occurs sporadically as well as in regular outbreaks. 
• Children are most susceptible, as they are less likely to have immunity. Typically, HFMD affects children younger than 10 years of age, and most commonly occurs among children younger than 4–5 years of age. 
• Outbreaks occur frequently among groups of children in nurseries, childcare centres, and schools, and spread within families is common. One prospective study found a rate of household transmission of enterovirus 71 (EV71) between 52–84% in children younger than 6 years of age.
• Most adults are immune following previous exposure during childhood. However, adult cases are not unusual, especially with Coxsackie virus A6 infection.
  • Adult females may be at higher risk than adult males, though related to increased contact with young children.
  • Immunocompromised adults are at increased risk of infection.

[Ventarola et al, 2015; Esposito, 2018; DermNet NZ, 2022; Leung, 2022; Yan, 2022; Zhu, 2023; Kalam, 2024]

What are the complications?

• Complications of hand, foot, and mouth disease (HFMD) are rare. 
  • Dehydration is the most common complication, as oral pain interferes with fluid intake.
  • Secondary bacterial infection of lesions is rare, but can occur.
  • Finger and toenail changes, including transverse lines in the nail bed, nail shedding, leukonychia, and discolouration (yellow to orange), can occur up to 2 months after the illness. Fingernails may be more commonly affected than toenails.
  • HFMD caused by the enterovirus 71 (EV71) strain is associated with rare, but serious, life-threatening neurological sequelae such as brainstem encephalitis, aseptic meningitis, acute flaccid paralysis, myoclonus, and autonomic dysregulation, leading to pulmonary oedema and myocardial impairment. The mortality rate in complicated cases is cited as 10–25.7%.
• Complications may arise with HFMD infection in pregnancy.
  • Case reports have described miscarriage, stillbirth, congenital malformation, intrauterine growth restriction, and hydrops fetalis following HFMD in pregnancy. However, causality is not proven, and a small retrospective cohort study of pregnant women with HFMD (n = 53) reported miscarriage and congenital malformation risks in keeping with the expected background incidence.
  • HFMD acquired around the time of delivery can lead to neonatal infection. This is mostly mild and self-limiting; however, neonatal complications, including coagulation disorders and severe hepatic, respiratory, cardiac, and neurological disease, have been documented. Reassuringly, these complications do not appear to be associated with the most common Coxsackie A16 strain.

[Ventarola et al, 2015; Esposito, 2018; Li et al, 2018; Giachè, 2021; DermNet NZ, 2022; Leung, 2022; Yan, 2022; NHS, 2024; Kalam, 2024]

What is the prognosis?

• The prognosis of hand, foot, and mouth disease (HFMD) is generally excellent, as it is most commonly a self-limiting disease.
  • HFMD caused by Coxsackie A16 is a mild disease, and the vast majority of people fully recover. 
    • Oral and skin lesions nearly always fully resolve without treatment in 7–10 days.
  • HFMD caused by Coxsackie A6 is also generally self-limiting, but the acute phase may be followed by desquamation of the palms and soles for several weeks, and onychomadesis (shedding of the nails) within 3–8 weeks of symptom onset.
  • HFMD caused by enterovirus 71 has a higher incidence of neurological involvement (such as aseptic meningitis and encephalitis), although this remains rare (particularly in Europe).
  • Globally, it is estimated that only around 1% of HFMD cases result in severe illness, and 0.03% result in death. Mortality risk is strongly associated with those experiencing severe illness, mainly related to enterovirus 71 infection.
• Infection results in immunity to the specific causative virus, but recurrence of HFMD can occur with a different member of the enterovirus (EV) group, as there is almost no cross-immunity between the different EV serotypes.
• Although rare in the UK, severe acute illness has been associated with long-term sequelae, including:
  • Neurological dysfunction — HFMD with CNS involvement and cardiopulmonary failure has been associated with subsequent facial nerve palsy, limb weakness and atrophy, dysphagia, central hypoventilation, seizure, psychomotor delay, and cognitive impairment.
    • A 2018 systematic review and meta-analysis identified nine studies that assessed the risk of neurological sequelae among people who survived HFMD associated with any CNS involvement, autonomic nervous system dysregulation, or cardiopulmonary failure. Within these studies, the maximum reported follow-up period was 3.4–34.8 months, and the pooled cumulative incidence was 9.8%.
    • Higher risks were described for those with more severe illness. Among people who survived severe HFMD associated with brainstem encephalitis, encephalomyelitis or any autonomic nervous system dysregulation, the pooled cumulative incidence was 16.1%. The pooled cumulative incidence was 38.5% among those who survived severe HFMD associated with cardiopulmonary failure.
  • Vision loss — people who experience ocular symptoms of HFMD (pseudomembranous conjunctivitis, outer retinitis, and maculopathy) usually recover within weeks to months, although some may experience residual vision loss.
    • Vision loss has only been reported in sporadic case reports, and as such, the absolute risk of this complication is undetermined. 

[Ventarola et al, 2015; Esposito, 2018; Jones, 2018; Li et al, 2018; DermNet NZ, 2022; Leung, 2022; Zhu, 2023; CDC, 2024; Machado, 2024; UKHSA, 2025a]

When should I suspect hand, foot, and mouth disease?

The diagnosis of hand, foot, and mouth disease (HFMD) is usually clinical, based on typical symptoms and signs.

• HFMD typically presents as a mild illness with:
  • Sore throat, with or without a low-grade fever.
  • Tender lesions in the mouth (enanthem) and/or a rash on the body (exanthem).
• Ask about the presence of prodromal symptoms.
  • The prodromal period may last 12–36 hours.
  • Early symptoms are fever (typically 38–39°C), malaise, loss of appetite, cough, abdominal pain, myalgia, and sore mouth or throat. Rarely, vomiting occurs if HFMD is caused by enterovirus 71.
• Examine the mouth for characteristic features.
  • Scattered ulcerative lesions of the oral cavity occur within 1–2 days.
    • Typically, they begin as 2–8 mm erythematous macules and papules, and appear most commonly on the hard palate, tongue, and buccal mucosa, but also on the lips and pharynx.
    • Lesions progress rapidly to vesicles, which readily erode, leaving shallow yellow-grey ulcers surrounded by an erythematous halo.
    • In severe cases, the lesions may coalesce, leaving the tongue red and oedematous.
    • Adults with HFMD may develop strawberry tongue rather than the typical enanthem.
• Examine the rash for characteristic features.
  • Macules and papules of the hands and feet usually soon follow the oral lesions.
    • Typically, they are 2–5 mm sparse erythematous macules and papules, often with a central greyish vesicle.
    • The sides of the fingers, dorsum of the hands, and margins of the heels are more frequently affected than the palms or the soles.
    • Lesions are frequently elliptical with the long axis running parallel to the skin lines.
    • The buttocks and groin area may also be affected, particularly in infants and young children, though typically lesions do not progress to vesiculation.
    • Lesions may be asymptomatic or painful.
    • Children with pre-existing eczema may experience lesions localized to the eczematous areas.
  • HFMD caused by Coxsackie virus A6 may present with a more widespread rash that extends beyond the palms and soles and may preferentially occur in areas prone to atopic dermatitis (the antecubital and popliteal fossae).
    • Petechiae and severe blistering or purpuric eruption may be observed.
    • There may be a more severe pyrexia and subsequent skin peeling and/or nail shedding.
    • Younger children may develop a significant erosive napkin dermatitis (nappy rash).
    • Vesicles appear to localize on the dorsal rather than the palmer surfaces of hands and feet.
    • There is a prominent perioral cutaneous eruption rather than intraoral.
• Ask about or consider factors that can influence transmission and HFMD severity:
  • Age — those under the age of 10 years are most commonly affected.
  • Close contact of someone known to have HFMD, such as another family member.
  • Attendance at childcare or educational settings.
  • People who are immunocompromised or receiving immunosuppressive treatment — infection may be more likely.
  • Recent travel to East or South-east Asia — possibility of HFMD caused by enterovirus 71 which, although rare, can result in a more serious illness. Additional symptoms which may indicate a more severe presentation include high fever, headache, and stiff neck or back pain.
• Pictures of typical HFMD lesions are available from DermNet NZ.
• Laboratory investigations (such as oral, skin, or rectal swabs) are not usually necessary in primary care owing to the self-limiting nature of the illness.

What else might it be?

It may be difficult to differentiate viral illness from more serious causes of fever and rash in young children.

• Conditions that may resemble hand, foot, and mouth disease (HFMD) include:
  • Herpangina — caused by Coxsackie A viruses, including A16, which presents with high fever, malaise, headache, and oral lesions, but has no associated exanthema (rash).
  • Herpes stomatitis — common in children and in immunocompromised people. For more information, see the CKS topic on Herpes simplex - oral.
  • Aphthous ulcers — can become herpetiform and lead to stomatitis. For more information, see the CKS topic on Aphthous ulcer.
  • Chickenpox — suggested by a very itchy rash, mainly limited to the trunk and extremities. For more information, see the CKS topic on Chickenpox.
  • Erythema multiforme/Stevens–Johnson syndrome — typically presents with target lesions on palms, soles, and distal limbs. Vesicles coalesce and ulcerate, and mucous membrane involvement can progress to life-threatening Stevens–Johnson syndrome.
  • Viral pharyngitis — for more information, see the CKS topic on Sore throat - acute.
  • Scarlet fever — for more information, see the CKS topic on Scarlet fever.
  • Kawasaki disease — a systemic vasculitis that primarily affects infants and young children; it causes fever, conjunctivitis, 'strawberry' tongue, peeling skin, polymorphous rash, and cervical lymphadenopathy. Rare complications include coronary artery dilatation and aneurysm formation.
  • Pompholyx eczema — blisters may develop on hands and feet.
  • Lichen planus — may present in the mouth with painful erosive lesions (Whickman striae).
  • Traumatic ulcers — such as from thermal trauma or buccal aspirin.
  • Gingivitis — for more information, see the CKS topic on Gingivitis and periodontitis.
  • Behçet's disease — typically recurrent aphthous stomatitis with genital ulceration, eye involvement, and skin lesions.
  • Pemphigus vulgaris or oral bullous pemphigoid — painful mouth ulcers are present, and skin lesions are usually evident elsewhere.
  • Rubella — very uncommon in the UK. Clinical features include rash, lymphadenopathy, arthritis, arthralgia, and non-specific symptoms such as low-grade fever, headache, malaise, nausea, mild upper respiratory tract symptoms, and non-purulent conjunctivitis. For more information, see the CKS topic on Rubella.
  • Bullous impetigo — characterized by large, fragile, flaccid bullae (fluid-filled lesions over 1 cm in diameter) that rupture and ooze yellow fluid, leaving a scaley rim (collarette). For more information, see the CKS topic Impetigo.
  • Scabies — typically presents with a linear distribution of erythematous papules, burrows and pruritus, which worsens at night. For more information, see the CKS topic Scabies.

Scenario: Management of hand, foot, and mouth disease

From birth onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of hand, foot, and mouth disease.

Search dates

August 2020 - May 2025

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• hand foot and mouth disease.tw. 
• enterovirus; coxsackievirus(s); coxsackie virus.tw.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.