History

The incubation period of hand-foot-and-mouth disease (HFMD) lasts approximately 1 week; patients then report a sore mouth or throat. Malaise may develop. Rarely, vomiting occurs in HFMD cases caused by EV-71.

Physical

Initially, macular lesions appear on the buccal mucosa, tongue, and/or hard palate. These mucosal lesions rapidly progress to vesicles that erode and become surrounded by an erythematous halo, as shown in the image below. Skin lesions, which present as tender macules or vesicles on an erythematous base, develop in approximately 75% of patients with HFMD. A fever of 38-39°C may be present for 24-48 hours.

The lower lip has an ulcer with an erythematous halo.

Atypical clinical features may be present. HFMD caused by coxsackievirus strains rarely presents with concomitant aseptic meningitis.^[3]HFMD caused by EV-71 has a higher incidence of neurologic involvement, including a poliolike syndrome, aseptic meningitis, encephalitis, encephalomyelitis, acute cerebellar ataxia, acute transverse myelitis, Guillain-Barré syndrome, opsomyoclonus syndrome, and benign intracranial hypertension.^[4]

Causes

HFMD is most commonly caused by coxsackievirus A16, but it is also caused by coxsackieviruses A5, A7, A9 A10, B2, and B5 and EV-71. Two major genotypes of EV-71, EV-71 B and C, have been identified as the strains principally involved in the EV-71 HFMD epidemics in Australia, Malaysia, Singapore, Republic of China, and Japan since 1997. These genotypes are considered particularly neurovirulent, accounting for the severe neurologic complications seen in EV-71 HFMD epidemics.^[15]

Differential Diagnoses

Du Z, Huang Y, Lawrence WR, Xu J, Yang Z, Lu J, et al. Leading Enterovirus Genotypes Causing Hand, Foot, and Mouth Disease in Guangzhou, China: Relationship with Climate and Vaccination against EV71. Int J Environ Res Public Health. 2021 Jan 2. 18 (1):[QxMD MEDLINE Link].
Tomba Ngangas S, Bisseux M, Jugie G, Lambert C, Cohen R, Werner A, et al. Coxsackievirus A6 Recombinant Subclades D3/A and D3/H Were Predominant in Hand-Foot-And-Mouth Disease Outbreaks in the Paediatric Population, France, 2010-2018. Viruses. 2022 May 17. 14 (5):[QxMD MEDLINE Link].
Chan KP, Goh KT, Chong CY, Teo ES, Lau G, Ling AE. Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore. Emerg Infect Dis. 2003 Jan. 9(1):78-85. [QxMD MEDLINE Link].
Chong CY, Chan KP, Shah VA, Ng WY, Lau G, Teo TE, et al. Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases. Acta Paediatr. 2003 Oct. 92(10):1163-9. [QxMD MEDLINE Link].
Chen TC, Chen GW, Hsiung CA, Yang JY, Shih SR, Lai YK, et al. Combining multiplex reverse transcription-PCR and a diagnostic microarray to detect and differentiate enterovirus 71 and coxsackievirus A16. J Clin Microbiol. 2006 Jun. 44(6):2212-9. [QxMD MEDLINE Link].
Thomas I, Janniger CK. Hand, foot, and mouth disease. Cutis. 1993 Nov. 52(5):265-6. [QxMD MEDLINE Link].
Toida M, Watanabe F, Goto K, Shibata T. Usefulness of low-level laser for control of painful stomatitis in patients with hand-foot-and-mouth disease. J Clin Laser Med Surg. 2003 Dec. 21(6):363-7. [QxMD MEDLINE Link].
Wang SM, Liu CC. Enterovirus 71: epidemiology, pathogenesis and management. Expert Rev Anti Infect Ther. 2009 Aug. 7(6):735-42. [QxMD MEDLINE Link].
Nhan LNT, Khanh TH, Hong NTT, Van HMT, Nhu LNT, Ny NTH, et al. Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 - 2018. PLoS Negl Trop Dis. 2020 Aug. 14 (8):e0008544. [QxMD MEDLINE Link].
Saeed A, Khan QM, Waheed U, Arshad M, Asif M, Farooq M. RT-PCR evaluation for identification and sequence analysis of foot-and-mouth disease serotype O from 2006 to 2007 in Punjab, Pakistan. Comp Immunol Microbiol Infect Dis. 2011 Mar. 34(2):95-101. [QxMD MEDLINE Link].
Kua JA, Pang J. The epidemiological risk factors of hand, foot, mouth disease among children in Singapore: A retrospective case-control study. PLoS One. 2020. 15 (8):e0236711. [QxMD MEDLINE Link].
Chen SC, Chang HL, Yan TR, Cheng YT, Chen KT. An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan. Am J Trop Med Hyg. 2007 Jul. 77(1):188-91. [QxMD MEDLINE Link].
Chang LY, Lin TY, Huang YC, Tsao KC, Shih SR, Kuo ML, et al. Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. Pediatr Infect Dis J. 1999 Dec. 18(12):1092-6. [QxMD MEDLINE Link].
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. 2007 Aug. 120(2):e244-52. [QxMD MEDLINE Link].
Ahmad K. Hand, foot, and mouth disease outbreak reported in Singapore. Lancet. 2000 Oct 14. 356(9238):1338. [QxMD MEDLINE Link].
Soylu A, Yıldız G, Torun Bayram M, Kavukçu S. IL-1β blockade in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: case-based review. Rheumatol Int. 2021 Jan. 41 (1):183-188. [QxMD MEDLINE Link].
No TH, Jo KM, Jung SY, Kim MR, Kim JY, Park CS, et al. Coxsackievirus A6-induced Hand-Foot-and-Mouth Disease Mimicking Stevens-Johnson Syndrome in an Immunocompetent Adult. Infect Chemother. 2020 Dec. 52 (4):634-640. [QxMD MEDLINE Link].
Farah M, El Chaer F, El Khoury J, El Zakhem A. Erythema multiforme-like hand, foot, and mouth disease in an immunocompetent adult: a case report. Int J Dermatol. 2020 Apr. 59 (4):487-489. [QxMD MEDLINE Link].
Liu J, Qi J. Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China, From 2008 to 2013. Front Pediatr. 2020. 8:323. [QxMD MEDLINE Link].
Tan CW, Lai JK, Sam IC, Chan YF. Recent developments in antiviral agents against enterovirus 71 infection. J Biomed Sci. 2014. 21:14. [QxMD MEDLINE Link].
Lalani S, Gew LT, Poh CL. Antiviral peptides against Enterovirus A71 causing hand, foot and mouth disease. Peptides. 2021 Feb. 136:170443. [QxMD MEDLINE Link].
Li J, Yin X, Lin A, Nie X, Liu L, Liu S, et al. EV71 vaccination impact on the incidence of encephalitis in patients with hand, foot and mouth disease. Hum Vaccin Immunother. 2021 Jan 31. 1-4. [QxMD MEDLINE Link].
Liu D, Leung K, Jit M, Yu H, Yang J, Liao Q, et al. Cost-effectiveness of bivalent versus monovalent vaccines against hand, foot and mouth disease. Clin Microbiol Infect. 2020 Mar. 26 (3):373-380. [QxMD MEDLINE Link].
Lee PI, Tsai TC, Huang YC, Wu CF, Hu YL, Lin TY. Effectiveness of case isolation and class suspension in mitigation of enterovirus transmission in children. J Infect Public Health. 2022 May. 15 (5):594-598. [QxMD MEDLINE Link].
Zare M, Jamalidoust M, Pouladfar GR, Amanati A, Shafaati M, Namayandeh M, et al. A case report of severe systemic infection with neurological HFMD symptoms followed by an accidental puncture of thumb during HFMD sample collection. IDCases. 2022. 27:e01434. [QxMD MEDLINE Link].

Media Gallery

The lower lip has an ulcer with an erythematous halo.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas M Kerkering, MD, FACP, FIDSA Professor of Medicine with Tenure, Division of Infectious Diseases, Virginia Tech Carilion School of Medicine; Adjunct Professor, Department of Population Studies, Masters of Public Health Program, Virginia Tech University, School of Veterinary Medicine

Thomas M Kerkering, MD, FACP, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Human and Animal Mycology, Medical Society of Virginia, Roanoke Academy of Medicine, Virginia Infectious Diseases Society, Wilderness Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Gary L Gorby, MD Associate Professor, Departments of Internal Medicine and Medical Microbiology and Immunology, Division of Infectious Diseases, Creighton University School of Medicine; Associate Professor of Medicine, University of Nebraska Medical Center; Associate Chair, Omaha Veterans Affairs Medical Center

Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences

Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS † Professor, Department of Medicine, Rutgers New Jersey Medical School

Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey

Disclosure: Nothing to disclose.

Stephen J Nervi, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Stephen J Nervi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Acknowledgements

Diane H Johnson, MD Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine

Diane H Johnson, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Women's Association, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Sections Hand-Foot-and-Mouth Disease (HFMD)
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Tables
References

Illness	Etiologic Agent	Usual Severity of Clinical Illness	Appearance of Lesions	Locations of Lesions	Other Features
HFMD	Coxsackie-virus A16 (most common), A5, A7, A9, A10, B2, B5 Enterovirus 71	Mild	Papules → Vesicles → ulcerations on an erythematous base Usually 2-6 mm	Gingiva Buccal mucosa Tongue Pharynx	Lesions may also be found on hands, feet, buttocks, and genitalia. Low-grade fever
Herpangina	Coxsackie-virus A1-A10, A16, A22 Echovirus 3, 6, 9, 16, 17, 25, 30	Moderate; can be severe	Papules → Vesicles → ulcerations on an erythematous base Usually 2-4 mm	Posterior oral cavity Tonsils, soft palate, uvula	Temperature generally high
Herpetic gingivostomatitis	Herpes simplex virus-1	Moderate to severe	Vesicles ulcerations	Anterior oral cavity Lips, gingiva, buccal mucosa	Temperature generally high Lymphadenopathy
Aphthous stomatitis	Unknown	Mild to severe	Ulcerations; larger than in viral enanthems	Lips, tongue, buccal mucosa; generally not diffuse	Afebrile May be recurrent
Stevens-Johnson syndrome	Immunologic	Moderate to severe	Coalescent vesicles, which then ulcerate	Lips, gingiva, buccal mucosa, tongue, pharynx	Targetlike cutaneous lesions Diffuse mucous membrane involvement

Hand-Foot-and-Mouth Disease (HFMD) Clinical Presentation

History

Physical

Causes

References

Tables

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